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    UNITED NATIONS ENVIRONMENT PROGRAMME
    INTERNATIONAL LABOUR ORGANISATION
    WORLD HEALTH ORGANIZATION


    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY



    ENVIRONMENTAL HEALTH CRITERIA 202





    SELECTED NON-HETEROCYCLIC 
    POLICYCLIC AROMATIC HYDROCARBONS














    This report contains the collective views of an international group of
    experts and does not necessarily represent the decisions or the stated
    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization.

    First and second drafts prepared by staff members at the Fraunhofer
    Institute of Toxicology and Aerosol Research, Hanover, Germany, under
    the coordination of Dr R.F. Hertel, Dr G. Rosner, and Dr J. Kielhorn,
    in cooperation with Dr E. Menichini, Italy, Dr P.L. Grover, United
    Kingdom, and Dr J. Blok, Netherlands. Dr P. Muller, Canada, and Dr R.
    Schoeny and Dr T.L. Mumford, USA, prepared and revised the drafts of
    Appendix I.


    Published under the joint sponsorship of the United Nations
    Environment Programme, the International Labour Organisation, and the
    World Health Organization and produced within the framework of the
    Inter-Organization Programme for the Sound Management of Chemicals



    World Health Organization
    Geneva, 1998

         The International Programme on Chemical Safety (IPCS),
    established in 1980, is a joint venture of the United Nations
    Environment Programme (UNEP), the International Labour Organisation
    (ILO), and the World Health Organization (WHO). The overall objectives
    of the IPCS are to establish the scientific basis for assessment of
    the risk to human health and the environment from exposure to
    chemicals, through international peer-review processes, as a
    prerequisite for the promotion of chemical safety, and to provide
    technical assistance in strengthening national capacities for the
    sound management of chemicals.

         The Inter-Organization Programme for the Sound Management of
    Chemicals (IOMC) was established in 1995 by UNEP, ILO, the Food and
    Agriculture Organization of the United Nations, WHO, the United
    Nations Industrial Development Organization, and the Organisation for
    Economic Co-operation and Development (Participating Organizations),
    following recommendations made by the 1992 United Nations Conference
    on Environment and Development, to strengthen cooperation and increase
    coordination in the field of chemical safety. The purpose of the IOMC
    is to promote coordination of the policies and activities pursued by
    the Participating Organizations, jointly or separately, to achieve the
    sound management of chemicals in relation to human health and the
    environment.

    WHO Library Cataloguing in Publication Data

    Selected non-heterocyclic polycyclic aromatic hydrocarbons.

    (Environmental health criteria ; 202)
    1. Polycyclic hydrocarbons, Aromatic  2.Environmental exposure
    3.Occupational exposure  4.Risk assessment - methods
    I.INternational Programme on Chemical Safety  II.Series

    ISBN 92 4 157202 7                  (NLM Classification: QD 341.H9)
    ISSN 0250-863X

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    (c) World Health Organization 1998

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         The mention of specific companies or of certain manufacturers'
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    that are not mentioned. Errors and omissions excepted, the names of
    proprietary products are distinguished by initial capital letters.

    CONTENTS

    NOTE TO READERS OF THE CRITERIA MONOGRAPHS

    PREAMBLE

    WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA
    FOR SELECTED NON-HETEROCYCLIC POLYCYCLIC AROMATIC HYDROCARBONS

    ENVIRONMENTAL HEALTH CRITERIA FOR SELECTED NON-HETEROCYCLIC POLYCYCLIC
    AROMATIC HYDROCARBONS

    1. SUMMARY
         1.1. Selection of compounds for this monograph
         1.2. Identity, physical and chemical properties, and analytical 
              methods
         1.3. Sources of human and environmental exposure
         1.4. Environmental transport, distribution, and transformation
         1.5. Environmental levels and human exposure
              1.5.1. Air
              1.5.2. Surface water and precipitation
              1.5.3. Sediment
              1.5.4. Soil
              1.5.5. Food
              1.5.6. Aquatic organisms
              1.5.7. Terrestrial organisms
              1.5.8. General population
              1.5.9. Occupational exposure
         1.6. Kinetics and metabolism
         1.7. Effects on laboratory mammals and  in vitro
         1.8. Effects on humans
         1.9. Effects on other organisms in the laboratory and the field

    2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL
         METHODS
         2.1. Identity
              2.1.1. Technical products
         2.2. Physical and chemical properties
         2.3. Conversion factors
         2.4. Analytical methods
              2.4.1. Sampling
                     2.4.1.1  Ambient air
                     2.4.1.2  Workplace air
                     2.4.1.3  Combustion effluents
                     2.4.1.4  Water
                     2.4.1.5  Solid samples
              2.4.2. Preparation

              2.4.3. Analysis
                     2.4.3.1  Gas chromatography
                     2.4.3.2  High-performance liquid chromatography
                     2.4.3.3  Thin-layer chromatography
                     2.4.3.4  Other techniques
              2.4.4. Choice of PAH to be quantified

    3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE
         3.1. Natural occurrence
         3.2. Anthropogenic sources
              3.2.1. PAH in coal and petroleum products
              3.2.2. Production levels and processes
              3.2.3. Uses of individual PAH
              3.2.4. Emissions during production and processing of PAH
                     3.2.4.1  Emissions to the atmosphere
                     3.2.4.2  Emissions to the hydrosphere
              3.2.5. Emissions during use of individual PAH
              3.2.6. Emissions of PAH during processing and use 
                     of coal and petroleum products
                     3.2.6.1  Emissions to the atmosphere
                     3.2.6.2  Emissions to the hydrosphere
                     3.2.6.3  Emissions to the geosphere
                     3.2.6.4  Emissions to the biosphere
              3.2.7. Emissions of PAH caused by incomplete combustion
                     3.2.7.1  Industrial point sources
                     3.2.7.2  Other diffuse sources

    4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION
         4.1. Transport and distribution between media
              4.1.1. Physicochemical parameters that dtermine
                     environmental transport and distribution
              4.1.2. Distribution and transport in the gaseous phase
              4.1.3. Volatilization
              4.1.4. Adsorption onto soils and sediments
              4.1.5. Bioaccumulation
                     4.1.5.1  Aquatic organisms
                     4.1.5.2  Terrestrial organisms
              4.1.6. Biomagnification
         4.2. Transformation
              4.2.1. Biotic transformation
                     4.2.1.1  Biodegradation
                     4.2.1.2  Biotransformation
              4.2.2. Abiotic degradation
                     4.2.2.1  Photodegradation in the environment
                     4.2.2.2  Hydrolysis
              4.2.3. Ultimate fate after use

    5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE
         5.1. Environmental levels
              5.1.1. Atmosphere
                     5.1.1.1  Source identification
                     5.1.1.2  Background and rural levels

                     5.1.1.3  Industrial sources
                     5.1.1.4  Diffuse sources
              5.1.2. Hydrosphere
                     5.1.2.1  Surface and coastal waters
                     5.1.2.2  Groundwater
                     5.1.2.3  Drinking-water and water supplies
                     5.1.2.4  Precipitation
              5.1.3. Sediment
                     5.1.3.1  River sediment
                     5.1.3.2  Lake sediment
                     5.1.3.3  Marine sediment
                     5.1.3.4  Estuarine sediment
                     5.1.3.5  Harbour sediment
                     5.1.3.6  Time trends of PAH in sediment
              5.1.4. Soil
                     5.1.4.1  Background values
                     5.1.4.2  Industrial sources
                     5.1.4.3  Diffuse sources
                     5.1.4.4  Time trends of PAH in soil
              5.1.5. Food
                     5.1.5.1  Meat and meat products
                     5.1.5.2  Fish and marine foods
                     5.1.5.3  Dairy products: cheese, butter, cream
                              milk, and related products
                     5.1.5.4  Vegetables
                     5.1.5.5  Fruits and confectionery
                     5.1.5.6  Cereals and dried food products
                     5.1.5.7  Beverages
                     5.1.5.8  Vegetable and animal fats and oils
              5.1.6. Biota
              5.1.7. Animals
                     5.1.7.1  Aquatic organisms
                     5.1.7.2  Terrestrial organisms
         5.2. Exposure of the general population
              5.2.1. Indoor air
              5.2.2. Food
              5.2.3. Other sources
              5.2.4. Intake of PAH by inhalation
              5.2.5. Intake of PAH from food and drinking-water
         5.3. Occupational exposure
              5.3.1. Occupational exposure during processing and use
                     of coal and petroleum products
                     5.3.1.1  Coal coking
                     5.3.1.2  Coal gasification and coal liquefaction
                     5.3.1.3  Pteroleum refining
                     5.3.1.4  Road paving
                     5.3.1.5  Roofing
                     5.3.1.6  Impregnation of wood with creosotes
                     5.3.1.7  Other exposures

              5.3.2. Occupational  exposure resulting from incomplete
                     combustion of mineral oil, coal, and their products
                     5.3.2.1  Aluminium production
                     5.3.2.2  Foundries
                     5.3.2.3  Other workplaces

    6. KINETICS AND METABOLISM IN LABORATORY MAMMALS AND HUMANS
         6.1. Absorption
              6.1.1. Absorption by inhalation
              6.1.2. Absorption in the gastrointestinal tract
              6.1.3. Absorption through the skin
         6.2. Distribution
         6.3. Metabolic transformation
              6.3.1. Cytochromes P450 and PAH metabolism
                     6.3.1.1  Individual cytochrome P450 enzymes
                              that metabolize PAH
                     6.3.1.2  Regulation of cytochrome P450 enzymes
                              that metabolize PAH
              6.3.2. Metabolism of benzo [a]pyrene
         6.4. Elimination and excretion
         6.5. Retention and turnover
              6.5.1. Human body burdens of PAH
         6.6. Reactions with tissue components
              6.6.1. Reactions with proteins
              6.6.2. Reactions with nucleic acids
         6.7. Analytical methods
    7. EFFECTS ON LABORATORY MAMMALS AND  IN VITRO
         7.1. Toxicity after a single exposure
              7.1.1. Benzo [a]pyrene
              7.1.2. Chrysene
              7.1.3. Dibenz [a,h]anthracene
              7.1.4. Fluoranthene
              7.1.5. Naphthalene
              7.1.6. Phenanthrene
              7.1.7. Pyrene
         7.2. Short-term toxicity
              7.2.1. Subacute toxicity
                     7.2.1.1  Acenaphthene
                     7.2.1.2  Acenaphthylene
                     7.2.1.3  Anthracene
                     7.2.1.4  Benzo [a]pyrene
                     7.2.1.5  Benz [a]anthracene
                     7.2.1.6  Dibenz [a,h]anthracene
                     7.2.1.7  Fluoranthene
                     7.2.1.8  Naphthalene
                     7.2.1.9  Phenanthrene
                     7.2.1.10 Pyrene
              7.2.2. Subchronic toxicity
                     7.2.2.1  Acenaphthene
                     7.2.2.2  Anthracene
                     7.2.2.3  Benzo [a]pyrene
                     7.2.2.4  Fluorene

                     7.2.2.5  Fluoranthene
                     7.2.2.6  Naphthalene
                     7.2.2.7  Pyrene
         7.3. Long-term toxicity
              7.3.1. Anthracene
              7.3.2. Benz [a]anthracene
              7.3.3. Dibenz [a,h]anthracene
         7.4. Dermal and ocular irritation and dermal sensitization
              7.4.1. Anthracene
              7.4.2. Benzo [a]pyrene
              7.4.3. Naphthalene
              7.4.4. Phenanthrene
         7.5. Reproductive effects, embryotoxicity, and teratogenicity
              7.5.1. Benzo [a]pyrene
                     7.5.1.1  Teratogenicity in mice of different
                              genotypes
                     7.5.1.2  Reproductive toxicity
                     7.5.1.3  Effects on postnatal development
                     7.5.1.4  Immunological effects in pregnant
                              rats and mice
              7.5.2. Naphthalene
                     7.5.2.1  Embryotoxicity
                     7.5.2.2  Toxicity in cultured embryos
         7.6. Mutagenicity and related end-points
         7.7. Carcinogenicity
              7.7.1. Single substances
                     7.7.1.1  Benzo [a]pyrene
                     7.7.1.2  Benzo [e]pyrene
              7.7.2. Comparative studies
                     7.7.2.1  Carcinogenicity
                     7.7.2.2  Further evidence
              7.7.3. PAH in complex mixtures
              7.7.4. Transplacental carcinogenicity
                     7.7.4.1  Benzo [a]pyrene
                     7.7.4.2  Pyrene
         7.8. Special studies
              7.8.1. Phototoxicity
                     7.8.1.1  Anthracene
                     7.8.1.2  Benzo [a]pyrene
                     7.8.1.3  Pyrene
                     7.8.1.4  Comparisons of individual PAH
              7.8.2. Immunotoxicity
                     7.8.2.1  Benzo [a]pyrene
                     7.8.2.2  Dibenz [a,h]anthracene
                     7.8.2.3  Fluoranthene
                     7.8.2.4  Naphthalene
                     7.8.2.5  Comparisons of individual PAH
                     7.8.2.6  Exposure  in utero 
                     7.8.2.7  Mechanisms of the immunotoxicity of PAH
              7.8.3. Hepatotoxicity
                     7.8.3.1  Benzo [a]pyrene
                     7.8.3.2  Comparisons of individual PAH

              7.8.4. Renal toxicity
              7.8.5. Ocular toxicity of naphthalene
              7.8.6. Percutaneous absorption
              7.8.7. Other studies
                     7.8.7.1  Benzo [k]fluoranthene
                     7.8.7.2  Benzo [a]pyrene
                     7.8.7.3  Phenanthrene
                     7.8.7.4  Comparisons of individual PAH
         7.9. Toxicity of metabolites
              7.9.1. Benzo [a]pyrene
              7.9.2. 5-Methylchrysene
              7.9.3. 1-Methylphenanthrene
         7.10. Mechanisms of carcinogenicity
              7.10.1. History
              7.10.2. Current theories
              7.10.3. Theories under discussion
                     7.10.3.1  Acenaphthene and acenaphthylene
                     7.10.3.2  Anthracene
                     7.10.3.3  Benzo [a]pyrene
                     7.10.3.4  Benz [a]anthracene
                     7.10.3.5  Benzo [c]phenanthrene
                     7.10.3.6  Chrysene
                     7.10.3.7  Cyclopenta [c,d]pyrene
                     7.10.3.8  Fluorene
                     7.10.3.9  Indeno[1,2,3- cd]pyrene
                     7.10.3.10 5-Methylchrysene
                     7.10.3.11 1-Methylphenanthrene
                     7.10.3.12 Naphthalene
                     7.10.3.13 Phenanthrene
                     7.10.3.14 Investigations of groups of PAH

    8. EFFECTS ON HUMANS
         8.1. Exposure of the general population
              8.1.1. Naphthalene
                     8.1.1.1   Poisoning incidents
                     8.1.1.2   Controlled studies
              8.1.2. Mixtures of PAH
                     8.1.2.1   PAH in unvented coal combustion
                               in homes
                     8.1.2.2   PAH in cigarette smoke
                     8.1.2.3   PAH in coal-tar shampoo
         8.2. Occupational exposure
         8.3. Biomarkers of exposure to PAH
              8.3.1. Urinary metabolites in general
              8.3.2. 1-Hydroxypyrene
                     8.3.2.1   Method of determination
                     8.3.2.2   Concentrations
                     8.3.2.3   Time course of elimination
                     8.3.2.4   Suitability as a biomarker
              8.3.3. Mutagenicity in urine
              8.3.4. Genotoxicity in lymphocytes

              8.3.5. DNA adducts
                     8.3.5.1   Method of determination
                     8.3.5.2   Concentrations
                     8.3.5.3   Suitability as a biomarker
              8.3.6. Antibodies to DNA adducts
              8.3.7. Protein adducts
              8.3.8. Activity of cytochrome P450
              8.3.9. Cell surface differentiation antigens in lung cancer
              8.3.10. Oncogene proteins

    9. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND THE FIELD
         9.1. Laboratory experiments
              9.1.1. Microorganisms
                     9.1.1.1   Water
                     9.1.1.2   Soil
              9.1.2. Aquatic organisms
                     9.1.2.1   Plants
                     9.1.2.2   Invertebrates
                     9.1.2.3   Vertebrates
                     9.1.2.4   Sediment-dwelling organisms
                     9.1.2.5   Toxicity of combinations of PAH
              9.1.3. Terrestrial organisms
                     9.1.3.1   Plants
                     9.1.3.2   Invertebrates
                     9.1.3.3   Vertebrates
         9.2. Field observations
              9.2.1. Microorganisms
                     9.2.1.1   Water
                     9.2.1.2   Soil
              9.2.2. Aquatic organisms
                     9.2.2.1   Plants
                     9.2.2.2   Invertebrates
                     9.2.2.3   Vertebrates
              9.2.3. Terrestrial organisms
                     9.2.3.1   Plants
                     9.2.3.2   Invertebrates
                     9.2.3.3   Vertebrates

    10   EVALUATION OF RISKS TO HUMAN HEALTH AND EFFECTS ON THE
         ENVIRONMENT
         10.1. Human health
              10.1.1. Exposure
                      10.1.1.1  General population
                      10.1.1.2  Occupational exposure
              10.1..2 Toxic effects
                      10.1.2.1  Bioavailability
                      10.1.2.2  Acute toxicity
                      10.1.2.3  Irritation and allergic sensitization
                      10.1.2.4  Medium-term toxicity
                      10.1.2.5  Carcinogenicity
                      10.1.2.6  Reproductive toxicity
                      10.1.2.7  Immunotoxicity
                      10.1.2.8  Genotoxicity

         10.2. Environment
              10.2.1. Environmental levels and fate
              10.2.2. Ecotoxic effects
                      10.2.2.1  Terrestrial organisms
                      10.2.2.2  Aquatic organisms

    11   RECOMMENDATIONS FOR PROTECTION OF HUMAN HEALTH AND THE
         ENVIRONMENT
         11.1. General recommendations
         11.2. Protection of human health
         11.3. Recommendations for further research
              11.3.1. General
              11.3.2. Protection of human health
              11.3.3. Environmental protection
              11.3.4. Risk assessment

    12   PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES
         12.1. International Agency for Research on Cancer
         12.2. WHO Water Quality Guidelines
         12.3. FAO/WHO Joint Expert Committee on Food Additives
         12.4. WHO Regional Office for Europe Air Quality Guidelines


    APPENDIX I. SOME APPROACHES TO RISK ASSESSMENT FOR POLYCYCLIC AROMATIC
    HYDROCARBONS
    I.1  Introduction
    I.2  Approaches to risk assessment
         I.2.1  Toxicity equivalence factors and related approaches
                I.2.1.1  Principle
                I.2.1.2  Development and validation
                         I.2.1.2.1  Derivation of the potency of
                                    benzo [a]pyrene
                         I2.1.2.2   Derivation of the relative potency of
                                    PAH other than benzo [a]pyrene
                I.2.1.3  Application
         I.2.2  Comparative potency approach
                I.2.2.1  Principle
                I.2.2.2  Development and validation
                I.2.2.3  Key implicit and explicit assumptions
                I.2.2.4  Application
         I.2.3  Benzo [a]pyrene as a surrogate for the PAH fraction
                of complex mixtures
                I.2.3.1  Principle
                I.2.3.2  Development and validation
                I.2.3.3  PAH profiles of complex mixtures
                I.2.3.4  Potency of complex mixtures
                I.2.3.5  Key implicit and explicit assumptions
                I.2.3.6  Application
    I.3  Comparison of the three procedures
         I.3.1  Individual PAH approach
         I.3.2  Comparative potency approach
         I.3.3  Benzo [a]pyrene surrogate approach

    APPENDIX II; SOME LIMIT VALUES
    II.1 Exposure of the consumer
    II.2 Occupational exposure
    II.3 Classification
         II.3.1 European Union
         II.3.2 USA

    REFERENCES

    RESUME

    RESUMEN
    

    Environmental Health Criteria

    PREAMBLE

    Objectives

         The WHO Environmental Health Criteria Programme was initiated in
    1973, with the following objectives:

    (i)    to assess information on the relationship between exposure to
           environmental pollutants and human health and to provide
           guidelines for setting exposure limits;

    (ii)   to identify new or potential pollutants;

    (iii)  to identify gaps in knowledge concerning the health effects of
           pollutants;
    (iv)   to promote the harmonization of toxicological and
           epidemiological methods in order to have internationally
           comparable results.

         The first Environmental Health Criteria (EHC) monograph, on
    mercury, was published in 1976; numerous assessments of chemicals and
    of physical effects have since been produced. Many EHC monographs have
    been devoted to toxicological methods, e.g. for genetic, neurotoxic,
    teratogenic, and nephrotoxic effects. Other publications have been
    concerned with e.g. epidemiological guidelines, evaluation of
    short-term tests for carcinogens, biomarkers, and effects on the
    elderly.

         Since the time of its inauguration, the EHC Programme has widened
    its scope, and the importance of environmental effects has been
    increasingly emphasized in the total evaluation of chemicals, in
    addition to their health effects.

         The original impetus for the Programme came from resolutions of
    the World Health Assembly and the recommendations of the 1972 United
    Nations Conference on the Human Environment. Subsequently, the work
    became an integral part of the International Programme on Chemical
    Safety (IPCS), a cooperative programme of UNEP, ILO, and WHO. In this
    manner, with the strong support of the new partners, the importance of
    occupational health and environmental effects was fully recognized.
    The EHC monographs have become widely established, used, and
    recognized throughout the world.

         The recommendations of the 1992 United Nations Conference on
    Environment and Development and the subsequent establishment of the
    Intergovernmental Forum on Chemical Safety, with priorities for action
    in the six programme areas of Chapter 19, Agenda 21, lend further
    weight to the need for EHC assessments of the risks of chemicals.

    Scope

         The Criteria monographs are intended to provide critical reviews
    of the effect on human health and the environment of chemicals,
    combinations of chemicals, and physical and biological agents. They
    include reviews of studies that are of direct relevance for the
    evaluation and do not describe every study that has been carried out.
    Data obtained worldwide are used, and results are quoted from original
    studies, not from abstracts or reviews. Both published and unpublished
    reports are considered, and the authors are responsible for assessing
    all of the articles cited; however, preference is always given to
    published data, and unpublished data are used only when relevant
    published data are absent or when the unpublished data are pivotal to
    the risk assessment. A detailed policy statement is available that
    describes the procedures used for citing unpublished proprietary data,
    so that this information can be used in the evaluation without
    compromising its confidential nature (WHO, 1990).

         In the evaluation of human health risks, sound data on humans,
    whenever available, are preferred to data on experimental animals.
    Studies of animals and in-vitro systems provide support and are used
    mainly to supply evidence missing from human studies. It is mandatory
    that research on human subjects be conducted in full accord with
    ethical principles, including the provisions of the Helsinki
    Declaration.

         The EHC monographs are intended to assist national and
    international authorities in making risk assessments and subsequent
    risk management decisions. They represent a thorough evaluation of
    risks and are not in any sense recommendations for regulation or
    setting standards. The latter are the exclusive purview of national
    and regional governments.

    Content

         The layout of EHC monographs for chemicals is outlined below.

    *    Summary: a review of the salient facts and the risk evaluation of
         the chemical
    *    Identity: physical and chemical properties, analytical methods
    *    Sources of exposure
    *    Environmental transport, distribution, and transformation
    *    Environmental levels and human exposure
    *    Kinetics and metabolism in laboratory animals and humans
    *    Effects on laboratory mammals and in-vitro test systems
    *    Effects on humans
    *    Effects on other organisms in the laboratory and the field
    *    Evaluation of human health risks and effects on the environment
    *    Conclusions and recommendations for protection of human health
         and the environment
    *    Further research

    *    Previous evaluations by international bodies, e.g. the
         International  Agency for Research on Cancer, the Joint FAO/WHO
         Expert  Committee on Food Additives, and the Joint FAO/WHO
         Meeting on Pesticide Residues

    Selection of chemicals

         Since the inception of the EHC Programme, the IPCS has organized
    meetings of scientists to establish lists of chemicals that are of
    priority for subsequent evaluation. Such meetings have been held in
    Ispra, Italy (1980); Oxford, United Kingdom (1984); Berlin, Germany
    (1987); and North Carolina, United States of America (1995). The
    selection of chemicals is based on the following criteria: the
    existence of scientific evidence that the substance presents a hazard
    to human health and/or the environment; the existence of evidence that
    the possible use, persistence, accumulation, or degradation of the
    substance involves significant human or environmental exposure; the
    existence of evidence that the populations at risk (both human and
    other species) and the risks for the environment are of a significant
    size and nature; there is international concern, i.e. the substance is
    of major interest to several countries; adequate data are available on
    the hazards.

         If it is proposed to write an EHC monograph on a chemical that is
    not on the list of priorities, the IPCS Secretariat first consults
    with the cooperating organizations and the participating institutions.

    Procedures

         The order of procedures that result in the publication of an EHC
    monograph is shown in the following flow chart. A designated staff
    member of IPCS, responsible for the scientific quality of the
    document, serves as Responsible Officer (RO). The IPCS Editor is
    responsible for the layout and language. The first draft, prepared by
    consultants or, more usually, staff at an IPCS participating
    institution is based initially on data provided from the International
    Register of Potentially Toxic Chemicals and reference data bases such
    as Medline and Toxline.

         The draft document, when received by the RO, may require an
    initial review by a small panel of experts to determine its scientific
    quality and objectivity. Once the RO finds the first draft acceptable,
    it is distributed in its unedited form to over 150 EHC contact points
    throughout the world for comment on its completeness and accuracy and,
    where necessary, to provide additional material. The contact points,
    usually designated by governments, may be participating institutions,
    IPCS focal points, or individual scientists known for their particular
    expertise. Generally, about four months are allowed before the
    comments are considered by the RO and author(s). A second draft
    incorporating the comments received and approved by the Director,
    IPCS, is then distributed to Task Group members, who carry out a peer
    review at least six weeks before their meeting.

         The Task Group members serve as individual scientists, not as
    representatives of any organization, government, or industry. Their
    function is to evaluate the accuracy, significance, and relevance of
    the information in the document and to assess the risks to health and
    the environment from exposure to the chemical. A summary and
    recommendations for further research and improved safety are also
    drawn up. The composition of the Task Group is dictated by the range
    of expertise required for the subject of the meeting and by the need
    for a balanced geographical distribution.

         The three cooperating organizations of the IPCS recognize the
    important role played by nongovernmental organizations, so that
    representatives from relevant national and international associations
    may be invited to join the Task Group as observers. While observers
    may provide valuable contributions to the process, they can speak only
    at the invitation of the Chairperson. Observers do not participate in
    the final evaluation of the chemical, which is the sole responsibility
    of the Task Group members. The Task Group may meet in camera when it
    considers that to be appropriate.

         All individuals who participate in the preparation of an EHC
    monograph as authors, consultants, or advisers must, in addition to
    serving in their personal capacity as scientists, inform the RO if at
    any time a conflict of interest, whether actual or potential, could be
    perceived in their work. They are required to sign a statement to that
    effect. This procedure ensures the transparency and probity of the
    process.

         When the Task Group has completed its review and the RO is
    satisfied as to the scientific correctness and completeness of the
    document, it is edited for language, the references are checked, and
    camera-ready copy is prepared. After approval by the Director, IPCS,
    the monograph is submitted to the WHO Office of Publications for
    printing. At this time, a copy of the final draft is also sent to the
    Chairperson and Rapporteur of the Task Group to check for any errors.

         It is accepted that the following criteria should initiate the
    updating of an EHC monograph: new data are available that would
    substantially change the evaluation; there is public concern about
    health or environmental effects of the agent because of greater
    exposure; an appreciable time has elapsed since the last evaluation.

         All participating institutions are informed, through the EHC
    progress report, of the authors and institutions proposed for the
    drafting of the documents. A comprehensive file of all comments
    received on drafts of each EHC monograph is maintained and is
    available on request. The chairpersons of task groups are briefed
    before each meeting on their role and responsibility in ensuring that
    these rules are followed.

    FIGURE 1

    WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR SELECTED
    NON-HETEROCYCLIC POLYCYCLIC AROMATIC HYDROCARBONS
    Hanover, Germany, 25-29 September 1995

     Members

    Dr P.E.T. Douben, Her Majesty's Inspectorate of Pollution, London,
    United Kingdom  (Chairman)

    Dr P.L. Grover, Institute for Cancer Research, Sutton, United Kingdom

    Dr R.F. Hertel, Bundesgesinstitut für gesundheitlichen
    Verbraucherschutz und Veterinarmedizin, Berlin, Germany

    Professor J. Jacob, Biochemisches Institut für Umweltcarcinogene,
    Grosshausdorf, Germany

    Dr J Kielhorn, Fraunhofer Institute for Toxicology and Aerosol
    Research, Hanover, Germany

    Dr R.W. Luebke, National Health and Ecology Effects Laboratory, US
    Environmental Protection Agency, Research Triangle Park, NC, USA
     (Joint Rapporteur)

    Mr H. Malcolm, Institute of Terrestrial Ecology, Monks Wood,
    Huntingdon, Cambridgeshire, United Kingdom  (Joint Rapporteur)

    Dr I. Mangelsdorf, Fraunhofer Institute for Toxicology and Aerosol
    Research, Hanover, Germany

    Dr E. Menichini, Istituto Superiore di Sanita, Rome, Italy

    Dr P. Muller, Ministry of Environment and Energy, Toronto, Ontario,
    Canada

    Dr J.L. Mumford, National Health and Environmental Effects Research
    Laboratory, US Environmental Protection Agency, Research Triangle
    Park, NC, USA

    Dr G. Rosner, Freiburg, Germany

    Dr R. Schoeny, National Center for Environmental Assessment, US
    Environmental Protection Agency, Cincinnati, OH, USA
    Dr T. Sorahan, Institute of Occupational Health, University of
    Birmingham, Birmingham, United Kingdom

    Dr Kimber L. White, Jr, Medical College of Virginia, Virginia
    Commonwealth University, Richmond, VA, USA  (Vice-Chairman)


     Secretariat

    Dr E. Smith, International Programme on Chemical Safety, World Health
    Organization, Geneva, Switzerland

    Dr. M. Castegnaro, International Agency for Research on Cancer, Lyon,
    France


     Assisting the Secretariat

    Dr S. Artelt, Fraunhofer Institute for Toxicology and Aerosol
    Research, Hanover, Germany

    Dr A. Boehncke, Fraunhofer Institute for Toxicology and Aerosol
    Research, Hanover, Germany

    Dr O. Creutzenburg, Fraunhofer Institute for Toxicology and Aerosol
    Research, Hanover, Germany

    1.  SUMMARY

    1.1  Selection of compounds for this monograph

         Polycyclic aromatic hydrocarbons (PAH) constitute a large class
    of compounds, and hundreds of individual substances may be released
    during incomplete combustion or pyrolysis of organic matter, an
    important source of human exposure. Studies of various environmentally
    relevant matrices, such as coal combustion effluents, motor vehicle
    exhaust, used motor lubricating oil, and tobacco smoke, have shown
    that the PAH in these mixtures are mainly responsible for their
    carcinogenic potential.

         PAH occur almost always in mixtures. Because the composition of
    such mixtures is complex and varies with the generating process, all
    mixtures containing PAH could not possible be covered in detail in
    this monograph. Thus, 33 individual compounds (31 parent PAH and two
    alkyl derivatives) were selected for evaluation on the basis of the
    availability of relevant data on toxicological end-points and/or
    exposure (Table 1). Since epidemiological studies, which are essential
    for risk assessment, were available only for mixtures, however,
    Sections 8 and 10 present the results of studies of mixtures of PAH,
    in contrast to the rest of the monograph.

         Numerous papers and reviews have been published on the
    occurrence, distribution, and transformation of PAH in the environment
    and on their ecotoxicological and toxicological effects. Only
    references from the last 10-15 years are cited in this monograph,
    unless no other information was available; reviews are cited for older
    studies and for further information.

    1.2  Identity, physical and chemical properties, and analytical
    methods

         The term 'polycyclic aromatic hydrocarbons' commonly refers to a
    large class of organic compounds containing two or more fused aromatic
    rings made up of carbon and hydrogen atoms. At ambient temperatures,
    PAH are solids. The general characteristics common to the class are
    high melting- and boiling-points, low vapour pressure, and very low
    water solubility which tends to decrease with increasing molecular
    mass. PAH are soluble in many organic solvents and are highly
    lipophilic. They are chemically rather inert. Reactions that are of
    interest with respect to their environmental fate and possible sources
    of loss during atmospheric sampling are photodecomposition and
    reactions with nitrogen oxides, nitric acid, sulfur oxides, sulfuric
    acid, ozone, and hydroxyl radicals.

         Ambient air is sampled by collecting suspended particulate matter
    on glass-fibre, polytetrafluoroethylene, or quartz-fibre filters by
    means of high-volume or passive samplers. Vapour-phase PAH, which
    might volatilize from filters during sampling, are commonly trapped by
    adsorption on polyurethane foam. The sampling step is by far the most
    important source of variability in results.


        Table 1. Polycyclic aromatic hydrocarbons evaluated in this monograph

                                                                                                                         

    Common name                   CAS name                             Synonyma                       CAS Registry No.
                                                                                                                         

    Acenaphthylene                Acenaphthylene                                                      91-20-3
    Acenaphthene                  Acenaphthylene, 1,2-dihydro-                                        208-96-8
    Anthanthrene                  Dibenzo[def,mno]chrysene                                            191-26-4
    Anthracene                    Anthracene                                                          120-12-7
    Benz[a]anthracene             Benz[a]anthracene                    1,2-Benzanthracene,            56-55-3
                                                                       tetraphene
    Benzo[a]fluorene              11 H-Benzo[a]fluorene                1,2-Benzofluorene              238-84-6
    Benzo[b]fluorene              11 H-Benzo[b]fluorene                2,3-Benzofluorene              243-17-4
    Benzo[b]fluoranthene          Benz[e]acephenanthrylene             3,4-Benzofluoranthene          205-99-2
    Benzo[ghi]fluoranthene        Benzo[ghi]fluoranthene               2,13-Benzofluoranthene         203-12-3
    Benzo[j]fluoranthene          Benzo[j]fluoranthene                 10,11-Benzofluoranthene        205-82-3
    Benzo[k]fluoranthene          Benzo[k]fluoranthene                 11,12-Benzofluoranthene        207-08-9
    Benzo[ghi]perylene            Benzo[ghi]perylene                   1,12-Benzoperylene             191-24-2
    Benzo[c]phenanthrene          Benzo[c]phenanthrene                 3,4-Benzophenanthrene          195-19-7
    Benzo[a]pyrene                Benzo[a]pyrene                       3,4-Benzopyreneb               50-32-8
    Benzo[e]pyrene                Benzo[e]pyrene                       1,2-Benzopyrene                192-97-2
    Chrysene                      Chrysene                             1,2-Benzophenanthrene          218-01-9
    Coronene                      Coronene                             Hexabenzobenzene               191-07-1
    Cyclopenta[cd]pyrene          Cyclopenta[cd]pyrene                 Cyclopenteno[cd]pyrene         27208-37-3
    Dibenz[a,h]anthracene         Dibenz[a,h]anthracene                1,2:5,6-Dibenzanthracene       53-70-3
    Dibenzo[a,e]pyrene            Naphtho[1,2,3,4-def]chrysene         1,2:4,5-Dibenzopyrene          192-65-4
    Dibenzo[a,h]pyrene            Dibenzo[b,def]chrysene               3,4:8,9-Dibenzopyrene          189-64-0
    Dibenzo[a,i]pyrene            Benzo[rst]pentaphene                 3,4:9,10-Dibenzopyrene         189-55-9
    Dibenzo[a,l]pyrene            Dibenzo[def,p]chrysene               1,2:3,4-Dibenzopyrene          191-30-0
    Fluoranthene                  Fluoranthene                                                        206-44-0
    Fluorene                      9H-Fluorene                                                         86-73-7
    Indeno[1,2,3-cd]pyrene        Indeno[1,2,3-cd]-pyrene              2,3-o-Phenylenpyrene           193-39-5
    5-Methylchrysene              Chrysene, 5-methyl-                                                 3697-24-3
    1-Methylphenanthrene          Phenanthrene, 1-methyl-                                             832-69-9

    Table 1. (continued)

                                                                                                                         

    Common name                   CAS name                             Synonyma                       CAS Registry No.
                                                                                                                         

    Naphthalene                   Naphthalene                                                         91-20-3
    Perylene                      Perylene                             peri-Dinaphthalene             198-55-0
    Phenanthrene                  Phenanthrene                                                        85-01-8
    Pyrene                        Pyrene                               Benzo[def]phenanthrene         129-00-0
    Triphenylene                  Triphenylene                         9,10-Benzophenanthrene         217-59-4
                                                                                                                         

    Extensive lists of synonyms have been imported by the IARC (1983) and Loening & Merritt (1990).
    a Common synonym appearing in the literature
    b Also reported as benzo[def]chrysene


         Air is sampled at the workplace at low flow rates; particles are
    collected on glass-fibre or polytetrafluoroethylene filters and
    vapours on Amberlite XAD-2 resin. Devices for sampling stack gases are
    composed of a glass-fibre or quartz-fibre filter in front of a cooler
    to collect condensable matter and an adsorbent (generally XAD-2)
    cartridge. Vehicle exhausts are sampled under laboratory conditions,
    with standard driving cycles simulating on-road conditions. Emissions
    are collected either undiluted or after dilution with filtered cold
    air.

         Many extraction and purification techniques have been described.
    Depending on the matrix, PAH are extracted from samples with a Soxhlet
    apparatus, ultrasonically, by liquid-liquid partition, or, after
    sample dissolution or alkaline digestion, with a selective solvent.
    Supercritical fluid extraction from various environmental solids has
    also been used. The efficiency of extraction depends heavily on the
    solvent used, and many of the solvents commonly used in the past were
    not appropriate. Extracted samples are usually purified by column
    chromatography, particularly on alumina, silica gel, or Sephadex LH-20
    but also by thin-layer chromatography.

         Identification and quantification are routinely performed by gas
    chromatography with flame ionization detection or by high-performance
    liquid chromatography (HPLC) with ultraviolet and fluorescence
    detection, generally in series. In gas chromatography, fused silica
    capillary columns are used, with polysiloxanes (SE-54 and SE-52) as
    stationary phases; silica-C18 columns are commonly used in HPLC. A
    mass spectrometric detector is often coupled to a gas chromatograph in
    order to confirm the identity of peaks.

         The choice of PAH to be determined depends on the purpose of the
    measurement, e.g. for health-orientated or ecotoxicological studies or
    to investigate sources. Testing for different sets of compounds may be
    required or recommended at national and international levels.

    1.3  Sources of human and environmental exposure

         Little information is available on the production and processing
    of PAH, but it is probable that only small amounts of PAH are released
    as a direct result of these activities. The PAH found principally are
    used as intermediates in the production of polyvinylchloride and
    plasticizers (naphthalene), pigments (acenaphthene, pyrene), dyes
    (anthracene, fluoranthene), and pesticides (phenanthrene).

         The largest emissions of PAH result from incomplete combustion of
    organic materials during industrial processes and other human
    activities, including:

    -    processing of coal, crude oil, and natural gas, including coal
         coking, coal conversion, petroleum refining, and production of
         carbon blacks, creosote, coal-tar, and bitumen;
    -    aluminium, iron and steel production in plants and foundries;
    -    heating in power plants and residences and cooking;
    -    combustion of refuse;
    -    motor vehicle traffic; and
    -    environmental tobacco smoke.

         PAH, especially these of higher molecular mass, entering the
    environment via the atmosphere are adsorbed onto particulate matter.
    The hydrosphere and geosphere are affected secondarily by wet and dry
    deposition. Creosote-preserved wood is another source of release of
    PAH into the hydrosphere, and deposition of contaminated refuse, like
    sewage sludge and fly ash, contributes to emissions of PAH into the
    geosphere. Little information is available about the passage of PAH
    into the biosphere. PAH occur naturally in peat, lignite, coal, and
    crude oil. Most of the PAH in hard coals are tightly bound within the
    coal structure and cannot be leached out.

         The release of PAH into the environment has been determined by
    identification of a characteristic PAH concentration profile, but this
    has been possible in only a few cases. Benzo [a]pyrene has frequently
    been used as an indicator of PAH, especially in older studies.
    Generally, emissions of PAH are only estimates based on more or less
    reliable data and give only a rough idea of exposure.

         The most important sources of PAH are as follows:

          Coal coking: Airborne emissions of PAH from coal coking in
    Germany have decreased significantly over the last 10 years as a
    result of technical improvements to existing plants, closure of old
    plants, and reduced coke production. Similar situations are assumed to
    exist in western Europe, Japan, and the USA, but no data were
    available.

          Production of aluminium (mainly special coal anodes),  iron, 
    and steel and the binding agents used in moulding sand  in foundries:
    Little information is available.

          Domestic and residential heating: Phenanthrene, fluoranthene,
    pyrene, and chrysene are emitted as major components. The emissions
    from wood stoves are 25-1000 times higher than those from
    charcoal-fired stoves, and in areas where wood burning predominates
    for domestic heating the major portion of airborne PAH may be derived
    from this source, especially in winter. The release of PAH during
    residential heating is thus assumed to be an important source in
    developing countries where biomass is often burnt in relatively simple
    stoves.

          Cooking: PAH may be emitted during incomplete combustion of
    fuels, from cooking oil, and from food being cooked.

          Motor vehicle traffic: The main compounds released from
    petrol-fuelled vehicles are fluoranthene and pyrene, while naphthalene
    and acenaphthene are abundant in the exhaust of diesel-fuelled
    vehicles. Although cyclopenta [cd]-pyrene is emitted at a high rate
    from petrol-fuelled engines, its concentration in diesel exhaust is
    only just above the limit of detection. The emission rates, which
    depend on the substance, the type of vehicle, its engine conditions,
    and the test conditions, range from a few nanograms per kilometre to
    > 1000 mg/km. PAH emissions from vehicle engines are dramatically
    reduced by fitting catalytic converter devices.

          Forest fires: In countries with large forest areas, fires can
    make an imprtant contribution to PAH emissions.

          Coal-fired power plants: PAH released into the atmosphere from
    such plants consist mainly of two- and three-ring compounds. In
    contaminated areas, the PAH levels in ambient air may be higher than
    those in the stack gases.

          Incineration of refuse: The PAH emissions in stack gases from
    this souce in a number of countries were < 10 mg/m3.

    1.4  Environmental transport, distribution, and transformation

         Several distribution and transformation processes determine the
    fate of both individual PAH and mixtures. Partitioning between water
    and air, between water and sediment, and between water and biota are
    the most important of the distribution processes.

         As PAH are hydrophobic with low solubility in water, their
    affinity for the aquatic phase is very low; however, in spite of the
    fact that most PAH are released into the environment via the
    atmosphere, considerable concentrations are also found in the
    hydrosphere because of their low Henry's law constants. As the
    affinity of PAH for organic phases is greater than that for water,
    their partition coefficients between organic solvents, such as
    octanol, and water are high. Their affinity for organic fractions in
    sediment, soil, and biota is also high, and PAH thus accumulate in
    organisms in water and sediments and in their food. The relative
    importance of uptake from food and from water is not clear. In
     Daphnia and molluscs, accumulation of PAH from water is positively
    correlated with the octanol:water partition coefficient ( Kow). In
    fish and algae that can metabolize PAH, however, the internal
    concentrations of different PAH are not correlated with the  Kow.

         Biomagnification - the increase in the concentration of a
    substance in animals in successive trophic levels of food chains - of
    PAH has not been observed in aquatic systems and would not be expected
    to occur, because most organisms have a high biotransformation
    potential for PAH. Organisms at higher trophic levels in food chains
    show the highest potential biotransformation.

         PAH are degraded by photodegradation, biodegradation by
    microorganisms, and metabolism in higher biota. Although the last
    route of transformation is of minor importance for the overall fate of
    PAH in the environment, it is an important pathway for the biota,
    since carcinogenic metabolites may be formed. As PAH are chemically
    stable, with no reactive groups, hydrolysis plays no role in their
    degradation. Few standard tests for the biodegradation of PAH are
    available  In general, they are biodegraded under aerobic conditions,
    the biodegradation rate decreasing drastically with the number of
    aromatic rings. Under anaerobic conditions, degradation is much
    slower.

         PAH are photooxidized in air and water in the presence of
    sensitizing radicals like OH, NO3, and O3. Under laboratory
    conditions, the half-life of the reaction with airborne OH radicals is
    about one day, whereas reactions with NO3 and O3 usually have much
    lower velocity constants. The adsorption of high-molecular-mass PAH
    onto carbonaceous particles in the environment should stabilize the
    reaction with OH radicals. The reaction of two- to four-ring PAH,
    which occur mainly in the vapour phase, with NO3 leads to nitro-PAH,
    which are known mutagens. The photooxidation of some PAH in water
    seems to be more rapid than in air. Calculations based on
    physicochemical and degradation parameters indicate that PAH with four
    or more aromatic rings persist in the environment.

    1.5  Environmental levels and human exposure

         PAH are ubiquitous in the environment, and various individual PAH
    have been detected in different compartments in numerous studies.

    1.5.1  Air

         The levels of individual PAH tend to be higher in winter than in
    summer by at least one order of magnitude. The predominant source
    during winter is residential heating, while that during summer is
    urban motor vehicle traffic. Average concentrations of 1-30 ng/m3 of
    individual PAH were detected in the ambient air of various urban
    areas. In large cities with heavy motor vehicle traffic and extensive
    use of biomass fuel, such as Calcutta, levels of up to 200 ng/m3 of
    individual PAH were found. Concentrations of 1-50 ng/m3 were detected
    in road tunnels. Cyclopenta [cd]pyrene and pyrene were present at
    concentrations up to 100 ng/m3. In a subway station, PAH
    concentrations of up to 20 ng/m3 were measured. Near industrial
    sources, the average concentrations of individual PAH ranged from 1 to
    10 ng/m3. Phenanthrene was present at up to a maximum of about 310
    ng/m3.

         The background values of PAH are at least one or two orders of
    magnitude lower than those near sources like motor vehicle traffic.
    For example, the levels at 1100 m ranged from 0.004 to 0.03 ng/m3.

    1.5.2  Surface water and precipitation

         Most of the PAH in water are believed to result from urban
    runoff, from atmospheric fallout (smaller particles), and from asphalt
    abrasion (larger particles). The major source of PAH varies, however,
    in a given body of water. In general, most samples of surface water
    contain individual PAH at levels of up to 50 ng/litre, but highly
    polluted rivers had concentrations of up to 6000 ng/litre. The PAH
    levels in groundwater are within the range 0.02-1.8 ng/litre, and
    drinking-water samples contain concentrations of the same order of
    magnitude. Major sources of PAH in drinking-water are asphalt-lined
    storage tanks and delivery pipes.

         The levels of individual PAH in rainwater ranged from 10 to 200
    ng/litre, whereas levels of up to 1000 ng/litre have been detected in
    snow and fog.

    1.5.3  Sediment

         The concentrations of individual PAH in sediment were generally
    one order of magnitude higher than those in precipitation.

    1.5.4  Soil

         The main sources of PAH in soil are atmospheric deposition,
    carbonization of plant material, and deposition from sewage and
    particulate waste. The extent of pollution of soil depends on factors
    such as its cultivation, its porosity, and its content of humic
    substances.

         Near industrial sources, individual PAH levels of up to 1 g/kg
    soil have been found. The concentrations in soil from other sources,
    such as automobile exhaust, are in the range 2-5 mg/kg. In unpolluted
    areas, the PAH levels were 5-100 µg/kg soil.

    1.5.5  Food

         Raw food does not normally contain high levels of PAH, but they
    are formed by processing, roasting, baking, or frying. Vegetables may
    be contaminated by the deposition of airborne particles or by growth
    in contaminated soil. The levels of individual PAH in meat, fish,
    dairy products, vegetables and fruits, cereals and their products,
    sweets, beverages, and animal and vegetable fats and oils were within
    the range 0.01-10 µg/kg. Concentrations of over 100 µg/kg have been
    detected in smoked meat and up to 86 µg/kg in smoked fish; smoked
    cereals contained up to 160 µg/kg. Coconut oil contained up to 460
    µg/kg. The levels in human breast milk were 0.003-0.03 µg/kg.

    1.5.6  Aquatic organisms

         Marine organisms are known to adsorb and accumulate PAH from
    water. The degree of contamination is related to the extent of
    industrial and urban development and shipping movements. PAH
    concentrations of up to 7 mg/kg have been detected in aquatic
    organisms living near industrial effluents, and the average levels of
    PAH in aquatic animals sampled at contaminated sites were 10-500
    µg/kg, although levels of up to 5 mg/kg were also detected.

         The average levels of PAH in aquatic animals sampled at various
    sites with unspecified sources of PAH were 1-100 µg/kg, but
    concentrations of up to 1 mg/kg were found, for example, in lobsters
    in Canada.

    1.5.7  Terrestrial organisms

         The concentrations of PAH in insects ranged from 730 to 5500
    µg/kg. The PAH content of earthworm faeces depends significantly on
    the location: those in a highly industrialized region in eastern
    Germany contained benzo [a]pyrene at concentrations up to 2 mg/kg.

    1.5.8  General population

         The main sources of nonoccupational exposure are: polluted
    ambient air, smoke from open fireplaces and cooking, environmental
    tobacco smoke, contaminated food and drinking-water, and the use of
    PAH-contaminated products. PAH can be found in indoor air as a result
    of residential heating and environmental tobacco smoke at average
    concentrations of 1-100 ng/m3, with a maximum of 2300 ng/m3.

         The intake of individual PAH from food has been estimated to be
    0.10-10 µg/day per person. The total daily intake of benzo [a]pyrene
    from drinking-water was estimated to be 0.0002 µg/person. Cereals and
    cereal products are the main contributors to the intake of PAH from
    food because they are a major component of the total diet.

    1.5.9  Occupational exposure

         Near a coke-oven battery, the levels of benzo [a]pyrene ranged
    from < 0.1 to 100-200 µg/m3, with a maximum of about 400 µg/m3. In
    modern coal gasification systems, the concentration of PAH is usually
    < 1 µg/m3 with a maximum of 30 µg/m3. Personal samples taken from
    operators of petroleum refinery equipment showed exposure to 2.6-470
    µg/m3. In samples of air taken near bitumen processing plants at
    refineries, the total PAH levels were 0.004-50 µg/m3. Near road
    paving operations, the total PAH concentrations in personal air
    samples were up to 190 µg/m3, and the mean value in area air samples
    was 0.13 µg/m3. The PAH levels in personal air samples taken at an
    aluminium smelter were 0.05-9.6 µg/m3, but urine samples of workers
    at an aluminium plant contained very low levels. Area air samples
    contained PAH concentrations of up to 5 µg/m3 in one German foundry,

    3-40 µg/m3 at iron mines and 4-530 µg/m3 at copper mines. The
    concentrations of PAH in cooking fumes in a food factory ranged from
    0.07 to 26 µg/m3.

    1.6  Kinetics and metabolism

         PAH are absorbed through the pulmonary tract, the
    gastrointestinal tract, and the skin. The rate of absorption from the
    lungs depends on the type of PAH, the size of the particles on which
    they are absorbed, and the composition of the adsorbent. PAH adsorbed
    onto particulate matter are cleared from the lungs more slowly than
    free hydrocarbons. Absorption from the gastrointestinal tract occurs
    rapidly in rodents, but metabolites return to the intestine via
    biliary excretion. Studies with 32P-postlabelling of percutaneous
    absorption of mixtures of PAH in rodents showed that components of the
    mixtures reach the lungs, where they become bound to DNA. The rate of
    percutaneous absorption in mice according to the compound.

         PAH are widely distributed throughout the organism after
    administration by any route and are found in almost all internal
    organs, but particularly those rich in lipids. Intravenously injected
    PAH are cleared rapidly from the bloodstream of rodents but can cross
    the placental barrier and have been detected in fetal tissues.

         The metabolism of PAH is complex. In general, parent compounds
    are converted via intermediate epoxides to phenols, diols, and
    tetrols, which can themselves be conjugated with sulfuric or
    glucuronic acids or with glutathione. Most metabolism results in
    detoxification, but some PAH are activated to DNA-binding species,
    principally diol epoxides, which can initiate tumours.

         PAH metabolites and their conjugates are excreted via the urine
    and faeces, but conjugates excreted in the bile can be hydrolysed by
    enzymes of the gut flora and reabsorbed. It can be inferred from the
    available information on the total human body burden that PAH do not
    persist in the body and that turnover is rapid. This inference
    excludes those PAH moieties that become covalently bound to tissue
    constituents, in particular nucleic acids, and are not removed by
    repair.

    1.7  Effects on laboratory mammals and  in vitro

         The acute toxicity of PAH appears to be moderate to low. The
    well-characterized PAH, naphthalene, showed oral and intravenous LD50
    values of 100-500 mg/kg body weight (bw) in mice and a mean oral LD50
    of 2700 mg/kg bw in rats. The values for other PAH are similar. Single
    high doses of naphthalene induced bronchiolar necrosis in mice, rats,
    and hamsters.

         Short-term studies showed adverse haematological effects,
    expressed as myelotoxicity with benzo [a]pyrene, haemolymphatic
    changes with dibenz [a,h]-anthracene, and anaemia with naphthalene;
    however, in a seven-day study by oral and intraperitoneal
    administration in mice, tolerance to the effect of naphthalene was
    observed.

         Systemic effects caused by long-term treatment with PAH have been
    described only rarely, because the end-point of most studies has been
    carcinogenicity. Significant toxic effects are manifested at doses at
    which carcinogenic responses are also triggered.

         In studies of adverse effects on the skin after dermal
    application, non- or weakly carcinogenic PAH such as perylene,
    benzo [e]pyrene, phenanthrene, pyrene, anthracene, acenaphthalene,
    fluorene, and fluoranthene were inactive, whereas carcinogenic
    compounds such as benz [a]anthracene, dibenz [a,h]-anthracene, and
    benzo [a]pyrene caused hyperkeratosis. Anthracene and naphthalene
    vapours caused mild eye irritation. Benzo [a]pyrene induced contact
    hypersensitivity in guinea-pigs and mice.

         Benz [a]anthracene, benzo [a]pyrene, dibenz [a,h]anthracene,
    and naphthalene were embrotoxic to mice and rats. Benzo [a]pyrene
    also had teratogenic and reproductive effects. Intensive efforts have
    been made to elucidate the genetic basis of the embryotoxic effect of
    benzo [a]pyrene. Fetal death and malformations are observed only if
    the cytochrome P450 monooxy-genase system is inducible, either in the
    mother (with placental permigration) or in the embryo. Not all of the
    effects observed can be explained by genetic predisposition, however:
    in mice and rabbits, benzo [a]pyrene had transplacental carcinogenic
    activity, resulting in pulmonary adenomas and skin papillomas in the
    progeny. Reduced fertility and oocyte destruction were also observed.

         PAH have also been studied extensively in assays for genotoxicity
    and cell transformation; most of the 33 PAH covered in this monograph
    are genotoxic or probably genotoxic. The only compounds for which
    negative results were found in all assays were anthracene, fluorene,
    and naphthalene. Owing to inconsistent results, phenanthrene and
    pyrene could not be reliably classified for genotoxicity.

         Comprehensive work on the carcinogenicity of PAH shows that 17 of
    the 33 studied are, or are suspected of being, carcinogenic (Table 2).
    The best-characterized PAH is benzo [a]pyrene, which has been studied
    by all current methods in seven species. PAH that have been the
    subject of 12 or more studies are anthanthrene, anthracene,
    benz [a]anthracene, chrysene, dibenz [a,h]-anthracene,
    dibenzo [a,i]pyrene, 5-methylchrysene, phenanthrene, and pyrene.

         Special studies of the phototoxicity, immunotoxicity, and
    hepatotoxicity of PAH are supplemented by reports on the ocular
    toxicity of naphthalene. Anthracene, benzo [a]pyrene, and some other
    PAH were phototoxic to mammalian skin and in cell cultures  in vitro 
    when applied with ultraviolet radiation. PAH have generally been

    reported to have immunosuppressive effects. After intraperitoneal
    treatment of mice with benzo [a]pyrene, immunological parameters were
    strongly suppressed in the progeny for up to 18 months. Increased
    liver regeneration and an increase in liver weight have also been
    observed. The effect of naphthalene in inducing formation of cataracts
    in the rodent eye has been attributed to the inducibility of the
    cytochrome P450 system in studies in which genetically different mouse
    strains were used.

         Theoretical models to predict the carcinogenic potency of PAH
    from their structures, based on a large amount of experimental work,
    were presented as early as the 1930s. The first model was based on the
    high chemical reactivity of certain double bonds (the K-region
    theory). A later systematic approach was based on the chemical
    synthesis of possible metabolites and their mutagenic activity. This
    'bay region' theory proposes that epoxides adjacent to a bay region
    yield highly stabilized carbonium ions. Other theoretical approaches
    are the 'di-region theory' and the 'radical cation potential theory'.

         Many individual PAH are carcinogenic to animals and may be
    carcinogenic to humans, and exposure to several PAH-containing
    mixtures has been shown to increase the incidence of cancer in human
    populations. There is concern that those PAH found to be carcinogenic
    in experimental animals are likely to be carcinogenic in humans. PAH
    produce tumours both at the site of contact and at distant sites. The
    carcinogenic potency of PAH may vary with the route of exposure.
    Various approaches to assessing the risk associated with exposure to
    PAH, singly and in mixtures, have been proposed. No one approach is
    endorsed in this monograph; however, the data requirements,
    assumptions, applicability, and other features of three quantitative
    risk assessment processes that have been validated to some degree are
    described.

    1.8  Effects on humans

         Because of the complex profile of PAH in the environment and in
    workplaces, human exposure to pure, individual PAH has been limited to
    scientific experiments with volunteers, except in the case of
    naphthalene which is used as a moth-repellant for clothing.

         After dermal application, anthracene, fluoranthene, and
    phenanthrene induced specific skin reactions, and benzo [a]pyrene
    induced reversible, regressive verrucae which were classified as
    neoplastic proliferations. The systemic effects of naphthalene are
    known from numerous cases of accidental intake, particularly by
    children. The lethal oral dose is 5000-15 000 mg for adults and 2000
    mg taken over two days for a child. The typical effect after dermal or
    oral exposure is acute haemolytic anaemia, which can also affect
    fetuses transplacentally.

    Table 2. Summary of results of tests for genotoxicity and
    carcinogenicity for the 33 polycyclic aromatic hydrocarbons studies

                                                                       

    Compound                          Genotoxicity    Carcinogenicity
                                                                       

    Acenaphthene                      (?)             (?)
    Acenaphthylene                    (?)             No studies
    Anthanthrene                      (+)             +
    Anthracene                        -               -
    Benz[a]anthracene                 +               +
    Benzo[b]fluoranthene              +               +
    Benzo[j]fluoranthene              +               +
    Benzo[ghi]fluoranthene            (+)             (-)
    Benzo[k]fluoranthene              +               +
    Benzo[a]fluorene                  (?)             (?)
    Benzo[b]fluorene                  (?)             (?)
    Benzo[ghi]perylene                +               -
    Benzo[c]phenanthrene              (+)             +
    Benzo[a]pyrene                    +               +
    Benzo[e]pyrene                    +               ?
    Chrysene                          +               +
    Coronene                          (+)             (?)
    Cyclopenta[cd]pyrene              +               +
    Dibenz[a,h]anthracene             +               +
    Dibenzo[a,e]pyrene                +               +
    Dibenzo[a,h]pyrene                (+)             +
    Dibenzo[a,i]pyrene                +               +
    Dibenzo[a,l]pyrene                (+)             +
    Fluoranthene                      +               (+)
    Fluorene                          -               -
    Indeno[1,2,3-cd]pyrene            +               +
    5-Methylchrysene                  +               +
    1-Methylphenanthrene              +               (-)
    Naphthalene                       -               (?)
    Perylene                          +               (-)
    Phenanthrene                      (?)             (?)
    Pyrene                            (?)             (?)
    Triphenylene                      +               (-)
                                                                       

    +, positive; -, negative; ?, questionable
    Parentheses, result derived from small database

         Tobacco smoking is the most important single factor in the
    induction of lung tumours and also for increased incidences of tumours
    of the urinary bladder, renal pelvis, mouth, pharynx, larynx, and
    oesophagus. The contribution of PAH in the diet to the development of
    human cancer is not considered to be high. In highly industrialized
    areas, increased body burdens of PAH due to polluted ambient air were
    detected. Psoriasis patients treated with coal-tar are also exposed to
    PAH.

         Occupational exposure to soot as a cause of scrotal cancer was
    noted for the first time in 1775. Later, occupational exposure to tars
    and paraffins was reported to induce skin cancer. The lung is now the
    main site of PAH-induced cancer, whereas skin tumours have become more
    rare because of better personal hygiene.

         Epidemiological studies have been conducted of workers exposed at
    coke ovens during coal coking and coal gasification, at asphalt works,
    foundries, and aluminium smelters, and to diesel exhaust. Increased
    lung tumour rates due to exposure to PAH have been found in coke-oven
    workers, asphalt workers, and workers in Söderberg potrooms of
    aluminium reduction plants. The highest risk was found for coke-oven
    workers, with a standardized mortality ratio of 195. Dose-response
    relationships were found in several studies. In aluminium plants, not
    only urinary bladder cancer but also asthma-like symptoms, lung
    function abnormalities, and chronic bronchitis have been observed.
    Coke-oven workers were found to have decreased serum immunoglobulin
    levels and decreased immune function. Occupational exposure to
    naphthalene for five years was reported to have caused cataract.

         Several methods have been developed to assess internal exposure
    to PAH. In most of the studies, PAH metabolites such as urinary
    thioethers, 1-naphthol, b-naphthylamine, hydroxyphenanthrenes, and
    1-hydroxypyrene were measured in urine. The latter has been used
    widely as a biological index of exposure.

         The genotoxic effects of PAH have been determined by testing for
    mutagenicity in urine and faeces and for the presence of micronuclei,
    chromosomal aberrations, and sister chromatid exchange in peripheral
    blood lymphocytes. In addition, adducts of benzo [a]pyrene with DNA
    in peripheral lymphocytes and other tissues and with proteins like
    albumin as well as antibodies to DNA adducts have been measured.

         1-Hydroxypyrene in urine and DNA adducts in lymphocytes have been
    investigated as markers in several studies. 1-Hydroxpyrene can be
    measured more easily than DNA adducts, there is less variation between
    individuals, and lower levels of exposure can be detected. Both
    markers have been used to assess human exposure in various
    environments. Increased 1-hydroxpyrene excretion or DNA adducts were
    found at various workplaces in coke plants, aluminum manufacturing,
    wood impregnation plants, foundries, and asphalt works. The highest
    exposures were those of coke-oven workers and workers impregnating
    wood with creosote, who took up 95% of total of PAH through the skin,
    in contrast to the general population in whom uptake via food and
    tobacco smoking predominate.

         Estimates of the risk associated with exposure to PAH and PAH
    mixtures are based on estimates of exposure and the results of
    epidemiological studies. Data for coke-oven workers resulted in a
    relative risk for lung cancer of 15.7. On this basis, the risk of the
    general population for developing lung cancer over a lifetime has been
    calculated to be 10-4 to 10-5 per ng of benzo [a]pyrene per m3 air.

    In other words, about one person in 10 000 or 100 000 would be
    expected to develop lung cancer in his or her lifetime as a result of
    exposure to benzo [a]pyrene in air.

    1.9  Effects on other organisms in the laboratory and the field

         PAH are acutely toxic to fish and  Daphnia magna in combination
    with absorption of ultraviolet radiation and visible light. Metabolism
    and degradation alter the toxicity of PAH. At low concentrations, PAH
    can stimulate the growth of microorganisms and algae. The most toxic
    PAH for algae are benz [a]anthracene (four-ring), the concentration
    at which given life parameters are reduced by 50% (EC50) being 1-29
    µg/litre, and benzo [a]pyrene (five-ring), with an EC50 of 5-15
    µg/litre. The EC50 values for algae for most three-ring PAH are
    240-940 µg/litre. Naphthalene (two-ring) is the least toxic, with
    EC50 values of 2800-34 000 µg/litre.

         No clear difference in sensitivity was found between different
    taxonomic groups of invertebrates like crustaceans, insects, molluscs,
    polychaetes, and echinoderms. Naphthalene is the least toxic, with
    96-h LC50 values of 100-2300 µg/litre. The 96-h LC50 values for
    three-ring PAH range between < 1 and 3000 µg/litre. Anthracene may be
    more toxic than the other three-ring PAH, with 24-h LC50 values
    between < 1 and 260 µg/litre. The 96-h LC50 values for four-, five-,
    and six-ring PAH are 0.2-1200 µg/litre. Acute toxicity (LC50) in fish
    was seen at concentrations of 110 to > 10 000 µg/litre of
    naphthalene, 30-4000 µg/litre of three-ring PAH (anthracene, 2.8-360
    µg/litre), and  0.7-26 µg/litre for four- or five-ring PAH.

         Contamination of sediments with PAH at concentrations of 250
    mg/kg was associated with hepatic tumours in free-living fish. Tumours
    have also been induced in fish exposed in the laboratory. Exposure of
    fish to certain PAH can also cause physiological changes and affect
    their growth, reproduction, swimming performance, and respiration.

    2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL METHODS

    2.1  Identity

         The name 'polycyclic aromatic hydrocarbons' (PAH) commonly refers
    to a large class of organic compounds containing two or more fused
    aromatic rings, even though in a broad sense non-fused ring systems
    should be included. In particular, the term 'PAH' refers to compounds
    containing only carbon and hydrogen atoms (i.e. unsubstituted parent
    PAH and their alkyl-substituted derivatives), whereas the more general
    term 'polycyclic aromatic compounds' also includes the functional
    derivatives (e.g. nitro- and hydroxy-PAH) and the heterocyclic
    analogues, which contain one or more hetero atoms in the aromatic
    structure (aza-, oxa-, and thia-arenes). Some authors refer to
    polycyclic aromatic compounds as 'polycyclic organic matter', and the
    term 'polynuclear' is frequently used for 'polycyclic', as in
    'polynuclear aromatic compounds'.

         More than 100 PAH have been identified in atmospheric particulate
    matter (Lao et al., 1973; Lee et al., 1976a) and in emissions from
    coal-fired residential furnaces (Grimmer et al., 1985), and about 200
    have been found in tobacco smoke (Lee et al., 1976b, 1981).

         The selection of PAH evaluated in this monograph is discussed in
    Section 1. The nomenclature, common names, synonyms, and abbreviations
    used are given in Table 1 in that section. The structural formulae are
    shown in Figure 1. Molecular formulae, relative molecular masses, and
    CAS Registry numbers are given in Table 3.

    2.1.1  Technical products

         Technical-grade naphthalene, also known as naphthalin and tar
    camphor, has a minimum purity of 95%. The impurities reported are
    benzo [b]thiophene (thianaphthene) when naphthalene is obtained from
    coal-tar and methylindenes when it is derived from petroleum (Society
    of German Chemists, 1989).

         Commercially available anthracene, also known by the trade name
    Tetra Olive N2G (IARC, 1983), has a purity of 90-95% (Hawley, 1987).
    The impurities reported are phenanthrene, chrysene, carbazole (Hawley,
    1987), tetracene, naphthacene (Budavari et al., 1989), and pyridine at
    a maximum of 0.2% (IARC, 1983). The following purities were reported
    for other technical-grade products: acenaphthene, 95-99%;
    fluoranthene, > 95% (Griesbaum et al., 1989); fluorene, about 95%;
    phenanthrene, 90%; and pyrene, about 95% (Franck & Stadelhofer, 1987).

         The other compounds are generally produced as chemical
    intermediates and for research purposes (see also sections 3.2.2 and
    3.2.3). Reference materials certified to be of geater than 99% purity
    are available for 22 of the PAH considered (Community Bureau of
    Reference, 1992); the remaining compounds are commercially available
    as chemical standards, with a purity of 99% or more.

    Table 3. Identity of polycyclic aromatic hydrocarbons covered in this
    volume ranked according to molecular mass

                                                                            

    Compound                     Molecular       Relative        CAS
                                 formula         molecular       Registry
                                                 mass            No.
                                                                            

    Naphthalene                  C10H8           128.2           91-20-3
    Acenaphthylene               C12H8           152.2           208-96-8
    Acenaphthene                 C12H10          154.2           83-32-9
    Fluorene                     C13H10          166.2           86-73-7
    Anthracene                   C14H10          178.2           120-12-7
    Phenanthrene                 C14H10          178.2           85-01-8
    1-Methylphenanthrene         C15H12          192.3           832-69-9
    Fluoranthene                 C16H10          202.3           206-44-0
    Pyrene                       C16H10          202.3           129-00-0
    Benzo[a]fluorene             C17H12          216.3           238-84-6
    Benzo[b]fluorene             C17H12          216.3           243-17-4
    Benzo[ghi]fluoranthene       C18H10          226.3           203-12-3
    Cyclopenta[cd]pyrene         C18H10          226.3           2720837-3
    Benz[a]anthracene            C18H12          228.3           56-55-3
    Benzo[c]phenanthrene         C18H12          228.3           195-19-7
    Chrysene                     C18H12          228.3           218-01-9
    Triiphenylene                C18H12          228.3           217-59-4
    5-Methylchrysene             C19H14          242.3           3697-24-3
    Benzo[b]fluoranthene         C20H12          252.3           205-99-2
    Benzo[j]fluoranthene         C20H12          252.3           205-82-3
    Benzo[k]fluoranthene         C20H12          252.3           207-08-9
    Benzo[a]pyrene               C20H12          252.3           50-32-8
    Benzo[e]pyrene               C20H12          252.3           192-97-2
    Perylene                     C20H12          252.3           198-55-0
    Anthanthrene                 C22H12          276.3           191-26-4
    Benzo[ghi]perylene           C22H12          276.3           191-24-2
    Indeno[1,2,3-cd]pyrene       C22H12          276.3           193-39-5
    Dibenz[a,h]anthracene        C22H14          278.4           53-70-3
    Coronene                     C24H14          300.4           191-07-1
    Dibenzo[a,e]pyrene           C24H14          302.4           192-65-4
    Dibenzo[a,h]pyrene           C24H14          302.4           189-64-0
    Dibenzo[a,i]pyrene           C24H14          302.4           189-55-9
    Dibenzo[a,l]pyrene           C24H14          302.4           191-30-0
                                                                            

    PAH considered (Community Bureau of Reference, 1992); the remaining
    compounds are commercially available as chemical standards, with a purity of
    99% or more.

    FIGURE 1

    FIGURE 1a

    2.2  Physical and chemical properties

         Physical and chemical properties relevant to the toxicological
    and ecotoxicological evaluation of the PAH are summarized in Table 4.
    It should be kept in mind that the values for any one parameter may be
    derived from different sources, with different methods of measurement
    or calculation, so that individual values cannot be compared directly
    unless the original sources are consulted. In particular, the vapour
    pressures reported in the literature for the same PAH vary by up to
    several orders of magnitude (Mackay & Shiu, 1981; Lane, 1989).
    Variations are also seen in the reported solubility in water of
    various PAH, although the values are generally within one order of
    magnitude (National Research Council Canada, 1983). Flash-points were
    available only for three compounds with high molecular mass (for
    naphthalene, 78.9°C by the open-cup method and 87.8°C by the closed-cup
    method; anthracene, 121°C by the closed-cup method; and phenanthrene,
    171°C by the open-cup method). Explosion limits were available only
    for naphthalene (0.9-5.9 vol %) and ananthrene (0.6 vol %) (Lewis,
    1992). Vapour density (air = 1) was 4.42 for naphthalene (IARC,
    1973), 5.32 for acenaphthene, 6.15 for anthracene (Lewis, 1992), 6.15
    for phenanthrene, and 8.7 for benzo[a]pyrene (National Institute for
    Occupational Safety and Health and Occupational Safety and Health
    Administration, 1981).

         The physical and chemical properties are largely determined by
    the conjugated alpha-electron systems, which vary fairly regularly
    with the number of rings and molecular mass, giving rise to a more or
    less wide range of values for each parameter within the whole class.
    At room temperature, all PAH are solids. The general characteristics
    common to the class are high melting- and boiling-points, low vapour
    pressure, and very low solubility in water. PAH are soluble in many
    organic solvents (IARC, 1983; Agency for Toxic Substances and Disease
    Registry, 1990; Lide, 1991) and are highly lipophilic.

         Vapour pressure tends to decrease with increasing molecular mass,
    varying by more than 10 orders of magnitude. This characteristic
    affects the adsorption of individual PAH onto particulate matter in
    the atmosphere and their retention on particulate matter during
    sampling on filters (Thrane & Mikalsen, 1981). Vapour pressure
    increases markedly with ambient temperature (Murray et al., 1974),
    which additionally affects the distribution coefficients between
    gaseous and particulate phases (Lane, 1989). Solubility in water tends
    to decreases with increasing molecular mass. For additional
    information, refer to section 4.1.

         PAH are chemically inert compounds (see also section 4.4). When
    they react, they undergo two types of reaction: electrophilic
    substitution and addition. As the latter destroys the aromatic
    character of the benzene ring that is affected, PAH tend to form
    derivatives by the former reaction; addition is often followed by
    elimination, resulting in net substitution. The chemical and
    photochemical reactions of PAH in the atmosphere have been reviewed


        Table 4. Physical and chemical properties of polycyclic aromatic compounds covered in this monograph, ranked by molecular mass

                                                                                                                                               

    Compound               Colour              Melting-   Boiling-    Vapour          Densityc     n-Octanol:    Solubility in    Henry's law
                                               pointa     point       pressure                     water         water at 25°C    constant at
                                               (°C)       (°C)        (Pa at 25°C)                 partition     (µg/litre)d      25°C (kPa)
                                                                                                   coefficient
                                                                                                   (log Kow)
                                                                                                                                               

    Naphthalene            Whiteb              81         217.9c      10.4g           1.15425 h    3.4j          3.17 x 104       4.89 x 10-2 k

    Acenaphthylene                             92-93                  8.9 x 10-1 g    0.89916/2 h  4.07f                          114 x 10-3 l
    Acenaphthene           Whiteb              95         279h        2.9 x 10-1 g    1.02490/4 h  3.92f         3.93 x 103       1.48 x 10-2 k
    Fluorene               Whitee              115-116    295e        9.0 x 10-2 g    1.2030/4 h   4.18m         1.98 x 103       1.01 x 10-2 n
    Anthracene             Colourlesso         216.4      342e        8.0 x 10-4 g    1.28325/4 h  4.5j          73               7.3 x 10-2 n
    Phenanthrene           Colourlessp         100.5      340h        1.6 x 10-2 g    0.9804 h     4.6j          1.29 x 103       3.98 x 10-3 k
    1-Methylphenanthrene                       123        354-355y                                 5.07s         255 (24°C)t
    Fluoranthene           Pale yellowh        108.8      375h        1.2 x 10-3 g    1.2520/4 h   5.22u         260              6.5 x 10-4
                                                                                                                                  (20 °C)w
    Pyrene                 Colourlesse         150.4      393h        6.0 x 10-4 g    1.27123/4 h  5.18j         135              1.1 x 10-3 n
    Benzo[a]fluorene       Colourlessx         189-190h   399-400y                                 5.32z         45
    Benzo[b]fluorene       Colourlessx         213.5      401-402y                    1.226aa      5.75z         2.0
    Benzo[ghi]fluoranthene Yellowbb            128.4      432cc                       1.34523 dd
    Cyclopenta[cd]pyrene   Orangex             170        439ee
    Benz[a]anthracene      Colourlessb         160.7      400b        2.8 x 10-5 g    1.226aa      5.61f         14
    Benzo[c]phenanthrene   Colourlessx         66.1                                   1.265ff
    Chrysene               Colourless          253.8      448h        8.4 x 10-5      1.27420/4 e  5.91u         2.0
                           with blue                                  (20°C)gg
                           fluoresenceb
    Triphenylene           Colourlessx         199        425bb                       1.3p          5.45hh        43
    5-Methylchrysene       Colourlessx         117.1      458ii                                                  62 (27°C)jj
    Benzo[b]fluoranthene   Colourlessi         168.3      481kk       6.7 x 10-5                   6.12f         1.2ll            5.1 x 10-5
                                                                      (20°C)gg                                   (20°C)w
    Benzo[j]fluoranthene   Yellowb             165.4      480ee       2.0 x 10-6 l                 6.12mm        2.5nn

    Table 4. (continued)

                                                                                                                                               

    Compound               Colour              Melting-   Boiling-    Vapour          Densityc     n-Octanol:    Solubility in    Henry's law
                                               pointa     point       pressure                     water         water at 25°C    constant at
                                               (°C)       (°C)        (Pa at 25°C)                 partition     (µg/litre)d      25°C (kPa)
                                                                                                   coefficient
                                                                                                   (log Kow)
                                                                                                                                               

    Renzo[k]fluoranthene   Pale yellowh        215.7      480h        1.3 x 10-8                   6.84m         0.76f            4.4 x 10-5
                                                                      (20°C)oo                                                    (20°C)w
    Benzo[a]pyrene         Yellowishe          178.1      496kk       7.3 x 10-7oo    1.351pp      6.50u         3.8              3.4 x 10-5
                                                                                                                                  (20°C)
    Benzo[e]pyrene         Pale yellowx        178.7      493kk       7.4 x 10-7qq                 6.44rr        5.07 (23°C)tt
    Perylene               Yellow to           277.5      503ss                       1.35v        5.3uu         0.4
                           colourlessc
    Anthanthrene           Golden yellowbb     264        547yy                       1.39v
    Benzo[ghi]perylene     Pale yellow-        278.3      545ii       1.4 x 10-8 ww   1.32920 xx   7.10u         0.26             2.7 x 10-5
                           greenbb                                                                                                (20°C)w
    Indeno[1,2,3-cd]pyrene Yellowi             163.6      536yy       1.3 x 10-8                   6.58f         62f              2.9 x 10-5
                                                                      (20°C)gg                                                    (20°C)w
    Dibenz[a,h]anthracene  Colourlessi         266.6      524yy       1.3 x 10-8      1.282i       6.50zz        0.5 (27°C)jj     7 x 10-6 l
                                                                      (20°C)
    Coronene               Yellowh             439        525aaa      2.0 x 10-10 qq  1.37b                      5.4uu            0.14
    Dibenzo[a,e]pyrene     Pale yellowh        244.4      592vv
    Dibenzo[a,h]pyrene     Golden yellowi      317        596vv
    Dibenzo[a,i]pyrene     Greenish-yellowishi 282        594vv       3.2 x 10-10 mm               7.30hh        0.17l            4.31 x 10-6 l
    Dibenzo[a,l]pyrene     Pale yellowi        162.4      595vv
                                                                                                                                               

    a From Karcheret al. (1985); Karcher (1988)
    b From Lewis (1992)
    c When two temperatures are given as superscripts, they indicate the specific gravity, i.e. the density of the substance at the first
      reported temperature relative to the density of water at the second reported temperature. When there is no value, or only one, for
      temperature, the datum is in grains per millilitre, at the indicated temperature, if any.

    Table 4 (continued)

    d From Mackay & Shiu (1977), except where noted
    e From Budavari (1989)
    f From National Toxicology Program (1993)
    g From Sonnefeld et al. (1983)
    h From Lide (1991)
    i From IARC (1977)
    j From Karickhoff et al. (1979)
    k From Mackay et al. (1979)
    l Calculated by Syracuse Research Center; from National Toxicology Program (1993)
    m Calculated as per Leo et al. (1971); from US Environmental Protection Agency (1980)
    n From Mackay & Shiu (1981)
    o When pure, colourless with violet fluorescence; from Budavari (1989)
    p From Hawley (1987)
    q From National Institute for Occupational Safety and Health and Occupational Safety and Health Administration (1981)
    r From Kruber & Marx (1938)
    s Calculated by Karcher et al. (1991)
    t From May et al. (1978)
    u From Bruggeman et al. (1982)
    v At ambient temperature; from Inokuchi & Nakagaki (1959)
    w From Ten Hulscher et al. (1992)
    x Personal observation by J. Jacob, Germany, on high-purity, certified reference materials
    y From Kruber (1937)
    z Calculated by Miller et al. (1985)
    aa From Schuyer et al. (1953)
    bb From IARC (983)
    cc From Kruber & Grigoleit (1954)
    dd From Ehrlich & Beevers (1956)
    ee Reported by Grimmer (1983a)
    ff From Beilstein Institute for Organic Chemistry (1993)
    gg Reported by Sims & Overcash (1983)
    hh Calculated by Yalkowsky & Valvani (1979)
    ii Calculated by White (1986)
    jj From Davis et al. (1942)
    kk From review by Bjorseth (1983); original references cited by White (1986)
    ll Temperature not given; reported by Sims & Overcash (1983)
    mm Calculated by National Toxicology Program (1993)
    nn Temperature not given; unpublished result cited by Wise et al. (1981)
    oo From US Environmental Protection Agency (1980)

    Table 4 (continued)

    pp From Kronberger & Weiss (1944)
    qq From review of Santodonato et al. (1981)
    rr Calculated by Ruepert et al. (1985)
    ss From Verschueren (1983)
    tt From Schwarz (1977)
    uu From Brooke et al. (1986)
    vv From Agency for Toxic Substances and Disease Registry (1990)
    xx From White (1948)
    yy Estimated from gas chromatographis retention time; from Grimmer (1983a)
    zz From Means et al. (1980)
    aaa From Von Boente (1955)


    (Valerio et al., 1984; Lane, 1989). After photodecomposition in the
    presence of air and sunlight, a number of oxidative products are
    formed, including quinones and endoperoxides. PAH have been shown
    experimentally to react with nitrogen oxides and nitric acid to form
    the nitro derivatives of PAH, and to react with sulfur oxides and
    sulfuric acid (in solution) to form sulfinic and sulfonic acids. PAH
    may also be attacked by ozone and hydroxyl radicals present in the
    atmosphere. The formation of nitro-PAH is particularly important owing
    to their biological impact and mutagenic activity (IARC, 1984a,
    1989a). In general, the above reactions are of interest with regard to
    the environmental fate of PAH, but the results of experimental studies
    are difficult to interpret because of the complexity of interactions
    occurring in environmental mixtures and the difficulty in eliminating
    artefacts during analytical determinations. These reactions are also
    considered to be responsible for possible losses of PAH during ambient
    atmospheric sampling (see section 2.4.1.1).

    2.3  Conversion factors

         Atmospheric concentrations of PAH are usually expressed as
    micrograms or nanograms per cubic meter. At 25°C and 101.3 kPa, the
    conversion factors for a compound of given relative molecular mass are
    obtained as follows:

              ppb = µg/m3 × 24.45/relative molecular mass

              µg/m3 = ppb × relative molecular mass/24.45.

         For example, for benzo [a]pyrene, 1 ppb = 10.3 µg/m3 and
    1 µg/m3 = 0.0969 ppb.

    2.4  Analytical methods

         Tables 5 and 6 present as examples a limited number of methods
    that are applied to 'real' samples of different matrices. The methods
    and sources were selected, as far as possible, according to the
    following criteria: accessibility of the bibliographic source,
    completeness of the description of the procedure, practicability with
    common equipment for this type of analysis (even if experienced
    personnel are required), recency, and whether it is an official,
    validated, or recommended method.

    2.4.1  Sampling

    2.4.1.1  Ambient air

         The physical state of PAH in the atmosphere must be considered
    when selecting the sampling apparatus. Compounds with five or more
    rings are almost exclusively adsorbed on suspended particulate matter,
    whereas lower-molecular-mass PAH are partially or totally present in
    the vapour phase (Coutant et al., 1988). When ambient air is
    monitored, it is common practice to monitor only particle-bound PAH


        Table 5. Analytical methods for polycyclic aromatic hydrocarbons in air

                                                                                                                                             

    Matrix         Sampling, extraction                       Clean-up                       Analysis     Limit of        Reference
                                                                                                          detectiona
                                                                                                                                             

    Ambient air    Sampling on GF+PUF, at 45 m3/h;            Liquid-liquid partition        GC/MS                        Yamasaki et al.
                   Soxhlet extraction with cyclohexane        with cyclohexane:                                           (1982)
                                                              H2O:DMSO, then CC
                                                              with SiO2
                   Sampling on GF+PUF, at 30 m3/h;            CC with Al2O3 +                HPLC/FL      0.01-0.7        Keller &
                   Soxhlet extraction with petroleum ether    SiO2                                        ng/m3           Bidleman (1984)
                   (GF) and DCM (PUF)
                   Sampling on GF (particle diameter          TLC with SiO2                  HPLC/UV      0.01-0.3        Greenberg et al.
                   < 15 µm), at 68 m3/h; Soxhlet extraction                                  + FL         ng/m3           (1985)
                   with cyclohexane, DCM, and acetone
                   Sampling on GF at 83 m3/h; sonication      TLC with SiO2                  GC/FID                       Valerio et al.
                   (cyclohexane)                                                                                          (1992)

    Emissions      Sampling by glass wool, condenser,         Liquid-liquid partition        GC/FID       10 ng/m3        Colmsjo et al.
    (municipal     and XAD-2; extraction with acetone         with DMF                                                    (1986a)
    incinerator)   (glass-wool and XAD-2, by Soxhlet)

    Vehicle        Sampling by GF and condenser; liquid-      CC with SiO2 and               GC/FID       2.5-20 ng       Grimmer et al.
    exhaust        liquid partition with acetone:H2O:         Selphadex LH-20                             per test        (1979)
                   cyclohexane and DMF:H,O:cyclohexane
                   Sampling in dilution tunnel by             Liquid-liquid partition        GC/FID or                    Westerholm et
                   PTFE-coated GF and condenser; Soxhlet      with cyclohexane:              GC/MS                        al. (1988)
                   extraction of filter (DCM) and             H2O:DMF
                   condensate (acetone); remaining
                   aqueous phase extracted with DCM

    Table 5. (continued)

                                                                                                                                             

    Matrix         Sampling, extraction                       Clean-up                       Analysis     Limit of        Reference
                                                                                                          detectiona
                                                                                                                                             

    Indoor air     Sampling on GF (particle diameter          TLC with acetyloxylated        Spectrofluorescence          Lioy at al. (1988)
                   < 10 µm) at 10 l/min; sonication           cellulose                      (benzo[a]pyrene only)
                   (cyclohexane)
                   Sampling on quartz-fibre filtre and                                       GC/MS                        Chuang at al.
                   XAD-4 at 226 l/min; Soxhlet extraction                                                                 (1991)
                   with DCM
                   Sampling on PTFE-coated GF at              filtration; then CC            HPLC/FL      0.02-0.12       Daisey & Gundel
                   20 l/minfor 24 h; Soxhlet extraction       SiO2 cartridge),                            ng/m3 b         (1993)
                   with DCM                                   optional
                   Sampling on GF and PUF, at 20 litres/min                                  GC/FID, GC/MS                US Environmental
                   for 24 h; Soxhlet extraction (10% ether:                                  or HPLC/UV + FL              Protection Agency
                   n-hexane)                                                                                              (1990)

    Workplace air  Sampling on PTFE filter and XAD-2                                         GC/FID       0.3-0.5 µg      NIOSH (1994a,b)
                   at 2 l/min; sonication or Soxhlet                                                      per sample
                   extraction of filterc, extraction of                                      HPLC/UV      0.05-0.8 µg
                   XAD-2 with toluene (for GC) or                                            + FL         per sample
                   acetonitrile (for HPLC)

    Workplace air  Sampling on filter (GF, quartz fibre,      CC (XAD-2)                     GC/FID       approx 0.5      German
                   PTFE or silver membrane) at 2 litres/min;                                              µg/m3           Research
                   sonication or Soxhlet extraction with                                                                  Commission
                   cyclohexane or toluene                                                                                 (1991)

    Tobacco        Sampling by acetone trap; solvent          CC (SiO2 + Sephadex            GC/MS +      ng/cigarette    Lee at al. (1976b)
    smoke          partition scheme (acids/bases/neutral      LH-20); then                   NMR
                   compounds/PAH)                             HPLC/UV
                                                                                                                                             

    Table 5 (continued)

    GC glass fibre; PUF, polyurethane foam; DMSO, dimethyl sulfoxide; CC, column chromatography; GC, gas chromatography;
    MS, mass spectrometry; DCM, dichloromethane; HPLC, high-performance liquid chromatography; FL, fluorescence detection;
    TLC, thin-layer chromatography; UV, ultraviolet detection; FID, flame-ionization detection; DMF, N-dimethylformamide;
    PTFE, polytetrafluoroethylene; NMR, nuclear magnetic resonance
    a Various PAH
    b The following PAH can be determined: fluoranthene, pyrene, chrysene, benzo[e]pyrene, benzo[b]fluoranthene,
      benzo[k]fluoranthene, benzo[a]pyrene, benzo[ghi]perylene, indeno[1,2,3-cd]pyrene.
    c Appropriate solvent must be determined by recovery tests on specific samples.


    Table 6. Analytical methods for polycyclic aromatic hydrocarbons in matrices other than air

                                                                                                                                            

    Matrix            Extraction                        Clean-up                  Analysis           Limit of            Reference
                                                                                                     detectiona
                                                                                                                                            

    Tap-water         Preconcentration on PUF;          Liquid-liquid partition   GC/FID or TLC      0.1 ng/litre        Basu & Saxena
                      extraction (with acetone and      with cyclohexane:         (Al2O3: acetyl                         (1978a)
                      cyclohexane)                      H2O:methanol and          celluose) with FL
                                                        cyclohexane: H2O:         detector
                                                        DMSO; then CC
                                                        OWN)

    Groundwater       Liquid-liquid partition with      CC (SiO2), if needed      GC/FID             µg/litre level      US Environmental
                      DCM                                                         GC/MS              10 µg/litre         Protection Agency
                                                                                  HPLC/UV + FL       0-01-2 µg/litre     (1986a)

    Wastewater        Liquid-liquid partition with      CC (SiO2), if needed      GC/FID or          0.01 -0.2 µg/litre  US Environmental
                      DCM                                                         HPLC/UV+FL         (by HPLC)           Protection Agency
                                                                                                                         (1984a)

    Seawater          Liquid-liquid partition with      CC (SiO2 + Al2O2)         GC/FID or                              Desideri at al.
                      n-hexane or CCl4                                            HPLC/UV                                (1984)

    Soil              Sonication with DCM               CC (Al2O2); then          GC/MS              1 µg/kg             Vogt at
                                                        liquid-liquid partition                                          al. (1987)
                                                        (n-hexane:H2O:DMSO)
                      Soxhlet extraction with DCM       CC (Florisil cartridge)   HPLC/UV + FL       1 µg/kg             Jones et a[.
                                                                                                                         (1989a)

    Sediment          Soxhlet extraction with DCM       CC (SiO2 + Sephadex       HPLC/DAD/MS                            Quilliam & Sim
                                                        LH20)                                                            (1988)

                      Sonication with acetone:          CC (Florisil)             HPLC/UV + FL       1-160 µg/kg         Marcus et al.
                      n-hexane                                                                                           (1988)

    Table 6. (continued)

                                                                                                                                            

    Matrix            Extraction                        Clean-up                  Analysis           Limit of            Reference
                                                                                                     detectiona
                                                                                                                                            

    Meat and fish     (I) digestion (alcoholic KOH),    Liquid-liquid partition   GC/FID             2.5-20 ng/          Grimmer &
    products (I),     then liquid-liquid partition      with cyclohexane:                            sample              Bohnke (1979b)
    vegetable oils    (methanol: H2O:cyclohexane)       H2O:DMF); then CC
    (II), and sewage  (II) dissolution in cyclohexane   (SiO2 + Sephadex
    sludge (III)      (III) refluxing with acetone      LH20)

    Food (total       Refluxing with alcoholic KOH,     Liquid-liquid partition   HPLC/FL            0.002-0.7 µg/kg     Dennis et al.
    diet)             extraction with isooctane         (isooctane:H2O:DMF);                                             (1983)
                                                        then CC (SiO2 cartridge)
                      Saponification with alcoholic     CC (SiO2)                 HPLC/FL            0.03-2 µg/kg        de Vos et al.
                      KOH, extraction with                                                                               (1990)
                      cyclohexane

                      Saponikation wit ahoholic         CC (Florisil); then       TLC/UV+FL          0.02 µg/kg          Howard (1979);
                      KOH, extraction with              liquid-liquid partition                      (benzo[a]pyrene)    Fazio (1990)
                      isooctane                         isooctane:H2O:DMSO)

    Seafood           Digestion with alcoholic KOH,     CC (Al2O3 + SiO2 +        HPLC/FL            0.01-0.6 µg/kg      Perfetti et al.
                      extraction with TCTFE             C18 cartridge)                                                   (1992)

    Smoked food       Digestion with alcoholic KOH,     CC (Al2O3 + SiO2);        HPLC/UV+FL         0.03-0.4            Joe et al. (1984)
                      extraction with TCTFE             liquid-liquid partition                      µg/kg
                                                        (cyclohexane:H2O:DMSO)

                      Refluxing with cyclohexane or     Liquid-liquid partition   TLC/FLb (only      0 0.5 ng/kg         IUPAC (1987)
                      TCTFE, extraction with            with cyclohexane:H2O:     benzo[alpyrene)
                      methanol:H2O                      DMF); then CC (SiO2)

    Solid waste       Soxhlet extraction with DCM       CC (SiO2), if needed      GC/FID             µg/kg level         US Environmental
                      or sonication with                                          GC/MS              1-200 mg/kg         Protection Agency
                      DGM:acetone                                                 HPLC/UV + FL       µg/kg level         (1986b)

    Table 6. (continued)

                                                                                                                                            

    Matrix            Extraction                        Clean-up                  Analysis           Limit of            Reference
                                                                                                     detectiona
                                                                                                                                            

    Mineral oil and   Liquid-liquid partition with      CC (SiO2 + Sephadex       GC/FID             100 ng/kg           Grimmer &
    fuel              cyclohexane:H2O:DMF)              LH20)                                                            Bohnke (1979a)

    Medicinal oil     Liquid-liquid partition           CC (SiO2 + Sephadex       HPLC/FL +          0.2-200 ng/kg       Geahchan at al.
    (cyclohexane: H2O:DMF)                              LH20)                     GC/FID                                 (1991)

    Plants            Sonication (acetonitrile),        CC (SiO2)                 GC/FID                                 Coates et al.
    extraction with pentane                                                                                              (1986)

    Urine             Adjusted to pH3, extraction       CC (SiO2 cartridge)       HPLC/FLc                               Becher & Bjorseth
                      in C18 cartridge, metabolites                                                                      (1983)
                      reduced with hydriodic acid

    Urine and         Addition of HCl, refluxing        CC (SiO2) + Sephadex      GC/MSd                                 Jacob at al. (1989)
    faeces            with toluene, addition of         LH20
                      methanol and diazomethanol in
                      ether (faeces saponified before
                      acidification)

    Tissue            Homogenization (benzene:          CC (Florisil)             GC/MS              5-50 µg/kg          Liao et al. (1988)
                      n-hexane)

    Skine             Sonication of exposure pads                                 HPLC/FL            6 ng/cm2            Jongeneelen et al.
                      with DCM, centrifugation                                                                           (1988a)

    Table 6. (continued)


    PUF, polyurethane foam; DMSO, dimethyl sulfoxide; CC, column chromatography; GC, gas chromatography; FID, flame ionization detection; FL,
    fluorescence detection; DCM, dichloromethane; MS, mass spectrometry; UV, ultraviolet detection; DAD, diode-array detector; DMF,
    N-dimethylformamide; TLC, thin-layer chromatography; TCTFE, 1,1,2-trichlorotrifluoroethane
    a Various PAH
    b Benzo[a]pyrene content estimated to be > 0.6 µg/kg (screening method)
    c Determination of unmetabolized and metabolized PAH
    d Determination of pyrene and 1-hydroxypyrene
    e Measurement of skin contamination with soft polypropylene exposure pads mounted on skin sites


    (Menichini, 1992a), probably because of the increased work involved in
    trapping volatile compounds, both in assembling the sampling unit and
    in analysing samples, and also because lighter compounds are of lesser
    toxicological interest. Of the PAH that are classified as 'probably'
    and 'possibly' carcinogenic to humans (IARC, 1987), only
    benz [a]anthracene is found at significant levels in the vapour phase
    (Van Vaeck et al., 1984; Coutant et al., 1988; Baek et al., 1992).

         Sampling is generally performed by collecting total suspended
    particulate matter for 24 h on glass-fibre filters by means of
    high-volume samplers. Other filters that have been used are quartz
    fibres (Hawthorne et al., 1992), polytetrafluoroethylene (PTFE)
    membranes (Benner et al., 1989; Baek et al., 1992), and, in
    comparisons, PTFE-coated glass fibres (Lindskog et al., 1987; De Raat
    et al., 1990). The effects of these materials on the decomposition of
    PAH during sampling have been compared (see section 2.2). Some studies
    indicated that higher recoveries are obtained with PTFE and
    PTFE-coated filters (Lee et al., 1980a; Grosjean, 1983); however, more
    recent investigations did not confirm this finding (Lindskog et al.,
    1987; Ligocki & Pankow, 1989; De Raat et al., 1990). Moreover, when
    cellulose acetate membrane filters were compared with glass-fibre
    filters, they had similar efficiency for collecting heavier PAH, but
    the former had greater efficiency for collecting three- and four-ring
    compounds (Spitzer & Dannecker, 1983).

         The most widely used method for trapping vapour-phase PAH is
    adsorption on plugs of polyurethane foam located behind the filter
    (Keller & Bidleman, 1984; Chuang et al., 1987; De Raat et al., 1987a;
    Benner et al., 1989; Hawthorne et al., 1992). This method is widely
    accepted, probably because of the low pressure drop, the low blanks,
    the low cost, and ease of handling. Among the other sorbents tested
    (see also reviews by Leinster & Evans, 1986; Davis et al., 1987),
    further polymeric materials have received particular attention,
    including Amberlite XAD-2 resin, which is a valid alternative to
    polyurethane foam (Chuang et al., 1987), Porapak PS, which has been
    successfully tested in combination with a silanized glass-fibre filter
    at a flow rate of 2 m3/h (Jacob et al., 1990a), and Tenax(R) (Baek
    et al., 1992).

         The trapped vapours contain both the PAH that were initially
    present in the vapour phase and those already collected on the filter
    and volatilized during sampling (the 'blowing-off' effect) (Van Vaeck
    et al., 1984; Coutant et al., 1988). The amount of PAH found in the
    vapour phase increases with ambient temperature (Yamasaki et al.,
    1982). Samplers incorporating an annular denuder, as well as a filter
    and back-up trap, have been used to investigate phase distribution and
    artefact formation (Coutant et al., 1988, 1992).

         Sampling times are restricted to 24 h in order to avoid sample
    degradation and losses. Grimmer et al. (1982) proposed a useful method
    for controlling losses due to chemical degradation and volatilization
    from filters which is based on the invariability of PAH profiles (i.e.
    the ratio of all PAH to one another) at different collection times.

    The adsorption of gas-phase PAH onto a quartz-fibre filter has been
    investigated as a possible sampling artefact (Hart & Pankow, 1994);
    the results suggested that overestimation of particle-associated PAH
    can be avoided by replacing quartz-fibre filters with a PTFE membrane
    filters, or can be corrected by using back-up quartz-fibre filters.

         Elutriators and cascade impactors have been used to achieve
    particle size-selective sampling of PAH (Menichini, 1992a).
    Instruments designed as additions to high-volume samplers are
    available, including 'PM10' inlets, which allow collection of airborne
    particles with a 50% cutoff at the aerodynamic diameter of 10 œm (US
    Environmental Protection Agency, 1987a; Lioy et al., 1988; Hawthorne
    et al., 1992), and cascade impactors (Van Vaeck et al., 1984; Catoggio
    et al., 1989).

         When PAH are collected in indoor air, samplers operating at 20 or
    200 litre/min are commonly used. The filter and sorbent materials are
    those used for outdoor air (Wilson et al., 1991; see also Table 5).

         The sampling step is by far the most important source of
    variability in the results of atmospheric PAH determination. Most
    investigations are difficult to compare because of differences in
    factors such as season, meteorological conditions, time of day, number
    and characteristics of sampling sites, and sampling parameters
    (Menichini, 1992a). Passive biological sampling has been investigated
    as an approach to long-term sampling of atmospheric PAH (Jacob &
    Grimmer, 1992), and preliminary correlation factors have been
    determined by comparing the PAH profiles in biological (plants,
    particularly) and air samples. Of the matrices tested, spruce sprouts
    were found to be the most suitable.

    2.4.1.2  Workplace air

         The general considerations described for ambient air are also
    valid for the working environment. Less volatile PAH may be retained
    than in ambient air because of the high temperatures that are often
    found at the workplace. In the potroom of an aluminium plant where
    Sœderberg electrodes were used, 42% of benz [a]anthracene was found
    in the vapour phase (Andersson et al., 1983), and in an iron foundry
    at a site where the temperature of the PAH source was 600-700°C, four-
    to seven-ring PAH represented about 70% of the total in the vapour
    phase (Knecht et al., 1986).

         Glass-fibre or PTFE filters are usually used to collect
    particle-bound PAH. A number of back-up systems can be used to
    efficiently trap volatile PAH, including liquid impingers and solid
    sorbents such as Tenax(R)-GC, Chromosorb, and XAD-2 (Bjorseth &
    Becher, 1986; Davis et al., 1987). The latter seems to be the most
    practical. The US National Institute for Occupational Safety and
    Health (1994a,b) recommended use of a PTFE-laminated membrane followed
    by a tube containing two sections of XAD-2. For sampling in bright
    sunlight, opaque or foil-wrapped filter cassettes can be used to
    prevent degradation.

         The exposure of workers is estimated by taking air samples at
    various locations in the workplace or by personal sampling, in which
    workplace air is pumped through a filter attached to clothing close to
    the breathing zone for a specified time. Both procedures provide an
    estimate and not a precise measurement of an individual's exposure.

    2.4.1.3  Combustion effluents

         The validity of a collected sample, i.e. the degree to which it
    reflects the 'true' composition of the emission, is a crucial factor
    in the determination of PAH in emissions. The problems associated with
    efficient collection of volatile PAH are enhanced when sampling
    combustion effluents, such as stack gases and vehicle exhausts,
    because of the elevated temperatures at sampling positions.

         A sampling device for stack gases is constituted by a glass- or
    quartz-fibre filter, followed by a special unit which generally
    consists in a cooler for collecting condensable matter and an
    adsorbent cartridge (Colmsjö et al., 1986a; Funcke et al., 1988).
    Tenax(R) has been used as an adsorbent (Jones et al., 1976), but
    XAD-2 seems to be more suitable (Warman, 1985) and is generally
    preferred. Two sampling procedures have been described in detail by
    the US Environmental Protection Agency (1986c). In the first
    ('Modified method 5 sampling train'), the unit basically includes a
    glass- or quartz-fibre filter kept at around 120°C, a condenser coil
    that conditions the gas at a maximum of 20°C, and a bed of XAD-2
    jacketed to maintain the internal gas temperature at about 17°C. The
    second ('Source assessment sampling system') is often used for
    stationary investigations (Warman, 1985). The apparatus consists of a
    stainless-steel probe, which enters an oven containing the filter,
    preceded by three cyclone separators in series, with cutoff diameters
    of 10, 3, and 1 œm; the volatile organic compounds are cooled and
    trapped on XAD-2. The sorbent is followed by a condensate collection
    trap and an impinger train.

         Motor vehicle exhausts are sampled under laboratory conditions,
    by chassis or engine dynamometer testing. Standard driving cycles are
    employed to simulate on-road conditions (Stenberg, 1985; see also
    section 3.2.7.2).

         Two basic techniques have been used to collect, sample, and
    analyse exhaust (Levsen, 1988; IARC, 1989a). In the first-raw gas
    sampling-the exhaust pipe is connected directly to the sampling
    apparatus; undiluted emissions are cooled in a condenser and then
    allowed to pass through a filter for collection of particulates
    (Grimmer et al., 1979, 1988a; Society of German Engineers, 1989). A
    second technique-dilution tube sampling-is now often used, in which
    hot exhaust is diluted with filtered cold air in a tunnel, from which
    samples are collected isokinetically. This technique simulates the
    process of dilution that occurs under real conditions on the road (US
    Environmental Protection Agency, 1992a).

         Particles are almost always collected on glass-fibre, glass-fibre
    with PTFE binder, quartz-fibre filters, or PTFE membranes; the latter
    have been reported to be particularly efficient and chemical inert
    (Lee & Schuetzle, 1983). Glass-fibre filters impregnated with liquid
    paraffin are also used (Grimmer et al., 1979; Society of German
    Engineers, 1989). Vapour-phase PAH (Stenberg, 1985) may be collected
    by cryo-condensation (Stenberg et al., 1983) or on an adsorbent trap
    with a polymeric material such as XAD-2 (Lee & Schuetzle, 1983).

         Artefacts may be introduced during collection on filters as a
    result of chemical conversion of PAH, particularly into nitro-PAH and
    oxidation products (Lee & Schuetzle, 1983; Schuetzle, 1983; IARC,
    1989a). These effects have not been fully evaluated.

    2.4.1.4  Water

         The concentrations of PAH in uncontaminated groundwater supplies
    and in drinking-water are generally very low, at 0.1 and 1 ng/litre
    (see sections 5.1.2.1 and 5.1.2.2). This implies that serious errors
    arising from adsorption losses and contamination occur during
    collection and storage of samples or that a preconcentration step may
    be needed to enrich the sample. It is recommended that sampling be
    performed on-site, directly in the extraction vessel (Smith et al.,
    1981).

         Various solid sorbents have been successfully used for
    preconcentration (Smith et al., 1981), including Tenax(R)-GC,
    prefiltered if necessary (Leoni et al., 1975); XAD resins (Griest &
    Caton, 1983); open-pore polyurethane foam (Basu et al., 1987); and
    prepacked disposable cartridges of bonded-phase silica gel (Chladek &
    Marano, 1984; Van Noort & Wondergem, 1985a). Solid sorbents have
    limitations when the sample contains suspended material, since
    adsorbed PAH may be lost by filtration (Van Noort & Wondergem, 1985a).

    2.4.1.5  Solid samples

         Some foodstuffs (Liem et al., 1992), soil, sediment, tissues, and
    plants usually require  homogenization before a sample is extracted.

    2.4.2  Preparation

         As most environmental samples contain only small amounts of PAH,
    sophisticated techniques are required for their detection and
    quantification. Therefore, efficient extraction from the sample matrix
    is usually followed by one or more purification steps, so that the
    sample to be analysed is as free as possible from impurities and
    interference. Many extraction and purification techniques and
    combinations ('isolation schemes') have been described, validated, and
    recommended, but no single scheme is commonly recognized as 'the best'
    for a given matrix. The isolation schemes have been classified
    according to groups of matrices (Jacob & Grimmer, 1979; Grimmer,
    1983a), as summarized briefly below.

         PAH are extracted from a sample (Lee et al., 1981; Santodonato et
    al., 1981; Grimmer, 1983a; Griest & Caton, 1983) with:

    -    a Soxhlet apparatus, from filters loaded with particulate matter,
         vehicle exhausts, or sediments;
    -    directly by liquid-liquid partition, for water samples; or
    -    after complete dissolution (e.g. fats and vegetable and mineral
         oils) or alkaline digestion of samples (e.g. meat products) by a
         selective solvent such as  N,N-dimethylformamide (Natusch &
         Tomkins, 1978) or dimethyl sulfoxide. Complete extraction of PAH
         from samples such as soot emitted by diesel engines, carbon
         blacks, and other carbonaceous materials is particularly
         difficult.

         Extraction of PAH from soil, sediment, sewage sludge, and vehicle
    exhaust particulates by refluxing with various solvents has been
    investigated. In all cases, toluene was found to be the most efficient
    solvent, especially for vehicle exhaust (Jacob et al., 1994).

         As an alternative to Soxhlet extraction, ultrasonic extraction
    (Griest & Caton, 1983) has advantages in terms of reduced time of
    extraction (minutes versus hours) and superior recovery efficiency and
    reproducibility, particularly for solid samples and filters loaded
    with particulate matter. Comparisons of techniques depend, however, on
    the matrix, solvent, and experimental conditions.

         Supercritical fluid extraction (Langenfeld et al., 1993) has
    gained attention as a rapid alternative to conventional liquid
    extraction from polyurethane foam sorbents (Hawthorne et al., 1989a),
    soil (Wenclawiak et al., 1992), and other environmental solids such as
    urban dust, fly ash, and sediment (Hawthorne & Miller, 1987). This
    technique can also be directly coupled with on-column gas
    chromatography (see section 2.4.3.1); the extract is quantitatively
    transferred onto the gas chromatographic column for a rapid (< 1 h)
    analysis with maximal sensitivity. This technique has been used for
    urban dust samples (Hawthorne et al., 1989b).

         Extracted samples are usually purified from interfering
    substances by adsorption column chromatography. The classical
    sorbents, alumina and silica gel, are widely used. In addition, the
    hydrophobic Sephadex LH-20 has been found to be suitable for isolating
    PAH from nonaromatic, nonpolar compounds, which is important if the
    sample is analysed by gas chromatography (Grimmer & Böhnke, 1979a); It
    has also been used in partition chromatography as a carrier of the
    stationary phase, to separate PAH from alkyl derivatives (Grimmer &
    Böhnke, 1979b). Chromatography on silica gel and Sephadex is often
    combined (Jacob & Grimmer, 1979; Grimmer, 1983a).

         Clean-up has also been achieved by eluting extracted samples
    through XAD-2 (soil samples: Spitzer & Kuwatsuka, 1986), XAD-2 and
    Sephadex LH-20 in series (foods: Vaessen et al., 1988), or Florisil
    (food, water, and sediment samples: references given in Table 6).

         Conventional chromatographic columns may be substituted by
    prepacked commercial cartridges, which have advantages in terms of
    time and solvents consumed and reproducibility. For example, silica
    cartridges have been used to purify foodstuffs (Dennis et al., 1983),
    urine (Becher & Bjorseth, 1983), vehicle emissions (Benner et al.,
    1989), mineral oil mist (Menichini et al., 1990), and atmospheric
    samples (Baek et al., 1992); soil samples have been cleaned up on
    Florisil cartridges (Jones et al., 1989a).

         Preparative thin-layer chromatography is also used for, e.g. air
    particulates (see Table 5) and vegetable oils (Menichini et al.,
    1991a).

         Handling of samples in the absence of ultraviolet radiation is
    recommended at all stages in order to avoid photodecomposition of PAH
    (Society of German Engineers, 1989; US Environmental Protection
    Agency, 1990; US National Institute for Occupational Safety and
    Health, 1994a,b). It is also generally recommended that possible
    sources of interference and contamination be controlled, particularly
    from solvents (US Environmental Protection Agency, 1984a, 1986b,
    1990), and that samples be refrigerated until extraction (US
    Environmental Protection Agency, 1984a; US National Institute for
    Occupational Safety and Health, 1994a,b).

    2.4.3  Analysis

         PAH are now routinely identified and quantified by gas
    chromatography or high-performance liquid chromatography (HPLC). Each
    technique has a number of relative advantages. Both are rather
    expensive, particularly HPLC, and require qualified operating
    personnel; nevertheless, they are considered necessary in order to
    analyse 'real' samples for a large number of PAH with accuracy and
    precision.

    2.4.3.1  Gas chromatography

         Excellent separation (< 3000 plates per meter) is obtained by
    the use of commercially available fused silica capillary columns,
    making it possible to analyse very complex mixtures containing more
    than 100 PAH.

         The most widely used stationary phases are the
    methylpolylsiloxanes: especially SE-54 (5% phenyl-, 1%
    vinyl-substituted) and SE-52 (5% phenyl-substituted), but SE-30 and
    OV-101 (unsubstituted), OV-17 (50% phenyl-substituted), Dexsil 300
    (carborane-substituted) and their equivalent phases are also used.
    Chemically bonded phases are used increasingly because they can be
    rinsed to restore column performance and undergo little 'bleeding' at
    the high temperatures of analysis (about 300°C) that are required for
    determining high-boiling-point compounds.

         Nematic liquid crystal phases (Bartle, 1985) have also been used
    to separate some isomeric compounds that are poorly resolved by
    siloxane phases, such as chrysene and triphenylene on
     N,N'-bis (para-methoxy-benzylidene)-a,a'-bi- para-toluidine
    (Janini et al., 1975) and
     N,N'-bis (para-phenylbenzylidene)-a,a'-bi- para-toluidine (Janini
    et al., 1976).

         Splitless or on-column injection is necessary to gain sensitivity
    in trace analysis, the latter being preferred as it allows better
    reproducibility. Flame ionization detectors are almost always used
    because of the excellent linearity, sensitivity, and reliability of
    their response. Since the signal is related linearly to the carbon
    mass of the compound, PAH are recorded in proportion to their
    quantities, and the chromatogram shows the quantitative composition of
    the sample directly. Because flame ionization detectors are
    non-selective, samples for gas chromatography must be highly purified.
    Peak identification, which is done routinely from data on retention,
    must be confirmed by analysing samples on a different gas
    chromatographic column, by an independent technique, such as HPLC, or
    by directly coupling a mass spectrometric detector to the gas
    chromatograph (Lee et al., 1981; Olufsen & Bjorseth, 1983; Bartle,
    1985; Hites, 1989).

         Mass spectrometers have gained wide acceptance. They are powerful
    tools for identifying compounds, especially when commercially
    available libraries of reference spectra are used to match the spectra
    obtained and to control the purity of a compound. As isomeric
    compounds often have indistinguishable spectra, however, the final
    assignment must also be based on retention.

         On-line coupling of liquid chromatography, capillary gas
    chromatography, and quadrupole mass spectrometry has been used to
    determine PAH in vegetable oils (Vreuls et al., 1991).

    2.4.3.2  High-performance liquid chromatography

         The packing material considered most suitable for separating PAH
    consists of silica particles chemically bonded to linear C18
    hydrocarbon chains; selection of the appropriate phase has been
    discussed in detail by Wise et al. (1993). Typically, 25-cm columns
    packed with 5-œm particles are used in the gradient elution technique,
    and the mobile phase consists of mixtures of acetonitrile and water or
    methanol and water ('reversed-phase HPLC'). As the efficiency of
    separation that can be achieved with HPLC columns is much lower than
    that with capillary gas chromatography, HPLC is generally less
    suitable for separating samples containing complex PAH mixtures.

         The advantages of HPLC derive from the capabilities of the
    detectors with which it is used. Those most widely used for PAH are
    ultraviolet and fluorescence detectors, generally arranged in series,
    with flow-cell photometers or spectrophotometers. Both, but especially
    the latter, are highly specific and sensitive: the detection limits
    with fluorescence are at least one order of magnitude lower than those
    with ultraviolet detection. The specificity of fluorescence detectors
    allows the determination of individual PAH in the presence of other
    nonfluorescing substances. In addition, since different PAH have
    different absorptivity or different fluorescence spectral
    characteristics at given wavelengths, the detectors can be optimized
    for maximal response to specific compounds. This may prove
    advantageous in the identification of unresolved components. In
    particular, wavelength-programmed fluorescence detection, to measure
    changes in excitation and emission wavelengths during a
    chromatographic run (Hansen et al., 1991a), is being used for the
    analysis of environmental samples (Wise et al., 1993). HPLC is
    suitable to a limited degree for lower-molecular-mass compounds like
    naphthalene, acenaphthene, and acenaphthylene, for which the detection
    limits are relatively high (US Environmental Protection Agency,
    1984a).

         Owing to the selectivity of packing materials, various isomers
    that cannot be separated efficiently on the usual capillary gas
    chromatographic columns can be resolved at baseline and identified by
    HPLC. Such isomers include the pairs chrysene-triphenylene and
    benzo [b]fluoranthene-benzo [k]fluorathene (Wise et al., 1980).
    Coupling of a mass spectrometer to HPLC has also been used in
    detecting PAH (e.g., Quilliam & Sim, 1988).

         As much information on isomeric structure can be obtained from
    spectra seen during the elution of chromatographic peaks, an
    ultraviolet diode-array detector has been used to confirm peaks (Dong
    & Greenberg, 1988; Kicinski et al., 1989). For applications of HPLC to
    determination of PAH, reference should be made to published reviews
    (Lee et al., 1981; Wise, 1983, 1985).

    2.4.3.3  Thin-layer chromatography

         Thin-layer chromatography is commonly used only for identifying
    individual compounds, such as benzo [a]pyrene, during screening
    (IUPAC, 1987) or for identifying selected PAH, such as the six PAH
    that WHO (1971) recommended be determined in drinking-water (Borneff &
    Kunte, 1979). It is an inexpensive, quick analytical technique but has
    low separation efficiency. The last parameter is improved by
    two-dimensional processes (see, e.g. Borneff & Kunte, 1979).
    Quantification may be done by spectrophotometric or
    spectrofluorimetric methods in solution after the scrubbed substance
    spot has been extracted (Howard, 1979; Fazio, 1990) or  in situ by
    scanning spectrofluorimetry (Borneff & Kunte, 1979).

         Acetylated cellulose is the adsorbent that has been used most
    widely for one-step separation of PAH fractions, and mixed aluminium
    oxide and acetylated cellulose have been used for two-dimensional
    development (Daisey, 1983).

    2.4.3.4  Other techniques

         A number of unconventional instruments and techniques based on
    spectro-scopic principles have been developed as possible alternatives
    to the chromatographic methods for PAH. Most of them are, however,
    expensive, require skilled personnel, and are not yet considered
    useful for the practising analyst (Wehry, 1983; Vo-Dinh, 1989).

         Low-temperature luminescence in frozen solutions ('Shpol'skii
    effect') has been used for various environmental samples, particularly
    to identify methylated PAH isomers (Garrigues & Ewald, 1987; Saber et
    al., 1987). This technique was used widely in the countries of former
    Soviet Union (Dikun, 1967). Synchronous luminescence and room
    temperature phosphorimetry have been reported to be simple,
    cost-effective techniques for screening PAH (Vo-Dinh et al., 1984;
    Abbott et al., 1986).

         Infrared analysis, particularly Fourier transform infrared
    spectroscopy coupled to gas chromatography (Stout & Mamantov, 1989),
    and capillary supercritical fluid chromatography (Wright & Smith,
    1989) have also been used. Various environmental samples have been
    analysed by packed column supercritical fluid chromatography, with
    rapid separation of PAH (Heaton et al., 1994).

    2.4.4  Choice of PAH to be quantified

         The choice of PAH depends on the purpose of the measurement. For
    example, carcinogenic PAH are of interest in studies of human health,
    but other, more abundant PAH may be of interest in ecotoxicological
    studies. Quantification of a number of PAH is advantageous when the
    profiles are to be correlated with sources and/or effects.

         Table 7 lists the PAH that are required or recommended to be
    determined at national or international levels. According to an EEC
    (1980) Directive, which followed a WHO (1971) recommendation, the
    concentrations of six reference compounds (also known as 'Borneff
    PAH') must be measured in drinking-water in order to check its
    compliance with the cumulative limit value for the PAH class. The
    choice of these six PAH by WHO was not based on toxicological
    considerations but on the fact that analytical investigations were
    then largely confined to these relatively easily detected compounds
    (WHO, 1984).


        Table 7. Some polycyclic aromatic hydrocarbons required or recommended for determination by various authorities

                                                                                                                    

    Compound                 WHO/EECa       US EPAb        European       Italyd         Norwaye
                             (drinking-     (waste         Aluminium      (air)                                     
                             water)         water)         Associationc                  Health         Environment
                                                                                                                    

    Acenaphthene                            X
    Acenapthylene                           X
    Anthracene                              X              X                                            X
    Anthanthrene                                                                         X              X
    Benz[a]anthracene                       X              X              X              X              X
    Benzo[a]fluorene                                       X
    Benzo[a]pyrene           X                             X              X              X              X
    Benzo[b]fluoranthene     X              X              X              X              X              X
    Benzo[b]fluorene                                       X
    Benzo[c]phenanthrene                                                                 X              X
    Benzo[e]pyrene                                         X
    Benzo[ghi]perylene       X              X              X                                            X
    Benzo[j]fluoranthene                    X                             X              X              X
    Benzo[k]fluoranthene     X              X              X              X              X              X
    Chrysene                                X              X                             X              X
    Cyclopenta[a]pyrene                                                                  X              X
    Dibenzo[a,e]pyrene                                     X                             X              X
    Dibenz[a,h]anthracene                   X              X              X              X              X
    Dibenzo[a,h]pyrene                                     X                             X              X
    Dibenzo[a,i]pyrene                                     X                             X              X
    Dibenzo[a,l]pyrene                                                                   X              X
    Fluoranthene             X              X              X                                            X
    Fluorene                                X
    Indeno[1,2,3-cd]pyrene   X              X              X              X              X              X
    Naphthalene                             X                                                           X
    Phenanthrene                            X              X                                            X
    Pyrene                                  X              X                                            X
    Triphenylene                                           X
                                                                                                                    

    Table 7 (continued)

    a Recommended by WHO (1971) and required by an EEC (1980) Directive
    b Required by the US Environmental Protection Agency (1984a) for the analysis of municipal and industrial
      wastewater
    c Recommended by the European Aluminium Association, Environmental Health and Safety Secretariat (1990)
    d Recommended by the Italian National Advisory Toxicological Committee for health-related studies
      (Menichini, 1992b)
    e Recommended at the International Workshop on polycyclic aromatic hydrocarbons (State Pollution Control
      Authority and Norwegian Food Control Authority, 1992) for studies of health and on the environment


         The method required by the US Environmental Protection Agency
    (1984a) for the analysis of municipal and industrial wastewater covers
    the determination of 16 'priority pollutant PAH' considered to be
    representative of the class. Outside the USA, this list of compounds
    is often taken as a reference list for the analysis of various
    environmental matrices.

    3.  SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

     Appraisal

         Coal and crude oils contain polycyclic aromatic hydrocarbons
    (PAH) in considerable concentrations owing to diagenetic formation in
    fossil fuels. The main PAH produced commercially are naphthalene,
    acenaphthene, anthracene, phenanthrene, fluoranthene, and pyrene. The
    release of PAH during production and processing, predominantly of
    plasticizers, dyes, and pigments, is of only minor importance. Most
    PAH enter the environment via the atmosphere from incomplete
    combustion processes, such as:

    -    processing of coal and crude oil: e.g. refining, coal
         gasification, and coking;
    -    heating: power plants and residential heating with wood, coal,
         and mineral oil;
    -    fires: e.g. forest, straw, agriculture, and cooking;
    -    vehicle traffic; and
    -    tobacco smoking.

         Industrial processes such as coal coking, aluminium, iron and
    steel production, and foundries make important contributions to the
    levels of PAH in the environment. An important indoor source of
    exposure to airborne PAH, especially in developing countries, is
    cooking fumes (see section 5.2).

         The hydrosphere and the geosphere are affected secondarily by wet
    and dry deposition. PAH are released directly into the hydrosphere,
    for example during wood preservation with creosotes. Deposition of
    contaminated refuse like sewage sludge and fly ash may cause further
    emissions into the geosphere.

         It is very difficult to identify a source on the basis of the
    ratio of the measured concentrations of different individual PAH, and
    such studies are in most cases inconclusive.

    3.1  Natural occurrence

         In some geographical areas, forest fires and volcanoes are the
    main natural sources of PAH in the environment (Baek et al., 1991). In
    Canada, about 2000 tonnes of airborne PAH per year are attributed to
    natural forest fires (Environment Canada, 1994). On the basis of
    samples from volcanoes, Ilnitsky et al. (1977) estimated that the
    worldwide release of benzo [a]pyrene from this source was 1.2-14
    t/year; no estimate was given of total PAH emissions from this source.

         Coal is generally considered to be an aromatic material. Most of
    the PAH in coal are tightly bound in the structure and cannot be
    leached out, and the total PAH concentrations tend to be higher in
    hard coal than in soft coals, like lignite and brown coal.
    Hydroaromatic structures represent 15-25% of the carbon in coal. The
    PAH identified include benz [a]anthracene, benzo [a]pyrene,

    benzo [e]pyrene, perylene, and phenanthrene (Neff, 1979; Anderson et
    al., 1986). Table 8 shows the typical contents of PAH in different
    crude oils, such as those derived from coal conversion or from shale.

    Table 8. Polycyclic aromatic hydrocarbon content of crude oils
    from various sources

                                                                       
    Compound                  PAH content (mg/kg) in crude oil from
                                                                       

                              Coala            Petroleum      Shale
                                                                       
    Acenaphthene              1700/1800        147-348        147-903
    Anthracene                4100             204-321        231-986
    Anthanthrene              Trace/< 800      NR             0.3
    Benz[a]anthracene         Trace/< 2200     1-7            1
    Benzo[a]fluorene          2100/2500        11-22          53
    Benzo[a]pyrene            < 500/< 1200     0.1-4          3-192
    Benzo[b]fluorene          < 1500/3400      < 13           140
    Benzo[c]phenanthrene      < 600/< 2200     NR             NR
    Benzo[e]pyrene            < 1200/1300      0.5-29         1-19
    Benzofluorenesb           < 500/< 1300     23             NR
    Benzo[ghi]fluoranthene    3200             NR             NR
    Benzo[ghi]perylene        4300/6600        ND-8           1-5
                                               ND-5
    Chrysene                  < 1500/2500      7-26           3-52
    Coronene                  NR               0.2            NR
    Dibenz[a,h]anthracene     NR               0.4-0.7        1-5
    Fluoranthene              < 1900/< 3700    2-326          6-400
    Fluorene                  5300/9900        106-220        104-381
    1-Methylphenanthrene      < 1200/< 5100    > 21           NR
    Naphthalene               100/2800         402-900        203-1390
    Perylene                  Trace/< 600      6-31           0.3-68
    Phenanthrene              12 000/20 400    > 129-322      221-842
    Pyrene                    14 200/35 000    2-216          18-421
    Triphenylene              NR               3/13           0.5
                                                                       

    From Guerin at al. (1978), Weaver & Gibson (1979), Grimmer at al.
    (1983a), Sporstol et al. (1983), IARC (1985, 1989b)
    Ranges represent at least three values; NR, not reported; ND, not
    detected
    a Two crude oils from coal conversion; single measurements
    b Isomers not specified

         Two rare PAH minerals have been described: the greenish-yellow,
    fluorescent curtisite from surface vents of hot springs at Skagg
    Springs, California, USA, and the bituminous mercury ore idrialite
    from Idria, Yugoslavia, the two main components of which are chrysene
    and dibenz [a,h]-anthracene. These minerals are assumed to have been
    formed by the pyrolysis of organic material at depths below that at
    which petroleum id generated (West et al., 1986).

    3.2  Anthropogenic sources

    3.2.1  PAH in coal and petroleum products

         Commercial processing of coal leads first to coal-tars, which are
    further processed to yield pitch, asphalt, impregnating oils
    (creosotes for the preservation of wood), and residue oils such as
    anthracene oil (IARC, 1985). The concentration of PAH in coal-tars is
    generally ¾ 1%; naphthalene and phenanthrene are by far the most
    abundant compounds, occurring at concentrations of 5-10%. Comparable
    levels were detected in high-temperature coal-tar pitches. The PAH
    content of soots is about one order of magnitude lower, and that of
    carbon and furnace blacks ranges from about 1 to 500 mg/kg, pyrene
    being present at the highest concentration (IARC, 1984a; Nishioka et
    al., 1986). The PAH contents of some impregnating oils, bitumens,
    asphalts, and roof paints are shown in Table 9. In bitumens, PAH
    constitute only a minor part of the total content of polyaromatic
    compounds.

        Table 9. Polycyclic aromatic hydrocarbon content of impregnating oils, bitumens, asphalts,
    and roof paints

                                                                                                
    Compound                 Concentration (mg/kg)
                                                                                                
                             Impregnating        Bitumens            Road tar (asphalt,  Roof
                             oils                (oil-derived)       coal-derived)       paint
                                                                                                

    Anthracene               1600-22 500         0.01-0.32           4170-14 400         2380
    Anthranthrene            NR                  Trace-1.8           NR                  NR
    Benz[a]anthracene        169-11 700          0.14-35             6820-24 100         6640
    Benzo[a]pyrene           45-3490             0.1-27              5110-10 400         5950
    Benzo[b]fluoranthene     42-3630             5                   4490-10 900         5420
    Benzo[e]pyrene           65-2020             0.03-52             3300-6750           3820
    Benzo[gh]perylene        57-570              Trace-15            2390-2730           3270
    Benzo[k]fluoranthene     24-2610             0.024-0.19          3170-7650           4470
    Chrysene                 NR                  0.04-34                                 NR
    Chrysene +               779-12 900          NR                  6820-26 100         7700
      triphenylene
    Coronene                 NR                  0.2-2.8             NR                  NR
    Fluoranthene             703-85 900          0.15-5              23 500-61 900       12 100
    Fluorene                 8040-58 400         NR                  6310-15 500         2220
    Indeno[1,2,3-cd]pyrene   57-273              Trace               3100-3530           3320
    Perylene                 66-744              0.08-39             1550-2300           1730
    Phenanthrene             7070-159 300        0.32-7.3            20 300-52 500       8180
    Pyrene                   604-46 400          0.08-38             15 100-42 500       8960
    Triphenylene             NR                  0.3-7.6             NR                  NR
                                                                                                

    From IARC (1985), Lehmann et al. (1986), Knecht & Woitowitz (1990);
    NR, not reported; ranges represent at least three values

         The concentrations of PAH in petrol and diesel fuels for vehicles
    and in heating oils are several parts per million. Almost all
    compounds are present at < 1 mg/kg; only phenanthrene, anthracene,
    and fluoranthene are sometimes found at > 10 mg/kg (Herlan, 1982).
    The PAH levels in unused engine lubricating oils are of the same order
    of magnitude. During the use of petrol-fuelled engine oils, the PAH
    content rises dramatically, by 30-500 times; in comparison, the total
    PAH levels in used diesel-fuelled engine oils were only 1.4-6.1 times
    greater than that in an unused sample. The major constituents of used
    oils are pyrene and fluoranthene, although benzo [b]fluoranthene,
    benzo [j]-fluoranthene, benzo [k]fluoranthene, benzo [a]pyrene, and
    dibenz [a,h]anthracene were also detected at considerable
    concentrations (IARC, 1984a; Carmichael et al., 1990).

         PAH have also been found in machine lubricating and cutting oils,
    which is of interest for the estimation of exposure in the workplace.
    The concentrations were < 7 mg/kg, although phenanthrene may have
    been present at a higher level (Grimmer et al., 1981a; Rimatori et
    al., 1983; Menichini et al., 1990; Paschke et al., 1992).

         PAH were detected in coloured printing oils, the concentrations
    of individual compounds varying between < 0.0001 and 63 mg/kg
    (Tetzen, 1989). By far the most abundant compounds were fluoranthene
    and pyrene (> 1 mg/kg); benzo [ghi]fluoranthene,
    cyclopenta [cd]pyrene, benz [a]anthracene, benzo [c]-phenanthrene,
    chrysene, triphenylene, benzo [b+j+k]fluoranthenes, benzo [a]pyrene,
    benzo [e]pyrene, anthanthrene, benzo [ghi]perylene,
    indeno[1,2,3- cd]pyrene, dibenz [a,h]anthracene, and coronene were
    found at concentrations of < 0.5 mg/kg.

    3.2.2  Production levels and processes

         Most of the PAH considered in this monograph are formed
    unintentionally during combustion and other processes. Only a few are
    produced commercially, including naphthalene, acenaphthene, fluorene,
    anthracene, phenanthrene, fluoranthene, and pyrene (Franck &
    Stadelhofer, 1987). The most important industrial product is
    naphthalene (see section 3.2.3). In 1987, about 220 kt of this
    compound were produced in western Europe, 190 kt in eastern Europe,
    170 kt in Japan, and 110 kt in the USA (Fox et al., 1988); in 1986,
    > 1 kt was produced in Canada (Environment Canada, 1994). In 1985,
    about 2.5 kt of acenaphthene and 20 kt of anthracene were produced
    worldwide (Franck & Stadelhofer, 1987). In 1986, 0.1-1 t anthracene
    and 1 t fluorene were produced in Canada (Environment Canada, 1994).
    In 1993, a major producer in Germany produced < 5000 t anthracene,
    < 1000 t acenaphthene, < 500 t pyrene, < 50 t phenanthrene, and
    < 50 t fluoranthene (personal communication, Rütgers-VfT AG, 1994).

         The substances are not synthesized chemically for industrial
    purposes but are isolated from products of coal processing, mainly
    hard coal-tar. The raw material is concentrated and the product
    purified by subsequent distillation and crystallization. Only
    naphthalene is sometimes isolated from pyrolysis residue oils, olefin

    fractions, and petroleum-derived fractions; it is also obtained by
    distillation and crystallization (Collin & Höke, 1985; Franck &
    Stadelhofer, 1987; Griesbaum et al., 1989; Collin & Höke, 1991). In
    the USA in 1970, the distribution of capacity was about 60% coal-tar-
    and 40% petroleum-derived naphthalene (Gaydos, 1981); more detailed
    data were not available. The purity of the technical-grade products is
    90-99% (Collin & Höke, 1985; Franck & Stadelhofer, 1987; Griesbaum et
    al., 1989; Collin & Höke, 1991; see also Section 2).

    3.2.3  Uses of individual PAH

         The uses of commercially produced PAH are as follows (Collin &
    Höke, 1985; Franck & Stadelhofer, 1987; Griesbaum et al., 1989; Collin
    & Höke, 1991):

    -     naphthalene: main use: production of phthalic anhydride
         (intermediate for polyvinyl chloride plasticizers); also,
         production of azo dyes, surfactants and dispersants, tanning
         agents, carbaryl (insecticide), alkylnaphthalene solvents (for
         carbonless copy paper), and use without processing as a fumigant
         (moth repellent) (see Figure 2);

    -     acenaphthene: main use, production of naphthalic anhydride
         (intermediate for pigments); also, for acenaphthylene
         (intermediate for resins);

    -     fluorene: production of fluorenone (mild oxidizing agent);

    -     anthracene: main use, production of anthraquinone (intermediate
         for dyes); also, use without processing as a scintillant (for
         detection of high-energy radiation);

    -     phenanthrene: main use, production of phenanthrenequinone
         (intermediate for pesticides); also, for diphenic acid
         (intermediate for resins)

    -     fluoranthene: production of fluorescent and vat dyes;

    -     pyrene: production of dyes (perinon pigments).

    3.2.4  Emissions during production and processing of PAH

         The emissions of PAH during industrial production and processing
    in developed countries are not thought to be important in comparison
    with the release of PAH from incomplete combustion processes, since
    closed systems and recycling procedures are usually used. Few data
    were available.

    3.2.4.1  Emissions to the atmosphere

         No data were available.

    FIGURE 2

    3.2.4.2  Emissions to the hydrosphere

         During the refining of aromatic hydrocarbons, and especially hard
    coal-tar, 80-190 t/year were estimated to be released to the
    hydrosphere in western Germany until 1987. This quantity was reduced
    to 8-19 t/year by the installation of new adsorption devices (sand
    filtration and adsorbent resin) by the two German hard coal-tar
    refineries in 1989 and 1991 (Klassert, 1993).

    3.2.5  Emissions during the use of individual PAH

         Only naphthalene is used directly (as a moth repellent) without
    further processing. On the assumption that all naphthalene-containing
    moth repellent is emitted into the atmosphere, the emissions would
    have been about 15 000 t/year in western Europe in 1986, about 4400
    t/year in Japan in 1987, and about 5500 t/year in the USA in 1987 (Fox
    et al., 1988).

    3.2.6  Emissions of PAH during processing and use of coal and petroleum
    products

         Coal coking, coal conversion by gasification and liquefaction,
    petroleum refining, and the production and use of carbon blacks,
    creosote, coal-tar, and bitumen from fossil fuels may produce
    significant quantities of PAH (Anderson et al., 1986). A great deal of
    information on emissions of PAH is available in the literature; this
    monograph gives an overview of the most reliable values. The emission
    profile depends on the source, and specific emission profiles are
    detectable only in the direct vicinity of the corresponding source.
    Generally, emissions are estimated on the basis of more or less
    reliable databases, which are not identified in most publications. The
    values reported give only a rough idea of the situation.

    3.2.6.1  Emissions to the atmosphere

          (a)  Coal coking

         During coal coking, PAH are released into the ambient air mainly
    when an oven is loaded through the charging holes and new coal is
    suddenly brought into contact with the hot oven, and from leaks around
    oven doors and battery-top lids (Bjorseth & Ramdahl, 1985; Slooff et
    al., 1989). The specific emission factor for both benzo [a]pyrene and
    benzo [e]pyrene during coal coking was 0.2 mg/kg coal charged (Ahland
    et al., 1985). The emission factor for total PAH was estimated to
    about 15 mg/kg coal charged (Bjorseth & Ramdahl, 1985).

         Stack gases were measured about 8 m away from the aperture
    through which coke was discharged at a Belgian coking battery.
    Although the effluent may have been slightly diluted with ambient air,
    the following PAH concentrations were detected: benz [a]anthracene
    plus chrysene, 580 ng/m3; benzo [k]fluoranthene, 500 ng/m3;
    benzo [a]pyrene plus benzo [e]pyrene, 470 ng/m3; fluoranthene, 330
    ng/m3; pyrene, 180 ng/m3 benzo [ghi]perylene, 140 ng/m3;

    anthracene plus phenanthrene, 130 ng/m3; and perylene, 44 ng/m3
    (Broddin et al., 1977).

         The release of total PAH in 1985 was estimated to about 630
    t/year in the USA, 18 t/year in Sweden, and 5.1 t/year in Norway
    (Bjorseth & Ramdahl, 1985). The authors emphasized that their data are
    subject to uncertainty and should be used only as an indication of the
    order of magnitude. In 1990, the total PAH emission in Canada was
    estimated to be 13 t/year (Environment Canada, 1994). Further
    estimates of total annual emissions of individual PAH compounds during
    the coking of coal are shown in Table 10.


        Table 10, Estimated annual emissions of polycyclic aromatic hydrocarbons during
    coal coking in the Netherlands and western Germany

                                                                                 

    Compound                 Annual       Year            Reference
                             emission
                             (t/year)
                                                                                 

    Netherlands
    Anthanthrene             0.5          Before 1989     Slooff at al. (1989)
    Benz[a]anthracene        0.3          1988            Slooff at al. (1989)
    Benzo[a]pyrene           0.1          Before 1989     Slooff at al. (1989)
    Benzo[ghi]perylene       0.2          1988            Slooff et al. (1989)
    Benzo[k]fluoranthene     0.1          1988            Slooff at al. (1989)
    Chrysene                 0.2          1988            Slooff at al. (1989)
    Fluoranthene             1.1          1988            Slooff at al. (1989)
    lndeno[1,2,3-cd]pyrene   0.1          1988            Slooff et al. (1989)
    Naphthalene              1.3          1987            Slooff et al. (1988)
                             2.0          Before 1989     Slooff et al. (1989)
    Phenanthrene             2.1          1988            Slooff et al. (1989)

    Western Germany
    Benzo[a]pyrene           1.1          1990            Ministers for the
                                                          Environment (1992);
                             1.7                          Zimmermeyer et al.
                                                          (1991)
    Naphthalene              10.0         1987            Society of German
                                                          Chemists (1989)
                                                                                 

         The emission factors for benzo [a]pyrene in the coking industry
    in the North-Rhine Westphalia area of Germany have been assumed to
    have been reduced to an average of about 60 mg/t coke. The newest
    plants have emission factors of 40 mg/t coke (Eisenhut et al., 1990).
    The reduction in PAH discharge was brought about by technical
    improvements to existing plants, closure of old plants and their
    partial replacement by new plants, and a reduction in coke production
    (Zimmermeyer et al., 1991). Decreasing trends in the annual emissions
    of airborne PAH during coke production are also assumed to have
    occurred in other industrialized countries (western Europe, Japan, and
    the USA), but no data were available.

          (b)  Coal conversion

         PAH emission factors measured in the USA during gasification of
    coal at the end of the 1970s ranged from about 1 µg/g burnt coal for
    chrysene and 1500 µg/g burnt coal for naphthalene. Three qualities of
    coal were analysed for naphthalene, acenaphthylene, fluorene,
    anthracene, phenanthrene, pyrene, benz [a]anthracene, chrysene,
    benzo [b]fluoranthene, benzo [k]fluoranthene, benzo [a]pyrene,
    benzo [ghi]perylene, indeno[1,2,3- cd]pyrene, and
    dibenzo [a,h]pyrene (Nichols et al., 1981). In 1981, the stack gas of
    one US pilot coal gasification plant with an outdoor filter contained
    0.2 and 2.1 µg/m3 naphthalene at two sampling times and 6.8 µg/m3
    phenanthrene (Osborn et al., 1984). Acenaphthylene was detected at
    concentrations of 0.11-0.12 µg/m3 in the stack gases of two Canadian
    pilot coal liquefaction plants (Leach et al., 1987).

          (c)  Petroleum refining

         The average profile of PAH compounds in petroleum refineries
    indicates that at least 85% of the total concentration is made up of
    two-ring compounds (naphthalene and its derivatives) and 94% of two-
    and three-ring compounds. Compounds with five rings or more
    contributed less than 0.1% at the catalytic cracking unit. In
    turn-round operations on reaction and fractionation towers,
    naphthalene and its methyl derivatives accounted for more than 99% of
    the total PAH (IARC, 1989b).

         Little information is available on the concentrations of PAH in
    stack gases. The levels in one French (Masclet et al., 1984) and two
    US petroleum refining plants (Karlesky et al., 1987) are available
    (Table 11); no information was given about the sampling site in the
    French facility, but sampling in the US plants was at the distillation
    device and below the cracking tower. The results depended on which
    fuel was burnt and the positioning and type of sampling device in the
    stack.

    Table 11. Polycyclic aromatic hydrocarbon concentrations
    in the stack gases of petroleum refinery plants in
    France and the USA

                                                             

    Compound                   Concentration (µg/m3)
                                                             
                               France      USA
                                                             

    Acenaphthene               NR          0.018-0.035
    Acenaphthylene             NR          0.013/0.019
    Anthracene                 3.9         0.003-0.041
    Benz[a]anthracene          1.6         0.051-0.801
    Benzo[a]pyrene             0.4         0.261-3.17
    Benzo[b]fluoranthene       1.3         0.323-0.616a
    Benzo[e]pyrene             2.8         NR
    Benzo[ghi]perylene         0.7         0.23/0.382
    Benzo[k]fluoranthene       0.5         NR
    Chrysene                   1.7         0.021-0.252
    Coronene                   1.0         NR
    Dibenzo[a,h]anthracene     NR          0.177
    Fluoranthene               2.3         0.030-0.577
    Fluorene                   2.4         0.041-2.48
    Indeno[1,2,3-cd]pyrene     1.2         0.25/0.538
    Naphthalene                NR          0.052-0.113
    Perylene                   ND          ND
    Phenanthrene               7.9         0.040-9.13
    Pyrene                     4.3         0.016-3.56
                                                             

    From Masclet et aL (1984) and Karlesky et al. (1987)
    NR, not reported; ND, not detected, limit of detection not
    stated; /, single measurements
    a Plus benzo[k]fluoranthene


         Few data are available on the total release of PAH into the
    atmosphere during petroleum refining. In western Germany, the
    emissions of naphthalene during petroleum refining, including hard
    coal-tar processing, were estimated to be 11 t/year (year not given;
    Society of German Chemists, 1989). In the Netherlands, the release of
    total PAH in 1988 was estimated to be about 7 t/year; the burning of
    pitch contributed 6.6 t/year, regeneration of catalyst, 0.4 t/year,
    and refining, < 0.01-0.1 t/year (Slooff et al., 1989). In Canada,
    about 0.1 t total PAH were emitted into the atmosphere in 1990
    (Environment Canada, 1994).

          (d)  Other processes

         In a US oil-furnace carbon black plant, the following mean
    emission factors per kg carbon black produced were found for
    individual PAH in three runs in the main vent gas: acenaphthylene,
    800 œg; pyrene, 500 œg; anthracene plus phenanthrene, 70 œg;
    fluoranthene, 60 œg; benzo [ghi]fluoranthene, 40 œg;
    benzo [b]fluoranthene plus benzo [j]fluoranthene plus
    benzo [k]fluoranthene, 30 œg; benzo [a]pyrene plus benzo [e]pyrene
    plus perylene, 30 œg; benzo [ghi]perylene plus anthanthrene, 23 œg;
    chrysene plus benz [a]anthracene, 9 œg; indeno[1,2,3- cd]pyrene,
    < 2 œg; and benzo [c]phenanthrene, < 2 œg. The release of PAH into
    ambient air cannot be estimated from these emission factors, however,
    as an additional combustion device is fitted in most US carbon-black
    plants in which the process vent gases are burnt (Serth & Hughes,
    1980).

         Compounds with five or more rings (e.g. benzo [a]pyrene)
    contributed about 0.3% to the total PAH released from the bitumen
    processing unit of a refinery (IARC, 1989b). The emissions of PAH from
    batch asphalt mixers are assumed to be low and to occur mainly in
    combustion gases (IARC, 1984a), although no experimental data were
    available.

         Few estimates have been made of the annual emissions of PAH from
    processes in which coal and coal products are used. The total release
    of PAH to the atmosphere during asphalt production in 1985 was
    estimated to be about 4 t in the USA, 0.1 t in Norway, and 0.3 t in
    Sweden (Bjorseth & Ramdahl, 1985). In Canada, the amount emitted in
    1990 was estimated to be about 2.5 t (Environment Canada, 1994). The
    amount released during carbon-black production and processing in 1985
    was estimated to be about 3 t in the USA and < 0.1 t in Sweden
    (Bjorseth & Ramdahl, 1985). In the Netherlands in 1988, about 3.3 t of
    total PAH were emitted during the storage and transport of anthracene
    oil, an intermediate in the processing of hard coal-tar (Slooff et
    al., 1989).

          (e)  Use of impregnating oils (creosotes) in wood preservation

         Estimates of the total input of PAH into the atmosphere from wood
    preservation with creosotes were available only for the Netherlands
    for unspecified years, at about 320 t/year (Slooff et al., 1989) and
    840 t/year (Berbee, 1992). In 1988, the PAH input during storage of
    preserved material was estimated by the same authors to be about 200 t
    naphthalene, 110 t phenanthrene, 30 t fluoranthene, 5 t anthracene,
    1.1 t benz [a]anthracene, and 0.02 t benzo [k]fluoranthene.

    3.2.6.2  Emissions to the hydrosphere

          (a)  Coal coking

         The concentrations of PAH reported in wastewater effluents are
    shown in Table 12. The removal of PAH by biological oxidation in two
    US coal coking plants was 93 to > 99%. Higher-molecular-mass PAH,
    benzo [a]pyrene, dibenz [a,h]anthracene, and benzo [ghi]perylene,
    comprised a greater fraction (about 60%) of the total PAH content in
    the effluent than in the input stream (Walters & Luthy, 1984). The
    total concentration of PAH discharged into the aqueous environment
    from a Norwegian coking plant was estimated to be about 23 kg/d
    (Berglind, 1982). On the basis of Dutch emission factors, the release
    in western Europe in 1985 of fluoranthene was calculated to be about 5
    t and that of benzo [a]pyrene about 0.7 t (Berbee, 1992). The total
    annual input of PAH into the aqueous environment of the Netherlands
    was estimated to be about 1.7 t (year not given; Slooff et al., 1989).

          (b)  Coal conversion

         The PAH content of wastewater from coal and shale conversion was
    < 0.5 mg/litre (Guerin, 1977). In raw, untreated wastewaters from a
    US pilot coal liquefaction plant, numerous PAH were found to emanate
    from the liquefaction section, the untreated hydrogenation section,
    and the still bottoms processing device when two kinds of coal were
    tested; for example, benzo [a]pyrene was found at a concentration of
    0.3-52 µg/litre (Robbins et al., 1981). Numerous PAH were found in raw
    wastewater samples from two US pilot coal gasification plants (Walters
    & Luthy, 1981; Abbott et al., 1986), the maximum level of
    benzo [a]pyrene being 5.0 µg/litre.

         No information was available about total PAH emissions into the
    aqueous environment from commercial coal conversion plants. In
    groundwater near a US in-situ coal gasification site, naphthalene was
    found at a concentration of 2.7 µg/litre and acenaphthene and fluorene
    at < 0.1 µg/litre (Pellizzari et al., 1979).

         Until 1988, the final effluent from the two hard coal-tar
    refineries in western Germany contained an average of 50 mg/litre
    naphthalene, with a maximum of 120 mg/litre. The annual emission of
    this compound was thus calculated to be about 80 t. By 1991, the
    estimated release of naphthalene had been reduced to about 8 t/year by
    the addition of adsorption devices (Klassert, 1993).

          (c)  Petroleum refining and offshore oil-well drilling

         PAH concentrations in wastewater effluents from these sources are
    summarized in Table 13. A refinery-activated sludge unit with a
    dual-media filter removed about 95% of the five-ring PAH and 99% of
    the four-ring PAH from the effluent of a petroleum refinery (Pancirov
    et al., 1980). A similar elimination efficiency was found for
    dissolved air flotation treatment of refinery wastewater and
    subsequent removal by activated sludge. Air stripping of the compounds

    in the sewage plant seemed to be of minor importance (Snider &
    Manning, 1982). The concentrations of PAH with more than three rings
    were found to be < 0.05 µg/litre even in the input to a sewage device
    and < 0.02 µg/litre in the final effluent (German Society for
    Mineral-oil and Coal Chemistry, 1984). The authors stated that these
    levels were of the same order of magnitude as the background
    concentrations in surface waters.

         The discharge of total PAH from a Norwegian petroleum refinery
    was about 0.26 kg/day (Berglind, 1982). The total concentration of PAH
    released into the North Sea from offshore oil-well drilling activities
    was about 2.5 t/year in 1987, comprising 2 t/year from drill rinsing
    and 0.2 t/year from shipping (Slooff et al., 1989).

          (d)  Use of impregnating oils (creosotes) in wood preservation

         PAH were detected at levels of milligrams per litre in
    groundwater under a former wood preserving facility in Florida, USA.
    The concentrations of lower-molecular-mass creosote constituents were
    smaller in the groundwater than in an unweathered standard, probably
    because of greater mobility and biodegradability (Mueller & Lantz,
    1993; Middaugh et al., 1994).

         Model experiments with fresh and seawater were carried out to
    determine the release of PAH from marine pilings made from southern
    pine and preserved with creosote (Ingram et al., 1982). The PAH levels
    per litre fresh water in the leachate at 20°C after immersion for
    three days were: naphthalene, 200-350 œg; acenaphthene, 190-230 œg;
    phenanthrene, 190-230 œg; fluorene, 120-150 œg; acenaphthylene, 51-88
    œg; anthracene, 48-76 œg; fluoranthene, 27-30 œg; pyrene, 12 œg; and
    benz [a]anthracene, 11-19 œg. The concentrations in seawater were
    three to four times lower. The amounts of PAH leached increased with
    increasing temperature. The concentrations in leachates from pilings
    that had been in seawater for 12 years were of the same order of
    magnitude. In contrast, rapidly decreasing PAH concentrations were
    found three months after the start of the experiment in runoff
    rainwater from spruce and pine pilings impregnated with hard coal-tar
    (van Dongen, 1987).

         The total PAH emissions into water and soil in the Netherlands
    from commercial wood preservation were about 28 t/year (year not
    given). The release of 10 PAH into water during the storage of
    creosote-preserved wood was about 16 t/year; the PAH measured were
    naphthalene, anthracene, phenanthrene, fluoranthene,
    benz [a]anthracene, benzo [a]pyrene, benzo [ghi]-perylene, and
    indeno[1,2,3- cd]pyrene) (Slooff et al., 1989).

         In Canada, the maximum release of PAH into water and soil from
    creosote-treated wood products was estimated to be 2000 t/year, on the
    basis of the PAH content of creosote, the volume of treated wood, the
    retention rates of the substances for different wood species, and an
    estimated 20% loss of PAH during the time the wood was in service,
    i.e. 40 years for pilings and 50 years for railroad ties (Environment
    Canada, 1994).

        Table 12. Polycyclic aromatic hydrocarbon concentrations (µg/litre) in
    wastewater effluents from coal coking plants

                                                                                

    Compound                 [1]     [2]    [3]a            [4]         [5]
                                                                                

    Acenapthene              NR      NR     NR              0.009-2.5   NR
    Acenaphthylene           NR      NR     NR              NR          NR
    Anthracene               0.31    NR     NR              0.0-2.0     0.1
    Anthanthrene             ND      NR     0.040/0.600     NR          NR
    Benzo[j+k]fluoranthene   NR      NR     NR              NR          NR
    Benz[a]anthracene        2.0     11.1   0.504/4.9       NR          NR
    Benzo[a]fluoranthene     0.8     NR     NR              NR          NR
    Benzo[a]pyrene           NR      3.8    0.622/4.841     4.7-25      NR
    Benzo[b]fluoranthene     NR      NR     NR              NR          NR
    Benzo[a]fluorene         0.81    NR     NR              NR          NR
    Benzo[c]phenanthrene     ND      NR     0.042/0.699     NR          NR
    Benzo[e]pyrene           NR      NR     0.323/2.928     NR          NR
    Benzofluoranthenesb      NR      6.9    1.010/8.741     NR          NR
    Benzo[ghi]fluoranthene   ND      NR     0.042/0.663     NR          NR
    Benzo[ghi]perylene       2.0     NR     0.445/2.835     0-9.0       NR
    Chrysene                 NR      7.2    0.732/6.440     1.8-42      NR
    Dibenz[a,h]anthracene    NR      NR     NR              0.06-3.0    NR
    Fluoranthene             2.8     11.2   NR              1.3-10      NR
    Fluorene                 NR      NR     NR              0.0-1.0     NR
    Indeno[1,2,3-cd]pyrene   NR      NR     0.371/3.051     NR          NR
    1-Methylphenanthrene     ND      NR     NR              NR          NR
    Naphthalene              NR      NR     NR              0-4.1       NR
    Perylene                 ND      NR     0.117/1.348     NR          NR
    Phenanthrene             0.4     NR     NR              0.45-2.3    0.5
    Pyrene                   4.0     12.9   NR              NR          0.38-60
                                                                                

    [1] Effluent channel water from one US coking plant (Griest, 1980);
    [2] Effluent channel water from one US coking plant (Griest at al., 1981);
    [3] Raw wastewater from two coking plants in western Germany (Grimmer at
        al., 1981 b);
    [4] Effluents from two US coking plants downstream of company-owned biological
        oxidation device (Walters & Luthy, 1984);
    [5] Final effluent after biological oxidation; no further information
        (Jockers at al., 1988) When the water samples were filtered through solid
        sorbents, the results may be underestimates of the actual content of
        polycyclic aromatic hydrocarbons (see section 2.4.1.4)
    ND, not detected, limit of detection not given; NR not reported
    a   /, single measurements
    b   Isomers not specified

    Table 13. Polycyclic aromatic hydrocarbons in effluents after wastewater
    treatment in petroleum refineries (µg/litre)

                                                                                    

    Compound                 [1]       [2]       [3]             [4]      [5]
                                                                                    

    Acenaphthene             NR        4.0       < 0.1-6         NR       NR
    Acenaphthylene           NR        1.8       < 0.1-< 1       NR       NR
    Anthracene               NR        11        < 0.01-< 2      0.26     NR
    Benz[a]anthracene        NR        0.6       < 0.02-< 1      NR       NR
    Benzo[a]pyrene           0.57      0.1       0.1-2.9         0.11     NR
    Benzo[b]fluoranthene     < 0.1     0.2       < 0.06          NR       NR
    Benzo[c]phenanthrene     NR        0.2       NR              NR       NR
    Benzo[e]pyrene           0.65      0.3       NR              NR       NR
    Benzo[ghi]fluoranthene   < 0.4     NR        NR              NR       NR
    Benzo[ghi]perylene       0.36      NR        < 0.2-< 1       NR       NR
    Benzo[j]fluoranthene     < 0.2     NR        NR              NR       NR
    Benzo[k]fluoranthene     < 0.2     0.4a      < 0.2           NR       NR
    Chrysene                 < 0.03    1.4b      < 0.02-1.4      NR       NR
    Coronene                 < 0.01    NR        NR              NR       NR
    Dibenz[a,h]anthracene    NR        NR        < 0.3-< 1       NR       NR
    Fluoranthene             < 0.2     16.0      < 0.1-< 10      0.26     NR
    Fluorene                 NR        3.4       < 0.1-< 1       1.2      NR
    Indeno[1,2,3-cd]pyrene   < 0.02    NR        < 1             NR       NR
    1-Methylphenanthrene     NR        4.2       NR              NR       NR
    Naphthalene              NR        2.4       < 0.1-< 10      15       0.06-9
    Perylene                 0.14      NR        NR              NR       NR
    Phenanthrene             NR        111.0     < 0.2-< 0.5     7.1      0.02-1.2
    Pyrene                   0.07      16.1      < 0.1-7         NR       NR
    Triphenylene             < 0.03    NR        NR              NR       NR
                                                                                    

    [1] Final effluent from one US petroleum refinery (Pancirov et al., 1980);
    [2] Effluent from one Norwegian petroleum refinery after treatment in
        oil-separation devices, oil traps, and retention ponds (Berglind, 1982);
    [3] Average results for final effluent from 17 US petroleum refineries
        (Snider & Manning, 1982);
    [4] Final effluent from one Australian petroleum refinery (Symons & Crick,
        1983);
    [5] Average results for the final effluent from six petroleum refineries
        in western Germany (German Society for Mineral-oil and Coal Chemistry,
        1984)
        When water samples were filtered through solid sorbents, the results may
        be underestimates of the actual PAH content (see section 2.4.1.4).
    NR, not reported
    a With benzo[j]fluoranthene
    b With triphenylene

          (e)  Other sources

         PAH may be released into the hydrosphere during leaching of
    stocks of coal by rain. In model leaching experiments, naphthalene,
    acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene,
    pyrene, chrysene, benz [a]anthracene, benzo [k]fluoranthene, and
    benzo [a]pyrene were detected at concentrations in the low microgram
    per litre range, with a maximum of 100 µg/litre; for example,
    benzo [a]pyrene was found at 0.6 µg/litre (Stahl et al., 1984;
    Fendinger et al., 1989).

         PAH were also found in sludge from US coke processing plants in
    the following concentrations (average of five samples): naphthalene,
    430 mg/kg; phenanthrene, 260 mg/kg; acenaphthene, 78 mg/kg; pyrene, 30
    mg/kg; chrysene, 28 mg/kg; benzo [a]pyrene, 3.8 mg/kg;
    benzo [b]fluoranthene, 3.8 mg/kg; and benzo [ghi]perylene, 0.9 mg/kg
    (Tucci, 1988).

         PAH may also leach into drinking-water from coal-tar or asphalt
    coatings on storage tanks and water distribution pipes. Samples from a
    five-year-old coal-tar-coated water tank in the USA contained 0.21
    µg/litre phenanthrene plus anthracene, 0.081 µg/litre fluoranthene,
    0.071 µg/litre pyrene, 0.025 µg/litre naphthalene, and 0.021 µg/litre
    fluorene (Alben, 1980). Measurements in numerous US drinking-water
    systems showed that PAH accumulate in the water during transport in
    these pipes. The total concentration of fluoranthene,
    benzo [j]fluoranthene, benzo [k]fluoranthene, benzo [a]pyrene,
    indeno[1,2,3- cd]-pyrene, and benzo [ghi]perylene after transport
    was in the low nanogram per litre range (Basu et al., 1987). In 1994,
    a PAH concentration of 2.7 µg/litre was measured in accordance with
    the German Directive on drinking-water (6.9 µg/litre measured in
    accordance with US regulations), which was due to transport through a
    tar-coated pipe in a central water reservoir; phenanthrene was present
    at a concentration of 2.8 µg/litre and pyrene at 1.2 µg/litre (State
    Chemical Analysis Institute, Freiburg, 1995). The release of PAH from
    this source cannot be estimated from the available data.

         During offshore oil and gas production, PAH-containing drilling
    muds are discharged directly into the sea. The PAH concentrations at
    some oil and gas platforms in the Gulf of Mexico and the North Sea
    were found to be 1900 µg/litre for naphthalene and < 0.01 µg/litre
    each for chrysene, benzo [b]fluo-ranthene, and
    dibenz [a,h]anthracene (van Hattum et al., 1993).

         The total PAH passing into the oceans from shipping have not been
    estimated. The worldwide discharge of PAH into the oceans from
    refineries, marine transportation, and industrial effluents of crude
    oil was estimated to be about 6 t/year in 1973 and 4.6 t/year in the
    early 1980s (Suess, 1976), but the basis for these estimates is
    unknown.

    3.2.6.3  Emissions to the geosphere

         The average PAH concentrations in soil from more than 20 former
    coking sites in Germany were: naphthalene, 1000 mg/kg; phenanthrene,
    500 mg/kg; fluoranthene, 200 mg/kg; pyrene, 200 mg/kg; anthracene, 50
    mg/kg; and benzo [a]pyrene, 3-5 mg/kg. During vertical leaching, the
    compounds are distributed according to their mobility. PAH with
    high-boiling points and low water solubility are present at the
    highest concentrations at the surface, and more mobile compounds
    accumulate in deeper soil layers. Naphthalene is usually leached into
    groundwater, in which it is relatively soluble (Hoffmann, 1993).

         The sediment of an effluent channel at one US coking plant
    contained the following concentrations of PAH (dry weight basis):
    fluoranthene, 31 mg/kg; pyrene, 23 mg/kg; benzo [b+j+k]fluoranthenes,
    23 mg/kg; benzopyrenes, 19 mg/kg; benz [a]anthracene, 15 mg/kg;
    chrysene plus triphenylene, 15 mg/kg; benzo [ghi]perylene, 7.3 mg/kg;
    benzo [a]fluorene, 7.2 mg/kg; anthracene, 6.7 mg/kg; perylene, 3.8
    mg/kg; phenanthrene, 3.6 mg/kg; benzo [b]fluorene, 3.2 mg/kg;
    benzo [ghi]fluoranthene, 2.3 mg/kg; anthanthrene, 2.3 mg/kg;
    benzo [c]phenanthrene, 2.1 mg/kg; and 1-methylphenanthrene, 0.71
    mg/kg. In the sediment of an effluent from one US petroleum tank farm,
    anthracene was detected at 3.4 mg/kg, benz [a]anthracene at 0.13
    mg/kg, and benzo [a]pyrene at < 0.049 mg/kg (Griest, 1980).

         Oily sludge originating from a dissolved air flotation unit of
    the treatment system of a US petrochemical plant effluent was applied
    to sandy loam samples seven times during a 920-day active disposal
    period followed by a 360-day inactive 'closure' period, and the
    decreases in the concentrations of fluorene, phenanthrene, anthracene,
    fluoranthene, pyrene, benz [a]anthracene, chrysene, triphenylene,
    benzo [ghi]fluoranthene, benzo [b]fluoranthene,
    benzo [j]fluoran-thene, benzo [k]fluoranthene, perylene,
    benzo [a]pyrene, benzo [e]pyrene, and benzo [ghi]perylene in soil
    were determined. The initial PAH levels ranged from 0.9 mg/kg
    benzo [j]fluoranthene to 270 mg/kg phenanthrene (dry weight basis).
    After 1280 days, the three-ring compounds (fluorene, phenanthrene,
    anthracene) had almost completely disappeared, with 0.2-6.9%
    remaining, the four-ring substances (fluoranthene,
    benz [a]anthracene, chrysene) had been partly degraded, and the
    five-ring compounds remained at fairly high concentrations (Bossert et
    al., 1984).

         PAH may be released into soil from polluted industrial sludges
    and during commercial wood preservation; however, no estimates of the
    total PAH input into this compartment were available.

    3.2.6.4  Emissions into the biosphere

         Use of anti-dandruff shampoos containing hard coal-tar may lead
    to increased body concentrations of PAH, as measured by urinary
    excretion of the PAH metabolite 1-hydroxypyrene. One shampoo had a
    total PAH content of 2800 mg/kg, including 290 mg/kg pyrene and 56

    mg/kg benzo [a]pyrene (no further specification) (van Schooten et
    al., 1994). Application of a 2% crude coal-tar solution in petrolatum
    led to significantly increased PAH levels in the blood of five
    volunteers (Storer et al., 1984; see also Section 8). Measurements of
    hard coal-tar-containing shampoos in Germany showed concentrations of
    7-61 mg/kg benzo [a]pyrene. In wood-tar-containing shampoos,
    benzo [a]pyrene was detected at concentrations in the low microgram
    per kilogram range, but 150 mg benzo [a]pyrene were found in one tar
    bath (State Chemical Analysis Institute, Freiburg, 1995).

    3.2.7  Emissions of PAH due to incomplete combustion

         PAH not only pre-exist in fossil fuels but more are formed during
    pyrolysis by a radical mechanism (see Zander, 1980). The domestic
    activities that may result in significant emissions of PAH emissions
    are vehicle traffic, tobacco smoking, broiling and smoking of foods,
    and refuse burning. The industrial activities that result in PAH
    release are aluminium production with use of Söderberg electrodes,
    iron and steel production, foundries, tyre production, power plants,
    incinerators, and stubble burning (Anderson et al., 1986)

    3.2.7.1  Industrial point sources

          (a)  Emissions to the atmosphere

          (i)  Power plants fired with coal, oil, and gas fossil fuels

         PAH emitted into the atmosphere from coal-fired power plants
    consist mainly (69-92%) of two- and three-ring compounds, i.e.
    naphthalene and phenanthrene and their mono- and dimethyl derivatives.
    Naphthalene is by far the major component of PAH fractions (31-35%),
    although high concentrations of phenanthrene and fluorene are also
    observed (Bonfanti et al., 1988). Specific emission factors of 0.02 œg
    emitted per kg combusted were measured for benzo [a]pyrene and 0.03
    µg/kg for benzo [e]pyrene (Ahland et al., 1985).

         The concentrations of PAH in stack gases from comparable coal-
    and oil-fired power plants are shown in Table 14. It is difficult to
    find a characteristic PAH profile for coal-fired plants. The
    concentrations were low during undisturbed combustion (Guggenberger et
    al., 1981; Warman, 1985). Low-molecular-mass PAH are found at higher
    concentrations than high-molecular-mass compounds in coal combustion
    effluents (Warman, 1985); the low-molecular-mass PAH phenanthrene,
    fluoranthene, and pyrene were detected at particularly high
    concentrations, whereas benzo [a]pyrene was found at a level typical
    of that in ambient air (Kanij, 1987). The specific emission factor for
    benzo [a]pyrene was 3.5-230 µg/t burnt coal (Ahland & Mertens, 1980).
    As the contribution of benzo [a]pyrene to the total release of PAH is
    small, it was considered not to be a suitable indicator for this
    source (Guggenberger et al., 1981). In contaminated areas, the PAH
    concentrations in ambient air may be higher than those in the stack
    gases, which result from after-burning (Guggenberger et al., 1981).


        Table 14. Concentrations of polycyclic aromatic hydrocarbons (ng/m3) in stack gases of coal- and oil-fired power plants

                                                                                                                            

    Compound                 Fuel      [1]             [2]         [3]              [4]         [5]             [6]a
                                                                                                                            

    Acenaphthene             Coal      NR              NR          NR               NR          NR              ND-24
    Anthracene               Coal      NR              0.5         < 10-1800        0.4-100     2-65            19-120
    Anthanthrene             Coal      NR              NR          NR               NR          < 0.2-< 0.6     NR
    Benz[a]anthracene        Coal      NR              0.6         < 20-1400        NR          1-40            NR
    Benzo[a]pyrene           Coal      < 0.1-0.7b      1.3         0.5-790          0.1-120     0.1-1.9         NR
                                       < 0.5c
                             Oil       < 0.5-7         NR          NR               NR          NR              NR
    Benzo[b]fluoranthene     Coal      < 0.1-3b,d      2.0         30/40k           NR          0.3-12          NR
                                       < 0.1-0.4c,d                (1/880e)
                             Oil       < 0.1-39a       NR          NR               NR          NR              NR
    Benzo[b]fluorene         Coal      NR              NR          NR               NR          < 2-< 6         NR
    Benzo[c]phenanthrene     Coal      NR              NR          0.2              NR          NR              NR
    Benzo[e]pyrene           Coal      NR              ND          < 10-810         NR          3-< 18          NR
    Benzo[ghi]perylene       Coal      NR              NR          < 10-1400        NR          NR              NR
                             Coal      < 0.5-3b        1.2         < 10-< 100       3-22        < 2-< 6         NR
                                       < 0.5c
                             Oil       < 0.5-40        NR          NR               NR          NR              NR
    Benzo[j]fluoranthene     Coal      NR              NR          NR               NR          < 5-< 13        NR
    Benzo[k]fluoranthene     Coal      < 0.1-2b        0.9         20               NR          1.7-2.5         NR
                                       < 0.1-1.3c
                             Oil       < 0.1-29        NR          NR               NR          NR              NR
    Chrysene                 Coal      NR              1.8         < 10-< 600       0.1-28      1-41            ND-56
                                                       < 10-310e
                                                       3.8g
    Coronene                 Coal      1-3b            0.9         < 100            NR          NR              NR
                                       < 2c
                             Oil       < 2-36          NR          NR               NR          NR              NR
    Dibenz[a,h]anthracene    Coal      < 0.5-2b        NR          < 100            NR          NR              NR
                                       < 0.5c
                             Oil       < 0.5-26        NR          NR               NR          NR              NR

    Table 14. (continued)

                                                                                                                            

    Compound                 Fuel      [1]             [2]         [3]              [4]         [5]             [6]a
                                                                                                                            

    Fluoranthene             Coal      NR              4.1         < 10-22 100      0.5-240     20-720          NR
    Fluorene                 Coal      NR              1.9         NR               NR          NR              2-140
    Indeno[1,2,3-cd]pyrene   Coal      NR              1.7         < 10-< 100       NR          < 0.1-< 1.4     NR
    1-Methylphenanthrene     Coal      NR              NR          < 20-90          NR          NR              NR
    Naphthalene              Coal      NR              NR          NR               10-1800     NR              420-2100
    Perylene                 Coal      < 0.1-0.2b      NR          NR               NR          NR              NR
                                       < 0.1c
                             Oil       < 0.1-15        ND          < 10-< 100       NR          < 0.2-0.9       NR
    Phenanthrene             Coal      NR              5.2         < 20-33 200      26-640      32-2930         NR
    Pyrene                   Coal      NR              1.3         9-5800           0.2-2850    5-335           ND-311
    Triphenyene              Coal      NR              NR          NR               NR          20-77           NR
                                                                                                                            

    [1] Coal- and oil-fired power plants in the former FRG (Guggenberger et al., 1981);
    [2] One French coal-fired power plant (Masclet at al., 1984);
    [3] 10 Swedish coal-fired power plants (Warman, 1985);
    [4] One US coal-fired power plant (Junk at al., 1986);
    [5] One Dutch coal-fired power plant (Kanij, 1987);
    [6] One German coal-fired power plant with circulating fluid bed combustion (Wienecke at al., 1992)
    NR, not reported; ND, not detected, limit of detection not given
    a Various coal qualities
    b Hard coal
    c Brown coal
    d With benzo[e]pyrene
    e Isomers not specified
    f With triphenylene
    g With benz[a]anthracene


         The inputs of PAH into the atmosphere from power plants were:
    about 0.001 t benzo [a]pyrene in western Germany in 1981 (Ahland et
    al., 1985) and 0.1 t in 1983 (Grimmer, 1983a); about 1 t/year total
    PAH in the USA; 0.1 t in Norway and 6.6 t in Sweden in 1985 (Bjorseth
    & Ramdahl, 1985); about 2 t total PAH in the Netherlands in 1988
    (Slooff et al., 1989); and about 11 t total PAH in Canada in 1990
    (Environment Canada, 1994). These numbers may be subject to
    uncertainty and should be used only as an indication of the order of
    magnitude of e.g. the concentration in stack gases that is to be
    expected from experimental values. Actual information on PAH emissions
    from oil- and gas-fired power plants was not available. PAH emissions
    from coal-fired power plants have been claimed to be negligible in
    Germany due to the installation of appropriate filter systems, despite
    the vast amount of stack gases produced (Zimmermeyer et al., 1991;
    Ministers for the Environment, 1992).

          (ii)  Incinerators

         Numerous PAH are formed under simulated incinerator conditions
    from plastics such as polystyrene, polyethylene, polyvinyl chloride,
    and their mixtures (Hawley-Fedder et al., 1984a,b,c, 1987). PAH were
    detected at the following concentrations in the stack gases from a
    British municipal incinerator: pyrene, 1.6 µg/m3; benz [a]anthracene
    plus chrysene, 0.72 µg/m3; fluorene, 0.58 µg/m3;
    benzo [ghi]perylene, 0.42 µg/m3; benzo [b]fluoranthene plus
    benzo [j]fluoranthene plus benzo [k]fluoranthene, 0.32 µg/m3;
    perylene, 0.18 µg/m3; indeno[1,2,3- cd]pyrene, 0.18 µg/m3;
    coronene, 0.04 µg/m3; and benzo [a]pyrene plus benzo [e]pyrene,
    0.02 µg/m3 (Davies et al., 1976). When PAH were sampled at a height
    of about 10 m above the ground in the 110-m chimney of an incineration
    plant in Sweden, no measurable amounts of PAH, at a limit of detection
    of 10 ng/m3, were found during normal operating conditions or during
    start-up in the morning; however, inactivity over a weekend resulted
    in detectable concentrations of individual PAH, covering three orders
    of magnitude up to around 100 µg/m3 (Colmsjö et al., 1986a).
    Comparable results were obtained at a pilot incineration plant in
    Canada (Chiu et al., 1991). Only phenanthrene plus anthracene was
    found in measurable amounts in the stack gas (limit of detection not
    stated). The total release of PAH from this plant was estimated to be
    80-100 ng/m3.

         The concentrations of PAH emitted in the stack gases from an
    Italian municipal solid waste incinerator were: 0.1-1.9 µg/m3
    indeno[1,2,3- cd]pyrene, 0.63 µg/m3 acenaphthene, 0.57-2.5 µg/m3
    phenanthrene, 0.36-4.4 µg/m3 perylene, 0.35-0.55 µg/m3
    benzo [e]pyrene, 0.25-3.6 µg/m3 benz [a]anthracene, 0.23 µg/m3
    benzo [k]fluoranthene, 0.22 µg/m3 dibenz [a,h]anthracene, 0.19
    µg/m3 benzo [b]fluoranthene, 0.15-0.67 µg/m3 pyrene, 0.15-0.73
    µg/m3 acenaphthylene, 0.11-0.23 µg/m3 chrysene, 0.08 µg/m3
    anthracene, 0.069 µg/m3 fluorene, 0.068-1.3 µg/m3 fluoranthene,
    0.05-1.1 µg/m3 benzo [a]pyrene, and 0.014-0.47 µg/m3

    benzo [ghi]perylene, depending on the firing conditions and the
    composition of the waste (Morselli & Zappoli, 1988).

         The benzo [a]pyrene concentrations in stack gases from
    commercial waste incinerators in western Germany were estimated to be
    1-6 µg/m3 (Johnke, 1992).

         Controlled incineration of automobile tyres for thermal and
    electric energy has been estimated to result in considerable release
    of PAH into the atmosphere. In laboratory experiments, the following
    concentrations were found in flue gas at an incineration temperature
    of 677°C (per kg rubber): 930 mg pyrene, 760 mg fluoranthene, 390 mg
    phenanthrene, 290 mg anthracene, 220 mg acenaphthylene, 120 mg
    chrysene, 84 mg benzo [b]fluoranthene plus benzo [j]fluoranthene
    plus benzo [k]fluoranthene, 66 mg benz [a]anthracene, 18 mg
    benzo [e]pyrene, 11 mg benzo [a]pyrene, 3.8 mg perylene, 3.3 mg
    benzo [ghi]fluoranthene, 2.0 mg dibenz [a,h]anthracene, 1.5 mg
    benzo [ghi]perylene, 1.2 mg naphthalene, and 0.5 mg
    indeno[1,2,3- cd]pyrene (Jacobs & Billings, 1985). On the basis of
    data from Hartung & Koch (1991) on the number of tyres incinerated in
    western Germany in 1987, the annual emissions from this source can be
    calculated as follows: 160 t pyrene, 130 t fluoranthene, 70 t
    phenanthrene, 50 t anthracene, 40 t acenaphthylene, 20 t chrysene, 14
    t benzo [b]fluoranthene plus benzo [j]fluoranthene plus
    benzo [k]-fluoranthene, 10 t benz [a]anthracene, 3 t
    benzo [e]pyrene, 2 t benzo [a]pyrene, 0.5 t
    benzo [ghi]fluoranthene, 0.3 t dibenz [a,h]anthracene, 0.3 t
    benzo [ghi]-perylene, 0.2 t naphthalene, and 0.1 t
    indeno[1,2,3- cd]pyrene.

         The total PAH levels in stack gases from incinerators in
    different countries were: Italy, 0.0075-0.21 mg/m3; Japan, 0.002-0.04
    mg/m3; Sweden, 0.001 mg/m3; and Canada, 0.00002-0.02 mg/m3 (WHO,
    1988). The results for traditional incinerators could not be compared
    with those for plants with additional abatement techniques on the
    basis of the available data. The total PAH emissions to the atmosphere
    resulting from incineration of refuse were about 0.001 t
    benzo [a]pyrene in western Germany in 1989 (Ministers for the
    Environment, 1992) and about 0.0003 t in 1991 (Johnke, 1992), about 50
    t total PAH in the USA, 0.3 t in Norway and 2.2 t in Sweden in 1985
    (Bjorseth & Ramdahl, 1985); and about 2.4 t total PAH in Canada in
    1990 (Environment Canada, 1994).

         In Germany, the contribution of stack gases from commercial
    incinerators is estimated to be < 4% of the total stack gas volume
    from combustion processes. One of the main confounders of and
    contributors to stack gases from combustion is motor vehicle traffic
    (Johnke, 1992), indicating that PAH released from incinerators are
    probably of minor importance.

          (iii)  Aluminium production

         The production of coal anodes, used in the electrolytic
    production of aluminium, from pitch and petroleum coke may still be an
    important source of PAH, but confirmatory data are not available.
    Estimates of PAH released during the production of aluminium in the
    Netherlands in 1988 ranged from about 0.3 t benzo [ghi]perylene to 24
    t naphthalene (Slooff et al., 1989). The estimated total airborne PAH
    released in 1985 was about 1000 t in the USA, 160 t in Norway, and 35
    t in Sweden (Bjorseth & Ramdahl, 1985). In 1990, the input of total
    PAH from this source into the atmosphere in Canada was 930 t
    (Environment Canada, 1994).

         In horizontal and vertical Söderberg aluminium production
    processes in Sweden, the emission factors per tonne of aluminium were
    0.11 kg benzo [a]pyrene and 4.4 kg total PAH for the horizontal
    process and 0.01 kg benzo [a]pyrene and 0.7 kg total PAH for the
    vertical process (Alfheim & Wikström, 1984). In a Norwegian vertical
    Söderberg aluminium production plant, the emission factors were
    0.005-0.015 kg/t aluminium for benzo [a]pyrene and 0.3-0.5 kg/t for
    total PAH (European Aluminium Association, 1990).

          (iv)  Iron and steel production

         The total emissions of PAH resulting from iron and steel
    production with carbon electrodes containing tar and pitch in Norway
    was estimated to be about 34 t in 1985 (Bjorseth & Ramdahl (1985), but
    the database for this estimate is limited. The release of total PAH
    from metallurgical processes in Canada where similar electrodes were
    used, including ferro-alloy smelters but excluding aluminium
    production, was estimated to be 19 t in 1990 (Environment Canada,
    1994).

          (v)  Foundries

         PAH are formed during casting by thermal decomposition of
    carbonaceous ingredients in foundry moulding sand, and they partly
    vaporize under the extremely hot reducing conditions at the
    mould-metal interface. Thereafter, the compounds are adsorbed onto
    soot, fume, or sand particles. Organic binders, coal powder, and other
    carbonaceous additives are the predominant sources of PAH in iron and
    steel foundries (IARC, 1984b).

         In pyrolysis experiments with green-sand additives, the highest
    PAH levels were found in coal-tar pitch, with values per kilogram of
    additive of 3100 mg benzo [a]pyrene, 3000 mg
    benzo [b+j+k]fluoranthenes, 3000 mg pyrene, and 2900 mg fluoranthene;
    the lowest levels were found in vegetable product additives, such as
    maize starch: 26 mg pyrene, 16 mg fluoranthene, 3 mg
    benzo [b+j+k]fluoranthenes, and 2 mg benzo [a]pyrene (Novelli &
    Rinaldi, 1979). Less than 0.002 mg/kg benzo [a]pyrene was found in
    foundry moulding sand when petrol resin, polystyrol, or polyethylene
    was used as the carrier and 7.5 mg/kg when hard coal was used as the

    carrier. The PAH content was directly correlated with the amount of
    hydrocarbon carrier in the sand (Schimberg et al., 1981).

         The following levels of PAH were found in the stack gases of one
    French automobile foundry: fluoranthene, 980 ng/m3;
    benz [a]anthracene, 830 ng/m3; benzo [a]pyrene, 570 ng/m3;
    benzo [b]fluoranthene, 460 ng/m3; indeno[1,2,3- cd]pyrene, 370
    ng/m3; anthracene, 250 ng/m3; benzo [k]fluoranthene, 220 ng/m3;
    perylene, 160 ng/m3; benzo [ghi]perylene, 130 ng/m3; chrysene, 110
    ng/m3; coronene, 28 ng/m3; and pyrene, 15 ng/m3. No further
    information was given about the sampling site (Masclet et al., 1984).
    The total emission of PAH into the atmosphere from iron foundries in
    the Netherlands was estimated to be about 1.3 t in 1988 (Slooff et
    al., 1989).

          (vi)  Other industrial sources

         The estimated release of 10 PAH into the atmosphere in the
    Netherlands in 1988 was about 1.3 t from sinter processes and 0.2
    t/year from phosphorus production (Slooff et al., 1989).

          (b)  Emissions to the hydrosphere

          (i)  Aluminium production

         PAH levels in wastewater from aluminium production in Norwegian
    plants are shown in Table 15. At the beginning of the 1970s, the
    release of anthracene and phenanthrene into the aqueous environment
    from aluminium production in western Europe was estimated to be 180
    t/year (Palmork et al., 1973). About 0.6 t/year are released into
    water by the aluminium producing industry in the Netherlands (Slooff
    et al., 1989).

          (ii)  Other industrial sources

         No recent data were available on PAH emissions into the aqueous
    environment from coal- or oil-fired power plants. PAH were found in
    the final effluent from a British municipal incinerator at
    concentrations ranging from < 0.01 µg/litre each for coronene and
    indeno[1,2,3- cd]pyrene to 0.62 µg/litre fluoranthene. The calculated
    daily output of single compounds was in the low milligram range, with
    a maximum of 16 mg/d. Actual data were not available (Davies et al.,
    1976).

         Numerous PAH were detected in the final effluent from a Norwegian
    ferro-alloy smelter in which the wastewater from gas scrubbers was
    treated by chemical flocculation. The concentrations were 50 µg/litre
    phenanthrene, 45 µg/litre pyrene, 40 µg/litre fluoranthene, 39
    µg/litre acenaphthylene, 27 µg/litre fluorene, 17 µg/litre
    acenaphthene, 13 µg/litre chrysene plus triphenylene, 11 µg/litre
    anthracene, 10 µg/litre naphthalene, 10 µg/litre benz [a]anthracene,
    9 µg/litre benzo [b]fluoranthene, 6 µg/litre benzo [j]fluoranthene

    plus benzo [k]fluoranthene, 6 µg/litre benzo [e]pyrene, 6 µg/litre
    benzo [a]pyrene, 3 µg/litre benzo [c]phenanthrene, 3 µg/litre
    indeno[1,2,3- cd]pyrene, 3 µg/litre benzo [ghi]perylene, 2 µg/litre
    benzo [a]fluorene, 2 µg/litre benzo [b]fluorene, 2 µg/litre
    perylene, and 1 µg/litre dibenz [a,h]-anthracene. The PAH contents of
    wastewater from gas washers in one Norwegian steel production plant
    were of the same order of magnitude (Berglind, 1982).


    Table 15. Polycyclic aromatic hydrocarbon concentrations [µg/litre]
    in wastewater from aluminium production in Norway

                                                                   

    Compound                       [1]            [2]        [3]
                                                                   

    Acenaphthene                   NR             NR         5
    Acenaphthylene                 NR             NR         1
    Anthracene                     1.1-2.8        0.9        10
    Anthenthrene                   < 1-3.2        NR         NR
    Benzo[b+k]fluoranthenes        6.8-38.1       NR         NR
    Benzo[j+k]fluoranthenes        NR             10.5       5
    Benz[a]anthracene              2.5-5.6        14.6       11
    Benzo[a]fluorene               1.5-3.4        8.2        13
    Benzo[a]pyrene                 1.3-7.4        13.5       4
    Benzo[b]fluoranthene           NR             21.2       9
    Benzo[b]fluorene               1.3-3.0        7.2        2
    Benzo[c]phenanthrene           NR             NR         3
    Benzo[e]pyrene                 2.6-16.4       17.0       5
    Benzo[ghi]perylene             NR             8.3        2
    Chrysene and triphenylene      5.8-16.0       27.3       17
    Coronene                       < 1-2.0        NR         NR
    Dibenz[a,h]anthracene          NR             NR         1
    Fluoranthene                   12.4-20.8      7.5        124
    Fluorene                       NR             NR         3
    Indeno[1,2,3-cd]pyrene         NR             8.1        2
    1-Methyphenanthrene            NR             0.4        NR
    Naphthalene                    NR             NR         1
    Perylene                       NR             3.2        1
    Phenanthrene                   14.0-23.1      1.8        34
    Pyrene                         5.6-15.3       6.4        76
                                                                   

    [1] Two samples of wastewater with two runs each from one aluminium
        production plant (Kadar at al., 1980);
    [2] Wastewater from one aluminiurn production plant; no further
        information (Olufsen, 1980);
    [3] Effluent from gas washers from one aluminium smelter (Berglind, 1982)
    When the water samples were filtered through solid sorbents, the results
    may be underestimates of the actual content (see section 2.4.1.4).
    NR, not reported

         The release of 10 PAH into water from different industries in the
    Netherlands was estimated to be 4 t/year (Slooff et al., 1989).

          (c)  Emissions to the geosphere

         The levels of PAH in ash samples from various incinerators are
    shown in Table 16. The values given by Eiceman et al. (1979) were
    based on the gas chromatographic responses of pyrene and
    benzo [a]pyrene. The concentrations of PAH in ashes from coal-fired
    power plants were of the same magnitude as the background levels of
    these compounds in soil, but fly ash from municipal waste incinerators
    may contain significantly higher levels (Guerin, 1977; Kanij, 1987).
    The total PAH content of filter residues in incinerators was about
    0.20-0.5 µg/g. The compounds are assumed to be tightly bound to
    particle surfaces and not mobile in an aqueous environment in the
    absence of organic solvents (WHO, 1988). In a comparison of 26
    incineration plants, combustion conditions were shown to have a marked
    influence on PAH release (Wild et al., 1992).

         The material dredged from harbour areas may have a significant
    PAH content (see also sections 5.3.3 and 5.3.4). The annual load of
    naphthalene, anthracene, phenanthrene, fluoranthene,
    benz [a]anthracene, chrysene, benzo [k]-fluoranthene,
    benzo [a]pyrene, benzo [ghi]perylene, and indeno[1,2,3- cd]pyrene
    in material dredged from Rotterdam harbour was about 12 t (year not
    given). The main PAH were fluoranthene and benz [a]anthracene (Slooff
    et al., 1989).

    3.2.7.2  Other diffuse sources

          (a)  Atmosphere

          (i)  Mobile sources

         PAH are released into the atmosphere by motor vehicle traffic.
    The profile of the PAH released and the quantity of PAH in the exhaust
    are fairly similar, independently of the type of engine and the PAH
    content of the fuel, indicating that the emitted compounds are formed
    predominantly during combustion (Meyer & Grimmer, 1974; Janssen, 1980;
    Stenberg, 1985; Williams et al., 1989). PAH accumulate in used engine
    oil, but the importance of the PAH content of engine oil on emissions
    is still under discussion. Janssen (1980), Pischinger & Lepperhoff
    (1980), and Stenberg (1985) assumed that the PAH content of the oil
    played only a minor role, but Williams et al. (1989) showed in tests
    with diesel fuel that it may contribute considerably to the release of
    particulate PAH. There is also doubt about whether PAH emissions are
    indepen-dent of the aromaticity of the fuel. Janssen (1980) stated
    that release of PAH into the atmosphere is not increased if the
    aromaticity does not exceed a concentration of 50% volume (see also
    Schuetzle & Frazier, 1986). According to Stenberg (1985), the release
    of PAH by automobile traffic is dependent on the:


        Table 16. Polycyclic aromatic hydrocarbon concentrations (µg/kg) in ash samples from coal-fired power plants and municipal waste and sewage
    sludge incinerators

                                                                                                                                              

    Compound                 Coal-fired       Municipal waste incinerators                                                         Sewage
                             power plants                                                                                          sludge
                                                                                                                                 incinerators
                             Netherlands      USA      Canada    Japan     Netherlands   Canada      UK              Italy         (UK)
                             [1]              [2]      [3]       [3]       [3]           [4]         [5] (mean)      [6]           [5]
                                                                                                                                              

    Acenaphthene +           NR               NR       NR        NR        NR            NR          1-258(7.8)      289-1022i     NR
      fluoranthene
    Acenaphthylene           NR               NR       NR        NR        NR            3.35        NR              5-1394        NR
    Anthracene               < 0.14-0.5       NR       10/500    10/10     200           NR          1-62(2.3)       42-651        NR
    Anthanthrene             < 0.24-< 0.5     NR       NR        NR        NR            NR          NR                            NR
    Benz[a]anthracene        < 0.6-< 1.2      NR       NR        NR        NR            NR          1-1646a(12)     280-1278      3a
    Benzo[a]fluoranthene     NR               36.8     NR        NR        NR            NR          NR                            NR
    Benzo[a]pyrene           < 0.29-< 1.8     NR       ND/400    ND/ND     ND            NR          1-596(8.2)      1014-3470     3
    Benzo[b]fluoranthene     < 0.6-< 0.29     NR       NR        NR        NR            NR          1-873(5.7)      1818          6
    Benzo[b]fluorene         < 2.0-< 4        11.8     NR        NR        NR            NR          NR                            NR
    Benzo[e]pyrene           < 2.9-< 6        NR       NR        NR        NR            NR          NR              458-1786      NR
    Benzo[ghi]perylene       < 1.6-1.7        NR       NR        NR        NR            NR          10-9507 (62.3)  700-2377      135
    Benzo[j]fluoranthene     < 4.5-< 9        NR       ND/400b   ND/NDb    NDb           NR          NR                            NR
    Benzo[k]fluoranthene     < 0.15-< 2.8     NR       NR        NR        NR            NR          1-276(1.5)      1535          NR
    Chrysene                 < 1.5-< 3        NR       NR        NR        NR            NR          NR              570-1973      NR
    Coronene                 NR               NR       NR        NR        NR            NR          3-238 (31.3)                  36
    Dibenz[a,h]anthracene    < 4.2-< 8.2      NR       NR        NR        NR            NR          1-167(5.2)      57/69         1
    Fluoranthene             1.1-5.2          < 13.4   2/500     3/ND      20            2.14-43.2   1-765 (8.6)     1684-10 890   1
    Fluorene                 NR               NR       ND/10     ND/ND     60            2.57/4.41   NR              45-522        NR
    Indeno[1,2,3-cd]pyrene   < 0.82-< 1.6     NR       NR        NR        NR            NR          NR              478-1343      NR
    Naphthalene              NR               8.3      NR        NR        NR            NR          4/15(0.2)                     NR
    Perylene                 < 0.16-< 0.3     NR       NR        NR        NR            NR          NR              259           NR
    Phenanthrene             4.0-43           17.6     NR        NR        NR            8.76-154c   2-5402 (36.5)   1616-7823     6
    Pyrene                   0.72-2.9         < 19.0   1/500     1/ND      10            2.47-19.6   1-3407 (45.3)   1863-8799     10
    Triphenylene             < 2.5-< 5.0      NR       NR        NR        NR            12.7a       NR                            NR
                                                                                                                                              

    Table 16 (continued)

    [1] Pulverized coal ash (Kanij, 1987);
    [2] Fly ash (Guerin, 1977);
    [3] Fly ash (Eiceman at al., 1979);
    [4] Fly ash (Chiu at al., 1991);
    [5] Fly ash 26 incinerators with different firing techniques (Wild et al., 1992);
    [6] Fly ash from electrostatic precipitator and scrubber (Morselli & Zappoli, 1988)
    NR, not reported; ND, not detected; /, single measurements
    a With chrysene
    b Isomers not specified
    c With anthracene
    i Only acenaphthene


    -     aromaticity of the fuel;

    -     starting temperature: Starting at -10°C results in threefold
         higher PAH emissions than a standardized cold start (+ 23°C); the
         emission factors measured by Larssen (1985) were significantly
         higher in winter than in summer.

    -     ambient temperature: Low ambient temperatures (5-7°C) increase
         PAH emissions from petrol-fuelled vehicles by five to 10 times,
         depending on the engine used.

    -     test conditions: Three standardized test cycles are in general
         use: a test developed by the Economic Commission for Europe of
         the United Nations (ECE) in Europe; the Federal Test Procedure
         (FTP) in the USA; and the Japanese test cycle in Japan. Emissions
         at cold start may be lower and those at hot start slightly higher
         in the FTP than in the ECE test, but overall agreement between
         the tests is good.

    -     air:fuel ratio (l): Small variations around l = 1, representing
         stoichiometric levels of fuel and air, do not affect PAH
         emissions significantly; richer mixtures lead to increasing PAH
         emissions, and bad ignition at l = 0.8 causes a sharp increase in
         PAH emissions.

    -     type of fuel: Emissions of the sum of phenanthrene,
         fluoranthene, pyrene, benzo [ghi]fluoranthene,
         cyclopenta [cd]pyrene, benz [a]-anthracene, chrysene,
         benzo [b]fluoranthene, benzo [k]fluoranthene, benzo [e]pyrene,
         benzo [a]-pyrene, indeno[1,2,3- cd]pyrene,
         benzo [ghi]-perylene, and coronene decreased in the FTP cycle as
         follows: diesel (total PAH; 960 µg/km) > petrol (170 µg/km) >
         petrol containing methanol or ethanol (43-110 µg/km) > methanol
         = liquefied petro-leum gas = catalyst-equipped petrol-fuelled
         vehicles (6-9 µg/km) (Stenberg, 1985). In comparable
         measurements, similar results were obtained but with a much lower
         average emission rate for diesel-fuelled vehicles: 186 µg/km for
         total PAH, including fluoranthene, pyrene, benz [a]anthracene,
         chrysene, benzo [b]-fluoranthene, benzo [e]-pyrene,
         benzo [a]pyrene, perylene, indeno[1,2,3- cd]pyrene,
         benzo [ghi]-perylene, and coronene. It was not stated whether
         the difference in the emission rates was due to the numbers of
         PAH chosen for analysis (Lies et al., 1986).

         PAH emissions in the exhaust from spark-ignition automobile
    engines can be reduced by operation with lean air:fuel ratios, smaller
    quenching distances in the combustion chamber, and increased cylinder
    wall temperatures in the engine (Pischinger & Lepperhoff, 1980;
    Lepperhoff, 1981). Diesel-fuelled engines with low emissions of total
    unburnt gaseous hydrocarbons have low rates of PAH emission. Control
    can therefore be achieved by using conventional techniques for
    reducing unburnt gaseous hydrocarbons (Williams et al., 1989).

         Fluoranthene and pyrene constitute 70-80% of total PAH emissions
    from vehicles (Lies et al., 1986; Volkswagen AG, 1989; see also Table
    17), whereas the emissions from one diesel-fuelled truck consisted
    mainly of naphthalene and acenaphthene (Nelson, 1989). Although
    cyclopenta [cd]pyrene is emitted at a high rate from petrol-fuelled
    engines, its concentration in diesel exhaust is just above the limit
    of detection, probably because the oxidizing conditions in
    diesel-fuelled engines decompose this relatively reactive compound
    (Lies et al., 1986).

         The amounts of PAH released from vehicles with three-way
    catalytic converters are much lower than those from vehicles without
    catalysts (Table 18). The total amount of PAH was increased by a
    factor of about 40 between new and used catalytic converters (Hagemann
    et al., 1982). PAH emissions from diesel-fuelled vehicles can be
    reduced by > 90% by a combination of a catalytic converter and a
    particulate trap, as shown by experiments with a heavy-duty
    diesel-fuelled truck (Westerholm et al., 1989). Westerholm et al.
    (1991) found benz [a]anthracene, benzo [b]fluoranthene,
    benzo [k]fluoranthene, benzo [e]-pyrene, benzo [a]pyrene,
    indeno[1,2,3- cd]pyrene, benzo [ghi]perylene, fluoranthene, pyrene,
    anthracene, and coronene in much lower amounts than other
    investigators, while some other PAH that were not measured by other
    investigators, especially phenanthrene and 1-methylphenanthrene, were
    detected at quite high concentrations. These differences are possibly
    due to the driving cycle used.

         Measurements made on particulate matter in the exhausts of light-
    and heavy-duty diesel-fuelled vehicles with different fuel qualities
    showed concentrations of 1 mg/kg each of benz [a]anthracene,
    benzo [b]fluoranthene plus benzo [j]fluoranthene, benzo [a]pyrene
    plus benzo [e]pyrene, and benzo [ghi]perylene and 290 mg/kg pyrene.
    The results were strongly dependent on the driving cycle and
    individual engine conditions (CONCAWE, 1992).

         The PAH concentrations measured in the exhaust gases of different
    vehicles are shown in Table 19. The differences in PAH emissions from
    petrol- and diesel-fuelled vehicles are still under discussion. When
    the data of Behn et al. (1985) are compared with those of Klingenberg
    et al. (1992), diesel-fuelled vehicles emitted larger amounts of PAH
    than petrol-fuelled vehicles. Benzo [a]pyrene was emitted at a rate
    of 6 µg/km from a petrol-fuelled vehicle without a catalyst and at 5
    µg/km from a diesel-fuelled vehicle (Gibson, 1982). When the PAH
    emissions from 10 petrol- and 20 diesel-engined vehicles were measured
    under three urban cycles, the mean emission factors (µg/km) for
    benzo [a]pyrene were 12 with petrol and 0.56 with diesel in a cold,
    low-speed cycle, 0.50 with petrol and 0.37 with diesel in a hot,
    low-speed cycle, and 0.37 with petrol and 0.24 with diesel in a hot,
    free-flow cycle (Combet et al., 1993). Considerably higher emission
    rates were found from four petrol-fuelled passenger cars without
    catalysts, 11 with catalysts, and eight diesel-fuelled passenger cars,
    two of which had oxidation catalysts, on a chassis dynamometer at the
    USA FTP 75 cycle. The diesel-fuelled vehicles emitted about as much

    benzo [a]pyrene as the petrol-fuelled vehicles without catalysts
    (5-25 µg/km), while the petrol-fuelled vehicles with catalysts had
    emission rates significantly below 2 µg/km. The diesel-fuelled
    vehicles with oxidation catalysts had emissions of about 5 µg/km
    (Klingenberg et al., 1992).

         The following emission factors were given for motorcycles and
    two-stroke mopeds: 1000 µg/km naphthalene, < 32-650 µg/km
    phenanthrene, < 11-170 µg/km anthracene, < 5-110 µg/km fluoranthene,
    < 2-11 µg/km chrysene, < 2-11 µg/km indeno[1,2,3- cd]pyrene,
    < 1-1200 µg/km benz [a]anthracene, 0-63 µg/km benzo [ghi]perylene,
    0-16 µg/km benzo [a]pyrene, and 0-11 µg/km benzo [k]fluoranthene
    (Slooff et al., 1989).

         Further PAH emissions may result from the abrasion of asphalt by
    vehicle traffic, so that PAH in asphalt and bitumens (see section
    3.2.1) may contribute considerably to the total PAH emissions due to
    automobile traffic. The abrasion caused by spiked tyres in winter was
    estimated to be 20-50 mg/km (Lygren et al., 1984).

         Another source of PAH from motor vehicle traffic is clutch and
    break linings, which are subject to considerable thermal stress,
    sometimes resulting in pyrolytic decomposition of abraded particles.
    Numerous PAH were found in the abraded dust of brake and clutch
    linings in one study, but the values show large standard deviations,
    due, presumably, to the fact that the substances are adsorbed onto
    asbestos fibres from which they are difficult to separate (Knecht et
    al., 1987). Total PAH release from clutch and brake linings cannot be
    estimated from the available data.

         Rubber vehicle tyres contain highly aromatic oils as softeners.
    These oils, which can contain up to 20% PAH, are used at
    concentrations of 15-20% in rubber blends (Duus et al., 1994). In
    Sweden, it was considered that the input of PAH to the atmosphere from
    rubber particles was important (National Chemicals Inspectorate,
    1994).

         According to estimates for Belgium, western Germany, and the
    Netherlands in 1985, the annual PAH input into the atmosphere from
    vehicle traffic ranges from < 10 t/year for benzo [ghi]fluoranthene,
    benz [a]anthracene, benzo [k]-fluoranthene, benzo [a]pyrene, and
    indeno[1,2,3- cd]pyrene, to < 10-20 t/year for anthracene,
    fluoranthene, and chrysene, to 10-70 t/year for phenanthrene, to about
    100-1000 t/year for naphthalene (Slooff et al., 1989). Values of the
    same order of magnitude were reported for emissions of naphthalene in
    1987 (Society of German Chemists, 1989) and benzo [a]pyrene in 1989
    in western Germany (Ministers for the Environment, 1992) and for total
    PAH in 1985 in Norway and Sweden (Bjorseth & Ramdahl, 1985). The total
    annual PAH input from vehicle traffic in the USA in 1985 was about
    2200 t/year (Bjorseth & Ramdahl, 1985). In Canada, the total PAH input
    was estimated to be about 200 t in 1990; 155 t were assumed to be due
    to diesel-fuelled and 45 t to petrol-fuelled vehicles (Environment
    Canada, 1994).


        Table 17. Polycyclic aromatic hydrocarbon emission factors (µg/km) for petrol-fuelled vehicles

                                                                                                                                      

    Compound                     [1]           [2]           [3]         [4]             [5]                    [6]         [7]
                                                                                                                                      

    Anthracene                   NR            0.7/0.7a      NR          2/99b           NR                     21-42       0.6
                                                                         37/1988c
    Anthanthrene                 NR            0.2/1.3       NR          NR              NR                     NR          NR
    Benzo[b+j+k]fluoranthene     NR            NR            NR          NR              NR                     NR          7.6
    Benzo[b+k]fluoranthene       NR            3.9/7.0       NR          NR              0.23-0.54/2.55-9.20    NR          NR
    Benz[a]anthracene            NR            5.7/5.9       3.5-9.0     NR              0.06-0.35/2.5-8.0      5-16        5.1
    Benzo[a]pyrene               NR            1.9/4.51      1.5-14.5    0.06-2/1-12b    0.06-0.62/1.30-10.4    2-11        3.7
    Benzo[e]pyrene               NR            2.6/6.2       NR          0.2/2-14b       0.08-0.54/2.54-9.20    NR          5.1
    Benzo[ghi]fluoranthene       NR            5.6/12        NR          NR              NR                     NR          8.8
    Benzo[ghi]perylene           NR            5.9/13        NR          NR              0.19-0.75/1.45-17.5    5-21        18.9
    Benzo[j]fluoranthene         NR            1.1/0.9       NR          NR              NR                     NR          NR
    Benzo[k]fluoranthene         NR            NR            NR          NR              NR                     0-5         NR
    Chrysene                     NR            6.7/8.7       NR          NR              0.12-0.73/2.78-23.1    11-42       7.7
    Coronene                     NR            6.5/12        1.5-20.0    NR              NR                     NR          29.5
    Cyclopenta[cd]pyrene         NR            2.9/12        NR          NR              NR                     NR          16.5
    Fluoranthene                 NR            14/20         NR          3/139-211b      2.7/43.3d              11-158      10.4
                                                                         ND/186-280c
    Indeno[1,2,3-cd]pyrene       NR            1.7/3.6       NR          NR              0.06-0.43/0.83-6.67    5-21        4.2
    Naphthalene                  8100-8600a    NR            NR          NR              NR                     2300f       NR
                                                                                                                210-2651
    Perylene                     NR            0.3/0.5       NR          NR              0.01-0.06/0.25-1.82    NR          NR
    Phenanthrene                 NR            2.6/2.9       NR          NR              NR                     84-210      1.8
    Pyrene                       NR            28/31         43-184      4-16/12-268b    2.9/43.0b              NR          19.2
                                                                         ND/124-360c
                                                                                                                                      

    Table 17 (continued)

    NR, not reported; ND not detected (detection limit not stated); /, single measurements
    a Two driving distances
    b Only particulate phase considered
    c Only gaseous phase considered
    d Average
    e Depending on analytical conditions
    f With converter

    [1] From measurements in tunnel with converters (Hampton at al., 1983);
    [2] One vehicle without converter (Alsberg et al., 1985);
    [3] Various tests conducted mainly in the 1970s, some unstandardized, different numbers of vehicles,
        without converters (Stenberg, 1985);
    [4] FTP cycle only, number of vehicles not given; year of manufacture 1980-85 = petrol-engine vehicles
        with converter; 1973-81 = petrol-engine vehicles without converter (Schuetzle & Frazier, 1986);
    [5] Various standardized test procedures; four petrol-engine vehicles without, seven with three-way-converter
        for each test, all with four or five cylinders (Volkswagen AG, 1988);
    [6] No information about test cycle or number of cars tested; city roads, motorways and other roads tested;
        no distinction between vehicles with and without converter, unless otherwise stated (Slooff et al.,
        1988, 1989);
    [7] One petrol-engine vehicle without converter in USFTP test cycle (Strandell at al., 1994)

    Table 18. Polycyclic aromatic hydrocarbon emission factors (µg/km) for diesel-fuelled vehicles

                                                                                                                            

    Compound                    [1]         [2]         [3]         [4]         [5]         [6]         [7]         [8]
                                                                                                                            

    Acenaphthene                NR          NR          NR          NR          NR          NR          41-128      NR
    Anthracene                  17/63       65-273a     1.2/3.0     NR          21-73b      3.3         2.9-26      4.6
                                            1305-5568c
    Benzo[b+j+k]fluoranthene    NR          NR          NR          NR          NR          NR          1.7-12d     5.0
    Benzo[b+k]fluoranthene      2.6/47      NR          3.9/6.1     5.57-14.96  NR          0.29        NR          NR
    Benz[a]anthracene           8/43a       NR          4.0/7.0     2.73-3.91   11-21b      0.47        0.7-9.6     2.0
    Benzo[a]fluorene            NR          NR          NR          NR          NR          2.4         NR          NR

    Benzo[a]pyrene              < 1/20      0.6-34a     1.6/2.2     2.09-7.23   1-5         < 0.06      0.5-3.2     1.5
    Benzo[e]pyrene              3/38        2-40a       2.5/4.1     2.40-52.8   NR          0.15        1.1-9.9     4.0
    Benzo[ghi]fluoranthene      NR          NR          4.0/12      NR          NR          1.5         NR          10.6
    Benzo[ghi]perylene          < 1/18      NR          1.9/3.1     2.84-26.3   9e          < 0.13      0.5-3.7     2.0
    Chrysene                    14/67       NR          11/25       4.7-21.1    16-42b      2.8f        3.5-28      3.7
    Coronene                    NR          NR          0.3/20.7    NR          NR          < 0.01      NR          NR
    Cyclopenta[cd]pyrene        NR          NR          3.6/3.9     NR          NR          0.18        NR          4.0
    Fluoranthene                58/200      139-580a    13/38       70g         21-105b     17          14-34       43.7
                                            186-771c
    Fluorene                    NR          NR          NR          NR          NR          NR          38-228      NR
    Indeno[1,2,3-cd]pyrene      NR          NR          1.5/2.3     0.89-7.52   9e          < 0.04      NR          1.2
    1-Methylphenanthrene        NR          NR          NR          NR          NR          41          NR          NR
    Naphthalene                 NR          NR          NR          NR          2100-6302b  NR          1030-1805   NR
    Perylene                    < 1/2       NR          NR          0.23-1      NR          < 0.01      NR          NR
    Phenanthrene                295/524     NR          4.6/25      NR          NR          2.9         79-308      54.8
    Pyrene                      < 0-9/22    24-734a     20/104      66.9g       NR          11          9-30        35.4
                                            702-982c
                                                                                                                            

    Table 18 (continued)


    NR, not reported; /, single measurements;
    [1] ECE test; two passenger cars with < 50 000 and > 100 000 km odometer readings (Scheepers & Bos, 1992);
    [2] FTP cycle; number of vehicles not given; year of manufacture, 1980-85 (Schuetzle & Frazier, 1986);
    [3] Chassis dynamometer; one heavy-duty vehicle (Westerholm et al., 1986);
    [4] Various standardized testing procedures; seven vehicles with four or five cylinders for each test (Volkswagen
        AG, 1988);
    [5] No information on test cycle or number of cars tested; three traffic situations (Slooff at al., 1989);
    [6] Bus cycle simulating public transport (duration 29 min; driving distance, 11.0 km; average speed, 22.9 km/h);
        one heavy-duty truck; measurement of particle phase (Westerholm at al., 1991);
    [7] Bus cycle (duration, about 10 min after warm-up, each ramp consisting of 10 s acceleration, 10 s constant speed
        of 12 km/h, 4.5 s deceleration, 7 s idling); three trucks and two buses without particle trap, two buses with
        particle trap (Lowenthal et al., 1994);
    [8] US FTP cycle; one passenger car (Strandell at al., 1994)
    a Particle phase
    b Automobiles and trucks
    c Gas phase
    d Isomers not specified
    e Trucks
    f With triphenylene
    g Average


    Table 19. Polycyclic aromatic hydrocarbon concentrations (µg/m3) in the
    exhaust gases of different vehicles

                                                                          

    Compound                 [1]            [2]            [3]
                                                                          

    Acenaphthene             NR             NR             < 0.02-0.81
    Acenaphthylene           NR             NR             < 0.02-4.16
    Anthracene               NR             NR             < 0.02-6.45
    Anthanthrene             0.02-0.07      0.11-0.12      NR
    Benz[a]anthracene        1.91-2.24      3.53-4.64      NR
    Benzo[a]pyrene           0.46-0.76      2.03-2.33      < 0.02-4.97
    Benzo[b]fluoranthene     1.53-2.04a     7.37-8.58a     0.06-6.63
    Benzo[b]fluorene         NR             NR             0.11-12.7
    Benzo[e]pyrene           1,07-1.24      2.46-2.90      0.09-6.16
    Benzo[ghi]fluoranthene   0.46-0.59      4.81-7.19      NR
    Benzo[ghi]perylene       0.76-1.04      3.42-4.41      0.22-1.81
    Benzo[k]fluoranthene     NR             NR             < 0.02-2.68
    Chrysene                 2.37-2.97b     7.37-8.58b     0.07-25.48
    Coronene                 0.26-0.30      1.82-2.32      < 0.02-1.80
    Cyclopenta[cd]pyrene     1.86/2.26      5.80-6.09      NR
    Dibenz[a,h]anthracene    0.04-0.07      0.32-0.35      < 0.02-0.44
    Fluoranthene             11.83-13.09    20.90-25.30    0.16-35.94
    Fluorene                 NR             NR             0.06-2.16
    Indeno[1,2,3-cd]pyrene   0.30-0.41      2.89-4.06      < 0.02-0.80
    Perylene                 0.10-0.26      0.21-0.33      0.13-5.55
    Phenanthrene             NR             NR             < 0.02-4.16
    Pyrene                   6.86-8.96      12.20-15.20    0.06-21.31
                                                                          

    NR, not reported; /, single measurements;
    [1] One vehicle with spark-ignition engine on chassis dynamometer
        at 75% of maximum engine performance (velocity, about 50 km/h)
        with varying test periods (Behn et al., 1985);
    [2] One turbo-charged diesel-fuelled vehicle on chassis dynamometer
        at 75% of maximum engine perfornance (velocity, about 50 km/h)
        and a test period of 0.5 h; three tests for each component
        (Behn at al., 1985);
    [3] Two diesel-fuelled truck engines at different engine speeds
        (Moriske at al., 1987)
    a With benzo[k]fluoranthene
    b With triphenylene

         Measurements of PAH concentrations in a Belgian highway tunnel in
    1991 were used to calculate emission factors of 2 µg/km for
    indeno[1,2,3- cd]pyrene and coronene and 32 µg/km for
    benzo [ghi]perylene. The corresponding annual PAH emissions in
    Belgium were estimated to be 0.11 t/year for perylene and anthanthrene
    and 1.3 t/year for benzo [ghi]perylene; the combined release of
    pyrene, benz [a]anthracene, chrysene, benzo [b]fluoranthene,
    benzo [j]fluoranthene, benzo [k]fluoranthene, benzo [a]pyrene,
    benzo [e]pyrene, perylene, anthanthrene, benzo [ghi]perylene,
    indeno[1,2,3- cd]pyrene, dibenzo [a,c]anthracene,
    dibenzo [a,h]anthracene, and coronene was 8.3 t/year (De Fré et al.,
    1994).

         The importance of PAH released by aircraft is also under
    discussion. While Bjorseth & Ramdahl (1985) classified the maximum
    emission in Norway and Sweden in 1985 of 0.1 t/year as small, Slooff
    et al. (1989) estimated that the release of naphthalene, anthracene,
    phenanthrene, fluoranthene, benz [a]-anthracene, chrysene,
    benzo [k]fluoranthene, benzo [a]pyrene, benzo [ghi]-perylene, and
    indeno[1,2,3- cd]pyrene was 51 t/year in 1985. The following
    concentration ranges were measured in the exhaust gases from two US
    by-pass turbine engines at various power settings: naphthalene,
    0.77-4.7 µg/m3; phenanthrene, 0.46-1.3 µg/m3; pyrene, 0.15-0.61
    µg/m3; fluoranthene, 0.13-0.51 µg/m3; acenaphthene, 0.03-0.21
    µg/m3; anthracene, 0.029-0.12 µg/m3; benzofluoranthenes
    (unspecified), 0.028-0.096 µg/m3 (isomers not specified); chrysene,
    0.026-0.064 µg/m3; benzo [a]pyrene, 0.021-0.073 µg/m3;
    benz [a]anthracene, 0.019-0.16 µg/m3; acenaphthylene, 0.017-0.31
    µg/m3; benzo [e]pyrene, 0.017-0.057 µg/m3; dibenz [a,h]anthracene,
    0.011-0.064 µg/m3; indeno[1,2,3- cd]pyrene, 0.011-0.054 µg/m3; and
    benzo [ghi]perylene, 0.011-0.045 µg/m3. Cyclopenta [cd]pyrene was
    not detected (limit of detection not stated) (Spicer et al., 1992).

          (ii)  Domestic residential heating

         The main PAH released by domestic slow-combustion furnaces and
    hard-coal and brown-coal coal stoves were fluoranthene, pyrene, and
    chrysene, which comprised 70-80% of the total PAH in model experiments
    (Ahland & Mertens, 1980). The specific emission factors for various
    fuels used in residential heating are shown in Table 20 for coal
    stoves and Table 21 for wood stoves (Bjorseth & Ramdahl, 1985).

         Few data are available on the release of PAH from oil stoves.
    Benzo [a]pyrene was detected at a concentration of < 0.05 µg/kg in
    one burner-boiler combination (Meyer et al., 1980), and 0.006 and 4
    µg/kg benzo [a]pyrene and 0.02 and 15 µg/kg benzo [e]pyrene were
    found during testing of atomizer and vaporizer oil heating techniques,
    respectively (Ahland et al., 1985). PAH emissions from residential oil
    heating seem to be about one order of magnitude lower than those from
    coal stoves.

        Table 20. Specific polycyclic aromatic hydrocarbon emission factors (mg/kg) for residential
    coal stoves

                                                                                                  

    Compound                  [1]        [2]           [3]            [4]         [5]       [6]
                                                                                                  

    Acenaphthene              NR         NR            NR             NR          65        NR
    Acenaphthylene            NR         NR            NR             0.427       NR        7.74
    Anthracene                0.0039     NR            > 0.595        2.113       26a,b     1.49
    Anthanthrene              NR         NR            0.03-0.08      0.665       NR        NR
    Benz[a]anthracene         NR         NR            1.04-3.68      7.181       NR        0.61
    Benzo[a]fluorene          0.0009     NR            NR             1.366       NR        NR
    Benzo[a]pyrene            0.0003     0.014-17.4    0.043-1.3      4.303       5c        NR
    Benzo[b]fluoranthene      0.0002     NR            2.028d         6.102       NR        NR
    Benzo[b]fluorene          0.0007     NR            NR             0.874       NR        NR
    Benzo[c]phenanthrene      NR         NR            1.462e         2.215       4         NR
    Benzo[e]pyrene            0.0005     0.09-16.2     0.40-1.70      3.994       NR        NR
    Benzofluoranthenesf       NR         NR            0.90-3.20      NR          6         NR
    Benzo[ghi]fluoranthene    NR         NR            NR             3.323       NR        0.67
    Benzo[ghi]perylene        0.0001     NR            0.30-0.50      3.855       NR        NR
    Benzo[j]fluoranthene      NR         NR            NR             6.782       NR        NR
    Benzo[k]fluoranthene      NR         NR            0.569          NA          NR        NR
    Chrysene                  0.0016g    NR            2.09           9.571       6h        0.68
                                                       1.39-5.60g
    Coronene                  NR         NR            0.081          1.898       NR        NR
    Cyclopenta[cd]pyrene      NR         NR            0.145          3.590       NR        NR
    Dibenz[a,h]anthracene     NR         NR            0.113          NR          5         NR
    Fluoranthene              0.016      NR            3.30-17.0      28.4        9a        3.47
    Fluorene                  NR         NR            < 0.065        1.05        44        1.64
    Indeno[1,2,3-cd]pyrene    0.0002     0.20-0.60     4.60           NR          4         NR
    1-Methylphenanthrene      NR         NR            NR             2.217       NR        NR
    Naphthalene               NR         NR            NR             NR          254       35.7
    Perylene                  NR         NR            0.20-0.50      1.134       NR        NR
    Phenanthrene              0.046      NR            > 3.69         3.984       NR        7.42
    Pyrene                    0.020      NR            2.98-12.0      26.589      8         3.38
    Triphenylene              NR         NR            0.804          NR          NR        NR
                                                                                                  

    Table 20 (continued)

    NR, not reported;
    [1] One new residential stove fuelled with charcoal (Ramdahl et al., 1982);
    [2] Five coal types: hard-coal and brown-coal briquettes and anthracite (Ahland etal., 1985);
    [3] Burning of brown coal in different domestic stoves; single values refer
        to one slow-combustion stove; ranges refer to one slow-combustion stove
        and one permanent built-in combustion stove at medium load (Grimmer et al.,
        1983a);
    [4] One slow combustion stove fueled with hard-coal briquettes (Grimmer at al., 1985);
    [5] One warm-air furnace and one hot-water boiler fuelled with three different bituminous
        coals (Hughes & DeAngelis, 1982);
    [6] Samples from chimney of a detached family house with brown-coal heating in Leipzig, Germany
        (Engewald et al., 1993)
    a In particulate phase
    b With phenanthrene
    c With benzo[e]pyrene and perylene
    d With benzo[j]fluoranthene
    e With benzo[ghi]fluoranthene
    f Isomers not specified
    g With triphenylene
    h With benz[a]anthracene

    Table 21. Specific polycyclic aromatic hydrocarbon emission factors
    (mg/kg) for residential wood stoves

                                                                            

    Compound                    [1]              [2]              [3]
                                                                            

    Anthracene                  0.119-1.859      10.4-146.3a      130/3600
    Benz[a]anthracene           0.060-0.781      NR               55/740
    Benzo[a]fluorene            0.018-0.845      NR               NR
    Benzo[a]pyrene              0.046-0.617      1.1-11.6b        NR
    Benzo[b]fluoranthene        0.108-1.016      NR               NR
    Benzo[b]fluorene            0.011-0.393      NR               NR
    Benzo[c]phenanthrene        NR               0.2-2.3          NR
    Benzo[e]pyrene              0.035-0.350      NR               NR
    Benzofluoranthenesc         NR               1.5-15.9         NR
    Benzo[ghi]fluoranthene      NR               0.4-6.7          NR
    Benzo[ghi]perylene          0.034-0.544      1.1-9.9          NR
    Chrysene                    0.481-0.829d     1.3-37.1e        67/770d
    Cyclopenta[cd]pyrene        0.04-0.720       0.5-8.9          15/800
    Fluoranthene                0.296-3.245      1.2-31.6         190/2300
    Indeno[1,2,3-cd]pyrene      0.033-0.415      NR               NR
    1-Methylphenanthrene        0.141-2.213      NR               NR
    Perylene                    0.023-0.274      NR               NR
    Phenanthrene                0.834-8.390      NR               480/7500
    Pyrene                      0.232-3.822      1.3-24.0         160/2100
                                                                            

    NR, not reported; /, single measurements;
    [1] One small residential wood stove burning spruce and birch; normal and
        slow burning of each kind of wood (Ramdahl at al., 1982);
    [2] One zero-clearance fireplace with heat circulation and two airtight
        wood stoves (baffled and non-baffled) fuelled with red oak and yellow
        pine with different moisture contents (Peters at al., 1981);
    [3] One wood-burning stove with and without catalytic combustor (Tan et
        al., 1992)
    a With phenanthrene
    b With benzo[e]pyrene and perylene
    c Isomers not specified
    d With triphenylene
    e With benz[a]anthracene

         Numerous PAH, including acenaphthene, acenaphthylene, fluorene,
    phenanthrene, anthracene, 1-methylphenanthrene, fluoranthene, pyrene,
    benzo [a]fluorene, benzo [ghi]fluoranthene, benzo [c]phenanthrene,
    cyclo-penta [cd]pyrene, benz [a]anthracene, chrysene plus
    triphenylene, benzo [b]-fluoranthene, benzo [j]fluoranthene,
    benzo [j]fluoranthene, benzo [e]pyrene, benzo [a]pyrene, perylene,
    indeno[1,2,3- cd]pyrene, benzo [ghi]perylene, and anthanthrene, were
    detected in atmospheric emissions from straw-burning residential
    stoves, at concentrations mainly in the range of 10 µg/kg to 19 mg/kg
    (Ramdahl & Muller, 1983).

         The total PAH content of barbecue briquettes was 2.5-13 µg/g
    sample. PAH were found in coal and charcoal briquettes but not in lava
    stones or pressed sawdust briquettes (Kushwaha et al., 1985).

         The PAH content of soot from domestic open fires was 3-240 mg/kg
    benzo [a]pyrene, 2-190 mg/kg chrysene, 2-100 mg/kg
    benz [a]anthracene,  1-77 mg/kg indeno[1,2,3- cd]pyrene, 2-39 mg/kg
    benzo [e]pyrene, 1-29 mg/kg benzo [ghi]perylene, 1-18 mg/kg
    coronene, 1-14 mg/kg perylene, and 1-12 mg/kg anthracene (Cretney et
    al., 1985).

         The amounts of PAH emitted from coal-fired domestic stoves seem
    to depend on the quality of the coal used and on the firing technique.
    Generally, hard coal has a higher energy content than other fuels;
    thus, less total PAH is emitted per unit of gained energy. The lowest
    specific emission factors for benzo [a]pyrene and benzo [e]pyrene
    were found with anthracite and the highest with gas coal and gas-flame
    coal (Ahland et al., 1985). Model experiments with a slow-combustion
    stove showed that pitch-bound hard-coal briquettes emitted about 10
    times more PAH than bitumen-bound briquettes (Ratajczak et al., 1984).
    The use of pitch-bound hard-coal briquettes for domestic heating may
    thus be an important source of PAH in the atmosphere. Use of this fuel
    was restricted by law to permanent combustion stoves in western
    Germany in 1974, and since 1976 only bitumen-bound hard-coal
    briquettes have been produced there (Ratajczak et al., 1984). There is
    no comparable information for other countries. The levels of airborne
    PAH from a permanent combustion stove burning brown coal were two to
    four times higher than those from a slow-combustion stove with a
    medium load (Grimmer et al., 1983a).

         About 25-1000 times more PAH are produced from burning wood than
    from the same mass of charcoal. Since the yield of energy per unit
    mass is similar, burning wood also produces more PAH per unit of
    energy. Burning conditions are apparently the major determinant of
    emission and are much more important than the kind of wood (Ramdahl et
    al., 1982). In areas where domestic heating is predominantly by wood
    burning, most airborne PAH may come from this source, especially in
    winter (e.g.Cooper, 1980). Using benz [a]pyrene as an indicator in
    extensive measurements in New Jersey, USA, the amounts emitted were
    found to be more than 10 times higher during the heating period than
    in seasons when heating is not required. An assessment of combustion
    source also showed that residential combustion of wood was the

    decisive factor (Harkov & Greenberg, 1985). About 43-47% of the total
    PAH released in winter in Fairbanks, Alaska, came from residential
    wood stoves (Guenther et al., 1988).

         The PAH concentrations in gases in the chimney stacks of
    residential coal and oil furnaces are given in Table 22. The highest
    levels were found during the start of the burning process (Brockhaus &
    Tomingas, 1976). Measurements with five qualities of coal showed that
    Extrazit(R), a specially treated coal, emitted smaller quantities of
    smoke and the lowest PAH levels, and anthracite briquettes emitted the
    highest levels. Presumably, the high PAH emissions from anthracite
    briquettes are due to the binding agent, hard coal-tar, which has an
    especially high PAH content. Furnaces with atomizer oil burners seemed
    to emit less PAH than those with vaporizers. Measurements in a
    slow-combustion stove and a tiled stove showed that the highest
    concentrations of PAH were associated with dust of a particle size of
    < 2.1 œm. As for residential heating with wood, in areas where the
    predominant form of domestic heating is coal burning, a major
    proportion of airborne PAH may come from this source, especially in
    winter (Moriske et al., 1987).


    Table 22. Polycyclic aromatic hydrocarbon concentrations (µg/m3)
    in stack gases from residential coal and oil stoves

                                                                  

    Compound                   Coal                Oil
                                                                  

    Benz[a]anthracene          0.0157-2630         0.2-0.6
    Benzo[a]pyrene             0.0016-1270         0.19-0.67
    Benzo[b]fluoranthene       0.0188-3270         0.004-0.68
    Benzo[e]pyrene             0.0261-3430         0.4-6.9
    Benzo[ghi]perylene         0.010-1670          0.41-3.4
    Benzo[k]fluoranthene       0.0044-1250         0.18-0.36
    Chrysene                   0.0142-2590         0.1-0.5
    Coronene                   0.003-710           0.15-0.47
    Dibenz[a,h]anthracene      0.002-410           NR
    Fluoranthene               0.0393-6830         0.0134
    Perylene                   0.0015-2730         0.31-0.8
    Pyrene                     0.0066-1650         0.1-0.9
                                                                  

    From Brockhaus & Tomingas (1976); one permanent combustion stove
    burning anthracite and brown-coal briquets and vaporizer and
    atomizer oil burners; NR, not reported

         Estimates of annual PAH emissions due to residential heating are
    available for a few countries:

    -    In western Germany, the benzo [a]pyrene emissions were about 10
         t in 1981 (Ahland et al., 1985), 7 t in 1985, and 2.5 t in 1988,
         mainly resulting from coal heating. The reduction in the release
         of PAH into the atmosphere due to domestic heating resulting from
         increasing use of oil and gas during the last 30-40 years was
         estimated to be 90-99% (Zimmermeyer et al., 1991).

    -    In the Netherlands, the estimated release in 1985 was < 1 t/year
         each for benzo [k]fluoranthene and indeno[1,2,3- cd]pyrene,
         < 10 t/year each for anthracene, fluoranthene,
         benz [a]anthracene, chrysene, benzo [a]-pyrene, and
         benzo[ghi]perylene, and 48-70 t/year each for naphthalene and
         phenanthrene, mainly resulting from wood heating (Slooff et al.,
         1989).

    -    The total PAH input, mainly from coal and wood heating, was about
         63 t in Norway, 130 t in Sweden, and 720 t in the USA in 1985
         (Bjorseth & Ramdahl, 1985).

    -    In Canada in 1990, the total PAH released due to residential
         heating, mainly wood burning, was about 500 t (Environment
         Canada, 1994).

          (iii)  Open burning

         PAH may be released to the atmosphere during forest and
    agricultural fires, burning of accidentally spilled oil, disposal of
    road vehicles and especially automobile tyres, open burning of coal
    refuse and domestic and municipal waste, and open fires. The release
    of PAH into the atmosphere from the burning of wastes, including road
    vehicles, in the open is decreasing in industrialized countries due to
    comprehensive regulations.

         Laboratory experiments with pine needles gave the following
    specific PAH emission factors (per kg pine needle): 980-20 000 œg
    pyrene, 690-15 000 œg fluoranthene, 580-12 000 œg anthracene plus
    phenanthrene, 540-29 000 œg chrysene plus benz [a]anthracene,
    420-6200 œg benzo [ghi]-perylene, 170-4300 œg
    indeno[1,2,3- cd]pyrene, 140-8800 œg benzo [c]-phenanthrene,
    130-13 000 œg benzofluoranthenes (isomers not specified), 61-800 œg
    benzo [e]-pyrene, 38-3500 œg benzo [a]pyrene, and 24-2100 œg
    perylene, depending on the amount of needles, area, and type of fire.
    Fires moving with the wind and low fuel loading resulted in
    significantly smaller amounts of PAH than fires moving against the
    wind and high fuel loading (McMahon & Tsoukalas, 1978). The emission
    factor for acenaphthene was 230-1000 µg/kg dry straw (Ramdahl &
    Mœller, 1983) and 660 µg/kg dry wood (Alfheim et al., 1984).

         In model experiments with crude oil spilled on water, numerous
    PAH were found, including acenaphthene, acenaphthylene, phenanthrene,
    anthracene, 1-methylphenanthrene, fluoranthene, pyrene, fluorene,
    benzo [a]fluorene, benzo [b]fluorene, benz [a]anthracene, chrysene
    plus triphenylene, benzo [b]-fluoranthene, benzo [ghi]fluoranthene,
    benzo [e]pyrene, benzo [a]pyrene, perylene,
    indeno[1,2,3- cd]pyrene, benzo [ghi]perylene, and coronene, at
    concentrations of ¾ 1000 mg/kg individual substance in both the soot
    and the burn residue (Benner et al., 1990). Even though the open
    burning of oil spilled on water results in a lower PAH content than in
    crude oil (see Table 8), this source may be of local importance, e.g.
    near tanker accidents.

         Between the early and the mid-1970s, the total release of PAH
    (including nitrogen-containing analogues and quinone degradation
    products) into the atmosphere in the USA due to open burning was
    estimated to be about 4000 t/year (Agency for Toxic Substances and
    Disease Registry, 1990). The total PAH input from forest and
    agricultural fires in 1985 was estimated to be 13 t in Norway, 1.3 t
    in Sweden, and 1000 t in the USA, and that from open fires to be 0.4 t
    in Norway and 100 t in the USA (Bjorseth & Ramdahl, 1985). The release
    of all PAH into the atmosphere from the burning of scrap electrical
    cable in 1988 was about 17 t (Slooff et al., 1989). In Canada in 1990,
    the total PAH emissions from agricultural burning and open-air fires
    were estimated to be about 360 t and those from forest fires to be
    about 2000 t (Environment Canada, 1994).

          (iv)  Other diffuse sources

         The total PAH released into the atmosphere in the Netherlands
    from roofing tar and asphalt in 1988 was estimated at 0.5 t/year
    (Slooff et al., 1989).

          (c)  Emissions to the hydrosphere

          (i)  Motor vehicle traffic

         The main source of PAH in the aqueous environment as a result of
    motor vehicle traffic is highway run-off, which contains asphalt and
    soot particles and is washed by rainfall and storm water or snow into
    surface waters and soil (see also 3.2.7.2 (a) (i)). The available data
    are summarized in Table 23. Higher PAH concentrations were found in
    highway run-off in winter than in summer; this was attributed to the
    increased abrasion of the road surface due to use of steel-studded
    tyres in winter (Berglind, 1982).

         It was estimated that an average of < 10 µg/km per vehicle per
    day of total PAH are transported via pavement runoff water. Most is
    transported to nearby surroundings as small particles of dust (see
    also section 3.2.7.2; Lygren et al., 1984). In contrast, storm water
    runoff near a US highway was of considerable importance for adjacent
    water bodies. In the test area, over 50% of the total PAH input into a
    nearby river came from highway runoff. The runoff loading factor was
    given as 24 mg/km per vehicle (Hoffman et al., 1985).

        Table 23. Polycyclic aromatic hydrocarbon concentrations (µg/litre) in highway runoff

                                                                                         

    Compound                   [1]             [2]             [3]       [4]       [5]
                                                                                         

    Acenaphthene               0.016/0.087     0.195/5.126     NR        NR        NR
    Acenaphthylene             0.045           0.557/16.804    NR        NR        NR
    Anthracene                 0.042-0.214     0.486/8.917     0.379     0.165     0.246
    Benzo[j+k]fluoranthene     0.089/0.277     NR              NR        NR        0.207
    Benz[a]anthracene          0.031-0.139     0.341/0.863     0.677     0.228     NR
    Benzo[a]fluorene           0.018-0.170     0.587           NR        0.179     0.396
    Benzo[a]pyrene             0.061-0.120     0.537/1.255     0.602     0.250     NR
    Benzo[b]fluoranthene       0.129/0.157     NR              NR        0.799     1.501
    Benzo[b]fluorene           0.033/0.097     0.356/0.366     NR        NR        0.192
    Benzo[c]phenanthrene       NR              0.250           NR        NR        NR
    Benzo[e]pyrene             0.108/0.202     0.238/1.665     0.609     0.360     0.630
    Benzofluoranthenesa        0.401/0.695     1.087/2.712     1.171     NR        NR
    Benzo[e]perylene           0.100-0.299     NR              0.551     0.391     0.319
    Chyrsene + triphenylene    0.194-0.433     1.472/2.752     1.147     0.665     1.070
    Fluoranthene               0.321-1.573     4.065/15.322    2.665     1.820     3.143
    Fluorene                   0.0088-0.564    0.432/11.093    0.096     0.485     1.237
    Indeno[1,2,3-cd]pyrene     0.061-0.154     0.344/0.666     NR        NR        NR
    1-Methylphenanthrene       0.030-1.073     0.637/2.308               1.366     2.117
    Naphthalene                NR              2.59            NR        0.123     0.195
    Perylene                   0.048           NR              NR        NR        NR
    Phenanthrene               0.068-2.668     3.297/38.10     1.385     4.055     6.787
    Pyrene                     0.363-1.449     3.026/12.094    2.002     1.886     3.066
                                                                                         
    NR, not reported; /, single measurements;
    [1] Run-off samples from a Norwegian highway north of Oslo in summer and winter
        1980-82 (Berglind, 1982);
    [2] Snow 20 and 50 m from the same highway in February 1981 (Berglind, 1982);
    [3] Snow from a frozen Norwegian lake 50 m from a highway with high traffic density in
        winter 1981-82 (Gjessing at al., 1984);
    [4] Snow from a Norwegian highway south of Oslo with concrete pavement, February 1972
        (Lygren at al., 1984);
    [5] Snow from a Norwegian highway south of Oslo with asphalt pavement, February 1972
        (Lygren et al., 1984)

    When the water samples were filtered through solid sorbents, the results may be
    underestimates of the actual content (see section 2.4.1.4).

    a Isomers not specified

          (ii)  Sewage treatment

         The concentrations of PAH in final effluents from municipal
    sewage treatment facilities are generally in the low microgram per
    litre range and are almost always < 0.1 µg/litre (Nicholls et al.,
    1979; Young et al., 1983; van Luin & van Starkenburg, 1984; Kröber &
    Häckl, 1989). Maximum values of 29 µg/litre naphthalene and 7 µg/litre
    acenaphthene were detected in one US sewage treatment plant, and 8
    µg/litre benzo [a]pyrene were found in one German plant (Young et
    al., 1983; Kröber & Häckl, 1989), but no explanation was given for
    these unusually high concentrations. It was concluded that final
    effluents contain PAH at a background level (van Luin & van
    Starkenburg, 1984).

         Naphthalene was found at a concentration of 9.3 kg/year in the
    final effluent from one US municipal sewage plant (Hoffman et al.,
    1984). The annual emissions of naphthalene, anthracene, phenanthrene,
    fluoranthene, benz [a]anthracene, chrysene, benzo [k]fluoranthene,
    benzo [a]pyrene, benzo [ghi]perylene, and indeno[1,2,3- cd]pyrene
    from Dutch sewage treatment plants into surface waters were estimated
    to be about 0.6 t. The amount of these PAH transported into the
    Netherlands from other European countries via the Rhine, Meuse, and
    Scheldt rivers was estimated to be 65 t/year (year and database not
    given). The main compounds were fluoranthene (18 t/year) and
    naphthalene (15 t/year) (Slooff et al., 1989).

          (iii)  Other sources

         PAH have been found in wastewaters from power stations, from
    garages with car-wash devices, and from a German car-wash storage tank
    at the following concentrations: fluoranthene, 1.3-7.7 µg/litre;
    pyrene, 3.5-28 µg/litre; benz [a]anthracene, 0.49-1.9 µg/litre;
    chrysene, 1.2-6.0 µg/litre; benzo [e]pyrene, 4.7-16 µg/litre;
    benzo [a]pyrene, 0.40-8.8 µg/litre; benzo [b]fluoranthene, 1.2-3.6
    µg/litre; and benzo [k]-fluoranthene, 0.51-0.72 µg/litre (Baumung et
    al., 1985). Wastewaters from power stations could be an important
    local source of PAH.

         Numerous PAH were detected in leachate plumes from refuse
    landfills in western Germany and the USA (Grimmer et al., 1981b; Götz,
    1984; Reinhard et al., 1984). Concentrations < 0.1 µg/litre were
    detected of benzo [ghi]-fluoranthene, benz [a]anthracene,
    benzo [c]phenanthrene, chrysene, benzofluoranthenes (isomers not
    specified), benzo [a]pyrene, benzo [e]pyrene, perylene,
    anthanthrene, benzo [ghi]perylene, and indeno[1,2,3- cd]pyrene
    (Grimmer et al., 1981b). Naphthalene was found at a concentration >
    100 µg/litre, and acenaphthene, fluorene, anthracene, phenanthrene,
    and pyrene were found at concentrations of 1-30 µg/litre (Götz, 1984;
    Reinhard et al., 1984). The importance of this source for groundwater
    pollution cannot be estimated from the available data.

          (c)  Emissions to the geosphere

          (i)  Motor vehicle traffic

         PAH were deposited within 100 m of a highway at a concentration
    of 100-200 µg/km per vehicle per day in winter as small particles of
    dust resulting from the abrasion of asphalt by steel-studded tyres
    (Lygren et al., 1984). Studies of adsorption on various soil types
    showed that most PAH in highway runoff is retained on the soil surface
    (Gjessing et al., 1984).

          (ii)  Open burning

         Phenanthrene, fluoranthene, triphenylene, benzo [k]fluoranthene,
    benzo [a]pyrene, benzo [ghi]perylene, indeno[1,2,3- cd]pyrene, and
    coronene were determined in the soil of burning sites in western
    Oregon, USA. Before burning, the PAH concentrations in the top 2 cm of
    the soil layer ranged from 0.8 ng/g dry weight for benzo [a]pyrene to
    4.4 ng/g for fluoranthene and triphenylene. One week after burning,
    the concentrations ranged from 0.9 ng/g for benzo [k]fluoranthene to
    19 ng/g for triphenylene. The finding that the PAH levels did not
    increase appreciably after burning indicates that the bulk of the PAH
    were retained within the litter rather than passing into the soil
    (Sullivan & Mix, 1983).

          (iii)  Disposal of sewage sludge and fly ash from incineration

         When sewage sludge is applied to soils, adsorbed PAH are added to
    the geosphere. The PAH concentrations in municipal aerobic and
    anaerobic sewage sludge are given in Table 24.

         In a detailed survey of the PAH concentrations in soil to which
    anaerobic sludges had been applied between 1942 and 1961 in the United
    Kingdom, the total PAH content increased to over 125 mg/kg up to 1948
    but had decreased to about 29 mg/kg by 1961. The authors attributed
    the declining levels to a decrease in atmospheric PAH contamination
    from smoke emissions (Wild et al., 1990). No seasonal variation in the
    content or profile of PAH was detected in western Germany by Grimmer
    et al. (1980), but Süss (1980) found the highest PAH load in sewage
    sludge in January-April and the lowest in July and October. Human
    faeces seemed to contribute little to the PAH content of sewage sludge
    (Grimmer et al., 1980). The most important emission sources could not
    be identified, but McIntyre et al. (1981) concluded that the PAH
    content of sewage sludge originating from British treatment works with
    significant flows of industrial effluent was higher than that in works
    dealing with predominantly domestic effluents.

         After application of compost over three years to an agricultural
    soil in Spain, no accumulation of PAH was observed (Gonzalez-Vila et
    al., 1988). It was shown, however, that the extent of accumulation is
    dependent on the duration, frequency, and concentration of
    application. After 10 years of sludge spreading, considerable
    quantities of PAH were detected in both a sandy loam and a clay soil


        Table 24. Polycyclic aromatic hydrocarbons concentrations (mg/kg dry weight) in municipal sewage sludge
                                                                                                                                           
    Compound                 [1]            [2]            [3]            [4]         [5]         [6]           [7]            [8]
                                                                                                                                           
    Acenaphthene             NR             NR             NR             NR          NR          NR            ND             NR
    Anthracene               NR             NR             NR             0.89-44     NR          NR            ND-10.0        NR
    Anthanthrene             0.00-2.10      0.03-1.8       NR             NR          NR          NR            NR             NR
    Benz[a]anthracene        0.62-19.0      0.91-17.3      NR             NR          NR          NR            ND-2.1         NR
    Benzo[a]fluorene         0.28-9.00      0.56-7.9       NR             NR          NR          NR            NR             NR
    Benzo[a]pyrene           0.54-13.3      0.41-14.3      0.12-9.14      NR          NR          0.29-2.00     ND-0.64        NR
    Benzo[b]fluoranthene     NR             NR             0.06-9.14      NR          < 1-1.3     0.29-1.80     ND-1.100       NR
    Benzo[e]pyrene           0.53-12.4      0.48-12.3      NR             NR          NR          NR            NR             NR
    Benzofluoranthenesa      1.07-23.7      1.02-24.8      NR             NR          NR          NR            NR             NR
    Benzo[ghi]perylene       0.40-8.70      0.34-10.9      0.06-9.14      NR          NR          < 0.1-3.41    ND-1.21        NR
    Benzo[k]fluoranthene     NR             NR             0.06-4.57      NR          NR          0.15-1.00     ND-0.500       NR
    Chrysene                 0.78-23.7      1.24-22.2      NR             0.25-13     NR          NR            NR             NR
    Dibenz[a,h]anthracene    NR             NR             NR             13          NR          NR            ND-0.25        NR
    Fluoranthene             0.61-51.6      4.10-28.2      0.34-11.45     0.35-7.1    < 1-10.4    0.54-7.67     0.216-5.14     5.2/5.6b
    Fluorene                 NR             NR             NR             NR          NR          NR            ND-2.9c        3.5/5.8
    Indeno[1,2,3-cd]pyrene   0.30-7.40      0.28-9.4       0.06-6.68      NR          NR          0.24-2.08     ND-0.640       NR
    Naphthalene              NR             NR             NR             0.9-70      NR          NR            NR             4.5/8.6
    Perylene                 0.14-6.40      0.09-3.1       NR             NR          NR          NR            NR             NR
    Phenanthrene             NR             NR             NR             0.89-44     NR          NR            0.30-40        15.2/18.6d
    Pyrene                   0.90-47.2      3.20-25.3      NR             0.33-18N    R           NR            ND-7.6         NR
                                                                                                                                           

    NR, not reported; /, single measurements; ND, not detected (limits of detection, 0.2-1 mg/kg);
    [1] Samples from 25 sewage treatment plants in western Germany 1976-78 (Grimmer et al., 1980);
    [2] Samples from three sewage treatment facilities in western Germany before 1979 (Suss, 1980);
    [3] Samples from 12 British sewage treatment works (McIntyre at al., 1981);
    [4] Samples from 20 US sewage treatment works (Naylor & Loehr, 1982);
    [5] Samples from six Dutch municipal sewage treatment plants (van Luin & van Starkenburg, 1984);
    [6] 31 sludge samples from different sewage treatment works in western Germany (Witte et al., 1988);
    [7] Anaerobic sludge samples from 13 sewage treatment plants in western Germany 1985-88 (Krober & Hackl, 1989);
    [8] Anaerobic sludge samples from one Spanish sewage treatment facility in spring 1985 and autumn 1986
       (Gonzalez-Villa at al., 1988).
    a Isomers not specified
    b With pyrene
    c With acenaphthylene
    d With anthracene


    (Diercxsens & Tarradellas, 1987). The annual addition of PAH to soil
    from sewage sludge in the Netherlands was estimated as follows: 0.1 t
    naphthalene, 0.1 t anthracene, 1.5 t phenanthrene, 2.3 t fluoranthene,
    0.6 t benzo [a]anthracene, 0.6 t chrysene, 0.4 t
    benzo [k]fluoranthene, 0.6 t benz [a]pyrene, 0.6 t
    benzo [ghi]-perylene, and 0.6 t indeno[1,2,3- cd]pyrene (year and
    database not given; Slooff et al., 1989).

         The annual contribution of PAH to landfill in the United Kingdom
    from fly ash from coal combustion (see also Table 16) exceeded that
    from municipal solid-waste incineration by a factor of about 10, with
    the exception of naphthalene, the level of which was about 20 000-fold
    higher in fly ash from coal combustion than in that from solid-waste
    incineration. The annual PAH loads from solid-waste incineration were
    about 0.01 kg naphthalene and 3.5 kg benzo [ghi]perylene, whereas
    those from coal combustion were about 15 kg each of anthracene,
    benzo [k]fluoranthene, and dibenz [a,h]anthracene and 1200 kg pyrene
    (Wild et al., 1992).

          (iv)  Waste dumping

         Soil cores taken from a hazardous waste disposal site in Spain
    containing petroleum tar residues and lubricating oils as the major
    organic wastes contained 62 mg/kg 1-methylphenanthrene, 53 mg/kg
    naphthalene, 52 mg/kg benzo [a]fluorene, 30 mg/kg
    benzo [ghi]fluoranthene, 25 mg/kg benzo [c]-phenanthrene, 0.5-0.71
    mg/kg acenaphthene, 0.2-48 mg/kg fluorene, 0.2-390 mg/kg phenanthrene,
    0.110 mg/kg anthanthrene, 0.1-210 mg/kg pyrene, 0.1-200 mg/kg
    acenaphthylene, 0.1-140 mg/kg anthracene, 0.1-140 mg/kg
    benzo [e]pyrene, 0.1-145 mg/kg benzo [a]pyrene, 0.1-50 mg/kg
    benzo [b]fluorene, 0.08-130 mg/kg chrysene plus triphenylene, 0.08-90
    mg/kg indeno[1,2,3- cd]pyrene, 0.06-130 mg/kg benz [a]anthracene,
    0.05-290 mg/kg fluoranthene, 0.03-75 mg/kg benzo [ghi]perylene,
    0.03-0.2 mg/kg perylene, and 0.01-0.4 mg/kg dibenz [a,h]anthracene
    (Navarro et al., 1991).

         There can be appreciable movement of PAH into soil from waste
    dumping, especially of hazardous refuse. The dumping conditions are
    decisive for the amount of PAH released. Annual emissions of PAH in
    the Netherlands in 1987 due to the spreading of contaminated composts
    onto soils were estimated to be 1 t benz [a]anthracene, 1 t chrysene,
    1 t benzo [k]fluoranthene, 0.5 t benzo [ghi]-perylene, 0.5 t
    indeno[1,2,3-cd]pyrene, and 0.4 t benzo [a]pyrene (Slooff et al.,
    1989).

          (d)  Biosphere

         Perch  (Perca fluviatilis) were not significantly contaminated
    after an oil spill in Finland due to a tanker accident. The
    concentrations of acenaphthene, acenaphthylene, fluorene,
    phenanthrene, anthracene, 1-methylphenanthrene, fluoranthene, pyrene,
    benzo [a]fluorene, benzo [b]fluorene, chrysene, triphenyl-ene, and
    benzofluoranthenes in both contaminated and control groups were

    between < 0.1 and 0.2 µg/kg each in muscle and < 0.1 and 16
    µg/kg in bile. The investigators concluded that the fish with the
    highest load would probably not have survived and others had moved to
    less contaminated areas. Additionally, the cold climate caused
    clumping of the spilled oil, which then drifted to the coast
    (Lindström-Seppä et al., 1989; see also sections 4.1.5.1 and 5.1.7.1).

    4.  ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

     Appraisal

         The transport and distribution of polycyclic aromatic
    hydrocarbons (PAH) in the environment depend on their physicochemical
    properties of very low solubility in water and low vapour pressure,
    and high partition coefficients for  n-octanol:water (log Kow) and
    organic carbon:water (log  Koc). PAH are stable towards hydrolysis
    as they have no reactive groups. In the gaseous phase, PAH and
    particularly those of higher molecular mass, are mainly adsorbed to
    particulate matter and reach the hydrosphere and geosphere by dry and
    wet deposition. Little is volatilized from water phases owing to their
    low Henry's law constants. The log  Koc values indicate strong
    adsorption to the organic matter of soils, so that migration does not
    usually occur. The log  Kow values indicate high bioaccumulation.

         Few experimental data are available on the biodegradation of PAH.
    In general, they are biodegradable under aerobic conditions, and the
    biodegradation rates decrease drastically with the number of aromatic
    rings. Under anaerobic conditions, biodegradation appears to be very
    slow.

         The bioconcentration factors measured in the water phase vary
    widely according to the technique used. High values are seen for some
    algae, crustaceans, and molluscs, but those for fish are much lower
    owing to rapid biotransformation. The bioaccumulation factors for
    aquatic and terrestrial organisms in sediment and soil are generally
    very low, probably because of the strong adsorption of PAH onto the
    organic matter of soils and sediments, resulting in low
    bioavailability.

         The photodegradation of PAH in air and water has been studied
    intensively. The most important degradation process in both media is
    indirect photolysis under the influence of radicals like OH, O3, and
    NO3. The measured degradation rate constants vary widely according to
    the technique used. Under laboratory conditions, the half-life of the
    reaction of PAH with airborne OH radicals is about one day. Adsorption
    of high-molecular-mass PAH onto carbonaceous particles in the
    environment has a stabilizing effect. Formation of nitro-PAH has been
    reported from two- to four-ring PAH in the vapour phase during
    photooxidation with NO3. For some PAH, photodegradation in water
    seems to be more rapid than in air.

         According to model calculations based on physicochemical and
    degradation parameters, PAH with four or more aromatic rings persist
    in the environment.

    4.1  Transport and distribution between media

    4.1.1  Physicochemical parameters that determine environmental transport
    and distribution

         The transport and distribution of PAH in the environment are the
    result of the following physicochemical parameters:

    -     Aqueous solubility: PAH are hydrophobic compounds with very low
         solubility in water under environmental conditions: the maximum
         at room temperature is 32 mg/litre for naphthalene, and the
         minimum is 0.14 µg/litre for coronene (see Table 4).

    -     Vapour pressure: The vapour pressure of PAH under environmental
         conditions is very low: the maximum at room temperature is 10.4
         Pa for naphthalene, and the calculated minimum is 3 × 10-12 Pa
         for dibenzo [a,i]pyrene (see Table 4).

    -     n-Octanol:water partition coefficient (log  Kow): The
         affinity of PAH to organic phases is much higher than that for
         water. The log  Kow values range from 3.4 for naphthalene to 7.3
         for dibenzo [a,i]pyrene (see Table 4), indicating that the
         potential for bioaccumulation is high.

    -     Organic carbon:water partition coefficient (log Koc): The
         sorption coefficients of PAH to the organic fraction of sediments
         and soils are summarized in Table 25. The high values indicate
         that PAH sorb strongly to these fractions. The wide variation in
         the results for individual compounds are due to the very long
         exposure necessary to reach steady-state or equilibrium
         conditions, which can lead to underestimation of sorption
         coefficients; furthermore, degradation in the overlying aqueous
         phase can lead to overestimates of the actual values.

    4.1.2  Distribution and transport in the gaseous phase

         PAH are emitted mainly to the atmosphere (see Section 3), where
    they can be both transported in the vapour phase and adsorbed onto
    particulate matter. The distribution between air and particulate
    matter under normal atmospheric conditions depends on the
    lipophilicity, vapour pressure, and aqueous solubility of the
    substance. Generally, PAH with few (two to four) aromatic rings occur
    in the vapour phase and are adsorbed, whereas PAH consisting of more
    aromatic rings exist mainly in the adsorbed state (Hoff & Chan, 1987;
    McVeety & Hites, 1988; Baker & Eisenreich, 1990). PAH are usually
    adsorbed onto particles like fly ash and soot that are emitted during
    combustion.


        Table 25. Organic carbon normalized sorption coefficients (Koc) of polycyclic aromatic hydrocarbons

                                                                                                            

    Compound                log Koc        Comments                              Reference
                                                                                                            

    Acenaphthene            5.38           Average on sediments                  Kayal & Connell (1990)
                            3.79           RP-HPLC on CIHAC                      Szabo et al. (1990)
                            3.59           RP-HPLC on PIHAC                      Szabo at al. (1990)
    Acenaphthylene          3.83           RP-HPLC on CIHAC                      Szabo et al. (1990)
                            3.75           RP-HPLC on PIHAC                      Szabo et al. (1990)
    Anthracene              4.42           Average sorption isotherms on         Karickhoff et al. (1979)
                                           sediment
                            3.74           Suspended particulates                Herbes et al. (1980)
                            4.20           Soil, shake flask, UV                 Karickhoff (1981)
                            3.95/4.73      Lake Erie with 9.6 mg C/litre         Landrum et al. (1984a)
                            4.87/5.70      Huron river with 7.8 mg C/litre       Landrum et al. (1984a)
                            4.20           Soil, shake flask, LSC                Nkedl-Kizza et al. (1985)
                            4.93           Fluorescence, quenching interaction   Gauthier et al. (1986)
                                           with humic acid
                            4.38           HPLC                                  Hodson & Williams (1988)
                            5.76           Average on sediments                  Kayal & Connell (1990)
                            4.41           RP-HPLC                               Pussemier et al. (1990)
                            4.53           RP-HPLC on CIHAC                      Szabo at al. (1990)
                            4.42           RP-HPLC on PIHAC                      Szabo at al. (1990)
    Benz[a]anthracene       4.52           Suspended particles                   Herbes et al. (1980)
                            6.30           Average on sediments                  Kayal & Connell (1990)
                            7.30           Specified particulate                 Bromen et al. (1990)
    Benzo[a]pyrene          6.66           LSC                                   Eadie et al. (1990)
                            6.26           Average on sediments                  Kayal & Connell (1990)
                            8.3            Specified particulate                 Broman et al. (1990)
                            4.0            Predicted to be dissolved             Broman et al. (1990)
    Benzo[e]pyrene          7.20           Specified particulate                 Broman at al. (1990)
                            4.00           Predicted to be dissolved             Broman at al. (1990)
    Benzo[k]fluoranthene    5.99           Average on sediments                  Kayal & Connell (1990)
                            7.00           Specified particulate                 Broman et al. (1990)
                            4.00           Predicted to be dissolved             Broman at al. (1990)

    Table 25. (continued)

                                                                                                            

    Compound                log Koc        Comments                              Reference
                                                                                                            

    Chrysene                6.27           Average on sediments                  Kayal & Connell (1990)
                            6.90           Specified particulate                 Broman et al. (1990)
                            4.0            Predicted to be dissolved             Broman at al. (1990)
    Coronene                7.80           Specified particulate                 Broman et al. (1990)
                            5.0            Predicted to be dissolved             Broman et al. (1990)
    Dibenz[a,h]anthracene   6.31           Average of 14 soil or sediment        Means et al. (1980)
                                           samples, shake flask, LSC
    Fluoranthene            6.38           Average on sediments                  Kayal & Connell (1990)
                            4.74           RP-HPLC on CIHAC                      Szabo et al. (1990)
                            4.62           RP-HPLC on PIHAC                      Szabo et al. (1990)
                            6.30           Specified particulate                 Broman et al. (1990)
                            4.0            Predicted to be dissolved             Broman et al. (1990)
    Fluorene                5.47           Average on sediments                  Kayal & Connell (1990)
                            3.76           RP-HPLC                               Pussemier et al. (1990)
                            4.15           RP-HPLC on CIHAC                      Szabo et al. (1990)
                            4.21           RP-HPLC on PIHAC                      Szabo et al. (1990)
    Naphthalene             3.11           Average sorption isotherms on         Karickhoff at al. (1979)
                                           sediments
                            2.38           Suspended particulates                Herbes et al. (1980)
                            2.94                                                 Karickhoff (1981)
                            3.0                                                  McCarthy & Jimenez (1985);
                                                                                 McCarthy et al. (1985)
                            2.73-3.91      Aquifer materials                     Stauffer et al. (1989)
                            3.15/2.76                                            Podoll et al. (1989)
                            5.00           Average on sediments                  Kayal & Connell (1990)
                            2.66           Average on sediments                  Kishi et al. (1990)
                            3.11           Soil, RP-HPLC                         Szabo et al. (1990)
                            3.29           Sandy surface soil                    Wood et al. (1990)

    Table 25. (continued)

                                                                                                            

    Compound                log Koc        Comments                              Reference
                                                                                                            

    Phenanthrene            4.36           Average sorption isotherms on         Karickhoff et al. (1979)
                                           sediments
                            4.28                                                 Hodson & Williams (1988)
                            6.12           Average on sediments                  Kayal & Connell (1990)
                            4.22           RP-HPLC on CIHAC                      Szabo et al. (1990)
                            4.28           RP-HPLC on PIHAC                      Szabo et al. (1990)
                            4.42           Sandy surface soil                    Wood et al. (1990)
    Pyrene                  4.92           Average isotherms on sediments        Karickhoff et al. (1979)
                            4.90           Sediment, shake flask, sorption       Karickhoff et al. (1979)
                                           isotherm
                            4.81           Average of soil and sediment          Means et al. (1979)
                                           Shake flask, LSC, sorption
                                           isotherms
                            4.80           Average of 12 soils and sediments     Means et al. (1980)
                                           Shake flask, LSC, sorption isotherms
                            4.78           Soil and sediment; calculated Kow     Means at al. (1980)
                            4.83           Sorption isotherms                    Karickhoff (1981)
                            3.11/3.46      Sediment suspensions                  Karickhoff & Morris (1985)
                            4.80/5.13                                            Hodson & Williams (1988)
                            5.65           LSC                                   Eadie et al. (1990)
                            5.29           Soil                                  Jury at al. (1990)
                            6.51           Average on sediments                  Kayal & Connell (1990)
                            4.83           RP-HPLC                               Pussemier et al. (1990)
                            4.82           RP-HPLC on CIHAC                      Szabo et al. (1990)
                            4.77           RP-HPLC on PIHAC                      Szabo et al. (1990)
                            6.50           Specified particulate                 Broman et al. (1990)
                            4.0            Predicted particulate                 Broman et al. (1990)
    Triphenylene            6.90           Specified particulate                 Broman et al. (1990)
                            4.00           Predicted to be dissolved             Broman et al. (1990)
                                                                                                            

    RP-HPLC, reversed-phase high-performance liquid chromatography; CIHAC, chemical-induced humic-acid column;
    PIHAC, physical-induced humic-acid column; UV, ultraviolet; C, carbon; LSC, liquid scintillation
    chromatography


         PAH are ubiquitous in the environment, probably because they are
    distributed for long distances without significant degradation (Lunde,
    1976; De Wiest, 1978; Bjorseth & Sortland Olufsen, 1983; McVeety &
    Hites, 1988), e.g. from the United Kingdom and the European continent
    to Norway and Sweden during winter (Bjorseth & Lunde, 1979). Washout
    ratios calculated from measurements in rain and snow in the area of
    northern Lake Superior, during one year showed that airborne PAH
    adsorbed onto particulate matter result in effective wet deposition,
    while gaseous PAH are removed to only a minor degree (McVeety & Hites,
    1988).

    4.1.3  Volatilization

         Henry's law constant gives a rough estimate of the equilibrium
    distribution ratio of concentrations in air and water but cannot
    predict the rate at which chemicals are transported between water and
    air. The constants for PAH are very low, ranging from 49 Pa .m3/mol
    for naphthalene to 0.000449 Pa .m3/mol for dibenzo [a,i]pyrene (see
    Table 4). The rates of removal and volatilization of PAH (Table 26)
    are strongly dependent on environmental conditions such as the depth
    and flow rate of water and wind velocity. Although PAH are released
    into the environment mainly in air, considerably higher concentrations
    are found in aqueous samples because of the low vapour pressure and
    Henry's law constants of PAH.

         The volatilization half-life for naphthalene from a 22.5-m water
    body was found experimentally to be 6.3 h, whereas the calculated
    value was 2.1 h (Klöpffer et al., 1982). Calculations based on a
    measured air:water partition coefficient for river water 1 m deep with
    a water velocity of 0.5 m/s and a wind velocity of 1 m/s gave a
    volatilization half-life of 16 h for naphthalene (Southworth, 1979).
    The value calculated for evaporative loss of naphthalene from a 1-m
    water layer at 25°C was of the same order of magnitude (Mackay &
    Leinonen, 1975). Naphthalene was volatilized from soil at a rate of
    30% after 48 h, with neglible loss of PAH with three or more rings
    (Park et al., 1990).

    4.1.4  Adsorption onto soils and sediments

         PAH are adsorbed strongly to the organic fraction of soils and
    sediments (see section 4.1.1 and Table 25). Some PAH may be degraded
    biologically in the aerobic soil layer, but this process is slow,
    because sorption to the organic carbon fraction of the soil reduces
    the bioavailability. For the same reason, leaching of PAH from the
    soil surface layer to groundwater is assumed to be negligible,
    although detectable concentrations have been reported in groundwater
    (see section 5.1.2.2).


        Table 26. Rates of volatilization of polycyclic aromatic hydrocarbons

                                                                                                                                            

    Compound               Rate constant    Half-life (h)a     Comments                                                 Reference
                                                                                                                                            

    Anthracene                                                 Removal rate constants (estimated) from                  Southworth (1977)
                                                               water column
                                                               At 25°C in midsummer sunlight:
                           0.002 h-1        347                - in deep, slow, somewhat turbid water
                           0.001 h-1        693                - in deep, slow, muddy water
                           0.002 h-1        347                - in deep, slow, clear water
                           0.042 h-1        17                 - in shallow, fast, clear water
                           0.179 h-1        3.9                - in very shallow, fast, clear water
                                            62                 Calculated half-life for a river 1 m deep                Southworth (1979)
                                                               with water velocity of 0.5 m/s and wind
                                                               velocity of 1 m/s
    Benz[a]anthracene                       500                Calculated half-life for a river 1 m deep                Southworth (1979)
                                                               with water velocity of 0.5 m/s and wind
                                                               velocity of 1 m/s
    Benzo[a]pyrene                          1550               Calculated half-life for a river 1 m deep                Southworth (1979)
                                                               with water velocity of 0.5 m/s and wind
                                                               velocity of 1 m/s
                           <1 × 10-5 S-1    > 19               Sublimation rate constant from glass                     Cope & Kalkwarf
                                                               surface at 24 °C at an airflow of 3 litre/min            (1987)
    Naphthalene            1.675 × 10-9                        Rate of evaporation estimated at 20 00                   Guckel at al. (1973)
                           mol.cm-2h-1                         and air flow of 50 litre/h
                                            7.15               Calculated half-life from 1 m depth of water             Mackay & Leinonen
                                                                                                                        (1975)
                                            16                 Half-life for surface waters                             Southworth
                                                                                                                        (1979)
                                            200                In a lake, considering current velocity and
                                                               wind speed in combination with typical
                                                               re-aeration rates
    Perylene               <1 × 10-5 S-1    > 19               Sublimation rate constant from glass                     Cope & Kalkwarf
                                                               surface at 24°C at an air flow of 3 litre/min            (1987)
    Pyrene                 1.1 × 10-4 S-1   1.8                Sublimation rate constant as loss from                   Cope & Kalkwarf
                                                               glass surface at 24°C at an air flow of 3 litre/min      (1987)
                                                                                                                                            

    Table 26 (continued)


    For comparison of results for which only rate constants are reported, half-lives have been estimated from the equation:

     t1/2 = In2
             k

    where  t1/2 is the half-life and  k is the rate constant. The calculated values are reported in italics.


    4.1.5  Bioaccumulation

         The ability of a substance to bioconcentrate in organisms in the
    aqueous phase is expressed as the bioconcentration factor. For
    substances like PAH, with high  n-octanol:water partition
    coefficients, long exposures are necessary to achieve equilibrium
    conditions, so that results obtained under non-equilibrium conditions
    can result in underestimates of the bioconcentration factor.
    Bioaccumulation may also vary with the metabolic capacity of the
    organism (see section 4.2.1.2).

         Bioconcentration can also be calculated as the ratio between the
    rates of uptake  (k1) and depuration  (k2). This method has the
    advantage that relatively short exposures can be used. It is therefore
    preferred for PAH, as constant concentrations of compounds like
    benzo [a]pyrene are very difficult to maintain over a long period.

    4.1.5.1  Aquatic organisms

         Aquatic organisms may accumulate PAH from water, sediments, and
    their food. In general, PAH dissolved in pore water are accumulated
    from sediment (McElroy & Sisson, 1989), and digestion of sediment may
    play an important role in the uptake of PAH by some species. Although
    organisms can accumulate PAH from food, the relative importance of
    uptake from food and water is not clear (Farrington, 1991).

         The bioconcentration factors of PAH in different species are
    shown in Table 27; this is not a comprehensive presentation of all of
    the available data but provides examples of the accumulation of some
    PAH in different groups of organisms. Species that metabolize PAH to
    little or no extent, like algae, oligochaetes, molluscs, and the more
    primitive invertebrates (protozoans, porifers, and cnidaria),
    accumulate high concentrations of PAH, as would be expected from their
    log  Kowvalues, whereas organisms that metabolize PAH to a great
    extent, like fish and higher invertebrates such as arthropods,
    echinoderms, and annelids, accumulate little or no PAH (James, 1989).
    Remarkably high bioconcentration factors have been measured for
    phenanthrene, anthracene, pyrene, benzo [a]anthracene, and
    benzo [a]pyrene in the amphipod  Pontoporeia hoyi, which has a
    20-50% lipid content by wet weight and no capacity to biotransform PAH
    (Landrum, 1988).

         The ratio of the concentration of an individual PAH in a
    bottom-dwelling organism and in the sediment, the bioaccumulation
    factor, is usually < 1 when expressed as wet weight. In a coastal
    area, the bioaccumulation factors for 16 PAH in polychaete species
    varied from 4.9 to 21.8 on a dry-weight basis (Bayona et al., 1991).
    Measurements of the concentrations of PAH in  P. hoyi and in the
    sediment at three sites with different organic carbon contents gave
    bioaccumulation factors close to 1 on a wet-weight basis, corrected
    for the 64-mm sieved fraction (Eadie et al., 1982). The lipid- and
    organic carbon-based bioaccumulation factors in clams  (Macoma 
     baltica) for naphthalene and chrysene added to sediment were 0.78

    and 0.16, respectively (Foster et al., 1987). In a study in which
    clams were exposed for 28 days to six sediments contaminated with
    different concentrations of PAH (and other organic pollutants) and
    with an organic carbon content of 0.86-7.4%, the bioaccumulation
    factors (normalized with respect to lipid content and organic carbon
    content) ranged from 0.15 to 0.85 (Ferraro et al., 1990).

         Species that can biotransform PAH have internal concentrations
    well below the concentration in the sediment. The average
    bioaccumulation factors (normalized with respect to lipid content and
    organic carbon content) for eel, pike, and roach at two locations were
    0.1 and 0.015. The lowest bioaccumulation factor was found at the site
    with the highest PAH concentration (128 mg/kg, organic carbon-based),
    probably due to the inductive capability of the fish to biotransform
    PAH. This was confirmed by the finding of increased hepatic metabolic
    activity for PAH in the fish (Van der Oost et al., 1991).

    4.1.5.2  Terrestrial organisms

         Little information is available on the accumulation of PAH in
    terrestrial organisms. The bioaccumulation factors of 22 PAH in the
    earthworm  Eisenia foetida at six sites varied from 0.23 to 0.6 on an
    ash-free dry-weight basis (Rhett et al., 1988).

         The half-life of labelled benzo [a]pyrene in crickets
     (Acheta domesticus) was 13 h; after 48 h, 36% of the injected dose
    was unchanged benzo [a]pyrene. After topical application of piperonyl
    butoxide, a known inhibitor of the mixed-function oxidase system, the
    level of polar metabolites in the excreta had decreased by
    approximately 75% within 8 h of injection of benzo [a]pyrene. After
    articular application of benzo [a]pyrene at 0.29 ng/µl in hexane,
    some of the dose accumulated internally; the highest level of polar
    metabolites was found after 24 h (Kumi et al., 1991).

         The concentration of PAH in vegetation is generally considerably
    lower than that in soil, the bioaccumulation factors ranging from
    0.0001-0.33 for benzo [a]pyrene and from 0.001-0.18 for 17 other PAH
    tested. It was concluded that some terrestrial plants take up PAH
    through their roots and/or leaves and translocate them to various
    other parts (Edwards, 1983).

         When bush beans (Phaseolus vulgaris Pr.) were exposed to
    radiolabelled anthracene in a nutrient solution for 30 days during
    flowering and seed production, more than 90% of the compound was
    metabolized. Of the total 14C radiolabel, 60% was found in the roots,
    3% in the stems, 3% in the leaves, 0.1% in the pods, and 17% in the
    nutrient solution; 16% was unaccounted for (Edwards, 1986).


        Table 27. Measured bioconcentration factors of polycyclic aromatic hydrocarbons in aquatic organisms

                                                                                                                                           

    Species               Analysis          Test     Concentration      Duration of        Bioconcentration     Type      Reference
                                            system   in water           exposure           factor (in
                                                     (µg/litre)         or uptake/         wet weight)
                                                                        depuration
                                                                        period
                                                                                                                                           

    Acenaphthene
    Fish
       Lepomis            14C               S        8.94               28 d               387                  Equi      Barrows et al.
       macrochirus                                                                                                        (1980)

    Anthracene
    Algae
       Chlorella fusca    HPLC              S        50                 1 d                7 770a               NS        Geyer et al.
                                                                                                                          (1984)
    Crustaceans
       Daphnia magna      14C, TLC          S        35                 1 d                511                  k1/k2     McCarthy et al.
                                                                                                                          (1985)
       Daphnia magna      HPLC              S        15                 1 d                970                  NS        Newsted & Giesy
                                                                                                                          (1987)
       Daphnia magna      HPLC              S        5.58               24 h               2699                 NS        Oris et al. (1990)
       Daphnia pulex      Spect             S        6                  24 h               917                            Southworth et al.
                                                                                                                          (1978)
       Hyalella azteca    14C               IF       0.0082             8 h/7 h            2089                 k1/k2     Landrum &
                          14C,TLC                                                          1 800                k1/k2      Scavia (1983)
                          14C               IF       0.0066             8 h/7 h            10985                k1/k2
                          14C, TLC                                                         9096                 k1/k2
       Pontoporeia hoyi   14C TLC           F        4-17               8 W d              16857                k1/k2      Landrum (1982)
       Pontoporeia hoyi   14C TLC           F        4.6-16.9           6 h/14 d           39727                k1/k2      Landrum (1988)
    Oligochaetes
       Stylodrilus        -C, TLC           F        < 6                6 hS d             5051                 k1/k2     Frank et al.
       heringianus                                                                                                        (1986)

    Table 27. (continued)

                                                                                                                                           

    Species               Analysis          Test     Concentration      Duration of        Bioconcentration     Type      Reference
                                            system   in water           exposure           factor (in
                                                     (µg/litre)         or uptake/         wet weight)
                                                                        depuration
                                                                        period
                                                                                                                                           

    Fish
       Lepomis            14C               S        0.7                4 h/60 h           900                  k1/k2     Spacie et al.
       macrochirus        14C, TLC                                                         675                       (1983)
       Leuciscus idus     UC                S        50                 3 d                910                  NS        Freitag A al.
       melanotus                                                                                                          (1985)
       Oncorhynchus       14C HPLC          R        12                 18h                190                  NS        Linder &
       mykiss             14C HPLC          R        12                 18 h               270                  NS        Bergman (1984)
       Oncorhynchus       14C HIPLC         R        50                 72 h/144 h         9000                 k1/k2     Linder et al.
       mykiss                                                                              9200                           (1985)
       Pimephales         HPLC              S        6.61               24 In              1016                 NS        Oris et al. (1990)
       promelas
    Benz[a]anthracene
    Algae
       Chlorella fusca    14C               S        50                 1 d                3180                 NS        Freitag et al.
                                                                                                                          (1985)
    Crustaceans
       Daphnis magna      14C TLC           S        0.8                1 d                2920                 k1/k2     McCarthy et al.
                                                                                                                          (1985)
       Daphnis pulex      Spect             S        6                  1 d                10109                          Southworth et al.
                                                                                                                          (1978)
       Daphnia pulex      HPLC              S        1.8                1 d                10226                NS        Newsted & Giesy
                                                                                                                          (1987)
       Pontoporaia hoyi   14C, TLC          F        0.62-1.11          6 h/14 d           63000                k1/k2     Landrum (1988)
    Fish
       Leuciscus idus     14C               S        50                 3 d                350                  NS        Freitag et al.
       melanotus                                                                                                          (1985)

    Table 27. (continued)

                                                                                                                                           

    Species               Analysis          Test     Concentration      Duration of        Bioconcentration     Type      Reference
                                            system   in water           exposure           factor (in
                                                     (µg/litre)         or uptake/         wet weight)
                                                                        depuration
                                                                        period
                                                                                                                                           

    Benzo[a]fluorene
    Crustaceans
       Daphnis magna      HPLC              S        4.8                1d                 3668                 NS        Newsted & Glesy
                                                                                                                          (1987)

    Benzo[b]fluorene
    Crustaceans
       Daphnia magna      HPLC              S        W                  1 d                7725                 NS        Newsted & Giesy
                                                                                                                          (1987)
    Benzo[a]pyrene
    Algae
       Periphyton         14C               F        1                  1 d                9000                 NS        Leversee et al.
                                                                                                                          (1981)
    Crustaceans
       Daphnis magna      14C               S/F      1                  6 h                2440                 k1/k2     Leversee et al.
                                                                                                                          (1981)
       Daphnia magna      14C                                                              3050                 NS        Leversee et al,
                          14C HPLC                                                         2837                 k1/k2     (1981)
       Daphnia magna      14C TLC           S        0.63               1 d                5770                 k1/k2     McCarthy et al.
                                                                                                                          (1985)
       Daphnia magna      HPLC              S        1.5                1 d                12761                NS       Newsted & Giesy
                                                                                                                          (1987)
       Daphnia pulex      14C               S        1.20               24 h               458                  NS        Trucco et al.
                          14C               S        0.47               24 h               745                  NS        (1983)
                          14C               S        5.42               24 h               803                  NS
                          14C               S        3.21               24 h               1 106                NS
                          14C               S        2.20               24 h               1 259                NS
                          14C               S        1.50               24 h               2 720                NS

    Table 27. (continued)

                                                                                                                                           

    Species               Analysis          Test     Concentration      Duration of        Bioconcentration     Type      Reference
                                            system   in water           exposure           factor (in
                                                     (µg/litre)         or uptake/         wet weight)
                                                                        depuration
                                                                        period
                                                                                                                                           

       Pontoporeia hoyi   14C, TLC          S        0.002-2.6          6 h/14 d           73 000               k1/k2     Landrum (1988)
    Oligochaetes
       Stylodrilus        14C, TLC          F        < 0.03             6 h/8 d            7 048                k1/k2     Frank et al.
       heringianus                                                                                                        (1986)
    Molluscs
       Mysis relicta      14C               F        -                  6 h/10-26d         8 297                k1/k2     Evans &
                                                                                                                          Landrum (1989)
       Ostrea edulis      14C, GLC          S        65.7               3 d                58                   NS        Riley et al.
       Ostrea edulis      14C, GLC          S        65.7               3 d                59                   NS        (1981)
       Ostrea edulis      14C, GLC          S        65.7               3 d                62                   NS
       Physa sp.          14C, GLC          S        2.5                3 d                2 177                NS        Lu et al. (1977)
       Rangia cuneata     14C               S        30.5               24 h               236                  NS        Neff & Anderson
                          14C               S        30.5               24 h               187                  NS        (1975)
    Insects
       Chironomus         14C               S        1                  8 h/48 h           970                  k1/k2     Leversee et al.
       riparius           14C                                                              600                  NS        (1981)
                          14C, HPLC                                                        166                  NS
       Culex pipiens      14C, GLC          S        2.5                3 d                37                   NS        Lu et al. (1977)
       quinquefasciatus
       Hexagenia limbata  14C, TLC          F        -                  6 h/14 d           5 870                k1/k2     Landrum & Poore
                                                                                                                          (1988)
    Fish
       Lepomis            14C-extraction    F        1                  2 d/4 d            3 208                k1/k2     Jimenez et al.
       macrochirus                                                                                                        (1987)
       Lepomis            14C               S/F      1                  4 h/4 h            4 700                k1/k2     Leversee et al.
       macrochirus        14C                                           4 h                120                  NS        (1981)
                          14C, HPLC                                     4 h                12.5                 NS
       Lepomis            14C               S        1                  4 h/20 h           4 900                k1/k2     Spacie et al.
       macrochirus        14C, TLC                                                         490                  k1/k2     (1983)

    Table 27. (continued)

                                                                                                                                           

    Species               Analysis          Test     Concentration      Duration of        Bioconcentration     Type      Reference
                                            system   in water           exposure           factor (in
                                                     (µg/litre)         or uptake/         wet weight)
                                                                        depuration
                                                                        period
                                                                                                                                           

       Lepomis            14C, TLC          S        0.5                5 h/100 h          2 657                k1/k2     McCarthy &
       macrochirus                                                                                                        Jimenez (1985)
       Leuresthes tenuis  Spect             S        2                  15 d               241                  Equi      Winkler et al.
                                                                                                                          (1983)
       Oncorhynchus       GC-HPLC           F        0.4                10 d               920                  NS        Gerhart &
       mykiss                                                                                                             Carlson (1978)
       Salmo salar        14C               S        1                  48 h/96 h          2 310                k1/k2     Johnsen et al.
                                                                                                                          (1989)

    Benzo[e]pyrene
    Crustaceans
       Daphnis magna      HPLC              S        0.7                1 d                25 200               NS        Newsted & Giesy
                                                                                                                          (1987)

    Benzo[ghi]perylene
    Crustaceans
       Daphnia magna      HPLC              S        0.2                1 d                28 288               NS        Newsted & Giesy
                                                                                                                          (1987)

    Benzo[k]fluoranthene
    Crustaceans
       Daphnia magna      HPLC              S        1.4                1 d                13 225               NS        Newsted & Giesy
                                                                                                                          (1987)

    Chrysene
    Crustaceans
       Daphnia magna      14C               S        48                 48 h/40 h          5 500                NS        Eastmond et al.
                                                                                                                          (1984)
       Daphnia magna      HPLC              S        0.7                1 d                6 088                NS        Newsted & Giesy
                                                                                                                          (1987)

    Table 27. (continued)

                                                                                                                                           

    Species               Analysis          Test     Concentration      Duration of        Bioconcentration     Type      Reference
                                            system   in water           exposure           factor (in
                                                     (µg/litre)         or uptake/         wet weight)
                                                                        depuration
                                                                        period
                                                                                                                                           

    Dibenz[a,h]anthracene
    Algae
       Chlorella fusca    14C               S        50                 1 d                2 398                NS        Freitag et al.
                                                                                                                          (1985)
    Crustaceans
       Daphnia magnia     HPLC              S        0.4                1 d                50 119               NS        Newsted & Giesy
                                                                                                                          (1987)
    Fish
       Leuciscus idus     14C               S        50                 3 d                10                   NS        Freitag et al.
       melanotus                                                                                                          (1985)

    Fluoranthene
    Crustaceans
       Crangon            HPLC              F        2.4                4 d/14 d           180                  k1/k2     McLeese &
       septemspinosa                                                                                                      Burridge (1987)
       Daphnia magna      HPLC              S        9                  1 d                1 742                NS        Newsted & Giesy
                                                                                                                          (1987)
    Molluscs
       Mya arenaria       HPLC              F        2.4                4 d/14 d           4 120                k1/k2     McLeese &
                                                                                                                          Burridge (1987)
       Mytilus edulis     HPLC              F        2.4                4 d/14 d           5 920                k1/k2     McLeese &
                                                                                                                          Burridge (1987)
    Polychaetes
       Neiris virens      HPLC              F        2.4                4 d/14 d           720                  k1/k2     McLeese &
                                                                                                                          Burridge (1987)
    Fish
       Oncorhynchus       GC-HPLC           F        3.31               21 d               378                  Equi      Gerhart &
       mykiss                                                                                                             Carlson (1978)

    Table 27. (continued)

                                                                                                                                           

    Species               Analysis          Test     Concentration      Duration of        Bioconcentration     Type      Reference
                                            system   in water           exposure           factor (in
                                                     (µg/litre)         or uptake/         wet weight)
                                                                        depuration
                                                                        period
                                                                                                                                           

    Fluorene
    Crustaceans
       Daphnia magna      HPLC              S        17                 1 d                506                  NS        Newsted & Giesy
                                                                                                                          (1987)
    Fish
       Lepomis            -                 IF       20, 37             30 d               1 800                Equi      Finger et al.
    macrochirus           -                 IF       86                 30 d               700                  Equi      (1985)
                          -                 IF       175, 353           30 d               200                  Equi
    Naphthalene
    Algae
       Selenastrum        GC                S        2,000              1 d                18 000b              NS        Casserly et al.
       capricornutum                                                                                                      (1983)
       Chlorella fusca    14C               S        50                 1 d                130a                 NS        Geyer et al.
                                                                                                                          (1984)
    Insects
       Somatochlora       Spect             S        10                 48 h               1 548                NS        Correa & Coler
       cingulata          Spect             S        100                48 h               178                  NS        (1983)
    Crustaceans
       Daphnia magna      14C, HPLC         S        1 000              1 d                19.3                 k1/k2     McCarthy et al.
                                                                                                                          (1985)
       Daphnia magna      14C               S        1 800              48 h/40 h          50                   NS        Eastmond et al.
                                                                                                                          (1984)
       Daphnia pulex      Spect             S        1 000              1 d                131                  k1/k2     Southworth et al.
                                                                                                                          (1978)
       Daphnia pulex      14C               S        2 292              4 h                677                  NS        Trucco et al.
                          14C               S        0.45               24 h               10 844               NS        (1983)
                          14C               S        2.742              4 h                2 337                NS

    Table 27. (continued)

                                                                                                                                           

    Species               Analysis          Test     Concentration      Duration of        Bioconcentration     Type      Reference
                                            system   in water           exposure           factor (in
                                                     (µg/litre)         or uptake/         wet weight)
                                                                        depuration
                                                                        period
                                                                                                                                           

    Fish
       Fundulus           14C               S        20                 4 h                2.2                  NS        DiMichele &
       heteroclitus                                                                                                       Taylor (1978)
       Lepomis            14C, HPLC         S        1 000              24 h/36 h          310                  k1/k2     McCarthy &
       macrochirus        14C, HPLC         S        100                24 h/36 h          320                  k1/k2     Jimenez (1985)
       Oncorhynchus       14C               S        23                 8 h/24 h           253                  k1/k2     Melancon & Lech
       mykiss                                                                                                             (1978)

    Perylene
    Algae
       Chlorella fusca    14C               S        50                 1 d                2 010                NS        Freitag et al.
                                                                                                                          (1985)

    Crustaceans
       Crangon            HPLC              F        0.4                4 d/14 d           175                  k1/k2     McLeese &
       septemspinosa                                                                                                      Burridge (1987)
       Daphnia magnia     HPLC              S        0.6                1 d                7 190                NS        Newsted & Giesy
                                                                                                                          (1987)
    Molluscs
       Mya arenaria       HPLC              F        0.4                4 d/14 d           100 000              k1/k2     McLeese &
                                                                                                                          Burridge (1987)
       Mytilus edulis     HPLC              F        0.4                4 d/14 d           105 000              k/q       McLeese &
                                                                                                                          Burridge (1987)
    Polychaetes
       Neiris virens      HPLC              F        0.4                4 d/14 d           180                  k1/k2     McLeese &
                                                                                                                          Burridge (1987)
    Fish
       Leuciscus idus     14C               S        50                 3 d                < 10                 NS        Freitag et al.
       melanotus                                                                                                          (1985)

    Table 27. (continued)

                                                                                                                                           

    Species               Analysis          Test     Concentration      Duration of        Bioconcentration     Type      Reference
                                            system   in water           exposure           factor (in
                                                     (µg/litre)         or uptake/         wet weight)
                                                                        depuration
                                                                        period
                                                                                                                                           

    Phenanthrene
    Bacteria
       Mixed              Spect             S        30-300             2 h                6 300c               NS        Steen &
                                                                                                                          Karickhoff (1981)
    Algae
       Selenastrum        GC                S        1000               1 d                36 970b              NS        Casserly et al.
       capricornutum                                                                                                      (1983)
       Chlorella fusca    14C               S        50                 1 d                1 760a               NS        Geyer et al.
                                                                                                                          (1984)
    Insects
       Hexagenia limbata  14C               F        -                  6 h/14 d           1640                 k1/k2     Landrum & Poore
                                                                                                                          (1988)
    Crustaceans
       Crangon            HPLC              F        4.3                4 d/14 d           210                  k1/k2     McLeese &
       septemspinosa                                                                                                      Burridge (1987)
       Daphnia magna      HPLC              S        40.1               1 d                323                  NS        Newsted & Giesy
                                                                                                                          (1987)
       Daphnia magna      14C               S        60                 48 h/40 h          600                  NS        Eastmond et al.
                                                                                                                          (1984)
       Daphnia pulex      14C               S        6.01               24 h               1 165                NS        Trucco et al.
                          14C               S        3.10               24 h               1 032                NS        (1983)
                          14C               S        3.45               24 h               1 424                NS
       Daphnia pulex      Spect             S        30                 1 d                325                  k1/k2     Southworth et al.
                                                                                                                          (1978)
       Pontoporeia hoyi   14C-TLC           F        0.7-7.1            6 h/14 d           28 145               k1/k2     Landrum (1988)
    Oligochaetes
       Stylodrilus        14C-TLC           F        < 200              6 h/8 d            5 055                k1/k2     Frank et al.
       heringianus                                                                                                        (1986)

    Table 27. (continued)

                                                                                                                                           

    Species               Analysis          Test     Concentration      Duration of        Bioconcentration     Type      Reference
                                            system   in water           exposure           factor (in
                                                     (µg/litre)         or uptake/         wet weight)
                                                                        depuration
                                                                        period
                                                                                                                                           

    Molluscs
       Mya arenaria       HPLC              F        4.3                4 d/14 d           1 280                k1/k2     McLeese &
                                                                                                                          Burridge (1987)
       Mytilus edulis     HPLC              F        4.3                4 d/14 d           1 240                k1/k2     McLeese &
                                                                                                                          Burridge (1987)
    Polychaetes
       Neiris virens      HPLC              F        4.3                4 d/14 d           500                  k1/k2     McLeese &
                                                                                                                          Burridge (1987)
    Pyrene
    Bacteria
       Mixed              Spect             S        1-20               2 h                24 600c              NS        Steen &
                                                                                                                          Karickhoff (1981)
    Algae
       Selenastrum        GC                S        500                1 d                55 800b              NS        Casserly et al.
       capricornutum                                                                                                      (1983)
    Crustaceans
       Crangon            HPLC              F        1.7                4 d/14 d           225                  k1/k2     McLeese &
       septemspinosa                                                                                                      Burridge (1987)
       Daphnis magna      HPLC              S        5.7                24 h               2 702                NS        Newsted & Giesy
                                                                                                                          (1987)
       Daphnis pulex      Sped              S        50                 24 h               2 702                k1/k2     Southworth et al.
                                                                                                                          (1978)
       Pontoporeia hoyi   14C-TLC           F        0.002-0.011        6 h/14 d           16 600               k1/k2     Landrum (1988)
    Molluscs
       Mya arenaria       HPLC              F        1.7                4 d/14 d           6 430                k1/k2     McLeese &
                                                                                                                          Burridge (1987)
       Mytilus edulis     HPLC              F        1.7                4 d/14 d           4 430                k1/k2     McLeese &
                                                                                                                          Burridge (1987)

    Table 27. (continued)

                                                                                                                                           

    Species               Analysis          Test     Concentration      Duration of        Bioconcentration     Type      Reference
                                            system   in water           exposure           factor (in
                                                     (µg/litre)         or uptake/         wet weight)
                                                                        depuration
                                                                        period
                                                                                                                                           

       Oligochaetes
       Stylodrilus        14C-TLC           F        < 26.4             6 h/8 d            6 588                k1/k2     Frank et al.
       heringianus                                                                                                        (1986)
    Polychaetes
       Neiris virens      HPLC              F        1.7                4 d/14 d           700                  k1/k2     McLeese &
                                                                                                                          Burridge (1987)
    Fish
       Oncorhynchus       GC-HPLC           F        3.89               21 d               72.2                 Equi      Gerhart &
       mykiss                                                                                                             Carlson (1978)

    Triphenylene
    Crustaceans
       Crangon            HPLC              F        0.5                4 d/14 d           270                  k1/k2     McLeese &
       septemspinosa                                                                                                      Burridge (1987)
    Daphnia magna         HPLC              S        1.7                1 d                9 066                NS        Newsted & Giesy
                                                                                                                          (1987)
    Molluscs
       Mya arenaria       HPLC              F        0.5                4 d/14 d           5 540                k1/k2     McLeese &
                                                                                                                          Burridge (1987)
       Mytilus edulis     HPLC              F        0.5                4 d/14 d           11 390               k1/k2     McLeese &
                                                                                                                          Burridge (1987)
    Polychaetes
       Neiris virens      HPLC              F        0.5                4 d/14 d           2 560                k1/k2     McLeese &
                                                                                                                          Burridge (1987)
                                                                                                                                           

    Table 27 (continued)


    14C, measurement of radioactivity in a liquid scintillation counter: as parent compounds cannot be differentiated from metabolites with
    this method, additional extraction is usually performed.
    S, static exposure system; Equi, at equilibrium Corg/Cw; HPLC, high-performance liquid chromatography; NS, not steady-state
    Corg/Cw;
    TLC, thin-layer chromatography; k1/k2, kinetics: uptake rate/depuration rate; Spect, spectroscopy; F, flow-through system;
    R, static renewal system; GLC, gas-liquid chromatography; GC, gas chromatography; IF, intermittent flow system
    a Based on dry weight (5 × wet weight)
    b Based on total suspended solids
    c Based on dry weight


    4.1.6  Biomagnification

         Biomagnification, the increase in the concentration of a
    substance in animals in successive trophic levels of food chains, has
    been determined in a number of studies. When  Daphnia pulex were
    exposed to water or algae contaminated with naphthalene, phenanthrene,
    benz [a]anthracene, or benzo [a]pyrene, naphthalene accumulated to
    the greatest extent from algal food, (bioconcentration factor, 11
    000), whereas benz [a]anthracene and benzo [a]pyrene accumulated
    more from water (bioconcentration factors, 1100 and 2700,
    respectively). It must be emphasized that because of the short
    exposure (24 h), the last two compounds would not have reached
    equilibrium (Trucco et al., 1983).

         In a study of bioaccumulation and biomagnification in closed
    laboratory model ecosystems, green algae  (Oedogonium cardiacum), D.
    magna, mosquito larvae  (Culex pipiens quinquefasciatus), snails
     (Physa sp.), and mosquito fish  (Gambusia affinis) were exposed for
    three days to 2 µg/litre of 14C-benzo [a]pyrene. Of the radiolabel
    accumulated, 88% was attached to parent compound in snails, 22% in
    mosquito larvae, and none in fish. The parent compound represented 46%
    of the total extractable radiolabel in mosquito larvae and 90% in
     Daphnia. The bioconcentration factors were 5300 for algae, 12 000
    for mosquito larvae, 82 000 for snails, 140 000 for  Daphnia, and 930
    for fish. Despite the apparent absence of bioconcentration in fish,
    accumulation is assumed to be due to food-chain transfer, as no
    accumulation of benzo [a]pyrene was found in a study of uptake from
    water. Biomagnification was also studied in a terrestrial-aquatic
    system, by adding 14C-benzo [a]pyrene to  Sorghum vulgare seedlings
    and allowing them to be eaten by fourth-instar salt-marsh caterpillar
    larvae  (Estigmene acrea); the labelled products entered the
    terrestrial and aquatic phases as products such as faeces. The
    food-chain organisms were the same as in the model aquatic ecosystem.
    After a 33-day interaction period, the concentrations of
    benzo [a]pyrene were 0.01 µg/litre water and 36.1 µg/kg algae, with
    bioconcentration factors of 3600, 490, 2100, and 30, respectively.
    Most of the radiolabel was found on polar products or as unextractable
    radioactivity, which comprised 25% of the total in snails, 63% in
    fish, 67% in mosquito larvae, and 79% in algae (Lu et al., 1977).

         Trophic transfer of benzo [a]pyrene metabolites between benthic
    organisms was studied by feeding  Nereis virens 14C-benzo [a]pyrene
    and harvesting them five days later. The worm homogenate contained 14%
    parent compound, 7.2% organic-soluble metabolites, 58% water-soluble
    metabolites, and 21% bound material. Flounder  (Pseudiopleuronectes 
     americanus) were then given doses of 4.8-19 œg of either pure
    benzo [a]pyrene homogenized in unexposed  Nereis or the
    worm-metabolite mixture by gavage and analysed after 24 h of
    incubation. On the basis of the radiolabel recovered from the fish
    tissues, assuming comparable accumulation efficiency, flounder appear
    to have at least a limited ability to accumulate polar, conjugated,
    and bound metabolic products of benzo [a]pyrene from the diet. The

    parent compound represented 5-15% of the radiolabel in liver and 6-7%
    in intestine; conjugated metabolites represented 40-60% of the label
    in liver and 60-70% in intestine; and bound metabolic products
    represented 30% in liver and 10-20% in intestine (McElroy & Sisson,
    1989).

    4.2  Transformation

         On the basis of model calculations, Mackay et al. (1992)
    classified some PAH according to their persistence in air, water,
    soil, and sediment (Table 28).


    Table 28. Suggested half-life classes of polycyclic aromatic
    hydrocarbons in various environmental compartments

                                                 

    Class        Half-life (h)
                                                 
                 Mean              Range
                                                 

    1                17            10-30
    2                55            30-100
    3               170            100-300
    4               550            300-1000
    5             1 700            1000-3000
    6             5 500            3000-10 000
    7            17 000            10 000-30 000
    8            55 000            > 30 000
                                                 

                                                                     

    Compound                 Air       Water     Soil      Sediment
                                                                     

    Acenalphthylene          2         4         6         7
    Anthracene               2         4         6         7
    Benz[a]anthracene        3         5         7         8
    Benzo[a]pyrene           3         5         7         8
    Benzo[k]fluoranthene     3         5         7         8
    Chrysene                 3         5         7         8
    Dibenz[a,h]anthracene    3         5         7         8
    Fluoranthene             3         5         7         8
    Fluorene                 2         4         6         7
    Naphthalene              1         3         5         6
    Perylene                 3         5         7         8
    Phenanthrene             2         4         6         7
    Pyrene                   3         5         7         8
                                                                     
    From Mackay et al. (1992)

    4.2.1  Biotic transformation

    4.2.1.1  Biodegradation

         Information on the biodegradation of PAH in water and soil under
    aerobic and anaerobic conditions is summarized in Table 29. The few
    results available from standard tests for biodegradation in water show
    that PAH with up to four aromatic rings are biodegradable under
    aerobic conditions but that the biodegradation rate of PAH with more
    aromatic rings is very low. Biodegradation under anaerobic conditions
    is slow for all components (Neff, 1979). The reactions normally
    proceed by the introduction of two hydroxyl groups into the aromatic
    nucleus, to form dihydrodiol intermediates. Bacterial degradation
    produces  cis-dihydrodiols (from a dioxetane intermediate), whereas
    metabolism in fungal or mammalian systems produces  trans-dihydrodiol
    intermediates (from an arene oxide intermediate). The differences in
    the metabolic pathways are due to the presence of the cytochrome P450
    enzyme system in fungi and mammals. Algae have been reported to
    degrade benzo [a]pyrene to oxides, peroxides, and dihydroxydiols (see
    below). Owing to the high biotransformation rate (see also section
    4.2.1.2), the concentrations of PAH in organisms and water are usually
    not in a steady state. Freely dissolved PAH may be rapidly degraded
    under natural conditions if sufficient biomass is available and the
    turnover rates are fairly high (see Table 29).

         Biodegradation is the major mechanism for removal of PAH from
    soil. PAH with fewer than four aromatic rings may also be removed by
    volatilization and photolysis (see also sections 4.1.4 and 4.2.2.1).
    The rate of biodegradation in soil depends on several factors,
    including the characteristics of the soil and its microbial population
    and the properties of the PAH present. Temperature, pH, oxygen
    content, soil type, nutrients, and the presence of other substances
    that can act as co-metabolites are also important (Sims & Overcash,
    1983). Biodegradation is further affected by the bioavailability of
    the PAH. Sorption of PAH by soil organic matter may limit the
    biodegradation of compounds that would normally undergo rapid
    degradation (Manilal & Alexander, 1991); however, no significant
    difference was found in the biodegradation rate of anthracene in water
    with 10 and 1000 mg/litre suspended material (Leslie et al., 1987). In
    Kidman sandy loam, the biodegradation rates varied between 0.23 h-1
    (or 5.5 d-1) for naphthalene and 0.0018 d-1 for fluoranthene (see
    Table 29). In a study with sandy loams, forest soil, and roadside soil
    partially loaded with sewage sludge from a municipal treatment plant,
    the following half-lives (in days) were found: 14-48 for naphthalene,
    44-74 for acenaphthene plus fluorene, 83-193 for phenanthrene, 48-210
    for anthracene, 110-184 for fluoranthene, 127-320 for pyrene, 106-313
    for benz [a]anthracene plus chrysene, 113-282 for
    benzo [b]fluoranthene, 143-359 for benzo [k]fluoranthene, 120-258
    for benzo [a]pyrene, 365-535 for benzo [ghi]perylene, and 603-2030
    for coronene (Wild & Jones, 1993).


        Table 29. Biodegradation of polycyclic aromatic hydrocarbons (PAH)

                                                                                                                                             

    Compound                Rate constant     Half-life            Comments                                              Reference
                                                                                                                                             

    Acenaphthene                              100% degradation     Significant degradation with rapid adaptation;        Tabak et al.
                                              after 7 d            static flask screening; settled domestic waste        (1981)
                                                                   as inoculum; experiments with 5 and 10 mg/litre
                                                                   PAH at 25°C; detection by GC

                                              295-2448 h           Aerobic half-life; aerobic soil column                Kincannon & Lin
                                                                                                                         (1985)

                                              1180-9792 h          Anaerobic half-life; estimated unacclimatized         Howard et al.
                                                                   aqueous aerobic biodegradation half-life              (1991)

                                              0% degradation       Japanese Ministry of Trade and Industry test          Japanese Ministry of
                                              after 7 d            with 100 mg/litre PAH and 30 mg/litre sludge          International Trade
                                                                                                                         and Industry (1992)

                                              < 3.2 year           Field tests of rural British soils amended with       Wild et al. (1991)
                                                                   metal-enriched sewage sludges with
                                                                   0.1-15.1 mg/kg PAH

    Acenaphthylene                            98% degradation      Significant degradation with rapid adaptation;        Tabak et al.
                                              after 7 d            statis flask screening; settled domestic waste        (1981)
                                                                   as inoculum; 5 or 10 mg/litre PAH at 25°C;
                                                                   detection by GC
                                              1020-1440 h          Aerobic half-life; soil column                        Kincannon & Lin
                                                                                                                         (1985)
                                              4080-5760 h          Anaerobic half-life; estimated unacclimatized         Howard et al.
                                                                   aqueous aerobic biodegradation                        (1991)

                                              0% degradation       Japanese Ministry of Trade and Industry test          Japanese Ministry of
                                              after 4 weeks        with 100 mg/litre PAH and 30 mg/litre sludge          International Trade
                                                                                                                         and Industry (1992)

    Table 29. (continued)

                                                                                                                                             

    Compound                Rate constant     Half-life            Comments                                              Reference
                                                                                                                                             

    Anthracene              0.061 h-1         10 h                 Microbial degradation in Third Creek water            Southworth
                                                                   incubated 18 h at 25°C:                               (1977)
                                                                   Removal rate constants from water column at
                                                                   25°C in midsummer sunlight:
                            0.060 h-1         12 h                 - in deep, slow, somewhat turbid water
                            0.030 h-1         23 h                 - in deep, slow, muddy water
                            0.061 h-1         11 h                 - in deep, slow, clear water
                            0.061 h-1         11 h                 - in shallow, fast, clear water
                            0.061 h-1         11 h                 - in very shallow, fast, clear water

                            0.035 h-1         20 h                 Microbial degradation rate constant                   Herbes et al.
                                                                                                                         (1980)

                                              51-92% degradation   Significant degradation with gradual                  Tabak et al.
                                              after 7 d            adaptation; static flask screening; settled           (1981)
                                                                   domestic waste as inoculum; experiments
                                                                   with 5 and 10 mg/litre PAH at 25°C; detection
                                                                   by GC

                                              1200-11 040 h        Aerobic half-life; aerobic soil die-away              Coover & Sims
                                                                                                                         (1987)
                                                                   20O g dry weight of soil at -0.33 bar                 Park et al.
                                                                   [33 kPa] soil moisture at 25°C:                       (1990)
                            0.0052 d-1        3200 h               - Kidman sandy foam; initial test
                                                                     concentration, 210 mg/kg
                            0.0138 d-1        1200 h               - McLaurin sandy loam; initial test
                                                                     concentration, 199 mg/kg

                                              4800-44 160 h        Anaerobic half-life; estimated unacclimatized         Howard et al.
                                                                   aqueous aerobic biodegradation half-life              (1991)

    Table 29. (continued)

                                                                                                                                             

    Compound                Rate constant     Half-life            Comments                                              Reference
                                                                                                                                             

                                              1.9% degradation     Japanese Ministry of Trade and Industry test          Japanese Ministry of
                                              after 2 weeks        with 100 mg/litre PAH and 30 mg/litre sludge          International Trade
                                                                                                                         and Industry (1992)

    Anthracene                                33% after 16 months  Degradation in soil in co-metabolic closed            Bossert &
                                                                   bottle with 1-phenyldecane as primary                 Bartha (1986)
                                                                   substrate; 20°C; initial test concentration,
                                                                   1 mg/g; abiotic loss, 60%

                                              5% after 56 d        Batch test with river water; initial concentration,   Fedorak et al.
                                                                   20 mg/litre related to dissolved organic carbon;      (1982)
                                                                   no mineralization during first 19 days; 20°C

                                                                   Serum bottle radiorespirometry in five soils          Grosser et al.
                                                                   contaminated with hydrocarbons:                       (1995)
                                              10-60% after 64 d    - initial concentration, 31.3 ng/g
                                                                   - Inoculated with enriched culture of
                                                                     Mycobacteriarn sp. and initial test concentration
                                                                     of 37.7 ng/g; biodegradation rate without
                                                                     enriched culture, 18% after 64 d

                                                                   Static test in bioreactor in enriched mixed           Walter et al.
                                                                   culture; anthracene oil (38 g/litre) which also       (1990)
                                                                   contained 62 mg/g fluorene; 30°C:
                                              100% after 3 d       - under aerobic conditions
                                              90% after 20 d       - under anaerobic conditions

                                              17-45 d              Aerobic degradation in surface Donneybrook            Bulman et al.
                                                                   sandy loam from Canadian pasture; initial test        (1987)
                                                                   concentrations, 5 and 50 mg/kg; up to 400 days'
                                                                   exposure at 20 00 and water-holding capacity of
                                                                   60% of the soil

    Table 29. (continued)

                                                                                                                                             

    Compound                Rate constant     Half-life            Comments                                              Reference
                                                                                                                                             

                                              7.9 years            Field tests of rural British soils amended with       Wild et al. (1991)
                                                                   metal-enriched sewage sludges with
                                                                   0.1-15.1 mg/kg PAH

    Benz[a]anthracene                         2448-16 320 h        Aerobic soil die-away at 10-30°C                      Groenewegen &
                                                                                                                         Stolp (1976); Coover
                                                                                                                         & Sims (1987)

                                              0% degradation       No significant degradation under conditions of        Tabak et al. (1981)
                                              after 7 d            method; static flask sceening; settled domestic
                                                                   waste as inoculum; experiment with 5 and
                                                                   10 mg/littre PAH at 25°C; detection by GC

                            0.0026 d-1        6400 h               Kidman sandy loam                                     Park et al. (1990)

                                              9792-65 280 h        Anaerobic half-life; estimated unacclimatized         Howard et al. (1991)
                                                                   aqueous aerobic biodegradation

                                              16% after            Degradation in soil in co-metabolic closed            Bossert & Bartha
                                              16 months            bottle with 1-phenyldecane as primary                 (1986)
                                                                   substrate; 20°C; initial test concentration,
                                                                   1 mg/g; abiotic loss, 18%

                                              0-40% after 64 d     Serum bottle radiorespirometry in five soils          Grosser et al.
                                                                   contaminated with hydrocarbons; initial               (1995)
                                                                   concentration, 31.3 ng/g

                                              130-240 d            Aerobic degradation in surface samples of             Bulman et al.
                                                                   Donneybrook sandy loam from Canadian                  (1987)
                                                                   pasture; initial test concentrations, 5 and
                                                                   50 mg/kg; up to 400 days' exposure at 20°C
                                                                   and water-holding capacity of 60% of the soil

    Table 29. (continued)

                                                                                                                                             

    Compound                Rate constant     Half-life            Comments                                              Reference
                                                                                                                                             

                                              8.1 years            Field tests of rural British soils amended with       Wild et al. (1991)
                                                                   metal-enriched sewage sludges with
                                                                   0.1-15.1 mg/kg PAH

    Benzo[a]pyrene          0.2-0.9                                Aquatic fate rate for bacterial protein               Barnsley (1975)
                            µmol.h-1mg-1

                            3.5 × 10-5 h-1    19 800 h             Estimated rate constant in soil and water             Ryan & Cohen
                                                                                                                         (1986)

                                              1368-12 702 h        Aerobic half-life at 10-30°C; soil die-away           Coover & Sims
                                                                                                                         (1987)

                                                                   200 g dry weight of soil at -0.33 bar                 Park et al. (1990)
                                                                   [33 kPa] soil moisture; 33 mg/kg at 25°C:
                            0.0022 d-1        7416 h               - Kidman sandy loam
                            0.0030 d-1        5496 h               - McLaurin sandy loam

                                              5472-50 808 h        Anaerobic half-life; estimated unacclimatized         Coover & Sims
                                                                   aqueous aerobic biodegradation                        (1987)

                                              < 8% after 160 d     Serum bottle radiorespirometry in five soils          Grosser et al.
                                                                   contaminated with hydrocarbons; initial               (1995)
                                                                   concentration, 105 ng/g

                                              218-347 d            Aerobic degradation in surface samples of             Bulman et al.
                                                                   Donneybrook sandy loam from Canadian                  (1987)
                                                                   pasture; initial test concentrations, 5 and
                                                                   50 mg/kg; up to 400 days' exposure at 20°C
                                                                   and water-holding capacity of 60% of the soil

                                              8.2 years            Field tests of rural British soils amended with       Wild et al. (1991)
                                                                   metal-enriched sewage sludges with
                                                                   0.1-15.1 mg/kg PAH

    Table 29. (continued)

                                                                                                                                             

    Compound                Rate constant     Half-life            Comments                                              Reference
                                                                                                                                             

    Benzo[b]fluoranihene                      8640-14 640 h        Aerobic half-life; estimated unacclimatized           Coover & Sims
                                                                   aqueous aerobic biodegradation                        (1987)

                                                                   200 g dry weight of soil at -0.33 bar                 Park et al. (1990)
                                                                   [33 kPa] soil moisture; initial test
                                                                   concentration, ± 38 mg/kg at 25°C:

                            0.0024 d-1        7056 h               - Kidman sandy loam
                            0.0033 d-1        5064 h               - McLaurin sandy loam

                                              34 560-58 560 h      Anaerobic half-life; estimated unacclimatized         Howard et al.
                                                                   aqueous aerobic biodegradation                        (1991)

                                              9 years              Field tests of rural British soils amended with       Wild et al. (1991)
                                                                   metal-enriched sewage sludges with
                                                                   0.1-15.1 mg/kg PAH

    Benzo[ghi]perylene                        14 160-15 600 h      Aerobic half-life; aerobic soil dieaway at            Coover & Sims
                                                                   10-30°C                                               (1987)

                                              56 640-62 400 h      Anaerobic half-life; aerobic soil dieaway at          Coover & Sims
                                                                   10-30°C                                               (1987)

                                              9.1 years            Field tests of rural British soils amended with       Wild et al. (1991)
                                                                   metal-enriched sewage sludges with
                                                                   0.1-15.1 mg/kg PAH

    Benzo[k]fluoranthene                      21 840-51 360 h      Aerobic half-life; aerobic soil dieaway               Coover & Sims
                                                                                                                         (1987)

                                              87 360-205 440 h     Anaerobic half-life; estimated unacclimatized         Howard et al.
                                                                   aqueous aerobic biodegradation                        (1991)

    Table 29. (continued)

                                                                                                                                             

    Compound                Rate constant     Half-life            Comments                                              Reference
                                                                                                                                             

                                              8.7 years            Field tests of rural British soils amended with       Wild et al. (1991)
                                                                   metal-enriched sewage sludges with
                                                                   0.1-15.1 mg/kg PAH

    Chrysene                                  59% degradation      Significant degradation with gradual                  Tabak et al. (1981)
                                              after 7 d            adaptation; static flask screening; settled
                                                                   domestic waste as inoculum; experiment
                                                                   with 5 mg/litre PAH at 25°C; detection by GC

                                              38% degradation      No significant degradation under conditions of        Tabak et al. (1981)
                                              after 7 d            method; static flask sceening; settled domestic
                                                                   waste as inoculum; experiment with 10 mg/litre
                                                                   PAH at 25°C; detection by GC

                                              8904-24 000 h        Aerobic half-life; aerobic soil dieaway               Coover & Sims
                                                                                                                         (1987)

                                                                   200 g dry weight of soil at -0.33 bar                 Park et al. (1990)
                                                                   [33 kPa] soil moisture; initial test
                                                                   concentration, ± 100 mg/kg at 25°C:
                            0.0019 d-1        8904 h               - Kidman sandy loam
                            0.0018 d-1        9288 h               - McLaurin sandy loam

                                              35 616-96 000 h      Anaerobic half-life; estimated unacclimatized         Howard et al.
                                                                   aqueous aerobic biodegradation                        (1991)

                                              11 % after 16        Degradation in soil in co-metabolic closed            Bossert & Bartha
                                              months               bottle with 1-phenyldecane as primary                 (1986)
                                                                   substrate; 20°C; initial test concentration,
                                                                   1 mg/g; abiotic loss, 5%

    Table 29. (continued)

                                                                                                                                             

    Compound                Rate constant     Half-life            Comments                                              Reference
                                                                                                                                             

                                              224-328 d            Aerobic degradation in surface samples of             Bulman et al.
                                                                   Donneybrook sandy loam from Canadian                  (1987)
                                                                   pasture; initial test concentrations, 5 and
                                                                   50 mg/kg; up to 400 days' exposure at 20°C
                                                                   and water-holding capacity of 60% of the soil

                                              8.1 years            Field tests of rural British soils amended with       Wild et al. (1991)
                                                                   metal-enriched sewage sludges with
                                                                   0.1-15.1 mg/kg PAH

    Coronene                                  16.5 years           Field tests of rural British soils amended with       Wild et al. (1991)
                                                                   metal-enriched sewage sludges with
                                                                   0.1-15.1 mg/kg PAH

    Dibenz[a,h]anthracene                     8664-22 560 In       Aerobic half-life; aerobic soil die-away              Coover & Sims
                                                                                                                         (1987); Park et al.
                                                                                                                         (1990)

                                                                   200 g dry weight of soil at -0.33 bar                 Park et al. (1990)
                                                                   [33 kPa] soil moisture; initial test
                                                                   concentration, ± 13 mg/kg at 25°C:
                            0.0019 d-1        8664 h               - Kidman sandy loam
                            0.0017 d-1        10 080 h             - McLaurin sandy loam

                                              No degradation       Degradation in soil in co-metabolic closed            Bossert & Bartha
                                              after 16 months      bottle with 1-phenyldecane as primary                 (1986)
                                                                   substrate; 20°C; initial test concentration,
                                                                   1 mg/g

    Table 29. (continued)

                                                                                                                                             

    Compound                Rate constant     Half-life            Comments                                              Reference
                                                                                                                                             

    Fluoranthene            2.2 × 10-3                             Aquatic fate rate with bacterial protein              Barnsley (1975)
                            µmol h-1mg-1
                                              100% degradation     Significant degradation with gradual adaptation;      Tabak et al. (1981)
                                              after 7 d            static flask screening; settled domestic waste
                                                                   as inoculum; experiment with 5 mg/litre PAH
                                                                   at 25°C; detection by GC

                                              0% degradation       No significant degradation under conditions of        Tabak et al. (1981)
                                              after 7 d            method; static flask screening; settled domestic
                                                                   waste as inoculum; experiment with 10 mg/litre
                                                                   PAH at 25°C; detection by GC

                                              3360-10 560 h        Aerobic half-life; aerobic soil dieaway               Coover & Sims
                                                                                                                         (1987)

                            0.19 h-1          3.6 h                In atmosphere                                         Dragoescu &
                                                                   Friedlander (1989)

                                                                   200 g dry weight of soil at -0.33 bar                 Park et al. (1990)
                                                                   [33 kPa] soil moisture; initial test
                                                                   concentration, 900 mg/kg at 25°C:
                            0.0018 d-1        9048 h               - Kidman sandy loam
                            0.0026 d-1        6432 h               - McLaurin sandy loam

                                              13 440-42 240 h      Anaerobic half-life; estimated unacclimatized         Howard et al.
                                                                   aqueous aerobic biodegradation                        (1991)

                                              34-39 d              Aerobic degradation in surface samples of             Bulman et al.
                                                                   Donneybrook sandy loam from Canadian                  (1987)
                                                                   pasture; initial test concentrations, 5 and
                                                                   50 mg/kg; up to 400 days' exposure at 20°C
                                                                   and water-holding capacity of 60% of the soil

    Table 29. (continued)

                                                                                                                                             

    Compound                Rate constant     Half-life            Comments                                              Reference
                                                                                                                                             

                                              7.8 years            Field tests of rural British soils amended with       Wild et al. (1991)
                                                                   metal-enriched sewage sludges with
                                                                   0.1-15.1 mg/kg PAH

    Fluorene                                  45-77% degradation   Significant degnadation with gradual adaptation;      Tabak et al. (1981)
                                              after 7 d            static flask screening; settled domestic waste
                                                                   as inoculum; experiment with 5 and 10 mg/litre
                                                                   PAH at 25°C; detection by GC

                                                                   Degradation of 30 µg/litre in natural river water     Lee & Ryan (1976)
                                                                   (Skidway River; salinity, 20%):
                                              100% after 1000 d    - Turnover time in June at incubation time of
                                                                     48 h
                                              0% after 72 h        - February or May

                                              30% after 1 week     Degradation of non-autoclaved groundwater             Lee et al. (1984)
                                                                   samples of ± 0.06 mg/litre by microbes

                                              768-1440 h           Aerobic half-life; aerobic soil diaway                Coover & Sims
                                                                                                                         (1987)

                                              3072-5760 h          Anaerobic half-life; estimated unacclimatized         Howard et al.
                                                                   aqueous aerobic biodegradation                        (1991)

                                              0% degradation       Japanese Ministry of Trade and Industry test          Japanese Ministry of
                                              after 4 weeks        with 100 mg/litre PAH and 30 mg/litre sludge          International Trade
                                                                                                                         and Industry (1992)

                                              100% after 36 h      Batch test with enriched culture of Arthrobacter      Grifoll et al.
                                                                   sp.; initial test concentration, 483 µmol/litre;      (1992)
                                                                   22°C

    Table 29. (continued)

                                                                                                                                             

    Compound                Rate constant     Half-life            Comments                                              Reference
                                                                                                                                             

                                              < 3.2 years          Field tests of rural British soils amended with       Wild et al. (1991)
                                                                   metal-enriched sewage sludges with
                                                                   0.1-15.1 mg/kg PAH

    Indeno[1,2,3-cd]pyrene                                         200 g dry weight of soil at -0.33 bar                 Park et al. (1990)
                                                                   [33 kPa] soil moisture; initial test
                                                                   concentration, ± 8 mg/kg at 25°C:
                            0.0024 d-1        6912 h               - Kidman sandy loam
                            0.0024 d-1        6936 h               - McLaurin sandy loam

    Naphthalene                                                    Degradation in natural river water (Skidway           Lee & Ryan
                                                                   River; salinity, 20%):                                (1976)
                                              500 d                - Turnover time in February at incubation
                                                                   time of 48 h; test concentration, 40 µg/litre
                                              46 d                 - Turnover time in May at incubation
                                                                   time of 24 h; test concentration, 40 µg/litre
                                              79 d                 - Turnover time in May at incubation time
                                                                   of 8 h; test concentration, 40 µg/litre
                                              30 d                 - Turnover time in May at incubation
                                                                   time of 24 h; test concentration, 130 µg/litre

                                                                   Degradation of 130 µg/litre in natural water          Lee & Ryan
                                              330 d                offshore with salinity of 35%: turnover time          (1976)
                                                                   in May at incubation time of 24 h

                            0.0403.3 × 10-6                        At depth of 5-10 m in laboratory water basin          Lee & Anderson
                            g/litre per d                                                                                (1977)

                                              100% after 8 d       In gas-oll-contaminated groundwater                   Kappeler &
                                                                   circulated through sand inoculated with               Wuhrmann
                                                                   groundwater under aerobic conditions                  (1978)

    Table 29. (continued)

                                                                                                                                             

    Compound                Rate constant     Half-life            Comments                                              Reference
                                                                                                                                             

                                              168 h                In oil-polluted estuarine stream                      Lee (1977)
                                              576 h                In clean estuarine stream
                                              1500 h               In coastal waters
                                              40 800 h             In the Gulf Stream

                                              12h                  Aerobic half-life; die-away in oil-polluted           Walker & Colwell
                                                                   creek                                                 (1976)

                                                                   Anaerobic half-life:                                  Hambrick et al.
                                              600 h                at pH 8                                               (1980)
                                              6200 h               at pH 5

                                              24-216 h             In deep, slowly moving, contaminated water            Herbes (1981);
                                                                                                                         Wakeham et al.
                                                                                                                         (1983)

                            0.23 h-1          3.O h                Microbial degradation rate constant                   Herbes et al. (1980)

                                              100% degradation     Significant degradation with rapid adaptation;        Tabak et al. (1981)
                                              after 7 d            static flask screening; settled domestic waste
                                                                   as inoculum; experiments with 6 and 10 mg/litre
                                                                   PAH at 25°C; detection by GC

                                              100% degradation     Degradation of non-autoclaved groundwater             Lee et al. (1984)
                                              after 7 d            samples of ± 0.04 mg/litre by microbes

                            0.024 d-1         693 h                Groundwater with nutrients and acclimatized           Vaishnav & Babeu
                                                                   microbes                                              (1987)
                            0.013 d-1         1279 h               River water with acclimatized microbes
                            0.018-1           924 h                River water with nutrients and acclimatized
                                                                   microbes

    Table 29. (continued)

                                                                                                                                             

    Compound                Rate constant     Half-life            Comments                                              Reference
                                                                                                                                             

                                                                   200 g dry weight of soil at -0.33 bar                 Park et al. (1990)
                                                                   [-0.0032 kPa] soil moisture; initial test
                                                                   concentration, 101 mg/kg at 25°C:
                            0.377 d-1         50 h                 - Kidman sandy loam
                            0.308 d-1         53 h                 - McLaurin sandy loam

                                              2% degradation       Japanese Ministry of Trade and Industry test          Japanese Ministry of
                                              after 4 weeks        with 30 mg/litre PAH and 100 mg/litre sAdge           International Trade
                                                                                                                         and Industry (1992)

                                              < 2.1 years          Field tests of rural British soils amended with       Wild et al. (1991)
                                                                   metal-enriched sewage sludges with
                                                                   0.1-15.1 mg/kg PAH

    Perylene                                  No degradation       Degradation in soil in co-metabolic closed            Bossert & Bartha
                                              after 16 months      bottle with 1-phenyldecane as primary                 (1986)
                                                                   substrate; 20°C; initial test concentration,
                                                                   1 mg/g

    Phenanthrene                              100% degradation     Significant degradation with rapid adaptation;        Tabak et al.
                                              after 7 d            static flask screening; settled domestic waste        (1981)
                                                                   as inoculum; experiments with 5 and 10 mg/litre
                                                                   PAH at 25°C; detection by GC

                                              383-4800 h           Aerobic half-life; aerobic soil die-away              Coover & Sims
                                                                                                                         (1987)

                                                                   200 g dry weight of soil at -0.33 bar                 Park et al. (1990)
                                                                   [-0.0032 kPa] soil moisture; initial test
                                                                   concentration, 900 mg/kg at 25°C:
                            0.0447 d-1        384 h                - Kidman sandy loam
                            0.0196 d-1        840 h                - McLaurin sandy loam

    Table 29. (continued)

                                                                                                                                             

    Compound                Rate constant     Half-life            Comments                                              Reference
                                                                                                                                             

                                              1536-19 200 h        Anaerobic half-life; estimated unacclimatized         Howard et al.
                                                                   aqueous aerobic biodegradation                        (1991)

                                              96 h                 Inorganic solution                                    Manilal & Alexander
                                              264 h                Kendaia soil                                          (1991)

                                              54% degradation      Japanese Ministry of Trade and Industry test          Japanese Ministry of
                                              after 4 weeks        with 100 mg/litre PAH and 30 mg/litre sludge          International Trade
                                                                                                                         and Industry (1992)

                                              > 62 % after         Degradation in soil in co-metabolic closed            Bossert & Bartha
                                              16 months            bottle with 1-phenyldecane as primary                 (1986)
                                                                   substrate; 20°C; initial test concentration,
                                                                   1 mg/g; abiotic loss significant

                                                                   Serum bottle radiorespirometry in five soils          Grosser et al. (1995)
                                                                   contaminated with hydrocarbons:
                                              38-55% after 64 d    - initial concentration, 31.3 ng/g
                                              80% after 32 d       - inoculated with enriched culture of
                                                                     Mycobacterium sp. and an initial test
                                                                   concentration of 17.9 ng/g

                                              9.7-14 d             Aerobic degradation in surface samples of             Bulman et al. (1987)
                                                                   Donneybrook sandy loam from Canadian
                                                                   pasture; initial test concentrations, 5 and
                                                                   50 mg/kg; up to 400 days' exposure at 20°C
                                                                   and water-holding capacity of 60% of the soil

                                              5.7 years            Field tests of rural British soils amended with       Wild et al.
                                                                   metal-enriched sewage sludges with                    (1991)
                                                                   0.1-15.1 mg/kg PAH

    Table 29. (continued)

                                                                                                                                             

    Compound                Rate constant     Half-life            Comments                                              Reference
                                                                                                                                             

    Pyrene                                    100% degradation     Significant degradation with rapid adaptation;        Tabak et al.
                                              after 7 d            static flask screening; settled domestic waste        (1981)
                                                                   as inoculum; experiment with 5 mg/litre
                                                                   PAH at 25°C; detection by GC

                                              0% degradation       No significant degradation under conditions of        Tabak et al.
                                              after 7 d            method; static flask screening; settled domestic      (1981)
                                                                   waste as inoculum; experiments with 5 and
                                                                   10 mg/litre PAH at 25°C; detection by GC

                                              5040-46 600 h        Aerobic half-life at 10-30°C; aerobic soil            Coover & Sims
                                                                   die-away                                              (1987)

                            0.29 h-1          2.4 h                In atmosphere                                         Dragoescu &
                                                                                                                         Friedlander
                                                                                                                         (1989)

                                                                   200 g dry weight of soil at -0.33 bar                 Park et al. (1990)
                                                                   [33 kPa] soil moisture; initial test
                                                                   concentration, ± 690 mg/kg at 25°C:
                            0.0027 d-1        6240 h               - Kidman sandy loam
                            0.0035 d-1        4776 h               - McLaurin sandy loam

                                              20 160-182 400 h     Anaerobic half-life; estimated unacclimatized         Howard et al.
                                                                   aqueous aerobic biodegradation                        (1991)

                                              70% after 16 months  Degradation in soil in co-metabolic closed            Bossert & Bartha
                                                                   bottle with 1-phenyldecane as primary                 (1986)
                                                                   substrate; 20°C; initial test concentration,
                                                                   1 mg/g; abiotic loss, 27%

    Table 29. (continued)

                                                                                                                                             

    Compound                Rate constant     Half-life            Comments                                              Reference
                                                                                                                                             

                                                                   Serum bottle radiorespirometry in five soils          Grosser et al.
                                                                   contaminated with hydrocarbons:                       (1995)
                                              25-70% after 64 d    - initial concentration, 8.5 ng/g
                                              54% after 32 d       - inoculated with enriched culture of
                                                                     Mycobacterium sp. and an initial test
                                                                     concentration of 7.7 ng/g

                                              52.4% after 96 h     Mineralization test with Mycobacterium sp.;           Heitkamp et al.
                                                                   24°C; initial test concentration, 0.5 mg/litre        (1988)

                                              48-58 d              Aerobic degradation in surface Donneybrook            Bulman et al. (1987)
                                                                   sandy loam from Canadian pasture; initial test
                                                                   concentrations, 5 and 50 mg/kg; up to 400 days'
                                                                   exposure at 20°C and water-holding capacity of
                                                                   60% of the soil

                                              8.5 years            Field tests of rural British soils amended with       Wild et al. (1991)
                                                                   metal-enriched sewage sludges with
                                                                   0.1-15.1 mg/kg PAH
                                                                                                                                             

    GC, gas chromatography In order to compare numbers when only rate constants are reported, the half-lives were estimated from the formula:

     t1/2 = In2
             k

    where  t1/2 is the half-life and  k is the rate constant. The calculated values are reported in italics.


         After biodegradation of pyrene by a  Mycobacterium sp.,  cis-
    and  trans-4,5-pyrene dihydrodiol and pyrenol were the initial ring
    oxidation products. The main metabolite was 4-phenathroic acid. The
    ring fission products were 4-hydroxyperinaphthenone and cinnamic and
    phthalic acids (Heitkamp et al., 1988).

         The pyrene-metabolizing  Mycobacterium sp. can also use
    phenanthrene and fluoranthene as the sole source of carbon.
    Phenanthrene was degraded and 1-hydroxy-2-naphthoic acid,
     ortho-phthalate, and protocatechuate were detected as metabolites.
    1-Hydroxy-2-naphthoic acid did not accumulate, indicating that it is
    further metabolized (Boldrin et al., 1993).

         A strain of  Arthobacter sp. was isolated that was capable of
    metabolizing fluorene as a sole energy source: 483 nmol/ml were
    degraded completely within 36 h, and four major metabolites were
    detected: 9-fluorenol, 9 H-fluoren-9-one, 3,4-dihydrocoumarin, and an
    unidentified polar-substituted aromatic compound. Fluorenol was not
    degraded further, suggesting that it and fluorenone are products of a
    separate metabolic pathway from that which produces dihydrocoumarin,
    the polar compound, and the energy for cell growth. The bacteria could
    also degrade phenanthrene (Grifoll et al., 1992).

         The degradation of PAH was studied in a culture made from
    activated sludge, polychlorinated biphenyl-degrading bacteria, and
    chlorophenol-degrading mixed cultures, adapted to naphthalene. The
    metabolites of naphthalene were 2-hydroxybenzoic acid and
    1-naphthalenol, those of phenanthrene were 1-phrenanthrenol and
    1-hydroxy-2-naphthalenecarboxylic acid, and that of anthracene was
    3-hydroxy-2-naphthalenecarboxylic acid. The authors concluded that the
    biotransformation pathway proceeds via initial hydroxylation to ring
    cleavage, to yield the  ortho or  meta cleavage intermediates, which
    are further metabolized via conventional metabolic pathways (Liu et
    al., 1992).

         The metabolism of PAH by fungi is similar to that by mammalian
    cells. For example,  Cunninghamella elegans in culture metabolizes
    benzo [a]pyrene to the  trans-7,8-diol, the  trans-9,10-diol,
    3,6-quinone, 9-hydroxybenzo [a]pyrene, 3-hydroxybenzo [a]pyrene, and
    7,8-dihydro-7,8-dihydroxybenzo [a]pyrene (Cerniglia, 1984). In a
    further experiment,  C. elegans metabolized about 69% of added
    fluorene after 24 h. The major ethyl acetate-soluble metabolites were
    9-fluorenone (62%), 9-fluorenol, and 2-hydroxy-9-fluorenone (together,
    7%). The degradation pathway was similar to that in bacteria, with
    oxidation at the C9 position of the five-member ring to form an
    alcohol and the corresponding ketone. 2-Hydroxy-9-fluorenone had not
    been found as a metabolite previously (Pothuluri et al., 1993).

    4.2.1.2  Biotransformation

         Biotransformation is often advanced as an explanation for the
    differences in PAH profiles seen in aquatic organisms and in the
    medium to which they were exposed. Furthermore, all of the metabolites
    of PAH may not have been identified or quantified. This section
    addresses biotransformation in organisms other than bacteria and
    fungi, which is discussed in section 4.2.1.1, above.

         The uptake of naphthalene and benzo [a]pyrene was studied in
    three species of marine fish: the mudsucker or sand goby
     (Gillichthys mirabilis), the sculpin  (Oligocottus maculosus), and
    the sand dab  (Citharichthys stigmaeus). In all three species,
    biotransformation took place rapidly in the liver. The uptake of
    naphthalene was greater than that of benzo [a]pyrene. The major
    metabolite of benzo [a]pyrene appeared to be
    7,8-dihydroxy-7,8-dihydroxy benzo [a]pyrene, while the major
    metabolite of naphthalene was 1,2-dihydro-1,2-dihydroxy-naphthalene.
    The gall-bladder was the major storage site for the PAH and their
    metabolites. Naphthalene and its metabolites were removed at a higher
    rate than benzo [a]pyrene and its metabolites (Lee et al., 1972).

         Transformation of naphthalene and benzo [a]pyrene in the
    bluegill sunfish  Lepomis macrochirus took place very rapidly,
    benzo [a]pyrene having the highest rate (McCarthy & Jimenez, 1985).
     L. macrochirus were exposed in a flow-through system to 4 nmol/litre
    benzo [a]pyrene for 48 h, followed by a 96-h depuration period, at 13
    or 23°C in the presence or absence of food. Both polar and nonpolar
    metabolites were found. After 48 h, the polar metabolites comprised
    10% of the benzo [a]pyrene metabolites in fed fish at 13°C, 20% in
    unfed fish at 23°C, and 30% in fed fish at 23°C (Jimenez et al.,
    1987). In rainbow trout  (Oncorhynchus mykiss) exposed to naphthalene
    at 0.5 mg/litre for 24 h, the bile contained 65-70% metabolites, the
    liver contained 5-10%, and muscle < 1% (Melancon & Lech, 1978).

         In  L. macrochirus exposed to 8.9 ± 2.1 µg/litre acenaphthene
    for 28 days, the half-life for metabolism was less than one day. No
    information was given on metabolites (Barrows et al., 1980).

         The depuration of anthracene was investigated in  O. mykiss 
    during simulated day and night cycles of 16 and 8 h, respectively.
    After a 96-h clearance period, the metabolites contributed 2-3% of the
    depurated substance, half of which came from the bile. No specific
    metabolites were reported (Linder & Bergman, 1984). After  L. 
     macrochirus had been exposed to anthracene at 8.9 µg/litre or
    benzo [a]pyrene at 0.98 µg/litre for 4 h, the rates of
    biotransformation were 0.26 and 0.082 nmol/g per h, respectively, and
    8% of the anthracene and 88% of the benzo [a]pyrene were metabolized
    (Spacie et al., 1983).

         Benzo [a]pyrene is transformed in the Japanese medaka
     (Oryzias latipes) and the guppy  (Poecilia reticulata), the main
    metabolite being the 7,8-diol-9,10-epoxide (Hawkins et al., 1988).

         Two benthic organisms, the European fingernail clam  (Sphaerium 
     corneum) and larvae of the midge  Chironomus riparius, both
    metabolized benzo [a]pyrene. In the larvae, the main metabolite
    appeared to be 3-hydroxybenzo [a]pyrene; a quinone isomer was also
    found. Only a very small amount of 3-hydroxy-benzo [a]pyrene was
    found in the clam. No diol metabolites were found in either species
    (Borchert & Westendorf, 1994). After exposure of the benthic
    oligochaete  Stylodrilus heringianus to either anthracene and pyrene
    or phenanthrene and benzo [a]pyrene, 2% degradation of each PAH was
    reported within 24 h (Frank et al., 1986).

         The half-lives for metabolism in  D. magna were 0.5 h for 1.8
    mg/litre naphthalene, 9 h for 0.06 mg/litre phenanthrene, and 18 h for
    0.023 mg/litre chrysene (Eastmond et al., 1984).

         In amphipod  Hyalella azteca was exposed to 0.043 nmol/ml
    anthracene for 8 h, the rates of biotransformation were 2.2 ± 0.5
    nmol/g dry weight per h with no substratum, 3.0 ± 0.8 in the presence
    of washed sand from a local lake, and 1.0 ± 0.15 in the presence of
    sediment from the lake (Landrum & Scavia, 1983).

         The amphipod  Rhepoxynius abronius metabolizes benzo [a]pyrene
    (Plesha et al., 1988). When two marine amphipods were exposed to a
    sediment containing 5.1 ng/mg of this compound,  R. abronius 
    metabolized 49% and  Eohaustorius washingtonianus metabolized 27% of
    the benzo [a]pyrene after one day. The main metabolites appeared to
    be 7,8-dihydro-7,8-dihydroxy-benzo [a]pyrene,
    9,10-dihydro-9,10-dihydroxybenzo [a]pyrene,
    3-hydroxy-benzo [a]pyrene, and 9-hydroxybenzo [a]pyrene. The ratio
    of 7,8-dihydro-7,8-dihydroxybenzo [a]pyrene to
    9,10-dihydro-9,10-dihydroxybenzo [a]pyrene in normal-phase
    high-performance liquid chromatography was 1.2 for  R. abronius and
    0.7 for  E. washingtonianus (Reichert et al., 1985).

         No biotransformation of benzo [a]pyrene or phenanthrene was
    found in mayflies  (Hexagenia limbata) or in the amphipod
     Pontoreia hoyi (Landrum & Poore, 1988).

         In a study of the route of metabolism of benzo [a]pyrene in
    green algae  (Selenastrum capricornutum) exposed to 1.2 µg/litre for
    four days, with simulated day and night periods, the major dihydrodiol
    metabolites identified were the  cis-4,5-diol (< 1%), the
     cis-7,8-diol (13%), the 9,10-diol (36%), and the  cis-11,12-diol
    (50%), demonstrating the presence of a dioxygenase enzyme for this
    type of algae (Lindquist & Warshawsky, 1985), as suggested by Cody et
    al. (1984). Payne (1977) reported, however, that aryl hydrocarbon
    hydroxylase was not present in  Fucus and  Ascophyllum sp. of marine
    algae.

         Benzo [a]pyrene was not biotransformed in periphyton after 0.25
    or 4 h. In cladocerans  (D. magna) exposed to 1.0 µg/litre
    benzo [a]pyrene, the biotransformation rate after exposure for 6 h
    was 1.07 ± 0.20 nmol/g dry weight per h. In midge larvae  (C. 
     riparius) exposed to 0.6-1.5 µg/litre, the biotrans-formation rate
    was 3.6 ± 0.7 nmol/g dry weight per h after exposure for 1 h and 2.7 ±
    0.3 after 4 h. In  L. macrochirus exposed to 1.0 µg/litre, the
    biotransformation rate was 0.20 ± 0.03 nmol/g dry weight per h after 1
    h and 0.37 ± 0.04 after 4 h. In chironomids, 3-hydroxybenzo [a]pyrene
    was the major metabolite after 8 h, representing 4.4% of the total
    water activity; smaller amounts of 7-hydroxy-benzo [a]pyrene and the
    9,10- and 7,8-dihydroxydiols of benzo [a]pyrene were also found
    (Leversee et al., 1981).

         After exposure of benthic species to benzo [a]pyrene for one to
    four weeks, the following percentages of metabolites were found:  E. 
     washingtonianus, 22% in the whole body;  R. abronius, 74% in the
    whole body; clams  (Macoma nasuta), < 5% in the body and < 5 in the
    hepatopancreas; shrimp  (Pandalus platyceros), 94% in the
    hepatopancreas; and the English sole  (Parophrys vetulus), 94% in the
    body, 99% in the liver and > 99% in the bile (Varanasi et al., 1985).

         Mosquito larvae  (C. pipens quinquefasciatus) were exposed for
    three days to 0.002 mg/litre benzo [a]pyrene in the presence or
    absence of the mixed-function oxidase inhibitor piperonyl butoxide at
    0.0025 mg/litre. Parent benzo [a]pyrene represented 22% of the
    excreted PAH in the absence of piperonyl butoxide and 86% in its
    presence. After three days' exposure of snails  (Physa sp.) to the
    same concentration of benzo [a]pyrene with or without piperonyl
    butoxide at 0.0025 mg/litre, parent benzo [a]pyrene represented 88%
    in the absence of the inhibitor and 85% in its presence. The authors
    suggested that snails are deficient in microsomal oxidases. In
    mosquito fish  (G. affinis) exposed similarly, no parent
    benzo [a]pyrene was found in the absence of piperonyl butoxide but
    21% in its presence (Lu et al., 1977).

         In an aquatic ecosystem, plankton, green algae  (Oedogonium 
     cardiacum), D. magna, mosquito larvae  (C. pipiens 
     quinquefasciatus), snails  (Physa sp.), and mosquito fish
     (G. affinis) were exposed to 0.002 mg/litre benzo [a]pyrene for
    three days. Parent benzo [a]pyrene represented 83, 90, 46, 70, and
    55% in the four organisms, respectively. The substance was metabolized
    to unidentified hydroxylated polar compounds. The finding of 55%
    parent benzo [a]pyrene in the fish was attributed to food-chain
    transfer, as none was found after direct exposure. A
    terrestrial-aquatic ecosystem was also exposed to benzo [a]pyrene by
    applying 0.2 mg of radiolabelled compound to  Sorghum vulgare 
    seedlings to simulate atmospheric fall-out and allowing them to be
    consumed by fourth-instar salt-marsh caterpillar larvae  (E. acrea). 
    Faecal products then entered the terrestrial and aquatic ecosystem
    described above, which was left for 33 days. The maximum radiolabel
    (0.005 ppm) was detected in the aquatic phase after 14 days.
    Unmetabolized benzo [a]pyrene accounted for 7.1% of the total
    extractable radiolabel in fish, 19% in snails, 32% in algae, and 34%

    in mosquitoes. Addition of the mixed-function oxidase inhibitor,
    piperonyl butoxide, resulted in 12% parent benzo [a]pyrene in fish,
    34% in snails, 48% in the algae, and no change in mosquitoes (Lu et
    al., 1977).

         The biotransformation of 19 PAH was studied in the food chain
    seston (plankton) -> blue mussel  (Mytilus edulis L.) -> common
    eider duck  (Somateria mollissima L.) in the open, northern Baltic
    Sea. The concentrations of the PAH in the eider duck showed the
    distribution gallbladder > adipose tissue > liver. There was a
    high flux of the PAH in the food chain, but the concentration did not
    increase with increasing trophic level, indicating that the PAH were
    biotransformed rapidly. There was little biotransformation in the
    plankton. The distribution of the PAH in blue mussels was different
    from that in plankton, perhaps due to metabolic activity in the
    mussel. Biotransformation of PAH with a relative molecular mass of 252
    was rapid in the ducks (Broman et al., 1990).

         In beans  (Phaseolus vulgaris L.) exposed to 15 œg anthracene
    per plant, uptake via the roots was rapid, 90% being metabolized
    within 30 days (Edwards, 1986).

         These investigations are summarized in Table 30. As the rate of
    metabolism depends not only on the species but also on factors such as
    temperature, pH, and other experimental conditions, the results are
    difficult to compare. Some general conclusions can, however, be drawn:

    -    The biotransformation potential of aquatic organisms depends on
         the activity of cytochrome P450-dependent mixed-function
         oxidases, which are important for oxidation, the first step in
         the metabolism of xenobiotics such as PAH (James, 1989).

    -    The tissues in which biotransformation mainly takes place are
         liver, lung, kidney, placenta, intestinal tract, and skin
         (Cerniglia, 1984).

    -    The initial transformation step in invertebrates usually occurs
         more slowly than in vertebrates (James, 1989). Monoxygenation of
         PAH is faster in higher invertebrates like arthropods,
         echinoderms, and annelids and slowest in more primitive
         invertebrates like protozoa, profina, cnidaria, and molluscs
         (Neff, 1979).

    -    In general, invertebrates excrete PAH metabolites inefficiently
         (James, 1989).

    -    In higher organisms and algae, metabolites are usually produced
         by monooxygenase activity, resulting in the formation of
         epoxides, phenols, diols, tetrols, quinones, and conjugates.

    -    It is not clear whether molluscs have cytochrome P450 activity
         (Moore et al., 1989).


        Table 30. Biotransformation of polycyclic aromatic hydrocarbons by various organisms

                                                                                                                                   

    Species                                Compound              Biotransformation rate           Reference
                                                                                                                                   

    Fungi
       Cunninghamella elegans              Benzo[a]pyrene        No information                   Cerniglia (1984)

    Algae
       Selenastrum capticornutum           Benzo[a]pyrene        Relatively fast                  Lindquist & Warshawsky (1985)
       Oedogenium cardiacum                Benzo[a]pyrene        15% after 3 d in                 Lu et al. (1977)
                                                                 aquatic ecosystem
       Fucus sp.                           Various               None                             Payne(1977)
       Ascophyllum sp.                     Various               None

    Molluscs
       Sphaerium corneum                   Benzo[a]pyrene        Very fast (no carcinogenic       Borchert & Westendorf (1994)
                                                                 metabolites)
       Physa sp.                           Benzo[a]pyrene        12% after 3 d                    Lu et al. (1977)
       Mytilus edulis L.                   Different             No information                   Broman et al. (1990)

    Crustaceae
       Hyalella azteca                     Anthracene            2.2 nmol/g dw/h in water         Landrum & Scavia (1983)
       Hyalella azteca                     Anthracene            3.0 nmol/g dw/h 5 water/         Landrum & Scavia (1983)
                                                                 sediment
       Daphnia magna                       Benzo[a]pyrene        1.07 nmol/g dw/h after 6 h       Leversee et al. (1981)
       Daphnia magna                       Benzo[a]pyrene        10% after 3 d in aquatic         Lu et al. (1977)
                                                                 ecosystem
       Pontoporeia hoyi                    Benzo[a]pyrene        None                             Landrum & Poore (1988)
       Pontoporeia hoyi                    Benzo[a]pyrene        None after 48 h                  Evans & Landrum (1989)
       Mysis relicta                       Benzo[a]pyrene        No information                   Evans & Landrum (1989)
       Rhepoxynius abronius                Benzo[a]pyrene        No information                   Plesha et al. (1988)
       Rhepoxynius abronius                Benzo[a]pyrene        74% after 1-4 weeks              Varanasi et al. (1985)
       Rhepoxynius abronius                Benzo[a]pyrene        49% after 1 d                    Reichert et al. (1985)
       Eohaustorius washingtonianus        Benzo[a]pyrene        27% after 1 d                    Reichert et al. (1985)
       Eohaustorius washingtonianus        Benzo[a]pyrene        22% after 1-4 weeks              Varanasi et al. (1985)

    Table 30. (continued)

                                                                                                                                   

    Species                                Compound              Biotransformation rate           Reference
                                                                                                                                   

       Pandalus platyceros                 Benzo[a]pyrene        < 5% after 1-4 weeks             Varanasi et al. (1985)
       Parophrys vetulus                   Benzo[a]pyrene        94% after 1-4 weeks              Varanasi et al. (1985)
       Daphnia magna                       Chrysene              50% after 18 h                   Eastmond et al. (1984)
       Daphnia magna                       Naphthalene           50% after 0.5 h                  Eastmond et al. (1984)
       Daphnia magna                       Phenanthrene          50% after 9 h                    Eastmond et al. (1984)

    Fish
       Lepomis macrochirus                 Acenaphthene          Half-life, < 1 d                 Barrows et al. (1980)
       Lepomis macrochirus                 Anthracene            8% after 4 h                     Spacie et al. (1983)
       Oncorhynchus mykiss                 Anthracene            2-3% after 24 h                  Linder & Bergman (1984)
       Gillichthys mirabilis               Benzo[a]pyrene        Rapid in liver                   Lee et al. (1972)
       Oligocottus maculosus               Benzo[a]pyrene        Rapid in liver                   Lee et al. (1972)
       Citharichthys stigmaeus             Benzo[a]pyrene        Rapid in liver                   Lee et al. (1972)
       Lepomis macrochirus                 Benzo[a]pyrene        Very fast                        McCarthy & Jimenez (1981)
       Lapomis macrochirus                 Benzo[a]pyrene        88% after 4h                     Spacie et al. (1983)
       Lepomis macrochirus                 Benzo[a]pyrene        0.20-0.37 nmol/g dry             Leversee et al. (1981)
                                                                 weight per h
       Oryzias latipes                     Benzo[a]pyrene        No information                   Hawkins (1988)
       Poecilia reticulata                 Benzo[a]pyrene        No information                   Hawkins (1988)
       Rhepoxynius abronius                Benzo[a]pyrene        None                             Plesha et al. (1988)
       Gambusia affinis                    Benzo[a]pyrene        100% after 3 d in water          Lu et al. (1977)
                                                                 40% after 3 d in aquatic
                                                                 ecosystem
       Gillichthys mirabilis               Naphthalene           Rapid in liver                   Lee et al. (1972)
       Oligocottus maculosus               Naphthalene           Rapid in liver                   Lee et al. (1972)
       Citharichthys stigmaeus             Naphthalene           Rapid in liver                   Lee et al. (1972)
       Lepomis macrochirus                 Naphthalene           Very fast                        McCarthy & Jimenez (1981)

    Worm
       Stylodrilus heringianus             Various               None                             Franck et al. (1986)

    Table 30. (continued)

                                                                                                                                   

    Species                                Compound              Biotransformation rate           Reference
                                                                                                                                   

    Insects
       Chironomus riparius                 Benzo[a]pyrene        Very fast (no carcinogenic       Bochert & Westendorf (1994)
                                                                 metabolites)
       Chironomus riparius                 Benzo[a]pyrene        2.7-3.6 nmol/g dry weight        Leversee et al. (1981)
                                                                 per h
       Hexagenia limbata                   Benzo[a]pyrene        None                             Landrum & Poore (1983)
       Culex pipiens                       Benzo[a]pyrene        78% after 3 d                    Lu et al. (1977)
       quinquefasciatus
       Somatochlora cingulata              Naphthalene           No information                   Correa & Coler (1990)

    Bird
       Somateria mollissima L.             Various               Fast for PAH with                Broman et al. (1990)
                                                                 molecular mass > 252

    Plant
       Phaseolus vulgaris L.               Anthracene            90% after 30 d                   Edwards (1986)
                                                                                                                                   


    -    In crustaceans, biotransformation differs greatly between species
         and for different PAH. Biotransformation of naphthalene,
         anthracene, phenanthrene, and chrysene appears to occur rapidly,
         while that of benzo [a]pyrene is generally slower. Only Reichert
         et al. (1985) reported significant degradation in  R. abronius 
         (49%) and  E. washingtonianus (27%) within one day.

    -    It is not clear how rapidly biotransformation occurs in insects.

    -    Too little information was available on algae, plants, and fungi
         for conclusions to be drawn.

    4.2.2  Abiotic degradation

         Abiotic processes may account for the removal of 2-20% of two-
    and three-ring PAH from soil (Park et al., 1990). In soils partly
    amended with PAH-containing sewage sludge, 24-100% was removed, and
    naphthalene was eliminated almost completely by volatilization and
    photodegradation (Wild & Jones, 1993).

    4.2.2.1  Photodegradation in the environment

         PAH can be expected to be photodegraded in air and water but to a
    very low extent in soils and sediments, owing to low light intensity.
    In natural waters, photodegradation takes place only in the upper few
    centimetres of the aqueous phase. Information on the photodegradation
    of PAH in air and water is summarized in Table 31; however, as the
    testing conditions varied widely, general conclusions cannot be drawn.

         PAH are photodegraded in air and water by two processes: direct
    photolysis by light with a wavelength < 290 nm and indirect
    photolysis by least one oxidizing agent such as OH, O3, and NO3 in
    air and ROO radicals in water. In general, indirect photolysis -
    photooxidation - is the more important process. The reaction rates of
    PAH with airborne OH radicals measured under standard conditions are
    given in Table 32, which shows that most of the calculated half-lives
    are one day or less. Under environmental conditions, PAH of higher
    molecular mass, i.e. those with more aromatic rings, are almost
    completely adsorbed onto fine particles (see section 4.1.2); this
    reduces the degradation rate markedly.

         Degradation half-lives of 3.7-30 days were reported for the
    reaction with NOx of various PAH adsorbed onto soot. The degradation
    was much slower in the absence of sunlight. PAH did not react
    significantly with SO2 (Butler & Crossley, 1981). PAH in wood smoke
    and gasoline exhaust did not degrade significantly during winter in
    extreme northern and southern latitudes owing to low temperatures and
    the low angle of the sun (Kamens et al., 1986a). In summer, however,
    at a temperature of 20°C, the half-lives of individual PAH were in the
    range of 30-60 min (Kamens et al., 1986b). The degradation rate
    increased further with increasing humidity (Kamens et al., 1991).


        Table 31. Photodegradation of polycyclic aromatic hydrocarbons

                                                                                                                                             
    Compound                Compartment           Photolysis           Half-life     Comments                                  Reference
                                                  rate constant        (h)
                                                                                                                                             

    Acenaphthene            Air, particles                                           Determined in rotary photoreactor         Behymer &
                                                                                     with 25 µg/g on:                          Hites (1985)
                                                                       2.0           - silica gel
                                                                       2.2           - alumina
                                                                       44            - fly ash

                            Water                 0.23 h-1             3.0           Rate constant in distilled water          Fukuda et al.
                                                                                                                               (1988)

    Acenaphthylene          Air, particles                                           Determined in rotary photoreactor         Behymer &
                                                                                     with 25 µg/g on:                          Hites (1985)
                                                                       0.7           - silica gel
                                                                       2.2           - alumina
                                                                       44            - fly ash

    Anthracene              Air, water                                 0.58          Measured in atmosphere and water          Southworth
                                                                                     from aqueous photolysis rate              (1979)
                                                                                     constant for midday summer sunlight
                                                                                     at 35°N

                            Air, particles                                           Determined with 25 µg/g on:               Behymer &
                                                                       2.9           - silica gel                              Hites (1985)
                                                                       0.5           - alumina
                                                                       48            - fly ash

                            Water                                                    Removal rate constants from water         Southworth
                                                                                     at 25°C in midsummer sunlight:            (1979)
                                                  0.004 h-1            173           - in deep, slow, somewhat turbid
                                                                                       water
                                                  <0.001 h-1           > 700         - in deep, slow, muddy water
                                                  0.018 h-1            38            - in deep, slow, clear water
                                                  0.086 h-1            8             - in shallow, fast, clear water
                                                  0.238 h-1            3             - in very shallow, fast, clear water

    Table 31. (continued)

                                                                                                                                             

    Compound                Compartment           Photolysis           Half-life     Comments                                  Reference
                                                  rate constant        (h)
                                                                                                                                             

                            Water                                                    Half-lives calclulated from average       Southworth
                                                                                     light intensity over 24 h:                (1977)
                                                                       1.6           - in summer
                                                                       4.8           - in winter

                            Water                                                    Half-lives calculated for direct          Zepp &
                                                                                     sunlight at 40°N at midday in             Schlotzhauer
                                                                                     midsummer:                                (1979)
                                                                       0.75          - near surface water
                                                                       108           - inland water
                                                                       125           - inland water with sediment
                                                                                       partitioning
                                                                       0.75          - direct photochemical
                                                                                       transformation near water surface

                            Water                 0.66 h-1             1.0           In distilled water                        Fukuda et al.
                                                                                                                               (1988)

    Benz[a]anthracene       Air, particles                                           First-order daytime decay rate            Kamens et al.
                                                                                     constants with soot particle loading of:  (1988)
                                                  0.0125 min-1         0.9           - 1000-2000 ng/mg
                                                  0.0250 min-1         0.5           - 30-350 ng/mg

                            Air, particles                                           Determined with ± 25 µg/g on:             Behymer &
                                                                       4.0           - silica gel                              Hites (1985)
                                                                       2.0           - alumina
                                                                       38            - fly ash

    Table 31. (continued)

                                                                                                                                             

    Compound                Compartment           Photolysis           Half-life     Comments                                  Reference
                                                  rate constant        (h)
                                                                                                                                             

                            Water                                                    Calculated rate constant in pure          Mill et al.
                                                                                     water:                                    (1981)
                                                  13.4 × 10-5s-1       1.4           - at 366 nm and in sunlight at
                                                                                       23-28°C, early March
                                                  2.28 × 1O-5s-1       8.4           - at 313 nm with 1% acetonitrile
                                                                                       in filter-sterilized natural water
                                                                       5             Early March

    Benzo[a]pyrene          Air, particles                                           Determined with 25 µg/g on:               Behymer &
                                                                       4.7           silica gel                                Hites (1985)
                                                                       1.4           - alumina
                                                                       31            - fly ash

                            Air particles                                            First-order daytime decay rate            Kamens et al.
                                                                                     constants with soot particle loading of:  (1988)
                                                  0.0090 min-1         1.3           - 1000-2000 ng/mg
                                                  0.0211 min-1         0.54          - 30-350 ng/mg

                            Air, particles        < 6.1 × 10-4 m/s                   Ozonization rate constant measured        Cope &
                                                                                     at 24°C with O3 = 0.16 ppm and            Kalkwarf
                                                                                     light intensity of 1.3 kW/m3              (1987)

                            Air                                        0.37-1.1      Estimated                                 Lyman et al.
                                                                                                                               (1982)

                            Air                                        1             Sunlight in mid-December                  Mill & Mabey
                                                                                                                               (1985)

    Table 31. (continued)

                                                                                                                                             

    Compound                Compartment           Photolysis           Half-life     Comments                                  Reference
                                                  rate constant        (h)
                                                                                                                                             

                            Air, water                                               Calculated rate constants for             Mill et al.
                                                                                     direct photolysis:                        (1981)
                                                  3.86 × 10-4s-1       0.69          - in pure water at 366 nm and in
                                                                                     sunlight at 23-28°C, late January
                                                  1.05 × 10-5s-1       1.1           - at 313 nm with 1-20% acetonitrile
                                                                                     in filter-sterilized natural
                                                                                     water, mid-December

                            Water                                                    Computed near-surface half-life for       Zepp &
                                                                                     direct photochemical transformation       Schlotzhauer
                                                                                     of a natural water body:                  (1979)
                                                                       0.54          - latitude 40°N, midday, midsummer
                                                                       77            - no sedimentmater partitioning
                                                                       312           - sediment; water partitioning in a
                                                                                       5-m deep inland water body

                            Air                                        > 1           Summer                                    Valerio et al.
                                                                       Days          Winter                                    (1991)

                            Methanol                                   2             Irradiated at 254 nm                      Lu et al. (1977)

    Benzo[b]fluoranthene    Air, particles                                           First-order daytime decay rate            Kamens et al.
                                                                                     constants with soot particle loading of:  (1988)
                                                  0.0065 min-1         1.8           - 1000-2000 ng/mg
                                                  0.0090 min-1         1.3           - 30-350 ng/mg

                            Air, water                                 8.7-720       Based on measured rate of                 Lane & Katz
                                                                                     photolysis in heptane irradiated with     (1977); Muel
                                                                                     light at > 290 nm                         & Saguem
                                                                                                                               (1985)

    Table 31. (continued)

                                                                                                                                             

    Compound                Compartment           Photolysis           Half-life     Comments                                  Reference
                                                  rate constant        (h)
                                                                                                                                             

    Benzo[ghi]perylene      Air, particles                                           Determined with 25 µg/g on:               Behymer &
                                                                       7.0           - silica gel                              Hites (1985)
                                                                       2.2           - alumina
                                                                       29            - fly ash

                            Air, particles                                           First-order daytime photodegradation      Kamens et al.
                                                                                     rate constants for adsorption             (1988)
                                                                                     on wood soot particles in an outdoor
                                                                                     Teflon chamber for soot loading of:
                                                  0.0077 min-1         1.5           - 1000-2000 ng/mg
                                                  0.0116 min-1         1.0           - 30-350 ng/mg

    Benzo[k]fluoranthene    Air, particles                                           First-order daytime decay constants       Kamens et al.
                                                                                     for soot loading of:                      (1988)
                                                  0.0047 min-1         2.5           - 1000-2000 ng/mg
                                                  0.0013 min-1         8.9           - 30-350 ng/mg


                            Air, water                                 3.8-499       Based on measured rate of photolysis      Muel &
                                                                                     in heptane under November                 Saguem
                                                                                     sunlight, adjusted by ratio of            (1985)
                                                                                     sunlight photolysis half-lives in
                                                                                     water: heptane

    Chrysene                Air, particles                                           Determined with 25 µg/g on:               Behymer &
                                                                       100           - silica gel                              Hites (1985)
                                                                       78            - alumina
                                                                       38            - fly ash

    Table 31. (continued)

                                                                                                                                             

    Compound                Compartment           Photolysis           Half-life     Comments                                  Reference
                                                  rate constant        (h)
                                                                                                                                             

                            Air, particles                                           First-order daytime decay constants       Kamens et al.
                                                                                     for soot loading of:                      (1988)
                                                  0.0056 min-1         2.1           - 1000-2000 ng/mg
                                                  0.0090 min-1         1.3           - 30-350 ng/mg

                            Air, water                                 4.4           Calculated for direct photochemical       Zepp &
                                                                                     transformation near surface of            Schlotzhauer
                                                                                     a water body at 40°N at midday in         (1979)
                                                                                     midsummer

                            Water                                      13            Estimated on basis of photolysis          Lyman et al.
                                                                                     in water in winter                        (1982)

    Dibenzo[a,h]anthracene  Air, water                                 782           Based on measured rate of photolysis      Muel &
                                                                                     in heptane in November sun                Saguem
                                                                       6             After adjusting ratio of sunlight         (1985)
                                                                                     photolysis in water: heptane

    Fluoranthene            Air, particles                                           Determined with 25 µg/g on:               Behymer &
                                                                       74            - silica gel                              Hites (1985)
                                                                       23            - alumina
                                                                       44            - fly ash

                            Air, water                                 63            Computed, adjusted for approximate        Lyman et al.
                                                                                     winter sunlight intensity                 (1982)

                            Air, water                                               Calculated photochemical transformation   Zepp &
                                                                                     near surface of water body:               Schlotzhauer
                                                                       21            - at 40°N, midday, midsummer              (1979)
                                                                       3800          - 5-m deep inland water body with
                                                                                       no sediment:water partitioning
                                                                       4800          - with sediment:water partitioning

    Table 31. (continued)

                                                                                                                                             

    Compound                Compartment           Photolysis           Half-life     Comments                                  Reference
                                                  rate constant        (h)
                                                                                                                                             

                            Water                                      3800          Summer sunlight in surface water          Mill & Mabey
                                                                                                                               (1985)

    Fluorene                Air, particles                                           Determined in rotary photoreactor         Behymer &
                                                                                     with 25 µg/g on:                          Hites (1985)
                                                                       110           - silica gel
                                                                       62            - alumina
                                                                       37            - fly ash

    Naphthalene             Water                                      13 200        Calculated, 5-m deep inland water         Zepp &
                                                                                                                               Schlotzhauer
                                                                                                                               (1979)

                            Water                 0.028 h-1            25            Half-life in distilled water              Fukuda et al.
                                                                                                                               (1988)

    Perylene                Air, particles                                           Determined with 25 µg/g on:               Behymer &
                                                                       3.9           - silica gel                              Hites (1985)
                                                                       1.2           - alumina
                                                                       35            - fly ash

                            Air, glass            < 4.7 × 10-5 m/s                   Ozonization rate constant measured        Cope &
                                                                                     from glass surface at 24°C with 03        Kalkwarf
                                                                                     - 0.16 ppm and light intensity of         (1987)
                                                                                     1.3 kW/m2

    Phenanthrene            Air, particles                                           Determined with 25 µg/g on:               Behymer &
                                                                       150           - silica gel                              Hites (1985)
                                                                       45            - alumina
                                                                       49            - fly ash
                            Water                                      3             Based on measured aqueous photolysis      Zepp &
                                                                                     quantum yields, midday, mid-summer,       Schlotzhauer
                                                                                     40°N                                      (1979)

    Table 31. (continued)

                                                                                                                                             

    Compound                Compartment           Photolysis           Half-life     Comments                                  Reference
                                                  rate constant        (h)
                                                                                                                                             

                            Air, water                                 25            Adjusted for approximate winter           Lyman et al.
                                                                                     sunlight intensity                        (1982)

                            Air, water                                               Calculated, direct sunlight photolysis,   Zepp &
                                                                                     midday, midsummer, 40°N:                  Schlotzhauer
                                                                       8.4           - near surface water                      (1970)
                                                                       1400          - 5-m deep inland water body with
                                                                                       no sediment:water partitioning
                                                                       1650          - with sedimentmater partitioning
                            Water                 0.11 h-1             6.3           Half-life in distilled water              Fukuda et al.
                                                                                                                               (1988)

    Pyrene                  Air, particles                                           Determined with 25 µg/ml on:              Behymer & Hites
                                                                       21            - on silica gel                           (1985)
                                                                       31            - on alumina
                                                                       46            - on fly ash
                            Air, particles                                           Adsorption on airborne particles          Valerio et al.
                                                                                     by sunlight:                              (1991)
                                                                       1             - in summer
                                                                       Days          - in winter

                            Air, water            1.014 h-1            0.68          Based on measured aqueous photolysis      Zepp &
                                                                                     quantum yields, midday,                   Schlotzhauer
                                                                                     summer, 40°N                              (1979)

                            Air, water                                 2.04          Based on measured aqueous photolysis      Lyman et al.
                                                                                     quantum yields, adjusted for              (1982)
                                                                                     approximate winter sunlight intensity

                            Air, glass            < 1.05 × 10-4 m/s                  Ozonization rate on glass surface         Cope &
                                                                                     at 24°C with O3 = 0.16 ppm and            Kalkwarf
                                                                                     light intensity of 1.3 kW/m2              (1987)

    Table 31. (continued)

                                                                                                                                             

    Compound                Compartment           Photolysis           Half-life     Comments                                  Reference
                                                  rate constant        (h)
                                                                                                                                             

                            Water                                                    Calculated, direct sunlight photolysis,   Zepp &
                                                                                     midday, midsummer, 40°N:                  Schlotzhauer
                                                                       0.58          - near surface water                      (1979)
                                                                       100           - 5-m deep inland water body with
                                                                                       no sediment:water partitioning
                                                                       142           - with sediment:water partitioning

                            Water                                      100           Summer sunlight photolysis in             Mill & Mabey
                                                                                     surface water                             (1985)
                                                                                                                                             

    In order to compare numbers reported only as rate constants, half-lives were estimated from the formula:

     t1/2 = In2
             k

    where  t1/2 is the half-life and  k is the rate constant. The calculated values are reported in italics.

    Table 32. Reactions of polycyclic aromatic hydrocarbons with hydroxy radicals

                                                                                                                                      

    Compound                 Oxidation rate     Photooxidation     Comments                                        Reference
                             constant           half-life (h)
                                                                                                                                      

    Acenaphthene             1 × 10-10          0.879-8.79         Based on estimated reaction rate                Atkinson (1987)
                                                                   constant with hydroxy radical in air
    Acenaphthylene           1.1 × 10-10        0.191-1.27         Based on estimated rate constant for            Atkinson (1987)
                                                                   reaction in air
    Anthracene               1.1 × 10-12cm3     58-580             Rate constant for gas-phase reaction            Biermann at al.
                             molec-1s-1                            with hydroxy radicals at 298 ± 1 K, based       (1985)
                                                                   the relative rate technique for propane
                                                0.501-5.01         Based on estimated rate constant for            Atkinson (1987)
                                                                   reaction with hydroxy radical in air
    Benz[a]anthracene                           0.801-8.01         Based on estimated rate constant for            Atkinson (1987)
                                                                   reaction with hydroxy radical in air
    Benzo[a]pyrene                              0.428-4.28         Based on estimated rate constant for            Atkinson (1987)
                                                                   reaction with hydroxy radical in air
    Benzo[b]fluoranthene                        1.43-14.3          Based on estimated rate constant for            Atkinson (1987)
                                                                   reaction with hydroxy radical in air
    Benzo[ghi]perylene                          0.321-3.21         Based on estimated rate constant for            Atkinson (1987)
                                                                   reaction with hydroxy radical in air
    Benzo[k]fluoranthene                        1.1-11             Based on estimated rate constant for            Atkinson (1987)
                                                                   reaction with hydroxy radical in air
    Chrysene                                    0.802-8.02         Based on estimated rate constant for            Atkinson (1987)
                                                                   reaction with hydroxy radical in air
    Dibenz[a,h]anthracene                       0.428-4.28         Based on estimated rate constant for            Atkinson (1987)
                                                                   reaction with hydroxy radical in air
    Fluoranthene                                2.02-20.2          Based on estimated rate constant for            Atkinson (1987)
                                                                   reaction with hydroxy radical in air
    Fluorene                 1.3 × 10-11        6.81-68.1          Based on estimated rate constant for            Atkinson (1987)
                                                                   reaction with hydroxy radical in air

    Table 32. (continued)

                                                                                                                                      
    Compound                 Oxidation rate     Photooxidation     Comments                                        Reference
                             constant           half-life (h)
                                                                                                                                      

    Naphthalene              2.16 × 10-11 cm3   2.7-27             Rate constant for reaction with hydroxy         Atkinson (1989)
                             molec-1s-1                            radicals using relative rate technique
                                                                   at 294 K
                             2 × 10-19 cm3      19-321             Upper limit was obtained for reaction
                             molec-1s-1                            with O3
                             2.35 × 10-11 cm3   2.7-27             Rate constant for gas-phase reaction            Biermann et al.
                             molec-1s-1                            with hydroxy radicals at 298 K, based           (1985)
                                                                   on relative rate technique from propene
    Phenanthrene             3.4 × 10-11 cm3    2-20               Rate constant for gas-phase reaction            Biermann et al.
                             molec-1s-1                            with hydroxy radicals at 298 K, based           (1985)
                                                                   on relative rate technique for propene
                             3.1 × 10-11        2.01-20.1          Half-life based on measured rate                Atkinson (1987)
                                                                   constants for reaction with hydroxy
                                                                   radical in air
    Pyrene                                      0.802-8.02 h       Based on estimated rate constant for            Atkinson (1987);
                                                                   reactions with hydroxy radical in air and       Atkinson & Carter
                                                                   with hydroxy radical and ozone                  (1984)
                                                                                                                                      

    To allow comparison when only rate constants are reported, half-lives were estimated from the following formula:

    t1/2 = In 2
           [x] ×  k

    where t1/2 is the half-life, [x] is the concentration of the radical with which the compounds react (i.e. hydroxyl or ozone),
    and  k is the rate constant. The calculated values are reported in italics.

    For the concentrations of the radicals, the following ranges of values were used; the lower values are estimates for rural
    areas and the higher ones for urban areas (Howard et al., 1991):
       [OH]air = 3-30 × 105 radicals/cm3
       [O3]air = 3-50 × 1012 molecules/cm3
       [OH]water = 5-200 × 10-17 mol/litre
       [RO2]water = 1-50 × 10-11 mol/litre
       [1O2]water = 1-100 × 10-15 mol/litre


         In a study of the fate of 18 PAH on 15 types of fly ash, carbon
    black, silica gel, and alumina, the PAH were stabilized, depending on
    the colour, which is related to the carbon content: the higher the
    carbon content, the more stable the PAH. The authors suggested that
    radiation energy is adsorbed by the organic matter of particulates,
    and PAH therefore do not achieve the excited state in which they can
    be degraded (Behymer & Hites, 1988). The half-lives for direct
    photolysis of various PAH adsorbed onto silica gel are in the range of
    hours (Vu-Duc & Huynh, 1991).

         A two-layer model has been proposed for the behaviour of
    naturally occurring PAH on airborne particulate matter, in which
    photooxidation takes place in the outer layer, and much slower, 'dark'
    oxidation takes place in the inner layer (Valerio et al., 1987). This
    model is in line with the results of Kamens et al. (1991), who
    reported that PAH on highly loaded particles degrade more slowly than
    those on particles with low loads. As PAH occur mainly on particulate
    matter with a high carbon content, their degradation in the atmosphere
    is slower than that of PAH in the vapour phase under laboratory
    conditions or adsorbed on synthetic materials like alumina and silica
    gel that have no or a low carbon content.

         Formation of nitro-PAH was found from the low-molecular-mass two-
    to four-ring PAH that occur in the atmosphere, predominantly in the
    vapour phase. The rate constants range from 5.5 × 10-12 cm3/molecule
    × s for acenaphthylene to 3.6 × 10-28 cm3/molecule × s for
    naphthalene, with corresponding half-lives ranging from 6 min to 1.5
    years. The yields were 1% or less (Atkinson et al., 1991; Atkinson &
    Arey, 1994).

         The rate of degradation of absorbed individual PAH seems to be
    independent of their physicochemical characteristics but dependent on
    their molecular structure. Thus, activated carbon from graphite
    particles effectively stabilized pyrene, phenanthene, fluoranthene,
    anthracene, and benzo [a]pyrene adsorbed onto coal fly ash against
    photochemical decomposition, but no stabilization was seen for
    fluorene, benzo [a]fluorene, benzo [b]fluorene,
    9,10-dimethyl-anthracene, or 4-azafluorene. The authors suggested that
    PAH that contain benzylic carbon atoms are less reactive than others
    (Hughes et al., 1980).

         PAH with vinylic bridges appear to degrade by direct photolysis
    more rapidly than those with only aromatic rings, both in air and in
    the aquatic environment (Hites, 1981).

         In measurements of the photodegradation of benz [a]anthracene
    and benzo [a]pyrene, addition of humic acids and purging of the
    solution with nitrogen reduced the reaction rates significantly (Mill
    et al., 1981). The authors concluded that light screening and
    quenching occurred with humic acids. The reduction in rate with
    exclusion of oxygen was probably due to a decrease in photooxidative
    processes. The first metabolites were mainly quinones.

    4.2.2.2  Hydrolysis

         PAH are chemically stable, with no functional groups that result
    in hydrolysis. Under environmental conditions, therefore, hydrolysis
    does not contribute to the degradation of PAH (Howard et al., 1991).

    4.3  Ultimate fate after use

         The main sinks for PAH are sediment and soil. The available
    information indicates that high-molecular-mass PAH are especially
    persistent in groundwater, soil, and sediment under environmental
    conditions.

    5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

    Appraisal

    Polycyclic aromatic hydrocarbons (PAH) occur in all environmental
    compartments. Ambient air, residential heating, and vehicle traffic
    are the main sources. The levels of individual substances vary over
    several orders of magnitude but are generally in the range < 0.1-100
    ng/m3.

    Surface waters are contaminated by PAH mainly through atmospheric
    deposition, urban runoff, and industrial activities such as coal
    coking and aluminium production. Apart from highly industrial polluted
    rivers, the concentrations of individual substances are generally
    < 50 ng/litre. High concentrations of PAH have been measured in
    rainwater and especially in snow and fog. The concentrations of PAH in
    sediments are in the low microgram per kilogram range.

    PAH levels in soils near industrial sources (e.g. coal coking) are
    especially high, sometimes up to grams per kilogram. In contrast,
    soils contaminated by atmospheric deposition or runoff have
    concentrations of 2-5 mg/kg of individual PAH, and the concentrations
    in unpolluted areas are in the low microgram per kilogram range.

    PAH have been detected in vegetables but are mainly formed during food
    processing, roasting, frying, or baking. The highest levels were
    detected in smoked meat and fish, at up to 200 µg/kg food for
    individual PAH.

    Five-fold increases in the concentrations of PAH in soil have been
    observed over a 150-year period, although there are indications that
    the concentrations of some PAH are decreasing. Similar findings have
    been reported for sediments, perhaps because of measures to reduce
    emissions.

    Aquatic animals are known to adsorb and accumulate PAH. Especially
    high concentrations were found in aquatic organisms from highly
    polluted rivers, at levels up to milligrams per kilogram. Of the
    terrestrial animals, earthworms are a good indicator of soil pollution
    with PAH. The benzo[a]pyrene concentrations in the faeces of
    earthworms living in a highly industrialized region were in the low
    milligrams per kilogram range.

    The main sources of exposure for the general population appear to be
    food and air. The estimated intake of individual PAH in the diet is
    0.1-8 µg/d. The main contribution appears to be that of cereals and
    cereal products, due to the large amounts consumed. In ambient air,
    the main sources are residential heating and environmental tobacco
    smoke; exposure to PAH from environmental tobacco smoke in indoor air
    is estimated to be 6.4 µg/day.

    Occupational exposure to PAH occurs via the lung and skin. High
    exposure occurs during the processing and use of coal and mineral oil
    products, such as in coal coking, petroleum refining, road paving,
    asphalt roofing, and impregnation of wood with creosotes; high
    concentrations are also found in the air of aluminium production
    plants and steel and iron foundries. No measurements were available
    for the primary production and processing of PAH.

    5.1  Environmental levels

    5.1.1  Atmosphere

    Relevant data on the occurrence of PAH in ambient air are compiled in
    Tables 33-36. The concentrations were determined mainly by gas
    chromatography and high-performance liquid chromatography, usually
    with enrichment by filtration through a solid sorbent. The amount of
    particle-bound PAH is therefore given. In studies in which
    vapour-phase PAH were also sampled, the results for the vapour and
    particulate phases were combined (for reviews, see Grimmer, 1979;
    Ministry of Environment, 1979; Grimmer, 1983b; Lee & Schuetzle, 1983;
    Daisey et al., 1986; Baek et al., 1991; Menichini, 1992a).

    5.1.1.1  Source identification

    Qualitative indications of different sources can be obtained by
    comparing the PAH profiles, i.e. the ratio between the total PAH
    concentration and that of a selected PAH, in air with those of samples
    representative of the emitting sources or by determining PAH that are
    emitted mainly from a specific source (Menichini, 1992a). Quantitative
    assignments are difficult to make, however, owing to the complexity of
    factors that affect the variability of PAH concentrations and
    profiles.

    Measurements were made at selected sources of PAH in the area of
    Chicago, USA, in 1990-92, in order to identify them: Five samples were
    taken 100 m directly downwind of a coke plant in an area that was not
    affected by steel-making facilities, four samples from diesel buses at
    a parking garage, three samples from petrol vehicles under warm-engine
    operating conditions at a public parking garage, five samples in
    heavily travelled tunnels during evening rush hours, and two samples
    from the roof directly downwind of the chimney of fireplaces burning
    seasoned oak. The authors give a source distribution pattern in
    percent related to the total mass of 20 PAH. Naphthalene made by far
    the largest contribution to petrol engine and coke oven emissions (55
    and 89%, respectively). The three-ring compounds acenaphthylene,
    acenaphthene, fluorene, phenanthrene, anthracene, and retene were
    detected in large amounts in diesel motor emissions (56%) and in wood
    combustion exhausts (69%). The four-ring fluoranthene, pyrene,
    benz [a]anthracene, chrysene, and triphenylene and the five-ring
    cyclopenta [cd]pyrene, benzo [b]fluoranthene,
    benzo [k]fluoranthene, benzo [a]pyrene, benzo [e]pyrene, and
    dibenzo [ghi]perylene together contributed 28% to diesel engine

    emissions, 25% to petrol engine emissions, and 20% to wood combustion
    emissions (Khalili et al., 1995).

    The winter levels of PAH are higher than the summer levels (Gordon,
    1976; Lahmann et al., 1984; Greenberg et al., 1985; Chakraborti et
    al., 1988; Catoggio et al., 1989), due to more intensive domestic
    heating and to meteorological (lower inversions during the winter) and
    physicochemical factors (temperature-dependent partition between
    gaseous and particulate phases). The ratios of benzo [a]pyrene:CO, in
    which CO was used as an 'inert' tracer of automotive emissions, in Los
    Angeles, USA, were higher at night (0.18-0.34) than in the day
    (0.12-0.14), and substantially more so during winter (0.14-0.34) than
    in summer (0.12-0.18), consistent with daytime loss of PAH by chemical
    degradation (Grosjean, 1983).

    In studies of sources of PAH at commercial, industrial, and urban
    sampling sites in Athens, Greece, the effects of wind velocity and
    thermal inversion were studied. There seemed to be no direct
    correlation between benzo [a]pyrene and lead levels, which would be
    expected if exhaust from cars run on leaded petrol were the
    preponderant source of PAH (linear regression coefficient, 0.32-0.38)
    (Viras et al., 1987).

    Differences in the composition of profiles of PAH from different
    sources can also be standardized by giving the concentrations relative
    to that of a specific PAH. For particle-bound PAH, benzo [e]pyrene
    has often been used as a reference compound, since it is
    photochemically stable and found mainly in the particulate phase (Baek
    et al., 1991).

    Cyclopenta [cd]pyrene is emitted particularly from petrol-fuelled
    automobiles (Grimmer et al., 1981c). Fluoranthene, pyrene,
    benzo [ghi]perylene, and coronene are also found in higher
    concentrations in condensates of vehicle exhausts (Baek et al., 1991).
    The contribution of vehicles and domestic heating has also been
    estimated as the ratio of indeno[1,2,3- cd]pyrene to
    benzo [ghi]-perylene concentrations. The ratio should be 0.37 for the
    PAH profile in traffic exhaust and 0.90 for domestic heating (Lahmann
    et al., 1984; Jaklin & Krenmayr, 1985). In a comparison of the PAH
    ratios determined in New Jersey, USA, with those reported in the
    literature for samples collected under similar conditions in street
    tunnels, the ratios coronene:benzo [a]pyrene and
    benzo [ghi]perylene:benzo [a]pyrene indicated that vehicle traffic
    was the major source of PAH during the summer (Harkov et al., 1984).

    Measurements in ambient air in North Rhine Westphalia, Germany, in
    1990 indicated that coronene is the most characteristic PAH for
    automobile traffic. At a ratio of benzo [a]pyrene:coronene of < 3.5,
    vehicle traffic is the dominant PAH source, whereas emissions with
    ratios > 3.5 are influenced by other sources. The benzo [a]pyrene
    levels were 0.66-5.0 ng/m3, and those of coronene 0.57-2.5 ng/m3
    (Pfeffer, 1994).

    In a study of the PAH concentrations during weekdays and weekends in
    South Kensington, London, United Kingdom, no distinct differences were
    observed in winter, but the average concentrations were 1.5-2.5 times
    higher during the week than during the weekends in summer. Likewise,
    the diurnal variations appeared to be less distinct during winter than
    summer (Baek et al., 1992).

    Measurements in streets with high traffic density in Stockholm,
    Sweden, showed that the concentration of PAH decreased by 25-50%
    during holidays in comparison with weekdays. Benzo [a]pyrene in
    street air was all particle-bound, while chrysene and lighter PAH
    occurred both on particles and in the vapour phase (Östman et al.,
    1991, 1992a,b).

    In a study of 15 PAH in the air of various areas in an industrial city
    in Germany with 700 000 inhabitants, the highest levels were detected
    in air affected by a coke plant, where benzo [a]pyrene was found at
    1.4-400 ng/m3 and cyclopenta [cd]pyrene at none detected to 120
    ng/m3. The concentrations measured in air affected by vehicle traffic
    were 11-110 ng/m3 benzo [a]pyrene and 0.1-440 ng/m3
    cyclopenta [cd]pyrene. Within 4 km, the average concentration of 88
    ng/m3 cyclopenta [cd]pyrene had dropped to 1.6 ng/m3. The levels
    were lower in areas where hand-stoked residential coal heating
    predominated (0.37 µg/m3 benzo [a]pyrene and none detected to 39
    µg/m3 cyclopenta [cd]pyrene) and where oil heating predominated
    (0.2-66 ng/m3 and none detected to 15 ng/m3, respectively). The
    concentration of PAH was three to four times higher between 7:43 and
    10:00 than between 10:00 and 15:46. Benzo [c]phenanthrene,
    cyclopenta [cd]pyrene, benzo [ghi]perylene, and coronene dominated
    the PAH in areas with heavy traffic, whereas chrysene,
    benzo [b]fluoranthene, and benzo [a]pyrene occurred at the highest
    concentrations in an area surrounding a coke plant (Grimmer et al.,
    1981c).

    The use of receptor-source apportionment modelling was examined,
    despite its limited applicability to reactive species, for the PAH
    profiles of emissions from a variety of sources (Daisey et al., 1986;
    Pistikopoulos et al., 1990). In one study, benzo [b]fluoranthene,
    benzo [k]fluoranthene, benzo [a]pyrene, benzo [ghi]perylene,
    indeno[1,2,3- cd]pyrene, and coronene were measured in the ambient
    air of the centre of Paris, France. The concentrations of PAH varied
    from 42% in winter to 72% in summer for petrol-fuelled vehicles, from
    25 to 40% for diesel-fuelled vehicles, and from about 30 to 2% for
    domestic heating. The winter-summer differences were due mainly to
    different emission patterns and not to changes in the rate of decay of
    PAH (Pistikopoulos et al., 1990). In another study, the contributions
    of PAH from five sources to ambient air were distinguished by use of
    fuzzy clustering analysis (Thrane & Wikström, 1984).

    The information on PAH levels in ambient air is discussed below
    according to possible source: background and rural, industrial
    emissions, and diffuse sources like automobile traffic and residential
    heating. Attribution of different studies to these sections was
    difficult because the sources of PAH emissions are often mixed. For
    example, Seifert et al. (1986) determined PAH in Dortmund 200 m from a
    coke plant; this study was deemed to relate to PAH levels resulting
    from industrial emissions. The concentrations of PAH attributable to
    mobile sources can be estimated by monitoring near areas with heavy
    traffic in the summer, but it is difficult to estimate the
    contribution of home heating, because in winter PAH in ambient air
    derive from both mobile sources and home heating. Furthermore,
    emissions from mobile sources may differ in winter from those in the
    summer because of meteorological and physicochemical factors
    (Greenberg et al., 1985; see also section 5.1.1.3).

    5.1.1.2  Background and rural levels

    The levels in ambient air of rural areas are summarized in Table 33.
    Background levels were measured about 25 km from La Paz, Bolivia, at
    an altitude of 5200 m (Cautreels & van Cauwenberghe, 1977) and on the
    island of Mallorca, Spain, at an altitude of 1100 m (Simó et al.,
    1990). The concentrations were generally 0.01-0.1 ng/m3. The average
    values in rural areas are usually 0.1-1 ng/m3. Average concentrations
    of 0.34 and 0.27 ng/m3 benzo [a]pyrene were measured in two rural
    areas in Japan in 1989, with a maximum concentration of 1.1 ng/m3
    (Okita et al., 1994).

    5.1.1.3  Industrial sources

    PAH levels in ambient air resulting mainly from industrial emissions
    are summarized in Table 34. The average concentrations of individual
    PAH at ground level were 1-10 ng/m3. In general, aluminium smelters
    and industrial processes for the pyrolysis of coal, such as coking
    operations and steel mills, result in higher levels of PAH than most
    other point industrial sources. Furthermore, the levels of PAH are
    much higher downwind from major sources than upwind.

    The highest levels of individual PAH were measured near an aluminium
    smelter in Hoyanger, Norway, with maximum concentrations of 10-100
    ng/m3. Phenanthrene was present at very high levels in ambient air
    contaminated by industrial emissions (Thrane, 1987). In Sundsvall,
    Sweden, near an aluminium production facility, 310 ng/m3
    phenanthrene, 190 ng/m3 naphthalene, 120 ng/m3 pyrene, and 84 ng/m3
    fluorene were detected (Thrane & Wikström, 1984).

    The concentration of benzo [a]pyrene in ambient air near an oil
    processing plant in Moscow was up to 13 ng/m3 (Khesina, 1994).
    Benzo [a]pyrene was detected at 15-120 ng/m3 and perylene at 3-37
    ng/m3 at 39 measuring stations in the heavily polluted area of Upper
    Silesia, Poland. The maximum values were 950 ng/m3 for
    benzo [a]pyrene and 270 ng/m3 for perylene (Chorazy et al., 1994).


        Table 33. Polycyclic aromatic hydrocarbon concentrations (ng/m3) in ambient air of background and rural areas

                                                                                                                                             

    Compound                [1]     [2]     [3]         [4]          [5]        [6]       [7]        [8]     [9]        [10]       [11]
                                                                                                                                             

    Acenaphthene                                                                                             0.32       6.3-23
    Anthracene                      0.004                                       0.05                 0.03    < 0.05     1.2-3.9    ND-0.05
    Anthanathrene                                       0.004-0.16              0.08      0.07                          ND-0.2     ND-0.04
    Benz[a]anthracene               0.005   0.12                                0.4                  0.40    0.07       1.8-3.2    0.16-0.39
    Benzo[a]fluorene                                                                                                    0.8-3.3
    Benzo[a]pyrene                  0.006   0.005       0.002-0.12   0.33/0.47  0.6       ND-0.52    0.45    0.08       0.8-2.5    0.41-0.45
    Benzo[b]fluoranthene                    0.02                                                     1.2                           0.45-0.58
    Benzo[b]fluorene                                                                                 0.24               0.5-2.4
    Benzo[c]phenanthrene                                                                                                           0.15-0.20
    Benzo[e]pyrene                  0.022   0.006       0.007-0.26              0.6                  0.59               1.8-5.8    0.44-0.65
    Benzo[ghi]fluoranthene                                                                                              ND-0.2
    Benzo[ghi]perylene              0.009   0.002       0.005-0.40              0.6       ND-0.58                       1.4-3.0    0.89-1.4
    Benzo[k]fluoranthene                    0.02        0.002-0.088                                  0.48                          0.17-0.25
    Chrysene                                0.07a                                                    1.0                           0.13-0.19
    Coronene                                            0.005-0.23              0.24      ND-0.22                       0.4-0.9    0.16-0.26
    Cyclopenta[cd]pyrene                                                        0.2                                                0.16-0.39
    Dibenzo[a,h]pyrene                                                          0.14                                               0.02-0.07
    Dibenzo[a,l]pyrene                                                                               0.53
    Fluoranthene            0.041   0.030   0.18                     0.20/0.26  1.2       ND         0.93    1.3        11-47      0.19-0.23
    Fluorene                                0.45                                                             0.66       14-32
    Indeno[1,2,3-cd]pyrene          0.006   0.02                                0.7                  0.72                          0.43-0.65
    1-Methylphenanthrene                                                        0.09                                    0.7-2.8
    Naphthalene                                                                                              ND         3.0-98
    Perylene                                            0.001-0.026             0.09                 0.08               ND-0.4
    Phenanthrene                    0.026   2.66                                0.4       ND-0.43            4.2        26-70      ND-0.03
    Pyrene                  0.034   0.024   0.34        0.010-0.15   0.15/0.15  1.3       ND         0.60    0.73       8.8-26     0.16-0.26
                                                                                                                                             

    Table 33 (continued)


    ND, not detected; /, single measurements;
    [1] About 25 km from La Paz, Bolivia, at 5200 m (Cautreels & van Cauwenberghe, 1977);
    [2] Mallorca, Spain, 1989 (Simo et al.,1991);
    [3] Lake Superior, USA, 1986; sum of vapour and particulate phases (Baker & Eisenreich,1990);
    [4] Latrobe Valley, Australia, (Lyall at al.,1988);
    [5] Belgium, (Van Vaeck et al.,1980);
    [6] Denmark (Nielsen, 1984);
    [7] Western Germany, 1981 (Pflock et al.,1983);
    [8] Oostvoorne, Netherlands, (De Raat et al.,1987b);
    [9] Canada, 1989-91 (Environment Canada, 1994);
    [10] Sidsjon, Sweden, 1980-81, sum of vapour and particulate phases (Thrane & Wikstrom, 1984);
    [11] Folkestone, Ashford, United Kingdom, 1986 (Baek et al., 1992)
    a With triphenylene
    Analysed by high-performance liquid chromatography or gas chromatography; only particulates sampled, unless otherwise stated

    Table 34. Polycyclic aromatic hydrocarbon concentrations (ng/m3) in ambient air near industrial emissions

                                                                                                                                               

    Compound                [1]         [2]       [3]        [4]       [5]     [6]        [7]       [8]        [9]        [10]       [11]
                                                                                                                                               

    Acenaphthene                                                       23      9.8-372    15-122               3.7
    Acenaphthylene                                                     747                                     0.01
    Anthracene                          2.9/3.4                        158     4.5-6.1    4.1-43    0.12/0.15  0.01-3.4              0.08-0.19
    Anthanthrene            0.001/3.0   0.2/1.1                                ND-3.0               0.15/0.15                        0.13-0.22
    Benz[a]anthracene                   0.28/1.2                       7.6     2.0-158    2.5-58    0.8/3.1    0.02-1.2              1.3-4.7
    Benzo[a]fluorene                                                           1.1-179
    Benzo[a]pyrene          0.002/1.5   0.5/3.5   25/37      6.3-6.7   5.3     1.1-61     2.1-36    0.14/0.11  0.20-0.11  1.8-3.1    1.1-2.6
    Benzo[b]fluoranthene                0.9/1.8                        4.8                                                           2.7-6.4
    Benzo[b]fluorene                                                           0.7-122                                               0.61-1.4
    Benzo[e]pyrene          0.004/1.4   1.8/3.2                        11.6    2.5-86                                                1.3-3.1
    Benzo[ghi]fluoranthene                                                     ND-0.5               0.26/0.35
    Benzo[ghi]perylene      0.003/1.5   4.2/7.1                        O.7     2.2-45               0.35/0.33  0.25
    Benzo[j]fluoranthene                0.3/0.8
    Benzo[k]fluoranthene    0.001/0.67  0.3/1.3              8.0                                                                     1.0-2.2
    Chrysene                            1.6/3.8              14.7                                   0.22/0.29  0.01-1.6              2.5-7.5
    Coronene                0.003/1.5   3.2/2.8              1.3-1.5   ND      0.6-9.0              0.25/0.26
    Cyclopenta[cd]pyrene                                               2.2
    Dibenzo[a,h]pyrene                                                 ND                                      277
    Dibenzo[a,l]pyrene                                                                                                               1.0-1.5
    Fluoranthene                        0.8/3.4                        88.3    20-812     22-272    0.12/0.20  0.02-10               2.3-3.3
    Fluorene                                                           502     27-419     16-46                0.02-0.86
    Indeno[1,2,3-cd]pyrene              0.4/0.3                        1.1     3.8-38               0.28/0.27  0.10-7.7              1.4-2.4
    1-Methylphenanthrene                                                       2.5-58
    Naphthalene                                                        22 400  9.0-193    3.1-26    0.03-0.06
    Perylene                0.001/0.2   0.3/1.2                                0.1-8.3              0.05/0.05  22                    0.23-0.61
    Phenanthrene                                                       500     54-1760    58-390    0.11/0.16  0.02-152
    Pyrene                              1.4/3.8                        56.3    16-491     14-207    0.17/0.35  0.006-28              1.6-2.1
                                                                                                                                               

    Table 34 (continued)

    ND, not detected; /, single measurements;
    [1] Three sampling sites near various industries in Latrobe Valley, Australia (Lyall et al., 1988);
    [2] Near various industries, USA, 1971-72 (Gordon & Bryan, 1973);
    [3] Near a coke plant, Dortmund, Germany, 1982-83 (Seifert et al., 1986);
    [4] Near a coke plant, Dortmund, Germany, 1989 (Buck, 1991);
    [5] 100 m directly downwind of a coke plant, Chicago, USA, 1990-92 (Khalili et al., 1995);
    [6] Near aluminium smelters, Norway and Sweden, 1980-82 (analytical method not given) (Thrane, 1987); vapour and particulate phase
        (Thrane & Wikstrom, 1984);
    [7] Near aluminium smelter, Canada, 1989-91 (Environment Canada, 1994);
    [8] Near incineration plant, Sweden (Colmsjo et al., 1986a,b);
    [9] Near refinery, USA, 1981-83 (Karlesky et al., 1987);
    [10] Brown coal industry area, western Germany, 1983 (Seifert et al., 1986);
    [11] Near harbours, Netherlands (De Raat et al., 1987b)

    Analysed by high-performance liquid chromatography or gas chromatography; only particulates sampled, unless otherwise stated


    In Ontario, Canada, up to 140 ng/m3 benzo [k]fluoranthene, 110
    ng/m3 perylene, 110 ng/m3 benzo [a]pyrene, 90 ng/m3
    benzo [ghi]perylene, and  43 ng/m3 fluoranthene were found near a
    steel mill (Potvin et al., 1980). The benzo [a]pyrene concentrations
    near coke ovens in urban areas of the USA were more than double those
    in urban areas without coke ovens (Faoro & Manning, 1981). These
    results are consistent with those of Grimmer et al. (1981c), who
    detected maximum levels of benzo [a]pyrene, chrysene,
    benzo [b]fluoranthene, benzo [j]fluoranthene, and
    benzo [k]fluoranthene in the area surrounding a coke plant.

    The PAH concentrations in ambient air 900 and 2500 m from a municipal
    incineration plant were of the same order of magnitude, and no
    significant contribution from the plant to the ambient PAH
    concentrations was observed (Colmsjö et al., 1986a).

    The PAH levels in an industrial area of Ahmedabad City, India, were
    significantly higher than those in a residential area. The highest
    levels were found during winter, and the rate of degradation of
    airborne PAH was predicted to be lowest in the monsoon season. The
    most striking finding was the high concentration of
    dibenz [a,h]anthracene in urban air (5.3-23 ng/m3) (Raiyani et al.,
    1993a). The limited resolution of PAH may have resulted in
    overestimation: for instance, the concentrations of
    benzo [ghi]perylene and indeno[1,2,3- cd]pyrene reported are one
    order of magnitude higher than that of dibenz [a,h]anthracene.

    5.1.1.4  Diffuse sources

    A special situation of local importance was the pollution of ambient
    air in Kuwait after the war in the Persian Gulf, due to burning of oil
    fields. The mean concentrations of benzo [a]pyrene at three sampling
    sites were 0.27-9.2 ng/m3, and the maximum was 26 ng/m3 (Okita et
    al., 1994). These values are within the range of those detected in
    urban areas (see below).

     (a)  Motor vehicle traffic

    The concentrations of PAH in the ambient air of various urban areas
    are listed in Table 35. The average levels of individual PAH were 1-30
    ng/m3. Relatively high concentrations of benzo [a]pyrene,
    benzo [ghi]perylene, phenanthrene, fluoranthene, and pyrene were
    measured.

    Total PAH concentrations of 43-640 ng/m3 were measured in London,
    United Kingdom, in 1991, nearly 80% of which consisted of
    phenanthrene, fluorene, and fluoranthene; benzo [a]pyrene and
    benz [a]anthracene were present at 1% or less (Clayton et al., 1992).


        Table 35. Polycyclic aromatic hydrocarbon concentrations (ng/m3) in ambient air of urban areas

                                                                                                                                  

    Compound                [1]     [2]        [3]        [4]     [5]       [6]         [7]          [8]       [9]        [10]
                                                                                                                                  

    Acenaphthene                                                            0.4-101                            2.7-6
    Acenaphthlene                                                           0.9-39                             4.4-130
    Anthracene              34      0.6-36                                  0.3-2.1                            3.5-25
    Anthanthrene            2.5     0.1-4.7               30                < 0.1-0.6   0.003-0.76
    Benz[a]anthracene       10      0.3-27                        1.2-13    0.2-1.4     0.10-25                0.3-7.6
    Benzo[a]fluorene                                                        0.1-0.9                            0.8-6.9
    Benzo[a]pyrene          9.3     0.3-20                29      1.2-11    < 0.1-1.9   0.074-15               0.2-5.7
    Benzo[b]fluoranthene                                  43                            1.0-36
    Benzo[b]fluorene                                                        0.1-0.8                            0.6-7.3
    Benzo[c]phenathrene     4.0     0.2-5.0
    Benzo[e]pyrene          8.4     0.4-17                16      1.7-15    < 0.1-1.2   0.40-27                0.4-6.5
    Benzo[ghi]fluoranthene  12      0.3-5.0                                 0.1-1.5                            0.5-7
    Benzo[ghi]perylene      14      0.5-12     1.6/13     27      2.1-11    0.2-3.5     0.45-31      0.9-2.4   0.6-18
    Benzo[j]fluoranthene                                                                0.17-13
    Benzo[k]fluoranthene                                  23                            0.29-25
    Chrysene                                                                0.3-2.5     0.56-29      3.6-5.6              3.3
    Coronene                10      0.3-5.5               12      0.88-2.0  0.1-2.4     0.22-3.3               0.4-19
    Cyclopenta[cd]pyrene    11      0.1-4.8               71                < 0.1-1.1                          0.1-6
    Dibenzo[a,h]pyrene                                            0.22-3.4              0.29-2.8
    Fluoranthene            72      6.2-108    0.40/14                      1.4-10      0.80-14      1.3-2.0   6.9-38     15
    Fluorene                                                                1.3-61                             16-86
    Indeno[1,2,3-cd]pyrene  8.6     0.4-12                31                < 0.1-2.9   0.39-30                0.4-7.6
    1-Methylphenanthrene                                                    0.3-2.5                            5-16
    Naphthalene                                                                                                14-63
    Perylene                2.3     0.1-4.3               4.8               < 0.1-0.4   0.011-4.4              0.1-1.3
    Phenanthrene            153     18-223                                  3.6-41                             32-105     111
    Pyrene                  74      2.9-67     0.34/12                      1.2-5.5     0.34-10                5.5-45     20
    Triphenylene                                                                        0.15-6.9
                                                                                                                                  

    Table 35 (continued)

    ND, not detected; /, single measurements;
    [1] Vienna, Austria, 1983-84; vapour and particulate phase (Jaklin & Krenmayr, 1985);
    [2] Linz, Austria, 1985; vapour and particulate phase (Jaklin et al., 1988);
    [3] Antwerp, Belgium (Van Vaeck et al., 1980);
    [4] Berlin, western Gemany, 1984-85 (Seifert et al., 1986);
    [5] Rhein/Ruhr area, western Germany, 1985-88; analytical method not stated (Buck et al., 1989);
    [6] Kokkola, Finland (Pyysalo et al., 1987);
    [7] St Denis, France, 1979-80 (Muel & Saguem, 1985);
    [8] Various cities, Greece, 1984-85 (Viras et al., 1987);
    [9] Oslo, Norway, 1981-83, vapour and particulate phase (Larssen, 1985);
    [10] Barcelona, Spain, 1988-89, vapour and particulate phase (Albaiges et al., 1991)

    Analysed by high-performance liquid chromatography or gas chromatography; only particulates sampled,
    unless otherwise voted

    Table 35 (continued)

                                                                                                                                           

    Compound                [11]    [12]    [13]         [14]     [15]          [16]          [17]       [18]     [19]         [20]
                                                                                                                                           

    Acenaphthene                                                  0.07-3.58     0.05-31.1
    Acenaphthylene          9.1     0.8                                                       0.9
    Anthracene              21      1.4                  2.8      0.01-8.28     0.20-39.8     0.1-0.9             ND-4.8       6.1/11
    Anthanthrene                                         0.63
    Benz[a]anthracene       4.1     0.4                  1.4      0.24-10.6     0.12-18.5     0.2-5.8    5-21     0.07-2.1
    Benzo[a]fluorene        5.0     0.7
    Benzo[a]pyrene          2.9     0.2     0.99/1.4     1.6      0.01-7.02     0.18-13.7     0.3-3.4    1-17     0.04-3.2     0.6/1.6
    Benzo[b]fluoranthene                                 1.8      0.01-3.04     0.13-14.8     0.2-3.7    5-30     0.10-3.7
    Benzo[c]phenanthrene                                 2.8
    Benzo[e]pyrene          3.5     0.4     1.1/2.0      2.3                                                                   2.1/2.1
    Benzo[ghi]fluoranthene  7.3     0.8
    Benzo[ghi]perylene      6.6     0.5     2.9/3.3      3.3      0.02-6.90     0.15-85.3
    Benzo[k]fluoranthene                                 0.75                   0.23-16.5     0.3-0.8    3-22     0.07-0.85
    Chrysene                5.1     0.8                  1.6      0.04-4.97     0.13-24.3     0.2-5.5             ND-2.3
    Coronene                4.1     0.3     2.4/1.7      1.7      0.02-3.72     0.17-6.92                         ND-16
    Cyclopenta[cd]pyrene    3.9     0.11                 4.1
    Dibenz[a,h]pyrene                                    0.12
    Fluoranthene            24      3.9                  3.5                    2.03-62.4     22-23      14-54    0.24-2.0     8.0/9.7
    Fluorene                                                      0.07-27.6     0.07-161
    Indeno[1,2,3-cd]pyrene  3.8     0.5                  1.6                                  0.3-4.4    4.24
    Naphthalene                                                                                                                15/75
    Perylene                1.0     0.1                                                                                        0.2/0.5
    Phenanthrene            76      11                   5.1      0.06-111      2.25-492      0.1-2.4                          78/81
    Pyrene                  28      32                   18       0.39-17.4     0.33-64.4     0.1-7.5             0.48-3.6     8.0/12
    Triphenylene
                                                                                                                                           

    Table 35 (continued)

    ND, not detected;/, single measurements;
    [11] Stockholm, Sweden, April 1991; vapour and particulate phases (Ostman et al.,1992a,b);
    [12] Stockholm, Sweden; 1992 vapour and particulate phases (Ostman et al.,1992a,b);
    [13] London, United Kingdom, 1985-87(Baek et al.,1992);
    [14] London, United Kingdom, 1987; vapour and particulate phases (Baek et al.,1992);
    [15] Manchester, United Kingdom, 1990-91; vapour and particulate phases (Clayton et al.,1992);
    [16] Various cities, United Kingdom, 1991-92; vapour and particulate phases (Halsall et al.,1994);
    [17] Lake Baikal shore, Russian Federation, 1993-94 (Grachev et al.,1994);
    [18] Zagreb, Croatia, 1977-82; determined by thin-layer chromatography and fluorescence detector (Bozicevic et al.,1987);
    [19] Los Angeles, USA, 1981-82 (Grosjean, 1983);
    [20] Los Angeles basin, USA, 1986; vapour and particulate phases (Arey et al.,1987)

    Table 35 (contd)

                                                                                                                                           

    Compound                [21]       [22]        [23]       [24]        [25]     [26]      [27]          [28]         [29]     [30]
                                                                                                                                           

    Acenaphthene                       3.3-9.0     0.06-5.2                                                             0.6
    Acenaphthylene                     < 11-47                                                                          1.9
    Anthracene                         1.9-4.5     0.45-3.8                                  0.17-0.57     0.12-0.52    0.2      2.5-5.5
    Anthanthrene                                              0.006-3.3   1-11
    Benz[a]anthracene       0.07-1.4   0.19-0.40   0.19-4.4                                  0.99-7.0      0.37-1.7     1.9      20-66
    Benzo[a]fluorene                                                                                                             1.8-6.3
    Benzo[a]pyrene          0.11-1.6   ND-0.03     0.09-1.7   0.006-1.8   8-38               1.6-8.4       ND-2.3       3.4      30-120
    Benzo[b]fluoranthene    0.17-1.7                                                         3.1-12                     3.0      109-200
    Benzo[b]fluorene                                                                         0.19-0.94
    Benzo[e]pyrene          0.03-11    ND-0.04                0.016-2.3   4-19               2.7-9.0                    2.3      49-182
    Benzo[ghi]fluoranthene  0.12-1.3
    Benzo[ghi]perylene      0.24-2.7                          0.027-4.7   11-33              3.2-12                     3.4      34-141
    Benzo[j]fluoranthene    0.08-1.1                                                                                             22-66
    Benzo[k]fluoranthene    0.09-0.97                         0.005-0.85                     1.8-7.7                    2.7
    Chrysene                0.22-5.3   0.38-0.57                          3-15                             0.29-1.4     2.4
    Coronene                0.14-1.6                          0.020-2.3   5.16
    Dibenzo[a,a]pyrene      0.06-2.7
    Dibenzo[a,h]pyrene                                                                       0.46-1.2                   5.3-23
    Dibenzo[a,l]pyrene      0.05-0.35
    Fluoranthene                       5.7-10      1.6-11                          14-79     1.5-8.3                    1.0      11-26
    Fluorene                           7.4-14      0.94-5.5                                  0.08-0.15     0.31-1.2     2.8
    Indeno[1,2,3-cd]pyrene  0.20-2.9                                      6-24               2.6-12                     3.1
    Naphthalene                        280-940     ND                                                      4.5-13
    Perylene                0.01-0.15                         0.001-0.24  2-9                0.51-1.2
    Phenanthrene                       21-35       2.2-35                                    0.79-2.6      0.52-2.4     0.7      12-21
    Pyrene                  0.12-2.8   4.8-10      1.4-6.9    0.008-0.66           16-69     1.5-9.0       0.46-4.0     3.8      20-44
    Triphenylene                                                                                                                 22-60
                                                                                                                                           

    Table 35 (continued)

    ND, not detected; /, single nwasureme4s;
    [21] New Jersey, USA, 1981-82 (Greenberg et al, 1985);
    [22] Portland, Oregon, USA, 1984 (Ligocki et al.,1985);
    [23] Urban area (not specified), Canada, 1989-91 (Environment Canada,1994);
    [24] Latrobe Valley, Australia (Lyall et al., 1988);
    [25] Christchurch, New Zealand, 1979 (Cretney et al., 1985);
    [26] Osaka, Japan, 1977-78; vapour and particulate phases (Yamasaki et al., 1982);
    [27] Osaka, Japan, 1981-82 (Matsumoto & Kashimoto, 1985);
    [28] La Plata, Argentina, 1985 (Catoggio et al., 1989);
    [29] Ahmedabad City, India, 1984-85 (Raiyani at al.,1993a);
    [30] Calcutta, India, 1984 (Chakraborti et al.,1988)

    Table 35 (continued)

                                                                                                                                           

    Compound                 [31]       [32]         [33]       [34]    [35]      [36]         [37]         [38]        [39]       [40]
                                                                                                                                           

    Acenaphthene                                                                                                        4.5
    Anthraceene                                      14-16      2.5     1.8                                 ND-34       8.7-23
    Anthanthrene                        0.15-0.63                                 0.001-0.21                            2-24
    Benz[a]anthracene        2.9-4.8                 99-139     23      6.5       0.028-4.8                 3.1-9.8
    Benzo[alpyrene           3.8-5.5    0.005-1.3    67-73      15      5.6       0.023-4.6    Trace-9.3    ND-44       1.9-7.7    19-72
    Benzo[blfluoranthene                1.0-3.1      130-133            0.46-16
    Benzo[b]fluorene                    0.07-0.18
    Benzo[c]phenanthrene                             33-37
    Benzo[e]pyrene           5.5-7.4    0.016-3.3    96         19      9.1       0.18-8.8     0.17-4.2     ND-370                 9-41
    Benzo[ghi]fluoranthene   3.0-4.9    0.024-0.98   30-33
    Benzo[ghi]perylene       7.0-13     0.004-3.2    49-61      12      7.9       0.21-12                   ND-74                  11-49
    Benzo[j]fluoranthene                                                          2.6-5.5
    Benzo[k]fluoranthene     3.4-5.0                                              0.12-7.4
    Chrysene                 4.3-6.5    0.34-0.49    237-261    43      16        0.22-8.9     0.22-6.4     ND-170                 7-71
    Coronene                            0.002-1.4    14-16      3.1     2.8       0.14-2.1     Trace-2.1    8-96                   4-18
    Cyclopenta[cd]pyrene                             ND         3.1     1.6
    Dibenzo[a,h]pyrene                                                            0.012-0.98
    Fluoranthene             3.4-4.9    0.14-1.2                                  0.32-8.6                  8-520       15-51
    Fluorene                                                                                                            15-26
    Indeno[1,2,3-cd]pyrene   5.1-9.1    0.022-2.0    57         11      5.5       0.16-9.6                                         9-43
    Naphthalene                                                                                                         44
    Perylene                            0.01-0.20    7.6-10                       0.004-0.88                ND-28                  3-21
    Phenanthrene                        0.002-1.1                                                           4-170       50-271
    Pyrene                   3.6-6.6    0.002-0.58                                0.13-6.7     0.21-8.6     ND-540      12-49
    Triphenylene             1.4-1.9    0.07-0.24                                 0.11-2.9                  ND-50
                                                                                                                                           

    ND, not detected; /, single measurements;
    [31] Various cities, China (Chen et al.,1981);
    [32] Various cities, China, 1986-88; determined by thin-layer chromatography and gas chomatography-mass spectroscopy (Chang et
         al., 1988; Simoneit et al., 1991);
    [33] Various locations with predominantly coal heating; Germany (analytical method not given) (Grimmer, 1980);
    [34] Essen, Germany, predominantly coal heating, 1978-79 (Buck, 1983);
    [35] Essen, Germany, predominantly oil heating, 1978-79 (Buck, 1983);
    [36] Antony, France, 1979-80 (Muel & Saguem, 1985);
    [37] Sutton Coldfield, United Kingdom, 1976-78 (Butler & Crossley, 1982);
    [38] Barrow, USA, fossil fuel combustion area, 1979 (Daisey et al., 1981);
    [39] Wood-heating area, Canada, 1989-91 (Environment Canada, 1994);
    [40] Christchurch, New Zealand, 1979 (Cretney et al., 1985)


    In Delft, the Netherlands, benzo [a]pyrene levels of up to 140 ng/m3
    were measured on a foggy day with low wind velocity near a major road.
    High concentrations of pyrene (220 ng/m3), benzo [ghi]perylene (130
    ng/m3), and coronene (21 ng/m3) were also found. At border crossings
    between the Netherlands and Germany on days with heavy traffic, the
    maximum levels of individual PAH were 1-54 ng/m3 (Brasser, 1980).

    PAH concentrations were determined in the centre of Paris, France, at
    the top of a 55-m tower and thus less likely than ground-level samples
    to be affected by traffic emissions and street dust; they can
    therefore be considered to be homogeneous and representative. The
    maximum levels found were 98 ng/m3 benzo [ghi]perylene, 60 ng/m3
    indeno[1,2,3- cd]pyrene, 34 ng/m3 coronene, 28 ng/m3
    benzo [b]fluoranthene, 13 ng/m3 benzo [a]pyrene, and 13 ng/m3
    benzo [k]fluoranthene (Pistikopoulos et al., 1990).

    The average concentration of individual PAH in particulate and vapour
    phases during a nine-day photochemical pollution episode in
    California, USA, in 1986 was 1 ng/m3. The maximum levels of
    acenaphthene, acenaphthylene, fluorene, and phenanthrene ranged from
    30 to 64 ng/m3 (Arey et al., 1991).

    In 1989, the average benzo [a]pyrene concentrations in five Japanese
    cities (Sapporo, Tokyo, Kawasaki, Nagoya, and Osaka) were 1.2-3.1
    ng/m3. A maximum level of 15 ng/m3 was detected in Tokyo (Okita et
    al., 1994). A detailed examination was undertaken of the molecular
    composition of PAH in street-dust samples collected from the Tokyo
    metropolitan area. Unsubstituted ring systems (i.e. parent PAH)
    ranging from phenanthrene with three rings to benzo [ghi]perylene
    with six rings were the primary components, three- and four-ring PAH
    (i.e. phenanthrene, fluoranthene, and pyrene) predominating. The
    concentrations of total PAH were of the order of a few micrograms per
    gram of dust. On the basis of the PAH profile, it was suggested that
    PAH in the dust of busy streets arose mainly from automobile exhausts,
    while residential areas received a greater contribution from
    stationary sources. In both types of dust, asphalt was thought to
    contribute to only a minor extent (Takada et al., 1990). Giger &
    Schaffner (1978) had come to the same conclusion some 20 years
    earlier.

    Benzo [a]pyrene was detected in ambient air in Moscow, Russian
    Federation, at concentrations of 5.4 ng/m3 at a regular traffic site
    and 20 ng/m3 at a crossroads with heavy traffic (Khesina, 1994).

     (b)  Road tunnels

    In road tunnels, the concentrations of individual PAH were usually
    1-50 ng/m3 (Table 36). Higher levels were reported in tunnels in
    western Germany, with concentrations of 84 and 96 ng/m3
    cyclopenta [cd]pyrene (Buck (1983) and 76 ng/m3 (Brasser, 1980) and
    110 ng/m3 pyrene (Benner et al., 1989).


        Table 36. Polycyclic aromatic hydrocarbon concentrations (ng/m3) in ambient air polluted predominantly by vehicle exhaust

                                                                                                                                        

    Compound                 [1]       [2]       [3]       [4]       [5]       [6]       [7]       [8]       [9]       [10]      [11]
                                                                                                                                        

    Acenaphthene                                                                                             168
    Acenaphthylene                                                   32                                      445
    Anthracene               8.6/9.8             2.3       55                                      0.6-12    177
    Anthanthrene                                           7.2                 1 500                                   0.1-4.5   2-82
    Benz[a]anthracene        37/44               0.6-1.9   16        20        12 000    102       1.9-2.9   90.2
    Benzo[a]fluorene                                                 18        2 800
    Benzo[a]pyrene           30        2-14      0.2-0.8   16        12        9 600     66        1.3-26    62.6      0.1-14    1-57
    Benzo[b]fluoranthene                                   2.3       8.8       12 000                        43.6
    Benzo[e]pyrene           28/32                                   11        9 600     69        1.5-19    55.5      01-12     3-43
    Benzo[ghi]fluoranthene                                 29        18                            3.2-26
    Benzo[ghi]perylene       40/47     4-16      0.4-2.6   44        30        19 000    85        1.8-18    17.0      0.6-27    20-213
    Benzo[k]fluoranthene                                   8.1       9.7       9 000                         41.2
    Chrysene                 54/58                         25        15        9 500                         77.9
    Coronene                 26/27     2-17      0.3-1.1   29        20        7 500               1.0-10    ND        0.3-14    9-156
    Cyclopenta[cd]pyrene     84/96                         40        31                            7.6-65    100
    Dibenzo[a,h]pyrene                                                                                       14.7
    Fluoranthene                                                     35        83        93        6.4-69    117
    Fluorene                                                                                                 406
    Indeno[1,2,3-cd]pyrene   18/22               0.3-1.3   16        13        9 400               0.3-15    20.0                6-70
    1-Methylphenanthrene                                                                           2.6-43
    Naphthalene                                                                                              8030
    Perylene                                               3.4       3.1       1 500                                             1-18
    Phenanthrene                                           8.1       243                           4.4-56    300
    Pyrene                             33-114              47        122       16 000    120       9.7-76    193       0.2-29
                                                                                                                                        

    Table 36 (continued)


    ND, not detected; /, single measurements;
    [1] Street tunnel (location not specified), western Germany, 1978-79 (Buck, 1983);
    [2] Coen Tunnel, Netherlands (Brasser, 1980);
    [3] Street tunnel in Lincoln, Netherlands, 1981 (Kebbekus et al., 1983),
    [4] Klara Tunnel, Sweden, 1983 (Colmsjo et al., 1986b);
    [5] Soderleds Tunnel, Sweden, 1991; vapour and particulate phases (Ostman et al., 1991);
    [6] Craeybeckx Highway Tunnel, Belgium, 1991 (De Fré et al., 1994);
    [7] Baltimore Harbor Tunnel, USA, 1975 (Fox & Staley, 1976);
    [8] Baltimore Harbor Tunnel, USA, 1985-86 (Benner et al., 1989);
    [9] Heavily travelled tunnel, Chicago area, USA, 1990-92 (Khalili et al., 1995);
    [10] Diesel bus garage, United Kingdom, 1979 (Waller et al., 1985);
    [11] Inside car park, New Zealand (Cretney et al., 1985)

    Analysed by high-performance liquid chromatography or gas chromatography; only particulates sampled, unless otherwise stated


    PAH were found at levels of up to 4 ng/m3 in an underground bus
    terminal in Stockholm, Sweden; and 21 ng/m3 fluoranthene, 11 ng/m3
    pyrene, and 8.1 ng/m3 phenanthrene were found in a subway station
    (Colmsjö et al., 1986b).

    Very high concentrations of PAH were found in the air of the
    Craeybeckx Highway Tunnel in Belgium, which was used daily by an
    average of 45 000 vehicles, of which 60% were petrol-fuelled passenger
    cars, 20% diesel-fuelled cars, and 20% trucks. Of the cars, only 3%
    had three-way catalysts (De Fré et al., 1994).

     (c)  Residential heating

    The PAH levels in ambient air resulting mainly from residential
    heating are included in Table 35, as the source cannot be identified
    properly (see section 5.1.1.1).

    The use of wood and coal for heating was the source of high levels of
    benzo [a]pyrene in Calcutta, India (up to 120 ng/m3; Chakraborti et
    al., 1988). The concentrations of individual PAH in Calcutta ranged
    from 1.3 to 200 ng/m3, the highest levels being those of
    benzo [e]pyrene, benzo [ghi]perylene, and benzo [b]fluoranthene.
    The average levels of individual PAH resulting from domestic heating
    in Christchurch, New Zealand were 1-210 ng/m3, benzo [ghi]perylene
    and coronene showing the highest levels (Cretney et al., 1985), and up
    to 43 ng/m3 were measured in Essen-Vogelheim, Germany (Buck, 1983).
    High concentrations of individual PAH were determined in a residential
    area heated primarily by coal, with levels of up to 260 ng/m3
    chrysene, benz [a]anthracene, and benzo [b]fluoranthene (Grimmer,
    1980).

    The following PAH levels were measured on a roof directly downwind of
    the chimney of a fireplace burning seasoned oak in the Chicago area,
    USA: 1.8 µg/m3 acenaphthylene, 0.40 µg/m3 naphthalene, 0.35 µg/m3
    anthracene, 0.22 µg/m3 phenanthrene, 0.20 µg/m3 benzo [a]pyrene,
    0.20 µg/m3 benzo [e]pyrene, 0.13 µg/m3 fluorene, 0.10 µg/m3
    pyrene, 0.096 µg/m3 fluoranthene, 0.052 µg/m3 acenaphthene, 0.045
    µg/m3 benzo [k]fluoranthene, 0.033 µg/m3 chrysene, 0.030 µg/m3
    cyclopenta [cd]pyrene, 0.023 µg/m3 benzo [b]fluoranthene, and 0.019
    µg/m3 benz [a]anthracene. The levels of indeno[1,2,3- cd]pyrene,
    dibenz [a,h]anthracene, benzo [ghi]perylene, and coronene were below
    the limit of detection (Khalili et al., 1995).

    In a comparison of the PAH concentrations in ambient air in eastern
    and western Germany, the concentrations in rural areas were 3-12 times
    higher in eastern than in comparable western parts of the country. The
    PAH profiles were slightly different: the concentrations of the
    lower-boiling-point PAH fluoranthene and pyrene were 110 and 68 ng/m3
    in eastern and 36 and 28 ng/m3 in western Germany. The differences
    may be due to the different types of brown and hard coal burnt (Jacob
    et al., 1993a).

    In 1991, PAH were determined in the air of Berchtesgaden, a national
    park in Germany, and of the Oberharz (Ministry of Environment, 1993).
    The concentration of phenanthrene, fluoranthene, and pyrene (about 14
    ng/m3) in the Oberharz was two to three times higher than in
    Berchtesgaden, due to the use of brown coal for heating. The levels of
    the other PAH were of the same order of magnitude: benz [a]anthracene
    and benzo [b]fluoranthene plus benzo [j]fluoranthene plus
    benzo [k]fluoranthene, about 5 ng/m3; and benzo [ghi]fluoranthene,
    benzo [c]phenanthrene, benzo [e]pyrene, benzo [a]-pyrene,
    indeno(1,2,3- cd)pyrene, dibenz [a,h]anthracene,
    benzo [ghi]perylene, anthanthrene, and coronene, < 1 ng/m3.

    A model calculation for Germany showed that 5000 oil-heated houses
    contributed to the pollution of ambient air by benzo [a]pyrene to the
    same extent as one coal-heated house. It was assumed that one German
    household consumes annually about 5000 litre of heating oil, producing
    a maximum of 5 mg of benzo [a]pyrene (about 1 µg/litre combusted
    oil). On the basis of a consumption of a similar amount of hard coal,
    the same household would have an output of 25 g benzo [a]pyrene
    (about 5000 µg/kg combusted hard coal) annually (J. Jacob, 1994,
    personal communication).

    5.1.2  Hydrosphere

    PAH are found in the hydrosphere (Borneff & Kunte, 1983; Müller,
    1987), mostly as a result of urban runoff, with smaller particles from
    atmospheric fallout and larger ones from asphalt abrasion (Hoffman et
    al., 1984). Long-range atmospheric transport of PAH has been well
    documented in different countries (Lunde & Bjœrseth, 1977; see also
    section 4.1.2). After PAH are emitted into the atmosphere, for example
    in motor vehicle exhaust, they are transferred into water by direct
    surface contact or as a result of rainfall (Grob & Grob, 1974; Van
    Noort & Wondergem, 1985a,b; Kawamura & Kaplan, 1986). The higher
    levels of PAH that are found during winter months reflect increased
    emissions resulting from domestic heating (Quaghebeur et al., 1983;
    Thomas, 1986; see also section 5.1.1.1); however, the major source of
    PAH varies for each body of water.

    Anthropogenic combustion and pyrolysis and urban runoff containing
    atmospheric fallout, asphalt particles, tyre particles, automobile
    exhaust condensate and particulates, and lubricating oils and greases
    were the major sources of PAH in lakes in Switzerland (Wakeham et al.,
    1980a,b).

    Comparisons between the levels of individual PAH in precipitation and
    those in surface water showed that all of the precipitation samples
    were more highly polluted with PAH, because they had been 'washed out'
    of the atmosphere. Nearly all of the samples contained > 100 ng/litre
    of fluoranthene, benzo [b]fluoranthene, pyrene,
    indeno[1,2,3- cd]pyrene, phenanthrene, and naphthalene. The highest
    levels of PAH in rainwater were found in Leidschendam, the
    Netherlands, where pyrene concentrations < 2000 ng/litre,

    fluoranthene concentrations < 1700 ng/litre, and benzo [a]pyrene
    and benzo [b]fluoranthene concentrations < 390 ng/litre were
    detected (van Noort & Wondergem, 1985b).

    Most surface water samples contained concentrations of < 50
    ng/litre of individual PAH. The levels in rainwater were 10-200
    ng/litre, whereas those in snow were < 1000 µg/kg, with a maximum
    of 6800 µg/kg for an individual PAH (Lygren et al., 1984). In one fog
    sample, benzo [a]pyrene was found at 880 ng/litre and fluoranthene at
    3800 ng/litre (Schrimpff, 1983: see section 5.1.2.4).

    In sediment the levels of individual PAH were usually 1000-10 000
    µg/kg dry weight, which are one order of magnitude higher than those
    in precipitation. Triphenylene was detected in samples of sediment
    from the Mediterranean Sea (France) at 2-600 µg/kg (Milano et al.,
    1985) and in samples from Lake Geneva (Switzerland) at 25 µg/kg
    (Dreier et al., 1985; see section 5.1.3).

    5.1.2.1  Surface and coastal waters

    The levels of individual PAH found in surface and coastal waters at
    various locations are summarized in Table 37. Rivers in Germany
    contained some PAH at concentrations of 1-50 ng/litre (Grimmer et al.,
    1981b; Ernst et al., 1986; Regional Office for Water and Waste
    Disposal, 1986; Kröber & Häckl, 1989) and fluoranthene, pyrene,
    chrysene, benzo [a]pyrene, and benzo [e]pyrene at concentrations
    < 100 ng/litre. The PAH levels in seawater from the German coast
    varied over one order of magnitude depending on the sampling site. In
    open seawater, the concentrations of two- to four-ring PAH -
    naphthalene, fluorene, phenanthrene, fluoranthene, and pyrene - were
    0.1-5 ng/litre, and those of five- to six-ring PAH ranged from < 0.01
    to 0.2 ng/litre. Near the coast, the concentration of five- to
    six-ring PAH increased with the content of particles, to which they
    have greater affinity than two- to four-ring PAH (German Federal
    Office for Sea Navigation and Hydrography, 1993).

    The maximum levels of PAH in the Rivers Thames and Trent in the United
    Kingdom were > 130 ng/litre. The highest levels of individual PAH in
    the River Thames were 360 ng/litre fluoranthene, 350 ng/litre
    benzo [a]pyrene, 210 ng/litre indeno[1,2,3- cd]pyrene, 160 ng/litre
    benzo [ghi]perylene, 140 ng/litre benzo [k]fluoranthene, and 130
    ng/litre perylene (Acheson et al., 1976). More recent data were not
    available.

    In Norway, the levels of most individual PAH were > 100 ng/litre. For
    example, surface water from Bislet Creek near Oslo contained
    fluoranthene, pyrene, phenanthrene, methylphenanthrene, naphthalene,
    acenaphthene, acenaphthylene, and fluorene at concentrations > 1000
    ng/litre (Berglind, 1982).


        Table 37. Polycyclic aromatic hydrocarbon concentrations (ng/m3) in surface and coastal waters

                                                                                                                                     

    Compound                  [1]       [2]         [3]      [4]        [5]       [6]        [7]      [8]       [9]        [10]
                                                                                                                                     

    Acenaphthene                                                                                                14-1232
    Acenaphthylene                                                                0.4-0.9                       12-1024
    Anthracene                1                                                              10                 18-932
    Anthanthrene                                             0.2-0.5    15/1.8
    Benz[a]anthracene         ND                    0.16     2.2-6.8    24/66                40/10    71-582
    Benzo[a]fluorene                                                                                            43/330
    Benzo[a]pyrene            1-23      0.8         0.39     1.2-7.3    87/25     18         10/60    ND-40     19-311     0.9
    Benzo[b]fluoranthene                0.1-0.5     0.07                                     80/20    ND-42     70-678     0.5-0.9
    Benzo[b]fluorene          38                                                                                17
    Benzo[c]phenanthrene                                     2.3-4.2    13/34                                   23-172
    Benzo[e]pyrene            2-40                  0.06     7.1-11     108/36                                  40-551
    Benzo[ghi]fluoranthene
    Benzo[ghi]perylene        ND        ND          < 0.05   3.7-7.0    61/16                50/10    ND-61     33-636     ND
    Benzo[k]fluoranthene                0.7-0.8     0.02     3.6-6.1    59/22                40/10    ND-24                0.2-0.5
    Chrysene                                                 11-15      36/87     14         10/10
    Coronene                                                 ND-2.4     15/4.3
    Cyclopenta[cd]pyrene                                     ND         ND
    Dibenzo[a,h]pyrene                              <0.03                                    30/10
    Fluoranthene              4-616     1.0-3.5     0.35     5.2/9.1    28/102    2.3-13     50/130   2-110     285-3269   3.4-5.1
    Fluorene                  2                     0.63                          0.6-1.2                       25-1995
    Indeno[1,2,3-cd]pyrene              Trace       < 0.03   2.8-6.1    63/13                50/20    ND-39     17-299     ND
    1-Methylphenanthrene                                                                                        30-1281
    5-Methylcholanthrene
    Naphthalene               4                                                                                 50-2090
    Perylene                                                 0.8-1.4    27                   20                 9/28
    Phenanthrene              3-136                 3.5                           1.5-9.1                       101-5656
    Pyrene                    5-402                 0.28     4.8/8.5    25/90     2.2-13     100/30             485-3099
    Triphenylene
                                                                                                                                     

    Table 37 (continued)


    ND, not detected; /, single measurements;
    [1] Lake water, Norway, 1981-82 (Gjessing et al., 1984);
    [2] Lake water, Switzerland (Vu Duc & Huynh, 1981);
    [3] Lake Superior, USA, 1986 (Baker & Eisenreich, 1990);
    [4] Elbe River, Germany, 1980 (Grimmer et al., 1981b);
    [5] Elbe River, main drainage channel, Germany, 1980 (Grimmer et al., 1981b);
    [6] Water in various rivers, Germany, 1981-83 (Ernst et al., 1986);
    [7] Water in various rivers, Germany, 1985; analytical method not given (Regional Office for Water and Waste Disposal,
        1986);
    [8] Water in various rivers, Germany, 1985-86; analytical method not given (Krober & Hackl (1989);
    [9] River water, Norway, 1979 (Berglind, 1982);
    [10] River water, Switzerland (Vu Duc & Huynh, 1981)

    Analysed by high-performance liquid chromatography or gas chromatography, unless otherwise stated. The results of studies
    in which water samples were filtered through solid sorbents may be underestimates of the actual PAH content (see section
    2.4.1.4).

    Table 37 (continued)

                                                                                                                                         

    Compound                  [11]      [12]        [13]       [14]     [15]      [16]        [17]       [18]        [19]        [20]
                                                                                                                                         

    Acenaphthene                                               ND-3     10                               0.08-1.1                50-100
    Acenaphthylene                                             ND-5                                      0.02-1.7                80-1300
    Anthracene                                                 ND-4     0.2       0.8-9.5                0.01-1.5    < 1-25      ND
    Anthanthrene                                                                                                                 NR
    Benz[a]anthracene                                          ND-5     0.3       ND-9.6                 0.04-6.8                ND
    Benzo[a]fluorene                                                                                                             NR
    Benzo[a]pyrene            0.1-1.8   130-150     0.1/0.2    ND-10    0.2-1.0                          0.03-8.8                ND
    Benzo[b]fluoranthene                                       ND-8                                      0.04-12
    Benzo[b]fluorene                                                              4.0-19                                         NR
    Benzo[c]phenanthrene                                                                                                         NR
    Benzo[e]pyrene                                                                                       0.02-8.8                ND
    Benzo[ghi]fluoranthene                                                                                                       NR
    Benzo[ghi]perylene        0.2-11    30-160      0.7/0.8    ND-10                                     0.02-3.8    < 0.3-16    50
    Benzo[k]fluoranthene      0.1-1.7   80-140      0.2/0.3    ND-13                                     0.02-7.7
    Chrysene                                                   ND-12                                                             NR
    Coronene                                                                                             0.01-1.4                NR
    Dibenzo[a,h]pyrene                                         ND-1                                                              100
    Fluoranthene              0.7-508   20-360      1.1/3.7    3-12     0.8       10-25       1.4-2.6    0.40-14                 NR
    Fluorene                                                   ND-2     0.7-15                1.9-5.2    0.33-3.2                70-2500
    Indeno[1,2,3-cd]pyrene    0.1-8.0   50-210      ND/0.2     ND-8                                      0.01-3.5                NR
    1-Methylphenanthrene                                                                                                         NR
    5-Methylcholanthrene                                                                                                         NR
    Naphthalene                                                4-34     3.6                              0.4-9.2                 NR
    Perylene                            40-130                                                           0.01-5.7                NR
    Phenanthrene                                               6-34     21-18     8.0-93      2.4-2.7    0.24-5.8    < 1-3       ND
    Pyrene                              50-260                 1-15     0.3-15    8.8-25      0.82-1.7   0.12-15     < 1-53      10-65
    Triphenylene                                                                                                                 NR
                                                                                                                                         

    Table 37 (continued)

    ND, not detected; /, single measurements;
    [11] River water, United Kingdom, 1974 (Lewis, 1975);
    [12] Water in various rivers, United Kingdom, analytical method not given (Acheson et al.,1976);
    [13] Water in various rivers, United Kingdom; analytical method not given (Sorrell et al., 1980);
    [14] River water, USA, 1984 (De Leon et al., 1986);
    [15] Surface water, Canada (Environment Canada, 1994);
    [16] River water, China, 1981 (Wu et al., 1985);
    [17] Coastal water, Germany, 1982 (Ernst et al., 1986);
    [18] Seawater, Germany, 1990 (German Federal Office for Sea Navigation and Hydrography, 1993);
    [19] Coastal water, Australia, 1983 (Smith et al., 1987);
    [20] Water (no further specification), Japan, 1974-91 (Environment Agency, Japan, 1993)

    Analysed by high-performance liquid chromatography or gas chromatography, unless otherwise stated. The results of studies
    in which water samples were filtered through solid sorbents may be underestimates of the actual PAH content (see section
    2.4.1.4).


    The highest concentrations of PAH in water in Canada were reported for
    water samples from ditches next to utility and railway lines near
    Vancouver. The highest mean concentrations were measured near utility
    poles treated with creosote, with values of 2000 µg/litre for
    fluoranthene, 1600 µg/litre for phenanthrene, and 490 µg/litre for
    naphthalene (Environment Canada, 1994).

    Four individual PAH were detected in seawater from Green Island,
    Australia. The highest levels of PAH found were 53 ng/litre pyrene, 25
    ng/litre anthracene, 16 ng/litre benzo [ghi]perylene, and 3 ng/litre
    phenanthrene, (Smith et al., 1987).

    The total content of phenanthrene, anthracene, fluoranthene, pyrene,
    benzo [b]fluorene, and benz [a]anthracene in the Yellow River,
    China, was 170 ng/litre (Wu et al., 1985; for individual PAH
    concentrations, see Table 37).

    The PAH levels found in the River Rhine in Germany and the Netherlands
    and in some of its tributaries are summarized in Table 38. Many
    investigators have detected PAH in the Rhine. The lowest
    concentrations of benzo [a]pyrene, < 10-20 ng/litre, were found in
    the Rhine at Lobith and Hagestein in Germany and at Lek in the
    Netherlands in 1987-90 (Association of Rhine and Meuse Water Supply
    Companies, 1987-90), when the levels of fluoranthene were 70-140
    ng/litre. In 1976-79, the Rhine at Lek and Waal contained < 10-580
    ng/litre of benzo [a]pyrene (Association of Rhine and Meuse Water
    Supply Companies, 1976-79), so that the levels had decreased by one
    order of magnitude within 14 years. The sum of fluoranthene,
    benzo [b]fluoranthene, benzo [k]fluoranthene, benzo [a]pyrene,
    benzo [ghi]perylene, and indeno[1,2,3- cd]pyrene) was 9-40 ng/litre
    at km 30 and 130-5700 ng/litre at km 853, indicating that the level of
    pollution increased markedly between the source and the estuary
    (Borneff & Kunte (1983). The average concentrations of individual PAH
    were 1-50 ng/litre, although individual PAH were found at
    concentrations in the range 100-200 ng/litre near Mainz, an
    industrialized town (Borneff & Kunte, 1964, 1965). In general, the PAH
    levels in the Rhine decreased by a factor of 3 between 1979 and 1989.

    The Emscher and Ruhr waterways in Germany have been heavily polluted
    (see Table 38). In 1985, the Emscher River contained 6400 ng/litre
    fluoranthene, 6000 ng/litre pyrene, 2000 ng/litre benz [a]anthracene,
    1100 ng/litre dibenz [a,h]anthracene, 910 ng/litre benzo [a]pyrene,
    880 ng/litre chrysene, 630 ng/litre indeno[1,2,3- cd]pyrene, 510
    ng/litre benzo [ghi]perylene, 270 ng/litre anthracene, 220 ng/litre
    perylene (Regional Office for Water and Waste Disposal, 1986), but by
    1989 the levels had decreased by about one order of magnitude
    (Regional Office for Water and Waste Disposal, 1990 ). The PAH
    concentrations in the Emscher were three times higher than those in
    the Rhine near Mainz. Between 1985 and 1989, the PAH levels in the
    Emscher decreased further by a factor of 15; however, the levels in
    the Ruhr remained about the same or increased slightly between 1979
    and 1985 (Regional Office for Water and Waste Disposal, 1986, 1988,
    1990).


        Table 38. Polycyclic aromatic hydrocarbon concentrations (ng/m3) in the River Rhine and some highly polluted tributaries

                                                                                                                                    

    Compound                 [1]         [2]         [3]         [4]         [5]         [6]         [7]         [8]         [9]
                                                                                                                                    

    Anthracene                                                   10                      270         25-260                  10
    Anthanthrene             0.9-11                                                                              1.3
    Benz[a]anthracene        6.1-31                              11-50                   1970        100-780     13          20
    Benzo[a]pyrene           0.8-36      ND-7        6-30        12-40       < 10-20     910         59-280      15          30
    Benzo[b]fluoranthene                 ND-8        7-30        12-40       < 10-30     880         62-310                  40
    Benzo[c]phenanthrene     1.5-9.1                                                                             1.9
    Benzo[a]pyrene           18-31                                                                               33
    Benzo[ghi]fluoranthene   1.0-11                                                                              2.2
    Benzo[ghi]perylene       15-29       ND-8        6-30        9-30        < 10-20     510         30-210      17          30
    Benzo[k]fluoranthene                 ND-4        2-14        6-20        < 10-40     440         36-150                  20
    Chrysene                 21-62                                                       1080                    27          30
    Dibenzo[a,h]pyrene                                           10-40                   1100        32-310                  30
    Fluoranthene                         4-18        15-61       25-77       20-140      6420        207-1700    60
    Indeno[1,2,3-cd]pyrene   9.5-27      ND-6        2-26        10-40       < 10-20     630         28-220      17          30
    Perylene                 ND-8.1                              10                      220         13/80       2.1         10
    Pyrene                                                       20-50                   6010        155-1100                50
                                                                                                                                    

    ND, not detected; /, single measurements;
    [1] Rhine, Germany, 1979 (Grimmer et al.,1981b);
    [2] Rhine, Germany, 1985-88, analytical method not given (Krober & Hackl, 1989);
    [3] Rhine, Netherlands, 1985-88 (Netherlands' Delegation, 1991);
    [4] Rhine, Germany, 1987-89, analytical method not given (Regional Office for Water and Waste Disposal, 1988, 1989, 1990);
    [5] Rhine, Netherlands; 1987-90, analytical method not given (Association of Rhine and Meuse Water Supply Companies, 1987-90);
    [6] Emscher, Germany, 1985, analytical method not given (Regional Office for Water and Waste Disposal, 1986);
    [7] Emscher, Germany, 1987-89, analytical method not given (Regional Office for Water and Waste Disposal, 1988, 1989, 1990);
    [8] Ruhr, Germany, 1979 (Grimmer et al., 1981b);
    [9] Ruhr, Germany, 1985, analytical method not given (Regional Office for Water and Waste Disposal, 1986)


    The PAH levels in the main drainage channels of the River Elbe,
    Germany, were one order of magnitude higher than in the river water
    (Grimmer et al., 1981b), owing to the high input of rainwater to the
    channels.

    5.1.2.2  Groundwater

    The PAH concentrations in uncontaminated groundwater in the
    Netherlands generally did not exceed 0.1 µg/litre, but levels of about
    30 µg/litre naphthalene, 10 µg/litre fluoranthene, and 1 µg/litre
    benzo [a]pyrene were reported in contaminated groundwater (Luitjen &
    Piet, 1983).

    Benzo [a]pyrene levels in groundwater in western Germany ranged from
    0.1 to 0.6 ng/litre and those of total PAH from 34 to 140 ng/litre
    (Andelman & Suess, 1970). Benzo [a]pyrene was also detected at levels
    of 0.1-5.0 ng/litre in groundwater (Woidich et al., 1976). More recent
    data were not available. Groundwater in the USA contained maximum
    concentrations of 0.38-1.8 ng/litre naphthalene, 0.02-0.04 ng/litre
    acenaphthene, and 0.008-0.02 ng/litre fluorene (Stuermer et al.,
    1982). Near a refinery at Pincher Creek, Alberta, Canada, the pyrene
    concentrations in groundwater showed a maximum of 300 µg/litre
    (median, 30 µg/litre); the maximum concentration of fluorene was 230
    µg/litre (median, 40 µg/litre). At Newcastle, New Brunswick, Canada,
    naphthalene was detected at concentrations up to 2.8 µg/litre and
    benzo [a]pyrene up to 0.32 µg/litre in groundwater near a
    wood-preserving plant (Environment Canada, 1994).

    5.1.2.3  Drinking-water and water supplies

    PAH levels were determined in drinking-water in samples from Canada,
    Scandinavia, and the USA up to 1982. The concentration of naphthalene
    was 1.2-8.8 ng/litre, that of benzo [a]pyrene was 0.2-1.6 ng/litre,
    and that of the sum of the six 'standard WHO' PAH (fluoranthene,
    benzo [b]fluoranthene, benzo [k]fluoranthene, benzo [a]pyrene,
    benzo [ghi]perylene, and indeno[1,2,3- cd]pyrene) was 0.6-24
    ng/litre. The highest levels of naphthalene (1300 ng/litre),
    benzo [a]pyrene (77 ng/litre), and the six WHO standard PAH (660
    ng/litre) were detected in raw water sources in the USA and in the
    Great Lakes area of Canada (Müller, 1987). More recent measurements
    are given in Table 39. Most samples contained 0.38-16 ng/litre

    naphthalene and < 0.04-2.0 ng/litre benzo [a]pyrene. In one set of
    water samples from the Netherlands, no PAH were detected, with a limit
    of detection for individual PAH of 4 ng/litre (de Vos et al., 1990).

    In a study of the changes in PAH concentrations after passage of water
    through tar-coated major distribution pipes, the level increased from
    an initial concentration of none detected-13 ng/litre to none
    detected-62 ng/litre. The finding that water in a few distribution
    lines had lower concentrations of PAH may be due to sorption of PAH on
    the surfaces of distribution pipes, chemical interaction with oxidants
    in water, or a dilution effect (Basu et al., 1987).

    Of 101 German drinking-water samples analysed in 1994, four exceeded
    the German drinking-water standard of 0.2 µg/litre for the sum of
    fluoranthene, benzo [b]fluoranthene, benzo [k]fluoranthene,
    benzo [a]pyrene, benzo [ghi]-perylene, and indeno[1,2,3- cd]pyrene.
    Heavy contamination had occurred after repairs to a pipeline coated
    with tar, and one drinking-water sample taken in a household contained
    2.7 µg/litre of these PAH, in addition to phenanthrene at 2.8 µg/litre
    and pyrene at 1.2 µg/litre (State Chemical Analysis Institute,
    Freiburg, 1995). The report stated that abrasion of particles from
    tar-coated drinking-water pipelines poses a hazard that is often
    difficult to judge since it is often not known what material was used
    decades previously.

    In Canada, the PAH concentrations in drinking-water were usually below
    or near the detection limits of 1-5 ng/litre, although concentrations
    of 5.0-21 ng/litre benzo [ghi]perylene, 1.0-12 ng/litre fluoranthene,
    1.0-5.0 ng/litre benzo [b]fluoranthene, 1.0-3.0 ng/litre
    benzo [k]fluoranthene, and 1.0-3.0 ng/litre benzo [a]pyrene were
    detected in some areas (Environment Canada, 1994).

    5.1.2.4  Precipitation

     (a)  Rain

    The concentrations of PAH found in precipitation in 1979-91 are
    summarized in Table 40. The levels of benzo [a]pyrene were < 1-390
    ng/litre. In an analysis of PAH in rainfall in Hanover, Germany,
    between July 1989 and March 1990, fluoranthene was the dominant
    component, followed by pyrene. The average concentration of all PAH
    increased from 351 ng/litre in summer to 765 ng/litre in the autumn of
    1989, while a slight decrease was observed in the winter of 1989-90.
    These results indicate that the increase in the level of PAH in
    precipitation in cold weather is due to an increase in residential
    heating and a slower rate of photochemical degradation (Levsen et al.,
    1991).


        Table 39. Polycyclic aromatic hydrocarbon concentrations (ng/litre) in drinking-water

                                                                                                                                      

    Compound                    [1]         [2]         [3]         [4]         [5]         [6]         [7]         [8]         [9]
                                                                                                                                      

    Acenaphthene                            0.6-4.0     7.4-14
    Acenaphthylene                          0.4-4.4     0.40-1.6
    Anthracene                              0.5-7       < 1.3-9.7
    Anthanthrene                            0.2
    Benz[a]anthracene           ND-1.9      0.4-5.5     0.12-1.5
    Benzo[a]fluoranthene                    0.1-3.3     0.05-4.2
    Benzo[a]pyrene              0.1-0.7     < 0.1-2.0   < 0.04-0.29             Trace-1.9   0.2-0.3                 0.2-1.6     < 5.0
    Benzo[b]fluoranthene        0.5-1.3     2.4-4.0     0.05-0.34               0.1-14                                          < 5-40
    Benzo[b]fluorene                        0.9         0.04-<1.4
    Benzo[e]phenanthrene                    0.9-1.5     0.28
    Benzo[e]pyrene                          0.2-4       < 0.1-0.41
    Benzo[ghi]fluoranthene                              0.36
    Benzo[ghi]perylene          0.3-0.9     0.4-1.1                             ND          0.4-0.7                 0.4-4.0     < 5.0
    Benzo[j]fluoranthene                                0.03-0.14                                                   0.2-1.2
    Benzo[k]fluoranthene        0.2-0.8                 0.02-0.10               0.2-4.9     0.1-0.3                 0.1-0.7     < 5-40
    Chrysene                    21-62                                                       1080                    27          30
    Dibenz[a,h]anthracene                   1.2
    Fluoranthene                3.5-6.5     1.7-18      < 0.58-24               0.7-3400    3.4-4.2     5-24        2.4-9.0     < 5-623
    Fluorene                                0.9-4       < 1.1-21                                        4-16
    Indeno[1,2,3-cd]pyrene      Trace-0.7   0.4-1.2                             ND-1.1      < 0.5                   0.7-2.2     < 5.0
    1-Methylphenanthrene                    0.5-1.0     0.14-13
    Naphthalene                             1.8-5       < 6.3-8.8   8                                   6-16
    Perylene                    Trace-0.2   0.2
    Phenanthrene                            2.5-46      < 2.2-64                            24-90
    Pyrene                      1.6-3.7     1.1-15      < 0.30-12                                                               40/40
                                                                                                                                      

    Table 39 (continued)

    ND, not detected; /, single measurements;
    [1] Austria; analytical method, in-situ fluorescence determination (Woidich et al., 1976);
    [2] Norway, 1978-80 (Berglind, 1982);
    [3] Norway, 1980-81 (Kveseth et al., 1982);
    [4] Switzerland, 1973 (Grob & Grob, 1974);
    [5] Switzerland (Vu Duc & Huynh, 1981);
    [6] United Kingdom; water reservoirs after treatment, 1974 (Lewis, 1975);
    [7] USA, 1976; analytical method, high-performance liquid chromtography and gas chromatography
        (Thruston, 1978);
    [8] USA, 1976-77; analytical method, thin-layer chromatography and gas-liquid chromatography with
        flame ionization detection (Basu & Saxena, 1978a,b);
    [9] Canada, treated drinking-water, 1987-90 (Environment Canada, 1994)

    Analysed by high-performance liquid chromatography or gas chromatography, unless otherwise stated.
    The results of studies in which water samples were filtered through sold sorbernts may be
    underestimates of the actual PAH content (see section 2.4.1.4).

    Table 40. Polycyclic aromatic hydrocarbon concentrations (ng/litre) in rainwater

                                                                                                                                         

    Compound                    [1]       [2]           [3]         [4]         [5]         [6]         [7]         [8]         [9]
                                                                                                                                         

    Acenaphthene                                                                                        3.2         1.2/16      2.5-8.5
    Acenaphthylene                                      130-200                                         14          4.7/55      23-59
    Anthracene                                                                                          8-19        0.88/23     2.0-7.9
    Benz[a]anthracene                     1.2-86        140         6-100       9-33        7-17        20-65                   1.6-4.5
    Benzo[a]fluoranthene                                                                                14-52
    Benzo[a]pyrene              5-17      1.1-187                   ND-390      10-37       7-26        5-36                    ND-0.18
    Benzo[b]fluoranthene                  2.9-166                   15-390      45-70       17-65
    Benzo[b]fluorene                                                                                                15
    Benzo[c]phenanthrene                                                                                            802
    Benzo[e]pyrene                        < 0.5a-149    217-290                                         7-62                    ND-0.51
    Benzo[ghi]perylene          7-29      1.7-109                               40-70       15-56       22
    Benzo[k]fluoranthene                  1.0-142                   6-190       17-30       9-28
    Chrysene                              2.9-141       30-120                  ND-67       21-29                               3.3-12
    Dibenz[a,h]anthracene                 < 0.5a-12                             7-20        3-12
    Fluoranthene                23-66     23-392        240-270     14-1650     66-180      87-189      115-162     1.7/110     28-70
    Fluorene                                            10-200                                          6-50        3.2/43      9.1-22
    Indeno[1,2,3-cd]pyrene                < 0.5a-137                ND-80       50-110      24-72       12
    1-Methylphenanthrene                                                                                8-26
    Naphthalene                                                                                         8-77        20/72       46-140
    Perylene                                                                                            2
    Phenanthrene                                        130-600                 30-133      79-113      158-238     24/140      61-130
    Pyrene                                9.5-304       25-60       ND-2000     ND-37       36-108      77-175                  24-56
                                                                                                                                         

    Table 40 (continued)

    ND, not detected; /, single measurements;
    [1] Bavaria, Germany, 1979-80; analytical method, high-performance thin-layer chromatography (Thomas, 1986);
    [2] Hanover, Germany, 1989-90 (Levsen et al., 1991);
    [3] Italy (Morselli & Zappoli, 1988);
    [4] Leidschendam, Netherlands, 1982 (Van Noort & Wondergem, 1985b);
    [5] Rotterdam, Netherlands, 1983 (Van Noort & Wondergem, 1985b);
    [6] Netherlands, 1983 (Den Hollander et al., 1986);
    [7] Oslo, Norway, 1978 (Berglind, 1982);
    [8] Oregon, USA, 1982 (Pankow et al., 1984);
    [9] Portland, USA, 1984 (Ligocki et al., 1985)

    a Detection limit for benzo[a]pyrene

    Analysed by high-performance liquid chromatography or gas chromatography, unless otherwise stated. The results
    of studies in which water samples were filtered through solid sorbents may be underestimates of the actual PAH
    content (see section 2.4.1.4).


    The concentrations of phenanthrene and fluoranthene in rainwater were
    noticeably higher than those at 200 m when sampled simultaneously, but
    no significant differences in the concentrations of
    benzo [k]fluoranthene, benzo [b]fluoranthene, benzo [a]pyrene,
    dibenz [a,h]anthracene, benzo [ghi]perylene, or
    indeno[1,2,3- cd]pyrene were found. The authors suggested that
    scavenging in and below clouds was responsible for the presence of PAH
    in rainwater (Van Noort & Wondergem, 1985b).

    The deposition rates of individual PAH in Cardiff, London, Manchester,
    and Stevenage, United Kingdom, were 0.3-20 µg/m2 per day. Anthracene
    accounted for about 25% of the deposition in London, followed by
    pyrene (16%), benzo [b]fluoranthene (16%), and benz [a]anthracene
    (13%) (Clayton et al., 1992).

    The rate of precipitation containing PAH after gravitational
    deposition by rain, snow, and particles was not affected by the type
    or structure of the receiving surface. Precipitation in a beech and
    spruce stand contained concentrations of 23-52 ng/litre fluoranthene,
    8.9-30 ng/litre benzo [ghi]-perylene, 6.4-27 ng/litre
    indeno[1,2,3- cd]pyrene, and 2.0-8.4 ng/litre benzo [a]pyrene. The
    deposition of PAH is in general higher under spruce stands because the
    rates of interception are higher than those in beech stands.
    Substantial amounts of PAH are transferred to the soil by litterfall,
    indicating adsorption of PAH on the surfaces of leaves and needles
    (Matzner, 1984).

     (b)  Snow

    The concentrations of PAH in snow samples are summarized in Table 41.
    A sample collected in Hanover, Germany, contained fluoranthene at 55
    ng/litre, pyrene at 31 ng/litre, and other PAH at concentrations up to
    9 ng/litre (Levsen et al., 1991). A sample of snow from Bavaria
    contained 200 ng/litre fluoranthene, 50 ng/litre benzo [ghi]perylene,
    and 29 ng/litre benzo [a]pyrene (Schrimpff et al., 1979).

    In Norwegian snow samples, the average concentrations of individual
    PAH were 10-100 ng/litre, but levels up to 6800 ng/litre were found of
    phenanthrene, 1-methylphenanthrene, fluoranthene,
    benzo [b]fluoranthene, and fluorene (Berglind, 1982; Gjessing et al.,
    1984; Lygren et al., 1984). Snow taken near a steel plant in Canada
    contained average levels of 50-500 ng/litre of individual PAH but
    higher amounts of phenanthrene, fluoranthene, and pyrene (Boom &
    Marsalek, 1988).

        Table 41. Polycyclic aromatic hydrocarbon concentrations (ng/litre) in snow

                                                                                           
    Compound                    [1]       [2]       [3]       [4]       [5]       [6]
                                                                                           
    Acenaphthene                                    10-13                         <50-98
    Acenaphthlene                                   19-47                         <50-153
    Anthracene                                      13-28     9-379     165-246
    Benz[a]anthracene                     2.6       21-47     15-677    228
    Benzo[a]fluoranthene                            13                  179-396
    Benzo[a]pyrene              29        3.0       23-77     54-602    250       <100-558
    Benzo[b]fluoranthene                  9.2                           799-1501  <100-647
    Benzo[b]fluorene                                11                  192
    Berzo[e]pyrene                        5.5       30-64     609       360-630
    Benzo[ghi]perylene          50        4.8       29-85     98-551    319-391   <100-466
    Benzo[k]fluoranthene                  2.8                                     <100-990
    Chrysene                              6.2
    Dibenz[a,h]anthracene                 <0.5a
    Fluoranthene                200       55        108-211   86-2665   1820-3143 <50-7020
    Fluorene                                        13-85     96        485-1237  <50-237
    Indeno[1,2,3-cd]pyrene                <0.5a     20-82                         <100-496
    I-Methylphenanthrene                                                1366-2117
    Naphthalene                                     50-94     36-67     123-195
    Perylene                                        12
    Phenanthrene                                    119-276   45-1385   4055-6787 <50-3560
    Pyrene                                31        68-143    55-2002             <50-3750
                                                                                           

    Analysed by high-performance liquid chromatography or gas chromatography, unless
    otherwise stated. The results of studies in which water samples were filtered through
    solid sorbents may be underestimates of the actual PAH content (see section 2.4.1.4).

    a Detection limit for benzo[a]pyrene
    [1] Bavaria, Germany, 1978; analytical method, high-performence thin-layer chromatography
        and gas chromatography-mass spectroscopy (Schrimpff et al., 1979);
    [2] Hanover, Germany, 1990 (Levsen et al., 1991);
    [3] Norway, 1979-81 (Berglind, 1982);
    [4] Norway, 1981-82 (Gjessing et al., 1984);
    [5] Norway (Lygren et al., 1984);
    [6] Near steel plant, Canada, 1986 (Boom & Marsalek; 1988)

     (c)  Hail

    The PAH levels in a hail sample collected in Hanover, Germany, were of
    the same order of magnitude as those in rain samples: fluoranthene,
    170 ng/litre; pyrene, 98 ng/litre; benzo [b]fluoranthene, 58
    ng/litre; chrysene, 47 ng/litre; benzo [e]pyrene, 40 ng/litre;
    indeno[1,2,3- cd]pyrene, 29 ng/litre; benzo [ghi]perylene, 27
    ng/litre; benzo [k]fluoranthene, 19 ng/litre; benz [a]an-thracene,
    16 ng/litre; benzo [a]pyrene, 12 ng/litre; and
    dibenz [a,h]anthracene, 3.3 ng/litre (Levsen et al., 1991).

     (d)  Fog

    The concentrations of PAH in fog are higher than those in rain. A fog
    sample collected in western Germany contained 360-3800 ng/litre
    fluoranthene and 130-880 ng/litre benzo [a]pyrene (Schrimpff, 1983).

    In fog samples collected during the autumn of 1986 in Zürich,
    Switzerland, the average concentrations of PAH found were 4400
    ng/litre fluoranthene, 2700 ng/litre benzo [b]fluoranthene, 2500
    ng/litre pyrene, 2200 ng/litre phenanthrene, 2100 ng/litre
    benzo [e]pyrene, 1400 ng/litre benz [a]anthracene, 1400 ng/litre
    indeno[1,2,3- cd]pyrene, 1200 ng/litre benzo [a]pyrene, 920 ng/litre
    anthracene, 860 ng/litre 1-methylphenanthrene, 750 ng/litre
    benzo [b]fluorene, 750 ng/litre perylene, 590 ng/litre
    benzo [k]fluoranthene, 540 ng/litre benzo [ghi]perylene, 340
    ng/litre anthanthrene, 260 ng/litre fluorene, and 160 ng/litre
    benzo [a]fluorene (Capel et al., 1991).

    5.1.3  Sediment

    PAH levels in sediments from rivers, lakes, seas, estuaries, and
    harbours are summarized in Tables 42-46.

    5.1.3.1  River sediment

    The concentrations of individual PAH in river sediments in 1987-91
    (Table 42) varied over a wide range; the maximum values were in the
    high nanogram per gram range.

    The levels of individual PAH in sediments from German rivers were
    about 4000 µg/kg for benzo [a]pyrene, fluoranthene, and
    benzo [b]fluoranthene and about 1500 µg/kg for pyrene,
    indeno[1,2,3- cd]pyrene, and benz [a]anthracene. The levels of other
    PAH generally did not exceed 500 µg/kg (Kröber & Häckl, 1989; Regional
    Office for Water and Waste Disposal, 1989). PAH were determined in
    many German river sediments. Table 42 gives data for three rivers: the
    Rhine and Neckar rivers are highly polluted, whereas the Gersprenz is
    relatively uncontaminated.

    The concentrations of PAH in the sediments of rivers around Aachen,
    Germany, were determined in different size fractions, which allowed
    the authors to locate where the sediment became contaminated (Lampe et
    al., 1991).

    The PAH concentrations in sediment from the River Elbe in Germany in
    1991 were of the same order of magnitude as those in Lake Plöner and
    Lake Constance, but the river sediment contained more PAH with a low
    boiling-point than the lake sediments. The ratio of fluoranthene to
    benzo [e]pyrene, taken as a marker of the emission of PAH from the
    combustion of brown coal, was 2.8-5.1, similar to those found in the
    Elbe sediment. It was concluded that the PAH in the sediment were due
    mainly to brown-coal combustion (German Ministry of Environment,
    1993).


        Table 42. Polycyclic aromatic hydrocarbon concentrations (µg/kg) in river sediments

                                                                                                                                               

    Compound                [1]       [2]        [3]        [4]          [5]      [6]         [7]    [8]       [9]   [10]     [11]    [12]
                                                                                                                                               

    Acenaphthene            ND-140                                                            14.5                   1 100    ND      0.04-130
    Acenaphthylene          ND                                                                9.7                    1 540    ND      0.7-671
    Anthracene              ND-1010   80-640     670/NR     ND/NR                             82.1   8-200     152   4 700            10-1200
    Benz[a]anthracene                 620-1700   10000/NR   50-90/NR                          450    ND-100    541   6 600            3.2-2100
    Benzo[a]pyrene          Q         400-1250   ND-8000/   20-90/10-80  1-760    70-11 960   454    ND-80     570   4 400            5-3700
                                                 ND-5300
    Benzo[b]fluoranthene              460-1290   ND-8700/   50-190/                           620    ND-50
                                                 ND-5600    26-150
    Benzo[e]pyrene                                                                                             596   4 900            0.9-1800
    Benzo[ghi]fluoranthene                                                                                     253                    NR
    Benzo[ghi]perylene      Q-578     340-750    ND-2900/   ND           10-70    60-7480     358    ND        353   7 400            3-1310
                                                 ND-1900
    Benzo[j]fluoranthene                                                                                       749
    Benzo[k]fluoranthene              230-650    ND-4000/   20-90/10-80                       408    ND-60     608
                                                 ND-2700
    Chrysene                ND-1549              6700/NR    ND-30/NR                          597              904                    NR
    Coronene                                                             20-260   150-2460                     284                    NR
    Cyclopenta[cd]pyrene                                                                                       15    1 100            NR
    Dibenz[a,h]anthracene             500-1070   2600/NR    ND-20/NR                          21     ND-200          2 800            8.1-340
    Fluoranthene            ND-4455   900-2470   ND-19000/               2-2360   190-29300   904    100-400   1013  13 000   ND-60   NR
                                                 100-380/
                                                 ND-12 600  52-310
    Fluorene                ND-260                                                            25.4   ND-2      26    3 000    ND/50   3-130
    Indeno[1,2,3-cd]pyrene            360-910    ND-6300/   ND/ND                             332              486   16 000           NR
                                                 ND-4200
    1-Methylphenanthrene                                                                                       145                    NR
    Naphthalene             ND-2630                                                           7.0                    3 800            ND
    Perylene                          120-320                                                        ND-100          2 400            NR
    Phenanthrene            ND-220               3300/NR    ND-40/NR                          361    10-400    563   10 000   ND/220  9-2800
    Pyrene                  ND-2526   680-3450   17000/NR   ND-130/NR                         736    80-300    940   9200     ND-160  20-3900
    Triphenylene                                                                                     10-80                            NR
                                                                                                                                               

    Table 42 (continued)

    NQ not detacted; /, single measurements; NR, not reported; Q, qualitative;
    [1] Czechoslovakia, 1988; reference weight not given (Holoubek et al., 1990);
    [2] Rhine, Germany, 1982-83 and 1987-88; analytical method and reference weight not given (Regional Office for Water and Waste Disposal, 1989);
    [3] Neckar, Germany, 1985-88; fine, unsieved sediment; analytical method not given (Krober & Hackl, 1989);
    [4] Gersprenz, Germany, 1985-88; fine, unsieved sediment; analytical method not given (Krober & Hackl, 1989);
    [5] Wildbach, Germany, 1989 (Lampe et al., 1991);
    [6] Haarbach, Germany, 1989 (Lampe et al., 1991);
    [7] River, Bremen, Germany, 1994 (Riess & Wefers, 1990;
    [8] Rhone, France, 1985 (Milano & Vernet, 1988);
    [9] Sweden, 1985 (Broman et al., 1987);
    [10] Black River, USA, 1984 (Fabacher et al., 1991);
    [11] Rainy River, Canada, 1986; reference weight not given (Merriman, 1988);
    [12] Japan, 1974-91 (Environment Agency, Japan, 1993)

    Analysed by high-performance liquid chromatography or gas chromatography and concentration in micrograms per kilogram dry weight


    The maximum levels of individual PAH in sediments in Czechoslovakia
    were 4500 µg/kg fluoranthene, 2600 µg/kg naphthalene, 2500 µg/kg
    pyrene, 1500 µg/kg chrysene, 1000 µg/kg anthracene, 580 µg/kg
    benzo [ghi]perylene, 260 µg/kg fluorene, 220 µg/kg phenanthrene, and
    140 µg/kg acenaphthene (Holoubek  et al., 1990).

    The levels of individual PAH in sediments from some of the most
    polluted areas in continental USA were summarized by Bieri et al.
    (1986). The levels usually ranged from 1000 to 10 000 µg/kg, but that
    in sediment from the Elizabeth River, Virginia, contained
    concentrations up to 42 000 µg/kg. Up to 39 000 µg/kg wet weight were
    found in the Detroit River (Fallon & Horvath, 1985).

    The concentrations of individual PAH in sediments from the Trenton
    Channel of the Detroit River, a waterway in a highly industrialized
    area, connecting Lake St Clair with Lake Erie. varied from not
    detected (< 4 µg/kg) to 22 000 µg/kg in different locations.
    Sediments from the southwest shore of Grosse Ile had low levels of
    contamination, while those in the vicinity of Monguagon Creek had high
    levels (Furlong et al., 1988).

    5.1.3.2  Lake sediment

    The concentrations of individual PAH found in lake sediments in
    1984-91 (Table 43) ranged from 1 to about 30 000 µg/kg dry weight. The
    total PAH concentrations in surface sediments from Lake Michigan, USA,
    were 200-6200 µg/kg dry weight (Helfrich & Armstrong, 1986).

    5.1.3.3  Marine sediment

    The concentrations of individual PAH in marine sediments in 1985-91
    (Table 44) varied widely, with maximum values up to about 4000 µg/kg.

    Sediments near power-boat moorings at the coral reef around Green
    Island, Australia, were found to contain measurable amounts of several
    PAH, strongly suggesting that they originated from fuel spillage or
    exhaust emissions (Smith et al., 1987).

    The benzo [a]pyrene level was 104-106 times higher in bottom
    sediments from the Baltic Sea than in water at the same location. The
    bottom sediments also contained more individual PAH than the
    corresponding water samples (Veldre & Itra, 1991).

    Maximum levels of 460 µg/kg benzo [a]pyrene and 400 µg/kg
    benzo [e]pyrene were determined in northern North Sea sediments in
    the vicinity of oil fields. The hydrocarbon concentrations were above
    the background levels only in water and sediments within a 2-km radius
    of platforms, where diesel-coated drill cuttings were dumped. The
    contribution of five- and six-ring compounds to the total PAH in
    sediments was unexpectedly high in samples unlikely to be contaminated
    by oil. Their source was probably windborne combustion products
    (Massie et al., 1985).

    Table 43. Polycyclic aromatic hydrocarbon concentrations (µg/kg)
    in lake sediments

                                                                    

    Compound                  [1]       [2]      [3]          [4]
                                                                    

    Anthracene                160                41-620
    Benz[a]anthracene         ND                 150-1700     41
    Benzo[a]pyrene                               180-2000     45
    Benzo[b]fluoranthene                                      200
    Benzo[e]pyrene            80                 140-1500     75
    Benzo[ghi]fluoranthene              75       18-270
    Benzo[ghi]perylene                           21-1600      107
    Benzo[k]fluoranthene                                      126
    Chrysene                            250                   124
    Coronene                            1
    Dibenz[a,h]anthracene                                     70
    Fluoranthene              66-248    390      330-3900     103
    Fluorene                                                  5.9
    Indeno[1,2,3-cd]pyrene              100      25-1500      279
    Naphthalene               ND
    Perylene                            50       47-540
    Phenanthrene              70-180    100      300-6600     81
    Pyrene                    110-122   340      210-3500     60
    Triphenylene                        25
                                                                    

    ND, not detected;
    [1] Lake Padderudvann, Norway; 1981-82; reference weight not given
        (Giessing et al., 1984);
    [2] Lake Geneva, Switzerland (Dreier et al., 1985);
    [3] Cayuga Lake, USA, 1978; concentrations are given as ng/g
        deepwater (Heit, 1985);
    [4] Lake Superior, USA (Hamburg Environment Office, 1993)

    Analysed by high-performance liquid chromatography or gas
    chromatography; concentration in micrograms per kilogram dry weight


        Table 44. Polycyclic aromatic hydrocarbon concentrations (µg/kg) in sea sediments
                                                                                                                                  
    Compound                    [1]         [2]         [3]         [4]         [5]         [6]         [7]         [8]
                                                                                                                                  
    Acenaphthene                            ND-6                                            NR
    Acenaphthylene                          ND-2000     0.6-4.3                             NR
    Anthracene                              3-800       0.3-2.1     6-42                    5-313                   < 0.06-1.0
    Anthanthrene                                                    29-74                   NR
    Benz[a]anthracene           5-39        1-900       0.8-19      9-150                   15-250                  < 0.01-6.0
    Benzo[a]fluoranthene                                            2-41                    NR
    Benzo[a]pyrene              16-25       6-2200      0.4-13      7-160       1100        14-265      0.2-460     < 0.004-4.3
    Benzo[b]fluoranthene        13-26       ND-3800                             1300        51-490
    Benzo[b]fluorene                                                2-38                    NR
    Benzo[e]pyrene              5.8-18                  0.6-15      9-125                   21-345      0.4-396     < 0.1-0.6
    Benzo[ghi]perylene                      ND-400                  12-225      700         < 10-623                < 0.01-2.6
    Benzo[k]fluoranthene        4.0-9.8     ND-3400                             600         10-180                  < 0.001-2.5
    Chrysene                    49                      1.0-12      8-165                   21-398                  < 0.04-0.8
    Coronene                                                        11-36                   NR
    Dibenzo[a,e]pyrene                                              7-79                    NR
    Dibenz[a,h]anthracene       2-7         ND-400      0.5-4.2     4-74                    NR
    Fluoranthene                ND/159      4-2000      0.4-31      12-230      2300        36-1913                 < 0.1-7.2
    Fluorene                                ND-100      0.5-3.1     1-12                    NR
    Indeno[1,2,3-cd]pyrene                                          8-200                   17-510
    Naphthalene                             ND-100      0.7-8.6     1-2b                    18-1074
    Perylene                                1-2200                  5-105                   24-178
    Phenanthrene                            1-1500      0.8-29      23-93                   11-971                  < 0.06-4.2
    Pyrene                      8-160       5-1600      1.6-40      10-145                  30-1697                 < 0.1-15
    Triphenylene                            2-600                                           NR
                                                                                                                                  

    ND, not detected /, single measurements; NR, not reported;
    [1] Baltic Sea, Estonia, reference weight not given (Veldre & Itra, 1991);
    [2] Mediterranean Sea, France (Milano et al., 1985);
    [3] Adriatic Sea, Italy, 1983 (Marcomini et al., 1986);
    [4] Ligurian Sea, Italy (Desideri et al., 1988);
    [5] Ketelmeer, Netherlands, 1987 (Netherlands' Delegation, 1991);
    [6] North Sea, Netherlands, within 70 km from the coast; 1987-88 (Compaan & Laane, 1992);
    [7] North Sea, United Kingdom, 1980 (Massie et al., 1985);
    [8] Great Barrier Reef, Australia, 1983 (Smith et al., 1987)
    Analysed by high-performance liquid chromatography or gas chromatography


    The following background concentrations have been reported in North
    Sea sediments: < 0.01-20 µg/kg dry weight benzo [a]pyrene, < 30
    µg/kg fluoranthene, < 6 µg/kg benzo (b)fluoranthene plus
    benzo (k)fluoranthene, < 5 µg/kg benzo [ghi]-perylene, and < 3
    µg/kg indeno[1,2,3- cd]pyrene (Compaan & Laane, 1992).

    5.1.3.4  Estuarine sediments

    The concentrations of individual PAH in estuarine sediments in 1981-92
    (Table 45) varied widely, with maximum values in the high microgram
    per gram range. Measurements in sediments from the Continental Shelf
    of the Atlantic Ocean and the Gironde Estuary, France, showed
    relatively little contamination with PAH when compared with sediments
    from more polluted European estuaries (Garrigues et al., 1987). The
    levels of PAH in estuarine sediments in the United Kingdom were 10-500
    µg/kg. Higher amounts of fluoranthene (1000-1900 µg/kg) and pyrene
    (790 µg/kg) were reported in estuaries of the River Mersey and the
    River Tamar (Readman et al., 1986).The total PAH concentrations in
    sediments from the Penobscot Bay region of the Gulf of Maine, USA,
    ranged from 290 to 8800 µg/kg, with a distinct gradient that decreased
    seawards. The PAH composition was uniform throughout Penobscot Bay.
    Particulates of combustion products transported in the atmosphere were
    suggested to be a major source of PAH contamination. The levels in
    Penobscot Bay sediments were significantly higher than expected for an
    area previously considered to be uncontaminated and fell within the
    range found in industrialized regions throughout the world (Johnson et
    al., 1985).

    The Saguenay Fjord is the major tributary that empties into the St
    Lawrence River estuary, and the area is highly industrialized. The PAH
    concentrations were maximal near the aluminium smelting plants that
    dominate the industrial sector and which were considered to be the
    major source of PAH, and the levels decreased with distance from this
    industrial zone. The concentrations of benzo [a]pyrene,
    benzo [e]pyrene, fluoranthene, benzo [b]fluoranthene,
    benzo [j]-fluoranthene, benzo [k]fluoranthene, chrysene and
    triphenylene, pyrene, indeno[1,2,3- cd]pyrene, benz [a]anthracene,
    dibenz [a,h]anthracene, perylene, benzo [ghi]perylene, and
    dibenzo [a,e]pyrene in sediments from the Saguenay Fjord ranged from
    2000 to 3800 µg/kg (dry or wet weight basis not given) (Martel et al.,
    1986).

    5.1.3.5  Harbour sediment

    The levels of individual PAH found in harbour sediments (Table 46)
    were higher than those in rivers, lakes, or oceans, concentrations
    < 650 µg/g being reported.


        Table 45. Polycyclic aromatic hydrocarbon concentrations (µg/kg) found in estuarine sediments

                                                                                                                                         

    Compound                 [1]       [2]       [3]       [4]       [5]       [6]       [7]       [8]       [9]       [10]      [11]
                                                                                                                                         

    Acenaphthene                                 NR                  NR                  210-670             310
    Acenaphthylene                               NR                  NR                  <10-160
    Anthracene                         0.1-18    10-50     30-210    11-93     ND-49     60-860              610
    Benz[a]anthracene        10-790    0.2-68    30-160    30-650    23-189    14-540    70-3200   5-140     2000
    Benzo[a]fluoranthene                         NR                  NR                            2-150
    Benzo[a]pyrene           10-560    <0.1-52   30-210    30-760    33-313    10-540    160/7200  4-150     2300      60-6800   20-60
    Benzo[b]fluoranthene               0.2-79    100-500             53-346    17-1000
    Benzo[e]pyrene           10-620    103       40-180    30-550    56-323              120-8200  1-150     2500
    Benzo[ghi]perylene                 1-72      120-490   70-410    66-403    23-641    <70-4200  3-96      1300
    Benzo[k]fluoranthene               <0.1-24   20-100              33-189    14-696
    Chrysene                 20-1210   0.2-46    30-180              37-263    9-578                         2900
    Cyclopenta[cd]pyrene                         NR                  NR                  300/830
    Dibenz[a,h]anthracene              0.5-12    NR                  8-50      2-120     550-4900            470
    Fluoranthene             30-1920   1-100     50-180    80-1880   85-506    156-3700  60-7200   14-410    3900
    Fluorene                           15        40-120              NR                  15-1500             390
    Indeno[1,2,3-cd]pyrene   20-630    61        60-240    30-420    50-343    9-228     <130-9000                     1800
    1-Methylphenanthrene                         NR                  NR                                      240
    Naphthalene                        43        NR                  NR                  80-2200             400
    Perylene                           2-52      NR                  NR                  270/880             650       60-4200   50-60
    Phenanthrene             30-1470   0.5-74    40-130    60-790    119-413   17-252    60-8700   5-300     2400
    Pyrene                   20-1980   0.5-102   50-220    60-1510   93-425    16-539    50-5400   4-380     4800
                                                                                                                                         

    ND, not detected; /, single measurements; NR, not reported;
    [1] Estuarine sediment of the River Elbe, Germany (Japenga at al., 1987);
    [2] Continental Shelf and Gironde estuary, France (Garrigues et al., 1987);
    [3] Wadden Sea, Netherlands, 1988 (Compaan & Laane, 1992);
    [4] Mersey, Dee and Tamar estuaries, United Kingdom, 1984 (Readman at al., 1986);

    Table 45 (continued)

    [5] Humber Estuary/the Wash, United Kingdom, 1990 (Compaan & Laane, 1992);
    [6] Gulf of Maine, Penobscot Bay, USA, 1982 (Johnson et al., 1985);
    [7] Great Lake tributaries, USA, 1984 (Fabacher at al., 1991);
    [8] Chesapeake Bay; USA, 1984-86 (Huggett et al., 1988);
    [9] Puget Sound, USA (Varanasi at al., 1992);
    [10] Yarra River estuary, Australia, 1976; analytical method: thin-layer chromatography with fluorescence detector (Bagg at al., 1981);
    [11] Mallacoota Inlet, Australia, 1976; analytical method: thin-layer chromatography with fluorescence detector (Bagg at al., 1981)

    Analysed by high-performance liquid chromatography or gas chromatography and concentration in micrograms per kilogram dry weight, unless
    otherwise stated

    Table 46. Polycyclic aromatic hydrocarbon concentrations (µg/kg) found in harbour sediments

                                                                                                                                        

    Compound                 [1]         [2]     [3]           [4]          [5]          [6]     [7]            [8]     [9]
                                                                                                                                        

    Acenaphthene                                 <260-2509                                                      50      3800
    Acenaphthlene                                <240-2700
    Anthracene                                   <30-27 200    1800/1700    ND-507               110-17 000     120     10 900
    Benz[a]anthracene                            <50-1991      3400/3400                         310-20 000     240     8800/414 000
    Benzo[a]pyrene           600-1500    400     <30-16 486    1800/2100    <70-94 984           300-19 000     340     8900/109 000
    Benzo[b]fluoranthene                 450     <35-17 182                 ND-4103              410-15 000
    Benzo[e]pyrene                                             930/930                           120-11 000
    Benzo[ghi]perylene                   300     <35-1079                                        210-12 000
    Benzo[k]fluoranthene                 200     <35-1430                                        150-22 000
    Chrysene                                     <30-13 900    3900/3800                         580-21 000
    Coronene                                                                             130
    Fluoranthene             2000-3600   850     <70-21 566    900/5800     <5-84 514                           640     34 200/60 700
    Fluorene                                     <60-24 530                              370     810-65 000     100     7000
    Indeno[1,2,3-cd]pyrene               300     <50-372                                         180-14 000     160     157 000/715 000
    1-Methylphenanthrene                                       2100/2300
    Naphthalene                                  <310-1564     1300/2000    <10-43 628                          400     198 000
    Perylene                                                   1100/1200
    Phenanthrene                                 <50-5001      4200/4000    45-63 683                           510     26 000/655 000
    Pyrene                                       <70-5179      6300/6400    196-66 831           610-40 000     740     22 800/413 000
                                                                                                                                        

    ND, not detected; /, single measurements;
    [1] Rotterdam, Netherlands (Japenga et al., 1987);
    [2] Rotterdam, Netherlands, 1990 (Netherlands' Delegation, 1991);
    [3] Hampton Roads, USA, 1982 (Alden & Butt, 1987);
    [4] New York Bight, USA, 1979; reference weight not given (Boehm & Fiest, 1983);
    [5] Boston, USA (Shiaris & Jambard-Sweet, 1986);
    [6] Black Rock, USA (Rogerson, 1988);
    [7] Various harbours of the Rhine, Germany, 1990 (Hamburg Environment Office, 1993);
    [8] Vancouver Harbour, Canada (Environment Canada, 1994);
    [9] Various harbours near steel mills, Canada (Environment Canada, 1994)
    Analysed by high-performance liquid chromatography or gas chromatography and concentration in micrograms per kilogram dry weight, unless
    otherwise stated


    5.1.3.6  Time trends of PAH in sediment

    The PAH levels in sediments taken at various depths indicate changes
    and trends in the sources of PAH, e.g. from coal combustion to oil and
    gas heating.

    Measurements in sediments from Plöner Lake, Germany, showed that the
    concentration of PAH in samples from the northern part of the lake,
    which is in a populated region situated near a railway, had increased
    fivefold since 1920, whereas those in the southern part had remained
    constant. The increase in the northern part was attributed to an
    increase in the number of PAH emitters. As most of the PAH in the
    sediment originated from coal combustion, the concentrations decreased
    when coal-fired railway engines were replaced in this area. The
    benzo [a]pyrene levels ranged from 240 to 2400 µg/kg dry weight
    (Grimmer & Böhnke, 1975). These findings are consistent with the
    results of time-dependent analyses of sediments from Lake Constance
    (Müller et al., 1977).

    A general trend in decreasing PAH concentrations from north to south
    was found in bottom sediments from the main stem of Chesapeake Bay,
    USA, thought to be due to the higher human population density in the
    northern region. Most of the compounds appeared to be derived from the
    combustion or high-temperature pyrolysis of carbonaceous fuels rather
    than from crude or refined oils. The levels of PAH remained relatively
    constant over the period 1979-86 at the locations examined. Naturally
    occurring PAH usually comprised less than 20% of the total; the
    finding of higher proportions may reflect riverine transport of older
    sediments to the area or scouring and removal of recently deposited
    sediments. The benzo [a]pyrene concentrations were 12-150 µg/kg dry
    weight (Huggett et al., 1988). Similar results were reported for
    sediments from Buzzard's Bay, USA (Hites et al., 1977).

    In a study of PAH in sediment samples from the lagoon of Venice,
    Italy, a historical reconstruction of the PAH depositions in a dated
    drilling core made it possible to distinguish between natural and
    anthropogenic combustion and between different PAH sources, including
    direct petroleum spills and sedimentary diagenesis. The predominance
    of unsubstituted homologues and the relative abundance of some
    individual components suggested combustion as the predominant source.
    The lowest values determined in the deepest strata were assumed to be
    background concentrations resulting from pre-industrial pyrolytic
    sources, such as forest fires and wood burning. The benzo [a]pyrene
    levels were 2.2-17 µg/kg dry weight (Pavoni et al., 1987).

    5.1.4  Soil

    A rough distinction can be made between local sources of pollution
    (point sources) and diffuse sources. Point sources can obviously give
    rise to significant local contamination of soil, whereas diffuse
    sources usually affect more widespread areas, though to a lesser
    extent. The main sources of PAH in soil are:

    -    atmospheric deposition after local emission, long-range
         transport, and pollution from combustion gases emitted by
         industry, power plants, domestic heating, and automotive exhausts
         (Hembrock-Heger & König, 1990; König et al., 1991) and from
         natural combustion like forest fires (Hites et al., 1980);

    -    deposition from sewage (sewage sludge and irrigation water) and
         particulate waste products (compost) (Hembrock-Heger & König,
         1990; König et al., 1991); and

    -    carbonization of plant material (Grimmer et al., 1972).

    The extent of soil pollution by PAH also depends on factors such as
    the cultivation and use of the soil, its porosity, its lipophilic
    surface cover, and its content of humic substances (Windsor & Hites,
    1978). There is a correlation between the organic content of a soil
    and the PAH concentration: humus contains more PAH than a soil with
    little humic content, such as sand (Grimmer et al., 1972; Matzner et
    al., 1981; Grimmer, 1993).

    This section addresses PAH in soil resulting mainly from industrial
    sources, automobile exhaust, and other diffuse sources and gives
    background values. Attribution of a study to a particular section was
    difficult, as the sources of PAH emissions are often mixed.

    5.1.4.1  Background values

    Table 47 gives background levels of PAH in soil in rural areas. In
    non-polluted areas, PAH concentrations were usually in the range 5-50
    µg/kg.

    5.1.4.2  Industrial sources

    The PAH levels in soil resulting mainly from industrial sources are
    given in Table 48.

    The PAH levels were determined in soil near one American plant where
    animal by-products and brewer's yeast had been processed since 1957.
    The operation had subsequently expanded to include the handling of
    solvents, flue dust, chips, acids, cyanides, and a wide variety of
    industrial waste. Extremely high PAH concentrations were found in the
    soil (Aldis et al., 1983).

    PAH were detected in the soil at the sites of former coking plants in
    Canada (Environment Canada, 1994). For example in Lasalle, Quebec, the
    benzo [a]-pyrene levels in 1985 ranged from none detected to 1300
    µg/g dry weight. The facility closed in 1976, and by 1991 the
    benzo [a]pyrene concentration was below 10 000 µg/kg. In Pincher
    Creek, Alberta, high levels of alkylated PAH were measured after a
    refinery was dismantled. Maximum concentrations of 260 µg/g dry weight
    each of fluoranthene and pyrene were measured; benzo [a]pyrene was
    not detected.

    Table 47. Polycyclic aromatic hydrocarbon concentrations
    (µg/kg dry weight) in soil of background and rural areas

                                                                   

    Compound                   [1]     [2]       [3]       [4]
                                                                   

    Acenaphthene               1.7     < 1-21
    Acenaphthylene                               ND/3.0
    Anthracene                                   1.2/4.2
    Benzo[a]pyrene             15      6-12      13/22     ND-4.0
    Benzo[b]fluoranthene                         14/25
    Benzo[ghi]perylene                           49/28     ND-3.3
    Benzo[k]fluoranthene                                   0.2-3.3
    Fluoranthene               22      8-28      35/73     ND-28
    Fluorene                   ND      < 1-10
    Indeno[1,2,3-cd]pyrene                                 0.5-4.0
    Naphthalene                46      13-60     3.8/11
    Phenanthrene               30      17-21     18/39     ND-76
    Pyrene                     20      9-25      29/42
                                                                   

    ND, not detected; /, single measurements;
    [1] Norway (depth, 0-10 cm), reference weight not given (Vogt at
    al., 1987);
    [2] Norway (Aamot et al., 1987);
    [3] Wales, United Kingdom (depth, 5 cm) (Jones et al., 1987);
    [4] Green Mountain (depth, 0-5 cm), USA (Sullivan & Mix, 1985)

    Analysed by high-performance liquid chromatography or gas
    chromatography



    PAH profiles were found to depend on the depth of soil from which the
    samples were taken. A comparison of soil samples from an area of clean
    air and from an industrialized area showed that the concentrations of
    PAH with lower boiling-points (fluoranthene, chrysene, and pyrene)
    decreased with depth, whereas those of PAH with higher boiling-points
    (indeno[1,2,3- cd]pyrene, dibenz [a,h]anthracene,
    benzo [ghi]perylene, and coronene) were relatively greater. The
    opposite would have been expected on the basis of the solubility of
    these PAH (Jacob et al., 1993b).

    Table 48. Polycyclic aromatic hydrocarbon concentrations
    (µg/kg dry weight) in soil near industrial emissions

                                                                   
    Compound                    [1]       [2]       [3]       [4]
                                                                   

    Acenaphthene                           54    5 090 000
    Anthracene                144 000                1 600     70
    Benz[a]anthracene          79 000              200 000
    Benzo[a]pyrene             38 000     321                 100
    Benzo[b]fluoranthene                                      200
    Benzo[e]pyrene             35 000
    Benzo[ghi]perylene                                        100
    Benzo[k]fluoranthene                           130 000    100
    Chrysene                                     1 210 000
    Fluoranthene              340 000     573      234 000    200
    Fluorene                               80    8 600 000
    Indeno[1,2,3-cd]pyrene                                    100
    Naphthalene                            48        5 200    2.4
    Perylene                   12 000
    Phenanthrene              506 000     353   20 000 000     40
    Pyrene                    208 000     459   16 000 000    100
                                                                   

    [1] Near coal gasification plant, Netherlands, concentrations in
        µg/kg wet weight (de Leeuw et al., 1986);
    [2] Norway, reference weight not given (Vogt et al., 1987);
    [3] Near processing plant, USA, 1982; maximum (Aldis et al.,
        1983); values, analytical method, and reference weight not
        given;
    [4] Area of an abandoned coal gasification plant, USA; reference
        weight not given (Dong & Greenberg, 1988)
    Analysed by high-performance liquid chromatography or gas
    chromatography


    5.1.4.3  Diffuse sources

     (a)  Motor vehicle and aircraft exhaust

    The concentrations of individual PAH in soil resulting mainly from
    motor vehicle exhaust (Table 49) usually range between 1 and 2000
    µg/kg. The PAH content of soil often decreased with increasing depth
    (Matzner et al., 1981; Wang & Meresz, 1982; Butler et al., 1984). Near
    a motorway in the Midlands, United Kingdom, PAH were determined at
    depths of 0-4 cm and 4-8 cm. Extremely high concentrations were found
    in the surface layer, but soil at a depth of 4-8 cm was two times less
    contaminated (Butler et al., 1984). The pollution may have been a
    result of airborne transport or of microbial or photochemical
    degradation (Hembrock-Heger & König, 1990). Comparably high levels of
    PAH were found at Reykjavik Airport, Iceland (Grimmer et al., 1972;
    see Table 49).

    Table 49. Polycyclic aromatic hydrocarbon concentrations (µg/kg dry
    weight) in soil of areas predominantly polluted by vehicle exhaust

                                                                          

    Compound                   [1]     [2]     [3]           [4]      [5]
                                                                          

    Acenaphthylene                                           71
    Anthracene                 0.2                           13       11
    Anthanthrene               0.4     149
    Benz[a]anthracene          2.3     430     169-3297               13
    Benzo[a]pyrene             3.2     785     165-3196      38       24
    Benzo[b]fluoranthene                                     41
    Benzo[e]pyrene             4.5     870     159-2293               29
    Benzo[ghi]perylene         7.1     1450                  168      46
    Benzo[k]fluoranthene                                              78
    Chrysene                   4.1     436     251-2703               39
    Coronene                   1.8     410     40-322                 37
    Dibenz[a,h]anthracene      1.1     351                            2
    Fluoranthene               6.5     1290    200-3703      91       37
    Fluorene                                                          5
    Indeno[1,2,3-cd]pyrene                                            36
    Naphthalene                                                       3
    Perylene                   0.6     157                            6
    Phenanthrene               17      1735                  92       45
    Pyrene                     3.5     1610    145-4515      72       61
                                                                          

    [1] Iceland (depth, 20 cm; reference weight not given) (Grimmer et
        al., 1972);
    [2] Reykjavik Airport, Iceland (surface soil; reference weight not
        given) (Grimmer et al., 1972);
    [3] United Kingdom, surface soil near motorway; analytical method,
        adsorbance measurement, reference weight not given) (Butler et al.,
        1984);
    [4] United Kingdom (urban soil; depth, 5 cm) (Jones et al., 1987);
    [5] Brisbane, Australia (Pathirana et al., 1994)

    Analysed by high-performance liquid chromatography or gas chromatography


     (b)  Other diffuse sources

    Table 50 gives the levels of PAH from unpecified sources in soil.
    Benzo [a]pyrene levels of 800 µg/kg were found in humus, 100-800
    µg/kg in garden soil, 35 µg/kg in forest soil, and 0.8-10 µg/kg in
    sand (Fritz, 1971).


        Table 50. Polycyclic aromatic hydrocarbon concentrations (µg/kg dry weight) in soil from areas polluted by various diffuse
    sources

                                                                                                                               

    Compound                 [1]       [2]       [3]       [4]       [5]       [6]       [7]       [8]       [9]       [10]
                                                                                                                               

    Acenaphthylene                                                   NR        NR                  3.8
    Anthracene                                                       NR        NR        ND-1.4              22-70
    Anthanthrene                                                     27        0.50      ND                  10-38
    Benz[a]anthracene                                                80        0.60      ND                  47-101
    Benzo[a]pyrene           273       10/6.2    24        0.8/357   116       1.50      ND-1.4    157       54-108
    Benzo[b]fluoranthene                                                                                     49-97
    Benzo[e]pyrene           23        20/22     50                  143       3.10      ND-5.0              47-116
    Benzo[ghi]perylene       106       15/33     32        0.9-339   98        3.0       ND                  64-147
    Benzo[k]fluoranthene                                                                                     31-62
    Chrysene                                                         NR        NR        ND-2.1              50-128
    Coronene                                                         49        0.70      ND-1.7              32-66
    Dibenz[a,h]anthracene    266       8.4/22    44                  44        0.60      ND-1.4              11-29
    Fluoranthene                                           2.5-444   254       2.1       ND-2.1    83        73-170    0.3-75
    Fluorene                                                         NR        NR                  14
    Indeno[1,2,3-cd]pyrene   30        6.4/7.9   21.4      1.2-545   127       3.3                           32-80
    Naphthalene                                                      NR        NR                  58
    Perylene                 3537      4.0/8.5   5.0                 NR        NR        ND                  19-71
    Phenanthrene                                                     NR        NIR       ND-18     78        31-106
    Pyrene                                                           150       0.80      ND-0.5    90        80-183    0.1-64
                                                                                                                               

    ND, not detected; /, single measurements; NR, not reported;
    [1] Germany, birch tree peat (Ellwardt, 1976);
    [2] Germany, black and white peat (Ellwardt, 1976);
    [3] Germany, sandy loam (Ellwardt, 1976);
    [4] Soiling mountain, Germany; depth, 0-15 cm; analytical method, high-performance thin-layer chromatography; reference
        weight not given (Matzner et al., 1981);
    [5] Germany, forest, brown soil, surface layer (Bachmann et al., 1994);

    Table 50 (continued)


    [6) Germany, forest, brown soil; depth, 0-2 cm (Bachmann et al., 1994);
    [7] Iceland; depth, 3-30 cm; reference weight not given (Grimmer et al., 1972);
    [8] Norway, bog soil; depth, 0-10 cm; reference weight not given (Vogt et al., 1987);
    [9] Toronto, Canada, virgin and cultivated soil; reference weight not given (Wang & Meresz 1982);
    [10] Nova Scotia, Canada (Windsor & Hites, 1978)

    Analysed by high-performance liquid chromatography or gas chromatography


    The PAH concentrations of cultivated soil were slightly higher than
    those in virgin soil. For example, the benzo [a]pyrene concentrations
    were 65-87 µg/kg in cultivated soil and 54 µg/kg in virgin soil (Wang
    & Meresz, 1982). The PAH levels in cultivated soils from German
    gardens at a maximum depth of 25 cm decreased from industrial areas
    (fluoranthene, 590-2500 µg/kg; benzo [a]pyrene, 220-1400 µg/kg) to
    rural areas (fluoranthene, 100-390 µg/kg; benzo [a]pyrene, 30-150
    µg/kg) and with soil depth (benzo [a]pyrene concentration, 280-3000
    µg/kg at 0-30 cm, 60-4600 µg/kg at 30-60 cm, and 10-7900 µg/kg at
    60-100 cm). High PAH concentrations were found at a depth of 100 cm in
    soil from an old industrial area and from an area filled with
    contaminated soil. In compost soil, benzo [a]pyrene was present at a
    concentration of 0.10-2.5 mg/kg in 1986 and 0.02-1.3 mg/kg in 1987
    (Crössmann & Wüstemann, 1992).

    Fluoranthene and pyrene were measured in soil samples, from a wooded
    area in Maine, a marshy area of South Carolina, a grassy, uncultivated
    meadow in Nebraska, a mossy area with pine needles in Wyoming, and a
    sandy desert area in Nevada, USA, and in dark brown, red clay, and
    light brown loam from Samoa. The highest levels of individual PAH (up
    to 80 µg/kg) were found in the soil from the wooded area in Maine. The
    levels in the marshy and grassy soils of South Carolina and Nebraska
    were 8.4-26 µg/kg. The other soils sampled contained fluoranthene and
    pyrene at levels < 1 µg/kg (Hites et al., 1980).

    In Iceland, the concentrations of individual PAH in lava soil at
    depths of 3 and 25 cm were near the limit of detection. Similar levels
    were found in vegetable soil at depths of 10 and 30 cm, but the
    concentrations at 10 cm were twice as high as those at 30 cm (Grimmer
    et al., 1972).

    Higher levels of PAH were found in the humus layer of spruce and beech
    forest ecosystems than in the mineral soil, but the spruce stand
    contained and stored more PAH than the beech stand (Matzner et al.,
    1981). Forest soils in Germany contain many PAH in large amounts;
    Table 48 shows the PAH concentrations in one forest brown soil. The
    first humic layer of the soil had the highest PAH concentration, and
    the level decreased with depth to below the limit of detection in
    layers below 10 cm (Bachmann et al., 1994).

    The concentrations of PAH were no higher in soil that had been treated
    with sewage sludge than in untreated soil, indicating that sewage
    sludge is not a major source of PAH (Hembrock-Heger & König, 1990;
    König et al., 1991).

    5.1.4.4  Time trends of PAH in soil

    Soil samples collected from Rothamsted Experimental Station in
    southeast England over a period of about 140 years (1846-1980) were
    analysed for PAH (Jones et al., 1987). All of the soils were collected
    from the plough layer (0-3 cm) of an experimental plot for which
    atmospheric deposition was the only source of PAH. The total PAH
    burden of the plough layer had increased by approximately fivefold

    since 1846. The concentrations of most of the individual PAH
    (anthracene, anthanthrene, fluorene, benzo [a]pyrene,
    benzo [e]pyrene, fluoranthene, benzo [b]fluoranthene,
    benzo [k]fluoranthene, chrysene, pyrene, indeno[1,2,3- cd]pyrene,
    phenanthrene, and benz [a]-anthracene) had increased by about one
    order of magnitude. For example, the benzo [a]pyrene level was 18
    µg/kg in 1846 and 130 µg/kg in 1980, and the anthracene level was 3.6
    µg/kg in 1846 and 13 µg/kg in 1980. The levels of coronene,
    acenaphthylene, acenaphthene, perylene, and benzo [ghi]perylene
    remained approximately the same, whereas the naphthalene content
    decreased from 39 µg/kg in 1846 to 23 µg/kg in 1980.

    5.1.5  Food

    In the past, benzo [a]pyrene was the most common PAH determined in
    foods and was used as an indicator of the presence of PAH (Tilgner,
    1968). The earliest measurements of PAH, in particular of
    benzo [a]pyrene, date to 1954; these were reviewed by Lo & Sandi
    (1978) and by Howard & Fazio (1980). The levels of individual PAH in
    foods in more recent studies are summarized in Tables 51-56.

    5.1.5.1  Meat and meat products

    The concentrations of individual PAH found in meat are shown in Table
    51.

    In a comparison of home and commercially smoked meats in Iceland, very
    little benzo [a]pyrene was detected in smoked sausage and mutton, but
    considerable amounts of benzo [a]pyrene and other PAH were found in
    home-smoked mutton and lamb, independently of whether they were
    covered with cellophane or muslin. About 60-75% of the total
    benzo [a]pyrene was detected in the superficial (outer) layers of the
    meat (Thorsteinsson, 1969). These findings are in agreement with those
    of Rhee & Bratzler (1970) for smoked bologna and bacon and with those
    of Tilgner (1958) and Gorelova et al. (1960).

    The amount of PAH formed during roasting, baking, and frying depends
    markedly on the conditions (Lijinsky & Shubik, 1964). In an
    investigation of the effect of the method of cooking meat, including
    broiling (grilling) on electric or gas heat, charcoal broiling, and
    broiling over charcoal in a no-drip pan, it was shown that the
    formation of PAH can be minimized by avoiding contact of the food with
    flames, cooking meat at lower temperatures for a longer time, and
    using meat with minimal fat (Lijinsky & Ross, 1967). The most likely
    source of PAH is melted fat that drips onto the heat and is pyrolysed
    (Lijinsky & Shubik, 1965). The exact chemical mechanism for the
    formation of PAH is unknown.


        Table 51. Polycyclic aromatic hydrocarbon concentrations (µg/kg fresh weight) in meat and meat products

                                                                                                                                               

    Compound                 [1]   [2]   [3]        [4]    [5]    [6]          [7]        [8]        [9]        [10]  [11]     [12]   [13]
                                                                                                                                               

    Anthracene                     0.9                                                                                20-31a   ND-2   0.5-133
    Anthanthrene                                                                                                      5-8      ND     ND-66.5
    Benz[a]anthracene        0.5   0.5   0.02-0.64  0.03          Trace-0.33a  0.02-0.03  O.04-0.38  0.04-0.13  0.05  16-37    ND-1   0.2-144
    Benzo[a]fluorene                                                                                                  17-28    1-2    ND-174
    Benzo[a]pyrene           0.1   0.6   0-02-0.45  0.02   0.05   O.01-0.14    0.01-0.04  0.04-0.26  0.03-0.26  0.05  26-42    ND-1   ND-212
    Benzo[b]fluoranthene     0.3   1.0                     0.30                                                 0.04  16-24           ND-92.3
    Benzo[b]fluorene                                                                                                  10-12    2-7    ND-71.9
    Benzo[c]phenathrene            1.4   0.03-0.36  0.06          Trace-0.18   0.03-0.04  0.05-0.21  0.05-0.10
    Benzo[e]pyrene                                                                                              0.03  6-9      ND-2   ND-80.9
    Benzo[ghi]perylene       0.2   0.6   0.03-0.31  0.03   3.75   Trace-0.12   0.03-0.04  0.06-0.27  0.05-0.19  0.05  10-17    ND-2   ND-153
    Benzo[j]fluoranthene                                                                                              5-7
    Benzo[k]fluoranthene     0.2   0.2                     0.05                                                 0.01  8-14            ND-172b
    Chrysene                       0.6                                                                          0.15                  0.3-140a
    Dibenz[a,h]anthracene                                                                                       0.01                  ND-8.8
    Fluoranthene             0.9   1.1                     7.8                                                  0.48  57-103   6-9    1.1-376
    Indeno[1,2,3-cd]pyrene   0.2   0.7   0.04-0.38  0.03   2.5    Trace-0.11   0.01-0.03  0.04-1.40  0.05/0.1         15-22    ND-5   ND-171
    1-Methylphenanthrene                                                                                              4-5      ND-3   0.5-57.6
    Perylene                                                                                                          ND-3     ND     ND-27.9
    Phenanthrene                   3.0                                                                                22-64    10-16  3.5-618
    Pyrene                                                                                                      0.55  38-63    5-7    1.2-452
                                                                                                                                               

    ND, not detected; /, single measurements;
    [1] Poultry and eggs, Netherlands, reference weight not given (de Vos et al., 1990);
    [2] Meat and meat products, Netherlands, reference weight not given (de Vos et al., 1990);
    [3] Smoked beef, Netherlands, reference weight not given (de Vos et al., 1990);
    [4] Unsmoked beef, Netherlands (de Vos et al., 1990);
    [5] Bacon, United Kingdom (Crosby et al., 1981);
    [6] Smoked meat, United Kingdom (McGill et al., 1982);
    [7] Unsmoked meat, United Kingdom (McGill et al., 1982);

    Table 51 (continued)

    [8] Smoked sausages, United Kingdom (McGill et al., 1982);
    [9] Unsmoked sausages, United Kingdom (McGill et al., 1982);
    [10] Meat, United Kingdom, reference weight not given (Dennis et al., 1983);
    [11] Mesquite wood cooked pattie (70-90 % lean), USA, reference weight not given (Maga, 1986);
    [12] Hardwood charcoal cooked pattie (70-90% lean), USA, reference weight not given (Maga, 1986);
    [13] Grilled sausages, Sweden, reference weight not given (Larsson et al., 1983)

    High-performance liquid chromatography or gas chromatography
    a In sum with triphenylene
    b In sum with benzo[j]fluoranthene


    In one study, the highest concentration of benzo [a]pyrene (130
    µg/kg) in cooked meat was found in fatty beef, and the concentration
    appeared to be proportional to the fat content (Doremire et al.,
    1979). Levels of about 50 µg/kg were detected in a charcoal-grilled
    T-bone steak (Lijinsky & Ross, 1967), in heavily smoked ham (Toth &
    Blaas, 1972), and in various other cooked meats (Potthast, 1980).
    Usually, benzo [a]pyrene levels up to 0.5 µg/kg have been found
    (Prinsen & Kennedy, 1977).

    In meat, poultry, and fish in Canada, benzo [k]fluoranthene was
    detected at concentrations up to 0.30 µg/kg and benzo [a]pyrene up to
    1.1 µg/kg (Environment Canada, 1994).

    Benzo [a]pyrene was found in some German meat products in 1994 at
    concentrations generally < 1 µg/kg . The highest concentration, 9.2
    µg/kg, was found in a ham from the Black Forest (State Chemical
    Analysis Institute, Freiburg, 1995).

    5.1.5.2  Fish and other marine foods

    Benzo [a]pyrene was found at levels ranging from none detected to 18
    µg/kg in smoked fish. The differences were probably due to factors
    such as the type of smoke generator, the temperature of combustion,
    and the degree of smoking (Draudt, 1963). The highest concentration of
    benzo [a]pyrene (130 µg/kg) in seafood was found in mussels from the
    Bay of Naples (Bourcart & Mallet, 1965), and a level of about 60 µg/kg
    was detected in smoked eel skin. Most of the fish analysed contained
    0.1-1.5 µg/kg (Steinig, 1976). Benzo [a]pyrene was also detected at
    levels up to 3.3 µg/kg in 21 samples of smoked fish, oysters, and
    mussels of various origins (Prinsen & Kennedy, 1977). The levels of
    individual PAH are summarized in Table 52.

    5.1.5.3  Dairy products: cheese, butter, cream, milk, and related
    products

    PAH were detected in considerable amounts in smoked cheese (Prinsen &
    Kennedy, 1977; Lintas et al., 1979; McGill et al., 1982; Osborne &
    Crosby, 1987a). The benzo [a]pyrene content of a smoked Italian
    Provola cheese was 1.3 µg/kg (Lintas et al., 1979). Concentrations of
    0.01-5.6 µg/kg fresh weight fluoranthene, benz [a]anthracene,
    benzo [c]phenanthrene, benzo [a]pyrene, benzo [ghi]perylene, and
    indeno[1,2,3- cd]pyrene were found in a smoked cheese sample and
    0.01-0.06 µg/kg in unsmoked cheese from the United Kingdom (McGill et
    al., 1982). In other unsmoked cheese samples from the United Kingdom,
    the individual PAH levels were between < 0.01 µg/kg for
    dibenz [a,h]anthracene and 1.5 µg/kg for pyrene. Similar
    concentrations of PAH were found in British butter and cream samples
    (Dennis et al., 1991).


        Table 52. Polycyclic aromatic hydrocarbon concentrations (µg/kg) found in fish and marine foods

                                                                                                

    Compound                    [1]     [2]         [3]       [4]     [5]         [6]
                                                                                                

    Acenaphthene
    Anthracene                  0.9     1.3-64.3    1.4-49.6
    Benz[a]anthracene           1.3     ND-11.2     ND-6.3            ND-86       Trace-0.09
    Benzo[a]pyrene              1.4     ND-5.5      ND-5.4    0.10    ND-18       Trace-0.35
    Benzo[b]fluoranthene        2.0     ND-3.9      ND-3.6    0.35
    Benzo[c]phenanthrene                                              ND-15       0.01-0.09
    Benzo[e]pyrene                      ND-2.8      ND-3.0
    Benzo[ghi]perylene          0.9     ND-2.8      ND-1.8    4.3     ND-25       Trace-0.39
    Benzo[k]fluoranthene        0.7     ND-6.7a     ND-5.1a   0.10
    Chrysene                    2.9     ND-13.0b    ND-9.4b
    Dibenz[a,h]anthracene
    Fluoranthene                1.8     1.4-79.9    1.7-48.4  2.4
    Fluorene
    Naphthalene
    Indeno[1,2,3-cd]pyrene      1.6     ND-7.1      ND-2.4    2.7     ND-37       ND-0.33
    Perylene                            ND-1.2      ND-1.0
    Phenanthrene                3.5     5-330       10.4-277
    Pyrene                              1.3-67.8    2.1-38.4
                                                                                                


    ND, not detected; NR, not reported;
    [1] Fish, Netherlands (de Vos et al., 1990);
    [2] Herring, whitefish, mackerel, eel, salmon, salmon trout, various fillets; all smoked;
        Sweden (Larsson, 1982);
    [3] Fish and fish products: sprats, herring, rainbow trout, caviar, herring paste, salmon
        paste; all smoked or canned; Sweden (Larsson, 1982);
    [4] Kippers, United Kingdom (Crosby et al., 1981);
    [5] Fish (smoked), United Kingdom, concentration in µg/kg wet weight (McGill et al., 1982);
    [6] Fish, unsmoked, United Kingdom, concentration in µg/kg wet weight (McGill et al., 1982)

    Table 52 (continued)

                                                                                                            
    Compound                    [8]     [9]       [10]         [11]          [12]        [13]        [14]
                                                                                                            
    Acenaphthene                                  < 2-5.13     2.22-22.3
    Anthracene                                    < 2-78.4     ND-5.88       ND-0.6      ND-1.9      < 0.05
    Benz[a]anthracene           0.14    1.6-7.5   < 2          0.14-5.31     0.8-3.0     0.8-20.9
    Benzo[a]pyrene              0.13    t-4.5     < 2-7.63     ND-5.33       0.4-1.0     0.2-12.2    < 0.004
    Benzo[b]fluoranthene        0.13                           0.13-5.77     4.5-12.2c   1.2-24.3c
    Benzo[e]pyrene              0.12                                         2.4-6.3     0.7-7.6
    Benzo[ghi]perylene          0.12                           0.17-30.9     0.4-0.8     0.3-5.7
    Benzo[k]fluoranthene        0.04                                         NR          NR          < 0.002
    Chrysene                    0.65              < 2          ND-15.9       3.2-8.8b    3.9-30.8b   < 0.03
    Dibenz[a,h]anthracene       0.03                           0.21-39.3     0.1-0.2d    <0.1-0.5d
    Fluoranthene                0.1               < 2-123.5    ND-32.7       5.1-17.5    4.5-18.7
    Fluorene                                      < 2-18.5     ND-65.7
    Napthalene                                    < 2-67.4     2.06-156.1
    Indeno[1,2,3-cd]pyrene                                     0.28-28.6     0.3-0.6     0.2-6.4
    Perylene                                                                 0.2-2.7     0.1-3.1     < 0.05
    Phenanthrene                                  < 2-100.8    5.84-87.2     2.1-4.2     1.9-19.6
    Pyrene                      0.79              < 2-144.9    ND-68.0       3.1-12.4    2.6-11.2    < 0.03
                                                                                                             

    ND, not detected; NR, not reported;
    [8] Fish, United Kingdom (Dennis et al., 1983);
    [9] Fish, Nigeria (Emerole et al., 1982);
    [10] Fresh fish from the Arabian Gulf: andag, sheim, gato, sheiry, faskar, chaniedah; after an oil spill
         (Al-Yakoob et al., 1993);
    [11] Fresh fish and shrimps, Kuwait, after Gulf war (Saeed et al., 1995);
    [12] Fresh oysters, various origins, concentration in µg/kg wet weight (Speer et al., 1990);
    [13] Canned or smoked oysters and mussels, various origins, concentration in µg/kg wet weight (Speer at
         al., 1990);
    [14] Clam, Australia; analytical method: fluorescence spectrophotometry: concentration in µg/kg wet weight
         (Smith et al., 1987)
    Analysed by high-performance liquid chromatography or gas chromatography; reference weight not given,
    unless otherwise stated
    a In sum with benzo[j]fluoranthene
    b In sum with triphenylene
    c Benzo[b+k]fluoranthenes
    d Dibenz[a,h+a,c]anthracenes


    In Finnish butter samples, most of the measured PAH (phenanthrene,
    1-methylphenanthrene, fluoranthene, pyrene, benzo [a]fluorene,
    benzo [ghi]-fluoranthene, cyclopenta [cd]pyrene, perylene,
    anthanthrene, benzo [ghi]pyrene, and indeno[1,2,3- cd]pyrene)
    occurred at levels < 0.1 µg/kg. The maximum level was 1.4 µg/kg
    fluoranthene (Hopia et al., 1986).

    The concentrations of fluoranthene, pyrene, benz [a]anthracene,
    chrysene, benzo [b]fluoranthene, benzo [k]fluoranthene,
    benzo [a]pyrene, benzo [e]pyrene, perylene, benzo [ghi]pyrene,
    indeno[1,2,3- cd]pyrene, and dibenz [a,h]anthracene were measured in
    milk, milk powder, and other dairy products in Canada (Lawrence &
    Weber, 1984), the Netherlands (de Vos et al., 1990), and the United
    Kingdom (Dennis et al., 1983, 1991). The concentrations ranged from
    < 0.01 µg/kg for benzo [k]fluoranthene and dibenz [a,h]anthracene
    to 2.7 µg/kg for pyrene.

    Canadian infant formula was found to contain 8.0 µg/kg fluoranthene,
    4.8 µg/kg pyrene, 1.7 µg/kg benz [a]anthracene, 0.7 µg/kg
    benzo [b]fluoranthene, 1.2 µg/kg benzo [a]pyrene, 0.6 µg/kg
    perylene, 0.3 µg/kg anthanthrene, and 1.2 µg/kg
    indeno[1,2,3- cd]pyrene (Lawrence & Weber, 1984). Slightly lower
    levels were detected in British samples in 1982-83 (Dennis et al.,
    1991).

    PAH were detected at levels of 0.003-0.03 µg/kg in human milk
    (Heeschen, 1985).

    5.1.5.4  Vegetables

    The levels of PAH found in vegetables in recent studies are listed in
    Table 53.

    Fluoranthene, but no other PAH, was reported to have been found in
    unspecified fruits and vegetables in Canada at levels of none detected
    to 1.8 µg/kg (Environment Canada, 1994). Kale was found to contain
    high concentrations of fluoranthene (120 µg/kg), pyrene (70 µg/kg),
    chrysene (62 µg/kg), and benz [a]anthracene (15 µg/kg), and PAH
    concentrations up to 7 µg/kg were determined in other vegetables
    (Vaessen et al., 1984). The differences in PAH content have been
    attributed to variations in the ratio of surface area:weight, in
    location (rural or industrialized), and in growing season. Washing (at
    20°C) vegetables contaminated by vehicle exhausts did not reduce the
    PAH contamination (Grimmer & Hildebrandt, 1965).

    In a comparison of the PAH contents of terrestrial plants grown in
    chambers containing 'clean air' and in the open field, the
    contamination was shown to be due almost exclusively to airborne PAH,
    which were not synthesized by the plants (Grimmer & Düvel, 1970) .


        Table 53. Polycyclic aromatic hydrocarbon concentrations (µg/kg) in vegetables

                                                                                                             

    Compound                   [1]     [2]         [3]     [4]        [5]         [6]         [7]     [8]
                                                                                                             

    Anthracene                         0.09-0.19           <0.1-0.3
    Benz[a]anthracene          15                          0.7-4.6    0.05-3.17   0.05-3.2    0.4     0.3
    Benzo[a]fluoranthene               0.08-2.6
    Benzo[a]pyrene             4.2     0.05-1.4    5.6     0.3-6.2    ND-1.42     0.05-3.0            0.2
    Benzo[b]fluoranthene                           6.1     0.5-7.3                0.9-3.2     0.2
    Benzo[b]fluorene                   0.11-2.8
    Benzo[c]phenanthrene       9.2                                    0.05-1.5
    Benzo[e]pyrene             7.9     0.07-2.2            0.5-6.7                                    0.2
    Benzo[ghi]perylene         7.7     0.13-2.1    10      0.5-10.8   ND-1.39     3.7-10      0.1
    Benzo[k]fluoranthene                           3.7                            ND-17       0.1
    Chrysene                   62                                                 2.4-4.0     0.8     0.5
    Dibenz[a,h]anthracene      1.0                                                                    0.04
    Dibenzo[a,h]pyrene         0.7
    Dibenzo[a,i]pyrene         0.3
    Fluoranthene               117     1.1-28      28      2.8-9.1                9.2-17
    Indeno[1,2,3-cd]pyrene     7.9     0.14-0.72   2.4     0.3-8.3    ND-1.92     1.8-4.2
    1-Methylphenanthrene               0.10-2.1            0.7-1.6
    Perylene                           0,05-0.75           <0.1-1.7
    Phenanthrene                       0.47-12             1.8-7.5
    Pyrene                     70      0.9-18              3.4-10.4
                                                                                                             

    ND, not detected;
    [1] Kale, Netherlands (Vaessen et al., 1984);
    [2] Lettuce, Finland, concentration in µg/kg fresh weight (Wickstrom et al., 1986);
    [3] Lettuce, Germany, from an industrial area (Ministry of Environment, 1994);
    [4] Lettuce, Sweden, concentration in µg/kg fresh weight (Larsson & Sahlberg, 1982);
    [5] Lettuce and cabbage, United Kingdom, concentration in µg/kg fresh weight (McGill et al., 1982);
    [6] Lettuce, India (Lenin, 1994);
    [7] Potatoes, Netherlands (de Vos et al., 1990);
    [8] Tomatoes, Netherlands (Vaessen et al., 1984)
    Analysed by high-performance liquid chromatography or gas chromatography; reference weight
    not given, unless otherwise stated


    The benzo [a]pyrene levels in potatoes in eastern Germany were
    0.2-400 µg/kg. The highest concentrations were detected in the peel of
    potatoes grown in soil containing 400 µg/kg benzo [a]pyrene, 750
    µg/kg benzo [e]pyrene, 1000 µg/kg benz [a]anthracene, 600 µg/kg
    chrysene, 160 µg/kg dibenz [a,h]anthracene, 1000 µg/kg
    benzo [b]fluoranthene, 2300 µg/kg phenanthrene, 1800 µg/kg pyrene,
    220 µg/kg benzo [k]fluoranthene, 500 µg/kg indeno[1,2,3- cd]pyrene,
    2500 µg/kg fluoranthene, and 120 µg/kg anthracene (Fritz, 1971, 1972,
    1983).

    High concentrations of PAH were detected in lettuce grown close to a
    highway; the levels of individual PAH decreased with distance from the
    road. Washing the vegetables reduced their content of
    high-molecular-mass PAH but not of phenanthrene (Larsson & Sahlberg,
    1982). In another study, the profiles of PAH in lettuce were similar
    to those in ambient air, indicating that deposition of airborne
    particles was the main source of contamination (Wickström et al.,
    1986).

    PAH concentrations were determined in fenugreek, spinach beet,
    spinach, amaranthus, cabbage, onion, lettuce, radish, tomato, and
    wheat grown on soil that had been treated with sewage sludge. The
    levels of individual PAH in lettuce leaves (Table 53) were one to two
    orders of magnitude lower than those in the sewage sludge and the soil
    on which the lettuce was grown (Lenin, 1994).

    The PAH levels in carrots and beans grown near a German coking plant
    were below 0.5 µg/kg wet weight. The levels of fluoranthene were 1.6-
    1.7 µg/kg and those of pyrene 1.0-1.1 µg/kg. Vegetables with large,
    rough leaf surfaces, such as spinach and lettuce, had PAH levels that
    were 10 times higher, perhaps due to deposition from ambient air
    (Crössmann & Wüstemann, 1992).

    5.1.5.5  Fruits and confectionery (Table 54)

    Higher concentrations of PAH were found in fresh fruit than in canned
    fruit or juice, and especially high concentrations of phenanthrene (17
    µg/kg) and chrysene (69 µg/kg) were found in nuts (de Vos et al.,
    1990). In 1982-83 in the United Kingdom, high PAH levels were found in
    samples of puddings, biscuits, and cakes, which were probably derived
    from vegetable oil. Similar concentrations of individual PAH were
    detected in samples of British chocolate (Dennis et al., 1991).

    5.1.5.6  Cereals and dried foods

    Wheat, corn, oats, and barley grown in areas near industries contained
    higher levels of PAH than crops from more remote areas. Drying with
    combustion gases increased the contamination by three- to 10-fold; use
    of coke as fuel resulted in much less contamination than oil (Bolling,
    1964). Cereals contained benzo [a]pyrene at levels of 0.2-4.1 µg/kg
    (Table 55). The highest concentrations, up to 160 µg/kg, were found in
    smoked cereals (Tuominen et al., 1988).


        Table 54. Polycyclic aromatic hydrocarbon concentrations (µg/kg) in fruits and confectionery

                                                                                                 

    Compound                   [1]      [2]      [3]      [4]      [5]      [6]      [7]
                                                                                                 

    Anthracene                                            0.4               0.3
    Benz[a]anthracene          0.5               0.11     4.2      0.2      4.2      0.08-2.73
    Benzo[a]pyrene                      0.1      0.07     0.2      0.3      0.4      0.04-2.20
    Benzo[b]fluoranthene       0.1      0.1      0.06     0.4      0.4      3.5      0.03-1.27
    Benzo[c]phenanthrene       0.5                        12                2.2
    Benzo[e]pyrene                               0.03                                0.08-2.92
    Benzo[ghi]fluoranthene     0.9                        0.9
    Benzo[ghi]perylene                  0.1      0.06     0.4      1.1      0.2      0.11-2.55
    Benzo[k]fluoranthene       0.1      0.1      0.02     0.1      0.1      0.5      0.04-1.36
    Chrysene                   0.5               0.23     69       0.5      36       0.09-2.84
    Dibenzo[a,h]pyrene                  0.01                                         < 0.01-0.23
    Fluoranthene               3.6      1.0      0.93     3.0      1.9      2.3      0.52-3.57
    Indeno[1,2,3-cd]pyrene                                0.4      0.4      0.2      0.10-3.18
    Phenanthrene               7.8                        17       2.9      3.2
    Pyrene                                       0.83                                0.59-2.37
                                                                                                 

    [1] Fresh fruit, Netherlands (de Vos et al., 19900:
    [2] Canned fruit and juices, Netherlands (de Vos et al., 1990);
    [3] Fruit and sugar, United Kingdom (Dennis et al., 1983);
    [4] Nuts, Netherlands (de Vos et al., 1990);
    [5] Biscuits, Netherlands (de Vos et al., 1990);
    [6] Sugar and sweets, Netherlands (de Vos et al., 1990);
    [7] Puddings, biscuits and cakes, United Kingdom (Dennis et al., 1991)

    Analysed by high-performance liquid chromatography or gas chromatography; reference weight not
    given

    Table 55. Polycyclic aromatic hydrocarbon concentrations (µg/kg) in cereals and dried foods

                                                                                                                          

    Compound                    [1]       [2]       [3]       [4]       [5]       [6]       [7]       [8]       [9]
                                                                                                                          

    Acenaphthene                          1.6       NR        NR                                      0.7       2.3
    Anthracene                            9.4       NR        NR                                      1.3       19/150
    Anthanthrene                                    NR        NR
    Benz[a]anthracene           0.1-42    11        0.69      0.11-0.21 2.5/3.7   0.6       0.3       <0.1/0.2  6.3/110
    Benzo[a]pyrene              ND-0.3    5.4       0.40      0.10-0.12 0.5/0.8   0.2                 0.3/0.4   0.6/160
    Benza[b]fluoranthene        0.1-0.5             0.28      0.07-0.09 0.9       0.2       0.1
    Benzo[e]pyrene                                  0.42      0.06-0.17                               0.1/0.7
    Benzo[ghi]perylene                              0.54      0.13-120
    Benzo[k]fluoranthene                            0.50      0.1-0.14
    Dibenz[a,h]anthracene       ND-1.2              0.06      0.01-0.02 3.6
    Fluoranthene                0.8-26    130       0.71      0.58-0.69 18/28     1.9       1.4       1.5/13    70/790
    Fluorene                              5.9       NR        NR                                      2.3/2.7   6.4/87
    Indeno[1,2,3-cd]pyrene      ND-0.4              1.08      0.24-0.33 1.4       0.2
    Perylene                    0.1-0.4   0.7       NR        NR                  94        NR        NR        14/2983/1
    Pyrene                      1.1-48    47        0.10      0.38-0.62 20/21     2.2       3.4       1.6/5.4   60/630
                                                                                                                          

    ND, not detected; /, single measurements; NR, not reported;
    [1] Barley malt, Canada (Lawrence & Weber, 1984);
    [2] Bran, Finland (Tuominen et al., 1988);
    [3] Bran, United Kingdom (Dennis et al., 1991);
    [4] High bran and granary bread, United Kingdom (Dennis et al., 1991);
    [5] Bran, Canada (Lawrence & Weber, 1984);
    [6] Corn bran, Canada (Lawrence & Weber, 1984);
    [7] Flaked milled corn, Canada (Lawrence & Weber, 1984);
    [8] Oats, Finland (Tuominen et al., 1988);
    [9] Smoked oats, barley and beans, Finland (Tuominen et al., 1988)

    Analysed by high-performance liquid chromatography or gas chromatography; reference weight not given

    Table 55 (contd)

                                                                                                                          
    Compound                    [10]   [11]       [12]         [13]       [14]      [15]         [16]         [17]
                                                                                                                          
    Acenaphthene                                               0.6/0.7              NR           NR           0.6
    Anthracene                                                 0.5                  NR           NR
    Anthanthrene                                  0.05-0.08                         NR           NR
    Benz[a]anthracene           0.4    ND-0.2     0.14-0.25    <0.1/<O.1  0.3-0.8   0.06-0.15    0.33-1.26    0.1
    Benzo[a]pyrene                     < 0.1      0.17-0.30    0.2/0.4    0.1       0.03-0.05    0.15-0.34
    Benzo[b]fluoranthene                                                  0.1/0.2   0.02-0.05    0.1-0.27
    Benzo[c]phenanthrene                                                            NR           NR
    Benzo[e]pyrene                     ND-0.1     0.16-0.29    0.2/0.4              0.06-0.16    0.28-0.81
    Benzo[ghi]fluoranthene                        0.05                              NR           NR
    Benzo[ghi]perylene                            0.20-0.35                         0.06-0.08    0.15-0.28
    Benzo[k]fluoranthene               ND-0.2a                                      0.02-0.07    0.15-0.31
    Chrysene                           0.3-0.7b                                     NR           NR
    Coronene                                      0.03-0.06                         NR           NR
    Cyclopenta[cd]pyrene                          0.07-0.13                         NR           NR
    Dibenz[a,h]anthracene                         0.03-0.05               3.0       < 0.01       0.01-0.02
    Fluoranthene                2.9    0.9-1.3    0.32-0.57    1.8/3.0    1.5-7.4   0.22-0.60    0.82-6.17    3.8
    Fluorene                                                   1.3/1.7              NR           NR           2.0
    Indeno[1,2,3-cd]pyrene                        0.16-0.29               3.0       0.08-0.15    0.30-0.65
    1-Methylphenanthrene               0.3
    Perylene                    0.1                            < 0.1/0.1  0.1-0.3   NR           NR
    Phenanthrene                       1.3-1.5                 9.9/10               NR           NR           14
    Pyrene                      2.8    1.6-2.3    0.22-0.39    1.6/5.5    2.6-8.5   0.26-1.18    1.41-10.86   2.6
                                                                                                                          
    ND, not detected; /, single measurements; NR, not reported;
    [10] Whole grain oats, Canada (Lawrence & Weber, 1984);
    [11] Whole-grain rye, Sweden, concentration in µg/kg fresh weight (Larsson, 1982);
    [12] Wheat grain, United Kingdom (Jones et al., 1989b);
    [13] Wheat, Finland (Tuominen et al., 1988);
    [14] Wheat, Canada (Lawrence & Weber, 1984);
    [15] Breakfast cereal, United Kingdom (Dennis et al., 1991);
    [16] Bran-enriched cereals, United Kingdom (Dennis et al., 1991);
    [17] Bolted rye flour, Finland (Tuominen et al., 1988)
    Analysed by high-performance liquid chromatography or gas chromatography; reference weight not given, unless
    otherwise specified
    a Benzofluoranthenes
    b In sum with triphenylene

    Table 55 (contd)

                                                                                                                          

    Compound                    [18]          [19]      [20]      [21]         [22]      [23]      [24]       [25]
                                                                                                                          

    Acenaphthene                NR            NR                  NR
    Anthracene                  NR            NR                  NR
    Anthanthrene                NR            NR                  NR
    Benz[a]anthracene           0.04-0.19     0.64      0.8       0.10-0.14    0.5       0.1       0.4
    Benzo[a]pyrene              0.02-0.09     0.43      0.8       0.05-0.15    0.2       0.3       0.8
    Benzo[b]fluoranthene        0.02-0.06     0.25      1.2       0.04-0.06    0.5       0.6       1.0        0.05
    Benzo[c]phenanthrene        NR            NR                  NR                               0.7
    Benzo[e]pyrene              0.10-0.23     0.35                0.06-0.12
    Benzo[ghi]fluoranthene      NR            NR                  NR
    Benzo[ghi]perylene          0.06-0.19     0.39      0.5       0.04-0.21    0.5       0.9       0.6
    Benzo[k]fluoranthene        0.03-0.08     0.35      0.6       0.04-0.1     0.1       0.3       0.5        0.08
    Chrysene                    NR            NR        1.0       NR           2.0                 1.3        0.4
    Coronene                    NR            NR                  NR
    Cyclopenta[cd]pyrene        NR            NR                  NR
    Dibenz[a,h]anthracene       <0.01-011     0.05                <0.01-0.01
    Fluoranthene                0.07-0.40     0.66      2.8       0.23-2.03    3.7       0.6       2.5
    Fluorene                    NR            NR                  NR
    Indeno[1,2,3-cd]pyrene      0.06-0.24     0.84      0.6       0.11-0.25    0.3       0.6       0.5
    1-Methylphenanthrene
    Perylene                    NR            NR                  NR
    Phenanthrene                NR            NR        3         NR           4.2       3.0       2.1
    Pyrene                      0.04-0.88     0.67                0.23-0.87
                                                                                                                          

    NR, not reported;
    [18] White four, United Kingdom (Dennis et al., 1991);
    [19] Granary flour, United Kingdom (Dennis et al., 1991);
    [20] Bread, Netherlands (de Vos et al., 1990);
    [21] White bread, 1982-83, United Kingdom (Dennis et al., 1991);
    [22] Noodles, pizza, Netherlands (de Vos et al., 1990);
    [23] Potato products, Netherlands (de Vos et al., 1990);
    [24] Rice, macaroni, Netherlands (de Vos et al., 1990);
    [25] Soups, Netherlands (de Vos et al., 1990)
    Analysed by high-performance liquid chromatography or gas chromatography; reference weight not given


    The PAH concentration in rye grown near a highway with high traffic
    density decreased slightly 7-25 m away from the road (Larsson, 1982).

    5.1.5.7  Beverages

    Benzo [a]pyrene was found at 0.8 µg/kg in coffee powder, 0.01
    µg/litre in brewed coffee, 9.51 µg/kg in tea leaves, and 0.02 µg/litre
    in brewed tea (Lintas et al., 1979). In 40 samples of tea leaves from
    India, China, and Morocco, the concentration of benzo [a]pyrene was
    generally 2.2-60 µg/kg, although concentrations up to 110 µg/kg were
    found in smoked teas (Prinsen & Kennedy, 1978).

    In samples of whisky and beer, the concentrations of six of 11 PAH
    (benzo [b]fluoranthene, benzo [k]fluoranthene, benzo [a]pyrene,
    benzo [ghi]-perylene, dibenz [a,h]anthracene, and
    indeno[1,2,3- cd]pyrene) were below or slightly above 0.01 µg/kg. The
    highest level determined (0.24 µg/kg) was that of pyrene (Dennis et
    al., 1991). The PAH content of the water used in the preparation of
    whisky and beer was not described.

    5.1.5.8  Vegetable and animal fats and oils

    The levels of PAH in oil products, butter, and margarine are listed in
    Table 56. Vegetable oils are reported to be naturally free of PAH, and
    contamination is due to technological processes like smoke drying of
    oil seeds or environmental sources such as exhaust gases from traffic.
    The PAH content of native olive oils was particularly high (Speer et
    al., 1990). The PAH content of coconut, soya bean, maize, and rapeseed
    oil was radically reduced during refining, particularly by treatment
    with activated charcoal (Larsson et al., 1987). This method is now
    widely used (Dennis et al., 1991).

    Benzo [a]pyrene was detected in 30 vegetable oils from Italy and
    France in 1994, including 17 grape-seed oils and one pumpkin-seed oil.
    The average concentration was 59 µg/kg, and the maximum value was 140
    µg/kg. Benzo [b]fluoranthene, benzo [k]fluoranthene,
    dibenz [a,h]anthracene, and indeno[1,2,3- cd]pyrene were also found
    in measurable amounts. The source of these high levels was the smoke
    in drying ovens (State Chemical Analysis Institute, Freiburg, 1995).

    Lard and dripping were found to contain levels of individual PAH
    ranging from < 0.01 µg/kg dibenz [a,h]anthracene) to 6.9 µg/kg
    fluoranthene (Dennis et al., 1991). High PAH levels were found in
    margarine samples in studies in Finland (Hopia et al., 1986), the
    Netherlands (Vaessen et al., 1988), New Zealand (Thomson et al.,
    1996), and the United Kingdom (Dennis et al., 1991) (see Table 56).

    5.1.6  Plants

    PAH with low molecular masses are more readily taken up by vegetation
    than those with higher molecular masses (Wang & Meresz, 1982).


        Table 56. Polycyclic aromatic hydrocarbon concentrations (µg/kg) in vegetable oils and related products

                                                                                                                                             

    Compound                 [1]        [2]         [3]       [4]        [5]    [6]          [7]         [8]         [9]         [10]
                                                                                                                                             

    Acenaphthene             NR         < 0.02-45   NR        NR         NR     NR           0.29        NR          NR          < 0.1 -11
    Anthracene               NR         < 0.02-460  <0.1-0.1  ND-4.8     ND-8   NR           0.04-0.92   NR          NR          < 0.2-5.6
    Anthanthrene             Trace-0.1  NR          NR        NR         NR     NR           0.03-0.53   NR          NR          < 0.1-2.7
    Benz[a]anthracene        NR         NR          0.7-6.1   ND-6.1     ND     0.30-7.46    NR          0.22-3.98   0.28-0.96   < 0.1-5.2
    Benzo[a]fluorene         NR         < 0.02-130  NR        NR         ND-2   NR           0.07-3.8    NR          NR          NR
    Benzo[a]pyrene           Trace-0.3  < 0.02-24   0.5-2.3   ND-4.1     ND     0.29-4.92    0.05-2.2    0.19-6.0    0.17-0.83   < 0.2-5.2
    Benzo[b]fluoranthene     Trace-0.1  < 0.02-91a  NR        ND-8.9a    ND     0.20-2.39    NR          0.16-3.0    0.09-0.37   < 0.2-9.2
    Benzo[b]fluorene         NR         < 0.02-45   NR        NR         ND     NR           0.03-2.1    NR          NR          NR
    Benzo[e]pyrene           NR         < 0.02-23   0.7-2.4   ND-3.8     ND     0.26-6.06    0.09-2.1    0.42-6.11   0.36-0.87   NR
    Benzo[ghi]fluoranthene   NR         < 0.02-1.3  NR        NR         ND     NR           0.14-4.9    NR          NR          NR
    Benzo[ghi]perylene       NR         < 0.02-10   0.5-1.7   ND-4.2     NR     0.06-5.23    0.02-1.4    0.38-5.21   0.17-1.16   < 0.2-10.6
    Benzo[k]fluoranthene     NR         NR          NR        NR         ND     0.24-3.17    NR          0.20-3.40   0.16-0.55   < 0.1-11.4
    Chrysene                 NR         NR          NR        0.1-8.6b   ND     0.39-10.3    NR          0.26-7.36   0.31-0.97   < 0.2-7.5
    Coronene                 NR         < 0.02      NR        NR         NR     NR           NR          NR          NR          NR
    Cyclopenta[cd]pyrene     NR         < 0.02-1.4  NR        NR         ND     NR           0.10-1.1    NR          NR          NR
    Dibenz[a,h]anthracene    0.7-1.1    < 0.02-1.1c NR        ND-0.2c    NR     <0.01-0.82   NR          0.05-1.02   0.04-0.11   < 0.1-9.2
    Fluoranthene             0.2-7.5    < 0.02-460  1.2-4.8   0.2-18.2   3-15   0.21-12.4    0.52-9.0    0.09-4.50   0.44-1.56   < 0.1-1.6
    Fluorene                 NR         < 0.02-200  NR        NR         ND-7   NR           0.08-1.6    NR          NR          < 0.2-2.1
    Indeno[1,2,3-cd]pyrene   Trace-0.5  < 0.02-0.85 0.3-1.7   ND-4.3     NR     0.59-6.78    0.03-1.1    0.49-9.14   0.43-1.17   < 0.2-9.7
    Naphthalene              NR         NR          NR        NR         NR     NR           NR          NR          NR          < 0.2-52
    1-Methylphenanthrene     NR         < 0.02-190  NR        NR         NR     NR           0.08-1.8    NR          NR          NR
    Perylene                 Trace-0.2  < 0.02-5.9  0.1-0.4   ND-0.9     NR     NR           0.02-0.57   NR          NR          NR
    Phenanthrene             NR         0.09-1400   0.9-1.6   ND-69.4    4-38   NR           0.29-6.0    NR          NR          < 0.2-4.6
    Pyrene                   0.2-1.4    < 0.02-330  1.1-4.2   0.1-13.6   2-14   0.58-17.2    0.59-15     0.29-6.03   0.44-1.88   < 0.1-1.7
                                                                                                                                             

    Table 56 (continued)

    ND, not detected; /, single measurements; NR, not reported;
    [1] Corn oil, canola, soya bean oil (Lawrence & Weber, 1984);
    [2] Corn oil, coconut oil (crude and deodorized), olive oil, soya bean oil, sunflower oil, sesame oil, flaw oil,
        wheatseed oil (Hopia et al., 1986);
    [3] Coconut oil (pure) (Sagredos et al., 1988);
    [4] Various olive oils, safflower oils, sunflower oils, maize germ oils, sesame oil, linseed oil, wheat germ oil
        (all native) (Speer et al., 1990);
    [5] Various olive oils (Menichini et al., 1991b);
    [6] Various unspecified oils (Dennis et al., 1991);
    [7] Four cooking margarines, seven table margarines (Hopia et al., 1986);
    [8] Margarine (Dennis et al., 1991);
    [9] Low-fat spread (Dennis et al., 1991);
    [10] Margarine (Thomson et al., 1996)

    Analysed by high-performance liquid chromatography or gas chromatography

    a Benzo[b+j+k]fluoranthenes
    b In sum with triphenylene
    c Dibenz[a,h+a,c]anthracenes


    In a study of PAH levels in soil (see section 5.1.4), leaf litter, and
    soil fauna (see section 5.1.7) from a roadside in Brisbane, Australia,
    vegetation height, soil depth, and distance from the roadside were
    found to be important in the distribution of PAH. The concentration of
    PAH in leaf litter declined exponentially with distance from the
    roadway, few PAH being detectable 30 m away. A decrease in PAH levels
    with height was found in the roadside vegetation canopy. In leaf
    litter, fluorene, phenanthrene, fluoranthene, pyrene, chrysene,
    benzo [k]fluoranthene, and benzo [ghi]perylene were present at
    concentrations of about 100 µg/kg wet weight. Naphthalene,
    benz [a]anthracene, benzo [e]pyrene, benzo [a]pyrene, and
    indeno[1,2,3- cd]pyrene were present at about 50 µg/kg wet weight,
    whereas anthracene was present at concentrations below 10 µg/kg wet
    weight. Perylene and dibenz [a,h]anthracene were not detectable. The
    tree  Casuarina littorina contained high levels of pyrene and
    chrysene (100 µg/kg wet weight each) and benzo [k]fluoranthene (72
    µg/kg wet weight); the concentrations of fluoranthene, phenanthrene,
    and benzo [ghi]-perylene were about 40 µg/kg wet weight. Perylene,
    indeno[1,2,3- cd]pyrene, dibenz [a,h]anthracene,
    benzo [ghi]perylene, and coronene were not detectable (Pathirana et
    al., 1994).

    The benzo [a]pyrene levels in spruce sprouts from a rural area of
    Germany (Bornhövede, Schleswig-Holstein) decreased from 2.6 µg/kg in
    1991 to 1.3 µg/kg in 1993. The concentrations of PAH with low
    boiling-points significantly decreased between 1991 and 1993; for
    example, that of fluoranthene decreased from 44 µg/kg in 1991 to 11
    µg/kg in 1993, perhaps due to a decrease in coal burning. The levels
    of phenanthrene, fluoranthene, pyrene, and benzo [b]fluoranthene plus
    benzo [j]fluoranthene plus benzo [k]fluoranthene were about 10
    µg/kg; those of benzo [ghi]fluoranthene, benzo [c]phenanthrene,
    benz [a]anthracene, benzo [e]pyrene, benzo [a]pyrene,
    indeno[1,2,3- cd]pyrene, benzo [ghi]perylene, and coronene were
    about 2 µg/kg; and those of anthracene, dibenz [a,h]anthracene, and
    anthanthrene were < 1 µg/kg. The PAH levels in spruce sprouts from
    the Saarland, an industrial area in Germany, were about 10 times
    higher than those in the Bornhöveder area, although these levels also
    decreased between 1991 and 1993: from 5.9 to 4.1 µg/kg for
    benzo [a]pyrene and 97 to 58 µg/kg for fluoranthene. the
    concentrations of pyrene were 40-50 µg/kg, those of
    benzo [b]fluoranthene plus benzo [j]fluoranthene plus
    benzo [k]fluoranthene were 20 µg/kg, and those of
    benzo [ghi]perylene, benzo [c]phenanthrene, benz [a]anthracene,
    benzo [e]pyrene, benzo [a]pyrene, indeno[1,2,3- cd]pyrene,
    dibenz [a,h]anthracene, benzo [ghi]perylene, anthanthrene, and
    coronene were < 10 µg/kg (Jacob & Grimmer, 1994, 1995). In 1994, the
    PAH levels had decreased further. Overall, a 25% decrease in the PAH
    levels in spruce sprouts was seen over the previous 10 years (Jacob &
    Grimmer, 1995).

    The PAH profiles in spruce sprouts and poplar leaves were reasonably
    similar in areas with clean air (Bavarian forests) and in
    industrialized areas (Saarland) of Germany, indicating that one
    emission source is predominantly responsible for air pollution by PAH.
    Hard-coal combustion resulted in a characteristic PAH profile (Jacob
    et al., 1993a).

    The concentrations of PAH in pine needles from Dübener Heide near
    Leipzig (Saxony, Germany) were similar to those from the Bornhöveder
    area (Schleswig-Holstein, Germany), with an average benzo [a]pyrene
    level of 2.3 µg/kg (Jacob & Grimmer, 1995).

    Beech leaves from the Harz mountains in Germany contained fluoranthene
    at a level of 5 µg/kg, whereas the concentrations of phenanthrene,
    pyrene, benzo [b]fluoranthene plus benzo [j]fluoranthene plus
    benzo [k]fluoranthene, anthracene, benz [a]anthracene,
    benzo [e]pyrene, benzo [a]pyrene, indeno[1,2,3- cd]pyrene,
    dibenz [a,h]anthracene, benzo [ghi]perylene, anthanthrene, and
    coronene were all < 2 µg/kg. Beech sprouts in an industrial area in
    eastern Germany contained 10-15 times higher levels of PAH, with
    fluoranthene at about 60 µg/kg, pyrene at about 30 µg/kg,
    benzo [b]fluoranthene plus benzo [j]-fluoranthene plus
    benzo [k]fluoranthene at about 10 µg/kg, and anthracene,
    benz [a]anthracene, benzo [e]pyrene, benzo [a]pyrene,
    indeno[1,2,3- cd]pyrene, benzo [ghi]perylene, coronene,
    dibenz [a,h]anthracene, and anthanthrene at < 2 µg/kg (Jacob &
    Grimmer, 1995).

    Comparable results were obtained in poplar leaves: those from the
    Saarland analysed in 1989, 1991, and 1993 had 10 times lower
    concentrations of PAH than those in Dübener Heide. The concentrations
    of phenanthrene, fluoranthene, and pyrene were about 20 µg/kg, those
    of benzo [b]fluoranthene plus benzo [j]fluoranthene plus
    benzo [k]fluoranthene were about 10 µg/kg, and those of anthracene,
    benz [a]anthracene, benzo [e]pyrene, benzo [a]pyrene,
    indeno[1,2,3- cd]pyrene, dibenz [a,h]anthracene,
    benzo [ghi]perylene, anthanthrene, and coronene were < 5 µg/kg
    (Jacob & Grimmer, 1995).

    5.1.7  Animals

    5.1.7.1  Aquatic organisms

    Aquatic invertebrates are known to adsorb and accumulate PAH from
    water (see section 4.1.5). The concentrations of PAH in aquatic
    organisms collected from various sites are listed in Tables 57-64. All
    of the sampling sites listed in Tables 57-60 were contaminated with
    industrial effluents, the major components of the PAH profile being
    benzo [b]fluoranthene, benz [a]anthracene, benzo [a]pyrene,
    benzo [e]pyrene, fluoranthene, pyrene, and phenanthrene. The average
    levels of PAH in aquatic organisms from these sites ranged from 1 to
    100 µg/kg; the differences in levels generally corresponded to the
    degree of industrial and urban development and shipping movements.

        Table 57. Polycyclic aromatic hydrocarbon concentrations (µg/kg dry weight)
    in bivalves and gastropods; main source, industrial emissions

                                                                                                  

    Compound                    [1]     [2]      [3]      [4]       [5]        [6]        [7]
                                                                                                  

    Acenaphthene                ND      ND       7                                        2.1/8.8
    Anthracens                                   9                                        9.0/25
    Benz[alanthracene           172     203      3        5-41      25-229
    Benzo[alpyrene              12      21       1        8.1       2-8        Trace-28   2.6/2.8
    Benzo[b]fluoranthene        23      25                          3-30       48-90
    Benzo[ejpyrene              17      10                          Trace-30   231-356
    Benzo[ghilperylene          ND               4                  5
    BenzoUlfluoranthene                 1.3
    Benzolk]fluoranthene        2.3
    Chrysene                    209     205
    Coronene                                     4
    Dibenzo(a,elpyrene                           2
    Dibenzo[e,ilpyrane                           4
    Dbenzo[a,lpyrene                             Trace
    Fluoranthene                18      62       7                  43-407     300-4992   26/61
    Fluorene                                     2                                        1.3/6.3
    1-Methylphenanthrene                                  2.9
    Naphthalene                                                                           15/3
    Perylene                                     8
    Phenanthrene                733     462      9        4.4       115-258    55-2542    66/194
    Pyrene                      85      131      4                  32-204     141-3128   23/40
    Triphenylene                ND
                                                                                                  

    ND, not detected; /, single measurement;
    [1] Whole cooked clam (Mya arenaria); oil-contaminated area (tanker accident), Canada, 1979;
        concentration in µg/kg wet weight (Sirota & Uthe, 1981);
    [2] Whole cooked mussel (Mytilus edulls); oil-contaminated area (tanker accident), Canada,
        1979; concentration in µg/kg wet weight (Sirota & Uthe, 1981);
    [3] Whole mussel (Mytilus galloprovincialis); Thermaikos Gulf, Aegean Sea, Greece (agricultural
        and industrial area); concentration in µg/kg wet weight (Iosifidou et al., 1982);
    [4] Whole scallop (Amusium pleuronectes); Gulf of Thailand, Thailand; reference weight not
        given (Hungspreugs et al., 1984);
    [5] Whole periwinkle (Littorina littorea); moderately polluted parts of North Sea coast,
        Norway, 1978-79 (Knutzen & Borland, 1982);
    [6] Whole limpet (Patella vulgata); moderately polluted parts of North Sea coast, Norway,
        1978-79 (Knutzen & Sortland, 1982);
    [7] Whole snails (Thais haemostoma), Pensacola Bay, USA; creosote contaminated; concentration
        in µg/kg wet weight (Rostad & Pereira, 1987)

    High-performance liquid chromatography or gas chromatography

    Table 58. Polycyclic aromatic hydrocarbon concentrations (µg/kg dry weight) in algae
    and water plants; main source, industrial emissions

                                                                                        

    Compound                 [1]    [2]      [3]          [4]        [5]         [6]
                                                                                        

    Benz[a]anthracene        5      4        31-325       45-431     3-40
    Benzo[alpyrene           4      5        Trace-64     Trace-<2   2-20
    Benzo[b]fluoranthene     4      5        7-76         6-12       5-31
    Benzo[e]pyrene           7      14       Trace-100    Trace-8    8-50        410
    Benzo[ghi]perylene              4                                            79
    Fluoranthene             45     32       40-412       15-900     <4-236
    Phenanthrene             87     34       31-325       45-431     109-146
    Pyrene                   36     20       28-286       15-388     <4-224      260
                                                                                        

    [1] Laminaria saccharins (whole); moderately polluted parts of North Sea coast,
        Norway, 1978-79 (Knutzen & Sortland, 1982);
    [2] Ceramium rubrum (whole), moderately polluted parts of North Sea coast, Norway,
        1978-79 (Knutzen & Sortland, 1982);
    [3] Bladder wrack (Fucus vesiculosus, whole), moderately polluted parts of North
        Sea coast, Norway, 1978-79 (Knutzen & Sortland, 1982);
    [4] Knotted wrack (Ascophyllum nodosum, whole), moderately polluted parts of North
        Sea coast, Norway, 1978-79 (Knutzen & Sortland, 1982);
    [5] Toothed wrack (Fucus serratus, whole), moderately polluted parts of North Sea
        coast, Norway, 1978-79 (Knutzen & Sortland, 1982);
    [6] Wakame seaweed, Japan (Obana et al., 1981a)

    High-performance liquid chromatography or gas chromatography

    Table 59. Polycyclic aromatic hydrocarbon concentrations (µg/kg wet weight) in lobsters; main
    source, industrial emissions

                                                                                                  

    Compound                    [1]      [2]       [3]           [4]          [5]          [6]
                                                                                                  

    Acenaphthene                ND       ND
    Benz[a]anthracene           684      ND/23     1620-23 400   34-604       762-32 700   17-900
    Benzo[a]pyrene              24       0.2/2.6   35-1000       2.0-40       711-1430     27-43
    Benzo[b]fluoranthene        24       1         155-2350      6-78         1020-3820    29-835
    Benzo[e]pyrene              57       5/8       415-9330      15-165       1550-3600    35-36
    Benzo[ghi]perylene          ND       ND/2      7-493         1.6-31       232-769      10-20
    Benzo[k]fluoranthene        7.6      0.3/0.6   43-588        1.6-25       502-955      15-26
    Chrysene                    445      ND        360-5050      5-79         252-1240     15-24
    Fluoranthene                318      ND/0.2    1910-12400    103-545      4220-15 200  68-442
    Indeno[1,2,3-cd]pyrene               5         38-855        3-45         486-931      12-40
    Phenanthrene                1588     ND        Trace-3470    Trace-650
    Pyrene                      488      ND        730-6710      32-265       2910-13 100  59-333
    Triphenylene                         ND/244    2520-23100    Trace-330
                                                                                                  

    ND, not detected; /, single measurements;
    [1] Homarus americanus (digestive gland), oil-contaminated area (tanker accident), Canada, 1979
        (Sirota & Uthe, 1981);
    [2] Homarus americanus (tail muscle), oil-contaminated area (tanker accident), Canada, 1979
        (Sirota & Uthe, 1981);
    [3] Homarus americanus (hapatopancreas), Sydney Harbour, near coking plant, Canada (Sirota
        et al., 1983);
    [4] Homarus americanus, (tail muscle), Sydney Harbour, near coking plant, Canada (Sirota
        et al., 1983);
    [5] Homarus americanus, (digestive gland), Sydney Harbour, near coking plant, Canada, 1982-84
        (Uthe & Musial, 1986);
    [6] Homarus americanus (tail muscle), Sydney Harbour, near coking plant, Canada, 1982-84
        (Uthe & Musial, 1986)

    High-performance liquid chromatography or gas chromatography


        Table 60. Polycyclic aromatic hydrocarbon levels (µg/kg dry weight) in fish and other aquatic species; main
    source, industrial emissions

                                                                                                                    

    Compound                  [1]     [2]         [3]         [4]         [5]      [6]       [7]      [8]       [9]
                                                                                                                    

    Acenaphthene              39                              Trace-0.9   130      < 25
    Acenaphthylene            270                             0.1-0.2
    Anthracene                                    ND          0.1-0.2     460      < 22               1000
    Benz[a]anthracene         22      ND-40       ND-< 0.1    0.1-88      1000     < 21      1-2      800       5
    Benzo[a]fluorene                                          02-0.6                                  500
    Benzo[a]pyrene            7       0.07-8.4    ND-< 0.1    0.1-0.5     570      < 20               ND        8
    Benzo[b]fluoranthene                          <O.1a                                                         28
    Benzo[b]fluorene                                          O.1-0.2
    Benzo[o]phenanthrene                                      Trace
    Benzo[e]pyrene            14                  ND-< 0.1    0.1-1.6     840      < 25                         25
    Benzo[ghi]perylene                            ND-< 0.1    0.2-18      75       < 25                         23
    Chrysene                  61                  < 0.1-2.1b              1500     < 22
    Dibenz[a,h]anthracene                         ND-< 0.1c               <100     < 25
    Fluoranthene              1800                0.1-9.1     1.2-5.6     4800     < 20      13-18    800       48
    Fluorene                                                  0.2-2.4     200      < 25               NDc
    Indeno[1,2,3-cd]pyrene                        ND-< 0.1    0.3-3.7     150      < 25
    1-Methylphonanthrene                                                  85       < 10
    Naphthalene                                               2.5-11      610      < 25
    Perylene                  6                   ND-< 0. 1   Trace-0.2   75       < 20
    Phenanthrene              2700    28-15 313   0.1-2.4     0.7-9.1     1400     < 20      32-50    900       71
    Pyrene                    1500                ND-10.0     0.7-3.7     2300     < 20      10-8     800       39
    Triphenylene                                                                                      800
                                                                                                                    

    Table 60 (continued)

    ND, not detected;
    [1] Bullhead catfish (Ictalurus nebulosus, whole); Black River, USA, near coking plant; concentration in
        µg/kg wet weight (Vassilaros et al., 1982);
    [2] Whole fish (unspecified); Hersey River, USA, creosote polluted; concentration in µg/kg wet weight
        (Black et al., 1981);
    [3] Bream (fillet and liver); River Elbe, Germany, industrial region of city of Hamburg (Speer et al., 1990);
    [4] Dabs (Limanda limanda, muscle, North Sea, United Kingdom, near Beatrice oil platform; concentration in
        µg/kg wet weight (McGill et al., 1987);
    [5] English sole (Parophrys vetulus, stomach contents); Mukilteo, USA, near petroleum storage tanks (Malins
        et al., 1985);
    [6] English sole (Parophrys vetufus, liver); Mukilteo, USA, near petroleum storage tanks (Malins et al., 1985);
    [7] Whole starfish (Asterias rubens), moderately polluted areas of North Sea coast, Norway, 1978-79 (Knutzen
        & Sortland, 1982);
    [8] Whole holothurians, Toulon, France; urban sewage (Milano et al., 1986);
    [9] Whole crumb-of-bread sponge (Hafichondria panicea); moderately polluted areas of North Sea coast, Norway,
        1978-79 (Knutzen & Sortland, 1982)

    High-performance liquid chromatography or gas chromatography

    a Benzo[b+j+k]fluoranthenes
    b In sum with triphenylene
    c Dibenz[a,h+a,c]anthracenes

    Table 61. Polycyclic aromatic hydrocarbon concentratrations (µg/kg dry weight) in bivalves (mussels and
    clams); background values

                                                                                                               

    Compound                    [1]       [2]       [3]       [4]       [5]       [6]       [7]       [8]
                                                                                                               

    Acenaphthene                NR                                                                    24/46
    Acenaphthylene              NR                                                                    34/130
    Anthracene                  0.7-19    9-15      149-243                                           36/43
    Benz[a]anthracene           NR                            0.1-0.8   2.9/42    < 1       31/94
    Benzo[a]pyrene              4.6-451   3/5       <0.8-2              3.5/8.7   < 1       1.3/26
    Benzo[b]fluoranthene        3.0-120                                 1.5/12              2.5/18
    Benzo[c]phenanthrone        5.3-280                                 3.1/55    < 1       26/94
    Benzo[e]pyrene              NR                  5-25
    Benzo[ghi]perylene          3.4-57                                  5.4/4.2   3         0.4/8.1
    Benzo[k]fluoranthene        1.0-43              1-2                 2.6/9.6             1.7/17
    Chrysene                    NR                                      7.6/27              86
    Coronene                                        < 10-24             1.3/2.7             0.7/4.6
    Dibenz[a,h]anthracene       NR                                      4.7/6.9             2.1/9.6
    Fluoranthene                16-288    23/43     8-23      0.7-7.2   11/111    17        47/180    72
    Indeno[1,2,3-cd]pyrene      ND-9.9                                  5.9/3.9             0.3/5.7
    1-Methylphenanthrene        22-708
    Naphthalene                 NR        5-4                                                         51/120
    Perylene                    4.2-59              < 5-26                        36
    Phenanthrene                21-570    7-109               0.1-1.7   12/155    18        108/216
    Pyrene                      6.6-394   9-77      15-38     0.3-6.6   6.2/62    23        25/109
    Triphenylene                7.5-300                                 7.9/43              27/106
                                                                                                               

    Table 61 (contd)

    ND, not detected; /, single measurements; NR, not reported;
    [1] Mussel (Mytilus edulis), Danish, German and Dutch Wadden Sea, 1989 (Compaan & Laane, 1992);
    [2] Mussel (Mytilus edulis); Finnish archipelago, Finland, 1978-79; concentration in µg/kg wet weight
        (Rainio et al., 1986);
    [3] Mussel (Mytilus edulis L.); North Sea coast, Netherlands; concentration in µg/kg wet weight
        (Boom, 1987);
    [4] Hard shell clam (Mercenaria mercenaria), Rhode Island (seafood stores), USA; concentration in µg/kg
        wet weight (Pruell et al., 1984);
    [5] Softshell clam (Mya arenaria), Coos Bay, Oregon, USA, 1978-79; reference weight not given (Mix &
        Schaffer, 1983);
    [6] Clam (Mya mercenaria); Chesapeake Bay, USA, 1984 (Bender & Huggett, 1988);
    [7] Mussel (Mytilus edulis); Yaquina Bay, USA, 1979-80; concentration in µg/kg wet weight (Mix & Schaffer,
        1983);
    [8] Rangia cuneata; Lake Pontchartrain, USA, 1980; concentration in µg/kg wet weight(McFall et al., 1985)

    Table 61 (contd)

                                                                                                               

    Compound                    [9]       [10]     [11]           [12]      [13]        [14]          [15]
                                                                                                               

    Acenaphthene                                                                                      16
    Acenaphthylene                                                                                    18
    Anthracene                                     < 0.05-3.2     <0.05
    Benz[a]anthracene           < 1-6     < 10                              1.0-1.8     ND-2.3
    Benzo[a]pyrene              30-168    < 10     < 0.003-0.02   < 0.004   0.41-1.8    0.40-2.6      1.0
    Benzo[b]fluoranthene                                                    1.0-1.8     0.83-1.9
    Benzo[c]phenanthrene        < 1-9
    Benzo[e]pyrene
    Benzo[ghi]perylene          < 1-10             < 0.05-0.3     <0.05     0.53-1.9    0.83-2.3
    Benzo[k]fluoranthene                           < 0.002-0.02   < 0.002   0.29-0.80   0.32-1.2
    Chrysene                                       < 0.03-1.4     <0.03
    Coronene
    Dibenz[a,h]anthracene
    Fluoranthene                < 1/52    < 1-370  < 0.04-0.70
    Fluorene
    Indeno[1,2,3-cd]pyrene
    1-Methylphenanthrene
    Naphthalene
    Perylene                    < 1-10    < 10-300 < 0.01-0.08
    Phenanthrene                < 1-15    < 1-60                                                      14
    Pyrene                      17/165    < 1-450  < 0.03-1.4     <0.03
    Triphenylene
                                                                                                               

    Table 61 (contd)

    [9]  Rangia cuneaya, Chesapeake Bay, USA, 1984 (Bender & Huggett, 1988);
    [10] Lampsilus radiata, Elliptio complanatus, Anodonata grandis; Lake George, Heats Bay USA
         (Heit et al., 1980);
    [11] Tridacna maxima, Great Barrier Reef, Australia, 1980-82; concentration in µg/kg wet weight
         (Smith et al., 1984);
    [12] Clam; Green Island, Great Barrier Reef, Australia, concentration in µg/kg wet weight
         (Smith et al., 1984);
    [13] Shortnecked clam; near Miyagi Prefecture, Japan, concentration in µg/kg wet weight
         (Takatsuki et al., 1985);
    [14] Mussel; near Miyagi Prefecture; Japan, reference weight not given (Takatsuki et al., 1985);
    [15] Perna viridis; Gulf of Thailand (mussel farm), Thailand, reference weight not given
         (Hungspreugs et al., 1984)

    High-performance liquid chromatography or gas chromatography;

    Table 62. Polycyclic aromatic hydrocarbon concentrations (µg/kg wet weight) in bivalves (Oysters); background values

                                                                                                                         

    Compound                   [1]      [2]          [3]            [4]             [5]          [6]             [7]
                                                                                                                         

    Acenaphthene               46                                   < 0.2-2.0                                    16
    Acenaphthylene             36                                   < 0.4-3.0
    Anthracene                 44                    < 1-40         < 0.08-0.9                   < 0.25-4.2
    Benz[a]anthracene          9.9      0.3-12       < 1-135                        1.1          1.5-10
    Benzo[a]pyrene                      0.5-1.6      50-285         < 0.01-5        0.6-2.6      0.78            3.5
    Benzo[b]fluoranthene                0.3-5.2                     < 0.03-6        3.0-20       2.2
    Benzo[c]phenanthrene                             < 1-70
    Benzo[e]pyrene                                   < 1-453                        2.8-32
    Benzo[ghi]perylene                  O.4-1.2      < 1-73         < 0.05-5        0.87         < 0.20-2.8
    Benzo[k]fluoranthene       12       0.1-0.9      < 0.06-5.1                     1.2                          < 0.01-< 3
    Chrysene                   58       1.3-14                      < 0.1-3
    Dibenz[a,h]anthracene                            < 1-20         < 0.01-< 4                   < 0.06
    Fluoranthene               80       0.9-94       < 1-450        0.4-22                                       470
    Fluorene                   21                                   0.1-0.8
    Indeno[1,2,3-cd]pyrene              1.7                         < 0.01-5
    1-Methylphenanthrene                                                                                         3.5
    Naphthalene                35                    5-48           0.8-7
    Perylene                                         < 1-130
    Phenanthrene               220      4.9-77       < 1-45         2-38                                         6.7
    Pyrene                     200      1.6-50       < 1-645        < 0.4-15        7.0-52
    Triphenylene                                                                                                 0.03
                                                                                                                         

    Table 62 (continued)

    [1] Crassostrea virginica, Lake Pontchartrain, USA, 1980 (McFall et al., 1985);
    [2] Crassostrea virginica; Palmetto Bay (Marina), USA (Marcus & Stokes, 1985);
    [3] Crassostrea virginica; Chesapeake Bay, USA, 1983-84; concentration in µg/kg dry weight (Bender & Huggett, 1988);
    [4] Saccostrea cucculata, Mermaid Sound, Australia, 1982 (Kagi et al., 1985);
    [5] Oyster, Japan (local market); 1977-78 (Obana et al., 1981a);
    [6] Oyster, near Miyagi Prefecture, Japan; reference weight not given (Takatsuki et al., 1985);
    [7] Ostrea plicatula; Gulf of Thailand, Thailand; reference weight not given (Hungspreugs et al., 1984)

    High-performance liquid chromatography or gas chromatography


        Table 63. Polycyclic: aromatic hydrocarbon concentrations (µg/kg wet weight)
    in crustacea (lobsters); background values

                                                                                       

    Compound                 [1]    [2]     [3]        [4]           [5]       [6]
                                                                                       

    Acenaphthene             ND     ND
    Benz[a]anthracene        655    179     9-38       Trace-133     6-79      6-17
    Benzo[a]pyrene           18     3.8     0.4-2.1    Trace-2       1.6-8     ND-1.6
    Benzo[b]fluoranthene     17     28      3-6.5      Trace-5.3     7-16      ND-0.8
    Benzo[e]pyrene           ND     170     12-23      ND-22         15-29     ND-3.6
    Benzo[ghi]perylene       11     63      1.4-6.8    Trace-2.0     2.4-10    ND-0.8
    Benzo[k]fluoranthene     2      4.4     0.8-1.9    Trace-11.6    1.9-8     ND-0.8
    Chrysene                 140    113     2.5-12     ND-14         2-43      ND
    Fluoranthene             ND     147     46-407     5.5-12        90-162    ND-34
    Fluorene                 ND     194
    Indeno[1,2,3-cd]pyrene   22     77      2.1-5.0    ND-3.7        Trace-5   ND-0.8
    Phenanthrene             ND     1197    20-345     ND-15
    Pyrene                   ND     174     ND-197     ND-5          35-46     ND-22
    Triphenylene             ND     1373    ND-141     ND-Trace
                                                                                       

    ND, not detected
    [1] Homarus americanus (digestive gland); Port Hood, Canada, 1979 (Sirota & Uthe, 1981);
    [2] Homarus americanus (digestive gland); Brown Bank (offshore), Canada, 1979 (Sirota & Uthe, 1981);
    [3] Homarus americanus (hepatopancreas); Morien Bay and Mira Bay, Canada (Sirota et al.,1983);
    [4] Homarus americanus (tail muscle); Moran Bayand, Mira Bay, Canada (Sirota et al., 1983);
    [5] Homarus americanus (digestive gland); Port Morien, Canada, 1982-84 (Uthe & Musial, 1986);
    [6] Homarus americanus (tail muscle); Port Morien, Canada, 1982-84 (Uthe & Musial, 1986)

    Analysed by high-performance liquid chromatography or gas chromatography


        Table 64. Polycyclic aromatic hydrocarbon concentrations (µg/kg wet weight) in fish and other aquatic species
    (background values)
                                                                                                                                 
    Compound                 [1]      [2]       [3]     [4]      [5]           [6]    [7]         [8]        [9]          [10]
                                                                                                                                 
    Anenaphthene                      ND-83             11                     7                  1-500
    Acenaphthylene                                                             43                 0.8-24
    Anthracene                                          10                            2.0-2.2     ND                      20
    Benz[a]anthracene                                                          4      4.0-26      1.2        1.6-7.5      20
    Benzo[a]fluorene                                                                                                      ND
    Benzo[e]pyrene                                               0.04-0.84     1      1.9-15      8          Trace-4.5    5
    Benzo[b]fluoranthene                                                              3.2-17
    Benzo[e]pyrene                                                                                ND
    Benzo[ghi]perylene                                                                2.0-14      16
    Benzo[k]fluoranthene                                                              2.1-11
    Chrysene                                    6                              3      3.4-26      NR
    Dibenz[a,h]anthracene                                                             1.2-4.13
    Fluoranthene             4-95               4       85                     9      ND-732                              20
    Fluorene                                            8.9                           ND-15       1-370                   ND
    Indeno[1,2,3-cd]pyrene                                                            ND-15       NR
    1-Methylphenanthrene                                                                          NR
    Naphthalene              45-215   ND-117
    Perylene                                                                                      NR
    Phenanthrene             8-142              2       157      2.3-35        36     23-43       ND                      40
    Pyrene                   2-62               4       30                     31     2.4-74      1.3-9.6                 ND
    Triphenylene                                                                                                          20
                                                                                                                                 

    ND, not detected; NR, not reported;
    [1] Various seafish (muscle, liver, gall), Finnish archipelago, Finland, 1979 (Rainio et al., 1986);
    [2] Edible tissues of various seafish, Arabian Gulf, Iraq (DouAbdul et al., 1987);
    [3] Whole bullhead catfish (ictalurus nebulosus), Buckeye Lake, USA (Vassilaros et al., 1982);
    [4] Whole bullhead catfish (Ictalurus, nebulosus;, whole), Black River, USA (West et al, 1985);
    [5] Whole fish, Hersey River, USA (Black et al., 1981);
    [6] Whole striped bass (Morone saxatillis); Potomac River, USA (Vassilaros et al., 1982);
    [7] White suckers (Catastomus commersoni); stomach contents; Lake Erie, USA (Maccubbin et al., 1985);
    [8] Various fish, Japan, 1970-91 (Environment Agency, Japan, 1993);
    [9] Fish bought in market, Ibadan, Nigeria; reference weight not given (Emerole et al., 1982);
    [10] Whole holothurians, France; concentration in µg/kg dry weight (Milano et al., 1986)
    Analysed by high-performance liquid chromatography or gas chromatography


    The levels in holothurians from urban sewage were 1-15 mg/kg (Milano
    et al., 1986).

    Concentrations of 1-5 mg/kg individual PAH were found in limpets
     (Patella vulgata) in the North Sea (Knutzen & Sortland, 1982). The
    PAH concentrations in two species of bivalves in Saudafjorden (Norway)
    near an iron alloy smelter decreased rapidly with distance from the
    source, but the compounds could still be detected more than 15 km
    away. High levels of individual PAH were reported in mussels
     (Modiolus modiolus), with maximum levels of 57 000 µg/kg
    benzo [b]fluoranthene, 25 000 µg/kg benz [a]anthracene, 23 000 µg/kg
    benzo [e]pyrene, 21 000 µg/kg benzo [a]pyrene, 20 000 µg/kg
    fluoranthene, 8200 µg/kg pyrene, 6000 µg/kg benzo[ghi]perylene, 4000
    µg/kg perylene, 2900 µg/kg benzo [a]fluorene, 2300 µg/kg
    benzo [b]fluorene, 2200 µg/kg dibenz [a,h]anthracene, 2000 µg/kg
    benzo [c]phenanthrene, 1100 µg/kg phenanthrene, 524 µg/kg anthracene,
    and 360 µg/kg anthanthrene (Bjœrseth, 1979). A very high level of
    anthracene (243 µg/kg) was found in mussels  (Mytilus edulis L.) in
    the North Sea near the Dutch coast (Boom, 1987). Mussels in the USA
    frequently contained up to 500 µg/kg of individual PAH (Heit et al.,
    1980; Mix & Schaffer, 1983).

    The levels of PAH in pooled mussel samples in 1986, 1988, and 1990 in
    Germany were about 10 µg/kg for fluoranthene, pyrene, chrysene plus
    triphenylene, benzo [b]fluoranthene plus benzo [j]fluoranthene plus
    benzo [k]fluoranthene, and benzo [e]pyrene and < 4 µg/kg for
    benzo [ghi]fluoran-thene plus benzo [c]phenanthrene,
    benz [a]anthracene, benzo [a]pyrene, indeno[1,2,3- cd]pyrene,
    dibenz [a,h]anthracene, benzo [ghi]perylene, anthanthrene, and
    coronene. The levels were high in the winter months and low in summer,
    with minima in June and April. The authors concluded that this
    seasonal variation was due to more intensive metabolic activity (Jacob
    & Grimmer, 1994).

    During 1978-79, the average total PAH concentrations in two
    subpopulations of softshell clams were 555 µg/kg in the industrialized
    bayfront area of Coos Bay, Oregon, and 76 µg/kg in a more remote
    environment. During 1979-80, low-molecular-mass, readily water-soluble
    PAH were one or two orders of magnitude more concentrated then
    high-molecular-mass, less water-soluble PAH in mussels  (M. edulis)
    (Mix & Schaffer, 1983).

    Individual PAH levels of 1-20 mg/kg were found in the hepatopancreas
    of lobsters  (Homarus americanus) in the south arm of Sydney Harbour,
    Canada, near a coking plant (Sirota et al., 1983), and levels of the
    same order of magnitude were found in the digestive gland (Uthe &
    Musial, 1986). The levels in digestive gland, tail muscle, and
    hepatopancreas from lobsters from other areas of Canada were 100-1000
    µg/kg (Sirota & Uthe, 1981; Sirota et al., 1983; Uthe & Musial, 1986).

    High PAH levels were found in oysters  (Crassostrea virginica) in
    Chesapeake Bay, USA, with maximum levels of 650 µg/kg pyrene, 450
    µg/kg benzo [e]pyrene, 450 µg/kg fluoranthene, 290 µg/kg
    benzo [a]pyrene, 130 µg/kg benz [a]anthracene, 130 µg/kg perylene,
    73 µg/kg benzo [ghi]-perylene, 70 µg/kg benzo [c]phenanthrene, 48
    µg/kg naphthalene, 45 µg/kg phenanthrene, 40 µg/kg anthracene, and 20
    µg/kg dibenz [a,h]anthracene. The levels of PAH in clams
     (Rangia cuneata) from Chesapeake Bay were 170 µg/kg
    benzo [a]pyrene, 170 µg/kg pyrene, 52 µg/kg fluoranthene, 15 µg/kg
    phenanthrene, 10 µg/kg perylene, 10 µg/kg benzo [ghi]perylene, 9
    µg/kg benzo [c]phenanthrene, and 6 µg/kg benz [a]anthracene (Bender
    & Huggett, 1988).

    Phenanthrene was found at 15 mg/kg in lampreys  (Pteromyzon sp.) in
    the Hersey River, USA, which was polluted with creosote used for wood
    preservation (Black et al., 1981).

    The viviparous blenny  (Zoarces viviparus) fish contained 0.06 µg/kg
    benzo [a]pyrene and 0.2-3.9 µg/kg phenanthrene and fluoranthene; the
    concentrations of other PAH were below the detection limit (0.01
    µg/kg). In bream  (Abramis brama) the levels were <  0.01-0.15 µg/kg
    benzo [a]pyrene and 1.3-15 µg/kg phenanthrene. Mussels  (Mytilus
    sp.) were shown to accumulate PAH and were thus a better marker for
    PAH contamination (Jacob & Grimmer, 1994, 1995).

    The concentrations of individual PAH in English sole
     (Paraphrys vetulus) taken from near petroleum storage tanks were 1-5
    mg/kg (Malins et al., 1985).

    5.1.7.2  Terrestrial organisms

    The liver of wild deer mice  (Peromyscus maniculatus) trapped at a
    PAH-contaminated site in South Carolina, USA (Whidbey Island Naval Air
    Station) had levels of PAH ranging from 0.075 for
    benzo [b]fluoranthene to 4.6 mg/kg for benz [a]anthracene.
    Acenaphthylene, acenaphthene, fluorene, benz [a]-anthracene,
    chrysene, benzo [b]fluoranthene, benzo [k]fluoranthene,
    dibenz [a,h]anthracene, and indeno[1,2,3- cd]pyrene were detected.
    Liver from mice at an uncontaminated reference site contained
    measurable amounts of only benz [a]anthracene (0.55 mg/kg) and
    acenaphthylene (2.2 mg/kg) (Dickerson et al., 1994).

    In a study of PAH levels in terrestrial organisms from a roadside in
    Brisbane, Australia, 16 PAH were determined: naphthalene, fluorene,
    phenanthrene, anthracene, fluoranthene, pyrene, benz [a]anthracene,
    chrysene, benzo [k]fluoranthene, benzo [e]pyrene, benzo [a]pyrene,
    perylene, indeno[1,2,3- cd]pyrene, dibenz [a,h]anthracene,
    benzo [ghi]perylene, and coronene. In the beetle  Laxta 
     granicollis, pyrene and benzo [ghi]perylene were present at the
    highest levels, at 20 µg/kg wet weight each; phenanthrene and
    fluoranthene were present at about 10 µg/kg; and the concentrations of
    other PAH were < 5 µg/kg. Naphthalene, anthracene,
    dibenz [a,h]anthracene, and coronene were not detected. Fluorene, at

    a concentration of 11 µg/kg wet weight, was the most abundant PAH in
    the beetle  Platyzosteria nitida; the concentrations of other PAH
    were < 5 µg/kg; whereas naphthalene, dibenz [a,h]anthracene, and
    coronene were not detected. In millipedes (myriapods),
    benzo [k]fluoranthene was the most abundant PAH (19 µg/kg wet
    weight); the pyrene concentration was 12 µg/kg; those of other PAH
    were < 5 µg/kg wet weight; and dibenz [a,h]anthracene and coronene
    were not detected. In centipedes  (Myriaod sp.), no PAH were
    detected. In slugs  (Arion ater), benzo [k]fluoranthene showed the
    highest concentration, at 19 µg/kg wet weight; the pyrene and
    naphthalene levels were about 10 µg/kg; those of other PAH were < 5
    µg/kg wet weight; and anthracene, perylene, dibenz [a,h]anthracene,
    and coronene were not detected. In earthworms  (Lumbricus 
     terrestris), benzo [ghi]perylene was the most abundant PAH (28
    µg/kg wet weight); phenanthrene, fluoranthene, pyrene, chrysene,
    benzo [k]fluoranthene, benzo [e]pyrene, benzo [a]pyrene were
    present at about 10 µg/kg; and naphthalene and dibenz [a,h]anthracene
    were not detected (Pathirana et al., 1994).

    The PAH concentrations in earthworms did not seem to be affected by
    the location in which the worms lived, but those in the faeces showed
    a significant dependence on location. In a survey of earthworm faeces
    from the Bornhöveder Lake district in 1988, the concentrations of
    phenanthrene, fluoranthene, pyrene, and benzo [b]fluoranthene plus
    benzo [j]fluoranthene plus benzo [k]fluoranthene were in the range
    of 45 µg/kg; those of benz [a]anthracene, chrysene plus triphenylene,
    benzo [e]pyrene, benzo [a]pyrene, indeno[1,2,3- cd]pyrene, and
    benzo [ghi]perylene were about 20 µg/kg; and those of anthracene,
    benzo [ghi]fluoranthene plus benzo [c]phenanthrene,
    dibenz [a,h]anthracene, anthanthrene, and coronene were < 5 µg/kg.
    Earthworm faeces in the Saarland contained 250-770 µg/kg
    benzo [a]pyrene, and  Allolobophora longa earthworm faeces from a
    highly industrialized region of eastern Germany (Halle, Leipzig)
    contained even higher concentrations: 37-2100 µg/kg benzo [a]pyrene
    and 36-1700 µg/kg benzo [e]pyrene. The faeces of the earthworm
     Lumbricus terrestris contained 4.6-55 µg/kg benzo [a]pyrene and
    6.5-50 µg/kg benzo [e]pyrene (Jacob & Grimmer, 1995).

    In insects near the Hersey River, USA, the maximum concentrations of
    PAH were 5500 µg/kg phenanthrene, 2900 µg/kg benz [a]anthracene, and
    730 µg/kg benzo [a]pyrene (Black et al., 1981).

    The lipid fraction of liver from herring gulls  (Larus argentatus)
    from Pigeon Island and Kingston, Ontario, Canada, contained 0.15 µg/kg
    anthracene, 0.082 µg/kg fluoranthene, 0.076 µg/kg pyrene, 0.05 µg/kg
    naphthalene, 0.044 µg/kg fluorene, 0.038 µg/kg acenaphthene, and 0.038
    µg/kg benzo [a]pyrene (Environment Canada, 1994). The concentrations
    of PAH in pooled samples taken from the eggs of herring gulls
     (Larus argentatus) on the German North Sea islands Mellum and
    Trischen during 1992-93 were below the limit of detection, except for
    that of phenanthrene, which was 1 µg/kg wet weight (Jacob & Grimmer,
    1994).

    5.2  Exposure of the general population

    Possible sources of nonoccupational exposure to PAH are:

    -    polluted ambient air (main emission sources: vehicle traffic,
         industrial plants, and residential heating with wood, coal,
         mineral oil) (see section 5.1.1);

    -    polluted indoor air (main emission sources: open stoves and
         environmental tobacco smoke) (see Table 65);

    -    tobacco smoking (see Table 66);

    -    contaminated food and drinking-water (see sections 5.1.5 and
         5.1.2.3)

    -    use of products containing PAH (coal-tar skin preparations and
         coal-tar-containing hair shampoos);

    -    ingestion of house dust; and

    -    dermal absorption from contaminated soil and water.

    5.2.1  Indoor air, tobacco smoke, and environmental tobacco smoke

    PAH are found in indoor air (Table 65) mainly as a result of tobacco
    smoking and residential heating with wood, coal, or, in some
    developing countries, rural biomass. The PAH levels in indoor air
    usually range from 1 to 50 ng/m3. The most abundant PAH were
    phenanthrene and naphthalene, with levels of up to 2300 ng/m3. Homes
    with gas heating systems had higher indoor levels than those with
    electric heating systems (Chuang et al., 1991), and even higher levels
    were detected in indoor air near open fireplaces (Alfheim & Ramdahl,
    1984). Airtight residential wood-burning stoves seemed to have a minor
    effect on the indoor air concentration of PAH (Alfheim & Ramdahl,
    1984; Traynor et al., 1987), but in homes with non-airtight wood
    stoves, 2-46 times higher PAH concentrations were found during heating
    periods than during periods without heating (Daisey et al., 1989).

    Emissions from unvented kerosene heaters can significantly affect
    indoor air quality in mobile homes, with a maximim value for
    naphthalene of 2300 ng/m3. Four of eight heaters investigated emitted
    PAH-containing particles at levels that exceeded the USA ambient air
    standards for airborne particles, with a 50% cutoff at the aerodynamic
    diameter of 10 µm. When the kerosene heaters were in operation, the
    concentrations of carcinogenic PAH (with four rings or more) in the
    mobile homes were increased by 10-fold (Mumford et al., 1991).


        Table 65. Polycyclic: aromatic hydrocarbon concentrations (ng/m3) in indoor air; main source, residential heating

                                                                                                                              

    Compound                     [1]      [2]      [3]      [4]     [5]    [6]            [7]         [8]           [9]
                                                                                                                              

    Acenaphthene                                                           NR                                       589-1649
    Acenaphthylene                                                         NR                                       60-592
    Anthracene                            5-30     408      5-15    84     NR                                       9.9-11
    Benz[a]anthracene                     3-9      2-6      3-13    145    NR                                       0.9-5.5
    Benzo[a]pyrene               13-370   0.3-12   1-7      3-23    150    < 0.009-1.34   0.34-3.5    2.0-490       8.5-29
    Benzo[b]fluoranthene                                                   < 0.007-0.68   0.17-3.8    1.4-420       5.6-21
    Benzo[e]pyrene                                                         < 0.06-1.36
    Benzo[ghi]perylene           14-340   0.4-10   1-7      3-30    125    < 0.01-6.20    0.37-3.7    2.8-450       0.4-7.5
    Benzo[k]fluoranthene         5-150    0.07-7   0.6-3    2-10    63     0.005-0.48     0.07-1.9    0.67-200      0.7-21
    Chrysene                              2-12     3-6      4-13    115    NR
    Coronene                                                               NR
    Cyclopenta[cd]pyrene                                                   NR
    Dibenzo[a,e]pyrene                                                     NR
    Dibenz[a,h]anthracene                                                  NR                                       3.3-25
    Fluoranthene                          16-56    16-24    16-50   208    0.07-1.18                                87-268
    Fluorene                                                               NR
    Indeno[1,2,3-cd]pyrene       20-560   1-16     1-8      3-22    130    < 0.02-3.54    1.1-6.1     3.9-740       2.3-11
    Phenanthrene                          120-400  120-200  140-290 555    NR                                       31-64
    Pyrene                                                                 0.02-1.53                                1.0-20
                                                                                                                              

    ND, not determined; NR, not reported; /, single measurements;
    [1] Wood-burning open fire-place, Netherlands (Slooff et al., 1989);
    [2] Wood in multi-burner, Netherlands (Slooff et al., 1989);
    [3] Coal, Netherlands (Slooff et al., 1989);
    [4] Briquettes, Netherlands (Slooff et al., 1989);
    [5] 'Icopower' heating, Netherlands (Slooff et al., 1989);
    [6] Wood heating in seven homes, USA (Daisey et al., 1989);
    [7] Wood burning in one home; volume, 236 m3; airtight stove, Truckee, USA, (elevation, 1800 m) (Traynor et al., 1987);
    [8] Wood burning in one home; volume, 236 m3; non-airtight stove, Truckee, USA (elevation, 1800 m) (Traynor et al., 1987);
    [9] Wood burning in one home with four different heaters, USA (Knight & Humphreys, 1985)

    Analysed by high-performance liquid chromatography or gas chromatography

    Table 65 (contd)

                                                                                                                              

    Compound                 [10]         [11]         [12]         [13]          [14]        [15]      [16]       [17]
                                                                                                                              

    Acenaphthene                                                    NR                                             1-258
    Acenaphthylene           10-120       21/68        25-36        NR                                             1-753
    Anthracene               1.5-15                    4.2-5.9      NR                                             0.1-80
    Benz[a]anthracene        0.24-3.4     0.72/2.8     0.55-1.0     ND-3.81       25 100      1000      4000       5-1021
    Benzo[a]pyrene           0.28-3.3     0.24/2.0     0.54-1.0     ND-4.13       14 700      600       3100       8-1645
    Benzo[b]fluoranthene                                            NR                                             2-930
    Benzo[b]pyrene           0.33-10                   1.4-3.0      NR                                             5-1106
    Benzo[ghi]perylene       0.32-2.5     0.22/3.7     0.72-1.0     ND-5.4                                         4-802
    Benzo[k]fluoranthene                                            ND-7.81a                                       4-824
    Chrysene                 0.58-7.2     1.5/3.1      1.4-2.2      0.18-8.61                                      7-1439
    Coronene                 0.31-1.4     0.07/2.3     0.55-0.58    ND-4.75                                        NR
    Cyclopenta[cd]pyrene     0.18-2.0     0.49/4.2     0.36-0.59    ND-2.38       10 700      400       5600       NR
    Dibenzo[a,e]pyrene                                              NR            11 700      600       200        NR
    Dibenz[a,h]anthracene                                           NR                                             8-958
    Fluoranthene             6.2-23       16/11        11           2.4-37.4                                       5-1095
    Fluorene                                                        NR                                             3-275
    Indeno[1,2,3-cd]pyrene   0.24-1.8     0.15/1.3     0.48-0.79    ND-3.53       8400        500       2000       4-670
    5-Methylcholanthrene                                            NR            7300        200       200        NR
    Naphthalene              750-2200     2300/950     1200-1600    NR                                             NR
    Phenanthrene             55-210       48/34        93-110       9.2-210                                        3-667
    Pyrene                   3.6-17       9.7/13       6.9-7.6      1.4-18.1                                       7-850
                                                                                                                              

    [10] Gas or electridy, USA (Wilson & Chuang, 1991);
    [11] Kerosene; unvented heaters in mobile homes, Apex, USA (Mumford et al., 1991);
    [12] Various heating in eight homes, Columbus, USA (Chuang et al., 1991);
    [13] Various heating in 33 homes, USA (Wilson et al., 1991);
    [14] Smoky coal, Xuan Wei, China (Mumford et al., 1987);
    [15] Smokeless coal, Xuan Wei, China (Mumford et al., 1987);
    [16] Wood, Xuan Wei, China (Mumford et al., 1987);
    [17] Various cooking fuels (cattle dung, wood, kerosene, liquid petroleum gas) in 60 homes, India
    (Raiyani et al., 1993b)

    a Sum of benzofluranthenes


        Table 66. Polycyclic aromatic hydrocarbon concentrations (ng/m3 in indoor air;
    main source, environmental tobacco smoke

                                                                                        

    Compound                    [1]     [2]     [3]        [4]      [5]           [6]
                                                                                        

    Acenaphthene                2.5     36
    Acenaphthylene              14      177
    Anthracene                  2.8     25      1.5        < 1
    Anthanthrene                0.5     1.5     < 1        2.5                    3
    Benz[a]anthracene           1.3     12      15         13
    Benzo[a]fluorene                            5.5                               39
    Benzo[a]pyrene              1.8     7.3     14         4.5      0.04-0.16     22
    Benzo[b]fluoranthene                                            0.06-0.08
    Benzo[b]fluorene                            2.5
    Benzo[e]pyrene              2.3     7.1     11         4.5                    18
    Benzo[ghi]fluoranthene      4.3     18      8.5        14
    Benzo[ghi]perylene          2.5     5.8     7          2        0.09-0.36     17
    Benzo[k]fluoranthene                                            0.02-0.06
    Coronene                    2.0     3.1
    Fluoranthene                14      41      5          16                     99
    Indeno[1,2,3-cd]pyrene      2.3     5.8     1          1.5      0.13-0.45
    1-Methylphenanthrene        6.6     38      < 1        3.5
    Perylene                    0.5     0.8     4          2.5                    11
    Phananthrene                38      168     3          1
    Pyrene                      13      32      13         21                     66
                                                                                        

    [1] Office room (volume, 88 m3; ventilation, 176 m3/h; background sample after weekend,
        Finland; vapour and particulate phase (Salomaa et al., 1988);
    [2] Office room (Volume, 88 m3; ventilation, 176 m3/h; 6 h; 96 cigarettes, American
        type, 10 different brands, both medium- and low tar, Finland; vapour and particulate
        phase (Salomaa et al., 1988);
    [3] House in a forest (room volume, 65 m3; air exchange, 2.0-2.3 turnovers/h); background
        sample, Norway (Alfheim & Ramdahl, 1984);
    [4] House in a forest (room volume, 65 m3; air exchange, 2.0-2.3 turnovers/h); with
        tobacco smoking, Norway (Alfheim & Ramdahl, 1984);
    [5] House in a residential, wooded area of Truckee, USA (elevation, 1800 m); volume,
        236 m3; no stove (Traynor et al., 1987);
    [6] Model room (volume, 36 m3); one air exchange/h, smoking of five cigarattes/h (Ministry
        of Environment, 1979))

    High-performance liquid chromatography or gas chromatography; concentration of particulate
    phase, unless otherwise stated

    Emissions from coal and wood combustion in open fires for cooking
    purposes in unvented rooms in Xuan Wei County, China, contained
    extremely high PAH concentrations (see also section 8). The highest
    concentration (benzo [a]pyrene at 15 000 ng/m3) was measured in
    fumes from smoky coal combustion. Coal combustion in open fires in
    Xuan Wei homes emitted 15 µg/m3 of carcinogenic PAH, while wood
    combustion emitted 3.1 µg/m3 (Mumford et al., 1987).

    Cooking with rural biomass in open fires also led to high PAH levels
    in indoor air, as measured in rural Indian households.
    Benzo [a]pyrene was measured at a concentration of about 4 µg/m3
    during the cooking period, which occupied about 10% of the household
    activities over the year. The cooking fuels included  baval, neem, 
    mango,  rayan, and crop residues (Smith et al., 1983). The total
    release of PAH into indoor air from this source is unknown but may be
    of major importance, especially in developing countries. Very low PAH
    emissions were found when liquid petroleum gas was used as a fuel for
    cooking (Raiyani et al., 1993b). In contrast, the PAH content of
    kitchen air in Berlin, in the industrialized part of Germany, was
    similar to that encountered in ambient air (Seifert et al., 1983).

    House dust may be another important source of indoor pollution with
    PAH. In a study of the homes of four smokers and four nonsmokers in
    Columbus, Ohio, USA, the sum of the concentrations of naphthalene,
    acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene,
    retene, fluoranthene, pyrene, benz [a]anthracene, chrysene,
    cyclopenta [cd]pyrene, benzo [b]fluoranthene,
    benzo [j]fluoranthene, benzo [k]fluoranthene, benzo [e]pyrene,
    benzo [a]pyrene, indeno[1,2,3- cd]pyrene, dibenz [a,h]anthracene,
    benzo [ghi]perylene, and coronene in house dust and in soil from the
    entryway, the pathway, and the foundation of the houses was 16-580
    mg/kg. The concentrations in house dust correlated well with those in
    the entryway soil samples, and a weaker correlation was found with the
    pathway soil samples, but the relationships were not statistically
    significant (Chuang et al., 1995).

    A special source of exposure to PAH is wood-heated saunas. The highest
    concentrations were found in a smoke sauna, the second highest in a
    preheated sauna where the flues were closed before use, and the lowest
    concentrations in a sauna heated by continuous burning of wood.
    Pyrene, fluoranthene, benz [a]anthracene, and phenanthrene were
    present at the highest levels  (100-330 µg/m3 air); other PAH were
    present at < 50 µg/m3. The concentrations decreased from
    benzo [e]pyrene > benzo [a]pyrene > benzo [a]fluorene >
    anthra-cene > benzo [b]fluorene > fluorene (Häsänen et al., 1983).

    The protocol of a study of total human environmental exposure included
    direct monitoring of exposure to benzo [a]pyrene by inhalation and
    ingestion during three periods of 14 days. The range and magnitude of
    dietary exposure (2-500 ng/day) was much greater than that by
    inhalation (10-50 ng/day). The levels of benzo [a]pyrene in indoor
    air were closely correlated with the ambient levels in most homes
    (Waldman et al., 1991).

    Indoor air concentrations of individual PAH due mainly to cigarette
    smoke are shown in Table 66, and the levels in mainstream and
    sidestream smoke of cigarettes are listed in Table 67. The average PAH
    levels ranged from 1 to 50 ng per cigarette, and the major components
    were phenanthrene, naphthalene, benzo [a]pyrene, benzo [e]pyrene,
    fluoranthene, and pyrene. Sidestream smoke was found to contain 10
    times more PAH than mainstream smoke. The levels in sidestream smoke
    were 42-2400 ng per cigarette (Grimmer et al., 1987). The PAH
    concentrations in the mainstream smoke from filter cigarettes
    increased with increasing puff volume (Funcke et al., 1986). In a
    pilot study in Columbus, Ohio, USA, naphthalene was the most abundant
    PAH; environmental tobacco smoke appeared to be the most significant
    source of indoor pollution (Chuang et al., 1991).

    Table 67. Concentrations of selected polycyclic aromatic hydrocarbons
    in cigarette smoke

                                                                          
    Compound                    Mainstream smoke      Sidestream smoke
                                (µg/100 cigarettes)   (µg/100 cigarettes)
                                                                          
    Anthracene                  2.3-23.5
    Anthanthrene                0.2-2.2               3.9
    Benz[a]anthracene           0.4-7.6
    Benzo[b]fluoranthene        0.4-2.2
    Benzo[b]fluoranthene        0.6-2.1
    Benzo[k]fluoranthene        0.6-1.2
    Benzo[ghi]fluoranthene      0.1-0.4
    Benzo[a]fluorene            4.1-18.4              75.0
    Benzo[b]fluorene            2.0
    Benzo[ghi]perylene          0.3-3.9               9.8
    Benzo[c]phenanthrene        Present
    Benzo[a]pyrene              0.5-7.8               2.5-19.9
    Benzo[e]pyrene              0.2-2.5               13.5
    Chrysene                    0.6-9.6
    Coronene                    0.1
    Dibenz[a,h]anthracene       0.4
    Dibenzo[a,e]pyrene          Present
    Dibenzo[a,h]pyrene          Present
    Dibenzo[a,i]pyrene          0.17-0.32
    Dibenzo[a,l]pyrene          Present
    Fluoranthene                1.0-27.2              126.0
    Fluorene                    Present
    Indeno[1,2,3-cd]pyrene      0.4-2.0
    5-Methylcholanthrene        0.06
    Perylene                    0.3-0.5               3.9
    Phenanthrene                8.5-62.4
    Pyrene                      5.0-27                39.0-101.0
    Triphenylene                Present
    1-Methylphenanthrene        3.2
                                                                          

    Adapted from International Agency for Research on Cancer (1985)

    In studies in eight healthy male smokers, aged 20-40 years, the
    benzo [a]pyrene intake from the smoking of 20 cigarettes per day was
    calculated to be 150-750 ng/d, assuming a deposition rate for
    particulate matter of 75% (Scherer et al., 1990).

    The total concentration of 14 PAH (fluoranthene, pyrene,
    benzo [a]fluorene, benz [a]anthracene, chrysene,
    benzo [b]fluoranthene, benzo [j]fluoranthene,
    benzo [k]fluoranthene, benzo [e]pyrene, benzo [a]pyrene, perylene,
    dibenz [a,h]-anthracene, benzo [ghi]perylene, and anthanthrene)
    measured in a 36-m3 room into which sidestream smoke from five German
    cigarettes was introduced every hour, with one air change per hour,
    was 429 ng/m3. Assuming that the daily inhalation volume for adults
    is 18 m3 and that 20 h/d are spent indoors, the volume of indoor air
    inhaled daily is 18 m3 × 20/24 = 15 m3. Thus, passive smokers are
    exposed daily to 15 × 429 = 6435 ng PAH, including 15 × 22 = 330 ng
    benzo [a]pyrene (Ministry of Environment, 1979). An intake of 11 ng
    benzo [a]pyrene was estimated in another study on the basis of an
    assumed breath volume of 0.5 m3/h , a deposition rate for particulate
    matter of 11%, and an exposure time of 8 h, after monitoring in an
    unventilated, 45-m3, furnished room (Scherer et al., 1990).

    5.2.2  Food

    Smoked and barbecued food in particular can contain PAH (Grimmer &
    Düvel, 1970; McGill et al., 1982; de Vos et al., 1990; Menichini et
    al., 1991b; see also section 5.1.5 and Tables 51-56). Preparation of
    food with contaminated drinking-water (see section 5.1.2.3) may also
    lead to exposure to PAH.

    In 1989 and 1990, the levels of naphthalene and alkylated derivatives,
    acenaphthene, acenaphthylene, fluorene, phenanthrene, anthracene,
    fluoran-thene, 1-methylphenanthrene, pyrene, benz [a]anthracene,
    chrysene, benzo [b]fluoranthene, benzo [k]fluoranthene,
    benzo [e]pyrene, benzo [a]pyrene, perylene,
    indeno[1,2,3- cd]pyrene, dibenz [a,h]anthracene, and
    benzo [ghi]-perylene were measured in salmon, herring, cod, rockfish,
    and halibut in the area of the Gulf of Alaska where oil spilled from
    the tanker  Exxon Valdez. As only the sums of the concentrations were
    considered, there was no apparent difference from those in fish
    samples taken from unpolluted control sites in 1989. In 1990, slightly
    elevated PAH concentrations were found at the polluted sampling site.
    Nevertheless, the fish from the area were considered to be safe for
    human consumption by these investigators (Saxton et al., 1993).

    In another special exposure situation, the average daily PAH intake of
    the inhabitants of Kuwait due to consumption of seafood after the war
    in the Persian Gulf was calculated to be 0.23 µg/day on the basis of
    the concentrations monitored in local fish and shrimps (Saed et al.,
    1995).

    5.2.3  Other sources

    Benzo [a]pyrene was detected in coal-tar-containing hair shampoos at
    levels of 7000-61 000 µg/kg, and a tar bath lotion contained 150 000
    µg/kg benzo [a]pyrene. No PAH were detected in hair shampoos made
    from wood tar (State Chemical Analysis Institute Freiburg, 1995). PAH
    are absorbed from coal-tar shampoos through the skin during hair
    washing. Exposure during one washing with this type of shampoo, which
    contains benzo [a]pyrene at 56 mg/kg, for anti-dandruff therapy
    results in absorption of 0.45 µg/kg body weight, assuming 20 g
    coal-tar, 70 kg body weight, and 3% dermal absorption (van Schooten et
    al., 1994; see also section 8).

    5.2.4  Intake of PAH by inhalation

    Estimates of PAH intake from air are summarized in Table 68.

    In an assessment of the risk for cancer due to air pollution in
    Germany, the average volume of air inhaled during heavy work was
    assumed to be 140 m3 per person per week. The maximum intake of
    airborne benzo [a]pyrene per week was thus estimated to be
    0.21 µg/week in rural areas, 0.84 µg/week in industrial areas, and
    7 µg/week near emission sources (State Committee for Air Pollution
    Control, 1992).

    On the basis of an average inhalation of 15 m3 air per day, exposure
    to benzo [a]pyrene was calculated to be 0.05 µg/d. In industrial
    areas, the exposure was calculated to be four times higher (0.19 µg/d)
    (Raiyani et al., 1993a).

    5.2.5  Intake of PAH from food and drinking-water

    Estimates of PAH intake from food are shown in Table 69. The values
    for benzo [a]pyrene range from 0.14-1.6 µg/d.

    The total dietary intake of some PAH in the United Kingdom was
    estimated to be (µg/person per day): 1.1 for pyrene, 0.99 for
    fluoranthene, 0.50 for chrysene, 0.25 for benzo [a]pyrene, 0.22 for
    benz [a]anthracene, 0.21 for benzo [ghi]perylene, 0.18 for
    benzo [b]fluoranthene, 0.17 for benzo [e]pyrene, 0.06 for
    benzo [k]fluoranthene, and 0.03 for dibenz [a,h]anthracene. The
    major contributors of PAH to the total dietary intake appeared to be
    oils and fats, with 28% from butter, 20% from cheese, and 17% from
    margarine, in respective dietary survey groups; cereals provided 56%
    from white bread and 12% from flour. The oils and fats had the highest
    individual PAH levels. Although cereals did not contain high levels of
    individual PAH, they were the main contributor by weight to the total
    in the diet. Fruits and vegetables contributed most of the rest of the
    PAH in the diet, while milk and beverages were of minor importance.
    Smoked meat and smoked fish made very small contributions to the food
    groups to which they belonged, which themselves were not major
    components of the diet (Dennis et al., 1983).


        Table 68 Estimated intake of polycyclic aromatic hydrocarbons (µg/day per person) from ambient air

                                                                                                                                        

    Compound                 [1]           [2]           [3]     [4]      [5]            [6]       [7]        [8]          [9]
                                                                                                                                        

    Anthracene                                           0.005                                     0.001
    Anthanthrene                                         0.015
    Benz[a]anthracene                                    0.030                                     0.013
    Benzo[a]pyrene           0.01-0.03a    0.0025-0.025  0.025   0.034a   0.0095-0.0435  0.004a    0.017      0.03-0.05    0.0005-0.20
                             0.02-0.12b
                             0.06-1.0c
    Benzo[b]fluoranthene                                 0.060                                     0.029
    Benzo[b]fluorene                                     0.002                                     0.002
    Benzo[e]pyrene                                       0.035                                     0.022
    Benzo[ghi]perylene                                   0.030                                     0.027
    Benzo[j]fluoranthene                                 0.010
    Benzo[k]fluoranthene                                 0.015                                     0.015
    Chrysene                                             0.035
    Coronene                                             0.025
    Dibenz[a,h]anthracene                                0.020                                     0.004
    Fluoranthene                                         0.040                                     0.016
    Fluorene                                                                                       0.0005
    Indeno[1,2,3-cd]pyrene                               0.030                                     0.024
    Perylene                                             0.015                                     0.003
    Phenanethrene                                        0.200                                     0.007
    Pyrene                                               0.040                                     0.017
    Triphenylene                                         0.220
                                                                                                                                        


    Table 68 (continued)


    [1] Germany (maximum concentrations) (State Committee for Air Pollution Control, 1992);
    [2] Italy (Menichini, 1992a);
    [3] Netherlands (maximum concentrations) (Guicherit & Schulting, 1985);
    [4] United Kingdom (maximum concentrations) (Butler & Crossley, 1979);
    [5] USA (Santodonato et al., 1980);
    [6] USA (WHO, 1987);
    [7] Japan (maximum concentrations) (Matsumoto & Kashimoto, 1985);
    [8] China (Chen et al., 1980);
    [9] India (Chakraborti et al., 1988)

    a Rural areas
    b Industrial areas
    c Near emission source

    Table 69. Estimated intake of polycyciic aromatic hydrocarbons (µg/day per person, maximum values) from food

                                                                                                                  

    Compound                    [1]       [2]        [3]        [4]         [5]      [6]      [7]     [8]
                                                                                                                  

    Anthracene                  5.6
    Anthanthrene                0.30
    Benz[a]anthracene           0.14
    Benzo[a]pyrene              0.36      0.14-1a    0.1-0.3b   0.12-0.42   0.5      0.5      0.48    0.16-1.6
                                                     0.2c
    Benzo[b]fluoranthene        1.0
    Benzo[ghi]perylene          7.6                                         0.3      0.9
    Benzo[j]fluoranthene        0.90
    Benzo[k]fluoranthene        0.30
    Chrysene                    0.90                                                 5.0
    Coronene                    0.09
    Dibenz[a,h]anthracene       0.10
    Fluoranthene                4.3                                         3        10
    Indeno[1,2,3-cd]pyrene      0.31                                        0.4      <0.3
    Perylene                    0.20
    Phenanethrene               2.0
    Pyrene                      4.0                                                  5.1
                                                                                                                  

    [1] Austria (Pfannhauser, 1991);
    [2] Germany (State Committee for Pollution Control, 1992);
    [3] Italy (Menichini, 1992a);
    [4] Netherlands (de Vos et al., 1990);
    [5] Market basket study, Netherlands (Vaessen et al., 1984);
    [6] Duplicate diet study, Netherlands (Vaessen et al., 1984);
    [7] United Kingdom (Dennis et al., 1983);
    [8] USA (Santodonato et al., 1980)

    a Concentration in µg/week
    b Adult non-smoker (70 kg)
    c Mean concentration


    In Sweden, the annual intake per person of the sum of fluoranthene,
    pyrene, benz [a]anthracene, chrysene, triphenylene,
    benzo [b]fluoranthene, benzo [j]-fluoranthene,
    benzo [k]fluoranthene, benzo [e]pyrene, benzo [a]pyrene, and
    indeno[1,2,3- cd]pyrene was about 1 mg. Cereals again seemed to be
    the main contributor (about 34%), followed by vegetables (about 18%)
    and oils and fats (about 16%). Although smoked fish and meat products
    had the highest PAH levels, they made a modest contribution since they
    are minor components of the usual Swedish diet (Larsson, 1986).

    5.3  Occupational exposure

    PAH have been measured in the air at various workplaces. Studies in
    which measurements were reported only as the benzene-soluble fraction
    or some other summarizing parameter affected mainly by PAH are not
    covered because they do not refer to individual substances. The
    presence of PAH metabolites in biological samples (urine, blood) from
    workers has been used as a biomarker, and 1-hydroxypyrene seems to be
    a suitable marker in some workplaces (see section 8.2.3). No data were
    available on occupational exposure during production and use.

    Occupational exposure to PAH occurs by both inhalation and dermal
    absorption. In coke-oven workers, 75% of their exposure to total
    pyrene and 51% of that to benzo [a]pyrene occurs by cutaneous
    transfer (Van Rooij et al., 1993a; see also section 6). The exposure
    of workers due to deposition of airborne pyrene on the skin, detected
    in wipe samples, can be summarized as follows: in refineries,
    < 0.0045 µg/cm2 (detection limit), 26 samples below detection limit;
    in hot-mix asphalt facilities, < 0.0045 µg/cm2, 25 samples below
    detection limit; during paving, < 0.13-0.31 µg/cm2 found in two of
    nine samples (assuming a body area of 1.8 m2, equivalent to 5600
    µg/person per day); in asphalt roofing manufacture, < 0.0045-0.0091
    µg/cm2 found in 1 of 29 samples (assuming a body area of 1.8 m2,
    equivalent to 170 µg/person per day); in application of asphalt
    roofing, < 0.0045 µg/cm2, 10 samples below detection limit; in a
    wood preserving plant, 47-1500 µg pyrene per person per day. These
    data indicate that skin penetration is an important factor in
    estimating total body exposure to PAH.

    5.3.1  Occupational exposure during processing and use of of coal and
    petroleum products

    The following section is based on data obtained up to the early 1980s
    which were compiled by the IARC (1984b, 1985, 1989b). More recent
    studies are presented in detail.

    5.3.1.1  Coal coking

    In studies of pollution of the atmosphere near coke-oven batteries,
    the concentration of benzo [a]pyrene varied from < 0.1 in
    administrative buildings and a pump house to 100-200 µg/m3 on the
    machinery and discharge side of a battery roof. At the top of a coke
    battery, the following concentrations of particulate and gaseous PAH

    were measured by stationary sampling: naphthalene, 0-4.4
    (particulate)/ 280-1200 (gaseous) µg/m3; acenaphthene, 0-17/6.0-100
    µg/m3; fluorene, 0-58/23-130 µg/m3; phenanthrene, 27-890/6.7-280
    µg/m3; anthracene, 9.6-310/6.0-91 µg/m3; 1-methylphenanthrene,
    2.7-21/0-7.0 µg/m3; fluoranthene, 45-430/0-24 µg/m3; pyrene,
    35-320/0-14 µg/m3; benzo [a]fluorene, 9.7-90/0-6.8 µg/m3;
    benzo [b]fluorene, 3.1-61/0-0.3 µg/m3; benzo [c]phenanthrene,
    2.6-49 µg/m3 (particulate); benz [a]anthracene, 5.4-160/< 0.4-1.6
    µg/m3; benzo [b]fluoranthene, 5.5-67/0-0.7 µg/m3;
    benzo [j]fluoranthene plus benzo [k]fluoranthene, 0-35/0-0.7 µg/m3;
    benzo [e]pyrene, 8-73/0-0.2 µg/m3; benzo [a]pyrene, 14-130/0-1.5
    µg/m3; perylene, 3.3-19/0-0.1 µg/m3; benzo [ghi]perylene, 8.7-45
    µg/m3 (particulate); anthanthrene, 2.6-62 µg/m3 (particulate); and
    coronene, 1.0-19 µg/m3 (particulate) (IARC, 1984b).

    At eight sites in a German coke plant in 1981, including the top of
    the oven and the cabin of a lorry driver, the following PAH
    concentrations were measured: 2.7 µg/m3 fluoranthene, 1.9-170 µg/m3
    pyrene, 0.38-37 µg/m3 benzo [c]phenanthrene, 0.22-21 µg/m3
    cyclopenta [cd]pyrene, 1.2-120 µg/m3 benz [a]anthracene, 0.71-79
    µg/m3 benzo [c]pyrene, 0.88-89 µg/m3 benzo [a]pyrene, 0.21-14
    µg/m3 perylene, 0.37-27 µg/m3 benzo [ghi]perylene, 0.18-17 µg/m3
    anthanthrene, and 0.93-6.5 µg/m3 coronene. The authors pointed out
    that the concentrations may have been much higher previously (Manz et
    al., 1983).

    Measurements with personal air samplers in Germany and Sweden showed
    benzo [a]pyrene concentrations varying from 0.16-33 µg/m3 for
    coke-oven operators to 4.7-17 µg/m3 for lorry drivers. The ranges of
    exposure to all PAH at different workplaces in the 1970s were: lorry
    driver, 170-1000 µg/m3; coke-car operator, 4.8-73 µg/m3; jamb
    cleaner, 62-240 µg/m3; door cleaner, 9.1-17 µg/m3; push-car
    operator, 9.4-62 µg/m3; sweeper, 110 µg/m3; quench-car operator, 5.7
    µg/m3; and wharf man, 360 µg/m3 (IARC, 1984b).

    Personal air samples taken from 56 Dutch coke-oven workers in 1986
    showed pyrene levels of < 0.6 µg/m3 (detection limit) to 9.8 µg/m3
    (Jongeneelen et al., 1990). The results of more recent measurements in
    personal air samples are shown in Table 70.

    5.3.1.2  Coal gasification and coal liquefaction

    The levels of individual PAH in area air samples in Norwegian and
    British coal gasification plants between the late 1940s and the mid
    1950s were in the low microgram per cubic millilitre range. In modern
    gasification systems, the concentrations of total PAH are usually <
    1 µg/m3, but in one of three plants examined the total aerial PAH
    load was about 30 µg/m3. Personal samples taken in modern coal
    gasification plants showed similar PAH concentrations (IARC, 1984b).


        Table 70. Workplace exposures to polycyclic aromatic hydrocarbons in the atmosphere of coke-oven batteries
    (µg/m3), determined from personal air samples

                                                                                                                    

    Compound                    [1]            [2]            [3]            [4]      [5]        [6]        [7]
                                                                                                                    

    Acenaphthene                                                                                 3.8
    Acenaphthylene                                                                               28
    Anthracene                                                               65                  16
    Anthanthrene                                                                                 2.4
    Benz[a]anthracene                          0.11-33.19                    96                  7.5
    Benzo[a]fluorene                                                         70                  3.7
    Benzo[a]pyrene              < 0.01-31.15a  0.03-12.63     0.9-46.02      38       0.1-29     7.3        1300
                                0.01-22.91b
    Benzo[b]fluoranthene                                                     42                             1500
    Benzo[b]fluorene                                                                  4.3
    Benzo[c]phenanthrene                                                              1.4
    Benzo[e]pyrene                                                                               4.7
    Benzo[ghi]fluoranthene                                                                       1.6
    Benzo[ghi]perylene                                                                           4.4
    Benzo[k]fluoranthene                                                     42
    Chrysene                                   0.08-13.17                    72
    Coronene                                                                                     3.2
    Cyclopenta[cd]pyrene                                                                         1.9
    Fluoranthene                0.12-17.00a                                  144                 22         4400
    Fluorene                                                                 109                 14
    Indeno[1,2,3-cd]pyrene                                                                       4.5
    1-Methylphenanthrene                                                                         3.4
    Naphthalene                 28-445a                                      650
    Perylene                                                                                     1.8
    Phenanthrene                0.07-8.53a                                   195                 49
    Pyrene                                                    2.36-98.63                         17         Trace
                                                                                                                    
    Table 70 (continued)

    [1] Finland; samples from one plant, 1988-90 (Yrjanheikki et al., 1995);
    [2] Italy; samples from 69 workers, six workplaces (Assennato et al., 1993a);
    [3] Italy; samples from three workplaces at battery top (Cenni et al., 1993);
    [4] Sweden; one typical sample (Andersson et al., 1983);
    [5] United Kingdom; samples from 12 plants (Davies et al., 1986);
    [6] USA; samples from topside coke-oven workers (Haugen et al., 1986,
    [7] India; samples from top of coke oven (Rao et al., 1987)

    a Area air samples
    b Personal air samples


    In a pilot coal liquefaction plant in the United Kingdom, monitoring
    of five operators for vapour-phase PAH gave following results:
    1900-3300 ng/m3 phenanthrene, 340-670 ng/m3 pyrene, 270-380 ng/m3
    fluoranthene, 29-130 ng/m3 anthracene, 22-1700 ng/m3 fluorene,
    < 1-1800 ng/m3 naphthalene, < 1-1000 ng/m3 acenaphthene, and
    < 1-8 ng/m3 acenaphthylene. The higher-molecular-mass PAH were not
    detected (limit of detection, 1 ng/m3). Pyrene was detected in the
    particulate phase at concentrations of 630-2900 ng/m3 (Quinlan et
    al., 1995a).

    5.3.1.3  Petroleum refining

    Personal samples from operators of catalytic cracker units and
    reaction and fractionation towers in a petroleum refinery showed total
    PAH levels of 2.6-470 µg/m3. During performance and turn-round
    operations on reaction and fractionation towers, naphthalene and its
    methyl derivatives accounted for more than 99% of the total PAH
    measured; exposure to anthracene, pyrene, chrysene, and
    benzo [a]pyrene was < 1 µg/m3. Area monitoring for these PAH
    during normal activities and during shut-down, leak-testing, and
    start-up operations after turn-rounds gave total PAH concentrations up
    to 400 µg/m3, most of the measurements being < 100 µg/m3 (IARC,
    1989b).

    The results of personal air sampling of workers at six jobs in seven
    American refineries in 1990-91 were as follows (mean and range): 5.5
    (< 0.25-10) µg/m3 naphthalene, 3.3 (< 0.44-24) µg/m3 acenaphthene,
    3.3 (< 0.19-26) µg/m3 acenaphthylene, 0.98 (< 0.085-7.9) µg/m3
    fluoranthene, 0.82 (< 0.055-6.7) µg/m3 phenanthrene, 0.78
    (< 0.13-5.3) µg/m3 benzo [e]pyrene, 0.65 (< 0.055-5.2) µg/m3
    benzo [b]fluoranthene, 0.47 (< 0.14-2.7) µg/m3 fluorene, 0.29
    (< 0.11-1.4) µg/m3 indeno[1,2,3- cd]pyrene, 0.18 (< 0.085-0.69)
    µg/m3 benz [a]anthracene, 0.16 (< 0.11-< 0.59) µg/m3
    benzo [a]pyrene, 0.063 (< 0.028-0.26) µg/m3 anthracene, < 0.11-
    < 0.2 µg/m3 pyrene, < 0.085-< 0.15 µg/m3 chrysene, < 0.085-
    < 0.15 µg/m3 benzo [k]fluoran-thene, < 0.11-< 0.2 µg/m3
    benzo [ghi]perylene, and < 0.11-< 0.2 µg/m3
    dibenz [a,h]anthracene. Dermal wipe samples from the back of the hand
    or from the forehead of workers showed PAH levels of < 0.0011-0.29
    µg/cm2, with the highest level for naphthalene and the lowest for
    anthracene (Radian Corp., 1991).

    5.3.1.4  Road paving

    In early studies on road paving operations, the total PAH
    concentrations reported in personal air samples were 4-190 µg/m3, and
    the mean in area air samples was 0.13 µg/m3. The benzo [a]pyrene
    concentration in stationary samples was < 0.05-0.19 µg/m3 (IARC,
    1985).

    The concentrations of individual PAH in fume condensates from paving
    asphalt were generally < 2 mg/kg condensate, varying by about seven
    times depending on the source of crude oil. The levels of
    benzo [a]pyrene, for example, were between 0.09 and 2.0 mg/kg
    (Machado et al., 1993).

    Fourteen stationary air samples from a road paving site in New Zealand
    in 1983 contained: 0.14-52 µg/m3 benz [a]anthracene plus chrysene,
    0.2-14 µg/m3 benzo [b]fluoranthene plus benzo [j]fluoranthene plus
    benzo [k]fluoranthene, 0.15-9.0 µg/m3 benzo [a]pyrene, 0.31-5.4
    µg/m3 benzo [e]pyrene, 0.039-2.2 µg/m3 perylene, 0.24-5.4 µg/m3
    benzo [ghi]perylene, and 0.03-6.3 µg/m3 indeno[1,2,3- cd]pyrene
    plus dibenz [a,h]anthracene (Swallow & van Noort, 1985). The
    concentrations in 17 stationary air samples from a road paving
    operation in New Zealand in another study (year not given) were:
    1.2-18 µg/m3 benz [a]anthracene plus chrysene, 1.1-11 µg/m3
    benzo [b]fluoranthene plus benzo [j]fluoranthene plus
    benzo [k]fluoranthene, 0.9-9.0 µg/m3 benzo [a]pyrene, 0.7-5.4
    µg/m3 benzo [e]pyrene, and 0.7-6.3 µg/m3 indeno[1,2,3- cd]pyrene
    (Darby et al., 1986). Concentrations of up to 1.3 µg/m3 were found
    for acenaphthene, < 0.13 µg/m3 for anthracene, and < 0.54
    µg/m3 pyrene in road-paving operations. The workers, and especially
    the machine driver, were exposed to a mixture of bitumen fumes and
    diesel exhaust gases for 4-6 h per day (Monarca et al., 1987).

    The PAH concentrations in personal air samples obtained from workers
    at six jobs in six paving operations in the USA in 1990 were (mean and
    range): 6.5 (1.3-15) µg/m3 naphthalene, 2 (< 0.54-6.9) µg/m3
    acenaphthene, 2 (< 0.24-8.1) µg/m3 acenaphthylene, 0.58
    (< 0.19-0.98) µg/m3 fluorene, 0.55 (< 0.085-1.3) µg/m3
    phenanthrene, 0.26 (< 0.11-0.37) µg/m3 fluoranthene, 0.17
    (< 0.13-< 0.31) µg/m3 pyrene, 0.16 (< 0.13-0.27) µg/m3
    benzo [e]pyrene, 0.13 (< 0.099-< 0.2) µg/m3 chrysene, 0.052
    (< 0.034-0.11) µg/m3 anthracene, < 0.099-< 0.12 µg/m3
    benz [a]anthracene, < 0.064-< 0.085 µg/m3 benzo [b]fluoranthene,
    < 0.099-< 0.12 µg/m3 benzo [k]fluoranthene, < 0.13-< 0.25 µg/m3
    benzo [a]pyrene, < 0.13-< 0.16 µg/m3 benzo [ghi]perylene,
    < 0.13-< 0.16 µg/m3 indeno[1,2,3- cd]pyrene, and < 0.13-< 0.16
    µg/m3 dibenz [a,h]anthracene. Dermal wipe samples from the back of
    the hand and from the forehead of workers contained PAH at <
    0.00004-0.43 µg/cm2, with the highest level for naphthalene and the
    lowest for anthracene and pyrene (Radian Corp., 1991).

    Measurements in the air in France during road paving with different
    bitumens and tars showed the highest benzo [a]pyrene concentrations
    with hard-coal tar (1-6 µg/m3) and the lowest with petroleum-based
    bitumen (0.004-0.007 µg/m3). In general, the benzo [a]pyrene levels
    in the workplace atmosphere were two to three orders of magnitude
    higher during paving operations with tar products than with bitumen
    products (Barat, 1991).

    5.3.1.5  Roofing

    The concentrations of PAH measured during roofing and roofing
    manufacture are shown in Table 71.

    The concentrations of individual PAH in fume condensates from roofing
    asphalt generated at 232 and 316°C the were usually < 10 mg/kg
    condensate, with higher levels only for naphthalene. They varied with
    the source of crude oil: those for benzo [a]pyrene were between 0.6
    and 2.8 mg/kg (Machado et al., 1993).

    Acenaphthene was detected at concentrations of 1.4-2.1 µg/m3 in
    personal samples from roofing workers at two US roofing sites in 1985
    (Zey & Stephenson, 1986); 0.8-22 µg/m3 phenanthrene were measured at
    one US roofing site in 1981 (Reed, 1983). Pyrene was measured at
    < 190 µg/m3 at three roofing sites in Canada (year not given)
    (Malaiyandi et al., 1986). Personal air samples from 12 roofers at one
    US roofing site contained benzo [a]pyrene at 0.53-2.0 µg/m3 in 1987
    (Herbert et al., 1990a). The workplace concentrations during bitumen
    and coal-tar pitch roofing, waterproofing, and flooring operations
    were of the same order of magnitude (IARC, 1985).

    Significant, 10-fold differences were found in the levels of
    anthracene, fluoranthene, pyrene, benz [a]anthracene,
    benzo [b]fluoranthene, benzo [k]-fluoranthene, benzo [a]pyrene, and
    benzo [ghi]perylene on skin wipes from the forehead taken before and
    after a shift in 10 US roofers in 1987 (Wolff et al., 1989a).
    Comparable results for benzo [a]pyrene levels were obtained for 12
    roofers at another US roofing site (Herbert et al., 1990a,b).

    Dermal wipe samples from the back of the hand or the forehead of
    workers at six asphalt roofing manufacturing sites in the USA showed
    PAH levels of < 0.12-5.5 µg/cm2, with the highest level for
    acenaphthylene and the lowest for fluoranthene, benz [a]anthracene,
    benzo [k]fluoranthene, and chrysene. Similar samples from workers at
    six asphalt roofing sites in the USA in 1990-91 showed PAH levels of
    < 0.0011-0.0045 µg/cm2, with the highest levels for pyrene,
    chrysene, and benzo [a]pyrene and the lowest for anthracene (Radian
    Corp., 1991).

    5.3.1.6  Impregnation of wood with creosotes

    Concentrations of PAH ranging from 0.05 µg/m3 benzo [a]pyrene to
    650 µg/m3 naphthalene were detected during the handling of
    creosote-impregnated wood for railroad ties in Sweden. Naphthalene,
    fluorene and phenanthrene were by far the most abundant compounds
    (> 100 µg/m3) (Andersson et al., 1983). Concentrations of 0.04-0.28
    µg/m3 anthracene and 0.11-7.7 µg/m3 pyrene were found at workplaces
    in Finland where railroad ties were manufactured (Korhonen & Mulari,
    1983), and concentrations of 1-19 µg/m3 anthracene, 6.5-61 µg/m3
    phenanthrene, and 0.6-13 µg/m3 pyrene were measured in one plant
    where railroad sleepers were impregnated and in another where poles


        Table 71. Exposure to polycyclic aromatic hydrocarbons (µg/m3) during roofing and roofing manufacture

                                                                                                                  

    Compound                    [1]                 [2]             [3]                      [4]
                                                                                                                  

    Acenaphthene                                                    < 0.52-3.2 (0.87)        < 0.6-6.7 (1.5)
    Acenaphthylene                                                  < 0.23-29 (7.1)          < 0.26-12 (2.9)
    Anthracene                                      0.5/1.5         < 0.033-0.069 (0.043)    < 0.037-0.042
    Anthanthrene                < 0.030
    Benz[a]anthracene           < 0.03-0.130        1.3/2.5         < 0.099-< 0.13           < 0.11-< 0.13
    Benzo[a]fluorene            0.03-0.080
    Benzo[a]pyrene              < 0.03-0.037        0.9/1.5         < 0.13-< 0.18            < 0.11-< 0.13
    Benzo[b]fluoranthene        < 0.03-0.093a       0.8/1.2         < 0.065-< 0.38 (0.13)    < 0.078-< 0.085
    Benzo[b]fluorene            0.051-0.093
    Benzo[e]pyrene              < 0.03-0.110                        < 0.13-3 (0.61)          < 0.15-< 0.17
    Benzo[ghi]fluoranthene      < 0.03
    Benzo[ghi]perylene          < 0.03-0.069        0.6/0.9         < 0.13-< 0.18            < 0.15-< 0.17
    Benzo[k]fluoranthene                            0.4/0.7         < 0.099-< 0.13           < 0.099-< 0.12
    Chrysene                    0.038-0.214                         < 0.099-< 0.13           < 0.11-< 0.13
    Coronene                    < 0.03
    Dibenz[a,h]anthracene       < 0.03                              < 0.13-< 0.18            < 0.15-< 0.17
    Fluoranthene                0.084-0.234         3.1/7           < 0.099-4 (0.64)         < 0.11-0.13
    Fluorene                                                        < 0.16-14 (2.5)          < 0.19-1.1 (0.44)
    Indeno[1,2,3-cd]pyrene      < 0.030                             < 0.13-< 0.18            < 0.15-0.94 (0.16)
    Naphthalene                                                     < 0.22-9.2 (5.2)         1.2-25 (7.5)
    Perylene                    < 0.030
    Phenanthrene                                                    < 0.065-1.7 (0.53)       < 0.078-1.4 (0.38)
    Pyrene                      0.035-0.183         2.6/5.4         < 0.13-3.4 (0.76)        < 0.15-< 0.73 (0.25)
                                                                                                                  

    /, single determinations; mean values shown in parentheses;
    [1] Germany; personal and area air samples from one bitumen roofing site (Schmidt, 1992);
    [2] USA; personal air samples from nine workers; 1987 (Wolff, M.S. et al., 1989);
    [3] USA; personal air samples from six asphalt roofing sites; 1990 (Radian Corp., 1991);
    [4] USA; personal air samples from six roofing manufacturing sites; 1990 (Radian Corp., 1991)

    a Benzo[b+j+k]fluoranthenes


    were preserved (year not given) (Heikkilä et al., 1987). In
    measurements of personal air samples from 10 workers in a Dutch plant
    for impregnation of railroad sleepers in 1991, 0.3-1.3 µg pyrene/m3
    was measured in the breathing zone and 47-1500 µg/d in pads placed on
    various areas of the skin of the workers. Dermal exposure was shown to
    be reduced by up to 90% by the use of protective clothing (Van Rooij
    et al., 1993b).

    5.3.1.7  Other exposures

    In area air samples taken near the bitumen processing devices of
    refineries, the total PAH levels varied from 0.004 to 50 µg/m3 (IARC,
    1985, 1989b).

    The use of lubricating oils may result in exposure to PAH. At two
    Italian glass manufacturing plants, phenanthrene, anthracene, pyrene,
    and fluoranthene were found in personal air samples at concentrations
    < 3 µg/m3 (year not given) (Menichini et al., 1990). The pyrene
    levels resulting from use of lubricating oils in Italian earthenware
    factories were 0.02-0.09 µg/m3; the benzo [a]pyrene concentration
    was below the limit of detection (Cenni et al., 1993). Measurable
    concentrations of individual PAH were detected in indoor air above
    asphalt floor tiles in e.g. warehouses, factories, and manufacturing
    plants. The concentrations at six sampling sites in Germany were
    between < 0.01 ng/m3 for benzo [ghi]perylene and 3.3 ng/m3 for
    chrysene. The concentrations of phenanthrene, pyrene, fluoranthene,
    chrysene, and benzo [b]fluorene in particular were higher than those
    in outdoor air (Luther et al., 1990).

    In two Swiss plants for the production of silicon carbide, personal
    air samples from four and five workers, respectively, contained the
    following PAH levels: 4-140 ng/m3 acenaphthylene, 8-86 ng/m3
    acenaphthene, 11-500 ng/m3 fluorene, 88-1400 ng/m3 phenanthrene,
    3-250 ng/m3 anthracene, 20-1100 ng/m3 fluoranthene, 30-2500 ng/m3
    pyrene, 7-6400 ng/m3 benz [a]-anthracene, 37-14 000 ng/m3 chrysene,
    11-3700 ng/m3 benzo [b]fluoranthene plus benzo [j]fluoranthene,
    3-470 ng/m3 benzo [k]fluoranthene, 18-3800 ng/m3 benzo [e]pyrene,
    4-630 ng/m3 benzo [a]pyrene, 2-250 ng/m3 indeno[1,2,3- cd]pyrene,
    2-520 ng/m3 dibenz [a,h]anthracene, 4-550 ng/m3
    benzo [ghi]-perylene, and 4-34 ng/m3 coronene (Petry et al., 1994).

    5.3.2  Occupational exposure resulting from incomplete combustion of
    mineral oil, coal, and their products

    5.3.2.1  Aluminium production

    Early measurements of atmospheric benzo [a]pyrene at workplaces in
    the aluminium industry showed concentrations of 0.02-970 µg/m3 in
    personal air samples and 0.03-5.3 µg/m3 in area air samples. In the
    atmosphere of an aluminium production plant, naphthalene, fluorene,
    phenanthrene, anthracene, fluoranthene, pyrene, benzo [a]fluorene,
    benzo [b]fluorene, benzo [c]phenan-threne, benz [a]anthracene,

    chrysene, triphenylene, benzo [b]fluoranthene plus
    benzo [k]fluoranthene, benzo [e]pyrene, benzo [a]pyrene,
    benzo [ghi]perylene, anthanthrene, and coronene were found at
    concentrations < 400 µg/m3. The most abundant compounds were
    phenanthrene, naphthalene, fluorene, fluoranthene, and pyrene, at
    concentrations > 100 µg/m3. The other substances occurred at
    concentrations < 10 µg/m3 (IARC, 1984b).

    The following concentrations of PAH were found in four stationary air
    samples from an aluminium smelter in New Zealand in 1979: 0.37-9.6
    µg/m3 benz [a]anthracene plus chrysene, 0.34-7.6 µg/m3
    benzo [b+j+k]fluoranthenes, 0.12-2.6 µg/m3 benzo [e]pyrene,
    0.19-4.1 µg/m3 benzo [a]pyrene, 0.05-1.5 µg/m3 perylene, 0.13-2.7
    µg/m3 indeno[1,2,3- cd]pyrene plus dibenz [a,h]anthracene, and
    0.12-3.3 µg/m3 benzo [ghi]perylene (Swallow & van Noort, 1985).

    Similar levels were found in a typical personal air sample from a
    Söderberg aluminium plant in Sweden (year not given) with, in
    addition, 27 µg/m3 phenanthrene, 20 µg/m3 fluoranthene, 2.8 µg/m3
    fluorene, 2.8 µg/m3 anthracene, 2.8 µg/m3 benzo [a]fluorene, and
    < 1.0 µg/m3 naphthalene (Andersson et al., 1983).

    In personal air samples from 38 workers in the Söderberg potroom of an
    aluminium smelter in the humid tropics (location not given), mean
    concentrations of < 1.0-48 µg/m3 benzo [a]pyrene and 3.5-130 µg/m3
    pyrene were detected (Ny et al., 1993).

    The arithmetic mean concentrations of PAH in workplace air samples
    from the Canadian aluminium industry were 1100 µg/m3 naphthalene, 130
    µg/m3 acenaphthene, 45 µg/m3 fluorene, 30 µg/m3 phenanthrene, 4.5
    µg/m3 anthracene, 1.1 µg/m3 fluoranthene, and 0.58 µg/m3 pyrene.
    The concentrations of benz [a]anthracene, chrysene, benzo [a]pyrene,
    and benzo [e]pyrene were < 0.01 µg/m3 (Lesage et al., 1987).

    Personal air samples from 18 workers in a US plant producing anodes
    for use in aluminium reduction (year not given) showed pyrene
    concentrations of 1.2-7.4 µg/m3 (Tolos et al., 1990).

    Urine samples from 11 workers in Norwegian Söderberg aluminium plants
    contained very low levels of unchanged PAH, although the
    concentrations in the workplace air greatly exceeded the
    concentrations in urban air. The total concentration of PAH
    metabolites in the samples was 1.5-6 greater than that in a control
    group (Becher & Bjœrseth, 1983).

    The PAH concentrations in the air of aluminium plants is reduced
    dramatically by the use of tempered anodes instead of Söderberg
    anodes. Measurements of benzo [a]pyrene levels in French factories
    showed 1-36 µg/m3 in potrooms with Söderberg anodes and 0.004-0.6
    µg/m3 in potrooms with tempered anodes (Barat, 1991).

    5.3.2.2  Foundries

    In personal air samples from workers in 10 Canadian foundries, mean
    concentrations of 0.14-1.8 µg/m3 benz [a]anthracene plus chrysene,
    0.09-1.2 µg/m3 benzo [a]pyrene, and 0.09-1.9 µg/m3
    dibenz [a,h]anthracene were measured. The benzo [a]pyrene levels in
    stationary air samples from six Finnish foundries were 0.01-13 µg/m3,
    depending on whether coal-tar pitch or coal powder was used as the
    moulding sand additive (IARC, 1984b).

    In another study, the highest individual PAH levels were found in coke
    making, moulding, and furnaces (Gibson et al., 1977). Personal air
    samples from 67 Finnish foundry workers in 1990-91 showed
    benzo [a]pyrene concentrations of 2-60 ng/m3 with a mean of 8.6
    ng/m3 (Perera et al., 1994). Depending on the foundry process and
    sand binder, the mean benzo [a]pyrene level in 29 French foundries
    varied from 3 to 2300 ng/m3 (Lafontaine et al., 1990).

    Concentrations of PAH measured in foundries are shown in Table 72.

    5.3.2.3  Other workplaces

    Personal air samples from German chimney sweeps (year not given; 115
    samples) showed an average benzo [a]pyrene level of 0.09 µg/m3, but
    eight of the samples exceeded 2 µg/m3. With an inhaled air volume of
    10 m3 per working day, the daily intake of benzo [a]pyrene was
    estimated to be 0.24-2.7 µg, with a median value of 1.3 µg (Knecht et
    al., 1989).

    In an Italian pyrite mine, pyrene levels of 0.03-0.21 µg/m3 were
    measured in personal and area air samples. The benzo [a]pyrene
    concentrations were below the limit of detection (Cenni et al., 1993).
    Area air samples taken in China showed total PAH levels of 3-40 µg/m3
    in two iron mines and 4-530 µg/m3 in four copper mines. Individual
    compounds were not identified, but the main components were
    naphthalene and acenaphthene in the iron mines and naphthalene,
    benz [a]anthracene, benzo [b]fluoranthene, benzo [a]pyrene,
    benzo [e]pyrene, and dibenz [a,h]anthracene in the copper mines. The
    PAH concentrations probably resulted from the drilling of holes with
    hydraulic or pneumatic drills and by the transport of broken ore in
    diesel-powered scoops (Wu et al., 1992).

    Area and personal air samples from workers in a railway tunnel in
    Italy showed pyrene levels of 0.04-0.30 µg/m3. The benzo [a]pyrene
    concentrations ranged from below the limit of detection to 0.04 µg/m3
    (Cenni et al., 1993).


    Table 72. Exposure to polycyclic aromatic hydrocarbons (µg/m3)
    in the atmosphere of foundries

                                                                    

    Compound                    [1]               [2]        [3]
                                                                    

    Acenaphthene                                             0.03
    Acenaphthylene                                           ND
    Anthracene                                    2.31       0.05
    Anthanthrene                                  0.64
    Benz[a]anthracene           0.008-0.221       0.67       0.01
    Benzo[a]fluorene                              0.48
    Benzo[a]pyrene              0.049-0.152       0.47       0.02
    Benzo[b]fluoranthene                          0.87a      0.003
    Benzo[b]fluorene                              0.41
    Benzo[e]pyrene                                0.48
    Benzo[ghi]fluoranthene                        0.15
    Benzo[ghi]perylene                            0.72       0.05
    Benzo[k]fluoranthene        0.037-0.458                  0.02
    Chrysene                                      0.82b      0.02
    Coronene                                      0.21
    Dibenz[a,h]anthracene                         0.20       ND
    Fluoranthene                                  1.56       0.13
    Fluorene                                                 0.08
    Indeno[1,2,3-cd]pyrene                        0.81       ND
    Naphthalene                                              9.68
    Perylene                                      0.21
    Phenanthrene                                  4.46       0.32
    Pyrene                                        1.74       0.01
                                                                    

    ND, not detected; /, single measurements;
    [1] Canada, steel foundry: coke making, moulding, furnaces,
        finishing, and cranes (Gibson et al., 1977);
    [2] Western Germany, one foundry, area air samples (Knecht et al.,
        1986);
    [3] Denmark, 70 workers, personal air samples; melting, machine
        moulding, casting, sand preparation (Omland et al., 1994)
    a In sum with benzo(j+k)fluoranthene
    b In sum with triphenylene


    In the air of fish and meat smokehouses in Denmark (year not given),
    the maximum concentration of naphthalene in stationary air samples was
    about 2900 µg/m3. The most abundant compounds were naphthalene,
    phenanthrene, pyrene, fluorene, anthracene, and fluoranthene
    (> 100 µg/m3) (Nordholm et al., 1986). The minimal values were
    < 1 µg/m3, benzo [a]pyrene being detected at minimal levels of
    0.08 µg/m3 in meat smokehouses and 0.4 µg/m3 in fish smokehouses
    (Hansen et al., 1991b), with a maximum concentration of 78 µg/m3
    (Nordholm et al., 1986).

    In a further study in nine Danish meat smokehouses, naphthalene was
    detected at 21 µg/m3, fluorene at 6.9 µg/m3, fluoranthene at 6.6
    µg/m3, phenanthrene at 5.6 µg/m3, acenaphthene at 5.2 µg/m3,
    chrysene at 1.2 µg/m3, anthracene at 1.1 µg/m3, pyrene at 0.2
    µg/m3, and benzo [ghi]perylene at 0.2 µg/m3 (Hansen et al., 1992).

    The concentrations of naphthalene, fluorene, anthracene, phenanthrene,
    pyrene, benzo [a]fluorene, chrysene, benzo [k]fluoranthene,
    benzo [a]pyrene, benzo [e]pyrene, benzo [ghi]perylene, and
    dibenz [a,h]anthracene in cooking fumes in a Finnish food factory,
    three restaurants, and one bakery (year not given) during the frying
    of meat and during deep-frying ranged between < 0.02 µg/m3 (the
    limit of detection) and 26 µg/m3. Naphthalene occurred at by far the
    highest concentration. Stationary air was sampled as close as possible
    to the active working area and the workers' breathing zone (Vainiotalo
    & Matveinen, 1993).

    6.  KINETICS AND METABOLISM IN LABORATORY MAMMALS AND HUMANS

     Appraisal

    Polycyclic aromatic hydrocarbons (PAH) are lipophilic compounds and
    can be absorbed through the lungs, the gastrointestinal tract, and the
    skin. In studies of the distribution of PAH in rodents, both the
    parent compounds and their metabolites were found in almost all
    tissues and particularly those rich in lipids. As a result of
    mucociliary clearance and hepatobiliary excretion, they were present,
    for example, in the gastrointestinal tract even when administered by
    other routes.

    The metabolism of PAH to more water-soluble derivatives, which is a
    prerequisite for their excretion, is complex. Generally, the process
    involves epoxidation of double bonds, a reaction catalysed by
    cytochrome P450-dependent mono-oxygenases, rearrangement or hydration
    of the epoxides to yield phenols or diols, respectively, and
    conjugation of the hydroxylated derivatives. The reaction rates vary
    widely: interindividual variations of up to 75-fold have been
    observed, for example, with human macrophages, mammary epithelial
    cells, and bronchial explants from different donors.

    All aspects of the absorption, metabolism, activation, and excretion
    of benzo[a]pyrene have been covered exhaustively in the published
    literature, but there is a dearth of information on many of the other
    PAH considered in this publication, particularly in humans. Thus, this
    overview sets out general principles and describes pathways relevant
    to benzo[a]pyrene in greater detail.

    Most biotransformation leads to detoxification products that are
    conjugated and excreted in the urine and faeces. The human body burden
    of PAH has not been extensively studied, but tissue samples taken at
    autopsy were found in one study to contain benzo[a]pyrene at an
    average of 0.3 µg/100 g dry tissue; lung contained 0.2 µg/100 g. In
    contrast, the pathways by which several PAH are metabolized to
    reactive intermediates that bind covalently to nucleic acids have been
    examined in great detail. Although the commonest mechanism in animals
    and humans appears to involve the formation of diol epoxides, radical
    cations and sulfate esters of hydroxymethyl derivatives may also be
    important in certain cases.

    6.1  Absorption

    PAH are lipophilic compounds, soluble in organic solvents, that are
    usually devoid of ionizable or polar groups. Like many other
    xenobiotic substances, they would be expected to dissolve readily in,
    and be transported through, the external and internal lipoprotein
    membranes of mammalian cells. This is confirmed by the uptake of PAH
     in vitro from media in which cells are maintained in culture and
    modified metabolically by enzymes of the endoplasmic reticulum.
    Furthermore, PAH are known to be able to cause biological effects
     in vivo in cells and tissues that are distant from their site of
    uptake by the organism.

    In humans, the major routes of uptake of PAH are thought to be through
    (i) the lungs and the respiratory tract after inhalation of
    PAH-containing aerosols or of particulates to which a PAH, in the
    solid state, has become absorbed; (ii) the gastrointestinal tract
    after ingestion of contaminated food or water; and (iii) the skin as a
    result of contact with PAH-bearing materials.

    6.1.1  Absorption by inhalation

    Investigations of the pulmonary absorption of PAH have frequently been
    clouded by the existence of the mucociliary clearance mechanism, by
    which hydrocarbons absorbed onto particulates that have been inhaled
    are swept back up the pulmonary tree and are swallowed, thus entering
    the organism through the gastrointestinal tract. Use of isolated
    perfused rat lungs, however, provided a clear demonstration that
    benzo [a]pyrene is absorbed directly through the pulmonary epithelia.
    After intratracheal administration, both the hydrocarbon and its
    metabolites were detected in effluent perfusion fluid (Vainio et al.,
    1976). Other studies have shown that benzo [a]pyrene administered
     in vivo as an aerosol is cleared from the lungs of rats by a
    biphasic process in which an initial rapid phase (tracheal clearance)
    is followed by a much slower second phase (alveolar clearance)
    (Mitchell, 1982). PAH absorbed onto particles may take very much
    longer to be cleared from rodent lungs, however, than the free
    hydrocarbons, and the factors that affect this clearance rate include
    the structure of the hydrocarbon and the dimensions and chemical
    nature of the particles onto which the PAH are absorbed (Henry &
    Kaufman, 1973; Creasia et al., 1976; Nagel et al., 1976). For example,
    while 50% of the benzo [a]pyrene coated onto carbon particles of
    15-30 µm was cleared from hamster lungs within 60 h, it took only 10 h
    to clear 50% of the benzo [a]pyrene that had been coated onto
    0.5-1.0-µm carbon particles. In a comparable experiment, however, when
    ferric oxide particles of either 0.5-10 or 15-20 µm were used as
    carriers for benzo [a]pyrene, 50% of the hydrocarbon was cleared in
    just over 2 h, and carrier particle size did not affect the clearance
    rates (Henry & Kaufman, 1973).

    Benzo [a]pyrene was metabolized by the epithelia lining the nasal
    cavities of hamsters, dogs, and monkeys when 14C-labelled hydrocarbon
    was instilled as an aqueous suspension (Dahl et al., 1985;
    Petridou-Fischer et al., 1988). From their studies with hamsters, the
    authors concluded that when frequent small doses of 650 ng at 10-min
    intervals were instilled into the nasal cavity, so as to imitate
    inhalation, some 50% of the benzo [a]pyrene was metabolized; a large
    fraction of the metabolites could be recovered from the mucus on the
    epithelial surfaces; and the nasal epithelia were comparable to those
    of the trachea and lungs in their ability to metabolize
    benzo [a]pyrene. Metabolites produced nasally would be expected to be
    swallowed and then absorbed in the gastrointestinal tract.

    In humans, the concentrations of benzo [a]pyrene and pyrene present
    in association with soot particles in the lungs were much lower than
    would have been expected from the soot content. Thus, only a trace of
    benzo [a]pyrene was found in one of 11 lung samples examined, in
    which the expected benzo [a]pyrene content ranged from 9 to 200 µg;
    in the other 10 samples, no benzo [a]pyrene was detected. Pyrene
    disappeared more slowly: all 11 lung samples contained the compound,
    at levels of 0.9-4.9 µg, whereas 3-190 µg might have been expected
    (Falk et al., 1958). The ability of pulmonary epithelial cells to
    metabolize PAH such as chrysene and benzo [a]pyrene to a variety of
    hydroxylated derivatives (Jacob et al., 1992) may facilitate the
    absorption and clearance of PAH from the lungs.

    6.1.2  Absorption in the gastrointestinal tract

    Indirect evidence for the gastrointestinal absorption of PAH was
    provided by Shay et al. (1949), who found that repeated intragastric
    instillation of 3-methylcholanthrene led to the development of mammary
    cancer. Mammary tumours can also be induced in rats by intracolonic
    adminstration of 7,12-dimethylbenz [a]anthracene (Huggins et al.,
    1961). (3-Methylcholanthrene and 7,12-dimethylbenz [a]anthracene are
    synthetic PAH that are potent carcinogens.) More direct investigations
    by Rees et al. (1971) showed rapid absorption of intragastrically
    administered benzo [a]pyrene; the highest levels of hydrocarbon were
    found in the thoracic lymph some 3-4 h after administration. In a
    report of studies of intact rats and intestinal sacs to examine the
    mechanisms involved in benzo [a]pyrene absorption, Rees et al. (1971)
    proposed that two sequential steps were involved, in which a phase of
    absorption by the mucosa is followed by diffusion through the
    intestinal lining. In a study with Sprague-Dawley rats, the presence
    of bile was found to increase intestinal absorption of PAH such as
    benzo [a]pyrene and 7,12-dimethylbenz [a]anthracene to a greater
    degree than that of anthracene and pyrene. The effect may be related
    to differences in the aqueous solubility of the PAH examined (Rahman
    et al., 1986). The composition of the diet also affects intestinal
    absorption of co-administered benzo [a]pyrene. Of the dietary
    components studied, soya bean oil and triolein gave rise to the
    highest levels of absorption of 14C-benzo [a]pyrene given orally at
    a dose of 8.7 µg to Wistar rats, while cellulose, lignin, bread, rice
    flake, and potato flake suppressed it (Kawamura et al., 1988).

    6.1.3  Absorption through skin

    PAH and PAH-containing materials have been applied dermally in
    solution in solvents such as acetone and tetrahydrofuran. Dermal
    transfer without use of a solvent was achieved by use of reconstituted
    vapour-particulate phases emitted from coal-tar and bitumen (Genevois
    et al., 1995) and by application in oil (Ingram et al., 1995).

    Absorption of PAH through the skin was observed indirectly when it was
    found that repeated topical application of 3-methylcholanthrene led to
    the appearance of mammary tumours in mice (Maisin & Coolen, 1936;
    Englebreth-Holm, 1941). The percutaneous mechanism of absorption is
    not universal, however, since although almost all of a dose of
    14C-benzo [a]pyrene applied to mouse skin appeared in the faeces
    within two weeks, very little dibenz [a,h]anthracene was absorbed in
    this way and most was lost through epidermal sloughing (Heidelberger &
    Weiss, 1951). Benzo [a]pyrene has been shown to be absorbed
    percutaneously  in vitro, by absorption from soil into human skin
    (Wester et al., 1990) and, after application as a solution in acetone,
    into discs of human, mouse, marmoset, rat, rabbit, and guinea-pig skin
    (Kao et al., 1985). In the latter experiments, marked interspecies
    differences were noted: 10% of the applied dose (10 µg/5 cm2) of
    14C-benzo [a]pyrene permeated mouse skin, 3% crossed human skin, and
    < 0.5% crossed guinea-pig skin within 24 h. It was concluded that
    both diffusional and metabolic processes are involved in the
    percutaneous absorption of benzo [a]pyrene.

    In Wistar rats that received 14C-pyrene as a solution in acetone on
    areas of shaved dorsal skin, the rate of uptake was relatively rapid
    (half-life, 0.5-0.8 d). The concentrations of pyrene were highest in
    the liver, kidneys, and fat, but those of pyrene metabolites were
    highest in the lungs. About 50% of an applied dose of 2, 6, or 15
    mg/kg bw was excreted in the urine and faeces during the first six
    days after treatment (Withey et al., 1993).

    In studies with 32P-postlabelling for the detection of DNA adducts,
    when complex mixtures of PAH, such as that present in used lubricating
    oil from petrol engines, in coal-tar, or in juniper-tar, were applied
    directly to mouse skin, appreciable, persistent levels of DNA adducts
    (50-750 amol/µg DNA [1 amol/µg DNA equivalent to 3.3 adducts/1010
    nucleotides]) were formed in the lungs (Schoket et al., 1989, 1990).
    The level of adducts in mouse skin was inversely related to the
    viscosity of the oil applied (Ingram et al., 1995).

    Evidence for percutaneous absorption of PAH has also been obtained in
    humans  in vivo. When 2% coal-tar in petroleum jelly was applied
    topically, phenanthrene, anthracene, pyrene, and fluoranthene were
    detected in peripheral blood samples (Storer et al., 1984). In
    addition, volunteers treated topically with creosote (100 µl) or
    pyrene (500 µg, applied as a solution in toluene) and a psoriasis
    patient who used a coal-tar shampoo excreted 1-hydroxypyrene in their
    urine. In each case, maximal excretion occurred 10-15 h after
    treatment (Viau & Vyskocil, 1995).

    6.2  Distribution

    The whole-body distribution of PAH has been studied in rodents. The
    levels found in individual tissues depend on a number of factors,
    including the PAH, the route of administration, the vehicle, the times
    after treatment at which tissues are assayed, and the presence or
    absence of inducers or inhibitors of hydrocarbon metabolism within the

    organism. The investigations have shown that (i) detectable levels of
    PAH occur in almost all internal organs, (ii) organs rich in adipose
    tissue can serve as storage depots from which the hydrocarbons are
    gradually released, and (iii) the gastrointestinal tract contains high
    levels of hydrocarbon and metabolites, even when PAH are administered
    by other routes, as a result of mucociliary clearance and swallowing
    or hepatobiliary excretion (Heidelberger & Jones, 1948; Heidelberger &
    Weiss, 1951; Kotin et al., 1959; Bock & Dao, 1961; Takahashi &
    Yasuhira, 1973; Takahashi, 1978; Mitchell, 1982).
    14C-Benzo [a]pyrene injected intravenously at 11 µg/rat was cleared
    rapidly from the bloodstream, with a half-life of < 1 min (Kotin et
    al., 1959), as confirmed by Schlede et al. (1970a,b), who also noted
    that the rate of clearance was increased when animals were pretreated
    with 20 mg/kg bw non-radioactive benzo [a]pyrene or 37 mg/kg bw
    phenobarbital, both of which can induce metabolism.

    The distribution of 3-methylcholanthrene in mice and their fetuses was
    studied by whole-body autoradiography. When 1 mg of 14C-labelled
    hydrocarbon is injected intravenously, it is not only widely
    distributed in maternal tissues but also crosses the placenta and can
    be detected in the fetuses (Takahashi & Yasuhira, 1973; Takahashi,
    1978), in which it induces pulmonary tumours (Tomatis, 1973; see also
    Section 7). The distribution of inhaled and intragastrically or
    intravenously administered benzo [a]pyrene and
    7,12-dimethylbenz [a]anthracene in rats and mice has also been
    studied, with similar results (Shendrikova & Aleksandrov, 1974;
    Shendrikova et al., 1973, 1974; Neubert & Tapken, 1988; Withey et al.,
    1992). Rapid transfer of radioactive benzo [a]pyrene across the
    placenta was confirmed in experiments in which the appearance of
    radioactivity in the umbilical vein of pregnant guinea-pigs was
    measured (Kelman & Springer, 1982).

    Samples of placenta, maternal blood, umbilical cord blood, and milk
    from 24 women in south India were examined for the presence of
    selected PAH. Although umbilical cord blood and milk showed the
    highest levels (benzo [a]pyrene, 0.005-0.41 ppm;
    dibenz [a,c]anthracene, 0.013-0.60 ppm; chrysene, 0.002-2.8 ppm),
    only 50% of the samples examined contained detectable levels. The
    authors concluded that developing fetuses and newborn infants were
    exposed to these PAH, probably from the maternal diet (Madhavan &
    Naidu, 1995).

    After intratracheal administration to mice and rats, the distribution
    of PAH was essentially similar to that found after intravenous or
    subcutaneous injection (Kotin et al., 1959), except for the expected
    high pulmonary levels. Detailed time-concentration curves for several
    organs have been obtained after inhalation of 3H-benzo [a]pyrene
    aerosols at 500 µg/litre of air (Mitchell, 1982). For example, 1 h
    after the end of administration, the highest levels were present in
    the stomach and small intestine; as these declined, the amounts of
    radioactivity in the large intestine and caecum increased. The
    elimination half-times in the respiratory tract were 2-3 h for the
    initial rapid phase and 25-50 h for the subsequent slow phase.

    6.3  Metabolic transformation

    The metabolism of PAH follows the general scheme of xenobiotic
    metabolism originally outlined by Williams (1959). The hydrocarbons
    are first oxidized to form phase-I metabolites, including primary
    metabolites, such as epoxides, phenols, and dihydrodiols, and then
    secondary metabolites, such as diol epoxides, tetrahydrotetrols, and
    phenol epoxides. The phase-I metabolites are then conjugated with
    either glutathione, sulfate, or glucuronic acid to form phase-II
    metabolites, which are much more polar and water-soluble than the
    parent hydrocarbons.

    The metabolism of PAH has been studied  in vitro, usually in
    microsomal fractions prepared from rat liver, although many other
    tissue preparations have also been used. Metabolism in such systems
    might be expected to be simpler than that in whole animals because the
    enzymes and co-factors necessary for sulfate, glutathione, or
    glucuronide conjugate formation may be removed, depleted, or diluted
    during tissue fractionation. Use of these systems appears to be
    justified, however, because the same types of phase-I metabolites are
    formed when animals are treated with simple hydrocarbons such as
    naphthalene as when the same hydrocarbon is incubated with hepatic
    microsomes or tissue homogenates (Boyland et al., 1964). The
    metabolism of PAH has thus been studied extensively in cells and
    tissues in culture, which metabolize hydrocarbons to both phase-I and
    phase-II metabolites and which probably better represent the
    metabolism of PAH that occurs  in vivo (for reviews see Conney, 1982;
    Cooper et al., 1983; Dipple et al., 1984; Hall & Grover, 1990; Shaw &
    Connell, 1994).

    Particular attention has been paid to the metabolism of PAH in human
    tissues that might be exposed to hydrocarbons present in food and in
    the environment and which are, therefore, potential targets for the
    carcinogenic action of PAH (Autrup & Harris, 1983). The cells and
    tissues examined include the bronchus, the colon, mammary cell
    aggregates, keratinocytes, monocytes, and lymphocytes. The metabolism
    of PAH by human pulmonary macrophages has also received attention
    (Autrup et al., 1978a; Harris et al., 1978a; Marshall et al., 1979)
    because it is conceivable that metabolism by these cells might be
    responsible, at least in part, for the high incidence of bronchial
    cancer in smokers (Wynder et al., 1970). Macrophages can engulf
    particulate matter that reaches the terminal airways of the lung and
    thus would be expected, especially in smokers, to contain PAH
    (Hoffmann et al., 1978). The macrophages and engulfed particulate
    matter can then be transported to the bronchi where proximate and
    ultimate carcinogens, formed by metabolism in the macrophages, could
    leave the macrophages and enter the epithelial cells lining the
    bronchi (Autrup et al., 1978a; Harris et al., 1978a). This is an
    attractive theoretical mechanism which could account for the high
    incidence of respiratory tumours at the junctions of the large bronchi
    and which is supported by experimental evidence.

    Extracts of organic material from isolated perfused lung tissues of
    rabbits that had been exposed intratracheally to benzo [a]pyrene with
    or without ferric oxide were analysed for benzo [a]pyrene metabolites
    and for mutagenicity. Extracts of lung tissue exposed to
    benzo [a]pyrene only were mutagenic and contained benzo [a]pyrene
    metabolites. When ferric oxide was co-administered, only the
    macrophage extracts were mutagenic, owing to relatively large amounts
    of unmetabolized benzo [a]pyrene. These experiments demonstrate that
    ferric oxide particles enhance the uptake of benzo [a]pyrene by lung
    macrophages and slow its metabolism beyond the 3-h period during which
    perfused lung systems can be maintained (Schoeny & Warshawsky, 1983).

    Administration of particles  in vitro enhances both the uptake and
    metabolism of benzo [a]pyrene by hamster alveolar macrophages (Griefe
    et al., 1988). Metabolites were found in both the cells and the
    culture medium. Subsequent studies showed that concurrent
    administration of benzo [a]pyrene and ferric oxide particles resulted
    in increased benzo [a]pyrene metabolism and release of superoxides
    (Greife & Warshawsky, 1993). In particular, the dihydrodiol fraction
    was increased. These studies indicate that particulates may act in
    lung cancer by changing the time frame for metabolism, shifting the
    site of metabolism to macrophages and enhancing the production of
    metabolites that are on the pathway to putative ultimate carcinogenic
    forms. In this context, it has been demonstrated that particles of
    various sorts exert different toxic effects on rat and hamster
    pulmonary macrophages  in vitro: ferric oxide and aluminium oxide
    particulates were toxic, while crystalline silica was not (Warshawsky
    et al., 1994).

    The conclusion that the macrophage is the principal metabolizing cell
    is further supported by the studies of Ladics et al. (1992a,b), who
    demonstrated that the macrophage population was the only one in murine
    spleen that could metabolize benzo [a]pyrene, while the other splenic
    cell types examined, including B cells, T cells, polymorphonuclear
    cells, and the splenic capsule, did not produce benzo [a]pyrene
    metabolites above the background level.

    Although the same types of metabolite are formed from PAH in many of
    the cell and tissue preparations examined in culture, the relative
    levels and the rates of formation of these metabolites depend on the
    type of tissue or cell that is being studied and on the species and
    strain of animal from which the metabolizing systems are prepared.
    With heterogeneous populations such as humans, the rate of metabolism
    depends on the individual from whom the tissues or cells are prepared.
    For example, a 75-fold variation in the extent of hydrocarbon
    activation was reported in studies of human bronchus (Harris et al.,
    1976), and similar variations were observed among human mammary cell
    aggregates (Grover et al., 1980; MacNicoll et al., 1980) and
    macrophages (Autrup et al., 1978a). The pattern and role of metabolism
    can also be varied by adding inhibitors of the enzymes that are
    responsible for metabolism or by pretreating either cells in culture
    or the animals from which the metabolizing systems are prepared with
    enzyme inducers.

    6.3.1  Cytochromes P450 and metabolism of PAH

    The cytochromes P450 (CYP) are a superfamily of haemoproteins that
    catalyse the oxidation of various endogenous molecules as well as
    xenobiotics, including PAH. To date, about 250 genes that encode these
    enzymes have been identified in various organisms. For classification
    purposes, the CYP have been organized into families and subfamilies
    according to their structural homology (Nelson et al., 1993).

    Certain CYP belonging to families 1, 2, and 3 are expressed in
    mammalian cells and are particularly important in xenobiotic
    metabolism, and one or more member of each family is capable of
    metabolizing one or more PAH (Guengerich & Shimada, 1991; Gonzalez &
    Gelboin, 1994). Most studies to compare the catalytic properties of
    different CYP have been carried out with model compounds such as
    benzo [a]pyrene. They show that the catalytic properties (e.g. the
     Vmax) of different CYP in PAH metabolism can differ essentially
    (Shou et al., 1994).

    In considering the contribution of a CYP enzyme to PAH metabolism
     in vivo, two other parameters in addition to the catalytic
    properties should be taken into account: the mode of regulation and
    tissue specificity in its expression. Combinations of the three
    factors should give an idea of the relative importance of an enzyme in
    PAH metabolism.

    6.3.1.1  Individual cytochrome P450 enzymes that metabolize PAH

     CYP1A: CYP1A appears to be the only enzyme with metabolic capability
    towards a wide variety of PAH molecules. It is expressed in various
    tissues but at a generally low constitutive level (Guengerich &
    Shimada, 1991). The induction of CYP1A1 is controlled by the Ah (aryl
    hydrocarbon) receptor, a transcription factor that can be activated by
    several ligands such as 2,3,7,8-tetradichlorobenzo- para-dioxin
    (TCDD) and PAH, with variable potency (Negishi et al., 1981). Thus,
    PAH and material containing PAH can regulate their own metabolism by
    inducing CYP1A1. After induction, CYP1A1 expression may reach high
    levels, e.g. in the placenta, lung, and peripheral blood cells;
    however, in the liver, the principal organ of xenobiotic metabolism,
    the level of expression is low even after induction, and other CYP
    appear to be more important, at least in the metabolism of
    benzo [a]pyrene (Guengerich & Shimada, 1991).

     CYP1A2: The other member of the CYP1A family, CYP1A2, also
    metabolizes PAH; however, its capacity to metabolize benzo [a]pyrene
    to the 3-hydroxy metabolite, for example, is about one-fifth that of
    CYP1A1 (Shou et al., 1994). Human CYP1A2 is nevertheless very active
    in forming benzo [a]pyrene 7,8-dihydrodiol (Bauer et al., 1995) and
    in forming diol epoxides from the 7,8-dihydrodiol (Shou et al., 1994).
    There is also evidence that CYP1A2 can activate
    7,12-dimethylbenz [a]anthracene to mutagenic species, albeit at a low
    rate (Aoyama et al., 1989).

    The expression of CYP1A2 is also regulated by the Ah receptor, but in
    not exactly the same way as CYP1A1 (Negishi et al., 1981). In the
    liver, for example, the level of CYP1A2 expression is much higher than
    that of CYP1A1 (Guengerich & Shimada, 1991). While the capacity of
    CYP1A2 to oxidize various PAH is more limited than that of CYP1A1, its
    role in reactions like diol epoxide formation from benzo [a]pyrene in
    the liver could be important because of its high level of expression.

     CYP1B: The CYP1B subfamily was discovered only recently. Once the
    enzyme had been isolated, it was found to be capable of metabolizing
    PAH. Interestingly, its expression is also under the control of the Ah
    receptor. Only limited information is available on its expression and
    catalytic properties in different tissues, but it seems to be
    expressed at least in mouse embryo fibroblasts (Savas et al., 1994),
    rat adrenal glands (Bhattacharyya et al., 1995), and several human
    tissues (Sutter et al., 1994). A number of PAH may act as substrates
    for this enzyme (Shen et al., 1994).

     CYP2B: When recombinant gene technology was used to express human
    CYP2B6 cDNA in a human lymphoblastoid cell line, this enzyme was shown
    to be capable of metabolizing benzo [a]pyrene to 3- and 9-phenols and
     trans-dihydrodiols (Shou et al., 1994). In addition, CYP2B enzymes
    may be involved in the metabolism of 7,12-dimethylbenz [a]anthracene
    (Morrison et al., 1991a).

    The constitutive levels of CYP2B enzymes are extremely low in human
    liver, but they are strongly induced by phenobarbital and
    phenobarbital-type inducers of CYP. Accordingly, immunological studies
    of inhibition have shown that the CYP2B enzymes may play a significant
    role in the metabolism of PAH, only when they are induced (Hall et
    al., 1989; Honkakoski & Lang, 1989).

     CYP2C: The CYP2C subfamily contains several members, some of which
    are expressed at high levels in human liver. More than one member of
    this subfamily may be capable of metabolizing PAH; thus, human CYP2C9
    and, to a lesser extent, CYP2C8 metabolize benzo [a]pyrene to 3- and
    9-phenols and  trans-dihydrodiols (Shou et al., 1994). In addition,
    CYP2C enzymes may play an essential role in the metabolism of
    benzo [a]pyrene and 7,12-dimethyl-benz [a]anthracene, particularly
    in phenobarbital-induced liver (Morrison et al., 1991a,b; Todorovic et
    al., 1991). In view of the relative abundance of CYP in human liver
    and their role in the metabolism of PAH, it has been suggested that
    some CYP2C enzymes play an essential role in hepatic PAH metabolism
    (Morrison et al., 1991b; Yun et al., 1992).

     CYP3A: CYP3A is one of the most abundant CYP enzymes in human liver,
    and it can metabolize benzo [a]pyrene and some of its dihydrodiols to
    several metabolic products (Shimada et al., 1989; Yun et al., 1992;
    Shou et al., 1994; Bauer et al., 1995). In one study, human CYP3A4 was
    the most important single enzyme in the hepatic 3-hydroxylation of
    benzo [a]pyrene (Yun et al., 1992).

    6.3.1.2  Regulation of cytochrome P450 enzymes that metabolize PAH

    All of the enzymes discussed above are inducible, and their level of
    expression can be enhanced by external stimuli. CYP1A and CYP1B are
    under the transcriptional control of the Ah receptor, which can be
    activated by numerous PAH and other planar hydrocarbons, including
    dioxins (Negishi et al., 1981; Guengerich & Shimada, 1991)

    CYP2B enzymes can also be induced by foreign compounds but not through
    the Ah receptor. The mechanism of induction of these enzymes is not
    well understood, but their prototype inducer is phenobarbital; several
    other drugs used clinically have similar effects (Gonzalez & Gelboin,
    1994).

    The regulation of CYP2C enzymes is complicated, and both endogenous
    factors such as steroid hormones and exogenous factors such as
    phenobarbital may be involved. Furthermore, different members of this
    subfamily are regulated differently. The CYP3A are also regulated by
    endogenous and exogenous factors; typical inducers of this subfamily
    are rifampicin, dexamethasone, certain macrolide antibiotics, and
    steroid hormones (Guengerich & Shimada, 1991).

    Genetic polymorphisms of CYP1A1, CYP1A2, and some CYP2C and CYP3A
    enzymes have also been described. Some of the genetic defects leading
    to the polymorphism have been identified and can be used to predict an
    individual's capacity to metabolize drugs, for example by the
    polymerase chain reaction. Genetic polymorphism may lead to dramatic
    changes in the capacity to metabolize PAH (Raunio & Pelkonen, 1994).

    Studies with a few prototype compounds such as benzo [a]pyrene and
    its metabolites and 7,12-dimethylbenz [a]anthracene indicate that
    several CYP are involved in PAH metabolism. As each has its own
    metabolic capacity, mode of regulation, and tissue-specific
    expression, the one that plays a key role in PAH metabolism  in vivo
    at any one time may vary and will depend on the compound being
    metabolized, pre-exposure to inducers of the CYP, the tissue and cell
    type where the metabolism is taking place, and the genotype of the
    individual in cases of genetic polymorphism.

    Many PAH that are metabolized by the CYP-dependent mono-oxygenases
    also induce the enzyme system. This ability of hydrocarbons to induce
    their own metabolism usually results in lower tissue levels and more
    rapid excretion of the hydrocarbon (Schlede et al., 1970b; Aitio,
    1974). Although CYP1A1 is mainly responsible for activation of PAH in
    the lung and CYP1A2 in the liver, most recent investigations have
    shown that other CYP isoforms may also contribute to the metabolism of
    PAH in mammals (Jacob et al., 1996). Thus, pretreatment of animals
    with inducers of mono-oxygenase systems is frequently associated with
    a decreased tumour incidence (Wattenberg, 1978). Conversely, studies
    with strains of mice that differ genetically in the capacity of their
    mono-oxygenase systems to be induced by PAH indicate that inducibility
    may also be associated with an increased tumorigenic or toxicological
    response (Nebert, 1980). Induction of the mono-oxygenase system by

    different types of inducers can result in different profiles of
    hydrocarbon metabolites, although the extent of the effect appears to
    be variable (Holder et al., 1974; Jacob et al., 1981a,b; Schmoldt et
    al., 1981). The metabolism of benzo [a]pyrene has been investigated
    in more detail than that of other hydrocarbons and is used here as an
    example.

    6.3.2  Metabolism of benzo[a]pyrene

    In early studies, the PAH metabolites isolated from or excreted by
    experimental animals were shown to consist of hydroxylated
    derivatives, commonly in the form of conjugates. Thus, the general
    scheme of xenobiotic metabolism outlined above applies to PAH. One of
    the principal interests in hydrocarbon metabolism arose, however, from
    the realization that hydrocarbons, like many other environmental
    carcinogens, are chemically unreactive and that their adverse
    biological effects are probably mediated by electrophilic metabolites
    capable of covalent interaction with critical macromolecules such as
    DNA. Identification of the biologically active metabolites of PAH,
    coupled with advances in both the synthesis of known and potential
    hydrocarbon metabolites and the analysis of metabolites by
    high-performance liquid chromatography, has led in the last two
    decades to a greatly enhanced appreciation of the complexity of
    hydrocarbon metabolism. Most of these metabolic interrelationships are
    illustrated for benzo [a]pyrene in Figure 3; the structures of some
    types of metabolites are given in Figure 4. The metabolism of
    benzo [a]pyrene and other PAH has been reviewed (for example, Sims &
    Grover, 1974, 1981; Conney, 1982; Cooper et al., 1983; Dipple et al.,
    1984; Hall & Grover, 1990).

    Benzo [a]pyrene is metabolized initially by the microsomal
    CYP-dependent mono-oxygenase system to several epoxides (Figure 3).
    Once formed, these epoxides (Sims & Grover, 1974) may spontaneously
    rearrange to phenols, be hydrated to dihydrodiols in a reaction that
    is catalysed by epoxide hydrolase (see review by Oesch 1973), or react
    covalently with glutathione, either chemically or in a reaction
    catalysed by glutathione  S-transferase (Chasseaud, 1979).
    6-Hydroxybenzo [a]pyrene is further oxidized either spontaneously or
    metabolically to the 1,6-, 3,6-, or 6,12-quinone, and this phenol is
    also a presumed intermediate in the oxidation of benzo [a]pyrene to
    the three quinones that is catalysed by prostaglandin H synthase. Two
    additional phenols may undergo further oxidative metabolism:
    3-hydroxybenzo [a]pyrene is metabolized to the 3,6-quinone, and
    9-hydroxybenzo [a]pyrene is oxidized to the K-region 4,5-oxide, which
    is hydrated to the corresponding 9-hydroxy 4,5-dihydrodiol (Jernström
    et al., 1978; for a formula showing a K-region, see Figure 11).
    Phenols, quinones, and dihydrodiols can all be conjugated to yield
    glucuronides and sulfate esters, and the quinones may also form
    glutathione conjugates (Figure 5).

    FIGURE 3

    FIGURE 4


    FIGURE 5

    In addition to being conjugated, dihydrodiols can undergo further
    oxidative metabolism. The mono-oxygenase system metabolizes
    benzo [a]pyrene 4,5-diol to a number of metabolites, while the
    9,10-dihydrodiol is metabolized predominantly to its 1- and 3-phenol
    derivatives, only minor quantities of a 9,10-diol-7,8-epoxide being
    formed. In contrast to 9,10-dihydrodiol metabolism, the principal
    route of oxidative metabolism of benzo [a]pyrene 7,8-dihydrodiol is
    to a 7,8-diol 9,10-epoxide, and triol formation is a minor pathway.
    The diol epoxides can themselves be further metabolized to triol
    epoxides and pentols (Dock et al., 1986) and can become conjugated
    with glutathione either through chemical reaction or via a glutathione
     S-transferase-catalysed reaction (Cooper et al., 1980; Jernström et
    al., 1985; Robertson et al., 1986). They may also spontaneously
    hydrolyse to tetrols, although epoxide hydrolase does not appear to
    catalyse this hydration. Further oxidative metabolism of
    benzo [a]pyrene 7,8-diol can also be catalysed by prostaglandin H
    synthase (Marnett et al., 1978; Eling et al., 1986; Eling & Curtis,
    1992), by a myeloperoxidase system (Mallett et al., 1991), or by
    lipoxygenases (Hughes et al., 1989). These reactions may be of
    particular importance in situations in which there are relatively low
    levels of CYP (i.e. in uninduced cells and tissues) or when chronic
    irritation and/or inflammation occurs, as during cigarette smoking
    (Kensler et al., 1987; Ji & Marnett, 1992). The products detected have
    included diol epoxides (Mallet et al., 1991; Ji & Marnett, 1992) and
    tetrols (Sivarajah et al., 1979). Taken together, these reactions
    illustrate that benzo [a]pyrene in particular, and PAH in general,
    can undergo a multitude of simultaneous or sequential metabolic
    transformations; they also illustrate the difficulty in determining
    which metabolites are responsible for the various biological effects
    resulting from treatment with the parent PAH.

    An additional complexity of hydrocarbon metabolism stems from the fact
    that the compounds are metabolized to optically active products.
    Figure 6 illustrates the stereoselective metabolism of
    benzo [a]pyrene to the 7,8-diol-9,10-epoxides. Four isomers may be
    generated, since each diastereomer can be resolved into two
    enantiomers. In rat liver microsomes, the (+) 7,8-epoxide of
    benzo [a]pyrene is formed in excess relative to the (-) isomer, such
    that more than 90% of the benzo [a]pyrene 7,8-oxide formed consists
    of the (+) enantiomer (Levin et al., 1982). The epoxide is then
    metabolized stereospecifically by epoxide hydrolase to the (-)
    7,8-dihydrodiol. This metabolically predominant dihydrodiol is
    metabolized in turn, primarily to a single diol epoxide isomer, the
    (+)  anti-benzo [a]pyrene 7,8-diol-9,10-epoxide. The biological
    significance of the stereoselective formation of the
    7,8-diol-9,10-epoxide isomers is that the metabolically predominant
    isomer is also the isomer with the highest tumour-inducing activity
    and that found predominantly to be covalently bound to DNA in a
    variety of mammalian cells and organs that have been exposed to
    benzo [a]pyrene.

    FIGURE 6

    Benzo [a]pyrene metabolism has been examined extensively in human
    tissue preparations, including human cells, explant cultures, tissue
    homogenates, and microsomal preparations. Table 73 lists some studies
    of the metabolism of benzo [a]pyrene in human tissues that included
    metabolites soluble in organic solvents and water-soluble conjugates.
    The results show that the metabolites produced by different human
    tissues are qualitatively similar and that the metabolites detected
    are the same as those formed in a variety of animal tissues.

    The metabolic profiles reported in human tissues are almost all
    identical to those seen for other eukaryotes, indicating the
    involvement of similar enzyme systems. The same types of reactive
    electrophilic intermediates found in other experimental systems also
    appear to be formed in human tissues (Autrup & Harris, 1983). So far,
    no differences in the metabolism or activation of benzo [a]pyrene
    have been reported that might account for differences in the
    susceptibility of different animal and human tissues to its
    carcinogenic properties (see Section 7). Studies with cultured cells
    and other substrates such as benz [a]anthracene, however, indicate
    that bioactivation of PAH is species-dependent (Jacob, 1996).

    6.4  Elimination and excretion

    Most metabolites of PAH are excreted in faeces and urine. As complete
    breakdown of the benzene rings of which unsubstituted PAH are composed
    does not occur to any appreciable extent in higher organisms, very
    little of an administered dose of an unsubstituted hydrocarbon would
    be expected to appear as carbon dioxide in expired air.

    The urinary excretion of PAH metabolites has been studied more
    extensively than faecal excretion, but the importance of the
    enterohepatic circulation of metabolites has led to increased research
    on the latter. Detailed studies of the metabolism and excretion of PAH
    in whole animals have been restricted mainly to the simpler compounds.
    Because of the toxicity of the larger hydrocarbons and the complexity
    of their metabolism, most studies on these compounds have been carried
    out in hepatic homogenates and microsomal preparations or with
    cultured cells (see above).

    Metabolism and excretion in whole animals have been examined with
    regard to naphthalene (Bourne & Young, 1934; Young, 1947; Booth &
    Boyland, 1949; Corner & Young, 1954; Corner et al., 1954; Boyland &
    Sims, 1958; Sims, 1959), anthracene (Boyland & Levi, 1935, 1936a,b;
    Sims, 1964), phenanthrene (Boyland & Wolf, 1950; Sims, 1962; Boyland &
    Sims, 1962a,b; Jacob et al., 1990b; Grimmer et al., 1991a), pyrene
    (Harper, 1957, 1958a; Boyland & Sims, 1964a; Jacob et al., 1989,
    1990b), benz [a]-anthracene (Harper 1959a,b; Boyland & Sims, 1964b),
    and chrysene (Grimmer et al., 1988b, 1990). A limited number of
    studies have been published on more complex compounds such as
    benzo [a]pyrene (Berenblum & Schoental, 1943; Weigert & Mottram,
    1946; Harper, 1958b,c; Falk et al., 1962; Raha, 1972; Jacob et al.,
    1990b), dibenz [a,h]anthracene (Dobriner et al., 1939; Boyland et
    al., 1941; La Budde & Heidelberger, 1958), and 3-methylcholanthrene


        Table 73. Metabolites of benzo[a]pyrene formed by human tissues and cells

                                                                                                               

    Tissue or       Type of metabolite detected                                         References
    cell type                                                                       
                    Dihydrodols    Phenols     Quinones     Tetrols     Conjugates
                                                                                                               

    Bronchus        +              +           +            +           +               Pal et al. (1975);
                                                                                        Cohen et al. (1976);
                                                                                        Harris et al. (1977);
                                                                                        Autrup et al. (1978a,
                                                                                        1980)
    Colon           +              +           +            +           +               Autrup et al. (1978b);
                                                                                        Autrup (1979)
    Endometrium     +              +           +                                        Mass et al. (1981)
    Fibroblasts     +                                                                   Baird & Diamond (1978)
    Kidney          +              +           +                                        Prough et al. (1979)
    Liver           +              +           +                        +               Selkirk et al. (1975);
                                                                                        Prough et al. (1979);
                                                                                        Pelkonen et al. (1977);
                                                                                        Diamond et al. (1980)
    Lung            +              +           +            +           +               Cohen et al. (1976);
                                                                                        Stoner et al. (1978);
                                                                                        Mehta et al. (1979);
                                                                                        Prough et al. (1979);
                                                                                        Sipal. et al. (1979)
    Lymphocytes     +              +           +                                        Booth et al. (1974);
                                                                                        Selkirk et al. (1975);
                                                                                        Vaught et al. (1978);
                                                                                        Okano et al. (1979);
                                                                                        Gurtoo et al. (1980)
    Macrophages     +              +           +            +           +               Autrup et al. (1978a);
                                                                                        Harris et al. (1978a,b);
                                                                                        Autrup et al. (1979);
                                                                                        Marshall et al. (1979)

    Table 73 (contd)

                                                                                                               

    Tissue or       Type of metabolite detected                                         References
    cell type                                                                       
                    Dihydrodols    Phenols     Quinones     Tetrols     Conjugates
                                                                                                               

    Mammary         +                                                                   Grover et al. (1980);
    epithelium                                                                          MacNicoll et al. (1980)
    Monocytes       +              +           +                                        Vaught et al. (1978);
                                                                                        Okano et al. (1979)
    Oesophagus      +              +           +            +                           Harris et al. (1979)
    Placenta        +              +           +                                        Namkung & Juchau (1980);
                                                                                        Pelkonen & Saarni (1980)
    Skin            +              +           +            +                           Fox et al. (1975);
                                                                                        Vermorken et al. (1979);
                                                                                        Parkinson & Newbold (1980);
                                                                                        Kuroki et al. (1980)
                                                                                                               


    (Harper, 1959a; Takahashi & Yasuhira, 1972; Takahashi, 1978). Much of
    the earlier qualitative work was reviewed by Boyland & Weigart (1947)
    and by Young (1950). The absorption and excretion of different
    hydrocarbons  in vivo can differ. For example, while almost all of a
    topically applied dose of benzo [a]pyrene appeared in mouse faeces
    (Heidelberger & Weiss, 1951), little dibenz [a,h]-anthracene was
    excreted by this route.

    In rats given PAH either singly or as mixtures, the faecal elimination
    of chrysene (25% of the dose) was not affected by co-administration of
    benz [a]anthracene, but that of benz [a]anthracene was doubled, from
    6 to 13% of the dose, when chrysene was given (Bartosek et al., 1984).
    Such effects are relevant to human pharmacokinetics, since exposure is
    almost always to mixtures of PAH. In workers in a coke plant exposed
    to mixtures of PAH, the amounts of phenanthrene, pyrene, and
    benzo [a]pyrene inhaled and the amounts of their principal
    metabolites excreted in the urine were correlated (Grimmer et al.,
    1994).

    In rats, the amount of benzo [a]pyrene 7,8-diol excreted in the urine
    is related to the susceptibility of individual animals to the
    carcinogenic effects of benzo [a]pyrene (Likhachev et al., 1992;
    Tyndyk et al., 1994). In studies of the disposition of
    benzo [a]pyrene in rats, hamsters, and guinea-pigs after
    intratracheal administration, the distribution of the hydrocarbon was
    qualitatively similar but quantitatively different. In Sprague-Dawley
    and Gunn rats and in guinea-pigs, the rate of excretion was dependent
    on the dose administered, but in hamsters the rate of excretion was
    independent of dose (0.16 or 350 µg 3H-benzo [a]pyrene) (Weyand &
    Bevan 1986, 1987a). Evidence for enterohepatic circulation of
    benzo [a]pyrene metabolites was obtained in Sprague-Dawley rats with
    bile-duct cannulae treated by intratracheal instillation with 1 µg/kg
    bw 3H-benzo [a]pyrene (Weyand & Bevan, 1986). The results of a study
    of the pharmacokinetics and bioavailability of pyrene in rats strongly
    suggested that enterohepatic recycling took place after oral or
    intravenous administration of 14C-labelled compound at 2-15 mg/kg bw
    (Withey et al., 1991).

    Other studies on the enterohepatic circulation of PAH in rats and
    rabbits have also shown that the significant amounts of metabolites
    excreted in the bile persist  in vivo because of enterohepatic
    circulation (Chipman et al., 1981; Chipman, 1982; Boroujerdi et al.,
    1981). For example, while some 60% of an intravenous dose of 3 µmol/kg
    bw 14C-benzo [a]pyrene was excreted in bile, only 3% appeared in
    urine within the first 6 h after injection (Chipman et al., 1981).
    Biliary metabolites of xenobiotic compounds are usually polar and
    nonreactive, but mutagenic or potentially mutagenic derivatives may be
    excreted by this route into the intestine (for a review, see Chipman,
    1982). Glucuronic acid conjugates of biliary metabolites can be
    hydrolysed by some intestinal flora to potentially reactive species
    (Renwick & Drasar, 1976; Chipman et al., 1981; Boroujerdi et al.,
    1981; Chipman, 1982). Thio-ether conjugates of hydrocarbons may also
    be involved in enterohepatic circulation (Hirom et al., 1983; Bakke et

    al., 1983), although there is no evidence that these represent a
    mutagenic or carcinogenic hazard to the tissues through which they
    pass.

    In a controlled study in humans, a 100-250-fold increase in dietary
    exposure to PAH, as measured by benzo [a]pyrene intake, resulted in a
    4-12-fold increase in urinary excretion of 1-hydroxypyrene. The
    authors concluded that dietary exposure to PAH is as substantial as
    some occupational exposures (Buckley & Lioy, 1992).

    6.5  Retention and turnover

    Very little is known about the retention and turnover of PAH in
    mammalian species. It can be deduced from the few data available on
    hydrocarbon body burdens (see below) that PAH themselves do not
    persist for long periods and must therefore turn over reasonably
    rapidly. During metabolism, PAH moieties become covalently bound to
    tissue constituents such as proteins and nucleic acids. Protein-bound
    metabolites are likely to persist, therefore, for periods that do not
    exceed the normal lifetime of the protein itself. Nucleic acid adducts
    formed from reactions of PAH metabolites can be expected to differ in
    their persistence in the body according to whether they are RNA or DNA
    adducts. Although most DNA adducts are removed relatively rapidly by
    repair, small fractions can persist for long periods. The persistence
    of these adducts in tissues such as mouse skin is of considerable
    interest since one of the basic features of the two-stage mechanism of
    carcinogenesis (Berenblum & Shubik, 1947) is that application of the
    tumour promoter can be delayed for many months without markedly
    reducing the eventual tumour yield.

    The persistence of adducts is also consistent with multistage theories
    of carcinogenesis, in which multiple steps in neoplastic
    transformation are dependent on the mutagenic and other actions of
    carcinogens.

    6.5.1  Human body burdens of PAH

    Since the effects of chemical carcinogens are likely to be related to
    both the dose and the duration of exposure, it is important to
    determine the human body load of carcinogens during a lifetime. It has
    been estimated that the total intake of PAH over a 70-year lifespan
    may amount to the equivalent of 300 mg of benzo [a]pyrene (Lutz &
    Schlatter, 1992); however, inhabitants of conurbations are likely to
    inhale additional amounts of PAH. Of course, much of the intake of PAH
    is metabolized and excreted. Thus, the pulmonary tissues of elderly
    town dwellers in Russia contained 1000 times less benzo [a]pyrene
    (< 0.1 µg per individual) than might have been expected from the
    estimated intake figures alone (Shabad & Dikun, 1959). Some
    experiments with cows and domestic fowl fed diets containing added
    benzo [a]pyrene tend to confirm this finding, since the meat, milk,
    and eggs produced were, after a suitable delay, reported to be much
    less heavily contaminated than might have been expected from the

    amounts of benzo [a]pyrene administered (Gorelova & Cherepanova,
    1970). More recent data are not available.

    The average benzo [a]pyrene levels (measured by ultraviolet
    spectroscopy) in tissues taken at autopsy from normal people of a wide
    age range were 0.32 µg/100 g dry tissue weight in liver, spleen,
    kidney, heart, and skeletal muscle and 0.2 µg/100 g in lung (Gräf,
    1970; Gräf et al., 1975).

    When cancer-free liver and fat from six individuals were assayed for
    nine hydrocarbons by co-chromatography with authentic standards,
    pyrene, anthracene, benzo [b]fluoranthene, benzo [ghi]perylene,
    benzo [k]fluoranthene, and benzo [a]pyrene were detected at average
    levels of 380 ppt (0.38 µg/kg wet weight) in liver and 1100 ppt (1.1
    µg/kg wet weight) in fat. Pyrene was the most abundant PAH present
    (Obana et al., 1981b).

    Samples of 24 bronchial carcinomas, taken during surgery or at autopsy
    from smokers and nonsmokers with a variety of occupations, were
    analysed for the presence of 12 PAH by thin-layer chromatography and
    fluorescence spectroscopy. Benzo [a]pyrene, benzo [b]fluoranthene,
    fluoranthene, and perylene were detected. Benzo [a]pyrene was
    present, but the other three PAH were found in only some of the
    samples. The average concentrations of benzo [a]pyrene were 3.5 µg/g
    in carcinoma tissue and 0.09 µg/g in tumour-free tissue (Tomingas et
    al., 1976).

    6.6  Reactions with tissue components

    The reactions of metabolites of PAH with tissue constituents
    (Weinstein et al., 1978) are relevant because they may indicate the
    mechanisms by which the hydrocarbons exert biological effects that
    include toxicity and carcinogenesis.

    6.6.1  Reactions with proteins

    Covalent interactions of PAH with protein in whole animals were first
    noted in 1951 (Miller, 1951). It was proposed that reactions with
    specific proteins might be involved in the initiation of malignancy in
    liver (Miller & Miller, 1953), skin (Abell & Heidelberger, 1962), and
    transformable cells in culture (Kuroki & Heidelberger, 1972). These
    findings were supported by evidence that hydrocarbon metabolites can
    react covalently with protein in microsomal incubates (Grover & Sims,
    1968), in preparations of nuclei (Vaught & Bresnick, 1976; Pezzuto et
    al., 1976, 1977; Hemminki & Vainio, 1979), and in cells and tissues
    maintained in culture, including human tissues (Harris et al., 1978b;
    MacNicoll et al., 1980). Although hydrocarbon metabolites often react
    at much greater rates with protein than with nucleic acids in the same
    biological system, relatively little attention has been paid to the
    nature of the hydrocarbon metabolites involved or to the specificity
    of these reactions, in terms of which proteins are most extensively
    modified and where and the effect that such modification might have on
    protein function. The evidence suggests, however, that the reactive

    species involved include diol epoxides. Thus, when protein isolated
    from the skin of mice that had been treated with benzo [a]pyrene was
    hydrolysed, tetrols were liberated, and the patterns of specific
    tetrols indicated that both  syn and  anti isomers of the
    benzo [a]pyrene 7,8-diol 9,10-oxides are involved in covalent
    reactions with protein (Koreeda et al., 1978). Studies of the covalent
    interactions of diol epoxides with nuclear proteins show that a
    variety of histones and non-histone proteins are modified (Kootstra &
    Slaga, 1979; Kootstra et al., 1979; Whitlock, 1979).

    6.6.2  Reactions with nucleic acids

    The covalent interactions of electrophilic metabolites of PAH with
    nucleic acids have been studied in much greater detail than those with
    protein, partly because characterization of the products might, in
    theory, be expected to be simpler, partly because the cellular nucleic
    acids are, as nucleophiles, more 'homogeneous' than proteins, but
    mainly because it has long been suspected that nucleic acid
    modifications could lead to a permanent alteration of cell phenotype.

    The covalent binding of a PAH (dibenz [a,h]anthracene) to DNA
     in vivo was first reported by Heidelberger & Davenport in 1961.
    Subsequent studies with naphthalene, dibenz [a,c]anthracene,
    dibenz [a,h]anthracene, benzo [a]-pyrene, 3-methylcholanthrene, and
    7,12-dimethylbenz [a]anthracene showed that the levels of DNA binding
    in mouse skin are correlated with carcinogenic potency, as measured by
    Iball's index (Brookes & Lawley, 1964).

    6.7  Analytical methods

    Of the methods used for the detection of carcinogen-DNA adducts
    (Phillips, 1990; Strickland et al., 1993; Weston, 1993), one of the
    most widely used is 32P-postlabelling, in which DNA is hydrolysed to
    nucleotides, modified nucleotides (i.e. adducts) are labelled with
    32P-phosphate, and the post-labelled adducts separated by thin-layer
    chromatography and/or high-performance liquid chromatography (for
    reviews of the method, see Phillips, 1991, and Phillips et al., 1993).
    The main advantages of the 32P-postlabelling assay are its high
    sensitivity and the fact that radiolabelled carcinogens and/or their
    metabolites need not be synthesized beforehand.

    A variety of physical methods have been described for the detection of
    adducts, including fluorescence line narrowing spectroscopy,
    synchronous fluorescence spectroscopy, and some specialized gas
    chromatography-mass spectrometry procedures (Weston, 1993). The
    physical methods combine high sensitivity with no requirement for
    prior radiolabelling of the carcinogens or their adducts and may be
    nondestructive. Sensitive methods involving antisera specific for
    carcinogen-DNA adducts have also been developed. These include
    radioimmunoassays, enzyme-linked immunosorbent assays, and
    immuno-affinity chromatography (Poirier, 1994).

    Information on the pathways thought to be involved in the metabolic
    activation of several PAH is given in Table 74. For PAH that have been
    extensively investigated, reviews are cited. In order to provide an
    overall view of activation, the Table also includes data on PAH not
    covered elsewhere in this monograph.

    Most of the metabolites that have been found to react with nucleic
    acids are vicinal diol epoxides, and most of these are diol epoxides
    of the 'bay-region' type, although there are certain exceptions (Table
    74). For example, activation of benzo [j]fluoranthene in mouse skin
    involves a diol epoxide that is not of the bay-region type (Weyand et
    al., 1993). Additionally, methyl-substituted PAH may become bound to
    hydroxymethyl derivatives which, when conjugated, yield electrophilic
    sulfate esters (Surh et al., 1989, 1990a,b).

    The sites of attack on nucleic acid bases are usually the extranuclear
    amino groups of guanine and adenine. When the reactions of the  syn 
    and  anti isomers of benzo [a]pyrene 7,8-diol-9,10-oxide with RNA,
    DNA, and homopolymers were examined in experiments in which the
    epoxide was incubated with the nucleic acid in a predominantly aqueous
    solution, RNA, DNA, poly G, poly A, poly C, poly (dG), poly (dA), and
    poly (dC) were modified, but there was little reaction with poly U,
    poly I, or poly (dT) (Weinstein et al., 1976; Jennette et al., 1977).
    Although many of the hydrocarbon-deoxyribonucleoside adducts formed in
    human cells and tissues treated with PAH have not been completely
    characterized, the available evidence, which is mostly
    chromatographic, suggests that in human bronchial epithelium, colon,
    mammary cells in culture, and skin the patterns of adducts formed are
    very similar to those formed in corresponding rodent tissues (Autrup
    et al., 1978a,b; Harris et al., 1979; Autrup et al., 1980; MacNicoll
    et al., 1980; Weston et al., 1983). The rates of reaction of diol
    epoxides with nucleic acids was in the general order: poly G > DNA >
    poly A > poly C (Jennette et al., 1977).

    Diol epoxides are also strongly suspected to react frequently with the
    N7 position of guanine. This type of modification has not been
    detected more often because N7-alkylated adducts are thought to have a
    relatively short half-life at pH 7 and would therefore be lost during
    the isolation and hydrolysis of DNA. In experiments in which care was
    taken to avoid adduct loss, reactions of benzo [a]pyrene diol epoxide
    with both the N2 and N7 positions of guanine residues in DNA were
    detected (Osborne et al., 1978). N7 adducts were not, however,
    detected in cells treated with  anti-benzo [a]pyrene
    7,8-diol-9,10-oxide (King et al., 1979).

    In studies of the role of radical cations in the activation of PAH
     in vitro, adducts were formed in which the 6 position of
    benzo [a]pyrene was covalently linked to the C8 and N7 positions of
    guanine and the N7 position of adenine, and the 7-methyl position of
    7,12-dimethylbenz [a]anthracene was covalently linked to the N7
    positions of guanine and adenine (see Figure 7; Cavalieri et al.,
    1993; Rogan et al., 1993). All of these adducts are depurination
    adducts, which may explain why they were not detected earlier


        Table 74. Pathways involved in the metabolic activation of polycyclic aromatic hydrocarbons to form ultimate carcinogens

                                                                                                                                      

    Compound                           Derivatives with highest          Putative ultimate carcinogen       Reference
                                       levels of biological activity
                                                                                                                                      

    Aceanthrylene                                                        1,2-Oxidea                         Nesnow et al. (1991)

    Benz[j]aceanthrylene                                                 ? 1,2-Oxideb                       Bartczak et al. (1987);
                                                                                                            Nesnow et al. (1988)

    Benz[l]aceanthrylene                                                 ? 1,2-Oxideb,c                     Nesnow et al. (1984);
                                                                                                            Bartzczak et al. (1987);
                                                                                                            Nesnow et al. (1988)

    Benz[a]anthracene                  3,4-Diold,e,f,g                   3,4-Diol 1,2-oxldea,b,c,f,g        Sims & Grover (1981);
                                       8,9-Diold                         8,9-Diol 10,1-oxidea,h             Conney (1982);
                                                                                                            Wood et al. (1983a)

    Benzo[b]fluoranthene               9,10-Dlold,f,i                    ? 910-Diol-11,12-oxide             Geddie et al. (1987);
                                                                         and 5/6-hydroxy-9,10-              Pfau et al. (1992)
                                                                         diol-11, 12-oxide

    Benzo[b]fluoranthene               ? 9,10-Diolf,j                    ? 9,10-Diol 11,12-oxidea           Rice et al. (1987);
                                                                                                            Weyand et al. (1993)
                                       ? 4,5-Diola                       ? 4,5-Diol 6,6a-oxidea             Weyand et al. (1987)

    Benzo[c]phenanthrene               3,4-Diold,e,f,g                   3,4-Diol 1,2-oxidea,b,c,f,g        Conney (1982);
                                                                                                            Levin et al. (1986);
                                                                                                            Agarwal et al. (1987);
                                                                                                            Dipple et al. (1987);
                                                                                                            Pruess-Schwartz et al.
                                                                                                            (1987)

    Benzo[a]pyrene                     7,8-Diold,e,f,h                   7,8-Diol 9,10-oxidea,b,c,g         Cooper et al. (1983);
                                                                                                            Osborne & Crosby (1987a)

    Table 74. (continued)

                                                                                                                                      

    Compound                           Derivatives with highest          Putative ultimate carcinogen       Reference
                                       levels of biological activity
                                                                                                                                      

    Benzo[e]pyrene                     9,10-Diolf                        ? 9,10-Diol 11,12-oxideg           Osborne & Crosby (1987b)

    Chrysene                           1,2-Diold,e,f                     1,2-Diol 3,4-oxidea,b,c,h          Conney (1982);
                                       9-Hydroxy 1,2-diold,e             9-Hydroxy-1,2-diol                 Hodgson et al. (1983);
                                                                         3,4-oxideb,c                       Glatt et al. (1986)

    Cyclopenta[cd]pyrene               -                                 ? 3,4-oxideb,c,h                   Gold & Eisenstadt (1980);
                                                                                                            Gold et al. (1980)

    15,16-Dihydro-11-methylcyclo-      3,4-Diold,f                       3,4-Diol 1,2-oxidea                Coombs & Bhatt (1987)
    penta[a]phenanthren-17-one

    15,16-Diydro-1,11-methano-         3,4-Diold                         3,4-Diol 1,2-oxide                 Coombs & Bhatt (1987)
    cyclopenta[a]phenanthren-17-one

    Dibenz[a,c]anthracene              10,11-Diold                       ? 10, 11-Diol 12,13-oxide          Sims & Grover (1981)

    Dibenz[a,h]anthracene              3,4-Diold,f,g,h                   ? 3,4-Diol 1,2-oxide and           Conney (1982);
                                                                         3,4:10,1 1-bis-diol-epoxides       Lecoq et al. (1991, 1992);
                                                                                                            Carmichael et al. (1993);
                                                                                                            Nesnow et al. (1994)

    Dibenzo[a,e]fluoranthene           12,13-Diold,f                     12,13-Diol 10-11-oxidea            Perin-Roussel et al.
                                                                                                            (1983,1984);
                                       3,4-Diold,f                       3,4-Diol 1,2-oxidea                Saguem et al. (1983a,b);
                                                                                                            Zajdela et al. (1987)

    Dibenzo[a,h]pyrene                 1,2-Diolf,g                       ? 1,2-Diol 3,4-oxideg              Chang et al. (1982)

    Dibenzo[a,l]pyrene                 ? 11,12 Diolf                     ? 11,12-Diol 13,14-oxide           Cavalieri et al. (1991)

    Table 74. (continued)
                                                                                                                                      

    Compound                           Derivatives with highest          Putative ultimate carcinogen       Reference
                                       levels of biological activity
                                                                                                                                      

    Dibenzo[a,i]pyrene                 3,4-Diolf,g                       ? 3,4-Diol 1,2-oxideg              Chang et al. (1982)

    7,12-Dimethylbenz[a]anthracene     3,4-Diold,e,f,h                   3,4-Diol 1,2-oxidea                Sims & Grover (1981);
                                                                                                            Conney (1982);
                                                                                                            Sawicki et al. (1983);
                                                                                                            Dipple et al.; 1984)

    7-Ethylbenz[a]anthracene           3,4-Diold                         ? 3,4-Diol 1,2-oxidea,b            McKay et al. (1988);
                                                                                                            Glatt et al. (1989)

    Fluoranthene                       Z3,Diold                          2,3-Diol 1,10b-oxidea              La Voie et al. (1982a);
                                                                                                            Rastetter et al. (1982);
                                                                                                            Babson et al. (1986a);
                                                                                                            Hecht et al. (1995)

    Indeno[1,2,3-cd]pyrene             1,2-oxideb,f                      ?                                  Rice et al. (1985)
                                       1,2-Diolf                                                            Rice et al. (1986)
                                       8-Hydroxyd
                                       9-Hydroxyd

    7-Methylbenz[a]anthracene          3,4-Diold,e,f,h                   3,4-Diol 1,2-oxidea,b              Sims & Grover (1981);
                                                                                                            McKay et al. (1988);
                                                                                                            Glatt et al. (1989)

    3-Methylcholanthrene               9,10-Diold,f,h                    ? 9,10-Diol 7,13-oxidea,f          Sims & Grover (1981);
                                                                         ? 3-Hydroxymethyl-9,10-            Conney (1982);
                                       diol 7,8-oxide                    DiGiovanni et al. (1985);
                                                                                                            Osborne et al. (1986)

    5-Methylchrysene                   1,2-Diold,f                       1,2-Diol 3,4-oxidea,c,h            Hecht et al. (1986);
                                                                                                            Brookes et al. (1986);
                                                                                                            Reardon et al. (1987);
                                                                                                            Hecht et al. (1987)
                                                                                                                                      

    Table 74 (continued)

    a DNA adducts characterized
    b Directly acting mutagen in S. typhimurium
    c Directly acting mutagen in V79 Chinese hamster cells
    d Mutagenic to S. typhimurium with metabolic activation
    e Mutagenic to V79 Chinese hamster cells with metabolic activation
    f Tumour initiator in mouse skin
    g Induces tumours in newborn mice
    h Transforms cells in culture
    i Not detected as a metabolite; activation may therefore occur via a different pathway.
    j Although the 45-diol is the most active derivative so far tested, there is some evidence that adducts arise from the 9,1-diol.


     in vivo. The formation of apurinic sites in DNA could lead to strand
    nicking (Gamper et al., 1977, 1980). When the positions of the nicks
    produced as a result of modification by benzo [a]pyrene
    7,8-diol-9,10-oxide were investigated with DNA of a defined sequence,
    nicking appeared to be the result of the loss of purines and
    pyrimidines that had been modified at the N7 position of guanine or at
    the N3 position of adenine and cytosine (Haseltine et al., 1980).

    In studies of the distribution of covalently bound benzo [a]pyrene
    moieties in chromatin, more was bound to the inter-nucleosomal spacer
    regions of DNA than to DNA in nucleosomes (Jahn & Litman, 1977, 1979;
    Kootstra & Slaga, 1980). One explanation for this finding may be that
    nucleosomal DNA is better protected from modification by the presence
    of nucleoproteins; results consistent with this suggestion have been
    obtained with mitochondrial DNA. Graffi (1940a,b,c) suggested that
    lipophilic PAH accumulate in lipid-rich mitochondria. Allen & Coombs
    (1980) and Backer & Weinstein (1980) showed much higher levels of
    modification of mitochondrial than nuclear DNA in cultured cells
    treated with either benzo [a]pyrene or the  anti-benzo [a]pyrene
    7,8-diol-9,10-oxide.

    The molecular properties of adducts of benzo [a]pyrene
    7,8-dihydrodiol-9,10-epoxides with DNA have been described (Geacintov
    1988; Jernström & Gräslund, 1994). Although the biological
    effectiveness of all types of hydrocarbon-nucleic acid adducts has not
    been determined, it has been shown that differences in the biological
    activities of 7-ethyl- and 7-methylbenz [a]-anthracene are not due to
    differences in the mutagenic potential of the adducts formed (Glatt et
    al., 1989). Similar conclusions were drawn from work with a series of
    bay-region and fjord-region diol epoxides (Phillips et al., 1991; see
    section 7.10 for a description of a fjord region). At present,
    therefore, all hydrocarbon-deoxyribonucleoside adducts should be
    regarded as potentially damaging to the organism.

    The relationships between DNA adduct formation and tumour incidence
    were examined by Poirier & Beland (1992) on the basis of data from
    long-term studies in rodents administered carcinogens. The tumour
    incidence was compared with adduct levels measured in target tissues
    during the first two months of exposure. In most cases, linear
    increases in DNA adduct levels with dose were reflected in linear
    increases in tumour incidence, although there were exceptions.

    In a comparison of the incidence of lung adenomas in strain A/J mice
    240 days after they had received a single intraperitoneal injection of
    benzo [a]pyrene, dibenz [a,h]anthracene, benzo [b]fluoranthene,
    5-methyl-chrysene, or cyclopenta [cd]pyrene with the levels of DNA
    adducts detected in the lungs by 32P-postlabelling between days 1 and
    21 after treatment, time-integrated DNA adduct levels were calculated
    and plotted against lung adenoma frequency. The slopes obtained were
    essentially similar for benzo [a]pyrene, benzo [b]fluoranthene,
    5-methylchrysene, and cyclopenta [cd]pyrene but were different for
    dibenz [a,h]anthracene. The authors concluded that 'essentially
    identical induction of adenomas as a function of [time-integrated DNA

    adduct levels] for these PAH suggests that the formation and
    persistence of DNA adducts determines their carcinogenic potency'
    (Ross et al., 1995).


    FIGURE 7


    7.  EFFECTS ON LABORATORY MAMMALS AND IN VITRO

     Appraisal

    Single doses of polycyclic aromatic hydrocarbons (PAH) have moderate
    to low toxicity, with LD50 values generally > 100 mg/kg bw after
    intraperitoneal or intravenous injection and > 500 mg/kg bw after
    oral administration. Because most of the experimental studies have
    addressed the carcinogenicity of PAH, the database on their short- and
    long-term toxicity is quite small. In short-term studies, effects on
    the haematopoietic system were observed, e.g. benzo [a]pyrene caused
    myelotoxicity and dibenz [a,h]anthracene caused haemolymphatic
    alterations in mice. Anaemia is a typical effect of naphthalene.
    Values for a no-observed-adverse-effect level (NOAEL) and a
    lowest-observed-adverse-effect level (LOAEL) have been obtained in
    90-day studies by oral administration. The NOAEL values based on
    haematological effects and hepato- and nephrotoxicity were 75-1000
    mg/kg bw per day for the noncarcinogenic PAH acenaphthene, anthracene,
    fluoranthene, fluorene, and pyrene.

    Few studies have been conducted on dermal or ocular irritation. PAH
    do, however, have adverse effects after dermal administration, such as
    hyperkeratosis, which are correlated with their carcinogenic potency.
    Anthracene and naphthalene were reported to cause mild ocular
    irritation. The ocular toxicity of naphthalene is characterized by
    cataract formation. Benzo [a]pyrene caused skin hypersensitization.
    Anthracene and benzo [a]pyrene have been shown to have phototoxic
    potential and benzo [a]pyrene, dibenz [a,h]anthracene, and
    fluoranthene to have immunotoxic potential.

    PAH can cross the placenta and induce adverse effects on the embryo
    and fetus. Benz [a]anthracene, benzo [a]pyrene,
    dibenz [a,h]anthracene, and naphthalene were found to be embryotoxic.
    Benzo [a]pyrene also reduced female fertility and had effects on
    oocytes and on postnatal development. Studies on the effects of
    benzo [a]pyrene in mice with different genotypes demonstrated the
    importance of the genetic predisposition of animals or embryos for the
    development of overt toxic effects. A crucial genetic property is the
    presence or absence of the arylhydrocarbon (Ah) receptor, which
    induces the monooxygenase system; organisms can thus be divided into
    Ah responders and Ah non-responders.

    Mutagenicity has been investigated intensively in a broad range of
    assays. The only compounds that are clearly not mutagenic are
    naphthalene, fluorene, and anthracene. The evidence for five PAH is
    considered to be questionable because of a limited database, while the
    remaining 25 PAH are mutagenic (see Table 87). Mutagenicity is
    strictly dependent on metabolic activation of parent compounds. In
    bacteria and other cell systems that have no metabolizing system, a
    9000 × g microsomal preparation of liver (S9 mix) must be added as a
    metabolic activator.

    Comprehensive work on the carcinogenicity of these compounds has
    yielded negative results for fluorene, anthracene,
    1-methylphenanthrene, triphenylene, perylene, benzo[ghi]fluoranthene
    and benzo[ghi]perylene, some of which have been shown to be
    mutagenic. The evidence for a further nine PAH was classified as
    questionable, while the other 17 compounds were carcinogenic.
    Generally, the site of tumour development depends on the route of
    administration but is not restricted to those sites. Tissues such as
    the skin can metabolize PAH to their ultimate metabolites, thus
    becoming target organs themselves, and metabolites formed in the liver
    can reach various sites of the body via the bloodstream. The
    carcinogenic potency of PAH differs by three orders of magnitude, and
    toxic equivalence factors have been used to rank individual PAH (see
    Appendix I).

    The various theories for the mechanism of the carcinogenicity of PAH
    take into account chemical structure and ionization potential. The
    most prevalent theories are those involving the bay region and radical
    cations. The bay-region theory is based on the assumption that diol
    epoxides of the parent compounds are the ultimate carcinogens, which
    react with electrophilic epoxide groups on N atoms of DNA purines. The
    radical cation theory postulates the one-electron oxidation of PAH to
    form strong electrophiles which then react with DNA bases. These
    theories have been confirmed experimentally by detection of the
    corresponding DNA adducts in the PAH that have been investigated.
    Nevertheless, there is general agreement that any one theory cannot
    cover the mechanisms of action of all PAH.

    7.1  Toxicity after a single exposure

    Few studies are available on the acute toxicity of PAH, except for
    naphthalene. The LD50 values (Table 75) indicate that the acute
    toxicity is moderate to low. The results of all of these studies are
    summarized, even when a study was old and followed a non-systematic
    protocol, in the absence of alternatives.

    7.1.1  Benzo [a]pyrene

    In young rats, a single intraperitoneal injection of 10 mg
    benzo [a]pyrene per animal caused an immediate, sustained reduction
    in the growth rate (Haddow et al., 1937). In mice, a single
    intraperitoneal injection (dose not specified) resulted in small
    spleens, marked cellular depletion, prominent haemosiderosis, and
    follicles with large lymphocytes, leading to death (Shubik & Della
    Porta, 1957). After a single application of 0.05 ml of a 1% solution
    in acetone to the interscapular area of hairless mice (hr/hr strain),
    the mitotic rate of epidermal cells was increased (Elgjo, 1968).

    7.1.2  Chrysene

    In young rats, single intraperitoneal injections of 30 mg chrysene per
    animal did not reduce growth (Haddow et al., 1937).


        Table 75. Toxicity of single doses of polycyclic: aromatic hydrocarbons

                                                                                                           

    Compound           Species     Route of             LD50 (mg/kg) or          Reference
                                   administration       LC50 (mg/litre)
                                                                                                           

    Anthracene         Mouse       Oral                 18 000                   Montizaan et al. (1989)
                       Mouse       Intraperitoneal      > 430                    Salamone (1981)
    Benzo[a]pyrene     Mouse       Oral                 > 1 600                  Awogi & Sato (1989)
                       Mouse       Intraperitoneal      approx. 250              Salamone (1981)
                       Mouse       Intraperitoneal      > 1 600                  Awogi & Sato (1989)
                       Rat         Subcutaneous         50                       Montizaan et al (1989)
    Chrysene           Mouse       Intraperitoneal      > 320                    Simmon et al. (1979)
    Fluoranthene       Rat         Oral                 2 000                    Smyth et al. (1962)
                       Rabbit      Dermal               3 180                    Smyth et al. (1962)
                       Mouse       Intravenous          100                      Montizaan et al. (1989)
    Naphthalene        Rat         Oral                 1 250                    Sax & Lewis (1984)
                       Rat (M)     Oral                 2 200                    Gaines (1969)
                       Rat (F)     Oral                 2 400                    Gaines (1969)
                       Rat         Oral                 9 430                    US Environmental Protection
                                                                                 Agency (1978a)
                       Rat         Oral                 1 110                    Montizaan et al. (1989)
                       Rat         Oral                 490                      Montizaan et al. (1989)
                       Rat         Oral                 1 800                    Montizaan et al. (1989)
                       Rat (M)     Dermal               > 2 500                  Gaines (1969)
                       Rat (F)     Dermal               > 2 500                  Gaines (1969)
                       Rat         Intraperitoneal      approx. 1 000            Bolonova (1967)
                       Rat (M)     Intraperitoneal      approx. 1 600            Plopper et al. (1992)
                       Rat         Inhalation           > 0.5 mg/litre (8 h)     US Environmental Protection
                                                                                 Agency (1978a)
                       Mouse (F)   Oral                 354                      Plasterer et al. (1985)
                       Mouse (M)   Oral                 533                      Shopp et al. (1984)
                       Mouse (F)   Oral                 710                      Shopp et al. (1984)
                       Mouse       Subcutaneous         5 100                    Sandmeyer (1981);
                                                                                 Shopp et al. (1984)
                       Mouse       Subcutaneous         969                      Sax & Lewis (1984)
                       Mouse       Intraperitoneal      150                      Sax & Lewis (1984)

    Table 75. (continued)

                                                                                                           

    Compound           Species     Route of             LD50 (mg/kg) or          Reference
                                   administration       LC50 (mg/litre)
                                                                                                           

                       Mouse       Intraperitoneal      380                      Warren et al. (1982)
                       Mouse (M)   Intraperitoneal      approx. 400              Plopper et al. (1992)
                       Mouse       Intravenous          100                      Sax & Lewis (1984)
                       Hamster (M) Intraperitoneal      approx. 800              Plopper et al. (1992)
                       Guinea-pig  Oral                 1 200                    Sax & Lewis (1984)
    Phenanthrene       Mouse       Oral                 700                      Montizaan et al. (1989)
                       Mouse       Oral                 1 000                    Montizaan et al. (1989)
                       Mouse       Intraperitoneal      700                      Simmon et al. (1979)
                       Mouse       Intravenous          56                       Montizaan et al. (1989)
    Pyrene             Mouse       Intraperitoneal      514 (7 d)                Salamone (1981)
                       Mouse       Intraperitoneal      678 (4 d)                Salamone (1981)
                                                                                                           

    LC50, median lethal concentration; LD50, median lethal dose; M, male; F, female


    7.1.3  Dibenz [a,h]anthracene

    One or two intraperitoneal injections of 3-90 mg
    dibenz [a,h]anthracene per animal within two days led to a reduction
    in the growth rate of young rats that persisted for at least 15 weeks
    (Haddow et al., 1937).

    7.1.4  Fluoranthene

    In young rats, a single intraperitoneal injection of 30 mg
    fluoranthene per animal did not inhibit growth (Haddow et al., 1937).

    7.1.5  Naphthalene

    After oral administration of 1-4 g/kg bw naphthalene to dogs or 1-3
    g/kg bw to cats, diarrhoea was observed. Rabbits given 1-3 g/kg bw
    showed corneal clouding (Flury & Zernik, 1935). After intravenous
    injection of 1-6 mg napthalene to white male rabbits weighing 3-4 kg,
    no haemolytic effect was seen (Mackell et al., 1951)

    In mice, Clara cells of the bronchiolar epithelium are the primary
    targets of low doses of naphthalene. Dose-dependent bronchiolar
    epithelial cell necrosis was detected after intraperitoneal injection
    of a single dose of 50, 100, or 200 mg/kg bw per day to mice (O'Brien
    et al., 1989). Severe bronchiolar epithelial cell necrosis was also
    seen in mice within 2-4 h after intraperitoneal injection of 200-375
    mg/kg bw; hepatic and renal necrosis were not observed (Warren et al.,
    1982). Alterations in the morphology of Clara cells were observed as
    early as 6 h after intraperitoneal injection of 64 mg/kg bw; ciliated
    cells were also affected after 24 and 48 h and at doses up to 256
    mg/kg bw. After a 4-h inhalation of 1.0 mg/litre naphthalene,
    bronchiolar necrosis was detected in mice but not in rats (Buckpitt &
    Franklin, 1989; see also section 7.2.1).

    After single injections of 50-400 mg/kg bw to mice, 100-800 mg/kg bw
    to hamsters, and 200-1600 mg/kg bw to rats, Clara cells in mice showed
    the effects described above; those of rats showed no significant
    effects, and minor effects were observed in hamsters. The trachea and
    lobar bronchi showed swelling and vacuolation of non-ciliated cells in
    mice, no effects in rats, and cytotoxic changes in hamsters. In the
    nasal cavity, cytotoxicity to the olfactory epithelium with necrosis
    was observed in mice and hamsters at 400 mg/kg bw and in rats at 200
    mg/kg bw (Plopper et al., 1992).

    Mice injected intraperitoneally with 200-600 mg/kg bw naphthalene
    showed dose-dependent abnormalities in the bronchial region (Clara
    cells) in studies in which the lungs were examined by scanning
    electron micrography. No pulmonary damage was detected at 100 mg/kg
    bw. Depletion of pulmonary glutathione, which protects against the
    toxicity of xenobiotics, was observed within 6 h of naphthalene
    administration (Honda et al., 1990).

    The doses and detailed findings of experiments with single doses of
    naphthalene are summarized in Table 76.

    7.1.6  Phenanthrene

    After acute intraperitoneal injection to rats (dose not specified),
    liver congestion with a distinct lobular pattern was observed as well
    as alterations in some serum parameters (Yoshikawa et al., 1987).

    7.1.7  Pyrene

    In young rats, single intraperitoneal injections of 10 mg pyrene per
    animal did not lead to a reduction in growth rate (Haddow et al.,
    1937).

    7.2  Short-term toxicity

    7.2.1  Subacute toxicity

    7.2.1.1  Acenaphthene

    Four of five mice given 500 mg/kg bw per day acenaphthene
    intraperitoneally for seven days survived (Gerarde, 1960).

    7.2.1.2  Acenaphthylene

    Nine of 10 mice given 500 mg/kg bw per day acenaphthylene for seven
    days survived (Gerarde, 1960).

    7.2.1.3  Anthracene

    Nine of 10 mice given 500 mg/kg bw per day anthracene for seven days
    survived (Gerarde, 1960). Oral administration of 100 mg/kg bw per day
    to rats for four days increased carboxylesterase activity in the
    intestinal mucosa by 13% (Nousiainen et al., 1984).

    7.2.1.4  Benzo [a]pyrene

    Death due to myelotoxicity was observed after daily oral
    administration of benzo [a]pyrene at 120 mg/kg bw to poor-affinity Ah
    receptor DBA/2N mice for one to four weeks, whereas high-affinity C57
    Bl/6N mice survived with no myelotoxicity for at least six months
    under these conditions (Legraverend et al., 1983).

    Rats given 50 or 150 mg/kg bw per day of benzo [a]pyrene orally for
    four days showed suppressed carboxylesterase activity in the
    intestinal mucosa. The NOAEL with respect to gastric, hepatic, and
    renal effects was 150 mg/kg bw per day (Nousiainen et al., 1984)


        Table 76. Toxicity of single doses of naphthalene

                                                                                                                                          

    Species             Sex           Route of           Dose (purity)      Effects                                      Reference
    (strain)            (no./sex      administration
                        per group)
                                                                                                                                          

    Dog                               Oral               1000-2000,4000     1000-2000: Light diarrhoea; 4000 mg:         Flury & Zernick
                                                         or 5000 mg/dog     lethal; 5000 my heavy diarrhoea              (1935)

    Cat                               Oral               1000-3000          Lethal                                       Flury & Zernick
                                                         mg/kg bw                                                        (1935)

    Rabbit                            Oral               1000-3000 and      1000-3000 mg: corneal clouding;              Flury & Zernick
                                                         3000 mg/kg bw      3000 mg death after 24 h                     (1935)

    Dog                 (1)           Oral               400 and 1800       400 mg: weakness, severe anaemia;            Zuelzer & Apt
                                                         mg/kg bw           1800 mg: weakness, vomiting, diarrhoea,      (1949)
                                                                            slight anaemia; complete recovery within
                                                                            1-2 weeks

    Mouse                             Inhalation         0.1 mg/litre, 4 h  Bronchiolar necrosis                         Buckpitt & Franklin
                                                                                                                         (1989)

    Mouse               M             Intraperitoneal    50,100,200,        Dose-dependent bronchiolar epithelial-cell   O'Brien et al.
    (Swiss-Webster                                       300 mg/kg bw       necrosis                                     (1989)


    Mouse               M (4-35)      Intraperitoneal    50,100,200,        Dose-dependent bronchiolar necrosis;         Plopper et al.
    (Swiss-Webster)                                      300, and 400       300 mg/kg: swollen cells in trachea          (1992)
                                                         mg/kg bw           400 mg/kg: cytotoxicity in olfactory
                                                         (> 99.9%)          epithelium

    Rat                 M (4-11)      Intraperitoneal    200,400,800,       Bronchiolar necrosis not observed; no        Plopper et al.
    (Sprague-Dawley)                                     and 1600 mg/kg     changes in trachea; 200 mg/kg: complete      (1992)
                                                         bw (> 99.9%)       necrosis of olfactory epithelium

    Table 76 (continued)

                                                                                                                                          

    Species             Sex           Route of           Dose (purity)      Effects                                      Reference
    (strain)            (no./sex      administration
                        per group)
                                                                                                                                          

    Rat                 M             Intraperitoneal    400-1600 mg/kg     No damage to lungs, liver, or kidneys        O'Brien et al.
    (Wistar)                                             bw                                                              (1985)

    Hamster             M (4-6)       Intraperitoneal    100,200,400        800 mg/kg: minor alterations in terminal     Plopper et al.
    (Syrian                                              and 800 mg/kg      bronchioles; cytotoxic changes in trachea;   (1992)
    golden)                                              bw (99.9%)         400 mg/kg: necrosis of olfactory epithelium

    Rabbit              M             Intraperitoneal    0.3-1.7 mg/kg bw   No haemolytic effects                        Mackell et al.
    (white)                                                                                                              (1951)
                                                                                                                                          

    M, male


    In Fischer 344/Crl rats exposed by inhalation to 7.7 mg/m3 of
    benzo [a]pyrene dust for 2 h/day, five days per week for four weeks,
    no respiratory tract lesions were observed, as measured by lung
    lavage, clearance of tagged particles, and histopathological findings
    (Wolff, R.K. et al., 1989).

    7.2.1.5  Benz [a]anthracene

    When benz [a]anthracene was given orally to rats daily for four days,
    the NOAEL with respect to gastric, hepatic, and renal effects was 150
    mg/kg bw per day. Carboxylesterase activity in the intestinal mucosa
    was suppressed (Nousiainen et al., 1984).

    7.2.1.6  Dibenz [a,h]anthracene

    Adverse haemolymphatic changes, including the appearance of
    extravascular erythrocytes in the lymph spaces and large pigmented
    cells, were reported after subcutaneous injection of male rats with
    0.28 mg per animal on five days per week for four weeks (Lasnitzki &
    Woodhouse, 1944).

    7.2.1.7  Fluoranthene

    All of 10 mice that received 500 mg/kg bw per day fluoranthene
    intraperitoneally for seven days survived (Gerarde, 1960).

    7.2.1.8  Naphthalene

    Anaemia was induced in three dogs by single oral doses of 3 or 9 g or
    a total dose of 10.5 g per animal given over seven days. All three
    animals showed neurophysiological symptoms and slight to very severe
    changes in haematological parameters. Full recovery was observed
    within 7-14 days (Zuelzer & Apt, 1949).

    No immunosuppressive effects were observed in a number of test
    systems. Tolerance to the effects of naphthalene was reported in mice
    after intraperitoneal injection for seven days. A sharp contrast
    between single and multiple doses was observed in the effects on the
    morphology of the bronchiolar epithelium. When naphthalene was given
    intraperitoneally at a dose of 50, 100, or 200 mg/kg bw per day as a
    single injection, dose-dependent bronchiolar epithelial cell necrosis
    was detected; however, when these doses were given daily for seven
    days, no significant effects were observed. Addition of 300 mg/kg bw
    on day 8 had no effect, whereas recovered sensitivity was observed
    with increasing time between the last dose and the challenge dose. A
    single dose of 300 mg/kg bw without pretreatment resulted in
    substantial denudation of the bronchiolar epithelium. This pattern was
    attributed to a reduction in metabolic activation of naphthalene due
    to a decrease in cytochrome P450 mono-oxygenase activity after
    multiple dosing. A rough correlation was observed in mouse lung (but
    not liver microsomes) between induction of tolerance and decreased
    metabolic formation of the 1 R, 2 S-epoxide enantiomer, which is

    responsible for tissue-selective toxicity. Such toxicity was
    demonstrated in mice both  in vivo and in isolated perfused lung
    (Buckpitt & Franklin, 1989).

    These studies are summarized in Table 77.

    7.2.1.9  Phenanthrene

    Oral administration of 100 mg/kg bw per day phenanthrene to rats for
    four days induced a 30% increase in carboxylesterase activity in the
    intestinal mucosa (Nousiainen et al., 1984).

    7.2.1.10  Pyrene

    Four of five mice injected intraperitoneally with 500 mg/kg bw per day
    pyrene for seven days survived (Gerarde, 1960).

    7.2.2  Subchronic toxicity

    7.2.2.1  Acenaphthene

    Administration of 175 mg/kg bw per day acenaphthene to mice by gavage
    for 90 days resulted in a NOAEL of 175 mg/kg bw per day and a LOAEL of
    350 mg/kg bw per day for hepatotoxicity (US Environmental Protection
    Agency, 1989a).

    7.2.2.2  Anthracene

    Four of five rats given 5 mg per animal anthracene subcutaneously for
    four months survived (Gerarde, 1960).

    Anthracene was administered to groups of 20 male and female CD-1 (ICR)
    BR mice by gavage at a dose of 0, 250, 500, or 1000 mg/kg bw per day
    for at least 90 days. No treatment-related effects were noted on
    mortality, clinical signs, body weights, food consumption,
    ophthalmological findings, the results of haematology and clinical
    chemistry, organ weights, organ-to-body weight ratios, and gross
    pathological and histopathological findings. The no-observed-effect
    level (NOEL) was the highest dose tested, 1000 mg/kg bw per day (US
    Environmental Protection Agency, 1989b).

    7.2.2.3  Benzo [a]pyrene

    Male Syrian golden hamsters were exposed by inhalation to 9.8 or
    44.8 mg/m3 benzo [a]pyrene for 4.5 h/day, five days per week for 16
    weeks. No neoplastic response was observed in the respiratory tract
    (Thyssen et al., 1980).

    The growth of rats was inhibited by feeding a diet enriched with
    benzo [a]pyrene at 1.1 g/kg for more than 100 days (White & White,
    1939).


        Table 77. Subacute and subchronic effects of naphthalene

                                                                                                                                              

    Species            Sex         Route of          Dose (purity)       Effects                                           Reference
    (strain)           (no./sex    administration
                       per group)
                                                                                                                                              

    Mouse              M,F         Oral              27, 53, and 267     In all groups, slight alterations in haemato      Shopp et al.
    (CD-1)             (40-112)                      mg/kg bw, 7 d/      logical parameters; humoral immune response       (1984)
                                                     week, 14 d          not affected. 27 and 53 mg/kg: no significant
                                                                         effects; 267 mg/kg: 5-10% mortality (m/f);
                                                                         significantly decreased terminal body weight
                                                                         (m/f); 30% decrease in thymus weight (m);
                                                                         significant decrease in weight of spleen (f);
                                                                         increase in lung weight (f)

    Mouse              M,F         Oral              5.3, 53, and 133    No obvious pulmonary effects or                   Shopp et al.
    (CDO)                                            mg/kg bw, 7 d/      immunotoxicity; significantly decreased           (1984)
                                                     week, 90 d          relative spleen weights (f); tolerance

    Mouse              M           Intraperitoneal   50, 100, and 200    No significant alterations in lung morphology;    Buckpitt & Franklin
    (Swiss-Webster)                                  mg/kg, 7 d          tolerance to 300 mg/kg on day 8                   (1989); O'Brien et
                                                                                                                           al. (1989)

    Rat                            Diet              2 g/kg diet,        Inhibition of growth; enlarged, fatty livers      White & White
                                                     100 d                                                                 (1939)

    Dog                (1)         Oral              122 g/kg bw per     Diarrhoea, weakness, lack of appetite, ataxia,    Zuelzer & Apt
                                                     day, 7 d            very severe anaemia; complete recovery            (1949)
                                                                         within 1-2 weeks
                                                                                                                                              

    M, male; F, female


    7.2.2.4  Fluorene

    Groups of 25 male and 25 female CD-1 mice were given 0, 125, 250, or
    500 mg/kg bw per day fluorene suspended in corn oil by gavage for 13
    weeks. Increased salivation, hypoactivity, and abdomens wetted with
    urine were observed in all treated males. The percentage of hypoactive
    mice was dose-related. In mice exposed at 500 mg/kg bw per day,
    laboured respiration, ptosis (drooping eyelids), and an unkempt
    appearance were also observed. A significant decrease in erythrocyte
    count and packed cell volume were observed in females treated with 250
    mg/kg bw per day fluorene and in males and females treated with 500
    mg/kg bw per day. The latter also showed a decreased haemoglobin
    concentration and an increased total serum bilirubin level. A
    dose-related increase in relative liver weight was observed in treated
    mice, and a significant increase in absolute liver weight was observed
    in the mice treated with 250 or 500 mg/kg bw per day. Significant
    increases in absolute and relative spleen and kidney weights were
    observed in males and females exposed to 500 mg/kg bw per day and in
    males at 250 mg/kg bw per day. The increases in absolute and relative
    liver and spleen weights in animals at the high dose were accompanied
    by increases in the amounts of haemosiderin in the spleen and in
    Kupffer cells of the liver. No other histopathological lesions were
    observed. The LOAEL for haematological effects was 250 mg/kg bw per
    day, and the NOAEL was 125 mg/kg bw per day (US Environmental
    Protection Agency, 1989c).

    In a similar study, fluorene at 35, 50, and 150 mg/kg bw increased the
    weight of the liver by about 20% in a dose-dependent fashion and the
    mitotic index of hepatocytes by sixfold after 48 h (Danz et al.,
    1991).

    7.2.2.5  Fluoranthene

    Groups of 20 male and 20 female CD-1 mice were given 0, 125, 250, or
    500 mg/kg bw per day fluoranthene by gavage for 13 weeks. A fifth
    group of 30 male and 30 female mice was used to establish baseline
    levels in blood. Body weight, food consumption, and haematological and
    serum parameters were recorded regularly throughout the experiment. At
    the end of 13 weeks, the animals were killed and autopsied; organs
    were weighed and a histological evaluation was made. All treated mice
    had dose-dependent nephropathy, increased salivation, and increased
    liver enzyme activities, but these effects were either not
    significant, not dose-related, or not considered adverse at 125 mg/kg
    bw per day. Mice exposed to 500 mg/kg bw per day had increased food
    consumption and increased body weight. Mice exposed to the two higher
    doses had statistically increased alanine aminotransferase activity
    and increased absolute and relative liver weights. Treatment-related
    microscopic liver lesions (indicated by pigmentation) were observed in
    65% of mice at 250 mg/kg bw per day and 88% of those at the highest
    dose. On the basis of the increased alanine aminotransferase activity,
    pathological effects in the kidney and liver, and clinical and
    haematological changes, the LOAEL was 250 mg/kg bw per day and the
    NOAEL 125 mg/kg bw per day (US Environmental Protection Agency, 1988).

    7.2.2.6  Naphthalene

    In a 90-day study in mice, naphthalene at oral doses up to 133 mg/kg
    bw caused neither mortality nor serious changes in organ weights
    (Shopp et al., 1984). These authors did not observe haemolytic anaemia
    in CD-1 mice after oral uptake, although this effect had been seen in
    human patients (Konar et al., 1939; Zuelzer & Apt, 1949; see Section
    8). It was suggested that glucose-6-phosphate dehydrogenase deficiency
    in erythrocytes, a prerequisite of haemolytic anaemia in adult humans,
    was not present in the mice (Shopp et al., 1984).

    In rats that ingested 150 mg/kg bw per day naphthalene for the first
    three weeks and 200-220 mg/kg bw per day for a further 11 weeks,
    reduced weight gain and food intake were observed. Later, the liver
    was found to be enlarged, with cell oedema and congestion of the liver
    parenchyma, and the kidneys showed signs of inflammation (Kawai,
    1979).

    The presence of 1 g/kg naphthalene in the feed of rats and rabbits for
    46-60 days led to cataracts (US Environmental Protection Agency,
    1984b; see also section 7.8).

    Administration to rabbits of 0.1-1 mg/kg bw per day naphthalene by
    subcutaneous injection for 123 days resulted in severe oedema and a
    high degree of vacuolar and collicular degeneration in the brain;
    necrosis of nerve cells also occurred. The author suggested that
    hypoxaemia resulting from haemolytic anaemia was responsible for this
    finding (Suja, 1967; cited by Kawai, 1979).

    Subacute and subchronic studies with naphthalene are summarized in
    Table 77.

    7.2.2.7  Pyrene

    The growth of rats was inhibited by feeding a diet enriched with
    benzo [a]pyrene at 2 g/kg for more than 100 days. The livers were
    enlarged and had a fatty appearance indicating hepatic injury (White &
    White, 1939).

    Groups of 20 male and 20 female CD-1 mice were given 0, 75, 125, or
    250 mg/kg bw per day pyrene in corn oil by gavage for 13 weeks and
    then examined for changes in body weight, food consumption, mortality,
    clinical pathological manifestations in major organs and tissues, and
    changes in haematology and serum chemistry. Nephropathy, characterized
    by the presence of multiple foci of renal tubular regeneration, often
    accompanied by interstitial lymphocytic infiltrates and/or foci of
    interstitial fibrosis, was present in four male control mice, one at
    the low dose, one at the medium dose, and nine the high dose. Similar
    lesions were seen in two, three, seven, and 10 female mice,
    respectively. The renal lesions in all groups were described as
    minimal or mild. Relative and absolute kidney weights were reduced in
    mice at the two higher doses. On the basis of nephropathy and

    decreased kidney weights, the low dose (75 mg/kg bw per day) was
    considered to be the NOAEL and 125 mg/kg bw per day the LOAEL (US
    Environmental Protection Agency, 1989d).

    7.3  Long-term toxicity

    Almost all of the long-term studies reported were designed to assess
    the carcinogenic potency of PAH and are therefore summarized in
    section 7.7. Information about the non-carcinogenic effects, such as
    growth inhibition, liver damage, and irritation, which occurred at
    concentrations that also caused carcinogenic effects is presented
    here. General effects, such as on mortality, body weight, and
    pathological findings at sacrifice, were not considered useful.

    7.3.1  Anthracene

    A group of 28 BD I and BD III rats received anthracene in the diet
    from the age of about 100 days, at a daily dose of 5-15 mg per rat.
    The experiment was terminated when a total dose of 4.5 g per rat had
    been achieved, on day 550. The rats were observed until they died;
    some lived for more than 1000 days. No treatment-related effects on
    lifespan or on gross or histological appearance of tissues were
    observed; haematological parameters were not measured (Schmähl, 1955).

    After weekly subcutaneous injections of anthracene at 0.25 mg per
    animal for 40 weeks, mice showed deposition of iron in lymph glands
    and a reduced number of lymphoid cells (Hoch-Ligeti, 1941).

    7.3.2  Benz [a]anthracene

    Weekly subcutaneous injection of 0.25 mg per mouse for 40 weeks
    resulted in deposition of iron in lymph glands and a reduced number of
    lymphoid cells (Hoch-Ligeti, 1941).

    7.3.3  Dibenz [a,h]anthracene

    Mice given weekly subcutaneous injections of 0.25 mg per animal for
    40 weeks had pale, soft, enlarged livers with signs of fatty
    degeneration. There was deposition of iron in lymph glands, and the
    number of lymphoid cells was reduced (Hoch-Ligeti, 1941).

    7.4  Dermal and ocular irritation and dermal sensitization

    The adverse dermatological effects observed in animals after acute and
    subchronic dermal exposure to PAH included destruction of sebaceous
    glands, dermal ulceration, hyperplasia, hyperkeratosis, and
    alterations in epidermal cell growth. Perylene, benzo [e]pyrene,
    phenanthrene, pyrene, anthracene, naphthalene, acenaphthalene,
    fluorene, and fluoranthene did not suppress the sebaceous gland index;
    benz [a]anthracene, dibenz [a,h]anthracene, and benzo [a]pyrene
    resulted in indices > 1 (Bock & Mund, 1958). In Swiss mice treated
    daily for three days with solutions of benzo [a]pyrene in acetone, a
    concentration of 0.1% destroyed less than half of the sebaceous
    glands, whereas 0.2% destroyed more than 50% (Suntzeff et al., 1955).

    7.4.1  Anthracene

    Anthracene is a primary irritant, and its fumes can cause mild
    irritation of the skin, eyes, mucous membranes, and respiratory tract.
    At a concentration of 4.7 mg/m3, mild skin irritation was found in
    50% of exposed mice (Montizaan et al., 1989). The median value for
    dermal irritant activity (ID50) in the mouse ear was 6.6 × 10-4
    mmol or 118 µg/ear; in comparison, the ID50 for benzo [a]pyrene was
    5.6 × 10-5 mmol per ear (Brune et al., 1978). Anthracene increases
    the sensitivity of skin to solar radiation (Gerarde, 1960). No contact
    sensitivity to anthracene was observed (Old et al., 1963).

    7.4.2  Benzo [a]pyrene

    Four adult female guinea-pigs were injected with a total of 250 µg
    benzo [a]pyrene in Freund's adjuvant, and two to three weeks later
    were tested for contact sensitivity with solutions of 0.001, 0.01,
    0.1, or 1% benzo [a]pyrene in acetone and olive oil. After 24 h, a
    slight to severe (0.001-1%) contact hypersensitivity was observed (Old
    et al., 1963).

    C3H mice were given an epicutaneous administration of 100 µg
    benzo [a]pyrene in 0.1% acetone solution into the abdominal skin.
    Five days later, contact hypersensitivity was elicited by applying 20
    µg benzo [a]pyrene to the dorsal aspect of the ear. The response was
    quantified by ear thickness, which reaced a maximum three to five days
    after challenge. The LOAEL for allergic contact sensitivity was thus
    120 µg (Klemme et al., 1987).

    The ID50 value for dermal irritant activity in the mouse ear was 5.6
    × 10-5 mmol per ear (Brune et al., 1978).

    7.4.3  Naphthalene

    A single dose of 100 mg naphthalene to the rabbit eye was slightly
    irritating, whereas application of 495 mg to rabbit skin, without
    occlusion, caused mild irritation (Sax & Lewis, 1984).

    7.4.4  Phenanthrene

    No contact sensitization to phenanthrene was observed (Old et al.,
    1963).

    7.5  Reproductive effects, embryotoxicity, and teratogenicity

    The mechanistic aspects of reproductive and embryotoxic effects are
    presented in detail and the results summarized in Tables 78-80. The
    genotype of mice is decisive for the manifestation of effects.

    Studies have been reported on anthracene, benz [a]anthracene,
    benzo [a]-pyrene, chrysene, dibenz [a,h]anthracene, and naphthalene.
    Embryotoxicity was reported in response to benz [a]anthracene,
    benzo [a]pyrene, dibenz [a,h]-anthracene, and naphthalene.

    Benzo [a]pyrene also had adverse effects on female fertility,
    reproduction, and postnatal development. In a study in young mice, an
    NOEL of 150 mg/kg bw per day was obtained for benzo [a]pyrene on the
    basis of effects on fertility (sperm in lumen of testes, size of
    litters) and embryotoxicity (malformations) (Rigdon & Neal, 1965).

    7.5.1  Benzo [a]pyrene

    7.5.1.1  Teratogenicity in mice of different genotypes

    Benzo [a]pyrene is embryotoxic to mice, and the effect is partly
    dependent on the genetically determined induction of the cytochrome
    P450 mono-oxygenase receptor, Ah, of the mother and fetus by PAH (see
    also section 7.10). In the case of an inducible mother
     (Ahb/ Ahb and  Ahb/ Ahd, B groups), the genotype of the
    fetus is not crucial because the active metabolites formed in the
    mother appear to cross the placenta, causing fetal death or
    malformation. In contrast, when the mother is non-inducible
     (Ahd/ Ahd, D group), the genotype of the fetus is important;
    one litter may contain both inducible and non-inducible fetuses.
    Another decisive factor is the route by which benzo [a]pyrene is
    given to the mother. Three studies of the genetic expression of
    effects are summarized below.

    Intraperitoneal injection of benzo [a]pyrene at 50 or 300 mg/kg bw on
    day 7 or 10 of gestation was more toxic and teratogenic  in utero in
    genetically inducible C57Bl/6  (Ahb/ Ahb) than in non-inducible
    AKR inbred mice  (Ahd/ Ahd). In AKR × (C57Bl/6)(AKR)F1 and
    (C57Bl/6)(AKR)F1 × AKR back-crosses (father × F1 mother), allelic
    differences at the  Ah locus in the fetus correlated with
    dysmorphogenesis. The inducible fetal  Ahb/ Ahd genotype results
    in more stillborn and resorbed fetuses,decreased fetal weight,
    increased frequency of congenital anomalies, and enhanced
    P1-450-mediated covalent binding of benzo [a]pyrene metabolites to
    fetal protein and DNA, when compared with fetuses of the non-inducible
     Ahd/ Ahd genotype (not-inducible) from the same uterus (see
    Table 78). In the case of an inducible mother  (Ahb/ Ahd),
    however, these parameters do not differ in  Ahb/ Ahd and
     Ahd/ Ahd individuals in the same uterus, presumably because the
    increased benzo [a]pyrene metabolism in maternal tissues and placenta
    cancels them out (Shum et al., 1979).

    An inducible genotype is not the only factor involved in the
    reproductive toxicity of benzo [a]pyrene. In a study in which C57Bl/6
    female mice  (Ah inducible) were mated with C57Bl/6, DBA/2, or BDF1
    male mice (B groups), and DBA/2 females (non-inducible) were mated
    with C57Bl/6, DBA/2, or BDF1 males (D groups) and received
    intraperitoneal injections of benzo [a]-pyrene, fetal mortality
    increased dose-dependently in all groups except the DBA/2 × DBA/2.
    Fetal body weight was reduced dose-dependently in all experimental
    groups, but the effect was more pronounced in D than B groups, as was
    a dose-dependent increase in the frequency of cervical ribs (for
    experimental details, see Table 78). These results suggest that


        Table 78. Embryotoxicity of polycyclic aromatic hydrocarbons in experimental animals

                                                                                                                                             

    Species            No. per   Route of          Duration, dose          Effects                                            Reference
                       (strain)  group             administration
                                                                                                                                             

    Anthracene
    Rat                          Gavage            Day 19 of gestation,    F1: no induction of BaP hydroxylase in liver       Welch et al.
    Sprague-                     60 mg/kg                                  compared with control (< 0.2 vs <0.2 units in      (1972)
                                 bw                                        controls)

    Benz[a]anthracene
    Rat                2         Subcutaneous      Day 1-11 or 1-15        F0: Day 10 and 12: severe vaginal haemorrhage;     Wolfe &
                                                   of gestation, 5 mg/     Day 14: intraplacental haemorrhage                 Bryan (1939)
                                                   animal per day          F1: fetal death and resorption up to day 18

    Rat                          Gavage            Day 19 of gestation,    F1: induction of BaP hydroxylase in liver          Welch et al.
    Sprague-Dawley                                 60 mg/kg bw             (12 vs < 0.2 units in controls)                    (1972)

    Benzo[a]pyrene
    Mouse              9         Diet              Day 5 or 10 of          F1: no malformations                               Rigdon &
    White                                          gestation until                                                            Neal (1965)
    Swiss                                          delivery, 50 mg/ky bw

    Mouse              6-17      Diet              Day 2-10 of             F1: increased intrauterine toxicity and            Legraverend
    C57BI/6N,                                      gestation, 120 mg/      malformations in Ahd/Ah7dembryos compared          et al. (1984)
    AKR/J, and                                     kg per day              with Ahb/Ahd embryos in pregnant Ahd/Ahd
    back-crosses                                                           mice (effect not seen in pregnant Ahb/Ahd mice)
    (reciprocal)

    Mouse              5-30      Intraperitoneal   Day 7, 10, or 12 of     200 mg/kg bw: F1: increase in stillbirths,         Shum et al.
    C57BI/6,                                       gestation, 50-300       resorptions, malformations (4-fold higher          (1979)
    AKR and                                        mg/kg bw                in pregnant C57BI than in AKR mice)
    back-crosses
    (reciprocal)

    Table 78. (continued)

                                                                                                                                             

    Species            No. per   Route of          Duration, dose          Effects                                            Reference
                       (strain)  group             administration
                                                                                                                                             

    Mouse              20        Intraperitoneal   Day 8 of gestation,     150 and 300 mg/kg bw: F0: increased fetal          Hoshino et al.
    C57BI/6,                                       150 or 300 mg/kg        mortality (except DBA/2 × DBA/2 offspring);        (1981)
    DBA/2, and                                                             reduced fetal body weight; increased number of
    back-crosses                                                           cervical ribs
    (reciprocal)                                                           300 mg/kg: F1: increased malformations
                                                                           (C57BI/6 × C57BI/6)

    Mouse                        Gavage            Day 7-16 of             F0: no toxicity                                    MacKenzie &
    CIT1                                           gestation, 10, 40, 160  F1: no toxicity                                    Angevine (1981)
                                                   mg/kg bw per day

    Rat                17        Subcutaneous      Day 1-11 or 16 of       F0: Days 10 and 12: profuse vaginal                Wolfe & Bryan
                                                   gestation, 5 mg/        haemorrhage; day 14: intraplacental                (1939)
                                                   animal per day          haemorrhage; F1: fetal death and resorption
                                                                           up to day 18

    Rat                          Gavage            Day 19 of gestation,    F1: induction of BaP-hydroxylase in liver          Welch al al.
    Sprague-Dawley                                 60 mg/kg bw             (20 vs < 0.2 units in controls)                    (1972)

    Rat                10-15     Subcutaneous      Day 6-8 or 6-11 of      F1: significant increase in number of resorptions  Bui et al.
    Sprague-Dawley                                 gestation, 50 mg/kg     and fetal wastage (dead fetuses plus resorption);  (1986)
                                                   bw per day              fetal weight reduced

    Chrysene
    Rat                          Gavage            Day 19 of gestation,    F1: induction of BaP hydroxylase in liver          Welch et al.
    Sprague-Dawley               60 mg/kg bw                               (6 vs < 0.2 units in controls)                     (1972)

    Dibenzo[a,h]anthracene
    Rat                          Gavage            Day 19 of gestation,    F1: induction of BaP hydroxylase in liver          Welch et al.
    Sprague-Dawley                                 60 mg/kg bw             (15 vs < 0.2 units in controls)                    (1972)

    Table 78. (continued)

                                                                                                                                             

    Species            No. per   Route of          Duration, dose          Effects                                            Reference
                       (strain)  group             administration
                                                                                                                                             

    Rat                38        Subcutaneous      Day 1-8 or 1-18 of      F0: Days 10 and 12: profuse vaginal haemorrhage;   Wolfe &
                                                   gestation, 5 mg/        day 14: intraplacental haemorrhage                 Bryan (1939)
                                                   animal per day          F1: fetal death and resorption up to day 18

    Naphthalene
    Mouse              50        Gavage            Day 7-14 of             F0: significant 15% increase in mortality;         Plasterer et
    CD-1                                           gestation, 300 mg/      significant reduction in weight gain               al. (1985)
                                                   kg bw per day           F1: significant reduction in number of live
                                                                           offspring; no malformations

    Mouse                        Gavage            Day 6-13 of             F0 increased mortality 10/50; control: 0/50);      Hardin et al.
    CD-1                                           gestation, 300 mg/      significant reduction in weight gain               (1987)
                                                   kg bw per day           F1: significant reduction in liveborns per litter

    Rat                10-15     Intraperitoneal   Day 1-15 of             F0: no toxicity                                    Hardin et al.
    Sprague-Dawley                                 gestation, 395 mg/      F1: no toxicity                                    (1981)
                                                   kg per day
                                                                                                                                             

    For genotypes of the mouse strains used see section 7.5.1.1


     Ah-inducible fetuses are more sensitive to lethal events, whereas
    those of non-inducible dams are more susceptible to a decrease in body
    weight and an increased incidence of cervical ribs. The incidence of
    external malformations may, however, differ in mice of different
    genotypes after treatment with benzo [a]-pyrene, even if both dams
    and fetuses are inducible (Hoshino et al., 1981).

    The toxicity of benzo [a]pyrene  in utero was investigated in
    pregnant  Ahd/ Ahd ×  Ahb/ Ahd F1 and  Ahb/ Ahd ×
     Ahd/ Ahd F1 back-crossed mice fed benzo [a]pyrene in the
    diet at 120 mg/kg daily on days 2-10 of gestation. Embryos of D
    females  (Ahd/ Ahd  genotype; non-inducible) showed more signs
    of toxicity and malforma-tions than  Ahd/ Ahd  embryos. Fetuses
    of B females  (Ahb/ Ahd  genotype) did not show these changes.
    The authors suggested that reduced benzo [a]pyrene metabolism in the
    intestine had caused high concentrations in the embryos, and more
    toxic metabolites (benzo [a]pyrene-1,6- and -3,6-quinones) were
    detected in the  Ahd/ Ahd embryos than in  Ahb/ Ahd
    embryos (Legraverend et al., 1984). These results were in contrast to
    those reported after intraperitoneal injection by Shum et al. (1979)
    and Hoshino et al. (1981). The route of administration can thus affect
    the magnitude of the observed effects (see also section 7.8.2.2).

    7.5.1.2  Reproductive toxicity

    A single intraperitoneal injection of benzo [a]pyrene reduced
    fertility and destroyed primordial oocytes of DBA/2N mice in a
    dose-dependent manner (Mattison et al., 1980; see also Table 79).

    In experiments with B6  (Ah-inducible) and D2 (non-inducible) mice,
    primordial oocytes of B6 mice underwent more rapid destruction after
    treatment with benzo [a]pyrene than those of D2 mice. This effect
    corresponded to a two- to threefold increase in ovarian
    arylhydrocarbon hydroxylase (AHH) activity in B6 mice after treatment.
    This correlation was not found in analogous experiments with D2B6F1
    mice, in which AHH activity was increased by two- to threefold, but
    the oocyte destruction was similar to that observed in D2 mice. This
    demonstrates an inconsistent consequence of strain differences in
    genotype (Mattison & Nightingale, 1980; see also Table 79). The sum of
    activation, detoxification, and repair seems to be decisive for the
    process of oocyte destruction (Figure 8).

    Benzo [a]pyrene and its three metabolites, benzo [a]pyrene
    7,8-oxide, benzo [a]pyrene 7,8-diol, and benzo [a]pyrene diol
    epoxide, were administered by injection at a single dose of 10 µg into
    the right ovary of B6, D2, and D2B6F1 mice. Ovarian volume, weight,
    and follicle numbers were measured after two weeks; various reductions
    were observed in all strains. There was also compesatory hypertrophy
    of the left ovary (Mattison et al., 1989; see also Table 79).

    FIGURE 8


        Table 79. Effects of benzo[a]pyrene on fertility in experimental animals

                                                                                                                                             

    Species          Sex/No.  Route of          Duration, dose                  Effects                               Reference
    (strain)         per      administration
                     group
                                                                                                                                             

    Mouse            M        Diet              Up to 30 days before mating,    NOEL: 150 mg/kg bw per day            Rigdon & Neal (1965)
    White            5                          37.5, 75, or 150 mg/kg bw       Parameters: sperm in lumen
                                                per day                         of testes; number of offspring

    Mouse            F        Diet              20 days before mating           NOEL: 150 mg/kg bw per day            Rigdon & Neal (1965)
    White            5-65                       37.5, 75, or 150 mg/kg bw       Parameter: number of offspring
    Swiss                                       per day

    Mouse            F        Intraperitoneal   Day 14 before mating,           10, 100 mg/kg bw: dose-dependent      Mattison et al. (1980)
    DBA/2N           15                         10, 100, 200, or 500 mg/kg      decrease in number of pups
                                                bw once                         200, 500 mg/kg bw: completely
                                                                                infertile; threshold: 3.4 mg/kg bw;
                                                                                50% effect dose: 25.5 mg/kg bw

    Mouse            F        Intraperitoneal   Day 21 before sacrifice,        Dose-dependent increase in            Mattison et al. (1980)
    DBX2N                                       5, 10, 50, 100, or 500 mg/kg    primordial oocyte destruction;
                                                bw once                         500 mg/kg: 100% destruction;
                                                                                threshold: 2.7 mg/kg bw; 50%
                                                                                effect dose: 24.5 mg/kg bw

    Mouse            F        Intraperitoneal   Day 13 before sacrifice,        100 mg/kg bw: significant increase    Mattison & Nightingale
    B6 and D2        5                          100 mg/kg bw once               in primordial oocyte destruction in   (1980)
                                                                                both genotypes; effects in B6 mice
                                                                                greater than in D2 mice

    Mouse            F        Intra-ovarian     Day 14 before sacrifice,        10 µg: decreased ovarian weight       Mattison et al. (1989)
    C57BI/6N (136),           injection         10 µg/right ovary once          (D2); decreased ovarian volume (D2
    DBA/2N (D2),                                                                and F1); decreased antral follicles
    D2B6F1(F1)                                                                  (F1) decreased number of small
                                                                                follicles (D2 and F1)

    Table 79. (continued)

                                                                                                                                             

    Species          Sex/No.  Route of          Duration, dose                  Effects                               Reference
    (strain)         per      administration
                     group
                                                                                                                                             

    Mouse            F        Intraperitoneal   1, 2, 3, and 4 weeks            500 mg/kg: 35% mortality              Swartz & Mattison,
    C57BI/6N         5                          before sacrifice; 1, 5,         1-500 mg/kg bw: dose- and time-       1985);
                                                10, 50, 100, or 500             dependent decrease in ovarian         Miller et al. (1992)
                                                mg/kg bw                        volume, total volume and number of
                                                                                corpora lutea/ovary (for last
                                                                                parameter, after 1 week threshold
                                                                                was about 1 mg/kq bw and ED50 1.6
                                                                                mg/kg bw);effect transitory in
                                                                                low-dose groups, butnot reversible
                                                                                in two highest by four weeks
                                                                                                                                             

    For genotypes of the mouse strains used see section 7.5.1.1


    7.5.1.3  Effects on postnatal development

    Three studies of the postnatal effects of benzo [a]pyrene on mouse
    offspring, with administration dermally, intraperitoneally, or orally,
    showed adverse effects, including an increased incidence of tumours,
    immunological suppression, and reduced fertility (see also Table 80).

    7.5.1.4  Immunological effects on pregnant rats and mice

    Benzo [a]pyrene given to pregnant rats on day 15 or 19 of gestation
    caused alterations at the thymic glucocorticoid receptors in the
    offspring, suggesting binding to the pre-encoded hormone receptors and
    interference with receptor maturation (Csaba et al., 1991; Csaba &
    Inczefi-Gonda, 1992; see also section 7.8.2.6).

    Strong suppression of immunological parameters was found in the
    progeny of mice that had been treated intraperitoneally with
    benzo [a]pyrene at mid-gestation (Urso & Johnson, 1987; see also
    section 7.8.2.6).

    7.5.2  Naphthalene

    7.5.2.1  Embryotoxicity

    Naphthalene was administered by gavage at 50, 150, or 450 mg/kg bw per
    day to pregnant Sprague-Dawley rats on days 6-15 of gestation, i.e.
    during the main period of organogenesis. The dams showed signs of
    toxicity including lethargy, slow breathing, prone body posture, and
    rooting, and these effects persisted after the end of dosing with the
    high dose. The body-weight gain of treated animals was reduced by 31
    and 53% in the groups at the two higher doses. Naphthalene did not
    induce fetotoxic or teratogenic effects, and the numbers of corpora
    lutea per dam, implantation sites per litter, and live fetuses per
    litter were within the range in controls. The maternal NOAEL was
    < 50 mg/kg bw per day (National Toxicology Program, 1991).

    In a second study, doses of 0, 20, 80, or 120 mg/kg bw per day were
    given to rabbits by gavage during days 6-19 of gestation. There were
    no signs of maternal toxicity, fetotoxicity, or developmental toxicity
    (National Toxicology Program, 1992a).

    7.5.2.2  Toxicity in cultured embryos

    Mice injected intraperitoneally on day 2 of gestation with 14 or 56
    mg/kg bw naphthalene were sacrificed 36 h later, and embryos were
    cultured  in vitro. Maternal doses below the LD50 value inhibited
    the viability and implantation capacity of the embryos, and attachment
    and embryonic growth  in vitro were markedly decreased (Iyer et al.,
    1990).


        Table 80. Effects of benzo[a]pyrene on postnatal development in experimental animals

                                                                                                                                             

    Species       Sex/No.   Route of            Duration, dose              Effects                                              Reference
    (strain)      per       administration
                  group
                                                                                                                                             

    Mouse         F         Dermal              Entire gestation period     F1- F4: sensitization of offspring: increased        Andrianova
    non-inbred                                  1 drop of 0.5% solution,    incidence of papillomas and carcinomas               (1971)
                                                twice per week; F1-F4       in all generations compared with animals
                                                treated with BaP, m         not treated in utero
                                                1x/week, f 2x/week

    Mouse         F         Intraperitoneal     Day 11-13 or 16-18          F1: no difference in birth rate, litter size of      Urso &
    C3H/Anf       25                            of gestation, 100 or        progeny compared to controls; severe suppression     Gengozian
                                                150 mg/kg                   of anti-SRBC PFC response up to 78 weeks of life     (1980)
                                                                            (see also section 7.8.2.6); 11-1 fold increase in
                                                                            tumour incidence (liver, lung, ovaries) after
                                                                            56-78 weeks

    Mouse         F         Gavage              Days 7-16 of                F1: 10 mg/kg markedly impaired fertility (by 20%)    MacKenzie &
    CD-1                                        gestation, 10, 40,          and reduced testis weight (by 40%), 34% sterility    Angevine
                                                160 mg/kg bw per day        of females; 40 and 160 mg/kg: fertility impaired     (1981)
                                                                            by > 900%/100%; testis weight reduced by > 800%;
                                                                            100%/100% sterility of females
                                                                                                                                             

    anti-SRBC PFC, anti-sheep red blood cell antibody (plaque)-forming cells


    In a subsequent study, three-day-old whole mouse embryos were
    collected at the blastocyst stage, cultured in NCTC 109 medium, and
    exposed to naphthalene at 0.16, 0.2, 0.39, or 0.78 mmol/litre for 1 h
    with and without S9. They were then transferred to toxicant-free
    medium, cultured for 72 h, and evaluated microscopically. Naphthalene
    was not directly embryotoxic, but growth and viability were decreased
    in the presence of S9, with 100% embryolethality at doses > 0.2
    mmol/litre; furthermore, hatching and attachment rates were
    significantly decreased. The approximate LC50 in S9-supplemented
    media was 0.18 mmol/litre (Iyer et al., 1991).

    7.6  Mutagenicity and related end-points

    Benzo [a]pyrene has been used extensively as a positive control in a
    variety of short-term tests. It is active in assays for the following
    end-points: bacterial DNA repair, bacteriophage induction, and
    bacterial mutation; mutation in  Drosophila melanogaster; DNA
    binding, DNA repair, sister chromatid exchange, chromosomal
    aberration, point mutation, and transformation in mammalian cells in
    culture; and tests in mammals  in vivo, including DNA binding, sister
    chromatid exchange, chromosomal aberration, sperm abnormalities, and
    somatic mutation at specific loci (Hollstein et al., 1979; De Serres &
    Ashby, 1981). Positive effects were seen in most assays for the
    mutagenicity of benzo [a]pyrene.

    A selection of these studies is summarized in Tables 81-88. All of the
    data available on the other PAH considered in this monograph were
    taken into account. Because of the amount of data, the purities of the
    chemicals tested and details of the assay conditions are omitted from
    the tables, but they do show the results obtained when S9 was used.
    Variations in the S9 metabolic activation component of the assay
    system, e.g. the age, sex, and strain of the rats used as a source of
    liver and any pretreatment with enzyme inducers such as Aroclor,
    3-methylcholanthrene, or phenobarbital, may markedly affect the
    results and may account for apparent discrepancies.

    DNA binding of benzo [a]pyrene was observed in various species. For
    example, adducts were found in cells from hamsters, mice (Arce et al.,
    1987), rats (Moore et al., 1982), and chickens (Liotti et al., 1988),
    in calf thymus DNA (Cavalieri et al., 1988a), and in human cell
    systems (Moore et al., 1982; Harris et al., 1984). Formation of DNA
    adducts was inhibited in the presence of scavengers of active oxygen
    species like superoxide dismutase, catalase, and citrate-chelated
    ferric iron, indicating that reactive oxygen species such as
    superoxide, OH radicals, and singlet oxygen may be involved in DNA
    binding (Bryla & Weyand, 1991). Benzo [a]pyrene at a total dose of 10
    mg/kg bw induced gene mutations in mice, as seen in the coat-colour
    spot test (Davidson & Dawson, 1976).

    The results of tests for reverse mutation in  Salmonella 
     typhimurimum (Ames test) and for forward mutation in
     S. typhimurimum strain TM677 are presented in Table 81. Bacterial
    tests for DNA damage  in vitro are shown in Table 82. The results of

    tests for mutagenicity in yeasts and  Drosophila melanogaster, 
    including host-mediated assays, are shown in Table 83. The results of
    various assays carried out on mammalian cells  in vitro are
    summarized in Tables 82-86. The results of tests  in vivo are shown
    in Tables 87 and 88.

    The activity of PAH in short-term tests is summarized in Table 89,
    which gives the evaluations of IARC (1983; see also Section 12) and
    the results of studies reported after 1983. Only three of the 33 PAH
    considered, i.e. anthracene, fluorene, and naphthalene were inactive
    in all short-term tests; 16 had mutagenic effects. Eight PAH showed a
    tendency for mutagenic activity, but the data are still too sparse to
    permit a final judgement. The available information on acenaphthene,
    acenaphthylene, benzo [a]fluorene, and coronene is still inadequate.
    As phenanthrene and pyrene showed inconsistent results in various
    experiments, they could not be clearly classified as mutagenic.

    7.7  Carcinogenicity

    Most of the studies that have been conducted on PAH were designed to
    assess their carcinogenicity. Studies on various environmentally
    relevant matrices such as coal combustion effluents, vehicle exhaust,
    used motor lubricating oil, and sidestream tobacco smoke showed that
    PAH are the agents predominantly responsible for their carcinogenic
    potential (Grimmer et al., 1991b). Because of the abundance of
    literature, only studies involving the administration of single PAH
    have been taken into account in this monograph.

    Benzo [a]pyrene has been tested in a range of species, including
    frogs, toads, newts, trout, pigeons, rats, guinea-pigs, rabbits,
    ferrets, ground squirrels, tree shrews, marmots, marmosets, and rhesus
    monkeys. Tumours have been observed in all experiments with small
    animals, and the failure to induce neoplastic responses in large
    animals has been attributed to lack of information on the appropriate
    route or dose and the inability to observe the animals for a
    sufficient time (Osborne & Crosby, 1987a). In studies with other PAH,
    benzo [a]pyrene was often used as a positive control and therefore
    administered at only one concentration. Benzo [a]pyrene has been
    shown to be carcinogenic when given by a variety of routes, including
    diet, gavage, inhalation, intratracheal instillation, intraperitoneal,
    intravenous, subcutaneous, and intrapulmonary injection, dermal
    application, and transplacental administration.

    Assessment of the carcinogenic potency of the selected PAH is
    restricted for various reasons: Many of the studies performed before
    about 1970 were carried out without controls, without clearly defined,
    purified test substances, or using experimental designs and facilities
    considered today to be inadequate. Despite these shortcomings, all of
    the available studies were taken into account, except for those on
    dibenz [a,h]anthracene and benzo [a]pyrene. An overview of the
    results, as reported by the authors, is given in Table 90. To
    facilitate appraisal of the studies, the penultimate column gives a
    classification of the substances as positive, negative, or

    questionably carcinogenic; indicates whether the tumour incidence was
    evaluated statistically; and judges that a study is valid or provides
    reasons suggesting that it is unreliable. The criteria used to
    classify a study as valid were (i) an appropriate study protocol, i.e.
    use of concurrent controls (sham or vehicle), 20 or more animals per
    group, and study duration at least six months; and (ii) sufficient
    documentation, including detailed description of administration,
    results, and the survival of animals. As the use of concurrent
    controls is important for making judgements, data for these are given
    with the results for treated groups. If control data are not
    mentioned, it is because they were not given in the original paper.

    In experiments by topical application, the lower, more volatile PAH
    partially evaporate, and therefore their doses may have varied. The
    substances may also decompose. Both features could lead to
    underestimations of carcinogenic potency if they are not taken into
    account.

    Table 91 shows the classification of the compounds as carcinogenic,
    noncarcinogenic, or questionably carcinogenic. In order to make these
    classifications, all of the studies were summarized according to
    species and route of administration. In cases of doubt, the judgement
    was based on valid studies only. For example, despite one positive but
    invalid result and two questionable (one valid, one invalid) results
    from 17 studies, anthracene was classified as negative; however,
    pyrene, for which one positive, valid result and three questionable,
    valid results were found in 15 studies, could not be classified as
    negative and the compromise 'questionable' was chosen.

    The PAH found not to be carcinogenic were anthracene,
    benzo [ghi]perylene, fluorene, benzo [ghi]fluoranthene,
    1-methylphenanthrene, perylene, and triphenylene. Questionable results
    were obtained for acenaphthene, benzo [a]-fluorene,
    benzo [b]fluorene, coronene, naphthalene, phenanthrene, and pyrene.
    The remaining compounds were found to be carcinogenic.

    The dermal route was the commonest mode of administration, followed by
    subcutaneous and intramuscular injection. In most studies, the site of
    tumour development is related closely to the route of administration,
    i.e. dermal application induces skin tumours, inhalation and
    intratracheal instillation result in lung tumours, subcutaneous
    injection results in sarcomas, and oral administration induces gastric
    tumours. Tumour induction is, however, not restricted to the obvious
    sites. For example, lung tumours have been observed after oral
    administration or subcutaneous injection of benzo [a]pyrene to mice
    and liver tumours following intraperitoneal injection. In two studies,
    lung tumours were found in mice after intravenous injection of
    benzo [a]pyrene and dibenz [a,h]anthracene. Thus, tissues such as
    the skin must be able to metabolize PAH to their ultimate metabolites
    and itself become a target organ; however, all PAH that reach the
    liver via the bloodstream can be metabolized there. The liver in turn
    is a depot from which the metabolites are distributed all over the
    body (Wall et al., 1991). The carcinogenic potency of the PAH differs

    by three orders of magnitude, and several authors have presented
    tables of toxic equivalence factors based on experimental results in
    order to quantify these differences. Carcinogenic potency cannot be
    based only on chemical structure but requires theoretical
    considerations and calculations (see section 7.10).

    Although this monograph primarily addresses single PAH, it was
    considered necessary for risk assessment to present some information
    on mixtures of PAH, to which humans are almost always exposed,
    predominantly adsorbed onto inhalable particles.

    Although the essential results of the studies of carcinogenicity are
    summarized in Table 90, special aspects and comparisons of individual
    PAH are presented in more detail below.

    7.7.1  Single substances

    7.7.1.1  Benzo [a]pyrene

    Oral administration of benzo [a]pyrene to male and female CFW mice
    induced gastric papillomas and squamous-cell carcinomas and increased
    the incidence of pulmonary adenomas (Rigdon & Neal, 1966). In other
    studies in which mice of the same strain were fed benzo [a]pyrene,
    pulmonary adenomas, thymomas, lymphomas, and leukaemia occurred,
    indicating that it can cause carcinomas distal to the point of
    application (Rigdon & Neal, 1969). The incidence of gastric tumours
    was 70% or more in mice fed 50-250 ppm benzo [a]pyrene for four to
    six months. No tumours were observed in controls (Rigdon & Neal, 1966;
    Neal & Rigdon, 1867; see also Table 90).

    In a study of the effects of benzo [a]pyrene given in the diet or by
    gavage in conjunction with caffeine, groups of 32 Sprague-Dawley rats
    of each sex were fed diets containing 0.15 mg/kg bw benzo [a]pyrene
    either five times per week or only on every ninth day. Tumours were
    observed in the forestomach, oesophagus, and larynx, at combined
    tumour incidences of 3/64, 3/64, and 10/64 in the controls and those
    at the low and high doses, respectively. In the study by gavage,
    groups of 32 rats of each sex were treated with benzo [a]pyrene at
    0.15 mg/kg bw in a 1.5% caffeine solution every ninth day, every third
    day, or five times per week. The combined incidences of tumours of the
    forestomach, oesophagus, and larynx were 3/64 in controls, 6/64 in
    rats at the low dose, 13/64 in those at the medium dose, and 14/64
    among those at the high dose (Brune et al., 1981).

    In hamsters exposed to 9.5 or 46.5 mg/m3  benzo [a]pyrene by
    inhalation for 109 weeks, a dose-response relationship was seen with
    tumorigenesis in the nasal cavity, pharynx, larynx, and trachea. The
    fact that lung tumours were not detected could not be explained
    (Thyssen et al., 1981). Hamster lung tissue can activate
    benzo [a]pyrene to carcinogenic derivatives (Dahl et al., 1985).

    Table 81.  Mutagenicity of polycyclic aromatic hydrocarbons to
    Salmonella typhimurium

                                                                  

    Compound              Result with   Reference
    Strain                metabolic
                          activation
                                                                  

    Acenaphthene
    TA98,TA100            -             Florin et al. (1980)
    TM677                 +             Kaden et al. (1979)
    TA98,TA100            +             Epler et al. (1979)
    TA100                 -             Pahlman & Pelkonen
                                        (1987)
    Acenaphthylene
    TA98,TA100            -             Florin et al. (1980)
    TM677                 +             Kaden et al. (1979)
    TA98,TA100            -             Bos et al. (1988)

    Anthanthrene
    TA98                  +             Hermann (1981)
    TA100                 +             LaVoie et al. (1979);
                                        Andrews et al. (1978)
    TA98                  -             Tokiwa et al. (1977)
    TM677                 +             Kaden et al. (1979)

    Anthracene
    TA98,TA100            -             Purchase et al. (1976)
    TA98,TA100            -             Epler et al. (1979)
    TA100                 -             LaVoie et al. (1979);
                                        Gelboin & Ts'o (1978)
    TA98, TA100,          -             McCann et al. (1975a);
    TA1535,TA1537,                      Salamone et al. (1979);
    TA1538                              Ho et al. (1981);
                                        Purchase et al.(1976)
    TA98,TA100            -             Bridges et al, (1981)
    TA98,TA100,           -             Simmon (1979)
    TA1535, TA1536,
    TA1537,TA1538
    TM677                 -             Kaden et al. (1979)
    TA97                  +             Sakai et al. (1985)
    TA98,TA100            -             Probst et al. (1981)
    TA100                 +             Carver et al. (1986)
    TA98,TA100            -             LaVoie et al.(1983a(1985)
    TA1535,TA1538         -             Rosenkranz & Poirier
                                        (1979)
    TA100                 -             Pahlman & Pelkonen
                                        (1987)
    TA98,TA100            -             Bos et al. (1988)
    TA98,TA100            -             Florin et al. (1980)

    Table 81.  (continued)

                                                                  

    Compound              Result with   Reference
    Strain                metabolic
                          activation
                                                                  

    Benz[a]anthracene
    TA100                 +             Epler et al. (1979);
                                        Bartsch et al. (1980)
    TA98,TA100            +             McCann et al. (1975a);
                                        Coombs et al. (1976);
                                        Simmon (1979); Salamone
                                        et al. (1979)
    TA1535,TA1538                       Rosenkranz & Poirier
                                        (1979)
    TA100                 +             Pahlman & Pelkonen
                                        (1987)
    TA98,TA100            +             Hermann (1981); Carver
                                        et al.(1986)
    TA100                 +             Bartsch et al. (1980)
    TM677                 +             Kaden et al. (1979)
    TA100                 +             Baker et al. (1980)
    TA98,TA100            +             Bos et al. (1988)
    TA98,TA100,           +             Probst et al. (1981)
    TA1535,TA1537
    TA98, TA100,
    TA1537, TA1538        ±             Dunkel et al. (1984)
    TA1535                -             Dunkel et al. (1984)
    TA98,TA100            +             Florin et al. (1980)
    TA1537,TA1538         -             Teranishi et al. (1975)
    TA98                  +             Tokiwa et al. (1977)

    Benzo[b]fluoranthene
    TA98                  +             Hermann (1981)
    TA100                 +             LaVoie et al. (1979);
                                        Hecht et al. (1980)
    TA100                 +             Amin et al, (1985a)
    TA98,TA100            -             Mossanda et al. (1979)

    Benzo[j]fluoranthene
    TA100                 +             LaVoie et al. (1980);
                                        Hecht et al. (1980)
    TM677                 +             Kaden et al. (1979)

    Benzo[k]fluoranthene
    TA100                 +             LaVoie et al. (1980);
                                        Hecht et al. (1980)
    TA98                  +             Hermann et al. (1980)

    Table 81.  (continued)

                                                                  

    Compound              Result with   Reference
    Strain                metabolic
                          activation
                                                                  

    Benzo[ghi]fluoranthene
    TA98                  ±             Karcher et al. (1984)
    TA100                 +             Karcher et al. (1984)
    TA98,TA100            +             LaVoie et al. (1979)

    Benzo[a]fluorene
    TA98, TA100,                        Salamone et al. (1979)
    TA1535, TA1537,
    TA1538
    TA100                 +             Epler et al. (1979)
    TA100                 -             LaVoie et al. (1980)
    TA98,TA100            -             Bos et al. (1988)
    TA98                  +             Tokiwa et al. (1977)

    Benzo[b]fluorene
    TA98, TA100           -             LaVoie et al. (1980)
    TA98, TA100,          -             Salamone et al. (1979)
    TA1535, TA1537,
    TA1538
    TM677                 +             Kaden et al. (1979)
    TA98,TA100            +             Bos et al. (1988)

    Benzo[ghi]perylene
    TA98, TA1538          +             Mossanda et al. (1979);
                                        Tokiwa et al. (1977);
                                        Katz et al. (1981)
    TA100                 +             Andrews et al. (1978);
                                        Katz et al. (1981);
                                        LaVoie et al. (1979);
                                        Salamone et al. (1979)
    TA1537,TA1538         +             Poncelet et al. (1978)
    TM677                 +             Kaden et al. (1979)
    TA97                  +             Sakai et al. (1985)
    TA100                 +             Carver et al. (1986)

    Benzo[c]phenanthrene
    TA98                  +             Salamone et al. (1979);
                                        Wood et al. (1980)
    TA100                 +             Carver et al. (1986)
    TA100                 +             Wood et al. (1980)
    TA98,TA100            +             Bos et al. (1988)

    Table 81.  (continued)

                                                                  

    Compound              Result with   Reference
    Strain                metabolic
                          activation
                                                                  

    Benzo[a]pyrene
    TA98                  +             Epler et al. (1979)
    TA100                 +             Andrews et al. (1978)
    TA98,TA100            +             LaVoie et al. (1979)
    TA98,TA100,           +             McCann et al. 1975a,b)
    TA1537,TA1538
    TM677                 +             Kaden et al. (1979)
    TM677                 +             Rastetter et al. (1982)
    TM677                 +             Babson et al. (1 986b)
    TA97,TA98,            +             Sakai et al. (1985)
    TA100
    TA98,TA100            +             Prasanna et al. (1987));
                                        Simmon (1979));
                                        Glatt et al. (1987)
    TA1535,TA1538         +             Rosenkranz & Poirier
                                        (1979)
    TA100                 +             Norpoth et al. (1984));
                                        Alzieu et al. (1987)); Carver
                                        et al. (1986)); Bos et al.
                                        (1988); Hermann (1981);
                                        Bruce & Heddle (1979);
                                        Marino (1987); Alfheim &
                                        Ramdahl (1984)
    TA98                  +             Lee & Lin (1988)
    TA100                 +             Pahlman & Pelkonen
                                        (1987)
    TA97,TA98,TA100       +             Marino (1987)
    TA97,TA98,TA100       +             Sakai et al. (1985)
    TA98,TA100            +             Devanesan et al. (1990)
    TM677                 +             Skopek & Thilly (1983)
    TA98,TA100,           +             Dunkel et al. (1984)
    TA1535, TA1537,
    TA1538
    TA98, TA100           +             Lofroth et al. (1984)
    TA98,TA100            +             Florin et al. (1980)
    TA98                  +             Tokiwa et al. (1977)

    Table 81.  (continued)

                                                                  
    Compound              Result with   Reference
    Strain                metabolic
                          activation
                                                                  

    Benzo[e]pyrene
    TA98                  +             LaVoie et al. (1979);
                                        Hermann (1981)
    TA100                 ±             Salamone et al. (1979)
    TA100                 +             Andrews et al. (1978);
                                        LaVoie et al., 1979)
    TA100                 ±             McCann et al. (1975a)
    TA1535,TA1538         -             Rosenkranz & Poirier
                                        (1979)
    TM677                 +             Kaden et al. (1979)
    TA100                 -             Epler et al. (1979)
    TA98,TA100,           +             Simmon (1979)
    TA1538
    TA97, TA100           +             Sakai et al. (1985)
    TA98, TA100,          ±             Dunkel et al. (1984)
    TA1535,TA1537,
    TA1538
    TA100                 +             Carver et al. (1986)
    TA100                 -             Pahlman & Pelkonen
                                        (1987)
    TA1537,TA1538         -             Teranishi et al. (1975)
    TA98                  +             Tokiwa et al. (1977)

    Chrysene
    TA100                 +             McCann et al. (1975a);
                                        LaVoie et al. (1979)
    TA98                  +             McCann et al. (1975a)
    TA100                 +             Wood et al. (1977)
    TA100                 +             Epler et al. (1979);
                                        LaVoie et al. (1979)
    TA100                 +             Salamone et al. (1979)
    TA1535,TA1536,        -             Simmon (1979)
    TA1537,TA1538
    TA98,TA100            +             Bhatia et al. (1987)
    TM677                 +             Kaden et al. (1979)
    TA1535,TA1538         -             Rosenkranz & Poirier
                                        (1979)
    TA97,TA100            +             Sakai et al (1985)
    TA98,TA100            +             Bos et al. (1988)
    TA98                  +             Hermann (1981)
    TA100                 +             Carver et al. (1986)
    TA100                 +             Pahlman & Pelkonen
                                        (1987)
    TA100                 +             Florin et al. (1980)
    TA98                  +             Tokiwa et al. (1977)

    Table 81.  (continued)

                                                                  

    Compound              Result with   Reference
    Strain                metabolic
                          activation
                                                                  

    Coronene
    TA98                  +             Mossanda et al. (1979)
    TA98                  +             Hermann (1981)
    TA98                  ±             Salamone et al. (1979)
    TA98                  +             Florin et al. (1980)
    TA98, TA1537,         +             Poncelet et al. (1978)
    TA1538
    TA97                  ±             Sakai et al. (1985)
    TM677                 -             Kaden et al. (1979)

    Cyclopenta[cd]pyrene
    TA98                  +             Wood et al. (1980)
    TA98,TA100,           +             Eisenstadt & Gold (1978)
    TA1537,TA1538
    TM677                 +             Kaden et al. (1979);
                                        Cavalieri et al. (1981a)
    TA98                  +             Reed et al. (1988)

    Dibenz[a,h]anthracene
    TA100                 +             Andrews et al. (1978);
                                        Epler et al. (1979);
                                        McCann et al. (1975a,b)
    TA100                 +             Salamone et al. (1979)
    TA98                  +             Baker et al. (1980)
    TA98                  +             Hermann (1981)
    TM677                 +             Kaden et al. (1979)
    TA100                 +             Wood et al. (1978)
    TA100                 +             Pahlman & Pelkonen
                                        (1987); Carver et al.,
                                        1986)
    TA98, TA100,          +             Probst et al. (1981)
    TA1537,TA1538
    TA100                 +             Platt et al. (1990)
    TA100                 +             Lecoq et al. (1989)
    TA1537,TA1538         -             Teranishi et al. (1975)

    Dibenzo[a,e]pyrene
    TA100                 +             LaVoie et al. (1979)
    TA1537,TA1538         +             Teranishi et al. (1975)
    TA98,TA100            +.±           Devanesan et al. (1990)

    Dibenzo[a,h]pyrene
    TA100                 ±             LaVoie et al. (1979)
    TA98,TA100            +             Wood et al. (1981)

    Table 81.  (continued)

                                                                  

    Compound              Result with   Reference
    Strain                metabolic
                          activation
                                                                  

    Dibenzo[a,i]pyrene
    TA100                 +             LaVoie et al. (1979);
                                        McCann et al. (1975a)
    TA100                 +             Baker et al. (1980)
    TA98                  +             Hermann (1981)
    TA98                  +             Wood et al. (1981)
    TA1537,TA1538         +             Teranishi et al. (1975)
    Not specified         +             Sardella et al. (1981)

    Dibenzo[a,l]pyrene
    TA98,TA100            +             Karcher et al. (1984)
    TA98                  +             Hermann (1981)
    TA98,TA100            +,±           Devanesan et al. (1990)

    Fluoranthene
    TA98                  +             Hermann et al. (1980)
    TA98                  +             Epler et al. (1979)
    TA100                 -             LaVoie et al. (1979)
    TA100                 +             LaVoie et al. (1982a)
    TA98, TA100,          -             Salamone et al. (1979)
    TA1535,TA1537,
    TA1538
    TA98,TA100            +             Poncelet et al. (1978)
    TA98,TA100            +             Mossanda et al. (1979)
    TM677                 +             Kaden et al. (1979)
    TM677                 +             Rastetter et al. (1982)
    TM677                 +             Babson et al. (1986b)
    TA97,TA98,TA100       +             Sakai et al. (1985)
    TA98,TA100            +             Bos et al. (1988)
    TA100                 +             Carver et al. (1986);
                                        Hermann (1981);
                                        LaVoie et al., 1979)
    TA98,TA100            +             Bos et al. (1987)
    TA97,TA102,           ±             Bos et al. (1987)
    TA1537
    TA1535                -             Bos et al. (1987)
    TA98,TA100            +             Bhatia et al. (1987)
    TA98,TA100            -             Florin et al. (1980)
    TA98                  -             Tokiwa et al. (1977)

    Table 81.  (continued)

                                                                  

    Compound              Result with   Reference
    Strain                metabolic
                          activation
                                                                  

    Fluorene
    TA98, TA100,          -             McCann et al. (1975a);
    TA1535,TA1537                       LaVoie et al. (1979,
                                        1980, 1981a)
    TM677                 -             Kaden et al. (1979)
    TA97                  -             Sakai et al. (1985)
    TA98,TA100            -             Bos et al. (1988)
    TA100                 -             Pahlman & Pelkonen
                                        (1987)

    Indeno[1,2,3-cd]pyrene
    TA98                  +             Hermann et al. (1980)
    TA100                 +             LaVoie et al. (1979)
    TA100                 +             Rice et al. (1985)

    5-Methylcholanthrene
    TA100                 +             Coombs et al. (1976);
                                        Gelboin & Ts'o (1978);
                                        LaVoie et al. (1979);
                                        McCann et al. (1975a);
                                        Hecht et al. (1978)
    TA100                 +             Amin et al. (1979)
    TA100                 +             El-Bayoumy et al. (1986)

    1-Methylphenanthrene
    TA100                 +             LaVoie et al. (1981b)
    TM677                 +             Kaden et al. (1979)
    TA97,TA98,TA100       +             Sakai et al. (1985)
    TA98,TA100            +             LaVoie et al. (1983b)

    Naphthalene
    TA98,TA100,           -             Florin et al. (1980)
    TA1535,TA1537
    TA98, TA100,          -             McCann et al. (1975a)
    TA1535,TA1537,
    TA1538
    TA98, TA100,          -             Purchase et al. (1976)
    TA1535,TA1538
    TA98                  -             Ho et al. (1981)
    TM677                 -             Kaden et al. (1979)
    G46, E. coli K12      -             Kramer et al. (1974)
    TA98,TA100            -             Epler et al. (1979)
    TA98,TA100            -             Mamber et al. (1984)

    Table 81.  (continued)

                                                                  

    Compound              Result with   Reference
    Strain                metabolic
                          activation
                                                                  

    TA97,TA98,TA100       -             Sakai et al. (1985)
    TA100                 -             Pahlman & Pelkonen
                                        (1987)
    TA98,TA100            -             Bos et al. (1988)

    Perylene
    TA98                  +             Ho et al. (1981)
    TA100                 +             LaVoie et al. (1979)
    TA98,TA100,           -             Salamone et al. (1979)
    TA1535, TA1537,
    TA1538
    TA98                  +             Hermann (1981)
    TA98                  +             Florin et al. (1980)
    TM677                 +             Kaden et al. (1979);
                                        Penman et al. (1980)
    TA100                 +             Carver et al. (1986)
    TA97,TA100            +             Sakai et al. (1985)
    TA98,TA100            +             Lofroth et al. (1984)
    TA100                 -             Pahlman & Pelkonen
                                        (1987)
    Phenanthrene
    TA100                 +             Oesch et al. (1981)
    TA100                 -             Wood et al. (1979)
    TA98                  +             Epler et al. (1979)
    TA98                  -             LaVoie et al. (1979, 1980)
    TA100                 -             LaVoie et al. (1981b)
    TA98,TA100            -             Probst et al. (1981)
    TA100                 -             LaVoie et al. (1979);
                                        LaVoie et al. (1980);
                                        Gelboin & Ts'o (1978);
                                        McCann et al. (1975a)
    TA98, TA100,          -             McCann et al. (1975a)
    TA1535,TA1537
    TA100                 +             Carver et al. (1986)
    TM677                 -             Kaden et al. (1979)
    TA97                  +             Sakai et al. (1985)
    TA98,TA100            ±             Bos et al. (1988)
    TA1535,TA1536,        -             Simmon (1979)
    TA1537,TA1538
    TA1535,TA1538         -             Rosenkranz & Poirier
                                        (1979)
    TA100                 -             Pahlman & Pelkonen
                                        (1987)

    Table 81.  (continued)

                                                                  

    Compound              Result with   Reference
    Strain                metabolic
                          activation
                                                                  

    TA98, TA100,          -             Dunkel et al. (1984)
    TA1535,TA1537,
    TA1538
    TA98,TA100            -             Florin et al. (1980)

    Pyrene
    TA98                  -             Ho et al. (1981);
                                        Rice et al. (1988a)
    TA98,TA100,           -             McCann et al. (1975a);
                                        LaVoie et al. (1979);
    TA1535,TA1537                       Ho et al. (1981)
    TA1537                +             Bridges et al. (1981)
    TA98,TA100            -             Salamone et al. (1979)
    TA98,TA100            -             Probst et al. (1981)
    TA1537                +             Epler et al. (1979)
    TM677                 +             Kaden et al. (1979)
    TA97                  +             Sakai et al. (1985)
    TA98,TA100            ±             Bos et al. (1988)
    TA100                 -             Carver et al. (1986);
                                        Hermann (1981)
    TA98,TA100            +             Bhatia et al. (1987)
    TA98, TA100,          -             Dunkel et al. (1984)
    TA1536,TA1537,
    TA1538
    TA100                 -             Pahlman & Pelkonen
                                        (1987)
    TA98,TA100            -             Florin et al. (1980)

    Triphenylene
    TA98                  +             Epler et al. (1979)
    TA98                  +             Tokiwa et al. (1977)
    TA98,TA100            +             Mossanda et al. (1979);
                                        Wood et al. (1980)
    TA98                  +             Hermann (1981)
    TA98,TA100            +             Poncelet et al. (1978)
    TM677                 +             Kaden et al. (1979)
    TA98,TA100            +             Bos et al. (1988)
    TA100                 +             Pahlman & Pelkonen
                                        (1987)
                                                                  

    TA, used to test reverse mutation to histidine non-auxotrophic mutants);
    TM, used to test forward mutation to 8-azaguanine-resistant mutants
    +, positive); -, negative); ±, inconclusive

        Table 82.  DNA damage induced by polycyclic aromatic hydrocarbons in vitro

                                                                                              

    Test system                          End-point   Metabolica    Resultb    Reference
                                                     activation
                                                                                              

    Prokaryotes
    Anthracene
    E. coli pol A-                       R           +             -          Rosenkranz &
                                                                              Poirier (1979)
    E. coli WP2, E. coli WP100           R           +             -          Member et al.
                                                                              (1983)
    E. coli WP2, E. coli WP67,           R           +/-           -          Tweats (1981)
    E. coli CM871
    E. coli PQ37                         R           +/-           -          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)

    E. coli WP2s(lambda)                 R           +/-           +          Rossman et al.
    prophage induction)                                                       (1991)
    B. subtilis                          R           +/-           -          Ashby & Kilby
                                                                              (1981)
    B. subtilis                          R           +/-           -          McCarroll et al.
                                                                              (1981)
    E. coli GY5027 (prophage             R           +             -          Mamber et al.
    induction)                                                                (1984)

    Anthranene
    E. coli PQ37                         R           +/-           +          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)
    Benz[a]anthracene
    E. coli pol A-                       R           +             -          Rosenkranz &
                                                                              Poirier (1979)
    E. coli WP2 uvrA                     R           +             -          Dunkel et al.
                                                                              (1984)
    E. coli PQ37                         R           +/-           +          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)

    Benzo[b]fluoranthene
    E. coli PQ37                         R           +/-           +          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)

    Table 82.  (continued)

                                                                                              

    Test system                          End-point   Metabolica    Resultb    Reference
                                                     activation
                                                                                              

    Benzo[ghi]fluoranthene
    E. coli PQ37                         R           +/-           -          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)

    Benzo[j]fluoranthene
    E. coli PQ37                         R           +/-           +          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)

    Benzo[a]fluoranthene
    E. coli PQ37                         R           +/-           -          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)

    Benzo[b]fluoranthene
    E. coli PQ37                         R           +/-           +          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)

    Bunzo[ghi]perylene
    E. coli PQ37                         R           +/-           +          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)

    Benzo[a]pyrene
    E. coli WP2, E. coli WP100           R           +             +          Mamber et al.
                                                                              (1983)
    E. coli GY5027                       R           +             +          Mamber et al.
                                                                              (1983)
    E. coli pol A-                       R           +             +          Rosenkranz &
                                                                              Poirier (1979)
    E. coli WP2, E. coli WP67,           R           +/-           +          Tweats (1981)
    E. coli CM871
    E. coli WP2 uvrA                     R           +             -          Dunkel et al.
                                                                              (1984)
    E. coli PQ37                         R           +/-           +/+        Mersch-
                                                                              Sundermann et
                                                                              al. (1992)
    B. subtilis                          R           +/-           +          McCarroll et al.
                                                                              (1981)
    E. coli WP2s(lambda)                 R           +/-           +          Rossman et al.
    prophago induction)                                                       (1991)

    Table 82.  (continued)

                                                                                              

    Test system                          End-point   Metabolica    Resultb    Reference
                                                     activation
                                                                                              

    Benzo[e]pyrene
    E. coli pol A-                       R           +             -          Rosenkranz &
                                                                              Poirier (1979)

    E. coli WP2 uvrA                     R           +             -          Dunkel et al.
                                                                              (1984)
    E. coli WP2s(lambda)                 R           +/-           +          Rossman et al.
    prophage induction)                                                       (1991)
    E. coli PQ37                         R           +/-           +          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)

    Chrysene
    E. coli pol A-                       R           +             -          Rosenkranz &
                                                                              Poirier (1979)
    E. coli PQ37                         R           +/-           +          Mersch-
                                                                              Sundermann at
                                                                              al. (1992)

    Coronene
    E. coli PQ37                         R           +/-           -          Mersch-
                                                                              Sundermann at
                                                                              al. (1992)

    Dibenz[a,h]anthracene
    E. coli                              R           +/-           +          Ichinotsubo et al.
                                                                              (1977)
    E. coli PQ37                         R           +/-           +          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)
    B. subtilis                          R           +/-           +          McCarroll et al.
                                                                              (1981)

    E. coli WP2s (lambda                 R           +/-           +          Rossman et al.
    prophage induction)                                                       (1991)

    Dibenzo[a,i]pyrene
    E. coli                              R           +/-           +          Ichinotsubo et al.
                                                                              (1977)
    E. coli PQ37                         R           +/-           +          Mersch-
                                                                              Sundermann et
                                                                              al.(1992)
    B. subtilis                          R           +/-           +          McCarroll et al.
                                                                              (1981)

    Table 82.  (continued)

                                                                                              

    Test system                          End-point   Metabolica    Resultb    Reference
                                                     activation
                                                                                              

    Dibenzo[a,h]pyrene
    E. coli PQ37                         R           +/-           +          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)

    Dibenzo[a,i]pyrene
    E. coli PQ37                         R           +/-           +          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)

    Fluoranthene
    E. coli WP2s (lambda                 R           +/-           -          Rossman et al.
    prophage induction)                                                       (1991)
    E. coli PQ37                         R           +/-           +          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)

    Fluoranthene
    E. coli WP2, E. coli WP100           R           +             -          Mamber et al.
                                                                              (1983)
    E. coli GY5027                       R           +             -          Mamber et al.
                                                                              (1984)
    E. coli PQ37                         R           +/-           -          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)

    Indeno[1,2,3-cd]pyrene
    E. coli PQ37                         R           +             -          Mersch-
                                                                              Sundermann et
                                                                              al.(1992)

    Naphthalene
    E. coli WP2, E. coli WP 100          R           +             -          Mamber et al.
                                                                              (1983)
    E. coli GY5027                       R           +             -          Mamber et al.
                                                                              (1984)
    E. coli PQ37                         R           +/-           -          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)

    Parylene
    E. coli PQ37                         R           +/-           -          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)

    Table 82.  (continued)

                                                                                              

    Test system                          End-point   Metabolica    Resultb    Reference
                                                     activation
                                                                                              

    Phenanthrene
    E. coli pol A-                       R           +             -          Rosenkranz &
                                                                              Poirier (1979)
    E. coli WP2 uvrA                     R           +             -          Dunkel et al.
                                                                              (1984)
    E. coli PQ37                         R           +/-           +          Mersch-
                                                                              Sundermann at
                                                                              al. (1992)
    E. coli WP2s (lambda                 R           +/-           +          Rossman et al.
    prophage induction)                                                       (1991)
    B. subtilis                          R           +/-           -          McCarroll et al.
                                                                              (1981)

    Pyrene
    E. coli                              R           +/-           -          Ashby & Kilbey
                                                                              (1981; De Serres
                                                                              & Ashby, 1981)
    E. coli WP2, E, coli WP100           R           +             -          Mamber et al.
                                                                              (1983)
    E. coli GY5027                       R           +             -          Mamber et al.
                                                                              (1984)
    E. coli WP2 uvrA                     R           +             -          Dunkel et al.
                                                                              (1984)
    E. coli WP2, E. coli WP67,           R           +/-           -          Tweats (1981)
    E. coli CM871
    E. coli PQ37                         R           +/-           -          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)
    B. subtilis                          R           +/-           -          Ashby & Kilbey
                                                                              (1981)
    B. subtilis                          R           +/-           -          McCarroll et al.
                                                                              (1981)
    E. coli WP2s (lambda                 R           +/-           -          Rossman et al.
    prophage induction)                                                       (1991)

    Triphenylene
    E. coli PQ37                         R           +/-           +          Mersch-
                                                                              Sundermann et
                                                                              al. (1992)

    Eukaryotes
    Acenaphthene
    Rat liver or lung                    DA          -             -          Beach & Gupta
                                                                              (1991)

    Table 82.  (continued)

                                                                                              

    Test system                          End-point   Metabolica    Resultb    Reference
                                                     activation
                                                                                              

    Anthracene
    Primary rat hepatocytes              UDS         -             -          Williams, 1977;
                                                                              Probst et al.
                                                                              (1981)
    Primary rat hepatocytes              R           -             -          Tong et al.
                                                                              (1983)
    HeLa cells                           UDS         +/-           -          Martin et al.
                                                                              (1978; Martin &
                                                                              McDermid
                                                                              (1981)
    Human skin fibroblasts               R                         -          Milo et al. (1978)
    Primary rat hepatocytes              UDS         -             -          Probst et al.
                                                                              (1981)
    Human peripheral blood               DA          -             -          Gupta et al.
    lymphocytes                                                               (1988)

    Benz[a]anthracene
    Primary rat hepatocytes              UDS         -             +          Probst et al.
                                                                              (1981)
    Primary rat hepatocytes              R           -             +          Tong et al.
                                                                              (1983)
    HeLa cells                           UDS         +/-           +          Martin et al.
                                                                              (1978)
    Rat or human mammary                 DS          -             ±          Mane et al.
    epithelial cells                                                          (1990)
    Hamster buccal pouch                 DS          -             -          Nagabhushan et
    (epithelial cells (inhibition                                             al. (1990)
    of DNA synthesis)
    Human peripheral blood               DA          -             +          Gupta et al.
    lymphocytes                                                               (1988)

    Benzo[b]fluoranthene
    Rat buccal mucosa                    DA          -             +          Autrup, & Autrup
    epithelial cells                                                          (1986)
    Human leukocytes                     DA          +             +          Roggeband et al.
                                                                              (1994a)

    Benzo[j]fluoranthene
    Rat buccal mucosa                    DA          -             +          Autrup & Autrup
    epithelial cells                                                          (1986)

    Benzo[k]fluoranthene
    Human leukocytes                     DA          +             +          Roggeband et al.
                                                                              (1994a)

    Table 82.  (continued)

                                                                                              

    Test system                          End-point   Metabolica    Resultb    Reference
                                                     activation
                                                                                              

    Benzo[a]pyrene
    Primary rat hepatocytes              UDS         -             +          Probst et al.
                                                                              (1981)
    Primary rat hepatocytes              R           -             +          Williams et al.
                                                                              (1982)
    C3H/1OT1/2 mouse clone 8                         -             ±          Lubet et al.
    (DNA breaks)                                                              (1983a)
    Human leukocytes                     DA          +             +          Roggeband et al.
                                                                              (1994a)
    Hamster or rat trachea               DA,         -             +          Roggeband et al.
    epithelial cells                     UDS                                  (1994b)
    HeLa cells                           UDS         +/-           +          Martin et al.
                                                                              (1978)
    Human skin fibroblasts               R           -             +          Milo et al. (1978)
    Human mammary cells                              -             +          Leadon et al.
    (oxidative DNA damage)                                                    (1988)
    Human fibroblasts                    UDS         +             +          Agrelo & Amos
                                                                              (1981)
    Human fibroblasts WI-38              UDS         +/-           +          Robinson &
                                                                              Mitchell (1981)
    Rat or human mammary                 R           -             +          Mane et al.
    epithelial cells                                                          (1990)
    Human bronchial cells                DA          -             +          Harris et al.
                                                                              (1984)
    Syrian hamster embryo cells          R           -             +          Casto (1979)
    Hamster buccal pouch                             -             +          Nagabhushan et
    epithelial cells (inhibition of                                           al. (1990)
    DNA synthesis)
    Rat buccal mucosa                    DA          -             +          Autrup & Autrup,
    epithelial cells                                                          (1986)
    Human peripheral                     DA          -             +          Gupta et al.
    lymphocytes                                                               (1988)
    Primary rat hapatocytes              DA          -             +          Monteith &
                                                                              Gupta (1992)
    Primary human hepatocytes            DA          -             +          Monteith &
                                                                              Gupta (1992)
    Calf thymus DNA                      DA          -             +          Bryla & Weyand
                                                                              (1991)
    Primary mouse epidermal              DA,         -             +          Gill et al. (1991)
    keratinocytes                        UDS
    Primary rat hepatocytes              R           -             +          Tong et al.
    (SCE)                                                                     (1983)

    Table 82.  (continued)

                                                                                              

    Test system                          End-point   Metabolica    Resultb    Reference
                                                     activation
                                                                                              

    Benzo[e]pyrene
    Primary rat hepatocytes              R           -             -          Tong et al.
    (SCE)                                                                     (1983)
    HeLa cells (UDS)                     UDS         +/-           +          Martin et al.
                                                                              (1978)
    Primary rat hepatocytes              R           -             -          Williams et al.
                                                                              (1982)
    Rat mammary epithelial                           -             -          Mane et al. cells
    (DNA synthesis)                                                           (1990)
    Syrian hamster embryo                R           -             -          Casto (1979)
    cells
    Human skin fibroblasts               R           -             -          Milo et al. (1978)

    Chrysene
    Primary rat hepatocytes              R           -             -          Tong et al.
                                                                              (1983)
    Human leukocytes                     DA          +             +          Roggeband et al.
                                                                              (1994a)

    Cyclopenta[cd]pyrene
    Rat liver or lung tissue             DA          -             +          Beach & Gupta
                                                                              (1991)
    Calf thymus DNA                      DA          +             +          Beach & Gupta
                                                                              (1994)

    Dibenz[a,h]anthracene
    Primary human foreskin               UDS         -             +          Lake et al.
    epithelial cells                                                          (1978)
    HeLa cells                           UDS         +/-           +          Martin et al.
                                                                              (1978)
    Syrian hamster embryo                R           -             -          Casto (1979)
    cells

    Primary rat hepatocytes              UDS         -             +          Probst et al.
                                                                              (1981)
    Mouse liver DNA                      DA          +             +          Lecoq et al.
                                                                              (1991)
    Human bronchial cells                DA          -             +          Harris et al.
                                                                              (1984)
    Hamster embryonic cells                                        +          Kuroki &
                                                                              Heidelberger
                                                                              (1972)
    C3H1OT1/2 mouse clone                DA          -             +          Nesnow et al.
    8 cells                                                                   (1994)

    Table 82.  (continued)

                                                                                              

    Test system                          End-point   Metabolica    Resultb    Reference
                                                     activation
                                                                                              

    Dibenzo[a,i]pyrene
    Primary rat hepatocytes              UDS         -             -          Probst et al.
                                                                              (1981)
    Fluorene
    Primary rat hepatocytes              UDS         -             -          Probst et al.
                                                                              (1981)
    Human leukocytes                     DA          +             +          Roggeband et al.
                                                                              (1994a)

    5-Methylcholanthrene
    Primary rat hepatocytes              UDS         -             +          Tong et al.
                                                                              (1981a)
    1-Methylphenanthrene
    Primary rat hepatocytes              UDS         -             +          Tong et al.
                                                                              (1981a)
    Chinese hamster ovary cells          DA          +             +          Dunn & Douglas
                                                                              (1991)

    Perylene
    Human peripheral blood               DA          -             -          Gupta et al.
    lymphocytes                                                               (1988)
    Syrian hamster embryo                R           -             -          Casto (1979)
    cells

    Phenanthrene
    Syrian hamster embryo                R           -             -          Casto (1979)
    cells

    Human foreskin epithelial            UDS         -             -          Lake et al.
    cells                                                                     (1978)
    Primary rat hepatocytes              UDS         -             -          Probst et al.
    (1981)
    Human skin fibroblasts               R                         -          Milo et al. (1978)

    Pyrene
    Syrian hamster embryo                R           -             -          Casto (1979)
    cells
    Human foreskin epithelial            UDS         -             -          Lake et al.
    cells                                                                     (1978)
    Primary rat hepatocytes              UDS         -             -          Probst et al.
                                                                              (1981)
    HeLa cells                           UDS         +/-           -          Martin et al.
                                                                              (1978)

    Table 82.  (continued)

                                                                                              

    Test system                          End-point   Metabolica    Resultb    Reference
                                                     activation
                                                                                              

    Human fibroblast cell line           UDS         +/-           +          Robinson &
    WI38                                                                      Mitchell (1981)
    Primary rat hepatocytes              R           -             -          Williams et al.
                                                                              (1982)
    Human skin fibroblasts               R                         -          Milo et al. (1978)
    Human skin fibroblasts               UDS         +             -          Agrelo & Amos
                                                                              (1981)
    Primary rat hepatocytes              R           -             -          Tong et al.
                                                                              (1983)
    Human peripheral blood               DA          -             -          Gupta et al.
    lymphocytes                                                               (1988)

    Triphenylene
    Human peripheral blood               DA          -             +          Gupta et al.
    lymphocytes                                                               (1988)
                                                                                              

    R, DNA repair; DA, DNA adducts; UDS, unscheduled DNA synthesis;
    SCE, sister chromatid exchange
    a  +, tested with metabolic activation; -, tested without metabolic activation;
       +/-, tested with and without metabolic activation
    b  Result: +, positive; -, negative; ±, inconclusive; positive results shown if
       positive only with activation

    Table 83. Mutagenicity of polycyclic aromatic hydrocarbons in yeasts and other
    eukaryotes, host-mediated mutagenicity, and mutagenicity in Drosophila

                                                                                              

    Test system                    End-point   Metabolic        Resultb      Reference
                                               activationa
                                                                                              

    Yeasts and other eukaryotes
    Anthracene
    Saccharomyces cerevisiae       MGC         -                -            Seibert et al.
    D4-RDII                                                                  (1981)
    Saccharomyces cerevisiae       MR          -                -            De Serres &
                                                                             Hoffman (1981)
    Benzo[a]pyrene
    Saccharomyces cerevisiae       MGC         -                -            Siebert et al.
    D4-RDII                                                                  (1981)
    Saccharomyces cerevisiae       NMR         -                +            DeSerres &
                                                                             Hoffmann (1981)
    Paramecium tetraurelia                     +                +            Smith-Sonneborn
    (survival)                                                               (1983)

    Chrysene
    Saccharomyces cerevisiae       MGC         -                -            Siebert et al.
    D4-RDII                                                                  (1981)

    Dibenz[a,h]anthracene
    Neurospora crassa                          -                +            Barrett & Tatum
                                                                             (1958)
    Saccharomyces cerevisiae       MGC         -                -            Siebert et al.
    D4-RDII                                                                  (1981)

    Naphthalene
    Paramecium tetraurelia                     +                -            Smith-Sonneborn
    (survival)                                                               (1983)

    Phenanthrene
    Saccharomyces cerevisiae       MGC         -                -            Siebert et al.
    D4-RDII                                                                  (1981)

    Pyrene
    Saccharomyces cerevisiae;      NMR;        -                -            De Serres &
    S. pombe                       FM                                        Hoffman (1981)

    Host-mediated mutagenicity
    Anthracene
    Salmonella typhimurium                     -                ±            Simmon et al.
    TA1530, TA1535,TA1538                                                    (1979)
    Saccharomyces cerevisiae       NMR         -                -            Simmon et al.
                                                                             (1979)

    Table 83. (continued)

                                                                                              

    Test system                    End-point   Metabolic        Resultb      Reference
                                               activationa
                                                                                              

    Benz[a]anthracene
    Salmonella typhimurium                     -                +            Simmon et al.
    TA1530,TA1535,TA1538                                                     (1979)
    Saccharomyces cerevisiae       NMR         -                -            Simmon et al.
                                                                             (1979)

    Benzo[a]pyrene
    Salmonella typhimurium                     -                -            Simmon et al.
    TA1530,TA1535,TA1538                                                     (1979); Glatt at
                                                                             al. (1985)
    Saccharomyces cerevisiae       NMR         -                -            Simmon et al.
                                                                             (1979)

    Benzo[e]pyrene
    Salmonella typhimurium                     -                -            Simmon et al.
    TA1538                                                                   (1979)

    Chrysene
    Salmonella typhimurium                     -                -            Simmon et al.
    TA1530,TA1535,TA1538                                                     (1979)
    Saccharomyces cerevisiae       NMR         -                -            Simmon et al.
                                                                             (1979)

    Phenanthrene
    Salmonella typhimurium                     -                -            Simmon et al.
    TA1530,TA1535                                                            (1979)
    Saccharomyces cerevisiae       NMR         -                -            Simmon et al.
                                                                             (1979)
    Drosophila malanogaster
    Anthracene                     R                            -            Fujikawa et al.
                                                                             (1993)

    Benz[a]anthracene              SLRL                         +            Fahmy & Fahmy
                                                                             (1973)
    Somatic mutation                                            -            Fahmy & Fahmy
                                                                             (1980)
                                   SLRL                         -            Zijistra & Vogel
                                                                             (1984)
                                   SMART                        +            Frolich & Wurgler
                                                                             (1990)
                                   R                            +            Fujikawa et al.
                                                                             (1993)

    Table 83. (continued)

                                                                                              

    Test system                    End-point   Metabolic        Resultb      Reference
                                               activationa
                                                                                              

    Benzo[a]pyrene                 SLRL                         ±            Vogel et al.(1983)
    Somatic mutation                                            +            Fahmy & Fahmy
                                                                             (1980)
                                   SLRL                         -            Zijistra & Vogel
                                                                             (1984)
                                   SLRL                         -            Valencia &
                                                                             Houtchens (1981)
    Somatic mutation                                            +            Batiste-Alentorn
                                                                             et al. (1991)
                                   SMART                        +            Frolich & Wurgler
                                                                             (1990)
                                   SLRL                         -            Valencia &
                                                                             Houtchens (1981)
                                   R                            +            Fujikawa et al.
                                                                             (1993)
    Benzo[e]pyrene                 R                            -            Fujikawa et al.
                                                                             (1993)
    Fluorene                       R                            -            Fujikawa et al.
                                                                             (1993)
    Pyrene                         R                            ±            Fujikawa et al.
                                                                             (1993)
                                                                                              

    MGC, mitotic gene conversion; NMR, number of mitotic recombinants; MR, mitotic recombination;
    SLRL, sex-linked recessive lethal mutation; R, DNA repair; FM, forward mutation;
    SMART, somatic mutation and recombination test

    a  +, tested with metabolic activation; -, tested without metabolic activation; tested with
       and without metabolic activation
    b  Result: +, positive; -, negative; ±, inconclusive; positive results shown if positive only
       with activation

    Table 84. Mutagenicity of polycyclic aromatic hydrocarbons in mammalian cells in vitro

                                                                                              

    Test system                    End-point   Metabolic        Resultb      Reference
                                               activationa
                                                                                              

    Anthracene
    Chinese hamster V79            HPRT        +/-              -            Knaap et al.
                                                                             (1981)
    Mouse lymphoma L5178Y          TK          +                -            Amacher &
                                                                             Turner (1980);
                                                                             Amacher et al.
                                                                             (1980)
    Human lymphoblastoid TK6       TK          +                -            Barfknecht et al.
                                                                             (1981)
    Fischer rat embryo             OR          +                -            Mishra et al.
                                                                             (1978)
    Human epithelial EUE cells     DTR         -                -            Rocchi et al.
                                                                             (1980)
    Mouse lymphoma L5178Y          TK          +/-              +            Myhr & Caspary
                                                                             (1988)

    Benz[a]anthracene
    Chinese hamster V79            HPRT        +                +            Krahn &
                                                                             Heidelberger
                                                                             (1977); Slaga et
                                                                             al. (1978)
    Chinese hamster V79            HPRT        +                -            Huberman
                                                                             (1975)
    Human lymphoblasts TK6         TK          +                +            Barfknecht et al.
                                                                             (1982)
    Human epithelial EUE cells     DTR         -                -            Rocchi et al.
                                                                             (1980)
    Human keratinocytes            HPRT        -                -            Allen-Hoffmann
                                                                             & Rheinwald
                                                                             (1984)
    Mouse lymphoma L5178Y          TK          +                +            Amacher &
                                                                             Turner (1980);
                                                                             Amacher et al.
                                                                             (1980)
    Mouse lymphoma L5178Y          TK          -                -            Amacher &
    (+ hamster hepatocytes)                                                  Paillet (1983)
    Mouse lymphoma L5178Y          TK          -                +            Amacher &
    (+ hamster hepatocytes)                                                  Paillet (1982)
    Rat liver epithelial ARL 18    HPRT        -                -            Tong et al.
                                                                             (1981a)
    Mouse lymphoma L5178Y          TK          +/-              +            Myhr & Caspary
                                                                             (1988)

    Table 84. (continued)

                                                                                              

    Test system                    End-point   Metabolic        Resultb      Reference
                                               activationa
                                                                                              

    Banzo[b]fluoranthene
    Chinese hamster V79            HPRT        +                -            Huberman
                                                                             (1975)

    Benzo[a]pyrene
    Chinese hamster V79            HPRT        +                +            Arce et al.(1987);
                                                                             Diamond et al.
                                                                             1980); Huberman
                                                                             (1975)
    Chinese hamster V79            HPRT        +                +            Krahn &
                                                                             Heidelberger
                                                                             (1977)
    Mouse lymphoma L5188Y          TK          -                +            Amacher &
    (+ hamster hepatocytes)                                                  Paillet (1982)
    Chinese hamster ovary          HPRT        +/-              +            Gupta & Singh
                                                                             (1982)
    Fischer rat embryo             OR          -                +            Mishra et al.
                                                                             (1978)
    Mouse lymphoma L5178Y          TK          -                +            Amacher &
    (+ hamster hepatocytes)                                                  Paillet (1983)
    Mouse lymphoma L5178Y          TK          +/-              +            Clive et al.
                                                                             (1979)
    Mouse lymphoma L5178Y          TK          +                +            Amacher &
                                                                             Turner (1980);
                                                                             Amacher et al.
                                                                             (1980); Arce et
                                                                             al.(1987)
    Mouse lymphoma L5178Y          TK          +                +            Wangenheim &
                                                                             Bolcsfoldi (1988)
    Human lymphoblasts AHH         TK          -                +            Crespi & Thilly
                                                                             (1984)
    Human lymphoblasts K6          TK          +/-              +            Crespi et al.
                                                                             (1985)
    Human epithelial EUE cells     DTR         -                +            Rocchi et al.
                                                                             (1980);
                                                                             Barfknecht et al.
                                                                             (1982)
    Human fibroblasts HS172        DTR         +/-              +            Gupta &
                                                                             Goldstein (1981)
    Human keratinocytes            HPRT        -                +            Allen-Hoffmann
                                                                             & Rheinwald
                                                                             (1984)

    Table 84. (continued)

                                                                                              

    Test system                    End-point   Metabolic        Resultb      Reference
                                               activationa
                                                                                              

    Rat liver epithelial cells                 -                +            Tong et al.
    ARL 18                                                                   (1981a)
    Chinese hamster ovary-AS52                                  +            Oberly et al.
    (chromosomal mutation)                                                   (1992)
    Human epithelial teratoma      HPRT        -                +            Huberman et al.
    P3 (cocultivated with human                                              (1984)
    carcinoma BJ cells)
    Chinese hamster lung cells     HPRT        -                +            Baird et al.
    V79                                                                      (1984)
    Mouse lymphoma L5178Y          TK          +/-              +            Myhr & Caspary,
                                                                             (1988)
    Mouse lymphoma L5178Y          TK          +/-              +            Rees et al.
                                                                             (1989)
    Mouse Balb/c-3T3               OR          -                +            Lubet et al.
                                                                             (1990)
    Mouse lymphoma L5178Y          TK          +/-              +            Jotz & Mitchell
                                                                             (1981)
    Benzo[e]pyrene
    Chinese hamster V79            HPRT        +                -            Hubermann
                                                                             (1978)
    Rat liver epithelial ARL 18    HPRT        -                -            Tong et al.
                                                                             (1981a)
    Mouse C3H10T1/2                OR          -                -            Gehly et al.
                                                                             (1982)
    Human epithelial teratoma P3   HPRT        -                -            Huberman et al.
                                                                             (1984)
    Chinese hamster lung cells     HPRT        -                -            Baird et al.
    V79                                                                      (1984)
    Fischer rat embryo cells       OR          +                -            Mishra et al.
                                                                             (1978)
    Mouse lymphoma L5178Y          TK          +/-              +            Myhr & Caspary
                                                                             (1988)
    Mouse lymphoma L517BY          TK          +/-              -            Clive et al.
                                                                             (1979)
    Mouse Balb/c-3T3               OR          -                -            Lubet et al.
                                                                             (1990)

    Chrysene
    Chinese hamster V79            HPRT        +                -            Huberman &
                                                                             Sachs (1976)
    Human lymphoblasts TK6         TK          +                +            Barfknecht et al.
                                                                             (1982)
    Human epithelial EUE           DTR         -                -            Rocchi et al.
                                                                             (1980)

    Table 84. (continued)

                                                                                              

    Test system                    End-point   Metabolic        Resultb      Reference
                                               activationa
                                                                                              

    Human epithelial teratoma P3   HPRT        -                +            Huberman et al.
    (cocultivated with human                                                 (1984)
    carcinoma BJ cells)

    Cyclopenta[cd]pyrene
    Human lymphoblastold HH-4      HPRT        +                +            Skopek et al.
                                                                             (1979)
    Mouse lymphoma L5178Y          TK          +/-              +            Gold et al. (1980)
    Human lymphoblasts TK6         TK          +                +            Barfknecht et al.
                                                                             (1982)
    Human lymphoblasts AHH1        TK          -                +            Crespi & Thilly
                                                                             1984)
    Chinese hamster V79            HPRT        -                +            Raven et al.
    (+ hamster embryo fibroblasts)                                           (1982)

    Dibenz[a,h]anthracene
    Chinese hamster V79            HPRT        +                +            Huberman &
                                                                             Sachs (1976);
                                                                             Huberman
                                                                             (1978)
    Chinese hamster V79            HPRT        +                +            Krahn &
                                                                             Heidelberger
                                                                             (1977)
    Human epithelial EUE           DTR         -                ±            Rocchi et
                                                                             al., 1980)

    Fluoranthene
    Human lymphoblastoid HH-4      HPRT        +                +            Thilly et al.
                                                                             (1980)
    Human lymphoblasts AHH1        TK          -                -            Crespi & Thilly
                                                                             (1984)
    Human lymphoblasts TK6         TK          +                +            Barfknecht et al.
                                                                             (1982)

    Fluorene
    Mouse lymphoma L5178Y          TK          +/-              +            Wangenheim &
                                                                             Bolcsfoldi (1988)

    1-Methylphenanthrene
    Human lymphoblastoid TK6       TK          +                +            Barfknecht et al.
                                                                             (1981)
    Human lymphoblasts AHH1        TK          -                +            Crespi & Thilly
                                                                             (1984)

    Table 84. (continued)
                                                                                              
    Test system                    End-point   Metabolic        Resultb      Reference
                                               activationa
                                                                                              

    Perylene
    Human lymphoblastoid TK6       HPRT        +                -            Penman et al.
                                                                             (1980)

    Phenanthrene
    Chinese hamster V79            HPRT        +                -            Huberman &
                                                                             Sachs (1976)
    Human lymphoblastoid TK6       TK          +                +            Barfknecht et al.
                                                                             (1981)
    Fischer rat embryo             OR          +                -            Mishra et al.
                                                                             (1978)

    Pyrene
    Mouse lymphoma L517BY          TK          +/-              +            Jotz & Mitchell
                                                                             (1981)
    Fischer rat embryo             OR          +                +            Mishra et al.
                                                                             (1978)
    Chinese hamster V79            HPRT        +                -            Huberman
                                                                             (1975)
    Mouse lymphoma L5178Y          TK          +                -            Amacher et al.
                                                                             (1980)
    Human lymphoblasts TK6         TK          +                -            Barfknecht et al.
                                                                             (1982)
    Chinese hamster ovary          HPRT                         -            Heflich et al.
                                                                             (1990)
    Human epithelial teratoma P3   HPRT        -                -            Huberman et al.
                                                                             (1984)
    Mouse lymphoma L5178Y          TK          +/-              +            Myhr & Caspary
                                                                             (1988)
    Mouse lymphoma L5178Y          TK          +/-              +            Wangenheim &
                                                                             Bolcsfoldi (1988)
    Rat liver epithelial ARL18     HPRT        -                -            Tong et al.
                                                                             (1981a)
    Mouse Balb/c-3T3               OR          -                ±            Lubet et al.
                                                                             (1990)

    Triphenylene
    Human lymphoblasts             TK          +                +            Barfknecht et al.
                                                                             (1982)
                                                                                              

    HPRT, hypoxanthine-guanine phosphoribosyl transferase reversion; TK, thymidine kinase
    reversion; OR, ouabain resistance; DTR, diphtheria toxin resistance
    a  +, tested with metabolic activation; - , tested without metabolic activation; +/-,
       tested with and without metabolic activation
    b  Result: +, positive; -, negative; ±, inconclusive; positive results shown if positive
       only with activation

    Table 85. Chromosomal effects of polycyclic aromatic hydrocarbons in mammalian cells in vitro

                                                                                                

    Test system                    End-point   Metabolic        Resultb      Reference
                                               activationa
                                                                                                

    Anthracene
    Chinese hamster D6             CA,         -                -            Abe & Sasaki
                                   SCE                                       (1977a)
    Rat liver epithelial ARL18     SCE         -                -            Tong et al.
                                                                             (1981b)
    Rat liver RL1                  CA          -                -            Dean (1981)

    Benz[a]anthracene
    Chinese hamster ovary          SCE         -                +            Pal (1981)
    Rat liver epithelial ARL18     SCE         -                ±            Tong et al.
                                                                             (1981b)
    Chinese hamster V79            SCE         -                ±            Mane et al.
    (coincubation with rat                                                   (1990)
    mammary epithelial cells)

    Benzo[a]pyrene
    Rat liver RL1                  CA          -                +            Dean (1981)
    Chinese hamster V79-4          CA,         -                -            Popescu et al.
    (+ feeder cells)               SCE                                       (1977)
    Chinese hamster lung           CA          +/-              +            Matsuoka et al.
                                                                             (1979)
    Mouse lymphoma L5178Y          CA          -                +            Arce et al. (1987)
    (+ hamster embryo cells)
    Human fibroblasts WI-38        CD          +/-              +            Weinstein et al.
                                                                             (1977)
    Chinese hamster V79            SCE         -                +            Arce et al.(1987);
    (+ hamster embryo cells)                                                 Wojciechowski et
                                                                             al. (1981)
    Chinese hamster Don-6          SCE         -                +            Abe et al.
                                                                             (1983a)
    Chinese hamster ovary          SCE         +/-              +            Husgafvel-
                                                                             Pursiainen et al.,
                                                                             1986)
    Chinese hamster ovary          SCE         +/-              +            Evans & Mitchell
                                                                             (1981)
    Rat pleural mesothelial        SCE         +/-              +            Achard et al.
    calls                                                                    (1987)
    Rat liver epithelial ARL 18    SCE         -                +            Tong et al.
                                                                             (1981b)
    Rat hepatoma Reuber            SCE         -                +            Dean et al.
    H4-II-E                                                                  (1983a)
    Rat oesophageal tumour         SCE         -                +            Abe et al.
    R1                                                                       (1983a)

    Table 85. (continued)

                                                                                                

    Test system                    End-point   Metabolic        Resultb      Reference
                                               activationa
                                                                                                

    Rat ascites hepatoma           SCE         -                +            Abe et al.
    AH6&B                                                                    (1983a)
    Human fibroblasts TIG-11       SCE         -                +            Huh et al. (1982)
    Human hepatoma cells           SCE         -                +            Huh et al. (1982)
    Human hepatoma C-HC-4          SCE         -                +            Abe et al.
    and C-HC-20                                                              (1983a,b)
    Chinese hamster V79            SCE         -                +            Mane et al.
    (coincubation rat/human                                                  (1990)
    mammary epithelial cells)
    Primary mouse epidermal        UDS         -                +            Gill et al. (1991)
    keratinocytes
    Human hepatoma (strain         SCE,        -                +            Natarajan &
    Hap G2)                        MN                                        Darroudi (1991)
    Mouse spleen lymphocytes       SCE         -                +            Wielgosz et al.
                                                                             (1991)
    Mouse C3H/10T1/2 clone 8       SCE         -                +            Krolewski et al.
                                                                             (1986)
    Human epithelial teratoma      SCE         -                +            Murison (1988)
    P3 (coincubation with rat
    hepatoma RL-12 cell line)
    Chinese hamster epithelial     SCE         -                +            DeSalvia et al.
    liver                                                                    (1988)
    Human lymphocytes              CD          +/-              +            Rees et al.
                                                                             (1989)

    Benzo[e]pyrene
    Rat liver epithelial ARL 18    SCE         -                -            Tong et al.
                                                                             (1981b)
    Mouse C3H 10T1/2               CA,         -                -            Gehly et al.
                                   SCE                                       (1982)
    Chinese hamster V79 cells      SCE         -                -            Mane et al.
    (coincubation with rat                                                   (1990)
    mammary epithelial cells)
    Human epithelial teratoma      SCE         -                -            Murison (1988)
    P3 (coincubation with human
    breast carcinoma cells
    BJ-015)

    Cyclopenta[cd]pyrene
    Mouse C3H/10T1/2 clone 8       SCE         -                +            Krolewski et al.
                                                                             (1986)
    Human epithelial teratoma      SCE         -                +            Murlson (1988)
    P3 (coincubation with human
    breast carcinoma cells BJ-015)

    Table 85. (continued)

                                                                                                

    Test system                    End-point   Metabolic        Resultb      Reference
                                               activationa
                                                                                                

    Dibenz[a,h]pyrene
    Chinese hamster ovary          SCE         -                +            Pal (1981)

    Fluoranthene
    Chinese hamster CHO-1          SCE         +/-              +            Palitti et al.
                                                                             (1986)
    Chinese hamster epithelial     SCE         -                -            DeSalvia et al.
    liver                                                                    (1988)

    Fluorene
    Chinese hamster lung           CA          +/-              +            Matsuoka et al.
    CHL                                                                      (1991)

    Naphthalene
    Mouse embryos (in vitro)       CA          +                +            Gollahon (1991);
                                                                             Gollahon et al.
                                                                             (1990)

    Perylene
    Chinese hamster V79            CA          -                +            Popescu et al.
                                                                             (1977)
    Chinese hamster V79            SCE         -                -            Popescu et al.
                                                                             (1977)

    Phenanthrene
    Chinese hamster V79-4          SCE         -                -            Popescu et al.
    (+ hamster feeder cells)                                                 (1977)
    Chinese hamster V79-4          CA          -                +            Popescu et al.
    (+ hamster feeder cells)                                                 (1977)
    Chinese hamster Don            CA,SCE                       -            Abe & Sasaki
                                                                             (1977b)
    Chinese hamster lung           CA                           -            Ishidate &
    CHL                                                                      Odashima
                                                                             (1977)
    Chinese hamster lung           CA          +/-              -            Matsuoka et al.
    CHL                                                                      (1979)

    Pyrene
    Rat liver epithelial ARL 18    SCE         -                -            Tong et al.
                                                                             (1981b)
    Chinese hamster D6             CA,         -                -            Abe & Sasaki
                                   SCE                                       (1977a)
    Chinese hamster ovary          SCE         +/-              +            Evans & Mitchell
                                                                             (1981)

    Table 85. (continued)

                                                                                                

    Test system                    End-point   Metabolic        Resultb      Reference
                                               activationa
                                                                                                

    Chinese hamster ovary          SCE         +/-              +            Perry &
                                                                             Thomson (1981)
    Chinese hamster V79-4          CA          -                +            Popescu et al.
                                                                             (1977)
    Chinese hamster V79-4          SCE         -                -            Popescu et al.
    (+ hamster feeder cells)                                                 (1977)
    Rat liver RL1                  CA          -                -            Dean (1981)
    Human fibroblasts WI-38        CD          +/-              -            Weinstein et al.
                                                                             (1977)
    Human hepatoma (strain         MN,         -                -            Natarajan &
    Hep G2)                        SCE                                       Darroudi (1991)
    Chinese hamster epithelial     SCE         -                -            DeSalvia et al.
    liver                                                                    (1988)
                                                                                                

    SCE, sister chromatid exchange; MN, micronucleus formation; CA, chromosomal aberration;
    CD, chromosomal damage
    a  +, tested with metabolic activation; -, tested without metabolic activation;
       +/-, tested with and without metabolic activation
    b  Result: +, positive; -, negative; ±, inconclusive; positive results shown if positive
       only with activation

    Table 86.  Morphological transformation of mammalian cell in vitro by
    polycyclic aromatic hydrocarbons

                                                                               

    Test system                              Resulta   Reference
                                                                               

    Anthracene
    Balb/c3T3 mouse cells                    -         DiPaolo et al. (1972)
    Guinea-pig fetal cells                   -         Evans & DiPaolo
                                                       (1975)
    Neonatal Syrian golden hamster           -         Purchase et al. (1976)
    kidney fibroblasts BHK21 C13
    Syrian hamster embryo cells              -         Pienta et al. (1977)
    Hamster BHK21 clone 13 cells             -         Grab et al. (1980)
    Syrian hamster embryo cells              -         Dunkel et al. (1981)
    Balb/3T3 mousecells                      -         Dunkel et al. (1981)
    Balb/3T3 mousecells                      -         Peterson et al. (1981);
                                                       Lubet et al. (1983a)
    Fischer rat embryo cells                 -         Mishra et al. (1978)
    Fischer rat embryo cells                 -         Dunkel et al. (1981)
    (leukaemia virus-infected)
    Fischer rat embryo cells                 +         Freeman et al. (1973)
    (Rauscher leukaemia virus-infected)
    C3H/10T1/2 mouse clone 8                 -         Dunkel et al. (1988)

    Benz[a]anthracene
    Syrian hamster embryo cells              +         Pienta et al. (1977);
                                                       DiPaolo et al. (1969,
                                                       1971)
    Mouse prostate C3HG23 cells              +         Marquardt &
                                                       Heidelberger (1972)
    C3H/10T1/2 mouse cells                             Nesnow &
                                                       Heidelberger (1976)
    Hamster BHK21 clone 13 cells             +         Greb et al. (1980)
    Hamster embryo cells                     -         Grover et al. (1971)
    Syrian hamster embryo cells              +         Dunkel et al. (1981)
    Syrian hamster lung cells FSHL           +         Emura et al. (1980)
    Mouse ventral prostate C3H               -         Marquardt et al.(1972);
    clone G23 cells                                    Grover et al. (1971)
    Balb/3T3 mouse clone 1-13 cells          +         Rundell et al. (1983)
    Balb/3T3 mouse cells                     ±         Dunkel et al. (1981)
    Fischer rat embryo cells
    (Rauscher leukaemia virus infected)      ±         Freeman et al. (1973)
    Fischer rat embryo cells                 +         Dunkel et al. (1981)
    (leukaemia virus-infected)
    Syrian hamster embryo cells              +         DiPaolo et al. (1985)

    Table 86.  (continued)

                                                                               

    Test system                              Resulta   Reference
                                                                               

    Benzo[b]fluoranthene
    Hamster BHP21 clone 13 cells             +         Greb et al. (1980)
    Syrian hamster lung FSHL cells           +         Emura et al. (1980)

    Benzo[k]fluoranthene
    Syrian hamster lung FSHL cells           -         Emura et al. (1980)

    Benzo[ghi]perylene
    Syrian hamster embryo cells              -         DiPaolo et al. (1985)

    Benzo[a]pyrene
    Golden hamster embryo cells              +         Mager et al. (1977)
    Hamster BHK21 clone 13 cells             +         Greb et al. (1980)
    Hamster embryo cells (SA7 virus-         +         Casto et al. (1977)
    transformed)
    Syrian hamster embryo cells              +         DiPaolo et al. (1969,
                                                       1971)
    Syrian hamster embryo cells              +         Dunkel et al. (1981)
    Syrian hamster embryo cells              +         Casto et al. (1977)
    Syrian hamster lung FSHL                 +         Emura et al. (1980,
                                                       1987)
    Syrian hamster SHE (SA7 virus-           +         Arce et al. (1987)
    transformed)
    C3H/10T1/2 mouse                         +         Arce et al. (1987);
                                                       Lubet et al. (1983b);
                                                       Peterson et al. (1981)
    Balb/3T3 mouse                           +         Dunkel et al. (1981)
    Balb/3T3 mouse clone A31-1-1             +         Little & Vetrovs (1988)
    Fischer rat embryo cells                 +         Mishra et al. (1978)
    Rat embryo cells (SA7 virus-             +         DiPaolo & Casto
    transformed)                                       (1976)
    Fischer rat embryo cells                 +         Freeman et al. (1973)
    (Rauscher leukaemia virus-infected)
    Fischer rat embryo cells                 +         Dunkel et al. (1981)
    (leukaemia virus-infected)
    Balb/c 3T3 mouse clone A31 cells         +         Albini et al. (1991)
    C3H/10T1/2 mouse clone 8 cells           +         Dunkel et al. (1988)
    C3H/10T1/2 mouse clone 8 cells           +         Krolewski et al. (1986)
    Balb/c3T3 mouse clone 1-13 cells         +         Rundell et al. (1983)

    Benzo[e]pyrene
    C3H/10T1/2 mouse cells                   -         Gehly et al. (1982)
    Fischer rat embryo cells                 -         Mishra et al. (1978)

    Table 86.  (continued)

                                                                               

    Test system                              Resulta   Reference
                                                                               

    Banzo[b]fluranthene
    Syrian hamster embryo cells              -         Pienta et al. (1977)
    Syrian hamster embryo cells              +         DiPaolo et al. (1969)
    C3H/10T1/2 mouse clone 8 cells           ±         Dunkel et al. (1988)
    Balb/c-3T3 mouse                         -         Lubet et al. (1990)
    Syrian hamster lung FSHL cells           ±         Emura et al. (1980)
    Syrian hamster embryo cells              -         Dunkel et al. (1981)
    Balb/3T3 mouse                           -         Dunkel et al. (1981)
    Hamster BHK21 clone 13 cells             +         Greb et al. (1980)

    Chrysene
    Syrian hamster embryo cells              +         Pienta et al. (1977)
    Mouse prostate C3HG23 cells              -         Marquardt et al. (1972)
    Hamster BHK21 clone 13 cells             +         Greb et al. (1980)
    Hamster epithelial lung                  +         Jacob et al. (1993c);
    cell line M3E3/C3                                  Riebelmre et al. (1993)

    Cyclopenta[cd]pyrene
    C3H10T1/2 mouse clone 8 calls            +         Gold et al. (1980)
    C3H/10T1/2 mouse clone 8 cells           +         Krolewski et al. (1986)

    Dibenz[a,h]anthracene
    Syrian hamster embryo cells              +         DiPaolo et al. (1969);
                                                       Pienta et al. (1977)
    C3H 10T1/2 mouse cells                   +         Reznikoff et al. (1973)
    C3H mouse prostate cells                 +         Chen & Heidelberger
                                                       (1969)
    C3HG23 mouse prostate cells              -         Marquardt et al. (1972)
    Hamster embryo cells                     -         Grover et al. (1971)
    Fischer rat embryo cells                 +         Freeman et al. (1973)
    (Rauscher leukaemia virus-infected)
    Hamster embryo cells (SA7 virus-         +         Casto (1973); Casto et
    transformed)                                       al. (1977)
    Hamster BHK21 clone 13 cells             +         Greb et al. (1980)
    C3H/10T1/2 mouse clone 8 cells           ±         Lubet et al. (1983a,b)
    Rat embryo cells (SA7 virus-             +         DiPaolo & Casto
    transformed)                                       (1976)
    C3H/10T1/2 mouse clone 8 cells           ±         Dunkel et al. (1988)
    C3H/10T1/2 mouse clone 8 cells           +         Nesnow et al. (1994)

    Fluoranthene
    Fischer rat embryo cells                 -         Freeman et al. (1973)
    (Rauscher leukaemia virus- infected)

    Table 86.  (continued)

                                                                               

    Test system                              Resulta   Reference
                                                                               

    Fluorene
    Balb/c3T3 mouse cells                    ±         Tonelli et al. (1979)

    Indeno[1,2,3-cd]pyrene
    Syrian hamster lung FSHLcells            +         Emura et al. (1980)

    Naphthalene
    Fischer rat embryo cells                 -         Freeman et al. (1973)
    (Rauscher leukaemia virus-infected)
    Human lung WI-38 cells                   -         Purchase et al. (1976)
    Syrian hamster kidney                    -         Purchase et al. (1976)
    BHK-21C13 cells
    Balb/c mouse mammary gland               -         Tonelli et al. (1979)
    Balb/c-3T3 mouse cells                   -         Rundell et al. (1983)

    Perylene
    Syrian hamster embryo cells              -         DiPaolo et al. (1985)
    Syrian hamster embryo cells              -         Casto (1979)

    Phenanthrene
    Mouse prostate C3HG23 cells              -         Marquardt et al. (1972)
    Syrian hamster embryo cells              -         Pienta et al. (1977)
    Balb/3T3 mouse cells                     -         Kakunaga (1973)
    Fetal guinea-pig cells                   -         Evans & DiPaolo
                                                       (1975)
    Syrian hamster embryo cells              -         DiPaolo et al. (1969);
                                                       Dunkel et al. (1981)
    Hamster BHK21 clone 13 cells             -         Greb et al. (1980)
    Hamster embryo calls (SA7                -         Casto et al. (1977)
    virus-transformed)
    C3H/10T1/2 mouse cells                   -         Peterson et al. (1981)
    C3H/10T1/2 mouse cells                   -         Lubet et al. (1983b)
    Balb/3T3 mouse cells                     -         Dunkel et al. (1981)
    Fischer rat embryo cells                 -         Mishra et al. (1978)
    Fischer rat embryo cells                           Freeman et al. (1973)
    (Rauscher leukaemia virus-infected)
    Fischer rat embryo cells (leukaemia      -         Dunkel et al. (1981)
    virus-infected)
    C3H/10T1/2 mouse clone 8 cells           -         Dunkel et al. (1988)

    Table 86.  (continued)

                                                                               

    Test system                              Resulta   Reference
                                                                               

    Pyrene
    Syrian hamster embryo cells              -         DiPaolo et al. (1969);
                                                       Pienta et al. (1977);
                                                       Casto (1979)
    C3H mouse prostate cells                 -         Chen & Heidelberger
                                                       (1969)
    Balb/C-3T3 mouse cells                   -         DiPaolo et al. (1972);
                                                       Kakunaga(1973)
    Fetal guinea pig cells                   -         Evans & DiPaolo
                                                       (1975)
    Fischer rat embryo cells                 -         Mishra et al. (1978)
    Hamswr embryo cells (SA7                 -         Casto et al.  (1977)
    virus-transformed)
    C3H/10T1/2 mouse clone 8 cells           ±         Dunkel et al. (1988)
    Balb/c-3T3 mouse                         -         Lubet et al. (1990)
                                                                               

    a Result; +, positive; ±, inconclusive; -, negative

    Table 87. Chromosomal effects of polycyclic aromatic hydrocarbons in
    mammalian cell systems in vivo, including DNA binding and adducts and
    sperm abnormalities

                                                                             

    Test system                            Resulta   Reference
                                                                             

    Anthracene
    Chinese hamster bone marrow:           -        Roszinsky-Kocher et al.
    CA, SCE                                         (1979)
    Mouse bone marrow: MN                  -        Salamone et al. (1981)
    Mouse: sperm abnormalities             -        Topham (1980)
    Chinese hamster V79 (mouse host-       -        Sirianni & Huang (1978)
    mediated):SCE
    Mouse peripheral blood: MN             -        Oshiro et al. (1992)
    Mouse skin : DNA binding               -        Reddy et al. (1984)

    Benz[a]anthracene
    Chinese hamster bone marrow:           +        Roszinsky-Kocher et al.
    SCE                                             (1979)
    Chinese hamster bone marrow: CA        -        Roszinsky-Kocher et al.
                                                    (1979)
    Long-Evans rat bone marrow: CA         -        Sugiyama (1973)
    Chinese hamster bone marrow            +        Peter et al. (1979)
    MN,CA
    NMRI mouse(in metaphase II             +        Peter et al. (1979)
    oocytes): CA
    Mouse gastrointestinal epithelial      -        Reddy et al. (1991)
    cells: nuclear anomalies
    Rat lung: DNA adducts,SCE, MN          +        Whong et al. (1992)
    Mouse skin: DNA binding                +        Reddy et al. (1984)
    Rat bone marrow and spleen             +        Zhong et al. (1995)
    cells: MN

    Benzo[b]fluoranthene
    Chinese hamster bone marrow:           +        Roszinsky-Kocher et al.
    SCE                                             (1979)
    Chinese hamster bone marrow: CA        -        Roszinsky-Kocher et al.
                                                    (1979)
    Mouse skin: DNA binding                +        Weyand et al. (1987)
    Lung, liver and peripheral             +        Ross et al. (1991); Ross
    lymphocytes of rats: DNA adducts                et al. (1992)
    Rat lung, liver; peripheral blood      +        Ross et al. (1991); Ross
    lymphocytes; whole blood cultures:              et al. (1992)
    SCE
    Mouse gastrointestinal epithelial      +        Reddy et al. (1991)
    cells: nuclear anomalies
    Rat peripheral blood lymphocytes:      +        Bryant et al. (1991)
    SCE, MN

    Table 87. (continued)

                                                                             

    Test system                            Resulta   Reference
                                                                             

    Mouse gastrointestinal epithelial      +        Reddy et al. (1991)
    cells: nuclear anomalies
    Mouse skin: DNA binding                +        Amin et al. (1991a)
    Mouse skin: DNA adducts, MN, UDS       +        Winker et al. (1995)

    Benzo[j]fluoranthene
    Mouse lung and liver cells:            +        Weyand & LaVoie (1988)
    DNA adducts
    Mouse skin: DNA adducts                +        Weyand et al. (1993)

    Benzo[k]fluoranthene
    Mouse skin: DNA binding                +        Weyand et al. (1987)
    Mouse lung and liver cells:            +        Weyand & LaVoie (1988)
    DNA adducts

    Benzo[ghi]perylene
    Mouse skin: DNA binding                +        Reddy et al. (1984)

    Benzo[a]pyrene
    Mouse: dominant lethal mutation        +        Epstein (1968)
    Mouse: dominant lethal mutation        +        Generoso et al. (1982)
    Mouse: spot test                       +        Russell (1977)
    Mouse: spot test                       +        Davidson & Dawson
                                                    (1976)
    Rat hepatocytes: UDS                   -        Miralis et al. (1982)
    Mouse germ cells: UDS                  -        Sega (1979)
    Mouse skin: DNA binding                +        Weyand et al. (1987);
                                                    Rice et al. (1984)
    Chinese hamster bone-marrow            +,+      Roszinsky-Kocher et al.
    cells: CA, SCE                                  (1979)
    Chinese hamster bone-marrow            +,+      Bayer (1978)
    cells: CA, SCE
    Mouse: CA; heritable translocations    -        Generoso et al. (1982)
    Mouse bone marrow: MN                  +        Salamone et al. (1981)
    Mouse bone marrow: MN                  -        Bruce & Heddle (1979)
    Chinese hamster bone-marrow            -        Bayer(1978)
    cells: MN
    Mouse: sperm abnormalities             +        Topham (1980)
    Mouse: sperm abnormalities             +        Bruce & Heddle (1979)
    Chinese hamster V79                    +        Sirianni & Huang (1978)
    (mouse host-mediated): SCE
    Mouse epidermal cells: DNA adducts     +        Albert et al. (1991a,b)
    Mouse bone marrow: MN                  +        Shimada et al. (1991)
    Mouse keratinocytes: MN                +        He & Baker (1991)
    Mouse lung and liver cells:            +        Weyand & LaVoie (1988)

    Table 87. (continued)

                                                                             

    Test system                            Resulta   Reference
                                                                             

    DNA adducts
    Mouse liver, lung and stomach:         +        Cummings et al. (1991)
    DNA adducts
    Rat peripheral lymphocytes: SCE        +        Li et al. (1991)
    Mouse bone marrow: MN                  +        Mavournin et al. (1990)
    Mouse bone marrow: MN                  +        Kliesch et al. (1982)
    Mouse bone marrow: MN                  +        Harper & Legator (1987)
    Mouse peripheral blood cells: MN       ±        Oshiro et al. (1992)
    Mouse gastrointestinal epithelial      +        Reddy et al. (1991)
    cells: nuclear anomalies
    Mouse bone marrow: SCE                 +        Wielgosz et al. (1991)
    Rat peripheral blood lymphocytes:      +        Willems et al. (1991)
    SCE, DNA adducts
    Rat liver cells: DNA adducts           +        Willems et al. (1991)
    Rat peripheral blood lymphocytes:      -        Willems et al. (1991)
    CA
    Chinese hamster cells: CA              +        Matsuoka et al. (1979)
    Mouse skin apithelial cells:           +        Hughes & Phillips (1991)
    DNA binding
    Human peripheral lymphocytes:          +        Haugen et al. (1986)
    DNA adducts
    Rat lung, liver and peripheral         +        Ross et al. (1991)
    lymphocytes: DNA adducts
    Mouse bone marrow: MN                  +        Awogi & Sato (1989)
    Mouse skin: DNA binding                +        Reddy et al. (1984)
    Mouse skin: DNA adducts                +        Oueslati et al. (1992)
    Mouse and rat bone marrow: MN          +        Shimada et al. (1992)
    Mouse bone marrow: CA                  +        Adler & Ingwersen (1989)

    Benzo[e]pyrene
    Chinese hamster bone-marrow            +        Roszinsky-Kocher et al.
    cells: SCE                                      (1979)
    Chinese hamster bone-marrow            -        Roszinsky-Kocher et al.
    cells: CA                                       (1979)
    Mouse gastrointestinal epithelial      -        Reddy et al. (1991)
    cells: nuclear anomalies
    Mouse skin: DNA binding                         Reddy et al. (1984)

    Chrysene
    Chinese hamster bone-marrow            +        Roszinsky-Kocher et al.
    cells: SCE                                      (1979)
    Chinese hamster bone-marrow            -        Roszinsky-Kocher et al.
    cells: CA                                       (1979)
    NMRI mice: metaphase II oocytes        +        Basler et al. (1977)
    Mouse keratinocytes: MN                +        He & Baker (1991)
    Mouse skin: DNA binding                +        Reddy et al. (1984)

    Table 87. (continued)

                                                                             

    Test system                            Resulta   Reference
                                                                             

    Dibenz[a,h]anthracene
    Chinese hamster bone-marrow            +        Roszinsky-Kocher et al.
    cells: SCE                                      (1979)
    Chinese hamster bone-marrow            -        Roszinsky-Kocher et al.
    cells: CA                                       (1979)
    Rat peripheral blood lymphocytes:      -        Bryant et al. (1990)
    SCE, MN
    Mouse skin: DNA binding                +        Lecoq et al. (1991)
    Mouse skin: DNA binding                +        Reddy et al. (1984)
    Rat bone-marrow and spleen             +        Zhong et al. (1995)
    cells: MN
    Rat lung: DNA adducts, MN, SCE         +        Whong et al. (1994)
    Mouse skin: DNA adducts, MN,           +        Winker et al. (1995)
    UDS

    Dibenzo[a,e]pyrene
    Mouse skin epithelial cells:           +        Hughes & Phillips (1991)
    DNA binding

    Dibenzo[a,i]pyrene
    Rat spleen cells: MN                   +        Zhong et al. (1995)
    Rat lung: DNA adducts, MN, SCE         +        Whong et al. (1994)

    Fluoranthene
    Mouse bone-marrow cells: SCE           -        Palitti et al. (1986)

    Indeno[1,2,3-cd]pyrene
    Mouse skin: DNA binding                +        Weyand et al. (1987)
    Mouse skin epithelial cells:           +        Rice et al. (1990)
    DNA binding

    5-Methylcholanthrene
    Mouse skin: DNA adducts                +        Amin et al. (1985a)

    Naphthalene
    Mouse bone-marrow cells: MN            -        Harper et al. (1984)

    Perylene
    Mouse skin: DNA binding                -        Reddy et al. (1984)

    Table 87. (continued)

                                                                             

    Test system                            Resulta   Reference
                                                                             

    Phenanthrene
    Chinese hamster bone-marrow            -        Bayer (1978); Roszinsky
    cells: CA                                       Kocher et al. (1979)
    Chinese hamster bone-marrow            +        Bayer (1978); Roszinsky
    cells: SCE                                      Kocher et al. (1979)
    Chinese hamster bone-marrow            -        Bayer(1978)
    cells: MN

    Pyrene
    Mouse bone marrow cells: SCE           -        Paika et al. (1981)
    Mouse bone marrow: MIN                 -        Salamone et al. (1981)
    Mouse bone marrow cells: MN            -        Tsuchimoto & Matter
                                                    (1981)
    Chinese hamster V79                    -        Sirianni & Huang (1978)
    (mouse host-mediated): SCE
    Mouse keratinocytes: MN                -        He & Baker (1991)
    Mouse peripheral blood cells: MN       -        Oshiro et al. (1992)
    Mouse gastrointestinal epithelial      -        Reddy et al. (1991)
    cells: nuclear anomalies
    Mouse: sperm abnormalities             -        Topham (1980)
    Mouse skin: DNA binding                -        Reddy et al. (1984)
                                                                             

    SCE, sister chromatid exchange; MN, micronucleus assay; CA, chromosomal
    aberrations; UDS, unscheduled DNA synthesis
    a  Result: +, positive; ±, inconclusive; -, negative

    Table 88.  Effects of polycyclic aromatic hydrocarbons on
    morphological transformation of mammalian cells in vivo

                                                                          

    Test system                        Resulta   Reference
                                                                          

    Anthracene
    Mouse bone-marrow cells            -         Salamone et al. (1981)
    Chinese hamster embryo cells       -         DiPaolo et al. (1973)

    Benzo[ghi]perylene
    Hamster embryos, transplacental    -         Quarles et al. (1979)
    exposure

    Benzo[a]pyrene
    Hamster embryos, transplacental    +         Quarles et al. (1979)
    exposure

    Phenanthrene
    Hamster embryos, transplacental    -         Quarles et al. (1979)
    exposure
                                                                          

    a +, positive; ±; inconclusive; -, negative

    Table 89. Overview of genotoxicity of polycyclic aromatic
    hydrocarbons

                                                                 

    Compound                    Results
                                                                 

    Acenaphthene                Inconsistent, limited database
    Acenaphthylene              Inconsistent, limited database
    Anthanthrene                Positive, limited database
    Anthracene                  Negative, with a few exceptions
    Benz[a]anthracene           Positive
    Benzo[b]fluoranthene        Positive
    Benzo[k]fluoranthene        Positive
    Benzo[k]fluoranthene        Positive
    Benzo[ghi]fluoranthene      Positive, limited database
    Benzo[a]fluorene            Inconsistent, limited database
    Benzo[b]fluorene            Inconsistent, limited database
    Benzo[ghi]perylene          Positive
    Benzo[c]phenanthrene        Positive, limited database
    Benzo[a]pyrene              Positive
    Benzo[e]pyrene              Positive
    Chrysene                    Positive
    Coronene                    Positive, limited database
    Cyclopenta[cd]pyrene        Positive
    Dibenz[a,h]anthracene       Positive
    Dibenzo[a,e]pyrene          Positive
    Dibenzo[a,h]pyrene          Positive, limited database
    Dibenzo[a,i]pyrene          Positive
    Dibenzo[a,l]pyrene          Positive, limited database
    Fluoranthene                Positive
    Fluorene                    Negative, with a few exceptions
    Indeno[1,2,3-cd]pyrene      Positive
    5-Methylchrysene            Positive
    1-Methylphenanthrene        Positive
    Naphthalene                 Negative
    Perylene                    Positive
    Phenanthrene                Inconsistent
    Pyrene                      Inconsistent
    Triphenylene                Positive
                                                                 


        Table 90. Carcinogenicity of polycyclic aromatic hydrocarbons in experimental animals

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    Acenaphthene
                    Mouse           100   Dermal   Dissolved in 90% benzene     9 months  No tumours observed             n       Kennaway
                                                                                                                          no/lc   (1924)

    'Pure'          Mouse,     m    85    Dermal   3 drops, 1x/week of          <1 year   After 12 months 5/85 survived   q       Graffi et al.
                    white                          approx. 300 solution, 1                with a total of 2 tumours; 0.4  no/ls   (1953)
                                                   year; initiation experiment            tumour/animal; promotor only:
                                                                                          0.08 tumour/animal
    Anthanthrene
                    Mouse           30    Dermal   0.3% in benzene,             Life      1/30 lung adenoma               n       Badger et al.
                                                   2 x/week, life                                                         no/ld   (1940)

    Recrystallized  Mouse,     f    20    Dermal   0.05 or 0.1%, 3 x/week,      15        0/20 with tumours               n       Hoffmann &
                    Ha/lcR/Mil                     12 months                    months                                    no/val  Wynder (1966)

    Recrystallized  Mouse,     f    30    Dermal   25 Kg/animal, 10 × over      6 months  2/25 papillomas; promotor       n       Hoffmann &
                    Swiss                          20 days; initiation                    only: 526                       no/val  Wynder (1966)
                    Ha/lcR/Mil                     experiment

    'Rigourously    Mouse,     f    13    Dermal   0.25 mg/animal, 4 x;         65 weeks  2/13 papillomas; promotor       n       Van Duuren et
    purified'       lcR(Ha                         initiation experiment                  only: 520 papillomas; control   no/val  al. (1968)
                                                                                          acetone: 0/20 papillomas

    Recrystallized  Mouse,     f    30    Dermal   43 µg/animal, 2 x/week,      < 100     1/30 with skin carcinoma;       n       Lijinsky &
                    Swiss                          75 weeks                               control: 2/30 with carcinomas   no/val  Garcia (1972)

    98.65%          Mouse,     f    40    Dermal   109 µg/animal, 2 x/week,     70 weeks  47% skin-tumour-bearing         p       Cavalieri et al.
                    Swiss                          30 weeks                               animals; solvent control: 0%    no/val  (1977)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    TLC-            Mouse,     f    30    Dermal   0.69 mg/animal, 1x;          35 weeks  18% with papillomas;            p       Scribner
    purified)       CD-1                           initiation experiment                  promoter only: 3%               no/val  (1973)

    > 99%           Mouse,     f    27    Dermal   221 µg/animal, 1x;           26 weeks  11 % papillomas; solvent        n       Cavalieri at
                    Sencar                         initiation experiment                  only: 9%                        yes/val al.(1989)

                    Mouse,     m/f  27    s.c.     0.6 mg/animal, 1x/month,               No local sarcomas observed      n       Lacassagne et
                    XVII                           3 months                                                               no/ln,  al. (1958)
                                                                                                                          ld

    99.4%           Rat        f    35    Intrapulm. 0.65 and 3.4 mg/kg, 1x     102/88    1/35 and 19/35 with lung        p       Deutsch-
                    Osborne-                                                    weeks     tumours; control: no tumours    yes/val Wenzel et al.
                    Mendel                                                                                                        (1983)

    > 99%           Rat,       f    20    Intra-   1.1 mg/gland, 1x, 8          40        1/20 with mammary tumours;      n       Cavalieri at
                    Sprague-              mammary  glands                       weeks     control: 0/21 or 2120           yes/val al. (1989)
                    Dawley                injection

    Anthracene
    Mouse                           2x100 Dermal   40% suspension/solution      5 months  0/100, 1/100 tumours            n       Kennaway
                                                                                                                          no/lc   (1924)

                    Mouse           44    Dermal   5%, 3x/week                  < 11      No skin tumours                 n       Miescher
                                                                                months                                    no/lc   (1942)

                    Mouse,          20    Dermal   1.5 mg/animal, 2x/day; 3     21        3/17 with tumours; promotor     n       Salaman & Roe
                    'S'                            days/week; total: 20 x;      weeks     only: 4/19                      yes/val (1956)
                                                   initiation experiment

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     f    5     Dermal   10% solution, 3x/week,       < 20      No skin tumours                 n       Wynder &
                    Swiss                          life                         months                                    no/ln,  Hoffmann
                    Millerton                                                                                             ld      (1959a)

    TLC-            Mouse,     f    30    Dermal   1.8 mg/animal, 1x;           35        14% with papillomas;            q       Scribner (1973)
    purified        CD-1                           initiation experiment        weeks     promoter only: 3%               no/val

                    Mouse,     m/f  24    Dermal   4 µg, 1 x/day, 5 days/week,  38        No increased tumour             n       Forbes et al.
                    Skh:hair                       38 weeks, then 2 h/day       weeks     frequency compared with         yes/val (1976)
                    less 1,                        UV                                     controls
                    outbred

                    Mouse,     f    20    Dermal   100 µg/animal, 10x on        24 weeks  15% with tumours; solvent:      n       LaVoie et al.,
                    Swiss                          alternate days; initiation             10%                             yes/val (1983a)
                    albino                         experiment
                    (Ha/lcR)

                    Mouse,     m/f  40-50 s.c.     5 mg/animal in tricaprylin;  < 22-28   0/26 sarcomas after 5 months    n       Steiner (1955)
                    C57BI                          1x                           months                                    yes/ld

                    Mouse,     m    5     i.p.     1000 mg/kg, 1 ×              < 5       No effects observed             n       Shubik & Della
                    Swiss                                                       months                                    no/ln   Porta (1957)

                    Rat             31    Oral     6 mg/animal/day, 7x/         33        22/31 alive after 1 year; no    n       Schmahl &
                                          (diet)   week                         monthns   tumours after 33 months         no/lc   Reuter, cited by
                                                                                                                                  Gerarde (1960)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    Highly          Rat,            28    Oral     5-15 mg/animal/day,          700 days  2/28 malignant tumours,         n       Schmahl (1955)
    purified        BD I/BD III           (diet)   6x/week, 78 weeks                                                      no/ld

                    Rat             10    s.c.     1 mg/animal, 1x/week,        < 103     No subcutaneous sarcomas        n       Boyland &
                                                   103 weeks                    weeks                                     no/ln   Burrows (1935)
                                                                                                                          ld

                    Rat,            5     s.c.     5 mg/animal, 6-7x            10        No tumours observed             n       Pollia
                    Wistar                                                      months                                    no/ln   (1941)

    Highly          Rat,            10    s.c.     20 mg/animal, 1x/week,       < 29      5/9 tumours (fibromas) at site  p       Druckrey &
    purified        BD I/BD III                    33 weeks                     months    injection                       no/ln,  Schmahl (1955)
                                                                                                                          ld

    Highly          Rat,            10    i.p.     20 mg/animal, 1x/week,       > 2 years 1/10 spindle-cell sarcoma       q       Schmahl (1955)
    purified        BD I/BD III                                                 33 weeks                                  no/ld

                    Rat,       f    60    Intrapulm. 0.5 mg/animal,             1x/year   No lung tumours; control: no    n       Stanton et al.
                    Osborne/                                                              tumours                         no/d    (1972)
                    Mendel

                    Rabbit          9     Cerebral 4-20 mg/animal, 1 ×          20-54     No glioma                       n       Russel (1947)
                                          implant                               months                                    no/in,
                                                                                                                          ld

    Benz[a]anthracene
                    Mouse,          8-19  Oral     0.5 mg/animal, 1x, 8x        16        0/13, 1/19 and 1/8 with         q       Bock & King
                    C57/BL                         or 16 × (highest dose),      months    papillomas; no carcinomas       yes/ln  (1959)
                                                   < 2 months                             observed; control: 0/12

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     m    20 or Oral     1.5 mg/animal, 3x/wk,        < 547-    100% hepatomas and 95%          p       Klein (1963)
                    B6AF1/J,        40             5 weeks                      600 days  pulmonary adenomas; solvent     no/val
                    newborn                                                               only: 10% hepatomas and
                                                                                          35% pulmonary adenomas

                    Mouse,     m    20    Oral     1.5 mg/animal, 1x/day,       < 568     80% hepatomas and 85%           p       Klein (1963)
                    B6AF1/J,                       2 days                       days      lung adenomas (inadequately     no/val
                    newborn                                                               reported)

    Purified        Mouse           30    Dermal   0.3% in benzene,             < 584     1/30 epitheliomas               n       Barry et al.
                                                   2x/week,life                 days                                      no/ld   (1935)

    'Pure'          Mouse,     m    75    Dermal   3 drops, 1x/week of 0.5%     < 1 year  After 12 months 9/75 survived   p       Graffi et al.
                    white                          solution, 1 year; initiation           with a total of 18 tumours; 2   no/val  (1953)
                                                   experiment                             tumours/animal; promotor only:
                                                                                          0.08 tumour/animal

    Recystallized   Mouse,     f    30    Dermal   66 µg/animal, 2x/week,       13-15.5   No tumours; solvent only: no    n       Miller & Miller
                    albino                         20 weeks                     months    tumours                         no/val  (1963)

                    Mouse,          20    Dermal   0.5% solution, 2x/week,      638 days  No tumours; control: no         n       Stevenson &
                    C3H                            638 days                               tumours                         no/val  von Haam
                                                                                                                                  (1965)

    Recrystallized  Mouse,          30-50 Dermal   0.0001-0,5 mg/animal in      < 88      Dose-dependent increase in      p       Bingham & Falk
                    C3H+e                          n-dodecane or 0. 1           weeks     malignant tumours; solvent      yes/val (1969)
                                                   mg/animal in toluene,                  control: no tumours
                                                   3x/week, 50 weeks

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    Recrystallized  Mouse,     f    20    Dermal   1 mg/animal, 1x; initiation  58-60     10/20 with papillomas;          p       Van Duuren et
                    Swiss                          experiment                   weeks     promotor only:1/20; solvent     no/val  al. (1970)
                    Millerton                                                   control: 0%
                    ICR/Ha

    TLC             Mouse,     f    30    Dermal   0.5 mg/animal, 1x;           35 weeks  62% with papillomas;            p       Scribner(1973)
    purified        CD-1                           initiation experiment                  promotor only: 3%               no/val

    > 99%           Mouse,     f    40    Dermal   90 µg/animal, 2x/week,       70 weeks  2.6% skin-tumour bearing        n       Cavalieri et al.
                    Swiss                          30 weeks                               animals; solvent control: 0%    no/val  (1977)

    > 99%           Mouse,     f    30    Dermal   0.46 mg/animal, 1x;          26 weeks  57% with papillomas;            p       Slaga et al.
                    CD-1                           initiation experiment                  promotor only: 6%               no/val  (1978)

                    Mouse,     f    30    Dermal   0.1 and 0.57 mg/animal,      27 weeks  14% and 36% (p < 0.05) with     p       Levin et al.
                    CD-1                           1x; initiation experiment              tumours; solvent control: 7%    yes/val (1984)

                    Mouse,     f    30    Dermal   0.23 and 0.57 mg/animal,     27 week   17% and 38% papillomas;         p       Weyand et al.
                    CD-11                          1x; initiation experiment              solvent control: 4%             yes/val (1990);Wood et
                                                                                                                                  al. (1980)

    Spectrometer    Mouse,     m/f  50    s.c.     5 mg/animal in tricaprylin;  < 22      8/46 sarcomas after 4 months;   p       Stainer & Falk
                    C57BI                          1x                           months    solvent control: 3/280          no/val  (1951)
                    control

                    Mouse,     m/f  40-50 s.c.     0.05, 0.2, 1, 5, or 10       < 22-28   5/44,11/45,15/44, 20/36 and     p       Steiner &
                    C57BI                          mg/animal in tricaprylin;    months    5/16 sarcomas                   yes/ld  Edgcomb
                                                   1x                                                                             (1952); Steiner
                                                                                                                                  (1955)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    Recrystallized  Mouse,     f    30    s.c.     0.94 mg/animal, 1x           < 15      No sarcomas; solvent control:   n       Miller & Miller
                    albino                                                      months    no tumours                      no/val  (1963)

                    Mouse           20    s.c.     5 mg in tricaprylin, 1x      638 days  No tumours; control: no         n       Stevenson &
                    C3H                                                                   tumours                         no/val  von Haam
                                                                                                                                  (1965)

                    Mouse,     m/f  10/10 s.c.     1 mg/animal, 1x/week,        60-80     8/10 m and 6/10 f with          p       Boyland & Sims
                    C57BL                          10 weeks                     weeks     sarcomas; control: 0/20 m       no/val  (1967)
                                                                                          and 0/20 f

                    Mouse,     m/f  87    s.c.     0.2 mg/animal in             70-75     70 weeks: 15/15 m and 2/18 f    p       Grover et al.
                    Swiss                          polyethylene glycol          weeks     with liver tumours, 4/15 m and  no/val  (1975)
                    newborn                        on days 0, 1 and 2 after               10/18 f with lung tumours;
                                                   birth                                  corrected control data: 4/22 m
                                                                                          and 1/23 f with liver tumours
                                                                                          and 3/22 m and 1/23 f with lung
                                                                                          tumours

                    Mouse,     m/f  140   i.p.     9.1, 18.2, and 36.4          26 weeks  10/47 m and 4/38 f with         n       Wislocki et al.
                    Swiss                          µg/animal on days 1, 8,                pulmonary tumours; solvent      no/val  (1979)
                    Webster                        and 15 after birth                     control: 7/43 and 2/24
                    BLU:Ha(ICR),
                    newborn

                    Mouse,          11    i.v.     10 mg/kg, 1x                 20 weeks  18% lung tumours;               n       Shimkin &
                    A                                                                     control: 21 %                   no/val  Stoner(1975)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,          52    Bladder  About 2 mg/animal, 1x        > 40      17/52 bladder carcinomas        p       Clayson et al.
                    C57 × IF F,           implant                               weeks     and 1/52 papillomas; control:   yes/val (1968)
                    hybrid                                                                4/89

                    Rat,       f    10    Oral     200 mg/rat, 1x               60 days   No tumours in treated animals;  n       Huggins &
                    Sprague-                                                              control: 8/164 after 310 days   no/ln,  Yang(1962)
                    Dawley                                                                                                lc

                    Rat,       m    25    Dermal   Saturated solution in        < 18      No tumours                      n       Tawfic(1965)
                    Donryu                         acetone,dropped at 2x/wk     months                                    no/ld
                                                   to cover 2 cm2, 5 months

    Recrystallized  Rat,       m     20   s.c.     1.88 mg/animal, 1x           > 4       No sarcomas; solvent control:   n       Miller & Miller
                    Holtzman                                                    months    no tumours                      no/val  (1963)

    TLC             Rat,       f    28    i.v.     2 mg/animal (=13 mg/kg),     98 days   No mammary tumours              n       Pataki &
    purified        Sprague-   3x                  on day 50, 53, and 56 of                                               no/ld   Huggins(1969)
                    Dawley                         age

    TLC             Rat,       m    8     i.m.     2.5 mg/animal into hind      270 days  No sarcomas; control: no        n       Pataki &
    purified        Long-                          leg, 1 × on day 25 of age              spontaneous sarcomas            no/ln   Huggins(1969)
                    Evans

    >99%            Rat,       f    20    Intra    0.91 and 3.7 mg into 5th     20 weeks  No mammary tumours;             n       Cavalieri et al.
                    Sprague-              mammary  mammary gland, 1 ×                     control: no tumours             no/val  (1988a)
                    Dawley                injection

    Chromatography  Hamster    m/f  50    Dermal   8 drops of a 0.5% solution,  < 85/61   No tumours                      n       Shubik et al.
    control         Syrian                         2x/week, 10 weeks            weeks                                     no/ln,  (1960)
                    golden                                                                                                ld

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Hamster,   m    5 or  Dermal   20 mmol/litre solution,      < 44      No tumours; control: no         n       Solt et al.
                    Syrian     26         (buccal  painting 2x/week, 5 or       weeks     tumours                         no/val  (1987)
                    golden                pouch)   20 weeks

                    Hamster    m    47 or Intra-   0.5 or 3 mg/animal per       < 110     No tracheal tumours; control:   n       Sellakumar
                    Syrian          33    tracheal week 30 or 15 weeks          weeks     no tumours                      yes/val Shubik (1974)
                    golden

    Benzo[b]fluoranthene
                    Mouse,     f    20    Dermal   0.01, 0.1 and 0.5%,          < 14,12,  0.01 %: 5% papillomas after     p       Wynder &
                    Swiss                          3x/week, life                and 8     14 months; 0.1%: 65%            no/ld   Hoffmann
                    Millerton                                                   months    papilomas and 85% carcinomas            (1959b)
                                                                                          after 12 months;0,5%: 100%
                                                                                          carcinomas after 5 months

                    Mouse,     f    20    Dermal   1 mg, 1x; initiation         63 weeks  18/20 papillomas, 5/20          p       Van Duuren et
                    Swiss                          experiment                             carcinomas; promotor only:      no/val  al. (1966)
                    ICR/Ha                                                                5/20, 1/20

    > 96%           Mouse,     f    40    Dermal   3.4,5.6,9.2 µg/animal,       < 2 years 5/15/540% with local tumours;   p       Habs et al.
                    NMRI                           2x/week, life                          control: no tumours             yes/val (1980)

                    Mouse,                Dermal   10-100 µg/animal;            20 weeks  Dose-related skin tumour        p       LaVoie et al.
                    CD-1                           initiation experiment                  incidence                       yes/val (1982b)

    > 99%           Mouse,     f    20    Dermal   4 and 10 nmol/animal,        34 weeks  45 and 95% tumour incidence;    p       Amin et al.
                    Cr1:CD-1                       10x every other day;                   solvent control: 5%             yes/val (1985a)
                    (ICR)BR                        initiation experiment

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     f    20    Dermal   0.025 and 0.1 mg/animal,     24 weeks  100 and 100% tumour             p       Weyand et al.
                    CD-1                           10x every other day;                   incidence; solvent control:     yes/val (1990)
                                                   initiation experiment                  10%

                    Mouse,     f    20    Dermal   3 and 10 µg/animal, 10x;     34 weeks  65 and 100% with tumours;       p       Amin et al.
                    Cr1:CD1                        initiation experiment                  solvent control: 15%            yes/val (1991a)
                    (ICR)BR

                    Mouse,     m/f  16/14 s.c.     0.6mg/animal, 1x/month,      approx.   8/16 m and 10/14 f with local   p       Lacassagne et
                    XVII nc/Z                      3 months                     200 days  sarcoma                         no/ld   al. (1963a)

    > 99%           Mouse,     m/f  15/17 i.p.     126 µg/animal in DMSO        < 52      53% hapatic, 18% lung           p       LaVoie et al.
                    CD-1                           on days 1,8, and 15 after    weeks     tumours; control: 6% hepatic    yes/val (1987)
                    newborn                        birth (total dose)                     tumours, no lung tumours

    99.5%           Rat,       f    35    Intrapulm.  0.1, 03 and 1 mg/animal,  110/113/  0/35, 1/35, and 9/35            p       Deutsch
                    Osborne/                       1x                           112       pulmonary carcinomas; 1/35,     yes/val Wenzel et
                    Mendel                                                      weeks     2/35, and 4/35 pleomorphic              al.(1983)
                                                                                          sarcomas; control: no tumours

                    Hamster,   m    47    Intra-   0.5 and 0.5 mg/animal        < 110     0/47 and 1/47 tracheal          n       Sellakumar &
                    Syrian                tracheal per week, 30 weeks           weeks     tumours; control: no tumours    yes/val Shubik (1974)
                    golden

    Berizo[j]fluoranthene
    Highly          Mouse,     f    20    Dermal   0.1 and 0.5%, 3x/week,       < 9 and 7 100%/95% with skin              p       Wynder &
    purified        Swiss                          life                         months    carcinomas                      no/ld   Hoffmann
                                                                                                                                  (1959b)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    96%             Mouse,     f    40    Dermal   3.4, 5.6, 9.2 µg/animal,     < 2 years 3, 3, and 5% with local         q       Habs et al.
                    NMRI                           2x/week, life                          tumours;controls: 0%            yes/val (1980)

    > 99%           Mouse,     f    20    Dermal   3, 10, 100 µg, 10x over 20   24 weeks  30, 55, and 95% with tumours    p       LaVoie et al.
                    Cr1:CD1                        days; initiation experiment            (papillomas/keratinizing        yes/val (1982b)
                    (ICR)BR                                                               lesions); 1 malignant lymphoma

                    Mouse,     f    20    Dermal   25, 75 µg, 10x over 20       24 weeks  70 and 90% with papillomas;     p       Rice et al.
                    CD-1                           days; initiation experiment            vehicle control: 10%            yes/val (1987)

    99%             Mouse,     m/f  21/18 i.p.     278 µg/animal in DMSO        < 52      81% males and 22% females       p       LaVoie et al.
                    CD-1                           on days 1, 8, and 15 after   weeks     with liver and lung tumours;    yea/val (1987)
                    newborn                        birth (total dose)                     control: 6%:0%

    99.9%           Rat,       f    35    Intrapulm.  0.8, 4, and 20 mg/kg, 1x  110/117/  1/35, 3/35 and 18/35            p       Deutsch-
                    Osborne/                                                    89 weeks  pulmonary carcinomas;           yes/val Wenzel et
                    Mendel                                                                control: no tumours                     al.(1983)

    Benzo[ghi]fluoranthene
    Highly          Mouse,     f    20    Dermal   0.1 and 0.5%, 3x/week,       < 13      No skin tumours                 n       Wynder &
    purified        Swiss                          life                         months                                    no/ld   Hoffmann
                                                                                                                                  (1959b)
                    Mouse,     f    20    Dermal   1 mg, 1x; initiation                   4/20 papillomas, no             n       Van Duuren et
                    Swiss                          experiment                             carcinomas; promotor only:      no/val  al. (1966)
                    ICR/Ha                                                                5/20, 1/20

    Benzo[k]fluoranthene
    Highly          Mouse,     f    20    Dermal   0.1 and 0.5%, 3x/week,       < 13      0/20 and 2/20 skin papillomas   q       Wynder &
    purified        Swiss                          life                         months                                    no/ld   Hoffmann
                                                                                                                                  (1959b)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     f    25    Dermal   1 mg/animal (total dose)     < 2 years No skin tumours; spontaneous    n       Mohr (1969)
                    NMRI                           in 50 aliquots                         tumours: 10%                    na/val

    > 96%           Mouse,     f    40    Dermal   3.4, 5.6, 9.2 µg/animal,     < 2 years 3, 0 and 0% with local          n       Habs et al.
                    NMRI                           2x/week, life                          tumours; control: no tumours    yes/val (1980)

    > 99%           Mouse,     f    20    Dermal   3, 10, 100 µg, 10x over      24 weeks  5, 25, and 75% with tumours     p       LaVoie et al.
                    Cr1:CD1                        20 days; initiation                    (papillomas/keratinizing        yea/val (1982b)
                    (ICR)BR                        experiment                             lesions)

                    Mouse      m/f  16/14 s.c.     0.6 mg/animal, 1x/month,     approx.   8/16 m and 5/14 f with local    p       Lacassagne et
                    XVII nc/Z                      3 months                     200       sarcomas                        no/ld   al.(1963a)
                                                                                days

    > 99%           Mouse,     m/f  16/18 i.p.     530 µg/animal in DMSO        < 52      19% males and 17% females       q       LaVoie et al.
                    CD-1                           on days 1, 8, and 15 after   weeks     with tumours; control: 6%:0%    yes/val (1987)
                    newborn                        birth (total dose)                     liver and lung tumours

    99.5%           Rat,       f    27-35 Intrapulm.  0.65, 3.4, and 17 mg/kg,  114/95/98 0/35, 3/31 and 12/27            p       Deutsch-
                    Osborne/                       1x                           weeks     pulmonary carcinomas;           yes/val Wenzel (1983)
                    Mendel                                                                control: no tumours

    Benzo[a]fluorene
                    Mouse,          20    Dermal   0.3%, 2x/week, life          < 20      No skin tumours; 4/20 lung      q       Badger et al.
                    stock'                                                      months    adenoma; 1/20 sebaceous         no/ld   (1942)
                                                                                adenoma

    > 99.5%         Mouse,     f    20    Dermal   100 µg, 10x over 20 days;    24 weeks  2/20 skin tumours; control:     n       LaVoie et al.
                    Swiss                          initiation experiment                  1/20                            yes/val (1981c)
                    Ha/ICR

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,          10    s.c.     5 mg/animal, at intervals    < 23      1/10 lung adenoma; no           n       Badger et al.
                    stock'                         of a few weeks, life         months    sarcomas                        no/ln,  (1942)
                                                                                                                          ld

    Benzo[b]fluorene
    99.5%           Mouse,     f    20    Dermal   100 µg, 10x over 20 days;    24 weeks  4/20 skin tumours; control:     q       LaVoie et al.
                    Swiss                          initiation experiment                  1/20                            yes/val (1981c)
                    Ha/ICR

    Benzo[ghi]perylene
                    Mouse,     f    50    Dermal   0.38% solution in benzene,             2/50 with skin tumours;         n       Lijinsky &
                    Swiss                          3x/week, life                          control: 1/59 skin carcinomas   no/val  Saffiotti (1965)

    Chromatography  Mouse,     f    20    Dermal   0.05% and 0.1 %, 3x/week,    15        1/20 and 0/20 skin papillomas;  n       Hoffmann &
    purified        Swiss Ha/I                     12 months                    months    solvent control: no tumours     no/val  Wynder (1966)
                    CR/Mil

    Chromatography  Mouse,     f    30    Dermal   25 µg/animal, 10x over 28    6 months  2/30 papillomas; control: 2/30  n       Hoffmann &
    purified        Swiss Ha/                      days; initiation experiment            0/20                            no/val  Wynder (1966)
                    ICR/Mil

                    Mouse,     f    50    Dermal   20 µg, 2 mg and 4 mg/        < 22.5    3/50, 6/50, and 4/50 with       n       Muller (1968)
                    NMRI                           animal, 2x/week, 25 weeks    months    tumours; vehicle control: 7/50  no/val

                    Mouse,     f    50    Dermal   1 and 2 mg/animal, 1x;       < 22.5    5/50 and 4/50 with tumours;     n       Muller (1968)
                    NMRI                           initiation experiment        months    vehicle control: 7/50           no/val

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    Rigourously     Mouse,     f    20    Dermal   0.8 mg/animal, 1x;           12-13     3/20 papillomas, 1/20           n       Van Duuren et
    purified        Swiss                          initiation experiment        months    squamous-cell carcinoma;        no/val  al. (1970)
                                                                                          vehicle control: 1/20 with
                                                                                          2 papillomas

    Highly          Mouse,     f    50    Dermal   5.5 and 16.5 µg/animal,      33 weeks  No tumours                      n       Goldschmidt et
    purified        ICR/Ha                         3x/week, 33 weeks                                                      no/lc   al. (1973

    Highly          Mouse,     f    50    Dermal   21 µg/animal, 3x/week,       52 weeks  No skin tumours; solvent        n       Van Duuren &
    purified        Swiss                          52 weeks                               control: no tumours             no/val  Goldschmidt
                    ICR/Ha                                                                                                        (1976)

                    Mouse,     f    50    s.c.     0.83 and 16.7 mg/animal,     < 22.5    5/50 and 4/40 with tumours;     n       Muller (1968)
                    NMRI                           1 x/2 weeks, 6 months        months    control:4/50                    no/val

                    Mouse,     f    20    s.c.     0.1, 1 and 10 mg/animal,     < 22      No skin or subcutaneous         n       Muller (1968)
                    NMRI                           1x/2 weeks, 20 weeks         months    tumours;other tumours same      no/val
                                                                                          as control

    98.5%           Rat,       f    34-35 Intrapulm.  0.65, 3.4, and 17 mg/kg,  109/114/  0/35, 1/35 and 4/34             n       Deutsch-
                    Osborne/                                                    106       pulmonary carcinomas effect     yes/val Wenzel et
                    Mendel                         1x                           weeks     of impurity suggested;                  al.(1983)
                                                                                          control: no tumours

    Benzo[c]phenanthrene
                    Mouse,          20    Dermal   Not specified                < 676     7 epitheliomas, 5 papillomas    p       Barry et al.
                                                                                days                                      no/ld   (1935)

                    Mouse,          40    Dermal   0.3%, 2x/week, < 19          < 19      1 papilloma, 4 squamous cell    q       Badger et al.
                                                   months                       months                                    no/ld   (1940)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,          20    Dermal   0.5% solution, 2x/week,      638 days  3 carcinomas, 2 sarcomas;       q       Stevenson &
                    C3H                            638 days                               control: no tumours             no/val  von Haam
                                                                                                                                  (1965)

                    Mouse,     f    30    Dermal   91 and 457 µg, 1x;           21 weeks  5/30 and 11/30 papillomas;      p       Levin et al.
                    CD-1                           initiation experiment                  control:no tumours                      (1980)

                    Mouse           10    s.c.     5 mg at intervals of         < 15      No injection-site tumours       n       Badger et al.
                                                   several weeks, life          months                                    no/ln,  (1940)
                                                                                                                          ld

                    Mouse           20    s.c.     5 mg in tricaprylin, 1x      638 days  3 sarcomas; controls: no        q       Stevenson &
                    C3H                                                                   tumours                         no/val  von Hearn
                                                                                                                                  (1965)

                    Rat,            6     s.c.     5 mg/animal; several         approx.   1/6 sarcoma at injection site   q       Badger et al.
                                                   repeated doses               18 months                                 no/ln,  (1940)
                                                                                                                          ld

    Benzo[a]pyrene
                    Mouse,     f    15    Oral     3 mg/animal in sesame        30 weeks  Increased pulmonary tumours     p       Wattenberg &
                    A/HeJ                          oil, 2x                                (16.6); control: 0.3            yes/val Leong(1970)

                    Mouse,     f    15    Oral     2 mg/animal, 3x, every       26 weeks  15/15 with forestomach          p       Sparnins et
                    A/J                            2 weeks                                tumours and 15/15 with          yes/val al. (1986)
                                                                                          pulmonary adenomas;no
                                                                                          control

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     m/f  25-73 Oral     0.004-1 mg/animal per        140-200   Dose-dependent gastric          p       Neal & Rigdon
                    CFW                   (diet)   day, < 110-165 days          days      tumours (0-90%);control: no     no/val  (1967)
                                                                                          tumours

                    Mouse,     m/f  9-26  Oral     1-20 mg/animal/day,          150-300   Dose-dependent gastric          p       Neal & Rigdon,
                    CFW                   (diet)   < 1-30 days                  days      tumours(0-100%); control:       no/val  (1967)
                                                                                          no tumours

                    Mouse,     m/f  60-175 Oral    0.25 and 1 mg/g food,        < 34      33 and 61 % with stomach        p       Rigdon & Neal
                    White                 (diet)   < 34 weeks                   weeks     tumours; 53 and 20% with        no/val  (1966)
                    Swiss                                                                 lung tumours;controls: 1 and
                                                                                          21%

                    Mouse,     f    20-30 Dermal   0.001, 0.005, and 0.01%,     < 21, 14, 3 and 43%, 63 and 73%, and      p       Wynder &
                    Swiss                          3x/week, life                and 11    951% and 95% with skin          no/ld   Hoffmann
                                                                                          carcinomas/papillomas                   (1959a)

                    Mouse,     f    20    Dermal   0.01, 0.05 and 0.5%,         < 12, 6,  85, 95, and 75% with skin       p       Wynder &
                    Swiss                          3x/week, life                and 6     carcinomas                      no/ld   Hoffmann
                    Millerton                                                   months                                            (1959b)

    Recrystallized  Mouse,     f    20    Dermal   0.05 and 0.1%, 3x/week,      15        17/20 and 19/20 skin tumours;   p       Hoffmann &
                    Swiss                          12 months                    months    solvent control: no tumours     no/val  Wynder (1966)
                    Ha/ICR/Mil

                    Mouse,     f    30    Dermal   25 µg/animal, 1/x over 28    6         24/30 papillomas; promotor      p       Hoffmann &
                    Swiss                          days; initiation experiment  months    only: 2/30                      no/val  Wynder (1966)
                    Ha/ICR/Mil

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     f    50    Dermal   20 and 200 µg/animal,        < 22.5    50/50 and 50/50 with skin       p       Muller (1968)
                    NMRI                           2x/week, 25 weeks            months    tumours;vehicle control: 7/50   no/val

                    Mouse,          20-30 Dermal   (a) 0.00002% in                        (a) 21% malignant tumours;      p       Bingham & Falk
                    C3H/He                         n-dodecane/decalin;                    (b) 50% tumours (three orders   yes/val (1969)
                                                   (b) 0.02% in decalin,                  of magnitude difference in dose)
                                                   3x/week, 50 weeks

                    Mouse,     f    30    Dermal   5 µg/animal, 10x, 20 days;   24 weeks  19/29 tumour-bearing animals    p       Hoffmann et al.
                    Swiss                          initiation experiment                  with 67 skin tumours; control:  no/val  (1972)
                    Ha/ICR/Mil                                                            1/30

                    Mouse,     f    20    Dermal   0.05 and 0.1 mg/animal;      6 months  13 and 18 with skin tumours;    p       Masuda &
                    Swiss ICR                      60x                                    no solvent control              no/val  Kagawa (1972)

                    Mouse,     f    20    Dermal   5 µg/animal, 3x/week,        < 72      13/20 with 22 skin tumours;     p       Hecht et al.
                    Swiss                          72 weeks                     weeks     4/20 with 4 carcinomas;         no/val  (1974)
                    Ha/ICR/Mil                                                            solvent control: no tumours

                    Mouse,     f    50    Dermal   5 µg/animal, 3x/week, life   440 days  16 animals with 26 tumours;     p       Van Duuren &
                    Swiss                                                                 control: no tumours             no/val  Goldschmidt
                    ICR/Ha                                                                                                        (1976)

                    Mouse,     f    20    Dermal   5 and 10 µg/animal,          62 weeks  Low dose: 10/20 with 19 skin    p       Hecht et al.
                    Swiss                          3x/week, 62 weeks                      tumours, 7/20 with 8            yes/val (1976b)
                    Ha/ICR                                                                carcinomas; high dose:18/20
                                                                                          with 70 skin tumours, 14/20
                                                                                          with 16 carcinomas; solvent
                                                                                          control: no tumours

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    99.9%           Mouse,     f    40    Dermal   100 µg/animal, 2x/week,      70 weeks  79% skin-tumour bearing         P       Cavalieri et al.
                    Swiss                          30 weeks                               animals;solvent control: no     no/val  (1977)
                                                                                          tumours

                    Mouse,     f    40    Dermal   1.7, 2.8, 4.6 µg/animal,     < 2 years 24, 69 and, 61 % with local     p       Habs et al.
                    NMRI                           2x/week, life                          tumours(high rate of systemic   yes/val (1980)
                                                                                          tumours);control: no tumours

    > 99.5%         Mouse,     f    20    Dermal   30 µg/animal, 10x on         24 weeks  93% with tumours; vehicle       p       LaVoie et al
                    Swiss                          alternate days; initiation             control: no tumours             no/val  (1981b)
                    Ha/ICR                         experiment

                    Mouse,     f    20    Dermal   3 µg, 10x over 20 days;      24 weeks  85% with tumours (papillomas/   p       LaVoie et al.
                    Cr1:CD1                        initiation experiment                  keratinizing lesions)           yes/val (1982b)
                    (ICR)BR

    > 96%           Mouse,     f    20    Dermal   2 and 4 µg/animal,           648 and   45% (10% papillomas/35%         p       Habs et al.
                    NMRI                           2x/week, life                528 days  carcinomas) and 85%             yes/val (1984)
                                                                                (mean)    (0%/85%) with skin tumours;
                                                                                          control: no tumours

    99.5%           Mouse,     m    50    Dermal   12.5 µg/animal, 2x/week,     < 99      94% with malignant skin         p       Warshawsky &
                    CH3/HeJ                        99 weeks                     weeks     tumours;solvent control: no     no/val  Barkley (1987)
                                                                                          tumours; untreated control: no
                                                                                          tumours

                    Mouse,     f    24    Dermal   0.8 µmol/mouse, 1x;          24 weeks  Enhanced incidence of skin      p       Cavalieri et al.
                    Sencar                         initiation experiment                  papillomas (80-92%)             no/val  (1988b)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     m    12    Dermal   1.2 mg/animal, 6 days/wk,    < 27      Multiple tumours;               p       Shubik & Della
                    Swiss                          19 weeks                     weeks     squamous-cell carcinomas        no/ln   Porta (1957)

    > 99%           Mouse,     f    20    Dermal   2.5 µg/animal, 10x over 20   24 weeks  89% tumours, 5.5 skin           p       Rice et al.
                    CD-1                           days; initiation experiment            tumours/animal; control: 5%     yes/val (1988b)

    > 99%           Mouse,     f    25    Dermal   2.5 µg/animal, 10x over 20   23 weeks  96% tumours, 3.4 skin           p       Rice et al.
                    CD-1                           days; initiation experiment            tumours/animal; control: no     yes/val (1990)
                                                                                          tumours

    Chromatography  Mouse,     f    23-24 Dermal   8.4, 25.2 and 75.7 µg/       15 weeks  10/23, 17/24 and 21/23 with     p       Cavalieri et al.
    purified        Sencar                         animal, 1x; initiation                 tumours; control: no tumours    yes/val (1991)
                                                   experiment

    Chromatography  Mouse,     f    24    Dermal   1, 5 and 25 µg/animal, 1 x;  27 weeks  1/24, 10/24 and 22/24 with      p       Cavalieri et al.
    purified        Sencar                         initiation experiment                  tumours; control: no tumours    yes/val (1991)

    Chromatography  Mouse,     f    24    Dermal   25 µg/animal, 1x; initiation 27 weeks  1/24 with tumours               p       Cavalieri et al.
    purified        Sencar                         experiment without                                                     yes/val (1991)
                                                   promotion

    HPLC            Mouse,     f    43-50 Dermal   16, 32, or 64 µg/animal,     < 35      1, 1.5 and 7.5 tumours/animal   p       Albert et al.
    control         ICR/Harlan                     1x/week, 29 weeks            weeks     after 35 weeks                  no/val  (1991a)

                    Mouse,     m    20    Dermal   100 µg/animal, 2x/week,                Tumours from 15 weeks           p       Andrews et al.
                    Balb/c                         3 weeks-5 months                       onwards                         no/val  (1991)

                    Mouse,     m/f  40-50 s.c.     0.09 mg/animal in            < 22-28   16/21 sarcomas after 5          p       Steiner (1955)
                    C57BI                          tricaprylin; 1x              months    months                          yes/ld

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     m/f  14/16 s.c.     0.6 mg/animal, 1x/month,     > 129/160 13/14 m and 8/16 f with local   p       Lacassagne et
                    XVII                           3 months                     days      sarcomas                        no/ld   al. (1958)
                                                                                (average
                                                                                latency)

                    Mouse,     m/f  154/  s.c.     0.6 mg/animal, 1x/month,     approx.   154/154 m and 112/162 f with    p       Lacassagne et
                    XVII nc/Z       162            3 months                     110/150   local sarcomas                  no/ld   al. (1963a)
                                                                                days

                    Mouse,          20    s.c.     0.1, 1 and 10 mg/animal,     17, 7, 6  All animals with sarcomas at    p       Muller (1968)
                    NMRI                           1 x/2 weeks, 20 weeks        months    injection site                  no/val

                    Mouse,     f    90    s.c.     25, 50, 100, 200 and 400     < 16      25, 50, 55, 75 and 65% with     p       Pott et al.
                    NMR1                           µg/animal, 1x                months    tumours; solvent control:       no/val  (1973)
                                                                                          < 5%

                    Mouse,     m/f  31-38 s.c.     0.01 and 0.1 mg/animal,      30 weeks  16 and 64% with lung            p       Rippe & Pott
                    newborn                        1x                                     tumours; control: 13% with      no/val  (1989)
                                                                                          lung tumours

    > 99%           Mouse,     m/f  17/14 i.p.     278 µg/animal in DMSO        < 52      76% hepatic and 64% lung        p       LaVoie et al.
                    CD-1                           on days 1, 8, and 15 after   weeks     tumours; control: 6% hepatic    yes/val (1987)
                    newborn                        birth (total dose)                     tumours, no lung tumours

    > 99%           Mouse,     m/f  28/27 i.p.     59.5 µg/animal on days       26 weeks  46 m, 70, f with lung tumours;  p       Busby et al.
                    Swiss-                         1, 8, and 15 after birth               vehicle control: 14 m, 7 f      yes/val (1989)
                    Webster                        (total dose)
                    BLU:Ha(ICR),
                    newborn

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,          10    i.v.     10 mg/kg, 1 ×                20 weeks  100% lung tumours; control:     p       Shimkin &
                    A                                                                     21%                             no/val  Stoner (1975)

                    Mouse,     f    19-22 Intra-   0.05 and 0.15 mg/animal,               27 and 42% with carcinomas      p       Pott et al.
                    NMRI                  tracheal 20x                                    in the respiratory tract;       na/val  (1978)
                                                                                          control: 9%

    99%             Mouse,     f    45;   Intra-   1 mg/animal, 1x/week,        < 18      No colonic tumours, 73% lung    p       Anderson et al.
                    ICR/Ha          60    colonic  14 weeks                     months    tumours, 94% forestomach        yes/val (1983)
                                    contr. instill-                                       tumours, 7% subcutaneous
                                          ation                                           sarcomas, 23% mammary
                                                                                          carcinomas; control: 25% lung
                                                                                          tumours, 20% forestomach
                                                                                          tumours, 9% mammary
                                                                                          carcinomas, no subcutaneous
                                                                                          sarcomas or colonic tumours

    99%             Mouse,     f    38;   Intra-   1 mg/animal, 1x/week,        < 18      No colonic tumours, 94% fore-   p       Anderson et al.
                    C57BI/6         45    colonic  14 weeks                     months    stomach tumours, 16%            yes/val (1983)
                                          instill-                                        peritoneal sarcomas, 28%
                                          ation                                           lymphomas; control: 21%
                                                                                          forestomach tumours, no sarcomas
                                                                                          or lymphomas or colonic tumours

                    Rat,       f    9     Oral     100 mg/kg, 1x                60 days   8/9 with mammary tumours;       p       Huggins &
                    Sprague-                                                              control: 8/164 in 310 days      no/ln,  Yang(1962)
                    Dawley                                                                                                lc

                    Rat        f    20    Oral     625 mg/animal, 1x/week,      90 weeks  67-77% with mammary             p       McCormick et
                    LEW/Mai                        8x; 50 mg/animal, 1 ×                  tumours; control: 30%           yes/val al. (1981)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Rat,       f    50    s.c.     33, 100, 900, and 2700       < 16      10, 15, 70 and 75% with         p       Pott et al.
                    Wistar                         µg/animal, 1x                months    tumours; solvent only: < 5%     no/val  (1973)

                    Rat,       f    37    i.p.     5 mg/animal; 1x; in bees'              (a) 89% abdominal tumours       p       Roller et al.
                    Wistar                         wax/tricaprylin 25/75 (a)    2 years   (mesotheliomas, sarcomas);      no/val  (1992)
                                                   or saline (b)                          (b) 50%; vehicle controls:
                                                                                          (a) 70%; (b) 3%

                    Rat,       f    13-17 Intra-   0.5, 1, or 2 mg/animal in    Life      7, 65, and 92% with lung        p       Davis et al.
                    Wistar                tracheal infusion; 1x/2 weeks; 18x              tumours; control: no tumours    yes/val (1975)

                    Rat,       m/f  15/15 Intra-   1 mg/animal, 1x/week,        Life      3/13 (m) and 3/14 (f) with      p       Ishinishi et al.
                    Wistar                tracheal 15x                          (mean,    malignant lung tumours          no/val  (1976)
                                                                                491/540   (mean: 22.2%); vehicle control:
                                                                                days)     0%

                    Rat,       f    36-40 Intra-   1 mg/animal; 20x                       19% with lung tumours;          p       Pott et al.
                    Wistar                tracheal                                        control: no tumours             no/val  (1987)

                    Rat,       m/f  20/20 Intra-   7 mg/kg, every 14 days,      < 781     19/20 m and 18/20 1 with lung   p       Steinhoff et al.
                    Sprague-              tracheal 22x (total dose: 154         days      tumours; vehicle control: 0%    no/val  (1991)
                    Dawley                         mg/kg)

    99.1%           Rat,       f    35    Intrapulm.  0.1, 0.3, or 1 mg/animal, 111/77/54 4/35, 21/35 and 33/35           p       Deutsch-
                    Osborne/                       1x                           weeks     pulmonary carcinomas; 6/35,     yes/val Wenzel et
                    Mendel                                                                2/35 and 0/35 pleomorphic               al.(1983)
                                                                                          sarcomas; control: no tumours

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Rat,       f    35    Intrapulm. 0.05, 0.1, or 0.2                    11, 17, and 46% with tumours;   p       Grimmer et al.
                    Osborne/                       mg/animal, 1X                          control: no tumours             yes/val (1987)
                    Mendel

    99.6%           Rat,       f    35    Intrapulm. 0.03, 0.1, or 0.3 mg/      < 135     8.6, 31.4, and 77.1% tumour     p       Wenzel-
                    Osborne/                       animal, 1x                   weeks     incidence; control: no tumours  yes/val Hartung et al.
                    Mendel                                                                                                        (1990)

                    Rat,       m    14-15 Intrapulm.  50, 100, or 200 µg/animal < 100     0/10, 3/10 and 4/9 lung         p       Horikawa et al.
                    Fischer                                                     weeks     tumours; control: no tumours    no/val  (1991)
                    344/Du Crj

                    Rat,            94    Intrabr- approx. 3-5 mg/animal, 1x    approx.   Carcinoma incidence: 17%        p       Laskin et al.
                                          onchial                               5 months                                  no/lc   (1970)
                                          pellet

    > 99%           Rat,       f    20    Intra-   1 and 4 mg into 5th          20 weeks  50 and 80% with mammary         p       Cavalieri et al.
                    Sprague-              mammary  mammary gland, 1x                      tumours; control: no tumours    no/val  (1988a)
                    Dawley

                    Rat        f    20    Intra-   63 and 252 µq/gland, 1x,     < 24      7/20 and 9/20 with mammary      p       Cavalieri et al.
                    Sprague-              mammary  8 glands                     weeks     tumours; control: 1/18          yes/val (1991)
                    Dawley                injection

    Recrystallized  Rat,       f    20    Pellet   0.5 and 1 mg; 1x             28        12 and 65% with carcinomas      p       Topping et al.
                    Fischer 344           implant- (implanted into tracheal     months    in tracheal transplants         yes/val (1981)
                                          ation    transplants)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Hamster,   m/f  13    Oral     2.5 mg/animal, 4             < 14      9/13 with forestomach cancer;   p       Chu &
                    Syrian                (diet)   days/week, < 14 months       months    2/13 with papillomas            no/val  Malmgren
                    golden                                                                                                        (1965)

    Chromatography  Hamster,   m/f  15/15 Dermal   4 drops of a 0.8% solution   < 99/68   m:1 small nodular melanotic     q       Shubik et al.
    control         Syrian                         in mineral oil, 1x/week, 8   weeks     lesion, 2 malignant             no/ln,  (1960)
                    golden                         weeks including a 30-week              lymphomas; f: no tumours        ld
                                                   interval

    Chromatography  Hamster,   m/f  5/5   Dermal   6 drops of 0.01% solution    < 70      No skin tumours                 n       Shubik et al.
    control         Syrian                         in acetone, 2x/week, 40      weeks                                     no/ln,  (1960)
                    golden                         weeks                                                                  ld

                    Hamster,   m    5 or  Dermal   20 mmol/litre solution,      < 44      10% buccal pouch carcinomas     p       Solt et al.
                    Syrian          28    (buccal  painting 2x/week, 5 or 20    weeks     after 40 week; control: no      no/val  (1987)
                    golden                pouch)   weeks                                  tumours

                    Hamster,   m    10    Inhalation 4.5 h/day, 5 days/week,    Life      No tumours                      n       Thyssen et al.
                    Syrian                         9.8 mg/m3 for 16 weeks or                                              no/ld   (1980)
                    golden                         44.8 mg/m3 for 10 weeks

                    Hamster,   m    24    Inhalation  2.2, 9.5, or 46.5 mg/m3,  109       Dose-dependent tumours in       p       Thyssen et al.
                    Syrian                         4.5 h/day in the first 10    weeks     nasal cavity, pharynx, larynx,  no/val  (1981)
                    golden                         weeks, thereafter 3 h/day,             and trachea; also in oesophagus
                                                   109 weeks                              and forestomach (papillomas,
                                                                                          polyps, squamous-cell
                                                                                          carcinomas); no lung tumours;
                                                                                          larynx most affected with 0,
                                                                                          31 and, 52% incidence; control:
                                                                                          no tumours

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    Pure            Hamster,   m/f  30/30 Intra-   3 mg/animal, 1x/wk, 15       < 45/60   14/19 and 21/21 with tumours    p       Saffiotti et al.
                    Syrian                tracheal week (mixed with inert       weeks     in respiratory tract; control:  no/val  (1968)
                    golden                         dust of haematite                      no tumours
                                                   [ferric oxide]

                    Hamster,   m    30    Intra-   3 mg/animal, 1x/week,        < 74      All with bronchioalveolar       p       Crocker et al.
                    Syrian                tracheal 14 weeks                     weeks     metaplasia; 5/19                no/val  (1970)
                    golden                                                                squamous-cell carcinomas,
                                                                                          3/19 adenomas, 1/19 tracheal
                                                                                          tumours

    Pure            Hamster,   m/f  30-50 Intra-   0.25, 0.5, 1, or 2 mg/       Life      Dose-related increase in        p       Saffiotti et al.
                    Syrian                tracheal animal, 1x/week, 30 wks                respiratory tract tumours;      no/val  (1972)
                    golden                         (mixed with inert dust of              control: no tumours
                                                   ferric oxide)

    Pure            Hamster,   m    30    Intra-   0.0625, 0.125, 0.25, 0.5,    78 weeks  Dose-related increase in        p       Feron et al.
                    Syrian                tracheal and 1 mg/animal, 1x/week,              respiratory tract tumours       no/val  (1973)
                    golden                         52 weeks                               (3-26%); controls: no tumours

                    Hamster,   m/f  25/25 Intra-   0.9 mg/animal per week,      < 100     17% (8/46) tumours in           p       Henry et al.
                    Syrian                tracheal 30 weeks                     weeks     respiratory tract; control:     no/val  (1975)
                    golden                                                                no tumours

                    Hamster,              Intra-   0.3 or 0.9 mg/animal,        < 2 years 17 and 68% with tumours         p       Pott et al.
                    Syrian                tracheal 1x/week, 20 weeks                                                      no/lc   (1978)
                    golden

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Hamster,   m    29    Intra-   0.125, 0.25, 0.5, or         Life      31, 83, 66, and 31% tumours     p       Ketkar et al.
                    Syrian                tracheal 1 mg/animal, 1x/week, life             in respiratory tract; control;  no/val  (1979)
                    golden                                                                no tumours

                    Hamster,   m    30    Intra-   5, 20 or 40 µg/animal,       Life      4/28, 5/27 and 7/28 with        q       Kunstler (1983)
                    Syrian                tracheal every 2 weeks, life                    meta plasia in respiratory      no/val
                    golden                                                                tract, malignant neoplasm
                                                                                          and 1 adenoma in high-dose
                                                                                          group; controls: 1/29 or 3/30

                    Hamster,        97    Intra-   3-5 mg                                 63/97 with lung cancers         p       Laskin et al.
                                          bronchial                                                                       no/val  (1970)
                                          pellets

                    Hamster,              Tracheal approx. 0.83 mg/animal,                Tracheal papillomas and         p       Mohr (1971)
                    Syrian                insuff-  3x/week, 1 year                        carcinomas                      no/lc
                    golden                lation

                    Hamster,              Bronchial                             150 days  > 90% with focal cancers        p       Benfield &
                    Syrian                implants                                                                        no/lc   Hammond
                    golden                                                                                                        (1992)

                    Dog                   Paren-                                > 8       First parenchymal cancer after  p       Benfield &
                                          chymal                                months    8 months; 7/12 dogs with        no/lc   Hammond
                                          implants                                        tumours                                 (1992)

                    Pig,       m/f  1/1   i.m.     4.8 mg/kg, 1x; 6 months      12        No sarcomas                     n       Kallistratos &
                    German                later 2.1 mg/kg, 1x                   months                                    no/val  Pfau (1971)
                    Edelland-
                    schwein

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Pig,       m/g  1/1   i.m.     6.3 mg/kg, 1x; 6 months      12        No sarcomas                     n       Kallistratos &
                    mini                           later 1.9 mg/kg, 1 ×         months                                    no/val  Pfau (1971)

                    Cattle,    m/f  1/1   i.m.     0.95 mg/kg, 1x; 6 months     29        No sarcomas                     n       Kallistratos &
                    German          later          0.75 mg/kg, 1x               months                                    no/val  Pfau (1971)
                    black/white

                    Monkeys    m/fm 1/1   s.c.     10 mg/animal, 1x             (a) >18   (a) 1/2 with local tumours      q       Noyes (1969)
                    (a)        /f   1/1            (coadministration with       months    (b) death within 5 weeks        no/ln
                    Saguinus                       10 mg DMBA at other site)    (b) < 5
                    oedipus;                                                    weeks
                    (b) S.
                    fusciocollis

                    Monkey,               s.c.     1 × (not specified)                    Fibrosarcomas                   p       Adamson &
                    Galago                                                                                                no/lc   Sieber (1983)
                    crassus

                    Monkey,         17    s.c.     30-90 mg/kg, multiple        < 18      No tumours observed;            n       Adamson &
                    Old world                      administration (not          years     survival: 9/17                  no/lc   Sieber (1983)
                                                   specified)

                    Monkey,    m/f  4/2   Intra-   3-15 mg, 1x/week (with       67-69     Bronchioalveolar metaplasia;    p       Crocker et al.
                    Galago                tracheal ferric oxide), up to 69      weeks     2/3 squamous carcinomas         no/val  (1970)
                    crassust                       weeks                                  arising from bronchus

    Benzp[e]pyrene
                    Mouse,     f    20    Dermal   0.1%, 3x/week, life          < 13      2/20 papillomas, 3/20           q       Wynder &
                    Swiss                                                       months    carcinomas                      no/ld   Hoffmann
                    Millerton                                                                                                     (1959a)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     f    20    Dermal   1 mg, 1x; initiation         64 weeks  2/20 with papillomas; pure      q       Van Duuren et
                    Swiss                          experiment                             substance: no tumours           no/val  al. (1968)
                    ICR/Ha

    TLC             Mouse,     f    20    Dermal   2.5 mg/animal, 1x;           35 weeks  85% with papillomas;            p       Scribner (1973)
    purified        CD-1                           initiation experiment                  promotor only: 3%               no/val

    Highly          Mouse,     f    50    Dermal   15 µg/animal, 3x/week,       368 days  No tumours observed; control:   n       Van Duuren &
    purified        ICR/Ha                         368 days                               no tumours                      no/val  Goldschmidt
                                                                                                                                  (1976)

    > 99%           Mouse,     f    30    Dermal   100 µg/animal, 2x/week,      30-40     At 30 wks: 68% papillomas,      p       Slaga et al.
                    CD-1                           30 weeks                     weeks     at 40 weeks: 24% carcinomas     no/val  (1979)

    > 99%           Mouse,     f    30    Dermal   100 and 252 µg/animal,       30-40     High dose: at 30 weeks, 19%     q       Slaga et al.
                    CD-1                           1 x; initiation experiment   weeks     papillomas; at 40 weeks, no     no/val  (1979)
                                                                                          carcinomas;vehicle control: et
                                                                                          30 weeks, 14% papillomas

    99%             Mouse,     f    30    Dermal   0.25, 0.63, or 1.5 mg/       26 weeks  15, 11, or 140% with            q       Buening et al.
                    CD-1                           animal, 1x;initiation                  papillomas; vehicle control:    no/val  (1980)
                                                   experiment                             7% papillomas

    > 95%           Mouse,     f    30    Dermal   0.5 mg/animal, 1 x;          15 weeks  17% with papillomas; vehicle    q       Slaga et al.
                    Sencar                         initiation experiment                  control:10%                     no/val  (1980, 1981)

    99%             Mouse,     m/f  30/30 i.p.     0.1, 0.2, 0.4, or 0.2, 0.4,  62-66     21/35 (m), 0/35 (f) or 12/30    q       Buening et al.
                    Swiss-Webster                  0.8 mg on days 1, 8, and     weeks     (m), 0/30 (f) with hepatic      no/val  (1980)
                    BLU:Ha(ICR),                   15 of life                             tumours; controls: 11/53 (m),
                    newborn                                                               0/24 (f)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    99.7%           Rat,       f    30-35 Intrapulm. 0.8, 4.2, or 20 mg/kg, 1x  117/111/  1 pulmonary sarcoma at          n       Deutsch-
                    Osborne/                                                    104       4.2 mg/kg; 1 squamous-cell      yes/val Wenzel et
                    Mendel                                                      weeks     carcinoma at 20 mg/kg; no               al.(1983)
                                                                                          tumours in controls

    Recrystallized  Rat,       f    20    Tracheal 1 mg, 1x                     28        No tumours                      n       Topping et al.
                    Fischer         pellet                                      months                                    yes/val (1981)
                    344

    Chrysene
                    Mouse           100   Dermal   1% in 90% benzene            < 11      No tumours                      n       Kennaway
                                                                                months                                    no/ld, (1924)
                                                                                                                          lc

    Purified        Mouse                 Dermal   7.5% in liquid paraffin or   78 or 50  6 or 18 benign, 1 or 9          q       Bottomley &
                                                   oleic acid, 5x/week, 78 or   weeks     malignant tumours               no/lc   Twort (1934
                                                   50 weeks

    Doubtful        Mouse           100   Dermal   (a) 0.3% in benzene or       < 704     (a) 1/100 papilloma and 1/100   n       Barry et al.
    Purity                          20             (b) 0.3% ln mouse fat,       days      epithelioma, (b) no tumours     no/ld   (1935)
                                                   2 x/week, life

    'Synthesized'   Mouse           20    Dermal   0.3% (pure), 2x/week,        440 days  No tumours                      n       Barry et al.
                                                   440 days                                                               no/lc,  (1935)
                                                                                                                          ld

                    Mouse           50    Dermal   (a) 0.3% in benzene,         < 797     (a) 2/50 papillomas,            n       Barry et al.
                                    100            (b) 7.5% in oleic acid,      days      (b) no tumours                  no/lc,  (1935)
                                                   2x/week, life                                                          ld

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    'Pure'          Mouse           50    Dermal   In benzene, 2x/week,         < 276     After 276 days at 11/50         n       Schurch &
                                                   276 days                     days      survivors, no tumours           no/lc,  Winterstein
                                                                                                                          ld      (1935)

                    Mouse,     m/f  10/10 Dermal   40 µg/animal, 2x/week,       31 weeks  1/15 carcinomas                 n       Riegel et al.
                    CF1                            31 weeks                                                               no/ld   (1951)

                    Mouse,     f    20    Dermal   1%, 3x/week, life            < 12      9/20 papillomas, 8/20           p       Wynder &
                    Swiss                                                       months    carcinomas; no solvent          no/ld   Hoffmann
                                                                                          control                                 (1959a)

                    Mouse,     f    20    Dermal   1 mg, 1x; initiation         63 weeks  16/20 papillomas, 2/20          p       Van Duuren et
                    Swiss                          experiment                             carcinomas; promotor only:      no/val  al. (1966)
                    ICR/Ha                                                                5/20, 1/20

    TLC             Mouse,     f    30    Dermal   1 mg/animal, 1x; initiation  35 weeks  73% with papillomas;            p       Scribner(1973)
    purified        CD-1                           experiment                             promotor only:3%                no/val

                    Mouse,     m    20    Dermal   75 µg/animal in decalin,     82 weeks  1/12 papillomas; solvent        n       Horton &
                    C3H                            2x/week, 82 weeks                      control:2/13 papillomas         no/ld   Christian (1974)

                    Mouse,     m    20    Dermal   75 µg/animal in decalin/     82 weeks  5/19 papillomas; 12/19          p       Horton &
                    C3H                            dodecane 50/50, 2x/week,               carcinomas; solvent control:    no/val  Christian (1974)
                                                   82 weeks; co-carcinogenicity           2/13 papillomas
                                                   experiment

    > 99.9%         Mouse,     f    20    Dermal   0.1 mg/animal/day, 110x;     22 weeks  11/18 papillomas/carcinomas;    p       Hecht et al.
                    Swiss                          initiation experiment                  chrysene only: 4/11 after 72    no/val  (1974)
                    Ha/ICR/Mil                                                            weeks; solvent control: no
                                                                                          tumours

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     f    30    Dermal   0.09, 0.29 and 0.91 mg/      26 weeks  25, 43 and 52% papillomas;      p       Levin et al.
                    CD-1                           animal, 1x; initiation                 promotor only: 7%               no/val  (1978)
                                                   experiment

    95%             Mouse,     f    30    Dermal   0.46 mg/animal, 2x;          26 weeks  21/30 papillomas; promotor      p       Wood et al.
                    CD-1                           initiation experiment                  only: 1/30                      no/val  (1979)

    98%             Mouse,     f    30    Dermal   0.57 mg/animal, 1x;          27 weeks  80% papillomas; promotor        p       Wood et al.
                    CD-1                           initiation experiment                  only: 4%                        yes/val (1980)

    > 95%           Mouse,     f    30    Dermal   0.46 mg/animal, 1x;          15 weeks  21/29 papillomas; promotor      p       Slaga et al.
                    Sencar                         initiation experiment                  only: 3/30                      no/val  (1980,1981)

                    Mouse,     f    30    Dermal   0.09 and 0.274 mg/animal,    26 weeks  43, 43% (or 39%) with skin      p       Chang et al.
                    CD-1                           1 x; initiation experiment             papillomas; vehicle control:    yes/val (1983)
                                                                                          100%

    > 99%           Mouse,     f    20    Dermal   3.4, 11.4 and 34 µg/         24 weeks  25, 90 and 95% with tumours;    p       Rice et al.
                    CD-1                           animal, 10x over 20 days;              0.5, 3, and 4.5 skin tumours/   yes/val (1988b)
                                                   initiation experiment                  animal; control: 20%

                    Mouse,     f    20    Dermal   7.5 µg/animal, 1x;           21 weeks  10% with skin tumours;          n       Amin et al.
                    CD-1                           initiation experiment                  solvent control:10%             yes/val (1990)

                    Mouse,     m/f  16/16 Dermal   365 µg/animal, 1x;           < 100     No skin tumours; solvent        n       Bhatt &
                    Sencar                         initiation experiment        weeks     control: no tumours             no/val  Coombs (1990)

    Purified        Mouse           50    s.c.     2 mg/animal, 1x              < 35      No tumours                      n       Bottomley &
                                                                                weeks                                     no/lc   Twort (1934)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    Purified        Mouse,          30    s.c.     10 mg/animal, 2x             15        No tumours                      n       Shear & Leiter
                    Jackson A                      (4-month interval)           months                                    no/ld   (1941)

    Spectrometer    Mouse,     m/f  50    s.c.     5 mg/animal in tricaprylin;  < 22      4/39 sarcomas after 4 months;   p       Steiner & Falk
    control         C57BI                          1x                           months    solvent control: 3/280          no/val  (1951)

                    Mouse,     m/f  40-50 s.c.     5 mg/animal in tricaprylin;  < 22-28   5/22 sarcomas after 5 months    p       Steiner (1955)
                    C57BI                          1x                           months                                    yes/ld

                    Mouse,     m    20    s.c.     1 mg/animal in arachis oil,  60-80     2/20 injection site tumours;    p       Boyland & Sims
                    C57BI                          1 x/week, 10 weeks           weeks     control: no tumours             no/val  (1967)

                    Mouse,     m/f  104   s.c.     0.1 mg/animal in poly-       70-75     70 weeks: 13/27m liver, 1/27    q       Grover et al.,
                    Swiss                          ethylene glycol on days      weeks     m and 1/21 f lung tumours;      no/val  (1975)
                    newborn                        1,2 and 3 after birth                  vehicle control: 9/30 m liver,
                                                                                          3/30 in and 1/15 f lung tumours

                    Mouse,          10    s.c.     1 mg, weekly; later 2 mg     350 days  No tumours; control: no         n       Barry & Cook
                                                   at longer intervals                    tumours                         no/ln,  (1934)
                                                                                                                          ld

    Purified        Mouse           50    i.p.     2 mg/animal, 1 ×             < 45      No tumours                      n       Bottomley &
                                                                                weeks                                     no/lc   Twort (1934)

    TLC             Mouse,     m/f  100   i.p.     Total dose 0.32 mg/animal    38-42     5/24 m and 2/11 f pulmonary     q       Buening et al.
    control         Swiss-                         in DMSO on days 1, 8         weeks     tumours; 6/24 m liver           yes/val (1979)
                    Webster                        and 15 after birth                     tumours; 1/24 m
                    BLU:Ha(ICR)                                                           lymphosarcoma; control:
                    newborn                                                               2/21 m and 7/38 1 lung tumours

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    Repurified,     Mouse,     m/f  80    i.p.     0.045, 0.09 and 0.18         39-41     Males: 4/27 lung and 6/27       p       Chang et al.
    256°C           Swiss-                         mg/animal in DMSO on         weeks     liver tumours; females; 1/11    yes/val (1983)
                    Webster                        days 1, 8 and 15 after birth           lung and 0/11 liver tumours;
                    BLU:Ha(ICR)                                                           vehicle control: no tumours
                    newborn

    > 98%           Mouse,     m/f  20-29 i.p.     6.3 and 210 µg/animal        26        7/10% and 15/0% m/f with        n       Busby et al.
                    Swiss-                         (total dose) in 3 aliquots   weeks     lung tumours; vehicle control:  yes/val (1989)
                    Webster                        on day 1, 8, and 15 after              14/7% m/f
                    BLU:Ha(ICR)                    birth
                    newborn

                    Rat             10    s.c.     2 mg/animal, weekly; later   < 626     4/10 tumours; control: 2/10     p       Barry & Cook
                                                   6 mg at longer intervals     days      sarcomas                        no/ln, (1934)
                                                                                                                          ld

    Purified        Rat             10    s.c.     1 mg/animal, weekly, 103     < 103     No tumours                      n       Boyland &
                                                   weeks                        weeks                                     no/ln   Burrows (1935)
                                                                                                                          ld

                    Rat,            5     s.c.     5 mg/animal, 7-9x            10        No tumours                      n       Pollia (1941)
                    Wistar                                                      months                                    no/ln

    99.6%           Rat,       f    35    Intrapulm.  1 and 3 mg/animal, 1 ×    < 135     14.3% and 28.6% tumour          p       Wenzel-
                    Osborne/                       weeks                                  incidence; control: no tumours  no/val  Hartung et al.
                    Mendel                                                                                                        (1990)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    Coronene
    > 96%           Mouse,     f    40    Dermal   5 or 15 µg/animal,           < 104     Low dose:1/39, high dose:       n       Habs et al.
                    NMRI                           4x/week, 104 weeks           weeks     2/40 local tumours at           yes/val (1980)
                                                                                          application site; vehicle
                                                                                          control: no tumours

    TLC             Mouse,     f    20    Dermal   0.1 mg, 5x; initiation       65 weeks  6/20 papillomas; promotor       q       Van Duuren et
    control         Swiss                          experiment                             only: 5/20; coronene only:      no/val  al. (1968)
                    ICR/Ha                                                                no tumours

    Cyclopenta[d]pyrene
    > 96%           Mouse,     f    40    Dermal   1.7, 6.8 and 27.2 µg/        112       Low dose: no tumours; high      q       Habs et al.
                    NMRI                           animal, 2x/week, 112         weeks     dose: 2/38 skin carcinomas,     yes/val (1980)
                                                   weeks                                  1/38 sarcomas;control: no
                                                                                          tumours

    > 98%           Mouse,     f    30    Dermal   23, 91, 226, 566 µg/         27 weeks  10, 21, 30, and 37%             p       Wood et al.
                    CD-1                           animal, 1x; initiation                 papillomas; promotor only: 4%   yes/val (1980)
                                                   experiment

    > 99.9%         Mouse,     f    30    Dermal   45, 136 and 407 µg/          57 weeks  Low dose: 17; med. dose: 11;    p       Cavalieri et al.
                    Swiss                          animal, 2x/week, 30 weeks              high dose: 7 skin tumours;      no/val  (1981b)
                                                                                          control: no tumours

    > 99.9%         Mouse,     f    30    Dermal   4.5, 14 and 41 µg/animal,    44 weeks  Low dose: 1/30; med. dose:      p       Cavalieri et al.
                    CD-1                           every other day, 20 days;              9/29; high dose: 6/29           no/val  (1981b)
                                                   initiation experiment                  papillomas; promotor only: 3/29

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     f    30    Dermal   10, 100 and 200 µg/          26 weeks  Low dose: 11 %; med. dose:      p       Raveh et al.
                    Sencar                         animal, 1x; initiation                 39%; high dose: 57%             no/val  (1982)
                                                   experiment                             papillomas; promotor only:
                                                                                          10%

    > 99%           Mouse,     m/f  8-14  i.p.     0.35, 0.7, 1.05, 1.4, and    26 weeks  62, 60, 56, 70, 86, 93%,        p       Busby et al.
                    Swiss-                         1.75 mg/animal (total dose)            77, 100, and 89, 100% m/f       yes/val (1988)
                    Webster                        in 3 aliquots on day 1, 8,             with lung tumours; vehicle
                    BLU:Ha(ICR)                    and 15 after birth                     control: 8, 8%
                    newborn

    > 99%           Rat,       f    20    Intra-   1.8 and 5.4 mg into 4th      < 34      No mammary tumours;             n       Cavalieri et al.
                    Sprague-              mammary  mammary gland, 1x            weeks     control: no tumours             no/val  (1988b)
                    Dawley

    Dibenz[a,h]anthracene
                    Mouse      m          Oral     1.5 mg/animal in PEG-400,    30 weeks  21 % forestomach papillomas;    q       Berenblum &
                    Swiss                          1 x; initiation experiment             promotor only: 14%              no/lc   Haran (1955)

                    Mouse      m/f  21/21 Drink-   0.8 mg/day/animal in olive   8-9       14/14 m and 13/13 f with        p       Snell & Stewart
                    DBA/2           con-  ing-     oil, 8-9 months              months    pulmonary adenomas; 14/14       no/val  (1962)
                                    trol: water                                           m and 10/13 f with alveologenic
                                    25/10                                                 carcinomas; control: 1 mouse
                                                                                          with tumour

                    Mouse,     f    20    Dermal   0.001, 0.01, and 0.1%,       < 21, 13  0.001%: 30% papillomas,         p       Wynder &
                    Swiss                          3x/week, life                or 9      30% carcinomas; 0.01%:          no/ld   Hoffmann
                    Millerton                                                   months    95/90% papilloma/carcinoma;             (1959a)
                                                                                          0.1%: 90%/75% papilloma/
                                                                                          carcinoma

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     m    < 50  Dermal   0.02 and 0.16 µg/animal,     32 weeks  33 and 38% with skin            p       Klein (1960)
                    Swiss                          1x; initiation experiment              tumours; acetone control: 13%   yes/val
                    albino
                    DBA/2Jax

    Chromatograph   Mouse,     f    20    Dermal   38 µg/animal, 2x/wk,         < 60      80% with skin tumours;          p       Lijinsky et al.
    recrystallized  Swiss                          44 weeks,                    weeks     vehicle control: 4%             no/val  (1965)

                    Mouse,     m/f  30/30 Dermal   m: 0.3% solution (= 1.5      < 29/22   m: 26% with papillomas after    p       Johnson (1968)
                    IF/Bcr                         mg/animal), 1x/week, 18      weeks     20 weeks, 100% after 29         no/val
                                                   weeks; f: 0.5% (= 1 mg/                weeks; f: 100% with breast
                                                   animal), 8x, every 2 weeks             tumours after 22 weeks

    > 99%           Mouse,     f    50    Dermal   1 drop, 3x/week, 112         112       6%, 8% and 32% with skin        p       Platt et al.
                    NMRI                           weeks; total doses: 37.8,    weeks     tumours; controls: 2-4%         no/val  (1990)
                                                   125, and 378 µg/animal

    > 99%           Mouse,     f    16    Dermal   83.5 and 167 µg/animal,      24 weeks  38 and 93% with skin tumours;   p       Platt et al.
                    NMRI                           1x; initiation experiment              vehicle control: no tumours     no/val  (1990)

                    Mouse           10    s.c./    0.2 mg/animal, 2x/week,      Life      3/10 with subcutaneous          p       Boyland &
                                          i.p.     50 weeks alternating                   sarcomas                        no/ln   Burrow, (1935)
                                                                                                                          ld

    Spectrometer    Mouse,     m/f  50    s.c.     0.02 mg/animal in            < 22      28/48 sarcomas after 4          p       Steiner & Falk
    control         C57BI                          tricaprylin; 1x              months    months solvent control: 3/280   no/val  (1951)

                    Mouse,     m/f  40-50 s.c.     0.02, 0.04 mg/animal in      < 22-28   7/21 and 6/18 sarcomas after    p       Steiner (1955)
                    C57BI                          tricaprylin; 1x              months    6 and 5 months                  yes/ld

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     m/f  20/19 s.c.     1 mg/animal, 1x/week,        60-80     20/20 m and 17/19 f with        p       Boyland & Sims
                    C57BL                          10 weeks                     weeks     sarcomas; control: no           no/val  (1967)
                                                                                          sarcomas

                    Mouse,     f    60    s.c.     10, 30, 90, 270 and 810      < 16      40, 35, 65, 75, and 90% with    p       Pott et al.
                    NMRI                           µg/animal, 1x                months    tumours                         no/val  (1973)

                    Mouse,     m/f  30    s.c.     0.15 and 0.3 mg/animal,      12 months B6 mice: 16/30 and 14/30; D2    p       Kouri et al.
                    B6, D2          (60)           1x                                     mice:1/30 and 0/30 with         no/val  (1983)
                                                                                          fibrosarcomas

    > 99%           Mouse,     f    47-50 s.c.     10, 30, 86 µg/animal, 1 ×    112       52, 46, and 63% with            p       Platt et al.
                    NMRI                                                        weeks     fibrosarcomas; controls: 2-6%   no/val  (1990)

    > 99%           Mouse,     m/f  40-50 s.c.     11.1 and 111 µg/animal       40 weeks  12/35 with pulmonary tumours;   p       Platt et al.
                    NMRI                           on day 2, 1x                           controls: 2/33 and 4/41         no/val  (1990)
                    newborn

                    Mouse,          10    i.v.     10 mg/kg, 1x                 20 weeks  100% lung tumours; control:     p       Shimkin &
                    A                                                                     21%                             no/val  Stoner(1975)

                    Rat             2x10  s.c.     2 mg/animal, weekly; later   < approx. 1/10 and 7/10 with tumours;     q       Barry & Cook
                                                   6 mg at longer intervals     200       control: 2/10                   no/ln,  (1934)
                                                                                days                                      ld

                    Rat             10-18 s.c./    1 mg/animal, 2x/week,        Life      3-6/10 and 9/18 with            p       Boyland &
                                    (6    i.p.     50 weeks                               subcutaneous sarcomas           no/ln   Burrows (1935)
                                    exp.) alterna-                                                                        ld
                                          ting

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Rat,            5     s.c.     5 mg/animal, 4-8x            10        2 with tumours after 8-9        p       Pollia (1941)
                    Wistar                                                      months    months                          no/ln

    99.3%           Rat,       f    35    Intrapulm. 0.1 mg/animal, 1x          < 123     57.1% tumour incidence;         p       Wenzel-
                    Osborne/                                                    weeks     control: no tumours             no/val  Hartung et
                    Mendel                                                                                                        al.(1990)

    > 99%           Rat,       f    20    Intra-   1.1 and 4.5 mg into 5th      20 weeks  No mammary tumours;             n       Cavalieri et al.
                    Sprague-              mammary  mammary gland, 1x                      control: no tumours             no/val  (1988a)
                    Dawley

    Chromatography  Hamster,   m/f  5/5   Dermal   8 drops of a 0.2% solution,  < 75      No tumours                      n       Shubik et al.
    control         Syrian          weeks          2x/week, 10 weeks                                                      no/ln,  (1960)
                    golden                                                                                                ld

                    Hamster,   m    46    Intra-   0.05 and 0.25 mg/animal,     < 110     0/46 and 0/46 respiratory tract q       Sellakumar &
                    Syrian                tracheal 1x/week, 30 weeks            weeks     tumours; control: no tumours    yes/val Shubik (11974)
                    golden

                    Hamster,              Intra-   10.3 and 0.9 mg/animal,      < 2 years 55 and 65% with tumours         p       Pott et al.
                    Syrian                trachea  1x/week, 20 weeks                                                      no/val  (1978)
                    golden

                    Monkey,                        Not specified                          No tumours                      n       Adamson &
                    Old world                                                                                             no/ld,  Sieber (1983)
                                                                                                                          lc

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    Dibenzo[a,e]pyrene
    Recrystallized  Mouse,     f    40/20 Dermal   0.05 and 0.1% solution,      15        16/40, 9/20 with papillomas     p       Hoffmann &
                    Swiss                          3x/week, 12 months           months    and 9/40, 6/20 with             no/val  Wynder (1966
                    albino                                                                epitheliomas; solvent
                    Ha/ICR/Mil                                                            control: no

    Recrystallized  Mouse,     f    28    Dermal   25 µg/animal, 10x over 20    6 months  10/28 papillomas; promotor      p       Hoffmann &
                    Swiss                          days; initiation experiment            only: 2/30                      no/val  Wynder (1966)
                    albino
                    Ha/ICR/Mil

    > 99%           Mouse,     f    21    Dermal   242 µg/animal, 1x;           26 weeks  240% papillomas; solvent        p       Cavalieri et al.
                    Sencar                         initiation experiment                  control: 9%                     yes/val (1989)

                    Mouse,     m/f  21/14 s.c.     0.6 mg/animal, 1x/month,     < 142     18/21 m and 14/14 f local       p       Lacassagne et
                    XVII nc/Z                      3 ×                          days m    sarcomas; no vehicle control    no/val  al. (1963b)
                                                                                or 126
                                                                                days f

                    Mouse      m/f  12/15 s.c.     0.6 mg/animal, 1x            < 196     10/12 m and 10/15 f local       p       Lacassagne et
                                                                                days m    sarcomas; no vehicle control    no/val  al. (1963b)
                                                                                or 220
                                                                                days f

    > 99%           Rat        f    19    Intra-   10 mg/gland, 1x, 8 glands,   < 40      1/19 with mammary tumours;      n       Cavalieri et al.
                    Sprague-              mammary                               weeks     control: 0/21 or 2/20           yes/val (1989)
                    Dawley

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    Dibenzo[a,h]pyrene
                    Mouse           74    Dermal   1 drop of a 0.15% solution   4.5       50% with skin tumours           p       Kleinenberg
                                                   alternate days, 55 or 86     months                                    no/lc   (1939)
                                                   times

    Recystallized   Mouse,     f    20    Dermal   0.05 and 0.1% solution,      11,15     16/20,15/20 with papillomas     p       Hoffmann &
                    Swiss                          3x/week, 12 months           months    and 13/20, 15/20 with           no/val  Wynder (1966)
                    albino                                                                epitheliomas; solvent
                    Ha/ICR/Mil                                                            control: no tumours

    Recrystallized  Mouse,     f    29    Dermal   25 µg/animal, 10x over 20    6 months  21/29 papillomas; promotor      p       Hoffmann &
                    Swiss                          days; initiation experiment            only: 2/30                      no/val  Wynder (1966)
                    albino
                    Ha/ICR/Mil

    96.6%           Mouse,     f    40    Dermal   120 µg/animal, 2x/week,      70 weeks  90% tumour incidence; solvent   p       Cavalieri et al.
                    Swiss                          30 weeks                               control: no tumours             no/val  (1977)

    Pure            Mouse,     f    30    Dermal   15.1, 60.5 and 181.4         17 weeks  55, 79, and 72% with skin       p       Chang et al.
                    CD-1                           µg/animal, 1x; initiation              tumours; controls: 0-10%        yes/val (1982)
                                                   experiment

    > 99%           Mouse,     f    24    Dermal   242 µg/animal, 1x;           26 weeks  75% papillomas; solvent         p       Cavalieri et al.
                    Sencar                         initiation experiment                  control: 9%                     yes/val (1989)

                    Mouse,     m/f  35/10 s.c.     0.6 mg/animal, 1x/month,     > 111/128 34/35 mand 1/10 f with local    p       Lacassagne et
                    XVII                           3 months                     days      sarcomas                        no/ld   al. (1958)
                                                   (average
                                                   latency)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     f    31    s.c.     0.2 mg/animal, 1x;           27 weeks  26/28 with tumours; solvent     p       Sardella et al.
                    CD-1                           initiation experiment                  control: 2/32                   no/val  (1981)

                    Mouse,     m/f  40    i.p.     3.8, 7.6 and 15.1 µg on      49-54     97% with pulmonary and 44%      p       Chang et al.
                    Swiss-                         days 1, 8 and 15 of life     weeks     with hepatic tumours; control:  yes/val (1982)
                    Webster                                                               pulmonary tumours 27%, no
                    BLU:Ha(ICR)                                                           hepatic tumours
                    newborn

    > 99%           Rat        f    20    Intra-   12 mg/gland, 1x, 8 glands    < 40      19/20 with mammary tumours;     p       Cavalieri et al.
                    Sprague-              mammary                               weeks     control: 0/21 or 2/20           yes/val (1989)
                    Dawley

    Dibenzo[a,i]pyrene
                    Mouse,     m    23    Dermal   1 drop of a saturated        > 7       21/23 papillomas and 8/23       p       Lacassagne et
                    XVII                           solution, 2x/week            months    epitheliomas;solvent control:   no/val  al. (1958)
                                                                                          no tumours (14 months)

                    Mouse,     f    20/10 Dermal   0.01 and 0.1 %, 3x/week,     < 16 and  0.01%: 10% papillomas, no       p       Wynder &
                    Swiss                          16 and 13 months             13 months carcinomas; 0.1%: 50%           no/ld   Hoffmann
                    Millerton                                                             papillomas, 10% carcinomas              (1959a)

    Recrystallized  Mouse,     f    20    Dermal   0.05 and 0.1 % solution,     15 months 16/40, 16/20 with papillomas    p       Hoffmann &
                    Swiss                          3x/week, 12 months                     and 13/20, 15/20 with           no/val  Wynder (1966)
                    albino                                                                epitheliomas; solvent
                    Ha/ICR/Mil                                                            control: no tumours

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    Recrystallized  Mouse,     f    30    Dermal   25 µg/animal, 10x over 20    6 months  12/30 papillomas; promotor      p       Hoffmann &
                    Swiss                          days; initiation experiment            only: 2/30                      no/val  Wynder (1966)
                    albino
                    Ha/ICR/Mil

                    Mouse,     f    20    Dermal   100 and 500 µg/animal,       22 weeks  40 and 80% with tumours;        p       Hecht et al.
                    Swiss                 1x; initiation experiment                       vehicle control: no tumours     no/val  (1981)
                    albino
                    Ha/ICR

    Pure            Mouse,     f    30    Dermal   15.1, 60.5 and 181.4 µg/     17 weeks  28, 67, and 70% with skin       p       Chang et al.
                    CD-1                           animal, 1x; initiation                 tumours; controls: 0-10%        yes/val (1982)
                                                   experiment

    > 99%           Mouse,     f    24    Dermal   242 µg/animal, 1x;           26 weeks  63% papillomas; solvent         p       Cavalieri et al.
                    Sencar                         initiation experiment                  control: 95%                    yes/val (1989)

                    Mouse,     m/f  17/18 s.c.     0.6 mg/animal, 1x/month,     3> 75/82  17/17 m and 16/18(f) with       p       Lacassagne et
                    XVII                           months                       days      local sarcomas                  no/ld   al. (1958)
                                                   (average
                                                   latency)

                    Mouse,     m/f  8/8   s.c.     2 mg/animal, 1x              2-3       100, 100% with skin tumours;    p       Waravdekar &
                    XVII/C57BI                                                  months    average latency: 74 days        no/ln,  Ranadive
                    hybrids                                                                                               ld      (1958)

                    Mouse,     m          s.c.     0.5 mg/animal, 1x            4-5       100% fibrosarcomas;             p       Homburger et
                    C57BL/6                                                     weeks     malignant cells identifiable    no/ld   al. (1962)
                                                                                          after 4-5 weeks

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     f    50    s.c.     0.1 mg/animal, 1x            75 weeks  40/41 with tumours; solvent     p       Sardella et al.
                    CD-1                                                                  control: no tumours             no/val  (1981)

                    Mouse,     m/f  40    i.p.     3.8, 7.6 and 15.1 µg on      49-54     97% with pulmonary and 54%      p       Chang et al.
                    Swiss-                         day 1, 8, and 15 of life     weeks     with hepatic tumours; control:  yes/val (1982)
                    Webster                                                               pulmonary tumours 27%, no
                    BLU:Ha(ICR)                                                           hepatic tumours
                    newborn

    > 99%           Rat,       f    19    Intra-   12 mg/gland, 1x, 8           < 40      18/19 with mammary tumours;     p       Cavalieri et al.
                    Sprague               mammary  glands                       weeks     control: 0/21 or 2/20           yes/val (1989)
                    Dawley

                    Hamster    m    6-10  s.c.     0.25, 0.5, 1 and 2 mg/       9-14      55, 90, 100, and 100% with      p       Wodinsky et al.
                    Syrian                         animal, 1x                   weeks     fibrosarcomas; vehicle control: no/val  (1964)
                                                                                (average  0%
                                                                                latency)

                    Hamster,   m/f  139/  s.c.     1 mg/animal, 1x              11 weeks  99/100% with fibrosarcomas      p       Wodinsky et al.
                    Syrian          157                                         (average                                  no/val  (1964)
                                                                                latency)

                    Hamster,   m    4/34  Intra-   0.5 and 2 mg/animal,         < 110     Tumours (i) 6/44 (trachea),     p       Sellakumar &
                    Syrian                tracheal weekly, 24 and 4 weeks,      weeks     37/44 (bronchi), 2/34           yes/val Shubik (1974)
                    golden                         respectively                           (trachea); (ii) 1/34 (larynx),
                                                                                          13/34 (bronchi); control: no
                                                                                          tumours

                    Hamster,   m/f  24/24 Intra-   0.5 and 1 mg/animal,                   65 and 75% respiratory          p       Stenback &
                    Syrian                tracheal 1 x/week, 17 and 12 weeks,             tumours (bronchi, trachea);     no/ld   Sellakumar
                    golden                         respectively                           shortest latency: 8 weeks               (1974)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Monkey,                        Not specified                          No tumours                      n       Adamson &
                    Old world                                                                                             no/lc   Sieber (1983)

    Dibenzo[a,l]pyrene
    Recrystallized  Mouse,     f    20    Dermal   0.05 and 0.1% solution,      11, 14    17/20, 18/20 with papillomas    p       Hoffmann &
                    Swiss                          3x/week, 12 months           months    and 17/20, 18/20 with           no/val  Wynder
                    albino                                                                epitheliomas; solvent                   (1966)
                    Ha/ICR/Mil                                                            control: no tumours

    Recrystallized  Mouse,          30    Dermal   25 µg/animal, 10x over 20    6 months  18/30 papillomas; 1/30          p       Hoffmann &
                    Swiss                          days; initiation experiment            epitheliomas; promotor          no/val  Wynder
                    albino                                                                only: 2/30                              (1966)
                    Ha/ICR/Mil

                    Mouse,     f    19-21 Dermal   55, 200, 240, 350 and 700    6 months  20, 19, 21, 19 and 16 with      p       Masuda &
                    Swiss ICR                      µg/animal given in 55, 40,             skin tumours; no solvent        no/val  Kagawa
                                                   24, 7 and 7 applications               control group                           (1972)

    > 99%           Mouse,     f    24    Dermal   242 µg/animal, 1x;           26 weeks  92% papillomas; solvent         p       Cavalieri et al.
                    Sencar                         initiation experiment                  control: 9%                     yes/val (1989)

    Pure, 161-      Mouse,     f    24    Dermal   10, 30 and 90 µg/animal,     15 weeks  23/24, 22/24 and 24/24 with     p       Cavalieri et al.
    162°C)          Sencar                         1x; initiation experiment              tumours;control; no tumours     yes/val (1991)

    Pure            Mouse,     f    24    Dermal   1.2, 6 and 30 µg/animal,     7 weeks   22/24, 20/24 and 20/24 with     p       Cavalieri et al.
                    Sencar                         1x; initiation experiment              tumours; 2 control: no tumours  yes/val (1991)

    Chomatography   Mouse,     f    24    Dermal   30 µg/animal, 1x; initiation 27 weeks  7/24 with tumours               p       Cavalieri et al.
    purified        Sencar                         experiment without                                                     yes/val (1991)
                                                   promotion

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     m/f  12/12 s.c.     0.6 mg/animal, 1x/month,     < 7       All animals with local          p       Lacassagne et
                    XVII                           2 months (some animals,      months    sarcomas (mean latent period:   no/val  al.(1968a)
                    nc/ZE                          3rd injection after 2 months)          120 days); control: no tumours

    > 99%           Rat,       f    9     Intra-   1.2 mg/gland, 1x, 8 glands   < 40      9/9 with mammary tumours;       p       Cavalieri et al.
                    Sprague-              mammary                               weeks     control: 0/21 or 2/20           yes/val (1989)
                    Dawley

                    Rat        f    20    Intra-   76 and 302 µg/gland, 1x,     < 24      20/20 and 19/20 with            p       Cavalieri et al.
                    Sprague-              mammary  8 glands                     weeks     mammary tumours; control:       yes/val (1991)
                    Dawley                                                                1/18

    Fluoranthene
                    Mouse,          2x10  Dermal   0.3% in benzene, 2x/week,    < 501     No tumours                      n       Barry et al.
                                                   life                         days                                      no/ld   (1935)

                    Mouse,     f    20    Dermal   0.1 % solution, 3x/week,     < 17      No papillomas or carcinomas     n       Wynder &
                    Swiss                          life                         months                                    no/ld   Hoffmann
                    Millerton                                                                                                     (1959a)

                    Mouse,     f    20    Dermal   1%, 3x/week, 12 months       15        At 12 months 0/20 tumours;      n       Hoffmann et al.
                    Swiss                                                       months    no vehicle control              no/val  (1972)
                    Ha/ICR/Mil

    99.9%           Mouse,     f    30    Dermal   0.1 mg/animal, 10x over      24 weeks  1/29 skin tumours; solvent      n       Hoffmann et al.
                    Swiss                          20 days; initiation                    control: 1/30                   no/val  (1972)
                    Ha/ICR/Mil                     experiment

    Recrystallized  Mouse,     m    15    Dermal   250 µg/animal in decalin,    82 week   No papillomas or carcinomas;    n       Horton &
                    C3H                            2x/week, 82 weeks                      solvent control: 2/13           no/val  Christian (1974)
                                                                                          papillomas

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    Purified,       Mouse,     f    50    Dermal   40 µg/animal, 3x/week,       440 days  No tumours observed;            n       Van Duuren &
    107-            Swiss                          life                                   controls: no tumours            no/val  Goldschmidt
    109°C)          ICR/Ha                                                                                                        (1976)

                    Mouse,     m/f  7/7   s.c.     10 mg/animal, 5x             19        No tumours                      n       Shear (1938)
                    Jackson A                                                   months                                    no/ld,
                                                                                                                          ln

                    Mouse,     m/f  10/10 s.c.     0.6 mg/animal, 1x/month,               No sarcomas                     n       Buu-Hoi (1964)
                    XVII nc/Z                      3x                                                                     no/ld,
                                                                                                                          ln

    99%             Mouse,     m/f  20-31 i.p.     0.7 and 3,5 mg/animal        24 weeks  23, 15, and 74, 38% m/f with    p       Busby et al.
                    Swiss-                         (total dose) in 3 aliquots             lung tumours; vehicle control:  yes/val (1984)
                    Webster                        on days 1, 8 and 15 after              4,14%
                    BLU:Ha(ICR)                    birth
                    newborn

    > 99.5%         Mouse,     m/f  22/30 i.p.     0.7 and 3.5 mg/animal        52 weeks  43, 35, and 65, 86% with lung   p       La Voie et al.
                    CD-1                           (total dose) in 3 aliquots on          tumours; 64, 0% and 100, 7%     yes/val (1994)
                    newborn                        days 1, 8, and 15 after birth          with hepatic tumours; vehicle
                                                                                          only: 17, 12% (lung) and 17, 6%
                                                                                          (liver)

    Fluorene
                    Mouse           100   Dermal   Dissolved in 90% benzene     9 months  No tumours                      n       Kennaway
                                                                                                                          no/ld,  (1924)
                                                                                                                          lc

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     m/f  10/10 Dermal   60 µg/animal, 2x/week,       31 weeks  No skin tumours                 n       Riegel et al.
                    CF1                            31 weeks                                                               no/ld   (1951)

    'Pure'          Mouse,     m    100   Dermal   3 drops, 1x/week of approx.  < 1 year  After 9 months 10/100           n       Graffi et al.
                    white                          3% solution, 1 year;                   survived, no tumours; promotor  no/val  (1953)
                                                   initiation experiment                  only: 0.08 tumour/animal

                    Mouse,     m    5     i.p.     1000 mg/kg, 1x               < 5       No effects                      n       Shubik & Della
                    Swiss                                                       months                                    no/ld   Porta (1957)
                                                                                                                          ln

                    Mouse,     m    10    s.c.     10 mg/animal, 7x over        19        No tumours                      n       Shear(1938)
                    Jackson A                      16 months                    months                                    no/ln,
                                                                                                                          ld

    Highly          Rat,       f    20    Oral     0.05% diet; 4.3 mg/rat per   10.7      2/11 carcinomas (renal pelvis,  q       Morris et al.
    purified        Buffalo               (diet)   day = 796 mg/rat (total      months    ureter); control: 4/16 with     no/ld   (1960)
                                                   intake) over 6 months                  carcinomas

    Highly          Rat,       f    18    Oral     0.05% diet; 4.6 mg/rat per   < 20.1    7/18 tumours; control: 4/18 or  q       Morris et al.
    purified        Buffalo               (diet)   day = 2553 mg/rat (total     months    15/18 tumours                   no/val  (1960)
                                                   intake) over 18 months

    Recrystallized  Mouse,     f    30    Dermal   25 µg/animal, 10x over 20    6 months  5/30 papillomas; promotor:      q       Hoffmann &
                    Swiss                          days; initiation experiment            2/30                            no/val  Wynder (1966)
                    Ha/ICR/Mil

    Recrystallized  Mouse,     f    20    Dermal   0.05 and 0.1 % solution,     15        Dioxane solvent: no tumours;    q       Hoffmann &
                    Swiss                          3x/week, 12 months           months    acetone solvent: dose-related   no/val  Wynder (1966)
                    albino                                                                tumour increase
                    Ha/ICR/Mil

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    > 96%           Mouse,     f    40    Dermal   3.4, 5.6, 9.2 µg/animal,     <2 years  3, 0, 0% with local tumours;    n       Habs at a
                    NMRI                           2x/week, life                          control: no tumours             yes/val (1980)

                    Mouse,     f    25    Dermal   100 µg/animal, 10x over      25 weeks  90% with skin tumours; vehicle  p       Rice et al.
                    Crl:CD1                        20 days; initiaton                     control: < 5%                   yes/val (1986)
                    (ICR)BR                        experiment

    > 99%           Mouse,     f    25    Dermal   110 µg/animal, 10x over      23 weeks  72% tumours, 2.1 skin           p       Rice et al.
                    CD-1                           20 days; initiation                    tumours/animal; control:        yes/val (1990)
                                                   experiment                             no tumours

                    Mouse,     m/f  14/14 s.c.     0.6 mg/animal, 1x/mth,       Average,  Sarcomas: 10/14 m and 1/14 f    p       Lacassagne et
                    XVII                           3 months                     265 days                                  no/val  al. (1963a)
                    nc/Z                                                        m, 145
                                                                                days f

    > 99%           Mouse,     m/f  11/9  i.p.     580 µg/animal in DMSO        < 52      9% hepatic or 0% lung           n       LaVoie et al.
                    CD-1                           on days 1, 8 and after       weeks     tumours; controls: 6%/0%        yes/val (1987)
                    newborn                        birth (total dose)

    99.4%           Rat,       f    35    Intra-   0.16, 0.83 and 4.15          116/109/  3/35, 8/35 and 21/35 with lung  p       Deutsch-
                    Osborne/              pulm.    mg/animal, 1x                92 weeks  tumours; control: no tumours    yes/val Wenzel et al.
                    Mendel                                                                                                        (1983)

    5-Methylcholanthrene
    > 99.9%         Mouse,     f    20    Dermal   0.1 mg/animal, 3x/week,      35 weeks  20/20 with 85 skin tumours      p       Hecht et al.
                    Swiss                          35 weeks                     (solvent  by 25 week; 20/20 with 99       no/val  (1974)
                    Ha/ICR/Mil                                                  control:  tumours and 12/20 with 37
                                                                                72 weeks) carcinomas by 35 wks; solvent
                                                                                          control: no tumours

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    > 99.9%         Mouse,     f    20    Dermal   10, 30 and 100 µg, 10x       24 weeks  Low dose: 20/20 mice with       p       Hecht et al.
                    Swiss                          over 20 days; initiation               110 skin tumours; med dose:     no/val  (1974)
                    Ha/ICR/Mil                     experiment                             20/20 with 160 skin tumours;
                                                                                          high dose: 17/18 with 96 skin
                                                                                          tumours; solvent control: no
                                                                                          tumours

                    Mouse,     f    20    Dermal   5 and 10 µg/animal,          62 weeks  Low dose: 9/20 with 22 skin     p       Hecht et al.
                    Swiss                          3x/week, 62 weeks                      tumours, 6/20 with 7            yes/val (1976a)
                    Ha/ICR                                                                carcinomas; high dose: 15/20
                                                                                          with 38 tumours, 10/20 with
                                                                                          12 carcinomas; solvent
                                                                                          control: no tumours

    Highly          Mouse,     f    20    Dermal   1 and 3 µg, 10x over         24 weeks  Low dose: 2/20 mice with 2      p       Hecht et al.
    purified        Swiss                          20 days; initiation                    skin tumours; high dose:        yes/val (1976a)
                    Ha/ICR                         experiment                             20/20 with 45 skin tumours
                                                                                          (1 carcinoma); solvent control:
                                                                                          no tumours

    > 99.9%         Mouse,     f    8x20  Dermal   3 and 10 µg, 10 × over 20    24 weeks  Low dose: 55-95% of mice        p       Hecht et al.
                    Swiss                          days; initiation experiment            with skin tumours; high dose:   yes/val (1978)
                    Ha/ICR/Mil                                                            80-90%; solvent control: no
                                                                                          tumours

    > 99.9%         Mouse,     f    20    Dermal   1 and 3 µg, 10x over 20      24 weeks  Low dose: 75% of mice with      p       Hecht et al.
                    Swiss Ha/ICR                   days; initiation experiment            skin tumours; high dose: 85%    no/val  (1979)
                    outbred

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     f    20    Dermal   1 or × or 3 µg/animal, 10x   21 weeks  55, 75, and 90% with skin       p       Amin et al.
                    Swiss CD-1                     over 20 days; initiation               tumours; solvent control: 5%    yes/val (1981)
                                                   experiment

    HPLC            Mouse,     f    20    Dermal   8 and 24 µg/animal, 1x;      26 weeks  80 and 90% tumour-bearing       p       Hecht et al.
    purified        CD-1                           initiation experiment                  animals; solvent control: 10%   yes/val (1985)

                    Mouse,     f    20    Dermal   8 µg/animal, 1x; initiation  21 weeks  65% with skin tumours;          p       Amin et al.
                    CD-1                           experiment                             solvent control: 5%             yes/val (1985b)

                    Mouse,     f    20    Dermal   24.2 µg/animal, 1x;          26 weeks  90% with tumours; 5.2           p       El-Bayoumy et
                    CD-1                           initiation experiment                  tumours/animal; solvent         no/val  al. (1986)
                                                                                          control: 10%/0.1

    > 99%           Mouse,     f    20    Dermal   3.6, 12.1 and 36 µg/         24 weeks  100, 100 and 100% with          p       Rice et al.
                    CD-1                           animal, 10x over 20 days;              tumours; 9.2, 10.7 and 9.4      yes/val (1988b)
                                                   initiation experiment                  tumours/animal; solvent
                                                                                          control: 20%

                    Mouse,     f    20    Dermal   8 µg/animal, 1x;initiaUon    21 weeks  85% with skin tumours;          p       Amin et al.
                    CD-1                           experiment                             solvent control: 10%            yes/val (1990)

                    Mouse,     f    20    Dermal   8 µg/animal, 1x; initiation  26 weeks  65% with skin tumours; solvent  p       Amin et al.
                    CD-1                           experiment                             control: 10%                    yes/val (1992)

                    Mouse,     m/m  20/   s.c.     2 mg/animal in tricaprylin,  6 months  Swiss mice: no local tumours;   q       Dunlap &
                    Swiss/          2x10           1x                                     16/20 mice died; C3H mice:      no/ld   Warren (1943)
                    C3H                                                                   7/10 or 3/10 local sarcomas

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    Highly          Mouse,     m    25    s.c.     50 µg/animal in              32 weeks  22/25 mice with 24              p       Hecht et al.
    purified        057BL                          trioctanoin, 1 x/2 weeks,              fibrosarcomas; vehicle          no/val  (1976b)
                                                   20 weeks                               control: no tumours

    HPLC            Mouse,     m/f  35/48 i.p.     1.9 µg/animal on day 1;      Weaned    20/21% with pulmonary           p       Hecht et al.
    purified        ICR/Ha                         3.9 µg on day 8; 7.8 µg      after 3   tumours; 23/12% with            yes/val (1985)
                    newborn                        on day 15                    weeks;    hepatic tumours; solvent
                                                                                sacri-    control: 4/7% and 2/2%
                                                                                ficed
                                                                                after 35
                                                                                weeks

    > 99%           Rat        f    20    Intra-   0.97 and 3.9 mg into 5th     20 weeks  No mammary tumours;             n       Cavalieri et al.
                    Sprague-              mammary  mammary gland, 1x                      control: no tumours             no/val  (1988a)
                    Dawley

    1-Methylphenanthrene
    >99.5%          Mouse,     f    20    Dermal   100 µg, 10x over 20 days;    24 weeks  No tumours; vehicle control:    n       LaVoie et al.
                    Swiss                          initiaton experiment                   no tumours                      no/val  (1981b)
                    Ha/ICR

    Naphthalene
                    Mouse                 Dermal   Several times/wk,            < 11      No skin tumours                 n       Kennaway
                                                   < 11 months                  months                                    no/lc   (1930)

    Highly          Mouse,          25;   Dermal   0.5% in benzene, 6x/week     Life      4/25 with lymphatic             q       Knake (1956)
    purified        SW inbred       con-           for 3 weeks, then 2x/wk for            leukaemia; 1/25 lymphosarcoma   no/lc,
                                    trol:          life                                   of thymus; 4/25 with benign     ln
                                    21                                                    tumours; benzene only: 2/21
                                                                                          with sarcomas; 1/21 with lung
                                                                                          adenoma

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     f    30    Dermal   0.25 mg/animal + 3 µg        78 weeks  5/30 lymphomas; inhibitory      q       Schmeltz et al.
                    ICR/Ha                         benzo[a]pyrene, 3x/wk,                 effect on skin tumours;         no/val  (1978)
                                                   78 weeks; co-carcinogenicity           naphthalene only: no skin
                                                   test                                   tumours

    98-99%          Mouse,     f    30    Inha-    0.05 and 0.15 mg/l,          6 months  29 and 30% with pulmonary       q       Adkins et al.
                    A/J                   lation   6 h/day, 5 days/week,                  tumours; control: 21%           yes/val (1986)
                                                   6 months                               (increase in treatment groups
                                                                                          not significant)

    > 99%           Mouse,     m/f  75    Inha-    0.053 and 0.16 mg/litre,     103       Significantly increased         q       Abdo et al.
                    B6C3F1          (150) lation   6 h/day, 5 days/week,        weeks     pulmonary alveolar and          yes/val (1992);
                                                   103 weeks                              bronchiolar adenomas in                 National
                                                                                          females; no cararacts                   Toxicology
                                                                                                                                  Program
                                                                                                                                  (1992b)

                    Mouse           23    Bladder  1x (dose unspecified)        7 months  1/23 bladder carcinoma after    -       Boyland et al.
                                          implant                                         1 month; "inert" substance:             (1964)
                                                                                          higher rate of bladder
                                                                                          carcinoma

                    Rat,            28    Oral     10-20 mg/animal,             Life      No tumours                      n       Schmahl
                    BDI/BDI II            (diet)   6x/week, 70 weeks                                                      no/ld   (1955)
                    inbred

                    Rat,            10    s.c.     20 mg/animal, 1x/week,       Life      No tumours                      n       Schmahl
                    BDI/BDI II                     40 weeks                                                               no/ln   (1955)
                    inbred

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    Crude,          Rat,            38    s.c.     0.5 g/kg, 2x/month, 3.5      Life      5 malignant tumours (4/38       q       Knake(1956)
    90%             'white'                        months                                 Imphosarcomas, 1/38 uterine     no/val
                                                                                          sarcoma); 1 benign tumour;
                                                                                          vehicle control: 1/38
                                                                                          lymphosarcoma and 1 benign
                                                                                          tumour

                    Rat,            10    i.p.     20 mg/animal, 1x/week,       Life      No tumours                      n       Schmahl
                    BDI/BDI II                     40 weeks                                                               no/ln   (1955)
                    inbred

    Perylene
    Recrystalized   Mouse,     f    20    Dermal   0.8 mg/animal, 1x;           58-60     3/20 papillomas; promotor       n       Van Duuren et
                    Swiss                          initiation experiment        weeks     only: 1/20 with papillomas;     no/val  al. (1970)
                    ICR/Ha                                                                pure substance only: no tumours

    Recrystallized  Mouse,     m    20    Dermal   75 µg/animal in decalin,     82 weeks  No skin tumours; solvent        n       Horton &
                    C3H                            2x/week, 82 weeks                      control: 2/13 papillomas        no/val  Christian
                                                                                                                                  (1974)

    Phenanthrene
                    Mouse           100   Dermal   Dissolved in 90% benzene     9 months  No tumours                      n       Kennaway
                                                                                                                          no/ld,  (1924)
                                                                                                                          lc

    'Pure'          Mouse,     m    100   Dermal   3 drops, 1x/week of approx.  < 1 year  After 12 months 6/100           n       Graft et al.
                    white                          3% solution, 1 year;                   survived with a total of 1      no/val  (1953)
                                                   initiation experiment                  tumour; 0.16 tumour/animal;
                                                                                          promotor only: 0.08
                                                                                          tumour/animal

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,          20    Dermal   54 mg/animal, 3x/wk, total:  24 weeks  5/20 survivors with 12          q       Salaman & Roe
                    'S'                            10x; initiation experiment             papillomas; promotor only:      yes/val (1956)
                                                                                          4/19 survivors/4 papillomas

    High purity     Mouse,     m/f  10/10 Dermal   0.3 mg, 4x on days 0, 2, 6   24 weeks  4/19 papillomas; solvent        q       Roe (1962)
                    'stock                         and 8; initiation experiment           control: 2/20                   yes/val
                    albino'

    TLC             Mouse,     f    30    Dermal   1.8 mg/animal, 1x;           35 weeks  40% with papillomas;            p       Scribner (1973)
    purified        CD-1                           initiation experiment                  promotor only: 3%               no/val

    > 98%           Mouse,     f    30    Dermal   1.8 mg/animal, 1x;           36 weeks  5/30 papillomas; solvent        q       Wood et al.
                    CD-1                           initiation experiment                  control: 2/30                   no/val  (1979)

                    Mouse,     f    20    Dermal   100 µg, 10x over 20 days;    24 weeks  No skin tumours observed;       n       LaVoie et al.
                    Swiss                          initiation experiment                  vehicle control: no tumours     no/val  (1981b)
                    Ha/ICR

                    Mouse,     m/f  40-50 s.c.     5 mg/animal in tricaprylin;  < 22-28   No sarcomas after 8 months      n       Steiner (1955)
                    C57BI                          1x                           months                                    yes/ld

                    Mouse,     m/f  10/10 s.c.     0.3 mg, 5x on days 0, 2,     24 weeks  3/17 papillomas; solvent        n       Roe (1962)
                    'stock                         4, 6 and 8; initiation                 control: 2/20                   yes/val
                    albino'                        experiment

                    Mouse,     m/f  57    s.c.     40 µg/animal; 1x             < 62      3/49 lung adenomas; control:    n       Grant & Roe
                    stock                          administered to neonatal     weeks     8/34 and 5/38                   yes/val (1963)
                    albino'                        mice
                    newborn

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    > 98%           Mouse,          100   i.p.     35, 70 and 140 µg/animal     38-42     6/35 pulmonary adenomas;        n       Beuning et al.
                    Swiss-                         in DMSO on days 1, 8         weeks     DMSO only: 9/59                 yes/val (1979)
                    Webster                        and 15 after birth
                    BLU:Ha(ICR)
                    newborn

                    Rat,       f    10    Oral     200 mg/rat, 1x; experiment   60 days   No tumours at 60 days;          n       Huggins &
                    Sprague-                       on mammary tumours                     controls: 8/164 after 310 days  no/ln,  Yang (1962)
                    Dawley                                                                                                lc

    99.9%           Rat,       f    35    Intrapulm. 1, 3 and 10 mg/animal, 1x  < 135     No tumours; control: no         n       Wenzel-Hartung
                    Osborne/                                                    weeks     tumours                         no/val  et al.(1990)
                    Mendel

    Pyrene
                    Mouse           2x20  Dermal   1% in benzene, 2x/week,      < 717     1/20 and 1/20 papillomas        n       Barry et al.
                                                   life                         days                                      no/ld   (1935)

                    Mouse           40    Dermal   0.3% in benzene, 2x/         < 680     No skin lesions                 n       Badger et al.
                                                   week, < 680 days             days                                      no/ld   (1940)

    'Pure'          Mouse,     m    150   Dermal   3 drops, 1x/week of a        < 1 year  After 6 months 18/150           n       Graffi et al.
                    white                          0.3% solution, 1 year;                 survived with a total of 1      no/val  (1953)
                                                   initiation experiment                  tumour; 0.06 tumour/animal;
                                                                                          promotor only: 0.08
                                                                                          tumour/animal

                    Mouse,          20    Dermal   25 mg/animal, 3x/week;       24 weeks  6/20 mice with 9 papillomas;    q       Salaman & Roe
                    'S'                            total:10x; initiation                  promotor only: 4/19 mice with   yes/val (1956)
                                                   experiment                             4 papillomas

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

                    Mouse,     f    5     Dermal   10%, 3 x/week, life          < 18      No skin tumours                 n       Wynder &
                    Swiss                                                       months                                    no/ld,  Hoffmann
                    Millerton                                                                                             ln      (1959a)

    TLC             Mouse,     f    30    Dermal   2 mg/animal, 1x; initiation  35 weeks  17% with papillomas;            q       Scribner (1973)
    purified        CD-1                           experiment                             promotor only: 3%               no/val

    High purity     Mouse,     m    20    Dermal   250 µg/animal in decalin,    82 weeks  3/13 papillomas; solvent        q       Horton &
                    C3H                            2x/week, 82 weeks                      control: 2/13                   no/val  Christian (1974)

    Recrystallized  Mouse,     f    50    Dermal   12 or 40 µg/animal,          < 440     No skin tumours observed;       n       Van Duuren &
                    Swiss                          3 x/week, 368 or 440 days    days      control: no tumours             no/val  Goldschmidt
                    ICR/Ha                                                                                                        (1976)

    High purity     Mouse,     f    50    Dermal   4 and 12 µg/animal + 5 µg    33 weeks  High dose: 13/50 papillomas,    n       Goldschmidt et
                    Swiss                          benzo[a]pyrene, 3x/week,               5/50 carcinomas; benzo[a]-      no/val  al. (1973)
                    ICR/Ha                         33 weeks; co-carcinogenicity           pyrene only: 6/50 papillomas;
                                                   test                                   pyrene only: no tumours

    Recrystallized  Mouse,     f    50    Dermal   4, 12 and 40 µg/animal       368 or    12/26/35 mice with papillomas,  p       Van Duuren &
                    Swiss                          + 5 µg benzo[a]pyrene,       440 days  6/20/26 with squamous cell      no/val  Goldschmidt
                    ICR/Ha                         3x/week, 368/368/440                   carcinomas; positive control:           (1976)
                                                   days; co-carcinogenicity               15, 11 tumours; solvent control:
                                                   test                                   no tumours

    > 98%           Mouse,     f    30    Dermal   20.2 and 80.9 µg/animal,     27 weeks  14 and 10% with tumours;        n       Wood et al.
                    CD-1                           1x; initiation experiment              vehicle control: 10%            yes/val (1980)

    Crystals        Mouse,     m/f  30    s.c.     10 mg/animal, 2 × at 4-      < 18      No malignant tumours            n       Shear & Leiter
                    Jackson A                      month interval               months                                    no/ld   (1941)

    Table 90. (continued)

                                                                                                                                               

    Purity          Species,   Sex  No./  Route of Dosage                       Study     Incidence and type of tumour    Result  Reference
                    strain          sex/  admin.                                duration                                  Stat./
                                    group                                       at death/                                 Val.
                                                                                sacrifice
                                                                                                                                               

    Recrystallized, Mouse,     m/f  23-28 i.p.     86.1 and 1750 µg/animal      26 weeks  17, 4, and 7, 12% m/f with      n       Busby et al.
    HPLC            Swiss-                         (total dose) in 3 aliquots             lung tumours; vehicle control:  no/val  (1989)
                    Webster                        on days 1, 8 and 15                    14, 7% m/f
                    BLU:Ha(lCR)                    after birth
                    newborn

    > 99%           Hamster,   m    48    Intra-   3 mg/animal, 1x/week,        < 110     1/48 tumours of the trachea,    n       Sellakumar &
                    Syrian                tracheal 30 weeks                     weeks     2/48 malignant lymphomas;       yes/val Shubik (1974)
                    golden                                                                control: 0/82 and 2/82

    Triphenylene
                    Mouse           10    Dermal   0.3% in benzene, 2x/         < 548     No skin lesions                 n       Barry et al.
                                                   week, life                   days                                      no/ln,  (1935)
                                                                                                                          ld

    Recrystallized  Mouse,     m    20    Dermal   250 µg/animal in decalin,    82 weeks  No skin tumours; solvent        n       Horton &
                    C3H                            2x/week, 82 weeks                      control: 2/13 papillomas        no/val  Christian
                                                                                          (1974)
                                                                                                                                               

    Result: p(ositive), n(egative), q(uestionable); Stat, statistical evaluation: yes or no; Val, validity: val, valid; ld, limited design; lc,
    limited documentation; ls, limited survival; ln, limited number of animals
    intrapulm., intrapulmonary injection; i.p., intraperitoneal injection; s.c., subcutaneous injection; i.m., intramuscular injection
    m, male; f, female
    TLC, thin-layer chromatography; DMSO, dimethylsulfoxide; HPLC, high-performance liquid chromatography; DMBA, 7,12-dimethylbenz[a]anthracene

    Table 91. Overview of carcinogenicity of polycyclic aromatic hydrocarbons

                                                                                                                                  

    Compound                Carcinogenicity  Species       Route of administration
                            (weight of                     No. of studies with positive, negative, and questionable results
                            evidence)                                                                                             
                                                           Oral        Dermal      s.c./i.m.   i.p./i.v.   inh./tr.    Other
                                                                                                                              
                                                           +   -   ±   +   -   ±   +   -   ±   +   -   ±   +   -   ±   +   -   ±
                                                                                                                                  

    Acenaphthene            Questionable     Mouse                         1   1
    Acenaphthylene                                         No studies
    Anthanthrene            Positive         Mouse                     2   6           1                   1               1
    Anthracene              Negative         Mouse                         6   1       1           1
                                             Rat           2                       1   2               1       1
                                             Rabbit                                                                        1
    Benz[a]anthracene       Positive         Mouse         2       1   7   4       4   2           2                   1
                                             Rat               1           1           2           1                       1
                                             Hamster                       2                                           1
    Benzo[b]fluoranthene    Positive         Mouse                     7           1           1
                                             Rat                                                           1
                                             Hamster                                                           1
    Benzo[j]fluoranthene    Positive         Mouse                     3       1               1
                                             Rat                                                           1
    Benzo[ghi]fluoranthene  (Negative)       Mouse                         2
    Benzo[k]fluoranthene    Positive         Mouse                     1   2   1   1                   1
                                             Rat                                                           1
    Benzo[a]fluorene        (Questionable)   Mouse                         1   1       1
    Benzo[b]fluorene        (Questionable)   Mouse                             1
    Benzo[ghi]perylene      Negative         Mouse                         8           2
                                             Rat                                                               1
    Benzo[c]phenanthrene    (Positive)       Mouse                     2       2       1   1
                                             Rat                                           1

    Table 91. (continued)

                                                                                                                                  

    Compound                Carcinogenicity  Species       Route of administration
                            (weight of                     No. of studies with positive, negative, and questionable results
                            evidence)                                                                                             
                                                           Oral        Dermal      s.c./i.m.   i.p./i.v.   inh./tr.    Other
                                                                                                                              
                                                           +   -   ±   +   -   ±   +   -   ±   +   -   ±   +   -   ±   +   -   ±
                                                                                                                                  

    Benzo[a]pyrene          Positive         Mouse         5           26          6           3           1           2
                                             Rat           2                       1           1           9           3
                                             Hamster       1           1   1   1                           11  1   1
                                             Dog                                                                       1
                                             Cattle                                    1
                                             Pig                                       2
                                             Monkey                                1   1   1               1
    Benzo[e]pyrene          Questionable     Mouse                     2   1   5                       1
                                             Rat                                                               1           1
    Chrysene                Positive         Mouse                     11  9   1   3   3   1   1   2   1
                                             Rat                                   1   2                   1
    Coronene                (Questionable)   Mouse                         1   1
    Cyclopenta[cd]pyrene    Positive         Mouse                     4       1               1
                                             Rat                                                                           1
    Dibenz[a,h]anthracene   Positive         Mouse         1       1   6           8           1
                                             Rat                                   2       1               1               1
                                             Hamster                       1                               1       1
                                             Monkey                                                                        1
    Dibenzo[a,e]pyrene      Positive         Mouse                     3           2
                                             Rat                                                                           1
    Dibenzo[a,h]pyrene      Positive         Mouse                     6           2           1
                                             Rat                                                                       1
    Dibenzo[a,i]pyrene      Positive         Mouse                     7           4           1
                                             Rat                                                                       1
                                             Hamster                               2                       2
                                             Monkey                                                                        1
    Dibenzo[a,l]pyrene      Positive         Mouse                     7           1
                                             Rat                                                                       2

    Table 91. (continued)

                                                                                                                                  

    Compound                Carcinogenicity  Species       Route of administration
                            (weight of                     No. of studies with positive, negative, and questionable results
                            evidence)                                                                                             
                                                           Oral        Dermal      s.c./i.m.   i.p./i.v.   inh./tr.    Other
                                                                                                                                  
                                                           +   -   ±   +   -   ±   +   -   ±   +   -   ±   +   -   ±   +   -   ±
                                                                                                                                  

    Fluoranthene            (Positive)       Mouse                         6           2       3
    Fluorene                Negative         Mouse                         3           1           1
                                             Rat               2
                                                           +   -   ±   +   -   ±   +   -   ±   +   -   ±   +   -   ±   +   -   ±
    Indeno[1,2,3-cd]pyrene  Positive         Mouse                     2   1   2   1               1
                                             Rat                                                           1
    5-Methylchrysene        Positive         Mouse                     13          1       1   1   1
                                             Rat                                                                           1
    1-Methylphenanthrene    (Negative)       Mouse                         1
    Naphthalene             (Questionable)   Mouse                         1   2                                   2       1
                                             Rat           1                           1   1       1
    Perylene                (Negative)       Mouse                         2
    Phenanthrene            (Questionable)   Mouse                     1   3   3       3           1
                                             Rat           1                                                   1
    Pyrene                  (Questionable)   Mouse                     1   7   3       1           1
                                             Hamster                                                           1
    Triphenylene            (Negative)       Mouse                         2
                                                                                                                                  

    +, positive; -, negative; questionable; parentheses, limited number of studies
    s.c., subcutaneous; i.m., intramuscular; i.p., intraperitoneal; i.v., intravenous; inh., inhalation; tr., intratracheal
    Other: e.g. intramammary injection, bladder implant, bronchial implant





    Epidermal cell kinetics, DNA adduct levels, and changes in skin
    morphology were measured in ICR/Harlan mice after 29 weekly topical
    applications of 16, 32, or 64 µg benzo [a]pyrene for up to 35 weeks.
    Initially, there was a linear increase in DNA adducts, which was much
    less steep at 64 µg and which did not correlate with the sharp rise in
    tumour response at that dose. A dose-dependent increase in the
    3H-thymidine labelling index, the mitotic index, and the incidence of
    pyknotic and dark cells indicated that benzo [a]pyrene induced
    extensive cytotoxicity and cell death, with regenerative
    proliferation. Virtually all of the initial tumours were papillomas,
    which required an average of eight weeks to progress to carcinomas,
    reflecting the tumour-promoting activity of benzo [a]pyrene in this
    model (Albert et al., 1991a,b).

    In a study with female Sprague-Dawley rats to elucidate whether the
    metabolites and DNA adducts of benzo [a]pyrene are formed in the
    liver or in target tissues, animals that had received a liver
    transplant were compared with normal animals. The liver was found to
    serve as a depot for PAH, in this case infused 3H-benzo [a]pyrene,
    which was converted into polar metabolites. A few hours later, polar
    metabolites and DNA adducts were found in target tissues of both
    groups (Wall et al., 1991).

    7.7.1.2  Benzo [e]pyrene

    The results of studies on benzo [e]pyrene are considered to be
    questionable or negative even though positive results were reported in
    two studies by dermal application, because no bay-region activation
    was found in liver tissue that would result in an 'ultimate'
    carcinogen, such as 9,10-dihydroxy-11,12-epoxy-9,10,11,12-
    tetrahydrobenzo [e]pyrene (Jacob et al., 1983).

    7.7.2  Comparative studies

    Comparative studies on the tumorigenic activity of individual PAH that
    have been used as the basis for comparative potency factors (see
    Appendix I) are summarized below. The detailed results of studies with
    individual PAH are given in Table 90. In general, the results of
    studies with skin painting and lung implantation were used for
    estimating comparative potencies in preference to those from
    initiation-promotion experiments and studies by intraperitoneal
    injection. No comparative studies have been carried out by oral
    administration.

    7.7.2.1  Carcinogenicity

     (a) Dermal exposure

    Skin painting: Solutions of 0.5% benzo [a]pyrene,
    benzo [b]fluoranthene, benzo [j]fluoranthene, or
    benzo [k]fluoranthene were applied dermally three times weekly to
    groups of 20 female Swiss Millerton mice for life, and the number of
    skin tumours was determined. The percentages of papillomas/ carcinomas

    induced by these compounds after four months were 70/20 with
    benzo [a]pyrene, 95/10 with benzo [b]fluoranthene, 40/5 with
    benzo [j]-fluoranthene, and none with benzo [k]fluoranthene. Minimal
    activity (10% papillomas) was induced by benzo [k]fluoranthene after
    11 months (Wynder & Hoffmann, 1959b). The order of potency was thus
    benzo [a]pyrene > benzo [b]-fluoranthene > benzo [j]fluoranthene
    > benzo [k]fluoranthene.

    In a similar regime, 0.01% solutions of benzo [a]pyrene or
    dibenz [a,h]anthracene applied dermally to groups of 20 mice induced
    10/10% and 15/5% papillomas/carcinomas, respectively after six months.
    A 0.1% solution of dibenzo [a,i]pyrene induced 10/0% tumours after
    seven months, and a 0.1% solution of benzo [e]pyrene induced 5/0%
    tumours after 10 months. A 1% chrysene solution induced 5/5%
    papillomas/carcinomas after eight months. A 0.1% solution of
    fluoranthene and 10% solutions of anthracene and pyrene had no
    activity (Wynder & Hoffmann, 1959a). The order of potency was thus
    benzo [a]pyrene = dibenz [a,h]anthracene > dibenzo [a,i]pyrene >
    chrysene > benzo [e]pyrene > fluoranthene, anthracene, pyrene.

    In a further study, the carcinogenicity of PAH was compared after
    dermal application to mice three times weekly, as above. A dose of
    0.05% induced the following percentages of papillomas/carcinomas after
    eight months: benzo [a]pyrene, 17/17; dibenzo [a,h]pyrene, 14/9;
    dibenzo [a,l]pyrene, 10/10; dibenzo [a,i]pyrene, 3/0;
    dibenzo [a,e]pyrene, 2/1 after 10 months; indeno[1,2,3- cd]pyrene,
    1/1 with 0.5% solution; and benzo [ghi]perylene, 0/0 (Hoffmann &
    Wynder, 1966). The order of potency was thus benzo [a]pyrene>
    dibenzo [a,h] -pyrene > dibenzo [a,l]pyrene > dibenzo [a,i]pyrene
    > dibenzo [a,e]pyrene > indeno[1,2,3- cd]pyrene >
    benzo [ghi]perylene.

    In a lifetime study by skin painting in female NMRI mice,
    benzo [a]pyrene and benzo [b]fluoranthene were carcinogenic,
    benzo [j]fluoranthene was weakly carcinogenic, and
    benzo [k]fluoranthene, indeno[1,2,3- cd]pyrene, and coronene had no
    carcinogenic effect (Habs et al., 1980). The order of potency was thus
    benzo [a]pyrene >> benzo [b]fluoranthene > benzo [j]fluoranthene
    > benzo [k]-fluoranthene, coronene, indeno[1,2,3- cd]pyrene.

     Initiation-promotion: Ten doses of PAH at a total dose of 0.25
    mg/mouse were applied every second day to the backs of Swiss Millerton
    mice, which were then promoted with 2.5% croton oil in acetone
    (Hoffmann & Wynder, 1966). The relative tumour-inducing activity was:
    benzo [a]pyrene > dibenzo  [a,h]pyrene > dibenzo [a,l]pyrene >
    dibenzo [a,i]pyrene > dibenzo [a,e]-pyrene > indeno[1,2,3-
     cd]pyrene > benzo [ghi]perylene.

    In an assay in CD-1 mice, 30 µg of several PAH were applied in 10
    doses over 20 days to the shaven backs of groups of 20 mice. Ten days
    after completion of the initiation, promotion was begun by thrice
    weekly application of 12- O-tetradecanoylphorbol 13-acetate in 0.1 ml
    acetone. The skin tumours induced were predominantly squamous-cell
    papillomas. After 20 weeks (10 weeks for benzo [a]pyrene), the
    percentages of skin tumour-bearing animals were 85% with
    benzo [a]pyrene, 45% with benzo [b]fluoranthene, 30% with
    benzo [j]fluoranthene, and 5% with benzo [k]fluoranthene. The
    vehicle controls had no tumours (La Voie et al., 1982b).

    Sencar mice were treated with the - [a,e]-, - [a,h]-, - [a,i]-, and
    - [a,l]- isomers of dibenzopyrene with TPA as a promoter,
    anthanthrene as the negative control and with vehicle and sham
    controls. Dibenzo [a,e]pyrene was a very weak tumour initiator and
    dibenzo [a,h]pyrene and dibenzo [a,i]pyrene were tumorigenic;
    dibenzo[a,l]pyrene was highly toxic and an extremely potent carcinogen
    (Cavalieri et al., 1989). In a further investigation of
    dibenzo[a,l]pyrene, with benzo [a]pyrene as the positive control,
    7,12-dimethylbenz [a]anthracene, recognized as the most potent
    carcinogenic PAH, was also tested at 4, 20, and 100 nmol of the PAH in
    the same regime as above. The tumorigenic activity of
    dibenzo[a,l]pyrene in mouse skin was inversely proportional to the
    dose, indicating that toxicity interferes with the initiation of
    tumours. When the effects of equimolar concentrations were compared,
    benzo [a]pyrene was a much weaker tumour initiator than
    dibenzo[a,l]pyrene (Cavalieri et al., 1991). The order of potency was
    thus dibenzo[a,l]pyrene > dibenzo[a,i]pyrene > dibenzo[a,h]pyrene >
    benzo [a]pyrene > dibenzo[a,e]pyrene.

    The relationship between the  Ah locus and the induction of
    subcutaneous fibrosarcomas was studied after administration of
    dibenz [a,c]anthracene and dibenz [a,h]anthracene to B6, D2, and
    B6D2F1 mice. The doses and results are shown in Table 92.
    Dibenz [a,c]anthracene was a weak tumour inducer in all groups
    tested. Dibenz [a,h]anthracene was a fairly potent inducer of
    subcutaneous tumours in B6 and B6D2F1 mice, but not in D2 mice. These
    results, with those of back-crossing experiments, demonstrate a strict
    correlation between the tumorigenicity of dibenz [a,h]anthracene and
    expression of the  Ahb allele (Kouri et al., 1983).

     (b)  Other routes

     Intraperitoneal injection in newborn mice: The tumorigenic activity
    of the nonalternant PAH benzo [b]fluoranthene,
    benzo [j]fluoranthene, and benzo [k]fluoranthene and of
    indeno[1,2,3- cd]pyrene and benzo [a]pyrene were evaluated by
    injecting a total of 0.5, 1.1, 2.1, 2.1, or 0.5 µmol of each compound,
    respectively, in dimethyl sulfoxide in aliquots of 5, 10, or 20 µl on
    days 1, 8, and 15 after birth to CD-1 mice (La Voie et al., 1987).
    Direct comparison was not possible owing to the differences in the
    total amount injected, but both benzo [b]fluoranthene and
    benzo [j]fluoranthene had significant tumorigenic activity, whereas

    neither benzo [k]fluoranthene nor indeno[1,2,3- cd]pyrene was
    tumorigenic under these conditions. There were problems with the
    solubility of indeno[1,2,3- cd]pyrene. The order of potency was thus
    benzo [a]pyrene > benzo [b]fluoranthene = benzo [j]fluoranthene >
    benzo [k]-fluoranthene, indeno[1,2,3- cd]pyrene.

     Intramammary injection: 7,12-Dimethylbenz [a]anthracene and
    dibenzopyrene isomers were tested with benzo [a]pyrene by
    intramammary injection. Dibenzo[a,e]pyrene was inactive, but
    dibenzo [a,l]pyrene was much more carcinogenic than
    7,12-dimethylbenz [a]anthracene. At these doses, benzo [a]pyrene had
    only marginal activity. Dibenzo [a,l]pyrene thus appears to have the
    highest mammary cancer potency of all PAH so far tested (Cavalieri et
    al., 1989).

     Lung implantation: The relative potencies of PAH to induce
    epidermoid carcinomas and pleomorphic sarcomas after intrapulmonary
    injection, with benzo [a]pyrene as the reference substance, were
    dibenz [a,h] anthracene, 1.91 > benzo [a]pyrene, 1.00 >
    anthanthrene, 0.19 > benzo [b]fluoranthene, 0.11 > indeno[1,2,3-
     cd]pyrene, 0.08 > chrysene, 0.03 = benzo [k]fluoranthene, 0.03 =
    benzo [j]fluoranthene, 0.03 > phenanthrene, 0.001.
    Benzo [ghi]perylene and benzo [e]pyrene had no tumour-inducing
    effect (Deutsch-Wenzel et al., 1983; Wenzel-Hartung et al., 1990).

     Subcutaneous injection: Dose-response curves for benzo [a]pyrene
    and dibenz [a,h]anthracene were established after a single
    subcutaneous injection of PAH in tricaprylin into the right axilla of
    male C3H mice; 99% of the tumours detected were spindle-cell sarcomas.
    The responses of vehicle controls were not reported. Under the
    conditions in this experiment, dibenz [a,h]anthracene was estimated
    to be 4.5 times more potent than benzo [a]pyrene (Bryan & Shimkin,
    1943).

    Eight of 10 male and six of 10 female C57 black mice had
    injection-site tumours 60-80 weeks after 10 weekly subcutaneous
    injections of 1 mg benz [a]anthracene, whereas 20/20 males and 17/20
    females had tumours after 1 mg dibenz [a,h]anthracene (Boyland &
    Sims, 1967).

    7.7.2.2  Further evidence

     (a)  Sebaceous gland assay

    Application of carcinogenic PAH to mouse skin leads to the destruction
    of sebaceous glands, hyperplasia, hyperkeratosis, and even ulceration
    (Bock, 1964). An assay of these glands has been used to screen the
    tumorigenic potential of PAH. Acute topical application of
    benzo [a]pyrene, benz [a]anthracene, or dibenz [a,h]anthracene was
    reported to suppress glandular activity (Bock & Mund, 1958). The order
    of potency was benzo [a]pyrene = dibenz [a,h]anthracene >
    benz [a]anthracene. In another study, the order of potency was
    benzo [a]pyrene > benzo [b]fluoranthene = benzo [j]fluoranthene =
    benzo [k]fluoranthene = indeno[1,2,3- cd]pyrene (Habs et al. 1980).

    Table 92. Subcutaneous fibrosarcomas induced by a dose of 300 µg per
    animal of isomers of dibenzanthracene in different mouse strains

                                                                          

    Dibenzanthracene    Strain                 Tumour       Carcinogenic
    isomer                                     incidence    index
                                                                          

    a,c                 B6                     1/30         1.1
                        D2                     0/30         0
                        B6D2F1                 1/30         1.2
    a,h                 B6                     14/30        24
                        D2                     0/30         0
                        B6D2F1                 33/60        30
                        B6D2F1 x D2            38/53        29
                        back-crosses
                        (Ahb/Ahd phenotype)
                        B6D2F1 × D2            0/33         0
                        back-crosses
                        (Ahd/Ahd phenotype)
                                                                          

    From Kouri et al. (1983)


     (b)  DNA adduct formation

    In a 32P-postlabelling test for covalent binding of PAH to DNA in
    mouse skin  in vivo after a single topical application, the relative
    ability to induce DNA adducts was benzo [a]pyrene >
    benz [a]anthracene = dibenz [a,h]anthracene = benzo [ghi]perylene
    (Reddy et al., 1984). DNA adducts were not induced by pyrene. In a
    similar study, the relative ability of PAH to bind covalently to DNA
    was benzo [b]fluoranthene > benzo [j]fluoranthene >
    benzo [k]fluoranthene > indeno[1,2,3- cd]pyrene (Weyand et al.,
    1987). In a study  in vitro, the relative ability for covalent
    binding of PAH to DNA was reported to be benzo [a]pyrene >
    dibenz [a,h]anthracene > benz [a]anthracene > pyrene >
    phenanthrene (Grover & Sims, 1968).

    7.7.3  PAH in complex mixtures

    In a PAH-rich emission mixture prepared by burning tar pitch with
    coal, the benzo [a]pyrene content was about 90 µg/m3, two to three
    times higher than the concentration measured in old coal plants. The
    tumour incidence in rats exposed for 16 h/day on five days per week
    for 22 months with a subsequent eight-month exposure to clean air was
    18%; the mortality rate was not increased in comparison with controls
    exposed to clean air. The lung tumour incidences in mice exposed to
    the same atmosphere for 10, 12, or 24 months were 86, 70, and 79%,
    respectively, with 3.5, 12.5, and 32% in concurrent controls. An
    additive or even potentiating carcinogenic effect with other

    respiratory-tract carcinogens was demonstrated. In contrast to a group
    exposed concurrently to diesel exhaust, the coal-tar pitch did not
    cause particle overload in the lung or impair lung clearance (Heinrich
    et al., 1986a,b).

    Female Wistar rats were exposed by inhalation to 1.1 (groups 1 and 2)
    or 2.6 mg/m3 (groups 3 and 4) of an aerosol of a PAH-rich hard
    coal-tar pitch condensate containing 20 or 50 µg/m3 benzo [a]pyrene
    (among other PAH), for 17 h per day on five days per week for 10
    (groups 1 and 3) and 20 months (groups 2 and 4) and then to clean air
    for 20 or 10 months. The aerosol contained benz [a]anthracene and
    chrysene at concentrations similar to that of benzo [a]pyrene.
    Increased mortality was observed due to the development of large,
    multiple tumours in the lungs and not to toxic effects. The lung
    tumour rates were 4, 33, 39, and 97% in groups 1,2, 3, and 4,
    respectively. Other groups exposed simultaneously to 2 or 6 mg/m3
    carbon black, which might serve as a PAH carrier, showed an additional
    increase in tumour rates, i.e. 89 and 72% in comparison with 39% in
    group 3. A group exposed only to carbon black had a tumour rate of
    18%. The authors therefore concluded that there was a more than
    additive carcinogenic effect after 10 months of exposure. A 'PAH
    depot' effect may be involved, in which the residence time of the PAH
    is prolonged due to attachment to the inert carbon black particles,
    with an extended period elution of adsorbed PAH. Furthermore, the
    irritating, inflammatory, and cell proliferation effects of carbon
    black enhance the probability of genotoxic effects in the lungs
    (Heinrich, 1989; Heinrich et al., 1994a). Most of the lung tumours
    observed after exposure to tar-pitch aerosol with or without carbon
    black were classified as squamous-cell carcinomas (Heinrich et al.,
    1994b).

    The preliminary findings of a study on coal gasification tars have
    been reported. Coal-tar is a complex mixture containing over 1000
    compounds, of which at least 30 are PAH, including benzo [a]pyrene.
    In a two-year bioassay for carcinogenicity, female B6C3F1 mice were
    fed up to 100 ppm benzo [a]pyrene or up to 1% coal-tar. Forestomach
    tumours were observed in mice fed benzo [a]pyrene, the incidence
    increasing sharply at doses between 5 and 25 ppm. Forestomach tumours
    were also seen in mice fed coal-tar, with a clear increase at 0.3%;
    the incidence was approximately the same at 0.3 and 0.6% but declined
    at 1.0%, due to mortality from small intestinal adenocarcinomas, which
    were not observed at doses below 0.6%. Steady-state DNA adduct levels
    were examined in the forestomachs and small intestines of mice fed
    benzo [a]pyrene or coal-tar for four weeks. Those fed
    benzo [a]pyrene had one major adduct, which also accounted for 10-25%
    of the adducts in the forestomachs of mice fed coal-tar. A linear
    dose-response relationship was observed between the dose of
    benzo [a]pyrene and the adduct levels in the forestomach. The adduct
    levels in the forestomachs of mice fed coal-tar increased in a
    relatively linear manner at doses above 0.3%. Total adducts and
    benzo [a]pyrene-adduct levels in the small intestine increased up to
    the 0.6% dose of coal-tar and then decreased (Culp et al., 1996).

    A two-stage study of carcinogenicity in female CD-1 mice was performed
    to assess the risk deriving from coal-tar formulations used for human
    therapeutic purposes, e.g. against dandruff or psoriasis (see also
    section 8.2.3). Mice were treated epicutaneously five times per week
    with 50 mg of a 1.5% coal-tar ointment for two weeks ('initiation'),
    followed by 'promotion' with 50 mg of a 0.1% dithranol cream, used
    against psoriasis, three times per week for 40 weeks. A single dose of
    50 µg benzo [a]pyrene was given as an initiator as a positive
    control. After 40 weeks of promoter treatment, 4/27 tumours were
    observed in the mice treated with coal-tar and 14/28 in those given
    benzo [a]pyrene; when coal-tar or dithranol was given alone, no
    tumours were observed (Phillips & Alldrick, 1994).

    7.7.4  Transplacental carcinogenicity

    7.7.4.1  Benzo [a]pyrene

    Clastogenic responses to benzo [a]pyrene and AHH inducibility were
    measured in 11-day-old embryos of genetically different mice (C57 and
    DBA mated  inter se and mixed) after transplacental treatment with
    150 mg/kg bw by garage 15 h before sacrifice. The rate of chromosomal
    aberrations was not correlated quantitatively with AHH activity. It
    was concluded that not only activation and detoxification of
    benzo [a]pyrene in maternal tissue but also other genetically
    controlled processes, such as repair and transformation of primary DNA
    lesions into true DNA discontinuities, are involved (Adler et al.,
    1989).

    Benzo [a]pyrene can cross the placenta in mice and rats (Shendrikova
    & Aleksandrov, 1974; Shendrikova et al., 1974; Takahashi, 1974;
    Baranova et al., 1976), but the concentration of 14C-benzo [a]pyrene
    was one to two orders of magnitude lower in mouse embryonic than
    maternal tissues after oral administration (Neubert & Tapken, 1988).
    Intraperitoneal administration of benzo [a]pyrene to Ha/ICR mice
    during the last half of pregnancy increased the incidences of
    pulmonary adenomas and skin papillomas in progeny nursed by foster
    mothers, excluding uptake of PAH via the milk (Bulay, 1970; Bulay &
    Wattenberg, 1971). A similar result was observed in A and C57B1 mice;
    furthermore, lung tumours were induced in Ha/ICR strain mice and liver
    tumours in the offspring of all three strains (Nikonova, 1977).
    Transplacental carcinogenesis has also been reported in rabbits
    (Beniashvili, 1978).

    Benzo [a]pyrene was given subcutaneously to strain A and C57B1 mice
    at 4 or 6 mg per animal once or twice on days 18 and 19 of gestation.
    The progeny of dams given a single dose of 4 mg had a significantly
    increased number of adenomas; the 6-mg dose induced 77% lung tumours
    in A mice and 12% in controls. The maximum dose, 12 mg, induced 32%
    liver tumours in male C57B1 mice and 9% in females, with 1% in
    controls (Nikonova, 1977).

    7.7.4.2  Pyrene

    The tumour incidence in the offspring of strain A mice was not
    increased by two subcutaneous injections of 6 mg pyrene on days 18 and
    19 of pregnancy (Nikonova, 1977).

    7.8  Special studies

    Adverse effects of PAH unrelated to cancer have also been seen.
    Proliferating tissues such as bone marrow, lymphoid organs, gonads,
    and intestinal epithelium are affected, but the major target organs
    seemed to be those of the haematopoietic and lymphoid systems.

    7.8.1  Phototoxicity

    Photodynamic compounds can generate superoxide anion radicals in the
    presence of near ultraviolet light. In the absence of oxygen, they act
    as photoreducing agents. The main effect is epidermal damage.

    7.8.1.1  Anthracene

    Increased dermal sensitivity to ultraviolet irradiation was seen in
    hairless mice after pretreatment with anthracene, but
    photocarcinogenesis was not significantly increased (Forbes et al.,
    1976; see also Table 92). In guinea-pigs treated six times on the
    dorsal skin with anthracene and then irradiated with ultraviolet
    light, a photoirritant reaction was observed that reached a maximum
    after a few hours but had faded by 24 h (Lovell & Sanders, 1992).

    Petroleum can photosensitize human skin to sunlight, resulting in
    erythema and pigmentation. Petroleum also enhanced the
    immunomodulatory effects of ultraviolet radiation on mammalian skin,
    with depletion of antigen-presenting cells which play a critical role
    by presenting antigen to thymus-derived lymphocytes. In tests of PAH
    that are present at relatively high concentrations in crude oils,
    anthracene but not phenanthrene or benzo [a]pyrene induced
    photosensitization of mouse skin  in vivo and  in vitro. Exposure of
    skin sections to anthracene at 5 µg/ml, equivalent to 125 ng/mouse,
    reduced the numbers of antigen-presenting cells and of Thy-1-positive
    dendritic cells (Burnham & Rahman, 1992).

    7.8.1.2  Benzo [a]pyrene

    Benzo [a]pyrene in the presence of near-ultraviolet radiation
    (290-400 nm) had phototoxic effects, observed as haemolysis of human
    erythrocytes and inactivation of  Escherichia coli (Kagan et al.,
    1989). A significant shortening of tumour-free survival was seen in in
    Balb/c mice exposed to ultraviolet irradiation before dermal treatment
    with benzo [a]pyrene. Ultraviolet irradiation had a systemic effect,
    enhancing subsequent dose-dependent tumour induction by
    benzo [a]pyrene (Gensler, 1988).

    7.8.1.3  Pyrene

    In six guinea-pigs given 5 µmol-5 mmol of pyrene dissolved in ethanol,
    a strong phototoxic reaction was observed 20 h after ultraviolet A
    irradiation at 1 × 103 J/m2 (320-400 nm) (Kochevar et al., 1982).

    When mast cells were isolated from Sprague-Dawley rats, incubated with
    25 µmol/litre pyrene, and irradiated with ultraviolet B radiation
    (280-320 nm) at 60 kJ/m2, they released 80% of their serotonin
    (Gendimenico & Kochevar, 1984).

    7.8.1.4  Comparisons of individual PAH

    The phototoxic effects of benzo [a]pyrene, benz [a]anthracene,
    indeno[1,2,3-cd]pyrene, fluoranthene, and perylene were compared by
    treating human fibroblasts with these PAH and then irradiating them
    with ultraviolet light (<400 nm). A good correlation was found
    between the phototoxic effects and known carcinogenic potency:
    benzo [a]pyrene and indeno[1,2,3- cd]pyrene were highly toxic,
    benz [a]anthracene was distinctly toxic, fluoranthene slightly toxic,
    and perylene not cytotoxic (Bauer et al., 1985).

    7.8.2  Immunotoxicity

    7.8.2.1  Benzo [a]pyrene

     (a) Intraperitoneal and intratracheal injection

    Mice injected intraperitoneally with a single dose of 50, 100, or 200
    mg/kg bw benzo [a]pyrene showed reduced thymic and splenic weights on
    day 5, and the splenocyte antibody-forming response of immunized mice
    was reduced by 60-90%. At the higher concentrations, lymphocyte
    proliferation was decreased significantly. Benzo [a]pyrene altered
    both humoral and cellular immunity; B cells were more susceptible than
    T cells (Xue et al., 1991).

    In a study of the effect of accumulation of benzo [a]pyrene in
    lymphoid organs on humoral immunity, B6C3F1 mice were given
    intratracheal instillations of 0.4, 4, or 40 mg/kg bw daily for seven
    days and immunized with sheep erythrocytes one day later; then, the
    number of antigen-specific, antibody-forming cells was measured. The
    spleen showed a decrease, but lung-associated lymph nodes showed
    either decreased (up to 60%) or increased (up to 100%) numbers,
    depending on whether sheep erythrocytes were given intratracheally or
    intraperitoneally (Schnizlein et al., 1987).

     (b)  Dermal exposure

    After dermal exposure of female B6C3F1 mice to 0, 5, 20, or 40 mg/kg
    bw per day for 14 days, dose-dependent suppression of the
    antibody-forming cell response to sheep erythrocytes was seen both
     in vivo and  in vitro, the number at 40 mg/kg bw being about 30% of
    the control value. The immunosuppression was similar when

    benzo [a]pyrene was administered at a high dose subcutaneously in
    corn oil. The antibody-forming cell response recovered by about day 60
    after dermal exposure, while no recovery was seen after subcutaneous
    injection (Parrott et al., 1989).

    Female B6C3F1 mice were exposed to benzo [a]pyrene at 0, 0.625, 2.5,
    5, 20, or 40 mg/kg bw per day for 28 days and were injected
    intravenously with sheep erythrocytes on days 11 and 25. An
    antigen-specific enzyme-linked immunosorbent assay to sheep
    erythrocyte membranes was used to measure the primary immunoglobulin M
    response on day 15 and the secondary immunoglobulin G response on day
    30. Significant suppression of the primary immunoglobulin M response
    was observed at doses of 5 mg/kg bw per day and more, but the serum
    titres of animals treated with 0.625 or 2.5 mg/kg bw per day did not
    differ from those of vehicle controls. The secondary immunoglobulin G
    response was significantly decreased at all doses (Deal, 1995).

     (c)  Comparisons of benzo[a]pyrene and benzo[e]pyrene

    The immunotoxic effects of benzo [a]pyrene and benzo [e]pyrene have
    been compared in several studies. In most, benzo [a]pyrene was
    clearly immunosuppressive, whereas benzo [e]pyrene was inactive.

     In vivo: After activation of splenic lymphocytes, mice were given
    single intraperitoneal injections of benzo [a]pyrene and
    benzo [e]pyrene at 2.5, 10, or 50 mg/kg bw for 24 or 48 h before
    sacrifice. Mononuclear cell populations were then assayed for AHH
    activity, blastogenesis, antigen-specific cell-mediated cytotoxicity,
    and the percentage of macrophages. Neither PAH had a significant
    effect on blastogenesis. Benzo [a]pyrene suppressed cell-mediated
    cytotoxicity of T cells by 40-80%, while benzo [e]pyrene had no
    effect. These results suggested that mitogen-activated, AHH-induced
    splenic lymphocytes metabolize benzo [a]-pyrene to immunocytotoxic
    metabolites. T cells are probably activated by early stimulation of T
    suppressor cells accompanied by an increase in T suppressor cell
    factors (Wojdani & Alfred, 1984).

    B6C3F1 mice were given 10 daily subcutaneous injections of
    benzo [a]pyrene and benzo [e]pyrene at doses of 5, 20, or 40 mg/kg
    bw over a 14-day period. Three to four days after the last dose,
    immune function was evaluated. Benzo [a]pyrene reduced the number of
    immunoglobulin M and G antibody plaque-forming cells in response to
    sheep erythrocytes and lipopolysaccharide, and the TNP-Ficoll
    plaque-forming cell response was depressed by 77%. These changes
    indicate altered differentiation and antibody production in mature B
    cells. No change in the plaque-forming cell response was observed
    after exposure to benzo [e]pyrene (Dean, J.H. et al., 1983).

    Mice were given subcutaneous injections of benzo [a]pyrene or
    benzo [e]pyrene at 5, 10, or 40 mg/kg bw daily for 11 days, followed
    by an injection of sheep erythrocytes. Benzo [a]pyrene suppressed the
    antibody response to DNP-Ficoll and sheep erythrocytes but not to

    lipopolysaccharide; benzo [e]pyrene was not immunosuppressive (White
    & Holsapple, 1984).

     In vitro: When benzo [a]pyrene was added to cultured mouse spleen
    cells  in vitro, a metabolism-activating system was not required to
    produce immunosuppression. Furthermore, addition of S9 did not
    increase the degree of immunosuppression produced by benzo [a]pyrene
    (White & Holsapple, 1984).

    In several antibody generating systems  in vitro, both
    benzo [a]pyrene and benzo [e]pyrene caused a significant,
    dose-dependent suppression of the T-dependent and polyclonal antibody
    responses. A similar result was found  in vitro after a 14-day
    exposure of mice to 40 mg/kg bw benzo [a]pyrene  in vivo, with 98%
    suppression of T-cell-dependent antibody. Benzo [a]pyrene-induced
    suppression is multicellular, and the greatest sensitivity is found
    early in the immune response. Since benzo [e]pyrene induced
    immunosuppression only at high concentrations, the preparation may
    have been contaminated with benzo [a]pyrene (Blanton et al., 1986).

    Benzo [a]pyrene and seven of its metabolites were evaluated for their
    ability to suppress the antibody-forming cell response to sheep
    erythrocytes  in vitro. Direct addition of benzo [a]pyrene or its
    7,8-diol to splenocyte cultures induced similar dose-dependent
    suppression of the antibody response to the T-dependent antigen, sheep
    erythrocytes. In contrast, exposure to the 4,5-diol, 9,10-diol,
    6,12-dione, 3-hydroxy, and 4,5-epoxide metabolites resulted in
    decreased antibody responses only with high concentrations; these were
    associated with decreased viability of the cultures. In addition,
    co-incubation with the cytochrome P450 inhibitor alpha-naphthoflavone
    attenuated the suppressive effects of benzo [a]pyrene and
    benzo [a]pyrene 7,8-diol (Kawabata & White, 1987).

    The anti-sheep erythrocyte plaque-forming cell and mixed lymphocyte
    responses were inhibited in murine splenic lymphocytes treated with
    benzo [a]pyrene at concentrations ranging from 10-4 to 10-8
    mol/litre, with maximal depression at 10-5mol/litre. Benzo [e]pyrene
    at the same concentrations did not suppress these responses (Urso et
    al., 1986).

    7.8.2.2  Dibenz [a,h]anthracene

    The immunosuppressive effects of dibenz [a,h]anthracene and
    3-methyl-cholanthrene were studied in AHH-inducible (C57B1/6) and
    non-inducible (DBA/2N) mice after intraperitoneal injection of 25, 50,
    or 100 mg/kg bw five days before challenge with sheep erythrocytes or
    after administration by gavage of 10-200 mg/kg bw per day for four
    days. Immunosuppression occurred in both strains but was more
    pronounced in the C57B1 mice after intraperitoneal injection. The DBA
    mice were more susceptible to 3-methyl-cholanthrene given by gavage.
    The authors suggest that PAH are rapidly metabolized and excreted
    after gavage in AHH-inducible mice, whereas in non-inducible mice they

    are absorbed and distributed to the target organs. AHH inducibility
    may thus play an important role in the immunosuppressive activity of
    PAH (Lubet et al., 1984a,b; see also section 7.5.2.1).

    7.8.2.3  Fluoranthene

    Murine bone-marrow stromal cells were used as a matrix for the growth
    and limited development of precursor B cells  in vitro, thus
    mimicking B lymphopoiesis  in vivo. Fluoranthene acutely suppressed B
    lymphopoiesis, and the precursor B cell populations exposed to 50
    µg/ml fluoranthene disappeared within two weeks. Lymphotoxicity was
    mediated by fluoranthene-induced programmed cell death (apoptosis): 5
    µg/ml reduced precursor B cell recoveries by > 95% within one or two
    weeks. Lower doses altered the dynamics of B cell lymphopoiesis,
    leading to accumulation of precursor B cells (Hinoshita et al., 1992).

    7.8.2.4  Naphthalene

    Naphthalene did not adversely affect the immune response in CD-1 mice
    of each sex given up to 133 mg/kg bw per day orally for three months.
    No alteration was seen in the lymphocyte proliferative response to the
    T-cell mitogens concanavalin A and phytohaemagglutinin, in the delayed
    hypersensitivity response to sheep erythrocytess, or in the popliteal
    lymph node response. Furthermore, bone-marrow function was not altered
    (Shopp et al., 1984).

    Naphthalene is known to induce pulmonary and renal toxicity which is
    mediated by its reactive, electrophilic metabolites 1,2-naphthalene
    oxide, 1-naphthol, and 1,4-naphthoquinone. The immune response of mice
    was, however, unaffected by a 90-day oral treatment with up to 25% of
    the LD50 value. Furthermore, the number of antibody-forming cells in
    splenocyte cultures was not affected by concentrations of naphthalene
    up to 200 µmol/litre; however, 200 µmol/litre of 1-naphthol and 7-20
    µmol/litre of 1,4-naphthoqninone suppressed the antibody-forming cell
    response and decreased cell viability. Splenic microsomes were unable
    to metabolize naphthalene, whereas liver microsomes generated 1,2-
    naphthalene diol and 1-naphthol. It was concluded that diffusion of
    liver metabolites to the spleen is insufficient to induce
    immunotoxicity (Kawabata & White, 1990).

    7.8.2.5  Comparisons of individual PAH

    The effects of exposure to each of 10 PAH on the immunoglobulin M
    antibody response to sheep erythrocytes were examined in B6C3F1 mice,
    with a further investigation of the relationship of the
     Ah gene complex to the immunosuppression. Mice were given
    subcutaneous injections over 14 days, and splenic antibody-forming
    cells were evaluated after immunization with sheep erythrocytes.
    Significant decreases of 55-91% were observed after treatment with
    dibenz [a,c]anthracene, dibenz [a,h]anthracene, benz [a]anthracene,
    and benzo [a]pyrene, but no significant effects were observed with
    anthracene, benzo [e]pyrene, perylene, or chrysene. Generally, the
    structure-activity relationship for immunosuppression was correlated

    strongly with that for carcinogenicity. Non-inducible DBA/2 mice had
    greater PAH-induced immunosuppression than AHH-inducible B6C3F1 mice
    (White et al., 1985).

    7.8.2.6  Exposure in utero

    Oral administration of benzo [a]pyrene at 2 mg/kg bw to Wistar rats
    on day 19 of gestation induced a relative decrease in the number of
    thymic glucocorticoid receptors in males and a relative increase in
    females at six weeks of age. In animals treated at six weeks of age,
    no change in the number or affinity of steroid receptors was seen in
    males, but there was a 40% decrease in females. The investigators
    concluded that benzo [a]pyrene binds to pre-encoded hormone receptors
    and interferes with their maturation. When benzo [a]pyrene was given
    on day 15 of gestation, a 30% decrease in the number of receptors was
    seen in the offspring (Csaba et al., 1991; Csaba & Inczefi-Gonda,
    1992).

    Strong suppression of the anti-sheep erythrocytes plaque-forming cell
    response, the mixed lymphocyte response, and the graft-versus-host
    response  in vivo were seen in the progeny of female mice that had
    been treated intraperitoneally with benzo [a]pyrene at a dose of 150
    mg/kg bw during mid-gestation (11-13 days). Immunodeficiency was seen
    within one week after birth and persisted for 18 months.
    Benzo [a]pyrene induced marked disorientation of T cells up to four
    weeks postnatally. Disruption of T-cell differentiation during
    ontogenesis was suggested, implying decreased resistance to the
    development of neoplasia (Urso & Gengozian, 1980; Urso & Johnson,
    1987). A two- to fourfold reduction in maternal leukocytes was seen
    within five days of an intraperitoneal administration of 150 µg
    benzo [a]pyrene on day 12 of gestation, which persisted to day 10
     post partum and was attributed to lymphocyte depletion. Thus,
    benzo [a]pyrene exacerbated the depression of leukocytes seen during
    pregnancy. After intraperitoneal injection, it can reach the
    lymphocytes, where metabolic activation may take place. Investigation
    of the maternal T-cell population, both during pregnancy and  post 
     partum, showed exacerbated decreases in the number of thymocytes
    present in the thymus. In the spleen, the number of thymocytes
    positive for LytI antigens was also depressed, whereas the number of
    Lyt 2+ cells was enhanced, reaching levels > 700 times those of
    controls. These results demonstrate disruption of the maternal T-cell
    repertoire (Urso et al., 1988; Urso & Johnson, 1988).

    7.8.2.7  Mechanisms of the immunotoxicity of PAH

    Although the mechanism(s) by which PAH adversely affect the immune
    system has not been defined, several have been proposed (Ladics &
    White, 1996). The mechanism that is most consistent with that accepted
    for the carcinogenesis of PAH is that their immunotoxicity is due not
    to the parent compound but to the reactive metabolites formed. These
    include the 7,8-diol-9,10-epoxide for benzo [a]pyrene (Kawabata &
    White, 1987) and the 3,4-diol-1,2-epoxide for the synthetic compound
    7,12-dimethylbenz [a]anthracene (Ladics et al., 1991). Several

    investigators have suggested that the mechanism of action of PAH
    results from their ability to enter the cell membrane and disrupt
    transduction of transmembrane signals and/or alter the conformation of
    receptors (Pallardy et al., 1992; Thurmond et al., 1989). It has also
    been suggested that PAH alter the immune response as a result of their
    ability to induce inappropriate alterations in the levels of various
    cytokines, such as interleukins 1 and 2 (Lyte et al., 1987; Meyers et
    al., 1988; Pallardy et al., 1989), and this mechanism is under active
    investigation. While interaction with the Ah receptor has been
    suggested as a possible mechanism of action of PAH, the contradictory
    results from immunotoxicological studies with genetically different
    strains of mice (high and low AHH responders) must be resolved.
    Studies primarily conducted  in vitro support the hypothesis that the
    immunomodulatory effects of PAH are the result of alterations in
    calcium mobilization (Burchiel et al., 1991).

    7,12-Dimethylbenz [a]anthracene has been extensively studied as a
    prototypic immunotoxicant. Exposure to this compound has been reported
    to decrease natural killer cell activity (Kimbar et al., 1986), to
    decrease resistance to challenge with tumour cells (Dean et al.,
    1986), and to increase susceptibility to chemically induced tumours
    (Elmets et al., 1988).  In vitro, 7,12-dimethylbenz [a]anthracene
    has been shown to suppress cytotoxic T-cell activity, possibly by
    inducing defects in antigen recognition (House et al., 1989) and/or in
    cytokine production (House et al., 1988). Oral administration of a
    cumulative dose of 14 mg/kg bw of 7,12-dimethylbenz [a]anthracene
    over 14 days suppressed proliferative responses by about 50% in
    splenic lymphocytes and by more than 70% in gut-associated lymphocytes
    (Burchiel et al., 1990).

    7,12-Dimethylbenz [a]anthracene-mediated immunosuppression was shown
    to persist for at least eight weeks (Ward et al., 1986; Burchiel et
    al., 1988). This compound also decreased resistance to bacterial (Ward
    et al., 1984) and viral (Selgrade et al., 1988) infections. Although
    no studies have been carried out on humans  in vivo, the IC50 for
    inhibition of the response of human tonsillar lymphocytes in culture
    to foreign tissue antigens was 10-40 µmol/litre; however, antibody
    secretion was affected only at a concentration of 100 µmol/litre (Wood
    & Holsapple, 1993).

    7.8.3  Hepatotoxicity

    7.8.3.1  Benzo [a]pyrene

    Non-responsive strains of mice (C57B1/6, C3H/HeN, and Balb/cAnN) had
    increased relative liver weights after they were fed for 180 days on a
    diet containing benzo [a]pyrene resulting in an intake of 120 mg/kg
    bw per day (Robinson et al., 1975).

    7.8.3.2  Comparisons of individual PAH

    The induction of several enzymes has been correlated with cancer
    promotion. Wistar rats treated orally with 100 mg/kg bw per day of
    benzo [a]pyrene, benz [a]anthracene, anthracene, chrysene, or
    phenanthrene for four days showed induction of cytosolic aldehyde
    dehydrogenase activity. Benzo [a]pyrene and benz [a]anthracene were
    much more effective than the other substances, increasing liver
    weights by 27 and 19%, respectively (Törrönen et al., 1981).

    The extent of liver regeneration that determines the ability to induce
    a proliferative response was investigated in partially hepatectomized
    rats fed diets containing various PAH for 10 days. Doses of 51.4 mg/kg
    bw per day acenaphthene or 180 mg/kg bw per day fluorene induced a
    significant increase in the rate of liver regeneration, but 15.4 mg/kg
    bw per day acenaphthene, 51.4 mg/kg bw per day benzo [a]pyrene, or
    514 mg/kg bw per day pyrene, anthracene, or phenanthracene had no
    effect (Gershbein, 1975).

    7.8.4  Renal toxicity

    Rats given 50-150 mg/kg bw benzo [a]pyrene orally over four days
    showed moderate induction of renal microsomal carboxylesterase
    activity; however, administration of 100 mg/kg bw per day anthracene
    or phenanthrene had no effect (Nousiainen et al., 1984).

    7.8.5  Ocular toxicity of naphthalene

    The development of cataracts in rats, mice, and rabbits after
    application of naphthalene is a toxic peculiarity of this compound.
    Attempts have been made to clarify the metabolic processes responsible
    for the formation of insoluble precipitates in the eye.

    Cataracts developed in the eyes of rabbits within a few days of
    repeated oral administrations of 0.5-1 g/kg bw per day. Oral
    administration was more effective than other modes of application
    (Pike, 1944). The oxidation products of naphthalene may reach the eye
    via the bloodstream, where 1,2-naphthoquinone is formed which can
    react with proteins and other cell components to form insoluble
    precipitates with a characteristic brown colour (Van Heyningen &
    Pirie, 1967).

    C57B1/6 mice, which are susceptible to induction of cytochromes P450,
    were given naphthalene by intraperitoneal administration at 500-2000
    mg/kg bw. Cataracts were induced in a dose-dependent manner within 8
    h. The effect was reduced by pretreatment with P450 inhibitors and
    antioxidants and was increased by pretreatment with P450 inducers or
    glutathione depletors. Cataracts were also induced in a dose-dependent
    manner by intraperitoneal injection of 1,2- or 1,4-naphthoqninone at
    5-250 mg/kg bw (molar potency about 10-fold higher). DBA/2 mice, which
    are resistant to induction of cytochromes P450, did not develop
    cataracts. The authors concluded that P450-dependent bioactivation was

    necessary to form reactive intermediates, which are assumed to be
    naphthoqninone or a free-radical derivative (Wells et al., 1989).

    When a lens cell line from transgenic mice was exposed to the
    1,2-dihydrodiol and 1,2-naphthoquinone metabolites of naphthalene, the
    dihydrodiol did not appear to be toxic but the naphthoquinone induced
    depletion of glutathione levels. Detoxification of naphthoquinone by
    the enzyme quinone oxidoreductase prevents formation of a semiquinone
    radical by two-electron reduction (Russell et al., 1991).

    All rats of various strains given naphthalene orally developed
    cataracts. The authors proposed that naphthalene dihydrodiol is
    produced in the liver, reaches the aqueous humour, and penetrates the
    lens, where it is metabolized to naphthoquinone. Feeding of 1-naphthol
    did not induce opacification (Xu et al., 1992).

    7.8.6  Percutaneous absorption

    As dermal penetration is one of the major routes of entry after
    occupational exposure, in-vivo and in-vitro models have been developed
    to assess it.

    In experiments  in vitro on the dermal penetration of
    benzo [a]pyrene and pyrene in guinea-pigs, pyrene was absorbed mainly
    by passive diffusion, but benzo [a]pyrene was biotransformed during
    absorption, and the 7,8,9,10-tetrol metabolite of the putative
    ultimate carcinogen was detected in the receptor fluid of diffusion
    cells (Ng et al., 1992).

    In skin preparations from mice, rats, rabbits, guinea-pigs, marmosets,
    and humans treated with benzo [a]pyrene, both the parent compound and
    a full spectrum of metabolites were detected, depending on metabolic
    viability, i.e. previously frozen skin preparations could not
    metabolize benzo [a]pyrene (Kao et al., 1985).

    14C-Benzo [a]pyrene was administered to the nuchal area of mice at
    doses of 1.25-125 µg/cm2, and the animals were sacrificed seven days
    later. Benzo [a]pyrene disappeared rapidly from the application site,
    at a rate of 6% within 1 h and 40% within 24 h; after seven days, 7%
    remained at the original site. Most of the benzo [a]pyrene was
    excreted via the hepatobiliary system and found in the faeces, with
    35% after 24 h, 58% after 48 h, and 80% after seven days. Only 10% of
    the radiolabel was detected in urine. Uptake was saturated at doses >
    15 µg/cm2, implying an enhanced risk for tumour induction in the skin
    epithelium (Sanders et al., 1986).

    The binding of benzo [a]pyrene to DNA and protein in mouse skin was
    15-20 times greater when acetone was used as the vehicle than with a
    low-viscosity oil (Ingram & Phillips, 1993). While acetone solutions
    of 14C-benzo- [a]pyrene readily penetrated skin from human cadavers,
    a significantly smaller amount moved from soil into skin. No
    partitioning of benzo [a]pyrene from human skin to plasma was

    observed. An experiment with rhesus monkeys  in vivo also showed
    significantly less absorption from soil (Wester et al., 1990).

    7.8.7  Other studies

    7.8.7.1  Benzo [k]fluoranthene

    Intraperitoneal injections of benzo [k]fluoranthene, a widespread
    PAH, to rats for three days induced maximal cytochrome P450/448
    activity. Liver microsomes were then prepared, and the metabolic
    profile of benzo [k]-fluoranthene was analysed by gas
    chromatography-mass spectrometry.  trans-5,6-, 8,9-, and mainly
    10,11-dihydrodiols were the primary metabolites in noninduced rats.
    Pretreatmant with PAH resulted in the generation of 5,6 and 8,9
    isomers as the main metabolites, due to induction of monooxygeuases;
    secondary metabolism to triols and tetrols was also induced. The
    putative ultimate carcinogen, 3,4-diol-1,2-epoxy benz [a]anthracene,
    was detected after pretreatment of liver microsomes with
    benzo [k]fluoranthene. The authors concluded that
    benzo [k]fluoranthene is a relevant component of environmental
    pollution and enhanced the carcinogenic risk of benz [a]anthracene
    (Schmoldt et al., 1981; Jacob et al., 1981a).

    7.8.7.2  Benzo [a]pyrene

    Rats were fed a diet containing 400 mg/kg benzo [a]pyrene with or
    without 2 g/kg of ß-carotene. Benzo [a]pyrene had no effect on serum
    retinol levels, but vitamin A levels were decreased in liver and small
    intestine at two weeks, with a 30% decline by four weeks. A similar
    effect was not observed in rats fed ß-carotene simultaneously. AHH can
    be induced by ß-carotene, but this may not be the mechanism by which
    tumours are prevented (Edes et al., 1991).

    The role of benzo [a]pyrene in the induction of arteriosclerosis was
    investigated by studying its effects on bovine arterial smooth muscle
    cells  in vitro. The number of cells was unchanged by exposure, but
    the secretion of newly synthesized collagen was decreased. Total
    cellular DNA was decreased and collagen secretion increased when the
    cells were preincubated with platelet factors rather than a serum-free
    medium (Stavenow & Pessah-Rasmussen, 1988).

    Microsomes from rat aorta transformed benzo [a]pyrene into various
    carcinogenic and toxic metabolites after induction with
    3-methylcholanthrene. Thus, carcinogenic metabolites of PAH deriving
    from cigarette smoke tars could cause endothelial injury, contributing
    to the role of cigarette smoking in arteriosclerosis (Thirman et al.,
    1994).

    7.8.7.3  Phenanthrene

    In a study of the oxidation of phenanthrene by liver microsomes from
    rats with or without pretreatment with inducers, microsomes from
    untreated rats produced only  trans-9,10-diol phenanthrene, but
    pretreatment with various PAH also led to oxidation at the 1,2 and 3,4
    positions. Considerable amounts of the proximal carcinogen 1,2-diol
    phenanthrene were detected, but the concentration of the ultimate
    carcinogen 1,2-diol-3,4-epoxide was very low. These results are in
    accordance with the questionable carcinogenic potency of phenanthrene
    (Jacob et al., 1982a; see Table 91).

    7.8.7.4  Comparisons of individual PAH

    Activation of platelets by calcium ionophore A23187 can mobilize
    intracellular stores of calcium ion and stimulate thromboxane
    biosynthesis, which can be measured as thromboxane B2 synthesis.
    Benz [a]anthracene, chrysene, benzo [a]pyrene, and
    benzo [ghi]perylene inhibited thromboxane B2 production in
    A-23187-induced, washed platelets from rabbits, while anthracene and
    pyrene appeared to stimulate thromboxane B2 synthesis. Fluoranthene,
    benzo [b]fluoranthene, benzo [k]fluoranthene, and benzo [e]pyrene
    had little or no effect on activation (Yamazaki et al., 1990).

    Benzo [a]pyrene, benzo [k]fluoranthene, benzo [b]fluoranthene,
    chrysene, benz [a]anthracene, pyrene, phenanthrene, and fluoranthene
    were toxic to human hepatoma cell cultures (HepG2), as measured with
    neutral red, whereas fluorene, anthracene, acenaphthene, and
    acenaphthylene were not (Babich et al., 1988).

    7.9  Toxicity of metabolites

    Derivatives of parent PAH have been tested for mutagenicity and
    carcinogenicity in a number of experiments in order to assign the
    effects to definite metabolites or to rank the potency of known
    metabolites of a parent compound. Some studies addressed the steric
    factors that determine mutagenic or carcinogenic effects, such as the
    diastereomers of epoxides and the role of the methyl group in 5- and
    6-methylchrysene. These studies are summarized in Tables 93 and 94,
    although a few of the studies are reported in detail below.

    7.9.1  Benzo [a]pyrene

    Benzo [a]pyrene is metabolized to about 20 primary and secondary
    oxidized metabolites and to a variety of conjugates. Several
    metabolites can induce mutations, transform cells, and bind to
    cellular macromolecules, but the 7,8-diol-9,10-epoxides are presently
    considered to be the major ultimate carcinogens (DePierre & Ernster,
    1978; Pelkonen & Nebert, 1982).


        Table 93. Mutagenicity of metabolites of polycyclic aromatic hydrocarbons

                                                                                                                                            

    Compound                Metabolite                 Test system                         Results            References
                                                                                                                                            

    Benzo[b]fluoranthene    9,10-Diol                  Mouse, dermal                       Positive           Amin et al. (1991a)
    Benzo[j]fluoranthene    9,10-Diol                  Mouse, dermal                       Positive           LaVoie et al. (1980; 1982b)
    Benzo[k]fluoranthene    9,10-Diol                                                      Positive           LaVoie et al. (1980)
    Benzo[a]pyrene          7,8-Diol-9,10-epoxide      Unscheduled DNA binding             Positive           Gill et al. (1991)
                            (syn + anti)               DNA synthesis                       Positive
                            7,8-Diol-9,10-epoxide      Hamster embryo cells,               Positive           Mager et al. (1977)
                            (2 stereoisomers)          transformation
                            1-Hydroxy                  Reverse mutation,                   Positive (±S9)     Schoeny et al. (1985)
                            2-Hydroxy                  S. typhimurium TA 1538,             Negative (S9)
                            3-Hydroxy                  TA98,TA100                          Positive (+S9)
                            4-Hydroxy                                                      Negative (±S9)
                            6-Hydroxy                                                      Positive (-S9)
                            7-Hydroxy                                                      Positive (+S9)
                            9-Hydroxy                                                      Positive (+S9)
                            10-Hydroxy                                                     Negative (±S9)
                            12-Hydroxy                                                     Positive (±S9)
                            1,6-Quinone                                                    Negative (±S9)
                            3,6-Quinone                                                    Positive (+S9)
                            4,5-Quinone                                                    Negative (±S9)
                            6,12-Quinone                                                   Negative (±S9)
                            trans-4,5-Diol                                                 Negative (±S9)
                            cis-4,5-Diol                                                   Positive (+S9)
                            trans-7,8-Diol                                                 Negative (±S9)
                            trans-9,10-Diol                                                Negative (±S9)
                            4,5-Epoxide                                                    Positive (±S9)
                            1-Hydroxy                  Forward mutation,                   Positive (+S9)     Schoeny et al. (1985)
                            2-Hydroxy                  S. typhimurium TM677                Negative (±S9)
                            3-Hydroxy                                                      Negative (±S9)
                            4-Hydroxy                                                      Negative (±S9)
                            6-Hydroxy                                                      Negative (±S9)
                            7-Hydroxy                                                      Positive (±S9)
                            9-Hydroxy                                                      Negative (±S9)
                            10-Hydroxy                                                     Negative (±S9)

    Table 93. (continued)
                                                                                                                                            
    Compound                Metabolite                 Test system                         Results            References
                                                                                                                                            
                            12-Hydroxy                                                     Negative (±S9)
                            1,6-Quinone                                                    Negative (±S9)
                            3,6-Quinone                                                    Negative (±S9)
                            4,5-Quinone                                                    Negative (±S9)
                            6,12-Quinone                                                   Negative (±S9)
                            trans-4,5-Diol                                                 Positive (+S9)
                            cis-4,5-Diol                                                   Positive (+S9)
                            trans-7,8-Diol                                                 Positive (+S9)
                            trans-9,10-Diol                                                Negative (±S9)
                            cis-7,8-Diol                                                   Positive (+S9)
                            4,5-Epoxide                                                    Positive (±S9)
    Benzo[e]pyrene          9,10-Diol-11,12-epoxide    Bacterial and mammalian cells       Weakly positive    Wood et al.(1980)
    Chrysene                1,2-Diol                   Bacterial and mammalian cells       Positive           Wood et al. (1977)
                            1,2-Diol-3,4-epoxide
                            5,6-Oxide                  S. cerevisiae, D4-RDII              Positive           Siebert et al. (1981)
    Cyclopenta[cd]pyrene    3,4-Diol                   Bacterial and mammalian cells,      Positive           Gold et al. (1980)
                                                       mutagenicity and transformation
                            trans-3,4-Epoxide          Calf thymus DNA, DNA binding        Positive           Beach et al. (1993)
    Fluoranthene            2,3-Diol                   Bacterial calls                     Positive           LaVoie et al. (1982a)
                            2,3-Diol-1,10b-epoxide     Bacterial calls:                    Positive           Rastetter et al. (1982)
                            1,10b-Diol-2,3-epoxide     S. typhimurium TM677                Weakly positive
                                                                                           or negative
    Dibenz[a,h]anthracene   3,4-Diol                   Bacterial cells                     Most mutagenic     Wood et al. (1978)
                                                                                           compound among
                                                                                           3 dihydrodols
                            5,6-Epoxide                Hamster embryo cells,               Positive           Huberman et al. (1972);
                            transformation                                                                    Marquardt et al. (1972)
    Dibenz[a,h]pyrene       1,2-Diol                   Bacterial cells                     Positive           Wood et al. (1981)
    Dibenz[a,i]pyrene       3,4-Diol                   Bacterial cells                     Positive           Wood et al. (1981)
    5-Methylcholanthrene    1,2-Diol and 7,8-diol      Bacterial cells                     Positive           Hecht et al. (1978)
                            5-Hydroxy                  S. typhimurium TA100                Weakly positive    Amin et al. (1979)
    1-Methylphenanthrene    1,4-Diol                   Bacterial cells                     Positive           LaVoie et al. (1981c)
                            5,6-Diol
    Phenanthrene            1,5-Diol,-3,4-epoxide      Bacterial and mammalian cells       Positive           Wood et al. (1979)
                            9,10-Oxide                 S. cerevisiae D4-RDII               Positive           Siebert et al. (1981)
                                                                                                                                            
    S9, 9000 × g microsomal fraction of liver

    Table 94. Carcinogenicity of metabolites of polycydic aromatic hydrocarbons

                                                                                                                                             

    Compound               Metabolite       Species, route of   Type of           Results                                  References
                                            administration      investigation,
                                                                duration, dose
                                                                                                                                             

    Benz[a]anthracene      3,4-Diol and     Mouse,              Carcinogenicity,  3R,4R-Diol: 71% with tumours;            Wislocki et al.
                           3,4-diol-1,2-    intraperitoneal     26 weeks          other enantiomer not tumorigenic;        (1979)
                             epoxide                                              3,4-diol-1,2-epoxide: 100% with tumours;
                                                                                  other enantiomer: 42%; control: 13%

    Benzo[b]fluoranthene   9,10-Diol        Mouse, dermal       Initiation        Positive                                 Amin et al.
                                                                                                                           (1991a)

    Benzo[j]fluoranthene   9,10-Diol        Mouse, dermal       Initiation        Positive                                 LaVoie et al.
                                                                                                                           (1980, 1982b)
                           4,5-Diol         Mouse, dermal       Initiation        2,3-Diol: 5-11 %; 4,5-diol: 78-100%;     Rice et al.
                           9,10-Diol                                              9,10-diol: 60%; control: 10%             (1987)
                           2,3-Diol

    Benzo[c]phenanthrene   1,2-Diol         Mouse, dermal       Initiation        1,2-Diol: 3-4% with tumours;             Levin et al.
                           3,4-Diol                                               3,4-diol: 28-47% with tumours;           (1980)
                           5,6-Diol                                               5,6-diol: 3-7% with tumours;
                           1,2-Epoxy-                                             1,2-epoxy-3,4-diol: 80-90% with tumours;
                             3,4-diol                                             control: no tumours
                           3,4-Diol-1,2-    Mouse, dermal       Initiation        95-100% with tumours; control: 10%       Amin et al.
                             epoxide                                                                                       (1993)
                           anti-3,4-Diol-   Rat,                Carcinogenicity   100 % with mammary tumours;              Hecht et al.
                             1,2-epoxide    intramammary        1 × 12.2 µmol     vehicle control: 3%                      (1994)

    Benzo[a]pyrene         7,8-Diol         Mouse,dermal        Carcinogenicity,  100% with skin tumours                   Conney (1982)
                                                                43 µg every 2
                                                                week; 60 weeks
                           anti-7,8-Diol-   Rat,                Carcinogenicity,  47% with mammary tumours; vehicle        Hecht et al.
                             9,10-epoxide   intramammary        1 × 12.2 µmol     control 3%                               (1994)

    Table 94. (continued)

                                                                                                                                             

    Compound               Metabolite       Species, route of   Type of           Results                                  References
                                            administration      investigation,
                                                                duration, dose
                                                                                                                                             

    Benzo[e]pyrene         4,5-Diol         Mouse, dermal       Initiation        No significant effect                    Buening et al.
                           9,10-Diol                                                                                       (1980); Slaga
                                                                                                                           et al. (1980,
                                                                                                                           1981)
                           9,10-Diol        Mouse, newborn,     Carcinogenicity   No induction of pulmonary tumours;       Buening et al.
                           9,10-Diol-       intrapentoneal                        significant induction of hepatic         (1980); Chang
                           11,12-epoxide                                          tumours                                  et al. (1981)

    Chrysene               1,2-Diol         Mouse, dermal       Initiation 0.4,   39, 60, and 79% with tumours;            Levin et al.
                                                                1.25, and 4       control: 7%                              (1978)
                                                                µmol/ animal, 1 x
                           1,2-Diol         Mouse, dermal       Initiation        1,2-Diol: positive                       Slaga et al.
                           4,5-Diol                                               3,4-Diol: negative                       (1980, Chang
                           1,2-diol,        Mouse, newborn      Carcinogenicity   Induction of pulmonary adenomas          Buening et al.
                           1,2-Diol-                                                                                       (1979); Chang
                           3,4-epoxide                                                                                     et al. (1983)

    Dibenz[a,h]anthracene  3,4-Diol         Mouse, dermal       Carcinogenicity   Induction of skin tumours; induction of  Buening et al.
                                                                                  pulmonary tumours in newborn mice        (1979); Slaga et
                                                                                                                           al.(1980), 1981)
                           5,6-Epoxide      Mouse, dermal       Initiation        Poorly active                            Van Duuren at
                                                                                                                           al. (1967)

    Dibenzo[a,h]pyrene     1,2-Diol         Mouse, dermal,      Initiation        Positive                                 Wood et al.
                                            intraperitoneal                                                                (1981)

    Dibenzo[a,h]pyrene     3,4-Diol         Mouse, dermal,      Initiation        Positive                                 Wood et al.
                                            intraperitoneal                                                                (1981)

    Indeno[1,2,3-cd]pyrene 1,2-Diol,        Mouse, dermal       Initiation        1,2-Diol: 80%, 1,2-oxide, 80%;           Rice et al.
                           1,2-Oxide                                              8-hydroxy, 30% tumour-bearing animals    (1986)
                           8-Hydroxy

    Table 94. (continued)

                                                                                                                                             

    Compound               Metabolite       Species, route of   Type of           Results                                  References
                                            administration      investigation,
                                                                duration, dose
                                                                                                                                             

    5-Methylcholanthrene   1,2-Diol         Mouse, dermal       Initiation,       1,2-Diol: 19/20 papillomas, 7/20         Hecht et al.
                           7,8-Diol                             3 µg/animal,      carcinomas; 7,8-diol: 10/20              (1980)
                           9,10-Diol                            10 × in 20 days   papillomas, no carcinomas; 9,10-diol:
                                                                                  no papillomas, no carcinomas

                           5-Hydroxy        Mouse, dermal       Initiation        45-950% with skin tumours; solvent       Amin et al.
                                                                                  control: 5%                              (1981)
                           1,2-Diol-        Mouse, newborn      Carcinogenicity   Induction of pulmonary tumours           Amin et al.
                             3,4-epoxide                                                                                   (1991b)
    Phenanthrene           1,2-Diol,        Mouse, dermal       Initiation        Very weakly positive                     Wood et al.
                           3,4-Diol                                                                                        (1979)
                           9,10-Diol
                           1,2-Diol-        Mouse, newborn      Carcinogenicity   No induction of pulmonary tumours        Buening et al.
                             3,4-epoxide                                                                                   (1979)
                                                                                                                                             


    Cytochrome P450-dependent metabolizing activity is low in skin. When
    14C-benzo [a]pyrene was incubated with arachidonic acid and cytosol
    prepared from rat, mouse, or human epidermis, benzo [a]pyrene 1,6-,
    3,6-, and 6,12-quinones and other metabolites were formed. These
    metabolic reactions were inhibited by selective inhibitors of
    lipoxygenase, demonstrating that human and rodent skin can metabolize
    benzo [a]pyrene through an arachidonic acid-dependent lipoxygenase
    pathway (Agarwal & Mukhtar, 1991). In cultures of normal human
    melanocytes, benzo [a]pyrene diols and small amounts of quinones and
    phenols were detected in the fraction extractable in organic solvents,
    and glucuronide and sulfate conjugates in the water-soluble fraction
    (Agarwal et al., 1991).

    The (+) anti-7,8-dihydrodiol-9,10-epoxide of benzo [a]pyrene reacts
    with DNA to yield almost exclusively the deoxyguanosine adduct, in
    which the epoxide function has reacted with the amino group at C2 of
    the guanine base. In mouse skin, this one adduct accounts for about
    97% of the total binding of benzo [a]pyrene to DNA (Jeffrey et al.,
    1976).

    Benzo [a]pyrene 7,8-dihydroxy-9,10-epoxide and two other metabolites
    (which were detected by trapping with exogenous DNA as described by
    Ginsberg & Atherholt, 1989) were present in all serum samples from
    mice of three strains and Sprague-Dawley rats after intraperitoneal
    injection of 50-200 mg/kg bw benzo [a]pyrene. It was concluded that
    transport can occur via the systemic circulation (Garg et al., 1991).

    Benzo [a]pyrene or its 4,5-oxide or 7,8-diol-9,10-epoxy metabolite
    was administered directly into Swiss mouse embryos at 0.1-4 µg per
    embryo on days 10, 12, and 14 of gestation. The 7,8-diol-9,10-epoxy
    metabolite was the most potent embryotoxic and teratogenic compound in
    fetuses examined on day 18, causing 85% embryolethality and 100%
    malformations. Benzo [a]pyrene and the other metabolite did not
    increase the incidence of malformations significantly (Barbieri et
    al., 1986).

    7.9.2  5-Methylchrysene

    Investigations of the reaction of 5-methylchrysene diol epoxide
    enantiomers with DNA bases and in  S. typhimurium showed the
    importance of both the absolute configuration and the position of the
    methyl group. The 5-methyl-chrysene 1 R,2 S-diol-3 S,4 R-epoxide,
    with the methyl group and epoxide ring in the same bay region, were
    the most reactive (Melikian et al., 1988).

    7.9.3  1-Methylphenanthrene

    Incubation of rat liver preparations with 1-methylphenanthrene gave
    rise to the 3,4- and 5,6-dihydrodiols of 1-hydroxymethylphenanthrene,
    1-methylphenanthrene, 1-hydroxymethyl-phenanthrene, and unidentified
    derivatives as metabolites; the dihydrodiols were mutagenic in the
    presence of an exogenous metabolizing system (LaVoie et al., 1981b).

    7.10  Mechanisms of carcinogenicity

    7.10.1  History

    In the early 1940s, theoretical chemistry was used to predict the
    chemical reactivity of PAH. Pullman (1945,1947) introduced the terms
    K- and L-region to describe the reactivity of PAH based on Hückel
    molecular orbital calculations (see Figure 9). Later, the term 'bay
    region' was introduced for molecular substructures that contribute to
    the formation of some ultimate carcinogens. Discrete values of complex
    delocalization energies at the K- and L-regions of a PAH were
    correlated with its carcinogenic potency. At the time, however, there
    was only a limited database on metabolic processes and little
    experimental confirmation, and the K-region theory was later found to
    be incompatible with the results of experimental work.

    7.10.2  Current theories

    Miller & Miller (1977) proposed the theory of reactive electrophiles
    in chemical carcinogenesis. According to this theory, PAH are
    activated by microsomal enzymes to proximate and finally ultimate
    carcinogens, which are characterized by an electrophilic centre that
    can react with nucleophilic sites on macromolecules such as DNA, RNA,
    and protein.

    After the discovery that diol epoxides are metabolites of PAH (Sims &
    Grover, 1974), a theoretical model was presented by Jerina et al.
    (1976), who found that synthesized arene oxides were mutagenic without
    metabolic activation. The bay-region theory states two prerequisites
    for carcinogenic potency: The epoxide group of an ultimate metabolite
    must be part of a bay region (see Figure 10), and the hydroxy groups
    of the diol epoxide are preferentially located in the 'pre-bay
    region'. The presence of the epoxide group on a saturated benzene ring
    in a bay region facilitates ring opening, i.e. the delocalization
    energy forming the carbonium ion is higher. This is important for
    reactions with DNA via a carbonium ion, which is an alkylating agent.
    For example, the metabolic pathway of benzo [a]pyrene is hypothesized
    to start with a 7,8 oxidation followed by hydrolysis to
    7,8-dihydrodiol, and terminated by 9,10-oxidation, yielding the
    ultimate carcinogen 7,8-dihydrodiol-9,10-epoxide. Calculation of the
    carbonium ion delocalization energies by the pertubational molecular
    orbital method results in a rough correlation with experimentally
    determined carcinogenic potency.

    The number of PAH tested for carcinogenicity in experimental animals
    doubled between the time that Jerina et al. (1976) published their
    work and 1980, to 50 compounds. A calculation of the carbonium ion
    delocalization energies at that time (Qianhuan, 1980) revealed a
    deviation from the energy-carcinogenicity correlation for compounds
    that had not been investigated by Jerina et al. To avoid the
    shortcomings of the bay-region theory, Qianhuan took into account the
    data on all PAH that had been tested for carcinogenicity and
    postulated the di-region theory, a bifunctional electrophilic theory

    FIGURE 9

    FIGURE 10

    based on the assumption that formation of two carbonium ions on the
    same PAH is responsible for carcinogenic activity. A quantitative
    equation involving the delocalization energies of the twin active
    regions was deduced. Principally, all of the already defined key
    regions of PAH (M, E, K, and L; see Figure 11) were used but with
    different implications. In this theory, the metabolic activation of
    PAH is dependent on two factors, a geometric and an energy factor. The
    angular ring, the subangular ring, and an active K region play
    decisive roles in carcinogenic potency, and two adequately active,
    adjacent regions are required.

    PAH are proposed to exert carcinogenicity mainly by DNA complementary
    cross-linking. Qualitative and quantitative data have been presented
    on the mechanism of formation of PAH-DNA adducts in the radical cation
    theory. PAH with relatively low ionization potential, which are the
    most potent carcinogens, are activated via cytochrome P450 by
    one-electron oxidation (radical cation), whereas PAH with relatively
    high ionization potential are activated by mono-oxygenation
    (bay-region diol epoxide). In experiments in rat liver microsomes in
    which potential DNA adducts were synthesized and used as standards,
    four depurination products (one-electron oxidation) and one stable
    product (diol epoxide pathway) of benzo [a]pyrene were detected
    (Cavalieri & Rogan, 1985; Cavalieri et al., 1993; Rogan et al., 1993).

    In a review of the evidence for the four mechanisms of PAH
    carcinogenesis, namely, the diol epoxide mechanism, the radical-cation
    mechanism, the quinone mechanism, and the benzylic oxidation
    mechanism, Harvey (1996) concluded that current research provided
    evidence for all four.

    7.10.3  Theories under discussion

    A molecular geometrical model has been proposed in which the
    carcinogenic potency of PAH is predicted from the centre(s) of highest
    chemical or biochemical reactivity, with the hypothesized introduction
    of a methyl group into the PAH. A good correlation was found between
    the predicted carcinogenicity of a series of 50 unsubstituted PAH and
    the results found in rats and mice. Bioalkylation is suggested to be
    catalysed by cytosolic methyl-transferase with S-adenosyl-L-
    methionine. In an experiment to confirm the model, rats were given
    subcutaneous injections of benz [a]anthracene, and 24 h later the
    tissue at the application site was homogenized and the assumed
    metabolites analysed by high-performance liquid chromatography, gas
    chromatography, and mass spectrometry. The bioalkylation product
    7-methyl-benz [a]anthracene was identified. Six noncarcinogenic
    hydrocarbons did not yield alkylated metabolites in this experimental
    approach. The authors concluded that bioalkylation, preferably in the
    meso-anthranic centres of high reactivity, is a structural
    prerequisite of carcinogenicity (Flesher & Myers, 1990, 1991; see also
    section 6.6.2).

    The binding of 1-hydroxymethylpyrene to DNA after intraperitoneal
    injection to rats was similar to the adduct pattern of its active
    metabolites 1-hydroxymethylpyrene sulfate and 1-chloromethylpyrene
    with isolated DNA, suggesting secondary activation of
    hydroxymethyl-PAH sulfates to chloromethyl-PAH (Monnerjahn et al.,
    1993).

    Transformation of PAH via their proximate carcinogens (e.g.
    benzo [a]-pyrene 7,8-diol) to the ultimate carcinogens (e.g.
    benzo [a]pyrene 7,8-diol-9,10-epoxide) is reported to be mediated by
    cytochrome P450 enzymes; however, two pathways unrelated to P450 have
    also been discussed. Peroxidase enzymes can transform benzo [a]pyrene
    7,8-diol to benzo [a]pyrene 7,8-diol-9,10-epoxide, but the process
    requires the presence of superoxide anions, hydrogen peroxides, and
    hydroxyl radicals produced by polymorphonuclear cells. This reaction
    was demonstrated in mouse skin after topical treatment with
    12- O-tetradecanoylphorbol 13-acetate. The catalytic activity of
    myeloperoxi-dase enhances the reactivity of oxygen species. This
    alternative mechanism may be important for human exposure to PAH
    because simultaneous chronic inflammation (e.g. due to smoking) often
    leads to increased numbers of inflammatory cells (Marnett et al.,
    1978; Kensler et al., 1987; Ji & Marnett, 1992).

    Epoxidation of benzo [a]pyrene 7,8-diol has also been reported to be
    mediated by lipoxygenase (Hughes et al., 1989; Agarwal & Muhktar,
    1991; see also section 7.9).

    7.10.3.1  Acenaphthene and acenaphthylene

    B6C3F1 mice were given a single intraperitoneal injection of 300
    mg/kg bw acenaphthene or acenaphthylene. Acenaphthylene caused a
    > 80-fold induction of hepatic microsomal methoxyresoforin
    O-deethylase activity, dependent on the  Cyp1a2 gene, which codes for
    an enzyme that catalyses the oxidative metabolism of diverse
    substrates; acenaphthene increased the activity by > 20-fold. The
    tricyclic PAH acenaphthene, acenaphthylene, anthracene, fluorane, and
    phenanthrene were not competitive inhibitors at the mouse hepatic
    cytosolic Ah receptor when tested together with 3H-labelled
    1,2,7,8-tetrachlorodibenzo- para-dioxin or benzo [a]pyrene. The
    authors suggested an association between the relatively nontoxic
    behaviour of the tricyclic PAH and the observed  Ah 
    receptor-independent induction of hepatic  Cyp1a2 expression
    (Chaloupka et al., 1994).

    7.10.3.2  Anthracene

    A single intraperitoneal injection of 300 mg/kg bw anthracene to
    B6C3F1 mice caused a > 10-fold induction of hepatic microsomal
    methoxyresofurin  O-deethylase (Chaloupka et al., 1994).

    7.10.3.3  Benzo [a]pyrene

    The toxic effects of benzo [a]pyrene in mice vary according to their
    genetic constitution (see also section 7.5). The crucial point appears
    to be the  Ah locus, which determines the inducibility of AHH. For
    example, administration of benzo [a]pyrene at 120 mg/kg bw per day in
    the diet induced aplastic anaemia and death in nonresponsive AKR/N
    mice  (Ahd/ Ahdtype) within four weeks, with hypocellular bone
    marrow, myeloid precursors, and promegakaryocytes; responsive AKR/N
    mice  (Ahb/ Ahbtype), however, were still healthy after six
    months. In contrast, when benzo [a]pyrene was given intraperitoneally
    at 500 mg/kg bw per day, responsive mice survived for a significantly
    shorter time than nonresponsive mice (Robinson et al., 1975). In order
    to explain these differences, Nebert et al. (1977) proposed that the
    gastrointestinal tract and liver of responsive mice have a greater
    capacity to detoxify an orally administered dose; however, if
    benzo [a]pyrene reaches their bone marrow and other distal tissues,
    metabolism there leads to increased formation of toxic metabolites.

    Mice with high-affinity Ah receptors showed no myelotoxicity after
    administration of 120 mg/kg bw per day benzo [a]pyrene in the diet
    for six months, but non-responsive mice at the same dose died within
    three weeks due to myelotoxic effects (Legraverand et al., 1983).

    After two oral administrations of 10 or 100 mg/kg bw benzo [a]pyrene,
    the numbers of sister chromatid exchanges and DNA adducts were
    significantly higher in AHH-non-inducible DBA/2 mice than in inducible
    C57B1/6 mice (Wielgosz et al., 1991).

    Because PAH produce tumours at the site of administration, it was
    suggested that they do not require metabolic activation; however, it
    was shown later that activation occurs in the target tissue. The
    arylkylating agent, for example the 7,8-dihydrodiol-9,10-epoxide of
    benzo [a]pyrene, reacts with DNA to yield almost exclusively the
    deoxyguanosine adduct. Methyl groups reaching into the bay region can
    enhance carcinogenic potency by steric effects (Dipple et al., 1990).

    Topical application of the prostaglandin synthetase inhibitor
    indomethacin after administration of benzo [a]pyrene to mice delayed
    the onset and reduced the size of the skin tumours. It was assumed
    that prostaglandin-induced suppression of cellular cutaneous immunity
    plays a role in carcinogenesis, as indomethacin can partially restore
    cutaneous immunity (Andrews et al., 1991).

    7.10.3.4  Benz [a]anthracene

    Benz [a]anthracene was not tumorigenic after intravenous or
    intramuscular injection in rats. The methyl substituant was shown to
    be of great importance in the carcinogenicity of this compound, as
    derivatives were highly carcinogenic when they possessed two or three
    methyl groups in any combination at position 6, 7, 8, or 12 (Pataki &
    Huggins, 1969).

    7.10.3.5  Benzo [c]phenanthrene

    Benzo [c]phenanthrene is unique among the PAH in that it has no bay
    region as such but has a 'fjord' region between positions 1 and 12
    (see Figure 12). The synthesized metabolite 3,4-dihydrodiol (but not
    the 1,2 or 5,6 derivative) was as mutagenic in the presence of liver
    microsomes as the parent compound (Croisy-Delcey et al., 1979).

    The four fjord diol epoxides of benzo [c]phenanthrene are very active
    tumour initiators. In studies of their reactions with DNA, each diol
    epoxide became bound covalently to DNA and showed a unique product
    distribution, with either a preference for reaction with
    deoxyadenosine residues or a more even distribution between
    deoxyguanosine and deoxyadenosine residues. A remarkable feature is
    the efficiency of covalent binding to DNA relative to DNA-catalysed
    hydrolysis. The authors reported a strong association between
    reactivity with adenine in DNA and tumour-initiating activity.
    Interaction with DNA can lead directly to activation of the
     ras protooncogene and to turnout initiation (Dipple et al., 1987).

    In cultures of cells from embryos of Sencar mice, Syrian hamsters, and
    Wistar rats, > 74% of all benzo [c]phenanthrene-deoxyribonucleoside
    adducts resulted from the 1 R,2 S-epoxy-3 S,4 R; deoxyadenosine
    and deoxyguanosine adducts were formed at a ratio of 3:1. The absolute
    configuration of the major metabolite and preference for adenosine
    residues have been found to be typical for other potent carcinogens
    (Pruess-Schwartz et al., 1987).

    7.10.3.6  Chrysene

    The metabolism of the weak carcinogen chrysene has been investigated
    in the presence and absence of other xenobiotics. The putative
    ultimate carcinogenic form of chrysene is the 1,2-dihydroxy-3,4-epoxy-
    1,2,3,4-tetrahydro metabolite, formed by the inducible cytochrome P450
    system. In rats treated with benzo [a]pyrene, benzo [b]fluoranthene,
    or benzo [j]fluoranthene, 1,2- and 3,4-oxidation were highly induced,
    and the 1,2,3-triol metabolite was produced, which is a derivative of
    the 1,2-dihydrodiol-3,4-epoxide. In the absence of induction, chrysene
    may not be metabolized to the ultimate carcinogen (Jacob et al.,
    1982b).

    7.10.3.7  Cyclopenta [cd]pyrene

    For most PAH, an initial epoxidation step catalysed by cytochrome
    P450-dependent mono-oxygenases is followed by a second epoxidation;
    however, cyclopenta [cd]pyrene has no bay region (Figure 13) and has
    been suggested to be activated by a single epoxidation at the
    cyclopenteno double bond, which may be possible in systems that
    generate peroxyl radicals. Reed et al. (1988) found that peroxyl
    radicals could activate the mutagenic potential of
    cyclopenta [cd]pyrene. This compound is a member of a subclass of PAH
    that have a non-aromatic double bond, which may form the centre for
    conversion to an ultimate mutagen.

    7.10.3.8  Fluorene

    A single intraperitoneal injection of 300 mg/kg bw fluorene to B6C3F1
    mice caused a greater than fivefold induction of hepatic microsomal
    methoxyresofurin  O-deethylase activity (Chaloupka et al., 1994; see
    also section 7.10.3.1).

    7.10.3.9  Indeno[1,2,3- cd]pyrene

    The 1,2-diol of indeno[1,2,3- cd]pyrene and its epoxide precursor,
    1,2-oxide were found to have similar carcinogenic potency in an
    initiation assay. This result is remarkable, because K-region
    dihydrodiols such as the 1,2-diol are generally considered to be
    detoxification products formed by hydrolysis of K-region oxides.
    Further metabolic activation of the 1,2-diol via epoxidation in the
    7-10 area was proposed because 8- and 9-hydroxy
    indeno[1,2,3- cd]pyrene had been detected as metabolites. If
    substantiated, this would be a unique activation mechanism for PAH
    (Rice et al., 1990).

    7.10.3.10  5-Methylchrysene

    The 5-methyl compound was the most tumorigenic of the methylchrysenes,
    probably owing to the presence of the methyl group in the same bay
    region as the epoxide ring (Hecht et al., 1987). Specific dihydrodiol
    epoxides of 5-methylchrysene are formed from their precursor
    dihydrodiols after topical application of 5-methylchrysene to mouse
    epidermis or injection into newborn mice. (±)- trans-1,2-Dihydroxy-
     anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methyl-chrysene was found to be
    the ultimate carcinogen (Hecht et al., 1985).

    5-Methylchrysene 1,2-diol and the 1,2-diol-3,4-epoxide are major
    proximate and ultimate carcinogens; the corresponding
    6-methylchrysene-1,2-diol is also a major metabolite but is much less
    tumorigenic, perhaps because of the different activity of the
    corresponding 3,4-epoxides. The formation of epoxide-type adducts from
    6-methylchrysene was only 5% of that observed for 5-methylchrysene
    (Amin et al., 1985b). In an investigation of the stereoselectivity of
    the metabolic activation of 5- and 6-methylchrysene in mouse skin
     in vivo and in rat and mouse liver  in vitro, using the resolved
    enantiomers as reference compounds, the  R,R-enantiomers predominated
    (> 90 %), and 5-methyl-chrysene-1 R,2 R-diol was the most
    tumorigenic compound in an initiation test (Amin et al., 1987).

    5-Methylchrysene is uniquely tumorigenic among the monomethylchrysene
    isomers. Its activity is due mainly to the highly tumorigenic diol
    epoxide, which has a methyl group and an epoxide ring in the same bay
    region. Of the isomers, only 5-methylchrysene can form this type of
    'methyl bay region diol epoxide' (Figure 14). Substitutions that
    inhibit its formation lead to a decrease in tumorigenicity (Amin et
    al., 1990).

    FIGURE 11

    FIGURE 12

    FIGURE 13

    FIGURE 14

    The tumorigenicity of racemic  anti-1,2-diol-3,4-epoxides of
    chrysene, 5-methyl-, 5-ethyl-, and 5-propylchrysene was determined in
    newborn mice. Only the 5-methyl compound was highly tumorigenic,
    demonstrating the importance of molecular shape for tumorigenicity. A
    methyl group in the same bay region as the epoxide ring leads to
    exceptional activity, and this may occur a consequence of DNA adduct
    conformation (Amin et al., 1991b).

    In a study of the binding of 3H-labelled  anti-5- and
     anti-6-methylchrysene-1,2-diol-3,4-epoxide to DNA in liver and lung
    of newborn mice after intraperitoneal administration on day 1 of life
    and sacrifice after 24 h, 1.1 pmol/mg DNA were found with the
    benzo [a]pyrene analogue, 0.5 pmol/mg DNA with the 5-methyl compound,
    and < 0.01 pmol/mg DNA with the 6-methyl compound, consistent with
    their known tumorigenic activities. When the parent compounds were
    tested in the same protocol, however, little radiolabel became
    associated with DNA adducts. Hence, it can be concluded that the
    dihydrodiols are the carcinogens in newborn mice (Melikian et al.,
    1991).

    The metabolism of 5-methylchrysene has also been investigated in mouse
    epidermis  in vivo. The diol precursors of 1,2-dihydroxy-3,4-epoxy
    5-methylchrysene and 7,8-dihydroxy-9,10-epoxy 5-methylchrysene were
    present in equivalent quantities at every time, and the ratio of DNA
    adducts with the two precursors was constant over time (Melikian et
    al., 1983).

    In a study of the correlation of the 5-methylchrysene-DNA adduct
    profile in lung tissue with the spectrum of mutations in the K- ras
    protooncogene of lung tumours, up to 200 mg/kg bw 5-methylchrysene
    were administered to A/J mice and the lungs were analysed for DNA
    adducts one to three days later. After a latent period of eight
    months, 90% all lung tumours had mutations of K- ras. 
     N2-Deoxyguanosine was detected as a possible promutagenic adduct
    (You et al., 1994).

    7.10.3.11  1-Methylphenanthrene

    An investigation of an extensive series of alkylated phenanthrenes
    suggests that the presence of a methyl substituent at, or adjacent to,
    the K region (9,10 position) and an unsubstituted angular ring
    adjacent to a free peri position are the prerequisites for mutagenic
    activity in  S. typhimurium. Substitution at the peri position was
    associated with lack of mutagenicity. A non-K-region dihydrodiol
    derived from 1-methylphenanthrene was a potent proximate mutugenic
    metabolite (LaVoie et al., 1983b).

    7.10.3.12  Naphthalene

    Severe bronchiolar epithelial-cell necrosis was reported in mice after
    intraperitoneal injection of naphthalene. Lung, liver, and kidney
    macromolecules were shown by a radiolabelling technique to be the main
    targets. Maximal binding of naphthalene was found 2-4 h after

    application, and a threshold was found at 200-400 mg/kg bw,
    corresponding to glutathione depletion. Covalent binding was highest
    in tissues with high cytochrome P450 mono-oxygenase activity, i.e.
    lung, liver, and kidney (Warren et al., 1982).

    7.10.3.13  Phenanthrene

    A single dose of 300 mg/kg of phenanthrene administered
    intraperitoneally to B6C3F1 mice caused > 20-fold induction of
    hepatic microsomal methoxy-resofurin  O-deethylase activity
    (Chaloupka et al., 1994; see also section 7.10.3.1).

    7.10.3.14  Investigations of groups of PAH

    In rats, expression of the  Cyp1A1 gene is closely associated with
    the inducibility of AHH, an enzyme important for bioactivation of PAH.
     Cyp1A1 is regulated by several factors, including the Ah receptor
    and the cytosolic 4S PAH-binding protein. The role of the latter
    protein was investigated with benzo [a]pyrene and benzo [e]pyrene in
    H4-II-E rat hepatoma cells. Both induced gene expression, as measured
    by ethoxyresorufin O-deethylase activity, but benzo [a]pyrene was
    about 25 times more potent than benzo [e]pyrene. Benzo [a]pyrene
    binds to both the Ah receptor and the 4 S protein, and
    benzo [e]pyrene only to the protein (Houser et al., 1992).

    A series of PAH were investigated in a novel short-term test for the
    detection of carcinogens, the initiator tRNA acceptance assay.
    Positive responses, i.e. > 15% stimulation, were induced by chrysene,
    benzo [c]-phenanthrene, dibenz [a,h]anthracene, benzo [a]pyrene,
    and dibenzo [a,i]pyrene; and negative responses were induced by
    naphthalene, anthracene, phenanthrene, pyrene, benz [a]anthracene,
    benzo [e]pyrene, perylene, and coronene. All of the potent
    carcinogens were active in this assay (Hradec et al., 1990).

    In a study of the non-carcinogenic PAH anthracene, fluorene, and
    naphthalene and several carcinogenic amine derivatives in rats,
    naphthalene failed to induce induce the cytochrome P450-dependent
    mixed-function oxidases, whereas anthracene was a weak and fluorene an
    effective inducer. A relationship was found between carcinogenicity
    and the ability to induce hepatic P450 activity. It was assumed that
    fluorene is not carcinogenic because it cannot form mutagenic
    intermediates (Ayrton et al., 1990).

    In a study of the induction of various PAH of the mono-oxygenase
    isoenzymes in mouse liver microsomes, the cytochrome P448 and P450
    groups were classified by using specific inhibitors in studies of
    7-ethoxycoumarin activity. According to the pattern of enzymes
    induced, the following groups were distinguished: (i) P448 type,
    including dibenz [a,h]anthracene and benzo [k]fluoranthene; (ii)
    mixed type, including pyrene, benzo [j]fluoranthene, and
    benzo [e]pyrene, in which two inhibitors acted on the enzyme
    reaction; and (iii) special P448 type consisting of
    indeno[1,2,3- cd]pyrene, in which one inhibitor stimulated the

    reaction. The PAH investigated were not a homogeneous group of
    selective P448 inducers. No correlation was found with mutagenic
    potency (Kemena et al., 1988).

    8.  EFFECTS ON HUMANS

     Appraisal

    There is little information on human exposure to single, pure
    polycyclic aromatic hydrocarbons (PAH). That which is available
    includes reports of accidental exposure to naphthalene and some data
    from defined short-term studies of volunteers. All other reports are
    of exposure to mixtures of PAH, which also contained other potentially
    carcinogenic chemicals, in occupational and environmental situations.
    Information on the health effects of these mixtures is confined to
    their carcinogenic potential, for which there is evidence from a
    number of epidemiological studies, especially for lung cancer and, in
    some cases, cancers of the skin and of the urinary bladder. Since
    single PAH and PAH mixtures are known to be carcinogenic in
    experimental animals, it is plausible to attribute the enhanced cancer
    risks seen in humans predominately to the PAH. In addition, the
    results of epidemiological studies are important in risk assessment.
    Therefore, in contrast to the preceding sections, the results of
    studies of PAH mixtures are also presented.

    Many workplaces have atmospheres with heavy loads of PAH. The cohorts
    affected are gas workers, those exposed at coke ovens, wood
    impregnation workers, people working at waste incinerators, workers in
    bus garages, workers in nickel and copper refineries and in aluminium
    smelters, asphalt workers, and chimney sweeps. Evaluation of the
    immunocompetence of coke-oven workers indicated decreased serum
    immunoglobulin levels and decreased immune function.

    Biomarkers used to assess exposure to PAH include hydroxyphenanthrenes
    and 1-hydroxypyrene in urine and DNA adducts in peripheral blood
    lymphocytes.

    8.1  Exposure of the general population

    8.1.1  Naphthalene

    Naphthalene is often used in houses as an insect repellant, mainly
    against moths, and many incidents of poisoning have been reported.
    Acute haemolytic anaemia is a typical systemic effect of oral, dermal,
    or inhalation exposure. The lethal oral doses determined in cases of
    accidental poisoning are 5-15 g for adults and 2 g within two days for
    a six-year old child. Repeated exposure to naphthalene fumes or dust
    has led to corneal ulceration, lenticular opacities, and cataracts
    (Sandmeyer, 1981). Some case reports are described in more detail
    below.

    8.1.1.1  Poisoning incidents

     (a)  Oral exposure

    Between 1949 and 1959, 10 cases of the oral poisoning by naphthalene
    in children were documented in the United States. The amounts were
    usually not specified but were in the order of grams. Some of the
    children developed haemolytic anaemia (Anziulewicz et al., 1959).

    The symptoms that developed after naphthalene intake included nausea,
    vomiting, and convulsions after one to several days, often followed by
    diarrhoea. Other symptoms were disturbances of consciousness,
    lethargy, ataxia, and, in severe cases, coma and hemiplegia.
    Haemolytic anaemia occurred concomitantly, with plasma haemoglobin
    contents of up to 40%, often followed by haemoglobinuria. Mild to
    severe jaundice can also occur; in one fatal case of poisoning, patchy
    liver necrosis was reported. Treatment consists of blood transfusions
    and additional alkalization of the urine; following this treatment,
    rapid recovery, without persistent damage, was observed (Konar et al.,
    1939). In five cases of acute haemolytic anaemia in children of about
    two years of age who had eaten moth balls consisting of pure
    naphthalene, there was complete recovery within one to four weeks
    after transfusion (Zuelzer & Apt, 1949; Mackell et al., 1951).

    Tests  in vitro revealed that it was not naphthalene itself but its
    metabolites a-naphthoquinone and a-naphthol that cause a decrease in
    reduced glutathione in erythrocytes. Whole blood from patients
    contained erythrocytes with defective glutathione metabolism. This
    defect is observed in about 15% of black males and 2% of black females
    (Zinkham & Childs, 1958).

     (b)  Dermal exposure

    The effects of skin contact in sensitive individuals range from
    irritation to severe dermatitis after exposure to quite small amounts
    of naphthalene, such as wearing clothes that had been treated with
    moth balls. Workers exposed to naphthalene may develop dermatitis on
    their hands, arms, legs, and abdomen (Gerarde, 1960). Cases of
    haemolytic anaemia have been reported in babies who absorbed
    naphthalene from nappies that had been stored with moth balls
    (Anziulewicz et al., 1959).

     (c)  Inhalation

    Haemolytic anaemia was also observed in babies who had inhaled
    naphthalene from moth ball-treated wool blankets (Valaes et al.,
    1963). The case of a man with exfoliative dermatitis was reported,
    which resolved after all contact with naphthalene was eliminated
    (Fanburg, 1940).

    8.1.1.2  Controlled studies

    When the forearm skin of three volunteers was treated with anthracene
    in a 2% benzene solution (dose not specified) and irradiated with a
    monochromator (340-380 nm), urticarial reactions were seen, with
    burning and erythema lasting for several days (Crow et al., 1961).

    Twelve healthy white men, 12-26 years old, with fair complexions were
    treated dermally with anthracene in an ethanolic acetone solution at
    25 µg/cm2 and received ultraviolet irradiation 2 h later. Specific
    skin reactions such as transient erythema, delayed erythema, and
    whealing were seen. The effect was related both to the anthracene and
    the amount of radiation energy. Controls who received no anthracene
    treatment but the same irradiation showed no sign of erythema (Kaidbey
    & Nonaka, 1984).

    Regressive verrucae were reported after up to 120 dermal applications
    of 1% benzo [a]pyrene to human skin over four months. The reversible
    and benign changes were thought to be neoplastic proliferations, but a
    group that did not receive benzene was not evaluated (Cottini &
    Mazzone, 1939). Similar epidermal changes and nucleolar enlargement
    were reported in volunteers painted daily for four consecutive days on
    1-cm2 areas of the upper back (Rhoads et al., 1954).

    8.1.2  Mixtures of PAH

    8.1.2.1  PAH in unvented coal combustion in homes

    Interdisciplinary studies were conducted to investigate exposure to
    PAH and the high lung cancer rates in a rural county, Xuan Wei,
    located in Yunnan Province, China (Mumford et al., 1987). Mortality
    from lung cancer in this county is five times the Chinese national
    average, especially among the women, who have the highest rate in
    China. Three communes had a mortality rate that was 24 times the
    national rate: 126 per 100 000 for women and 118 per 100 000 for men
    during 1973-79. An unusual observation in Xuan Wei is the similarity
    of the lung cancer rates in men, most of whom are smokers, and women,
    most of whom are not (< 0.1% smoke). The mortality rate from lung
    cancer was correlated with domestic use of 'smoky' coal
    (medium-volatile bituminous coal with low sulfur and high ash) for
    cooking and heating, but not with use of wood or smokeless coal.
    Monitoring of air during cooking inside the homes showed that women
    were exposed to extremely high levels of PAH, with a mean
    benzo [a]pyrene concentration of 14.7 µg/m3, comparable to the
    levels to which coke-oven workers are exposed. They were also exposed
    < 24 mg/m3 of submicron particles containing up to 82% of the
    organic matter. The major organic components of smoky coal emissions
    are the three- to five-ring alkylated PAH, which contributed 43% of
    the organic mass of the particles and 61% of the total mutagenicity in
    assays in  S. typhimurium. The four-ring PAH were the most
    tumorigenic (Chuang et al., 1992). Organic extracts of particles from
    coal smoke were more potent in initiating tumours in Sencar mouse skin
    than those from wood and smokeless coal combustion and were complete

    carcinogens (Mumford et al., 1990). Xuan Wei residents exposed to
    smoky coal emissions had significantly more 9-hydroxy benzo [a]pyrene
    in their urine, and cells obtained by bronchial alveolar lavage had
    more DNA adducts (detected by 32P-postlabelling) than those of
    controls (Lewtas et al., 1993). High ratios of the concentrations of
    methylated PAH and parent PAH (9.8:1 for women and 5.8:1 for men) in
    urine samples from Xuan Wei residents confirmed that they were exposed
    to high concentrations of alkylated PAH. Thus, alkylated PAH may play
    an important role in the etiology of lung cancer in Xuan Wei (Mumford
    et al., 1995).

    1-Hydroxypyrene was used as a urinary biomarker to monitor the
    exposure of urban populations to PAH originating from coal burning. A
    good correlation was found between the concentrations of pyrene and
    benzo [a]pyrene in ambient in air and 1-hydroxypyrene in urine (Zhao
    et al., 1990; see also section 8.3.2).

    8.1.2.2  PAH in cigarette smoke

    A large volume of literature exists on the effects of tobacco smoke on
    human lungs (see IARC, 1986). On the basis of more than 100
    prospective and retrospective studies in more than 15 countries,
    cigarette smoke has been shown to be by far the most important single
    factor contributing to the development of lung cancer. Other types of
    cancer caused by cigarette smoking include cancers of the oral
    cavities, larynx, pharynx, oesophagus, bladder, renal pelvis, renal
    adenocarcinoma, and pancreas.

    Levels of 11 ng per cigarette benzo [a]pyrene were found in
    mainstream smoke and 103 ng per cigarette in sidestream smoke; the
    corresponding values were 6.8 and 7.6 ng per cigarette for
    benzo [e]pyrene, 20 and 497 ng per cigarette for chrysene and
    triphenylene, and 13 and 204 ng per cigarette for benz [a]anthracene
    (Grimmer et al., 1987). In sidestream smoke, PAH with four or more
    rings were responsible for 83% of the total carcinogenic activity
    (Grimmer et al., 1988c).

    8.1.2.3  PAH in coal-tar shampoo

    Of eight commercially available coal-tar shampoos, that with the
    highest PAH content (100 times that of the others), containing, e.g.
    285 mg/kg pyrene and 56 mg/kg benzo [a]pyrene, was chosen for testing
    in 11 healthy people. A dose of 20 g shampoo was used in the evening
    (see section 8.2.3), and the internal dose of PAH was assessed as
    urinary 1-hydroxypyrene. One day after exposure, the internal dose was
    10 times higher than the background level, similar to that measured in
    coke-oven workers (van Schooten et al., 1994). The potential
    carcinogenicity of coal-tar shampoo formulations has been studied (see
    section 7.7). It has been suggested that modest therapeutic doses of
    agents containing coal-tar and dithranol are tumorigenic after
    combined application and that their use should be reviewed (Phillips &
    Alldrick, 1994).

    8.2  Occupational exposure

    No studies on occupational exposure to single PAH were available, as
    in general, industrial workers using or producing coal or coal
    products are exposed to mixtures of PAH (see section 5.3). Table 95
    lists workplaces in which there is exposure to PAH and the types of
    employees exposed. Epidemiological studies have been conducted on
    workers exposed at coke ovens in coal coking and coal gasification, at
    asphalt works, at foundries, and at aluminium smelters and to diesel
    exhaust. Details of the most recent and most important cohort and
    case-control studies are given in Tables 96 and 97 (for reviews of
    these studies, see also IARC 1983, 1984a,b, 1985).

    Levels of exposure to single PAH in these occupations have been
    reported (see section 5.3). In the following text, levels of exposure
    to 'total PAH' are also given, as reported by the authors; however,
    'total PAH' represents only the sum of a limited number of compounds
    that have been quantified, i.e. the selection of the investigator, and
    such measurements cannot be compared for the purpose of evaluating
    levels or risks of pollution.

    All benzo [a]pyrene concentrations are reported for comparative
    purposes, as it is the only PAH that has been determined in almost all
    investigations because of its well-known carcinogenicity. It is
    commonly used as an indicator of the level of particle-bound PAH, and
    particularly of carcinogenic ones, but PAH profiles may vary according
    to source.

    The first attribution of a PAH-related cancer to an occupational
    exposure was that of Pott in 1775, who described the susceptibility of
    English chimney sweeps to scrotal cancer (Pott, 1775); a second was
    published by Butlin in 1892. Easily avoidable dermal cancers are
    seldom seen today, owing to better personal hygiene and better working
    conditions, but the number of respiratory cancers is still
    significantly higher in occupational cohorts than in the general
    population. In a study of Swedish chimney sweeps who were exposed to
    < 9 µg/m3 benzo [a]pyrene, significantly increased rates of lung
    tumours were observed, with a standardized mortality rate (SMR) of
    2.06 (Table 96; Gustavsson et al., 1988); however, chimney sweeps were
    also exposed to arsenic, chromium, cadmium, nickel, sulfur dioxide,
    carbon monoxide, organic solvents, and asbestos.

    Most important for an evaluation of the possible risk for cancer due
    to exposure to PAH are studies of workers exposed at coke ovens in
    coke plants or in coal-gasification processes, where the PAH
    concentrations are considerable, with levels of 1 mg/m3 total PAH and
    300 µg/m3 benzo [a]pyrene (Lindstedt & Sollenberg, 1982; Swaen et
    al., 1991; see also section 5.3). The concentrations to which workers
    are exposed are not available in most epidemiological studies,
    however, and coke-oven workers may be exposed to several other
    carcinogenic compounds, such as 2-naphthylamine, arsenic, and benzene.

    Table 95. Occupations in which there is exposure to polycyclic
    aromatic hydrocarbons

                                                                          

    High exposure

    -    coke ovens
    -    coal gasification plants
    -    chimney sweeping
    -    petroleum refineries (mainly exposed to naphthalene and its methyl
         derivatives)
    -    impregnation of wood with creosotes (mainly exposed to
         naphthalene, phenanthrene, and fluorene)
    -    handling of creosote-impregnated wood (e.g. railroad and utility
         workers, carpenters, mainly exposed to naphthalene, phenanthrene,
         and fluorene)

    Medium exposure

    -    asphalt and pavement work
    -    roofing
    -    aluminium production
    -    graphite electrode production (e.g. anode production for the
         aluminiurn industry)
    -    founding (processing of e.g. steel and other alloys, from coal
         additives in moulding sand)
    -    smokehouses (processing of meat and fish)

    Low exposure

    -    mechanics, bus garage workers, and machinists (from diesel and
         spark-ignition engine exhaust gases)
    -    mining (from diesel engine exhaust gases)
    -    use of lubricating and cutting oils (e.g. in steel production)
    -    cooking
                                                                          


        Table 96. Epidemiological studies of lung caner in cohorts exposed to polycyclic aromatic hydrocarbons

                                                                                                                                               

    Group, no.,   Comparison       Exposure concentration,    Deaths           Dose-response, remarks          Other tumour sites  Reference
    workplace,    group, no.       exposure to other                                                           and diseasesa
    study period  workplace        chemicals, smoking habits  No.  SMR, RR                                                       
                                                                   (95% Cl)                                    Type         SMR,
                                                                                                                            RR
                                                                                                                                               

    Coal coking
    5321,         10 497           Coal-tar pitch volatiles;b 255  1.95        Risk decreased with period      All causes,  1.08   Costantino
    coke oven     non-oven,        3.2 mg/m3 (topside),            (1.59-2.33) follow-up; findings             all cancers, 1.34   et al. (1995);
    1952-82,      steel industry   2.0 (top-side parttime),                    consistent across racial        prostate     1.57   Rockette &
                                   0.88 (side); no                             categories; strong                                  Redmond
                                   information on smoking                      correlation with duration of                        (1985);
                                   habits concentration                        exposure and exposure                               Redmond
                                                                                                                                   (1983)

    5639          National         No information on          62   1.29        Strong correlation with         Total        1.19   Swaen et al.
    coke plant,   population       smoking habits                  (0.99-1.66) exposure concentration;         mortality,   1.66   (1991)
    1945-84       (Netherlands)                                                risks increased in              respiratory  3.08
                                                                               comparison with workers at      disease,
                                                                               a nitrogen fixation plant       liver

    536,          National         information on smoking     25   2.38***     Coke-oven workers: 1.75         All causes,  1.41   Chau et al.
    coke plant    population       habits                                      (2 cases); near oven            all cancers, 1.33   (1993)
    1963-87       (France)                                                     workers: 2.52** (8 cases);      cardio-      1.33
                                                                               unexposed workers: 2.28*        vascular
                                                                               (6 cases)                       disease
                                                                               Risk increased (not
                                                                               significant) for workers in
                                                                               oldest plant

    6767,         National         Some information on        167  1:17*       -                               -            -      Hurley et al.
    coke plant    population       smoking habits                                                                                  (1983)
                  (Scotland,
                  England, Wales)

    Table 96. (continued)

                                                                                                                                               

    Group, no.,   Comparison       Exposure concentration,    Deaths           Dose-response, remarks          Other tumour sites  Reference
    workplace,    group, no.       exposure to other                                                           and diseasesa
    study period  workplace        chemicals, smoking habits  No.  SMR, RR                                                       
                                                                   (95% Cl)                                    Type         SMR,
                                                                                                                            RR
                                                                                                                                               

    subcohorts:
    1617, coke    -                -                          34   0.94        No clear correlation with       -            -
    oven,                                                                      duration of exposure; problems
    1966-78                                                                    in classification of exposure
                                                                               (risk increase with > 5 years
                                                                               and > 10 years exposure)
    1158, coke    -                -                          32   1.05        Lung cancer risk increased      -            -
    oven,                                                                      in younger workers; no clear
    1967-80                                                                    correlation with duration of
                                                                               exposure and exposure
                                                                               concentration; problems in
                                                                               classification of exposure

    Coal gasification
    2449+1176     National         2-Naphthylamine,           99   3.82b       RR given for groups with        Bladder      2.35   Doll et al.
    (2 cohorts),  population       2 µg/m3; some              23   2.72        regular exposure; also          cancer              (1972)
    1953-65       (England and     information on                              increased risk in group with
                  Wales)           smoking habits                              intermittent exposure;
                                                                               correlation with exposure
                                                                               concentration and duration
                                                                               of exposure

    724,1953-80   (a) 3792, same   Median of 8 measurements:  68   3.53**a     No correlation with             All cancers, 1.98   Manz et al.
                  plant, not at    total dust, max.                            duration of exposure; 88% of    urinary      4.35   (1983)
                  coke-oven        264 mg/m3, BaP, 28                          workers with > 10 years'        system
                  (b) 681,         µg/m3, max. 89;                             exposure                        cancers
                  office and       some information on
                  administration   smoking habits

    Table 96. (continued)

                                                                                                                                               

    Group, no.,   Comparison       Exposure concentration,    Deaths           Dose-response, remarks          Other tumour sites  Reference
    workplace,    group, no.       exposure to other                                                           and diseasesa
    study period  workplace        chemicals, smoking habits  No.  SMR, RR                                                       
                                                                   (95% Cl)                                    Type         SMR,
                                                                                                                            RR
                                                                                                                                               

                  (a) local
                  population
                  (Hamburg)

    295,          Local worker     BaP top of ovens:          4    0.82        Owing to incomplete employment  All causes   1.27   Gustavsson
    1966-86       population       1964: 4.3 µg/m3                 (0.22-2.11) registers, only workers                             & Reuterwall
                                   (0.007-33)                                  with short and recent exposure                      (1990);
                                   1965: 0.52 µg/m3                            selected; no correlation with                       Gustavsson
                                   (0.021-1.29); no                            duration of exposure                                (1989);
                                   differences in smoking                                                                          Gustavsson
                                   habits between exposed                                                                          et al. (1987)
                                   and controls

    Asphalting
    679, paving,  National         Fume condensate;           25   2.90        SMR for lung cancer given       All causes,  1.63   Hansen
    1959-86       population       flooring: 0.5-260 mg/m3;        (1.88-4.29) only for workers aged 40-89     all cancers  2.25   (1989);
                  (Denmark)        median,19.7, manual                         years; overall mortality        Workers             Hansen et
                                   road paving: 4.3-3.4 mg/m3;                 excess primarily in younger     aged 40-89          al., 1991c,
                                   total PAH: median, 183                      age groups                      years: liver 4.67   1992;
                                   µg/m3; BaP, 4 µg/m3;                                                        cirrhosis           Wong et al.
                                   some information on                                                                             (1992)
                                   smoking habits

    2572, paving, National         -                          7    1.10        Follow-up too short             All causes,  0.69   Engholm et
    1971-79 to    population                                  8    1.24                                        stomach      2.01   al. (1991);
    1985          (Sweden)                                         (0.53-2.34)                                 cancer              Partanen &
                                                                                                                                   Boffetta
                                                                                                                                   (1994)

    Table 96. (continued)

                                                                                                                                               

    Group, no.,   Comparison       Exposure concentration,    Deaths           Dose-response, remarks          Other tumour sites  Reference
    workplace,    group, no.       exposure to other                                                           and diseasesa
    study period  workplace        chemicals, smoking habits  No.  SMR, RR                                                       
                                                                   (95% Cl)                                    Type         SMR,
                                                                                                                            RR
                                                                                                                                               

    704, roofing, National         -                          3    2.79        Follow-up too short             All causes   0.91   Engholm et
    1971-79 to    population                                  4    (0.99-9.31)                                                     al. (1991);
    1985          (Sweden)                                                                                                         Partanen &
                                                                                                                                   Boffetta
                                                                                                                                   (1994)

    Paving,       -                -                          332  1.21        Meta-analysis of 11 studies     Stomach,     1.33   Partanen &
    roofing,                                                       (1.08-1.30)                                 bladder,     1.38   Boffetta
    others                                                                                                     skin, non-   1.74   (1994)
                                                                                                               melanoma,    1.41
                                                                                                               leukaemia

    Paving        -                -                          167  0.87        Meta-analysis of 3 studies      Skin, non-   2.18
                                                                   (0.74-1.01)                                 melanoma

    Roofing       -                -                          118  1.96        Meta-analysis of 4 studies      Stomach      1.71
                                                                   (1.46-2.11)

    Creosote
    impregnation
    922           National         -                          13   0.79        -                               Skin, non-   2.37   Karlehagen
                  populations                                      (0.42-1.35)                                 melanoma            et al. (1992)
                  (Sweden and
                  Norway)

    Table 96. (continued)

                                                                                                                                               

    Group, no.,   Comparison       Exposure concentration,    Deaths           Dose-response, remarks          Other tumour sites  Reference
    workplace,    group, no.       exposure to other                                                           and diseasesa
    study period  workplace        chemicals, smoking habits  No.  SMR, RR                                                       
                                                                   (95% Cl)                                    Type         SMR,
                                                                                                                            RR
                                                                                                                                               

    Tar distillation
    76,           449,             PAH: 29 µg/m3,             4          Total rate of tumours                 0            -      Schunk
    1962-72       rubber           BaP: 4 µg/m3; some                    increased (RR 3 and 3.4);                                 (1979)
                  industry;        information on                        3 tumours of the digestive
                  national         smoking habits                        system latency, 10.1-
                  population                                             17.5 years
                  (Germany)

    Foundries
    2990          General          No information on          224   1.44**                                     Respiratory         Egan-Baum
    (2651 white   population       smoking habits             white white                                      disease:            et al. (1981)
    males; 339    (USA)                                       males,males;                                     white males  1.10
    black males),                                             39    76**                                       black males  1.24
    steel, iron,                                              black black                                      Pneumo-
    non-ferrous,                                              males males                                      coniosis:
    1961-71                                                                                                    black males  5.76
                                                                                                               Respiratory
                                                                                                               tuberculosis:
                                                                                                               white males  2.32
                                                                                                               All cancers:
                                                                                                               white males  1.10
                                                                                                               black males  1.24

    439,          Regional         Data from 1977; total      21   2.50**      Correlation with duration       -            -      Gibson et al.
    steel         population       dust, 1.76-5.11 mg/m3;                      of exposure; no correlation                         (1977)
    foundry,      (Toronto)        respirable dust, 0.69-2.65                  between latency and exposure
    1967-77                        mg/m3; no cristobalite                      concentration
                                   or tridymite; coal-tar pitch
                                   volatiles, 0.19-0.43 mg/m3;
                                   BaP, 0.049-0.152 µg/m3;

    Table 96. (continued)

                                                                                                                                               

    Group, no.,   Comparison       Exposure concentration,    Deaths           Dose-response, remarks          Other tumour sites  Reference
    workplace,    group, no.       exposure to other                                                           and diseasesa
    study period  workplace        chemicals, smoking habits  No.  SMR, RR                                                       
                                                                   (95% Cl)                                    Type         SMR,
                                                                                                                            RR
                                                                                                                                               

    1718,         General          Some information on        11   2.04        No clear correlation with       -            -      Moulin et al.
    steel or      population       smoking habits                  (1.02-3.64) duration of exposure or                             (1990)
    ferro-        (France)                                                     latency
    chromium
    production,
    31 years

    4227,         General          -                          17   0.88        -                               Liver        1.74   Moulin et al.
    steel plant,  population                                       (0.51-1.40)                                 cirrhosis           (1993)
    two cohorts,  (France)
    1969-84

    210,          -                -                          2    0.68        -                               -            -
    subcohort:                                                     (0.08-2.45)
    ferroalloy
    workshop

    477,          -                -                          11   2.29        No clear correlation with       -            -
    subcohort:                                                     (1.14-4.09) duration of exposure or
    steel foundry                                                              latency; significantly
                                                                               increased for > 30 years
                                                                               since first employment

    Table 96. (continued)

                                                                                                                                               

    Group, no.,   Comparison       Exposure concentration,    Deaths           Dose-response, remarks          Other tumour sites  Reference
    workplace,    group, no.       exposure to other                                                           and diseasesa
    study period  workplace        chemicals, smoking habits  No.  SMR, RR                                                       
                                                                   (95% Cl)                                    Type         SMR,
                                                                                                                            RR
                                                                                                                                               

    10 491,       General          -                          441 1.47***      SMRs increased for all          Stomach      1.37   Sorahan
    steel         population                                                   foundry occupations             cancer              & Cooke
    foundry,      (England and                                                 (fettling shop, pattern,                            (1989)
    20 years,     Wales)                                                       machine, maintenance,
    1946-65 to                                                                 inspection); some
    1985                                                                       correlation with latency;
                                                                               no significant correlation
                                                                               with duration of exposure

    6494,         General          2 plants, around           77   0.99        Except for 1 plant, furnace     -            -      Kjuus et al.
    production of population       furnaces:PAH, 3-49 µg/m3;       (0.78-1.24) workers showed no increase                          (1986)
    ferrosilicon  (Norway)         anode paste plant: 2-20         SIR         in rate of lung cancer (8
    ferromanganese,                µg/m3; total dust: 10-30                    cases); increase in anode pass
    6 plants,                      mg/m3; manganese:                           plant workers (3 cases); no
    1953-82                        0.5-2 mg/m3 Some                            correlation with duration
                                   information on smoking                      of exposure
                                   habits

    5579,         (a) National     -                          74   (b) 1.17    Information on                  Malignant    2.05   Sherson &
    iron, steel,  population                                                   employment available only       respiratory         Iversen
    1967-69       (Denmark),                                                   for 1967-69 and 1972-74;        tumours,            (1986)
    non-ferrous   (b)Economically                                              misclassification possible;     respiratory  1.54
    foundries,    active                                                       some correlation with           disease
    1972-74       population,                                                  duration of exposure            excluding
    (part to      (c) Skilled                                                                                  silicosis,
    1980)         and unskilled                                                                                all causes   1.11
                  manual workers

    Table 96. (continued)

                                                                                                                                               

    Group, no.,   Comparison       Exposure concentration,    Deaths           Dose-response, remarks          Other tumour sites  Reference
    workplace,    group, no.       exposure to other                                                           and diseasesa
    study period  workplace        chemicals, smoking habits  No.  SMR, RR                                                       
                                                                   (95% Cl)                                    Type         SMR,
                                                                                                                            RR
                                                                                                                                               

    8147,         National         No information on          72   1.23 white  No correlation with duration    -            -      Andjelkovich
    iron foundry, population       smoldng habits                  males       of exposure; smoking may                            et al. (1990)
    1950-85       (USA)                                            (0.96-1.54) be responsible for lung
                  Local population                                 67          cancer
                                                                   132 non-
                                                                   white males
                                                                   (1.02-1.67)

    Aluminium production
    22 010,       General          No information on          272  0.964       Highest SMR > 25 years          All causes,  85.6   Rockette &
    15 plants,    population       smoking habits                              of exposure in Soderberg        all          88.6   Arena (1983)
    1946-77,      (USA)                                                        proccess: SMR 2.0 based         malignant
    Soderberg                                                                  on 5 deaths; some               tumours
    prebake                                                                    correlation with duration of
                                                                               exposure and latency

    6455,         General          Some information on        37   1.14        Electrolysis workers:           -            -      Mur et al.
    11 plants,    population       smoking habits                  (0.85-1.48) SMR, 1.36 (4 deaths);                               (1987)
    Soderberg     (France)                                                     no correlation with duration
    prebake,                                                                   of exposure or latency
    1950-76

    4213, 1 plant General          Coal-tar pitch volaties    32   0.93        For > 20 benzene-soluble        Brain,       2.17   Spinelli et al.
    Soderberg,    population       low: < 0,2 mg/m3;               (0.68-1.25) material of coal-tar pitch      bladder(SIR) 1.69   (1991);
    1954-85       (British         medium: 0.2-1; high:                        volatiles years: SIR 1.43;                          Ronneberg &
                  Columbia)        > 1; information on                         correlated with duration of                         Langmark
                                   smoking habits                              exposure; some correlation                          (1992)
                                                                               with latency; adjustment for
                                                                               smoking: no change in lung
                                                                               cancer risk

    Table 96. (continued)

                                                                                                                                               

    Group, no.,   Comparison       Exposure concentration,    Deaths           Dose-response, remarks          Other tumour sites  Reference
    workplace,    group, no.       exposure to other                                                           and diseasesa
    study period  workplace        chemicals, smoking habits  No.  SMR, RR                                                       
                                                                   (95% Cl)                                    Type         SMR,
                                                                                                                            RR
                                                                                                                                               

    5406,         (a) Regional     No information on          101  1.43*       SMRs for workers exposed        All cancers, 1.23   Gibbs (1985);
    3 plants,     population       smoking habits                              to tar, SMR significantly       respiratory  1.65   Gibbs &
    Soderberg,    (Quebec)                                                     increased compared with         disease,            Horowitz
    prebake,      (b) Local                                                    local population and            pneumonia    1.99   (1979)
    1954-85       population                                                   never-exposed workers           and bronchitis,
                                                                               Significant correlation         oeosophageal 1.53
                                                                               with duration of exposure;      and gastric
                                                                               correlation with latency;       tumours
                                                                               risk decreased in later
                                                                               periods (1974-77)

    5485,         -                -                          12   1.69        SMR increased in relation       -            -      Gibbs (1985);
    Soderberg,                                                                 to local population                                 Gibbs &
    1950-51;                                                                                                                       Horowitz
    1977                                                                                                                           (1979)

    694           General          Some information on        19   1.16        Workers with at least 3         -            -      Ronneberg &
    Soderberg,    population       smoking habits                  (0.70-1.81) years of employment; some                           Andersen
    prebake       (Norway)                                         (SIR)       correlation with duration of                        (1995)
    1962-91                                                                    exposure and latency

    Other workplaces
    2219,         General          -                          29   0.85        -                               All causes,  0.67   Tate et al.
    11 carbon     white                                            0.57-1.21)                                  circulatory  0.60   (1987)
    plants,       population                                                                                   disease,
    1974-83       (USA)                                                                                        respiratory  0.51
                                                                                                               disease

    Table 96. (continued)

                                                                                                                                               

    Group, no.,   Comparison       Exposure concentration,    Deaths           Dose-response, remarks          Other tumour sites  Reference
    workplace,    group, no.       exposure to other                                                           and diseasesa
    study period  workplace        chemicals, smoking habits  No.  SMR, RR                                                       
                                                                   (95% Cl)                                    Type         SMR,
                                                                                                                            RR
                                                                                                                                               

    176,          Regional         Total dust: 5-100 mg/m3;        1.97        -                               -            -      Gustavsson
    waste         population       some information on             (1.21-2.75)                                                     & Reuterwall
    incinerator,                   smoking habits                                                                                  (1990);
    1951-85                                                                                                                        Gustavsson
                                                                                                                                   (1989)

    Nickel/copper Regional         Laboratory fume            50   1.47        Lung tumours correlated         -            -      Verma et al.
    smelter and   population       generation experiments          (1.02-1.81) with duration of exposure                           (1992)
    refinery;     (Ontario)        showed high                                 only it exposed to PAH
    special                        concentrations of PAH
    subcohorts                     (asphalt > tar > mastic);
    exposed to                     no information on smoking
    tar                            habits
                                                                                                                                               

    OR, odds ratio; RR, relative risk; SMR, standard mortality ratio; SIR, standard incidence ratio; BaP, benzo[a]pyrene
    SMR or RR for whole study population is given; results for special subcohorts, subdivided by e.g. level or duration of exposure or
    latency, are given under remarks, unless otherwise stated
    * Statistically significant at p < 0.01; ** statistically significant at p < 0.01; *** statistically significant at p < 0.001
    a Only statistically significant (p < 0.05) increased or decreased rates are shown; unless otherwise stated, refers to mortality
    b Benzene-soluble fraction of total particulate matter

    Table 97. Case-control studies of cancer types possibly associated with exposure to polycyclic aromatic hydrocarbons PAH)

                                                                                                                                               

    Cases, no.,     Exposure:         Controls: no., matching             Odds ratio     Remarks                            Reference
    tumour type,    PAH analysed,                                         (95% Cl)
    study group     exposure
                    concentration
                                                                                                                                               

    Lung tumours

    NR              Exhaust from      Patients with cancer of prostate,   1.41           2 miles from coke oven; some       Lyon et al. (1981)
                    coke plant        breast, or brain                                   correlation with distance from
                                                                                         coke oven, highest at 2 and 3
                                                                                         miles distance; effect may also
                                                                                         be due to occupational exposure

    Asphalt         -                 -                                   1.12           Meta-analysis of 5 studies         Partanan & Boffetta
    workers,                                                              (0.93-1.34)                                       (1994)
    paving,
    roofing,
    others,

    113             Iron foundry      249 all other deaths in cohort of   2.36*          OR for workers aged 42-64;         Egan-Baum et al.
    cohort of       versus steel or   foundry workers except non-         1.19           of workers aged > 65, only 65%     (1981)
    foundry         non-ferrous       malignant respiratory disease                      successfully traced
    workers         foundry           and other cancers

    12,             Occupation in     58 from cohort of steel foundry     4.51                                              Moulin et al. (1990)
    cohort of steel stainless-steel   workers
    workers         versus ferro-
                    chromium

    (a) 51, (b) 47, BaP: 0.1-15       From cohort of iron foundry         -              More cases exposed to high PAH     Tola et al. (1979)
    cohort of iron  µg/m3; small      workers                                            concentrations than controls, not
    foundry         differences       (a) 153, matched by age and                        statistically significant; some
                    between           intensity of exposure, no cancer                   information on smoking habits
                    workplaces        cases

    Table 97. (continued)

                                                                                                                                               

    Cases, no.,     Exposure:         Controls: no., matching             Odds ratio     Remarks                            Reference
    tumour type,    PAH analysed,                                         (95% Cl)
    study group     exposure
                    concentration
                                                                                                                                               

                                      (b) 47, also same time of entry
                                      into foundry
                                      (c) 27, cases compared with
                                      expected contribution of
                                      exposure of foundry workers

    74, cohort of   Exposure to       1138, manual workers at same        2.00           Figure given for exposure for      Armstrong et al.
    aluminium       coal-tar pitch    plant, not matched, similar         (1.33-2.75)    20-41 years at Soderberg pots,     (1994)
    production      volatiles;        distribution of birth years                        no data for exposure to
    workers,        measurements of                                                      benzene-soluble material in
    Soderberg       benzene-soluble                                                      general; strong correlation with
    and prebake     material; estimated                                                  exposure concentration, duration
    process         concentrations for                                                   of exposure and latency;
                    different job                                                        adjustment for smoking: no
                    categories; 0-3.5                                                    difference in risk
                    mg/m3

    45 butchers     Combustion        (a) 99 all butchers and             0.84           Smoking habits available           Gustavsson (1989)
    and slaughter-  products, only    slaughter-house workers dying       (0.40-1.77)
    house           low, intermittent from malignant disease
    workers, 11     exposure to       (b) 100 random sample of all
    years           PAH               deceased butchers and
                                      slaughter-house workers
                                      (a) and (b) except tumours related
                                      to chemical exposure

    Table 97. (continued)

                                                                                                                                               

    Cases, no.,     Exposure:         Controls: no., matching             Odds ratio     Remarks                            Reference
    tumour type,    PAH analysed,                                         (95% Cl)
    study group     exposure
                    concentration
                                                                                                                                               

    Skin tumours
    376 patients    Occupational      752 general population; 752         1.14           No correlation with duration of    Kubasiewicz et al.
    with skin       exposure to       patients from hospitals                            exposure; no increased risk for    (1991)
    cancer          PAH               randomly sampled                                   other exposures related to PAH,
                                                                                         i.e. tar, pitch, soot, coke,
                                                                                         bituminous mass; smoking habits
                                                                                         not availalble

    Renal-cell carcinoma
    1982-87,        Occupational      64 patients with haematuria,        2.54           Exposure to coal, tar, or pitch    Sharpe et al. (1989)
    hospitals in    exposure to       61 controls and cases not treated   (0.96-6.99)    RR for exposure to coal increased
    Montreal,       hydrocarbons      with haemodialysis                  0.29           from 10 to 24 years of age; strong
    Canada                            (predisposes for renal cancer)      (0.16-.74)     correlation with duration of exposure
                                                                                         and exposure concentration; no
                                                                                         correlation with latency (no case or
                                                                                         control with latency < 20 years);
                                                                                         smoking habits: no significant
                                                                                         difference between cases and
                                                                                         controls; history of smoking > 20
                                                                                         cigarettes per day associated with
                                                                                         tendency to higher stage disease

    Table 97. (continued)

                                                                                                                                               

    Cases, no.,     Exposure:         Controls: no., matching             Odds ratio     Remarks                            Reference
    tumour type,    PAH analysed,                                         (95% Cl)
    study group     exposure
                    concentration
                                                                                                                                               

    Urinary bladder cancer
    138/(66+ 69),   Occupational      414, from cohort                    2.63           Data consistent with former study; Tremblay et al.
    1970-88         exposure to                                           (1.29-5.37),   strong correlation with exposure   (1995); Theriault et
    aluminium       benzene-soluble                                       adjusted       concentration and duration of      al. (1984)
    plant,          material                                              for smoking    exposure highest risk: Soderberg
    Soderberg       or BaP                                                               potroom workers: 5.15; 1930-54:
                                                                                         BaP, max, 51.5 µg/m3;
                                                                                         benzene-soluble material, max
                                                                                         10 mg/m3; 1985-89: BaP, max,
                                                                                         3.1 µg/m3; benzene-soluble
                                                                                         material, max, 0.36 mg/m3

    General         Contact with      From population                     2.61           All figures given for 8-28 years   Risch et al. (1988)
    population,     diesel or traffic                                     (0.70-12.5)    employed
    1979-82         fumes
                    Aluminium                                             1.69
                    smelting                                              (1.24-2.31)
                    Contact with                                          3.11
                    tars, asphalt                                         (1.19-9.68)
                                                                                                                                               

    OR, odds ratio; RR, relative risk; SMR, standard mortality ratio; SIR, standard incidence ratio; NR, not reported; BaP, benzo[a]pyrene
    SMR or RR for whole study population is given; results for special subcohorts, subdivided by e.g. level or duration of exposure,
    latency, are given under remarks, unless otherwise stated
    a Only statistically significant increased or decreased rates, unless otherwise siated, mortality
    * statistically significant at p < 0.05
    ** statistically significant at p < 0.01
    *** statistically significant at p < 0.001


    A significantly increased risk for lung cancer (SMR, 1.95) was found
    among a cohort of over 5000 workers who were heavily exposed at coke
    ovens in coke plants and were followed-up for over 30 years. Although
    no data were available on smoking habits, the observed effect is not
    likely to be due to smoking since unexposed steel workers in a
    comparison group were assumed to have similar smoking habits. In
    addition, a high correlation was seen between the risk for respiratory
    cancer and the concentration and duration of exposure. The authors
    noted however, that the rates of respiratory cancer decreased during
    the follow-up period, suggesting that implementation of emission
    controls and occupational exposure limits has been beneficial
    (Costantino et al., 1995). The increased risk found in this study was
    also seen in other studies, including some on coal gasification (Doll
    et al., 1972; Manz et al., 1983; Swaen et al., 1991). Other studies,
    however, and especially those involving small cohorts, did not show
    increased rates for lung cancer among coke-oven workers (Hurley et
    al., 1983; Gustavsson & Reuterwall, 1990; Chau et al., 1993).

    Coke-oven workers in China who were exposed to PAH were reported to
    have decreased titres of immunoglobulins M, G, and A in their serum
    and decreased immune function (Lei, 1993).

    Several epidemiological studies have been performed on the potential
    risks of handling asphalt (for a review, see Partanen & Boffetta,
    1994; see also Table 96). The job descriptions included: roofer,
    waterproofer, highway maintenance worker, production of hot-lay
    asphalt, slater, grader, paver, surfacer, and mastic asphalt worker.
    Their exposure to PAH depended on the type of asphalt involved. When
    bitumen is used as the binder, the PAH content is relatively low, with
    about 200 µg/m3 total PAH and up to about 5 µg/m3 benzo [a]pyrene
    (Hansen, 1989; see also section 5.3); bitumen binders contain
    primarily asphaltenes, straight and branched aliphatic hydrocarbons,
    naphthene aromatics, and resins. Most of the PAH are removed by vacuum
    distillation, but they may be formed during cracking operations or be
    reintroduced in the flux used in blended or fluxed bitumens. Coal-tars
    and coal-tar pitches have been used as binders, especially in the
    past, and may contain substantial amounts of PAH (Partanen & Boffetta,
    1994). These workers may also be exposed to several other substances,
    such as silica, limestone, and asbestos (Chiazze et al., 1991;
    Partanen & Boffetta, 1994). In the meta-analysis of Partanen &
    Boffetta (1994), increased risks for lung tumours were seen for both
    pavers and roofers; tumours of the stomach, bladder, and skin and
    leukaemia were also observed. The excess risks were more pronounced
    for roofers than for pavers. It is not clear however, if these effects
    are due to exposure to PAH, as it could not be determined whether the
    carcinogenicity was due to exposure to bitumen or to tar fumes.

    Workers are exposed dermally to very high concentrations of PAH when
    impregnating wood with creosote, as shown by measuring biomarkers,
    especially the excretion of 1-hydroxypyrene in urine (see section
    8.3.2). In a cohort study on 922 creosote-exposed workers, a
    significant increase in the risk for skin cancer (SIR, 2.37) and
    increased risks for lip cancer and malignant lymphoma were observed.

    Since the work involves some time outdoors, it cannot be ruled out
    that exposure to sunlight contributed to the risks for cancers of the
    skin and lip (Karlehagen et al., 1992).

    The PAH concentrations in iron, steel, and other ferroalloy foundries
    reach levels of 50 µg/m3 and that of benzo [a]pyrene about 10 µg/m3
    (Verma et al., 1992; see also section 5.3). Workers in these plants
    also have nearly ubiquitous exposure to silica sand. Silicosis and
    other chronic respiratory abnormalities have been reported for decades
    to be the major health problems of foundry workers. These workers are
    also exposed to asbestos, used for heat protection and insulation
    around furnaces, to benzene, toluene, formaldehyde, iron, and,
    depending on the kind of metal or alloy, to metals such as lead,
    chromium, manganese, nickel, copper, cadmium, and zinc. Increased
    mortality from lung cancer has been observed consistently in many
    studies of foundry workers (Palmer & Scott, 1981; Andjelkovich et al.,
    1990). When the results of all the relevant studies are combined, the
    SMR is 1.43 (Andjelkovich et al., 1990); however, those authors argue
    that the elevated risk is due to smoking, because the SMRs did not
    increase with time since first employment in a foundry or with the
    length of employment in a foundry. Furthermore, the incidence of
    emphysema, which can also be attributed to smoking, is increased in
    epidemiological studies of foundry environments.

    Information on the possible risks for cancer due to exposure to PAH
    can also be obtained from studies of workers in aluminium plants. Two
    types of anode are used: the continuous Söderberg anode and the
    prebaked anode. Both are manufactured from coal-tar pitch and coke,
    and coal-tar pitch volatiles evaporate from them during baking. The
    exposure is heavier in potrooms where the Söderberg process is used,
    because the anodes are baked continuously. With use of prebaked
    anodes, exposure to PAH may occur in the carbon area where the anodes
    are prebaked. During Söderberg electrolysis, workers may be exposed to
    0.3-3.5 mg/m3 of benzene-soluble organic material and 3-35 µg/m3
    benzo [a]pyrene; workers in the carbon area are exposed to
    0.4-1.2 mg/m3 benzene-soluble organic material and 0.4-1.2 µg/m3
    benzo [a]pyrene. Similar concentrations have been detected in other
    parts of such plants (Rœnneberg & Langmark, 1992). These workers are
    also exposed to fluorides, carbon dioxide, sulfur dioxide, magnetic
    fields, hot work environments, and, in some cases, asbestos.

    In a large case-control study, an increased risk for lung cancer was
    found with exposure in a Söderberg potroom, and a significant
    correlation was seen between the increased risk and the duration and
    concentration of exposure and latency. Adjustment for smoking did not
    alter the correlation (Armstrong et al., 1994). Similar increases were
    detected in cohort studies (Rockette & Arena, 1983; Mur et al., 1987).
    The studies differed with regard to the magnitude of the risk and the
    presence of a dose-response relationship (see also reviews by Abramson
    et al., 1989; Rœnneberg & Langmark, 1992). In some studies, however,
    few cases were available (Rockette & Arena, 1983; Mur et al., 1987;
    Rœnneberg & Andersen, 1995).

    Work in potrooms where Söderberg electrolytic cells were used was also
    associated with an increased risk for urinary bladder cancer (Spinelli
    et al., 1991; Rœnneberg & Langmark, 1992; Tremblay et al., 1995). This
    risk may be due to exposure not only to PAH but also to aromatic
    amines, which have been detected in the potrooms (Tremblay et al.,
    1995).

    Asthma-like symptoms, lung function abnormalities, and chronic
    bronchitis have also been detected in workers in aluminium plants
    (reviewed by Abramson et al., 1989; Kongerud et al., 1994), but the
    quality of the studies in which these effects were shown is variable.
    These diseases are believed to be due not to PAH but rather to
    exposure to alumina, cryolite, carbon, fluorides, and sulfur dioxide;
    however, the causative agents have yet to be defined.

    Increased risks for lung cancer were found in several studies of
    workers exposed to diesel exhausts (WHO, 1996). In comparison with the
    occupations described above, the concentrations of PAH to which these
    workers are exposed are usually relatively low. The benzo [a]pyrene
    concentrations in automobile repair shops and garages reach about 70
    ng/m3 (Waller, 1981; Lindstedt & Sollenberg, 1982; Waller et al.,
    1985), and truck drivers are exposed to less than 10 ng/m3 (Guillemin
    et al., 1992).

    The finding of an increased risk for lung cancer must always be
    interpreted in relation to the influence of tobacco smoking. The
    tobacco smoking habits were seldom known for all of the persons
    studied, but there are several reasons for concluding that the
    increased risks for lung cancer are not due solely to tobacco smoking:

    The general population is often used as a reference group, but their
    lung cancer rate is usually lower than that of the working population
    because fewer members of the general population are tobacco smokers
    (Gibson et al., 1977; Hansen et al., 1989; Andjelkovich et al., 1990;
    Moulin et al., 1993). Calculations presented by several authors
    indicate that differences in tobacco smoking habits can contribute
    only about 20% of the excess risk for lung cancer (Hurley et al.,
    1983; Maclaren & Hurley, 1987; Gustavsson et al., 1988; Andjelkovich
    et al., 1990; Moulin et al., 1993). Greater contributions are
    improbable, since other illnesses usually linked to tobacco smoking
    have not been observed to occur more frequently than in controls.

    Another reason for excluding tobacco smoking as the major reason for
    the increased lung tumour rates is that increased risks also have been
    found in studies in which the controls were workers with other
    occupations, and not the general population. In this case, it can be
    assumed that the tobacco smoking habits are similar, and it is
    probable that the increased risks are due to the exposure conditions
    and not to tobacco smoking (Costantino et al., 1995). In addition,
    several studies show a strong correlation between the risk for
    respiratory cancer and the concentration and duration of exposure and
    latency. Finally, in studies in which the information on tobacco
    smoking habits was good and adjustments could be made for the

    influence of tobacco smoking (Spinelli et al., 1991; Armstrong et al.,
    1994), tobacco smoking had no effect on the cancer risk. As no
    information is available about the comparative cancer risks of
    non-smokers and smokers, however, the increased risk for lung cancer
    may always represent a combined risk due to tobacco smoking and the
    exposure conditions.

    Although workers are always exposed to several substances, it seems
    plausible to attribute the increased lung cancer risks at least
    partially to PAH. The increased risk is seen for workers in several
    occupations which have exposure to PAH in common. Although other
    carcinogenic chemicals were present, they differed with each
    occupation. Airborne high-molecular-mass PAH, which are considered to
    be the most carcinogenic, are adsorbed mainly onto particulate matter
    (see section 4.1.2), and it was often difficult to distinguish the
    toxicological effects caused by particles from those caused by the PAH
    themselves.

    8.3  Biomarkers of exposure to PAH

    Several methods have been developed to assess internal exposure to PAH
    after exposure in the environment and in workplaces, which can be used
    to evaluate the adequacy of protective regulations. In most studies,
    metabolites of PAH were measured in urine, 1-hydroxypyrene being
    widely used.

    The genotoxic effects of PAH have been determined in tests for
    mutagenicity in urine and faeces, micronucleus formation, chromosomal
    aberration and sister chromatid exchange in peripheral blood
    lymphocytes, adducts of benzo [a]pyrene with DNA in peripheral
    lymphocytes, and other tissues and with proteins such as albumin; and
    antibodies to DNA adducts. In addition, oncogene expression and
    immunostaining of differentiation antigens on lung cell surfaces have
    been measured as biological indexes of the risk for lung cancer.

    8.3.1  Urinary metabolites in general

    The metabolites measured in urine and faeces include urinary
    thioethers (Burgaz et al., 1992), 1-naphthol (Bieniek, 1994; Hansen et
    al., 1994, 1995), b-naphthylamine (Hansen et al., 1994), hydroxy
    phenanthrenes (Martin et al., 1989; Adlkofer et al., 1990; Grimmer et
    al., 1994; Mannschreck et al., 1996), and 1-hydroxypyrene.

    No difference in thioether excretion in urine was observed between
    controls and coke-oven workers or workers in coke and
    graphite-electrode-producing plants. It was concluded that the
    determination of thioethers in urine is of little value, since smoking
    is a strong confounding factor (Ferreira et al., 1994a,b; Reuterwall
    et al., 1991).

    A good correlation was found with the excretion of hydroxylated
    phenanthrenes and 1-hydroxypyrene in urine (Mannschreck et al., 1996).
    When phenanthrene, pyrene, and benzo [a]pyrene metabolites are
    determined simultaneously, precursors of carcinogens are also
    measured, thus providing an estimate of individual risk (Grimmer et
    al., 1993).

    8.3.2  1-Hydroxypyrene

    1-Hydroxypyrene, a metabolite of pyrene, was introduced as a biomarker
    of exposure to PAH by Jongeneelen et al. (1986) and has since been
    widely used. Its advantages are that pyrene is present in all PAH
    mixtures at relatively high concentrations (2-10%), and in certain
    environments the pyrene content of the total PAH is fairly constant
    (Zhao et al., 1990; Buchet et al., 1992; Jongeneelen, 1994). In
    studies at different workplaces, a strong correlation was found
    between the pyrene concentrations in air and those of
    benzo [a]pyrene, other selected PAH, and total PAH (Jongeneelen et
    al., 1990; Tolos et al., 1990; Zhao et al., 1990; Van Rooij et al.,
    1992; Ferreira et al., 1994a,b; Jongeneelen, 1994; Elovaara et al.,
    1995; Levin et al., 1995; Ovrebo et al., 1995; Quinlan et al., 1995a).
    Pyrene is metabolized predominantly to 1-hydroxypyrene (Grimmer et
    al., 1993, 1994; Levin et al., 1995), which can be measured easily. In
    contrast to other PAH metabolites, which are excreted mainly in
    faeces, 1-hydroxypyrene is excreted in urine.

    8.3.2.1  Method of determination

    The method of determination consists of enzymatic hydrolysis of
    conjugated 1-hydroxypyrene in urine samples, followed by solid-phase
    extraction and high-performance liquid chromatographic separation with
    fluorescence detection (Jongeneelen et al., 1986). An enzyme-linked
    immunosorbent assay has also been used (Santella et al., 1994).

    In most publications, the concentrations of metabolites in urine are
    adjusted to that of creatinine in order to compensate for variations
    in urine flow rates; however, it must be borne in mind that creatinine
    excretion fluctuates widely because of internal and external factors.
    Therefore, correction of the concentrations of chemicals in urine in
    this way does not necessarily improve the correlation with exposure
    (Levin et al., 1995). For comparisons, a mean urinary creatinine
    concentration of 13 mmol/litre can be assumed, giving the
    relationship:

          1 µmol 1-hydroxypyrene per mol creatinine

                     = 1.93 µg/g creatinine

                     = approx. 3 ng/ml urine.

    Since most authors give 1-hydroxypyrene concentrations in µmol/mol
    creatinine, that unit is used in the following text and tables.

    8.3.2.2  Concentrations

     (a)  General population

    The concentrations of 1-hydroxypyrene in urine from the general
    population exposed to PAH are compiled in Table 98. The background
    concentrations of 1-hydroxypyrene in different countries range from
    0.06 to 0.23 µmol/mol creatinine. No difference related to age or sex
    was seen (Zhao et al., 1992), and ethanol consumption did not
    influence 1-hydroxypyrene concentrations (Van Rooij et al., 1994a).

    For nonsmokers, food accounted for 99% of the total daily pyrene
    intake (Van Rooij et al., 1994a). Five volunteers who ate low-PAH
    meals and high-PAH meals showed 100- to 250-fold increases in
    benzo [a]pyrene dose, accompanied by a four- to 12-fold increase in
    1-hydroxypyrene excretion in urine (Buckley & Lioy, 1992). A 10- to
    80-fold increase was detected in one subject who ate 9 oz (250 g) of
    charcoal-grilled beef. In this study of 10 subjects, an eightfold
    interindividual variation in urinary excretion of 1-hydroxypyrene was
    found after one day. As this variation was not appreciably altered
    after adjustment of the 1-hydroxypyrene concentration by urinary
    creatinine concentration or individual body weight, it was assumed to
    be due to individual differences in the rate of absorption,
    metabolism, or excretion of pyrene (Kang et al., 1995).

    The intake of pyrene from cigarette smoking (12 nmol/day) is about the
    same as the dietary intake from normal food (9.4 nmol/day) (Van Rooij
    et al., 1994a). Tobacco smokers who are not otherwise exposed to PAH
    have about twice the level of 1-hydroxypyrene in their urine as
    nonsmokers (Jongeneelen et al., 1990; Sherson et al., 1992; Van Rooij
    et al., 1994a; Levin et al., 1995), although no significant difference
    was found in some studies (Jongeneelen et al., 1988b; Zhao et al.,
    1992; Ny et al., 1993).

    Urine samples from schoolchildren living along arterial roads in Tokyo
    had 1.1-1.6 times more urinary 1-hydroxypyrene than those from
    children in a less polluted suburban area (Kanoh et al., 1993). Much
    higher levels were detected in persons living in highly industrialized
    regions in Poland, due to emissions from coke-oven plants. The
    concentrations are a maximum of twice as high in winter as in summer
    (Jongeneelen, 1994; Ovrebo et al., 1995). 1-Hydroxypyrene levels of up
    to 1.5 µmol/mol creatinine have been detected in towns in China (Zhao
    et al., 1990, 1992).

    Very high exposure to PAH occurs during application of coal-tar
    ointments or shampoos by patients with eczema or psoriasis. The mean
    1-hydroxypyrene concentrations reached 500 µmol/mol creatinine, and
    the maximum value was 5000 µmol/mol creatinine (Santella et al.,
    1994).

        Table 98. Concentrations of 1-hydroxypyrene in urine (µmol/mol creatinine) in the general
    population

                                                                                                

    Type of exposure or         No. of      1-Hydroxypyrene                Reference
    population investigateda    subjects                         
                                            Median         Range
                                            or meanb
                                                                                                

    Non-smokers

    General population,         28          0.06c          < 0.02-0.17     Goen et al. (1995)
    southern Germany
    General population          49          < 0.02c        0.02-0.28       Goen et al. (1995)
    Southern Germany
    Students and university     24          0.23d          -               Jongeneelen et
    personnel,                                                             al. (1986)
    Netherlands
    University staff,           52          0.26           -               Jongeneelen et
    Netherlands                                                            al. (1988b)
    University staff,           39          0.12e          0.04-029        Van Rooij et al.
    Netherlands                                                            (1994a)
    Students and university     15          0.24e          -               Burgaz et al.
    staff, Turkey                                                          (1992)

    Smokers

    General population,         21          0.12c          < 0.02-0.68     Goen et al. (1995)
    Germany
    General population,         20          0.14c          < 0.02-0.3      Goen et al. (1995)
    Germany
    Students and university     22          0.27d          -               Jongeneelen et
    staff, Netherlands                                                     al.(1986)
    Students and university     38          0.28           -               Jongeneelen et
    staff, Netherlands                                                     al. (1988b)
    Students and university     37          0.25e          0.10-0.79       Van Rooij et al.
    staff, Netherlands                                                     (1994a)
    Students and university     14          0.33e          -               Burgaz et al.
    staff, Turkey                                                          (1992)

    Smoking status not specified

    Persons in urban and        27          0.20d          -               Elovaara et al.
    rural areas Estonia                                                    (1995)
    Persons from rural areas,   81          -              0.19-0.27       Ovrebro et al.
    Biala Podlaska, Poland                                                 (1995)
    Students and university     18 N        0.077d         0.002-0.57      Viau et al. (1993)
    staff, Montreal, Canada     3 S
    Healthy volunteers,         36 N        0.14e          0.02-0.98       Santella et al.
    Columbia, MO, USA           17 S                                       (1994)

    Table 98. (continued)

                                                                                                

    Type of exposure or         No. of      1-Hydroxypyrene                Reference
    population investigateda    subjects                         
                                            Median         Range
                                            or meanb
                                                                                                

    Polluted ambient air

    School children,            NR          -              approx.0.4-0.6  Kanoh et al.
    Tokyo, Japan, M+F, Nf                                                  (1993)
    Urban population            74 N        0.68e          -               Zhao et al. (1992)
    Beijing, China              84 S        0.76e
    Urban population,           13 N        1.55e          -               Zhao et al. (1990)
    Shenyang, China, F
    Urban population,           17 N        1.20e          -               Zhao et al. (1990)
    Taiyuan, China, F
    Urban population,           15 N        0.67e          -               Zhao et al. (1990)
    Beijing, China, F
    Urban population,           15 N        0.72e          -               Zhao et al. (1990)
    Beijing, China, F (girls)
    Urban population,           72          0.66e          -               Jongeneelen
    Bytom, Silesia,                                                        (1994)
    Poland (boys)
    Urban population,           76          0.59e          -               Jongeneelen
    Bytom, Silesia,                                                        (1994)
    Poland (girls)
    Gliwice, Silesia, Polandg   30          -              0.84-1.54       Ovrebro et al.
                                                                           (1995)

    Other exposures

    Windsurfers sailing on      6           0.32e          0.16-0.81       Jongeneelen
    polluted water, Ketelmeer,                                             (1994)
    Netherlands

    Therapeutic treatment with coal-tar

    Patients with eczema        5           -              approx.50-500   Jongeneelen et
                                                                           al. (1986)
    Patients with psoriasis     4           -              13.2-811c       Clonfero et al.
                                                                           (1989)
    Patients with psoriasis     53          547e           10-5160         Santella et al.
                                                                           (1994)
    Patient with psoriasis      1           3.45           -               Viau et al. (1995)

    Table 98. (continued)

                                                                                                

    Type of exposure or         No. of      1-Hydroxypyrene                Reference
    population investigateda    subjects                         
                                            Median         Range
                                            or meanb
                                                                                                

    Food

    Eating 9 oz [250 g]         10          approx.0.5e,h  -               Kang et al. (1995)
    char-broiled beef                                      0.15-1.2
                                                                                                

    N, non-smokers; S, smokers; M, males; F, females; NR, not reported
    a  Unless otherwise stated, male persons were investigated; in some cases, insufficient
       characterization of exposure given
    b  1-Hydroxypyrene concentration in urine (µmol/mol creatinine), range, and, if available,
       median concentration; otherwise, geometric or arithmetic means
    c  Calculated from 1-hydroxypyrene concentrations given in original reference as µg/g
       creatinine.
    d  Geometric mean
    e  Arithmetic mean
    f  Benzo[a]pyrene measured at 0.0006-0.0024 µg/m3 by stationary sampling
    g  Benzo[a]pyrene measured at 0.009-0.041 µg/m3 by stationary sampling
    h  Calculated from 1-hydroxypyrene concentrations given in original reference as ng/ml
       urine or pmol/ml urine


     (b)  Workplaces

    1-Hydroxypyrene concentrations have been measured in the urine of
    persons at various workplaces (Table 99); the urine of concurrent
    controls was examined in most investigations. Unexposed workers at the
    same plant, such as administrative workers, had slightly higher
    1-hydroxypyrene concentrations than the general population (Zhao et
    al., 1990; Buchet et al., 1992; Ny et al., 1993; Levin et al., 1995).

    The highest 1-hydroxypyrene excretion, up to 90 µmol/mol creatinine,
    was found in urine from workers impregnating wood with creosote,
    although the PAH levels in the air were quite low. The high exposure
    can be attributed to significant dermal uptake, which is several times
    higher than that by inhalation (see below).

    Other workplaces where there is heavy exposure are coke ovens,
    coal-liquefaction plants, aluminium plants, and plants producing
    carbon or graphite electrodes. The concentrations of 1-hydroxypyrene
    in the urine of workers at these sites were 1-10 µmol/mol creatinine.


        Table 99. Concentration of 1-hydroxypyrene in urine (µmol/mol creatinine) at industrial workplaces without and with
    exposure to polycyclic aromatic hydrocarbons

                                                                                                                          

    Type of exposure,               Benzo[a]pyrene     No. of       1-Hydroxypyrene              Reference
    population investigateda        (µg/m3)b           subjects                               
                                                                    Median        Range
                                                                    or meanc
                                                                                                                          

    Controls

    Unexposed workers in            -                  120          0.11          < 0.05-1.08    Boogaard and van
    petrochemical industry                                                                       Sittert (1994, 1995)

    Office workers at graphite      -                  9N           0.33d         -              Buchet et al. (1992)
    electrod- producing plant                          6S           0.36d

    Unexposed workers in coke       -                  137          0.26e,f       0.01-1.04      Ferreira et al. (1994a,b)
    and graphite electrode-
    producing plants

    Workers in administration of    -                  13N          N: 0.05f      < 0.05-0.12    Goen et al. (1995)
    municipal waste incineration                       8S           S: 0.09f      < 0.05-0.67

    Workers in water supply         -                  119          0.008         -              Hanson et al. (1994)
    plants, cotton manufacture,
    garbage recycling

    Workers in various              -                  121          0.012e        -              Hansen et al. (1995)
    environments

    Unspecified control group       -                  52N          0.26          -              Jongeneelen et al. (1988b)
                                                       38S          0.28

    Workers in shipping yards       -                  14N          0.17d         -              Jongeneelan et al. (1990)
    at hot rolling mill                                28S          0.51d
    Industry, Netherlands           -                  28           0.51          -

    Table 99. (continued)

                                                                                                                          

    Type of exposure,               Benzo[a]pyrene     No. of       1-Hydroxypyrene              Reference
    population investigateda        (µg/m3)b           subjects                               
                                                                    Median        Range
                                                                    or meanc
                                                                                                                          

    Coke-oven office workers                                                                     Levin et al. (1995)
      Before renovation             -                  8N           0.18g         -
      After renovation              -                  8N           0.09g         -

    Construction workers            -                  34 N         0.4g          -              Levin et al. (1995)

    Water supply workers            -                  26 N         N: 0          0-0.010        Omland et al. (1994)
                                                       42S          S: 0          0-0.022

    Unexposed workers               -                  10N          N: 0.05d,f    < 0.03-0.12    Schaller et al. (1993)
                                                       10S          S: 0.21d,f    0.03-1.2

    Workers in water                -                  20N          N: 0.16e      0.1-0.22       Sherson et al. (1992)
    purification plants,                               26S          S: 0.26e      0.18-0.34
    Denmark

    Guards in aluminium plant       -                  9            0.31d         -              Ny et al. (1993)

    Maintanance work in             -                  48           0.61e,f       -              Van Hummelen et al. (1993)
    blast furnace

    Office workers in steel         -                  10           0.51e         -              Zhao et al. (1990)
    plant

    Coke ovens
    Work at topside oven            0.8-32             3 N          N: 5.7d,f     -              Buchet et al. (1992)
                                    5.9d               3 S          S: 6.1d,f

    Work at benchside               -                  4 N          N: 1.2d,f     -
                                                       6 S          S: 0.75d,f

    Table 99. (continued)

                                                                                                                          

    Type of exposure,               Benzo[a]pyrene     No. of       1-Hydroxypyrene              Reference
    population investigateda        (µg/m3)b           subjects                               
                                                                    Median        Range
                                                                    or meanc
                                                                                                                          

    Various occupations             0.39-13            93 N         N: 2.7f       0.25-16        Cenni et al. (1993)
      near ovens                                       68 S         S: 3.5f       0.29-29
    Subgroup topside                2.18               21           6.64f         0.29-29
    Subgroup of larry-car           -                  12           7.76f         3.5-16
      operators

    Workers with various            -                  41 N         0.94e         -              Clonfero et al. (1995)
    tasks                                              65 S         1.53e

    Workers at two coke-            -                  54           0.78e,f       0.01-48        Ferreira et al. (1994a,b)
    oven plants

    Work at two top side            -                  19           3.3d          0.8-7.5        Jongeneelen et al. (1990)
    ovens                                              9            2.7d          1.3-6.5

    Other work: coke side,          -                  25           1.9d          0.6-4.1
    push side, maintenance

    Coke oven                       0.9-37             10           4.7g          0.3-30g        Levin et al. (1995)
      Before renovation,            4
      various occupations
      After renovation              0.2-6.8            10           1.3g          0.3-5.7g
                                    0.7

    Coke workers at 3 plants        0.72-1.5           66           2.45-13.48    -              Ovrebro et al. (1995)

    Oven workers                                       33           0.39e,f       -              van Hummelen et al. (1993)
                                                       7 N
                                                       26 S

    Table 99. (continued)

                                                                                                                          

    Type of exposure,               Benzo[a]pyrene     No. of       1-Hydroxypyrene              Reference
    population investigateda        (µg/m3)b           subjects                               
                                                                    Median        Range
                                                                    or meanc
                                                                                                                          

    Subgroup at top side            -                  7            0.85e,f       -

    Personnel at coke side,         -                  13           2.64          0.54-11        Van Rooij et al, (1994b)
    push side, top side,
    miscellaneous
    Workers at top of ovens         -                  15 S         4.34e         -              Zhao et al. (1990)

    Workers at top or side          -                  12 S         2.87e         -
    of ovens

    Coal liquefaction
    Engineers (control room         -                  5            8.53          -              Quinlan et al. (1995b)
    and plant operations)
    Technicians (plant              -                  5            3.74          -
    maintenance)

    Petrochemical industry
    Various operations              -                  -            -             0.25-0.68      Boogaard & van Sittert
    Workers inspecting furnace,     -                  -            -             max. 1.56      (1994, 1995)
      replacing burners in boilers,
      manufacturing rubber grades
    Subgroup: production of         < 0.01-< 0.22      1
      needle coke from ethylene
      cracker residue:
      Maintenance                                      3            1.02          0.16-5.51
      Operation                     < 0.17             12           1.13          0.22-13.2

    Coal-tar distillation           -                  4            -             3.7-11.8       Jongeneelen et al. (1986)
    operators, cleaner

    Table 99. (continued)

                                                                                                                          

    Type of exposure,               Benzo[a]pyrene     No. of       1-Hydroxypyrene              Reference
    population investigateda        (µg/m3)b           subjects                               
                                                                    Median        Range
                                                                    or meanc
                                                                                                                          

    Creosote impregnation
    Wood impregnation plant         -                  19           1.6d,e        0.18-10        Viau et al. (1993)

    Wood impregnation plant         0.01-0.05          6            97e           -              Elovaara et al. (1995)
                                    (0.012d)

    Wood impregnation plant         -                  1            20-90                        Jongeneelen et al. (1988b)


    Aluminum production
    Soderberg type anodes:
      Potroom workers,              1.9-36             9            0.4-3.6g
      respiratory protection        2.8                             2.1g          -              Levin et al. (1995)
      50% of time

      Potroom workers               -                  -            -             -              Ny et al. (1993)
      Electricians, technicians,    -                  5            0.69d         -
      engineers, laboratory
      workers, industrial
      hygiene personnel
      Foremen, technicians,         0.88d              4            2.6d          -
      tappers, crucible cleaner
      Crane operators, all-         7.9d               8            14d           -
      rounders, electrician
      Potmen                        2.2d               9            31d           -
      Electrode men                 37d                4            40            -

    Table 99. (continued)

                                                                                                                          

    Type of exposure,               Benzo[a]pyrene     No. of       1-Hydroxypyrene              Reference
    population investigateda        (µg/m3)b           subjects                               
                                                                    Median        Range
                                                                    or meanc
                                                                                                                          

    Prebake type anodes:
      Electrode production          -                  20                         0.17-27        Van Rooij et al. (1992)
        compartment
      Paste plant                   1.3                8            3.0d          1.6-7.4
      Bake oven                     0.3                5            4.4d          0.98-13
      Pot relining department       1.2                7            6.0d          1.9-12
      Anode bake area               -                  28           -             0.55-3.6       Tolos et al. (1990)

    Anodes from liquid              -                  17           -             2.1-37f        Schaller et al. (1993)
    pitch and coke

    Anodes not specified            -                  28           4.2f          0.05-65        Goen et al. (1995)

    Production of electrodes
    Graphite electrodes             -                  15           3.2f          -              van Hummelen et al. (1993)

    Graphite electrodes                                                                          Buchet et al. (1992)
      End-product conditioning      0.002-0.4          3N           N: 0.55f      -
                                    0.03d              7S           S: 0.55f
      Second thermal treatment      0.002-0.5          8N           N: 0.57f      -
        of electrodes               0.03d              17S          S: 0.79f
      Progressive heating of raw    0.002-1.9          2N           N: 2.53f      -
        electrodes                  0.04d              4S           S: 3.13f
      Maintenance and repair        0.002-7.5          15N          N: 1.21f      -
                                    0.21d              2S           S: 3.76f
      Grinding and mixing of raw    0.57-25            5N           N: 2.98f      -
        components                  5.4d               9S           S: 2.83f
      Electrode impregnation        0.83-73            3N           N: 4.14f      -
                                    62d                5S           S: 4.96f

    Table 99. (continued)

                                                                                                                          

    Type of exposure,               Benzo[a]pyrene     No. of       1-Hydroxypyrene              Reference
    population investigateda        (µg/m3)b           subjects                               
                                                                    Median        Range
                                                                    or meanc
                                                                                                                          

    Graphite electrodes             -                  93           1.7e,f        0.03-20        Ferreira et al. (1994a,b)

    Carbon electrodes I             -                  6            5.8f          3.7-43         Goen et al. (1995)
    Carbon electrodes II            -                  3            12.7f         9.4-15
    Carbon electrodes III           -                  14           8.4f          1.1-65

    Graphite electrodes                                                                          Mannschreck et al. (1996)
      Crushing                      0.09e              2            5.0e,f        0.6-9.4
      Baking                        1.1-12e            30           12f           0.9-170
      Graphitization                0.01-0.11e         24           0.9f          0.1-3.3
      Impregnation                  0.44-1.1e          9            11f           3.2-42
      Conditioning                  0.01e              2            1.2e,f        0.9-1.5

    Carbon black
    Plants manufacturing            -                  5            -             0.32-0.35      Gardiner et al. (1992)
    carbon black

    Newspaper printing ink          -                  1N           0.47          -              Jongeneelen et al. (1988b)
                                                       1S           0.67

    Road paving
    Bitumen and coal-tar binders    -                  43           -             0.9-2.8        Jongeneelen et al. (1988a)

    Bitumen and coal-tar binders    -                  28           -             0.9-3.2        Jongeneelen et al. (1988b)

    Bitumen binder                  -                  18 N         N: 0.53e      -              Burgaz et al. (1992)
                                                       21S          S: 0.67e

    Bitumen binder                  -                  3            0.6e          -              Jongeneelen et al. (1988b)

    Table 99. (continued)

                                                                                                                          

    Type of exposure,               Benzo[a]pyrene     No. of       1-Hydroxypyrene              Reference
    population investigateda        (µg/m3)b           subjects                               
                                                                    Median        Range
                                                                    or meanc
                                                                                                                          

    Bitumen binder                  < 0.05             57           0.7g          -              Levin et al. (1995)

    Impregnation of road            -                  38           4.26f         0.62-22        Goen et al. (1995)
    stones with coal-tar

    Foundries
    Iron foundry, melting,          0.02               25 N         N: 0.022      0.006-0.075    Omland et al.(1994)
    machine moulding, casting,                         45S          S: 0.027      0.006-0.16
    sand preparations; high
    concentration in casting
    and mouding

    Iron foundry                    < 0.002            14           2.7e          0.3-6.3        Santella et al. (1993)
                                    0.005-0.012        14           1.8e          0.3-4.2
                                    > 0.012            18           3.6e          0.5-9.7

    Iron foundry I                  0.00               19           0.013         -              Hansen et al. (1994)
                                    0-0.39             14           0.017
    Iron foundry II                 0.00               13           0.031         -
                                    0-0.039            24           0.022
                                    > 0.039            18           0.027

    Iron foundry                    -                  16 N         N: 0.11e      0.09-0.13      Sherson et al. (1992)
                                    20S                S: 0.42e     0.025-0.59

    Steel plant                     -                  12S          1.34e         -              Zhao et al. (1990)

    Diesel exhaust
    Railway tunnel under            < 0.000-0.04       5N           N: 0.08f      0.04-0.31      Cenni et al. (1993)
    construction                                       8S           S: 0.18f      0.08-0.38

    Table 99. (continued)

                                                                                                                          

    Type of exposure,               Benzo[a]pyrene     No. of       1-Hydroxypyrene              Reference
    population investigateda        (µg/m3)b           subjects                               
                                                                    Median        Range
                                                                    or meanc
                                                                                                                          

    Gate-keepers of harbour         -                  3N           N: 0.47e      -              Jongeneelen et al. (1988b)
    terminal for containers                            4S           S: 0.67e

    Waste incinerations
    Municipal waste incineration    -                  53           0.08f         < 0.05-0.41    Goen et al. (1995)
    Industrial waste incineration   -                  43           0.06f         < 0.05-0.47

    Garbage incineration plant      -                  35N          N. 0.12d,f    < 0.05-0.41    Schaller et al. (1993)
                                                       17S          S: 0.22d,f    0.07-0.41

    Miscellaneous workplaces
    Glass manufacture               -                  10           0.85          0.2-3.8        Goen et al. (1995)

    Lubricating oils in             -                  7N           0.32f         0.12-0.77      Cenni et al. (1993)
    earthenware factories

    Clean-up of soil of a dump      -                  29           0.11d         0.01-0.75      Viau et al. (1993)
    contaminated with coal-tars
    derived from pyrolysis
    of used tyres after major fire

    Chimney sweeping                -                  27           0.05-1.4      -              Goen et al. (1995)
                                                       0.36f

    Meat smoking                    -                  13           < 0.05-0.57   -
                                                       0.21f

    Fire fighting                   0.03-0.7           S            -             0.65-1.0
                                                       N                          0.51-0.6
                                                                                                                          

    Table 99 (continued)

    N, non-smokers; S, smokers; M, males; F, females
    a  Unless otherwise stated, male persons were investigated; in some cases, insufficient characterization of
       exposure given
    b  Benzo[a]pyrene, stationary or personal sampling
    c  1-Hydroxypyrene concentration in urine (µmol/mol creatinine), range, and, if available, median concentrations;
       otherwise, geometric or arithmetic means. Maximum concentrations are given, in post shift samples, in some
       studies from the end of the week. Figures are given for the whole study population and on subgroups with high
       exposure.
    d  Geometric mean
    e  Arithmetic mean
    f  Calculated from 1-hydroxypyrene concentrations given in original publication as µg/g creatinine or µg/litre.
    g  Calculated from 1-hydroxypyrene concentrations, given in the original publication as ng/ml urine


    The manufacture and handling of bitumens did not result in a
    significant increase in urinary excretion of 1-hydroxypyrene
    (Jongeneelen et al., 1988a,b; Knecht & Woitowitz, 1990; Burgaz et al.,
    1992), suggesting that the main source of exposure to PAH during
    paving is the coal-tar used as a binder and not the bitumen itself
    (Knecht & Woitowitz, 1990).

    In some studies of occupationally exposed individuals, the difference
    in urinary 1-hydroxypyrene concentration between smokers and
    nonsmokers was greater than expected, suggesting a more than additive
    effect of exposure and smoking on the body burden (Jongeneelen et al.,
    1990; Sherson et al., 1992; Ovrebo et al., 1994; Clonfero et al.,
    1995; Ovrebo et al., 1995; van Schooten et al., 1995). It was
    hypothesized that the induced P450 enzymes in smokers result in faster
    biotransformation and less efficient ciliary clearance of particles in
    the upper airways (Van Rooij et al., 1994a).

    The 1-hydroxypyrene concentrations in urine correlated in most cases
    with the PAH concentrations in air (Buchet et al., 1992; Levin et al.,
    1995; Mannschreck et al., 1996). The weak correlation between the
    levels of pyrene in air and 1-hydroxypyrene concentrations in urine
    was attributed to extensive dermal uptake of the PAH (Van Rooij et
    al., 1992, 1993a,b; Ovrebo et al., 1995). The 1-hydroxypyrene
    concentrations in urine correlated quite well with exposure of the
    skin, monitored by analysing absorbent pads attached to skin sites
    during shifts (Van Rooij et al., 1992, 1993a,b).

    Significant dermal uptake, representing up to 95% of the total, was
    concluded from the results of several studies of workers exposed at
    coke ovens, in coal-liquefaction plants, in the petrochemical
    industry, in aluminium reduction plants, in a graphite electrode
    plant, in a needle-coke plant, during road paving, and while
    impregnating wood with creosote oil (Jongeneelen et al., 1990; Van
    Rooij et al., 1992, 1993a,b; Boogaard & van Sittert, 1994; Ferreira et
    al., 1994a,b; Van Rooij et al., 1994b; Boogaard & van Sittert, 1995;
    Elovaara et al., 1995; Quinlan et al., 1995a,b,c). For example,
    workers impregnating wood with creosote had an average, estimated
    dermal uptake that was 15 times higher than the estimated respiratory
    uptake (Van Rooij et al., 1993b).

    Use of dermal protection in the form of impermeable polyvinyl chloride
    suits led to a substantial decrease in the urinary concentrations of
    1-hydroxy-pyrene (Boogard & van Sittert, 1994, 1995). Frequent changes
    of work clothes and underclothes reduced 1-hydroxypyrene excretion by
    37-55% (Van Rooij et al., 1994b; Quinlan et al., 1995c).

    8.3.2.3  Time course of elimination

    The excretion of 1-hydroxypyrene increased significantly between the
    beginning and end of a shift and from one day to another during one
    week. Decreases were observed between two shifts, but the high values
    did not drop to the preshift level of the day before (Jongeneelen et
    al., 1988b, 1990; Tolos et al., 1990; Buchet et al., 1992; Van Rooij

    et al., 1992; van Hummelen et al., 1993; Van Rooij et al., 1993b;
    Omland et al., 1994; Van Rooij et al., 1994b; Elovaara et al., 1995;
    Quinlan et al., 1995a,b; van Schooten et al., 1995). After an
    exposure-free weekend, the 1-hydroxypyrene concentrations in the urine
    of heavily exposed workers did not drop to control levels (Jongeneelen
    et al., 1988b, 1990; Viau et al., 1993; Elovaara et al., 1995; Quinlan
    et al., 1995b). The baseline values in exposed workers are slightly
    higher than those in unexposed controls (Jongeneelen et al., 1988a,
    1990; Tolos et al., 1990; Quinlan et al., 1995a,b).

    Elimination of 1-hydroxypyrene is biphasic, a moderately rapid phase
    being followed by a second, much slower elimination (Jongeneelen et
    al., 1988b, 1990; Viau et al., 1995). The half-lives of the first
    phase have been determined at various workplaces and for
    non-occupationally exposed persons after inhalation, dermal, and oral
    exposure. Regardless of the route of exposure, they range from 4.4 to
    48 h, most values being about 16 h (Jongeneelen et al., 1988b, 1990;
    Buchet et al. 1992; Buckley & Lioy, 1992; Schaller et al., 1993;
    Boogard & van Sittert, 1994; Quinlan et al., 1995a,b; Viau & Vyskocil,
    1995; Viau et al., 1995). In one study, a half-life of 16 days was
    given for the slower phase (Jongeneelen et al. 1988b). This slow
    elimination suggests that pyrene accumulates in a secondary
    compartment, most probably adipose tissue, from which it is released
    only slowly (Jongeneelen et al., 1990).

    8.3.2.4  Suitability as a biomarker

    When 1-hydroxypyrene was used as a biomarker for exposure to PAH, the
    oral, dermal, and inhalation routes were all shown to be important.
    Furthermore, low levels of exposure to PAH can be determined. A great
    advantage is that the determination of urinary 1-hydroxypyrene is easy
    and rapid and thus well suited for use in large-scale epidemiological
    studies.

    Comparison of different work environments may, however, be difficult,
    because the proportion of pyrene in the total PAH or in comparison
    with benzo [a]pyrene may vary (Jongeneelen et al., 1990; Buchet et
    al., 1992; van Rooij et al., 1993a; Boogard & van Sittert, 1994;
    Hansen et al., 1994). For example, the creosote oil used in a wood
    impregnation plant contained about 3.4% pyrene and less than 0.0004%
    benzo [a]pyrene. Levels of 2-10% pyrene and 0.4-0.6% benzo [a]pyrene
    are found in coal-tar, which is the main PAH contaminant in the coke
    industry, in the primary aluminium industry, and during road paving
    with tar. Polluted ambient air contains about 6.5% benzo [a]pyrene
    and 1.8-2.7% pyrene (IARC, 1985; Zhao et al., 1990).

    It is not currently possible to assess the risk presented by exposure
    to PAH on the basis of urinary 1-hydroxypyrene concentrations, as
    epidemiological studies have not demonstrated a relationship with
    long-term effects. An indirect dose-response relationship between
    urinary 1-hydroxypyrene level and the relative risk for lung cancer
    has, however, been estimated for coke-oven workers: 2.3 µmol
    1-hydroxypyrene per mol creatinine was estimated to be equal to a

    relative risk for lung cancer of approximately 1.3 (Jongeneelen,
    1992). Because of the varying composition of PAH mixtures, this risk
    estimation cannot be used for other workplaces or ambient air, where a
    correction factor may be necessary.

    8.3.3  Mutagenicity in urine

    The mutagenicity of urine from persons exposed to PAH has been assayed
    in a number of studies by Ames' test with  Salmonella typhimurium
    TA98 or TA100, with and without metabolic activation. In most of these
    studies, several urine samples from both control and exposed subjects
    could not be assayed because of the toxicity of the urine (Heussner et
    al., 1985; Jongeneelen et al., 1986; Clonfero et al., 1989, 1990;
    Ferreira et al., 1994b; Santella et al., 1994; Clonfero et al., 1995).

    Although tobacco smoke was mutagenic in the presence of metabolic
    activation, no increase in mutagenic activity was found in most
    studies of workers exposed in occupations such as coking (Reuterwall
    et al., 1991; Ferreira et al., 1994a,b), coal-tar distillation
    (Jongeneelen et al., 1986), work in Söderberg potrooms of aluminium
    plants (Krokje et al., 1988), in anode plants (Clonfero et al., 1984;
    Venier et al., 1985; Krokje et al., 1988; Clonfero et al., 1990), and
    in a graphite electrode plant (Ferreira et al., 1994a). Only the heavy
    exposure of patients with psoriasis to coal-tar applications (Clonfero
    et al., 1989, 1990; Santella et al., 1994) and of workers at coke
    ovens (Mielzynska & Snit, 1992; Clonfero et al., 1995) and in a carbon
    plant (Heussner et al., 1985) resulted in mutagenic urine. Ames' test
    therefore appears not to be sensitive enough to detect the presence of
    urinary mutagens due to occupational exposure to low levels of PAH
    (Becher et al., 1984; Clonfero et al., 1989, 1990).

    Expectorate from workers in a coke plant and in Söderberg potrooms in
    an aluminium plant showed significantly increased mutagenicity in
    Ames' test with  S. typhimurium TA98 and TA100 in the presence of
    metabolic activation (Krokje et al., 1988; Krokje, 1989).

    8.3.4  Genotoxicity in lymphocytes

    Genotoxic effects in lymphocytes have been proposed as markers for
    exposure to PAH. In studies of iron foundry workers with relatively
    low exposure to PAH, elevated frequencies of mutation at the  hprt
    locus in lymphocytes correlated approximately with the levels of DNA
    adducts (Perera et al., 1993, 1994). In one study of coke-oven
    workers, significant differences from controls were found in the
    number of single-strand DNA breaks; however, there was no difference
    between tobacco smokers and nonsmokers (Salagovic et al., 1995).

    No increases in the rates of micronuclei, chromosomal aberrations, or
    sister chromatid exchange were detected in workers at coke ovens
    (Reuterwall et al., 1991), a carbon plant (Heussner et al., 1985), an
    aluminium plant (Becher et al., 1984), or a graphite electrode plant
    (van Hummelen et al., 1993) or in chimney sweeps (Carstensen et al.,
    1993), although in most cases significant effects of smoking could be

    detected. In one study in which an increase was found, there was no
    difference between tobacco smokers and nonsmokers (Bender et al.,
    1988; Salagovic et al., 1995). Environmental pollution in Silesia was
    associated with significant increases in the frequencies of sister
    chromatid exchange and chromosomal aberration in peripheral blood
    cells, independently of smoking (Perera et al., 1992).

    8.3.5  DNA adducts

    DNA adducts with reactive metabolites (mainly diol epoxides) of
    benzo [a]pyrene and other PAH have been identified in numerous
    studies (see Section 6). For example, cigarette smokers have higher
    levels of adducts with PAH in their lungs than nonsmokers, and there
    is a linear relationship between adduct levels and daily or lifetime
    cigarette consumption (Phillips et al., 1988).

    As binding of electrophilic PAH metabolites to DNA is thought to be a
    key step in the initiation of cancer, measurement of DNA adducts could
    be an indicator of exposure to PAH and also of cancer risk. As a
    surrogate for lung tissue, which is an important target organ for PAH
    in humans, the more easily accessible nucleated blood cells and blood
    proteins (haemoglobin, albumin) have been investigated.

    8.3.5.1  Method of determination

    The methods for measuring DNA adducts include immunoassays with
    polyclonal and monoclonal antibodies (enzyme-linked immunosorbent
    assay [ELISA] and ultrasensitive enzymatic radioimmunoassay),
    32P-postlabelling, and synchronous fluorescence spectrophotometry.
    Direct comparisons of adduct levels determined by different techniques
    may be misleading, however, because different end-points are measured.
    For example, polyclonal and monoclonal antisera recognize not only the
    benzo [a]pyrene diol epoxide adducts against which they are raised,
    but also benz [a]anthracene, chrysene, benzo [k]fluoranthene, and
    dibenz [a,c]anthracene, which also form N2 guanine adducts. The
    32P-postlabelling assay is even less specific, as it may detect
    several aromatic and hydrophobic adducts (Dell'Omo & Lauwerys, 1993).

    The detection limits for the three methods are one adduct per 107-108
    nucleotides for the immunological methods (Dell'Omo & Lauwerys, 1993)
    and synchronous fluorescence spectrometry (Dell'Omo & Lauwerys, 1993;
    Rojas et al., 1995) and up to one adduct per 1010 nucleotides in the
    32Ppostlabelling assay (Beach & Gupta, 1992; Dell'Omo & Lauwerys,
    1993; Ovrebo et al., 1994). DNA adducts may be overlooked with
    32P-postlabelling, because of incomplete nuclease P1 digestion,
    resistance to 32P-labelling, dephosphorylation of certain adducts, or
    co-migration with normal nucleotides (Herbert et al., 1990b; Beach &
    Gupta, 1992; Kriek et al., 1993; Segerbäck & Vodicka, 1993; Pavanello
    & Levis, 1994). This method is being improved (Segerbäck & Vodicka,
    1993; Szyfter et al., 1994).

    The results obtained when the different methods were applied in
    parallel were usually similar, but the magnitude of the effect
    differed (Ovrebo et al., 1990, 1992; Pavanello & Levis, 1994; Perera
    et al., 1994). For example, in one study of psoriasis patients treated
    with coal-tar, 20-100 times higher levels were found with ELISA than
    with the 32P-postlabelling method (Pavanello & Levis, 1994). In
    another study, the 32P-postlabelling method was more sensitive than
    the ELISA (Kriek et al., 1993). Considerable differences were found in
    DNA adduct levels in interlaboratory comparisons (Hemminki et al.,
    1990a; Beach & Gupta, 1992; Kriek et al., 1993; Phillips & Castegnaro,
    1993).

    In the descriptions below, the DNA adduct levels are expressed as
    number of adducts per 108 nucleotides or fmol/µg DNA; 33.2 fmol/µg
    DNA corresponds to one adduct per 108 nucleotides. Since the levels
    in background samples and also in samples from exposed subjects are
    sometimes below the limit of detection, the number of positive samples
    is often given as well (Herbert et al., 1990a,b; Dell'Omo & Lauwerys,
    1993).

    8.3.5.2  Concentrations

    In general, exposures that lead to the excretion of high
    concentrations of 1-hydroxypyrene in urine also lead to elevated DNA
    adduct levels. Table 100 gives the DNA adduct levels derived from
    studies in which air concentrations and DNA adduct levels were
    measured in parallel. Although the concentrations of PAH that occur
    under different exposure conditions differ by orders of magnitude (see
    section 5.3), the differences in DNA adduct levels are quite small, in
    contrast to the results of experiments on excretion of
    1-hydroxypyrene. Table 101 summarizes the results of an investigation
    of workers in an aluminium reduction plant where the two methods were
    applied (van Schooten et al., 1995).

    In all populations studied, there is substantial interindividual
    variation in PAH-DNA adduct levels, after exposure by inhalation or
    orally, which is greater than that described for 1-hydroxypyrene
    excretion in urine (Hemminki et al., 1990a,b; Santella et al., 1993;
    Szyfter et al., 1994; Rojas et al., 1995). In one study, about 50-fold
    interindividual variations were reported among controls and about
    100-fold variations among coke-oven workers (Rojas et al., 1995). The
    variations are probably due to differences in the induction of AHH
    activity in lymphocytes and in the resulting detoxification of
    carcinogenic PAH, the ability to repair DNA lesions, and the turnover
    of damaged cells (Dell'Omo & Lauwerys, 1993; Szyfter et al., 1994;
    Kang et al., 1995; Rojas et al., 1995). These interindividual
    variations result in a wide overlap in the ranges of values between
    exposed and unexposed subjects in all studies.


        Table 100. DNA-polycyclic aromatic hydrocarbon adduct levelsa in various situations of exposure

                                                                                                                                           

    Population                  Benzo[a]pyrene   Method of           Exposed                   Controls                  Reference
    investigated,               (µg/m3)          detection                                                            
    type of emission                                                 No. of      No. of DNA    No. of     No. of DNA
                                                                     subjects    adducts/108   subjects   adducts/108
                                                                     nucleotides                          nucleotides
                                                                                                                                           

    Polluted ambient air
    Industrialized area,        0.015-0.057      32P-Postlabelling   15          13            13         2.3            Hernminki et al.
    Silesia, Poland                                                                                                      (1990a)
    Industrialized area                          32P-Postlabelling   19          14            15         4.8            Motykiewicz
    Silesia, Poland                                                                                                      (1995)
    Winter inversion,           0.002-0.008      32P-Postlabelling   29          2.6-6.8       -          -              Binkova et al.
    Teplice, Czech                                                                                                       (1995)
    Republic
    Burning of smoky            19               Immunoassay         18          7.7           18         5.2            Mumford et al.
    coal at home, with                                                                                                   (1993)
    and without
    chimneys, China

    Coke ovens
    Door maintenance            2.3-6.5          Immunoassay         11          5.8b          -          -              Assennato
                                                                                                                         (1993a)
    Work topside                7.3              Fluorescence        13          ND-73b        -          -              Haugen et al.
                                                 spectrophotometry                                                       (1986)
                                                 immunoassay
    Battery work                0.54-90          32P-Postlabelling   31          15            13         2.3            Hemminki et al.
                                                                                                                         (1990a)
    Working at high and         0.001-0.009      32P-Postlabelling   31          2.2           22         2.2            Yang et al.
    low traffic density                                                                                                  (1996)
    areas

    Table 100. (continued)

                                                                                                                                           

    Population                  Benzo[a]pyrene   Method of           Exposed                   Controls                  Reference
    investigated,               (µg/m3)          detection                                                            
    type of emission                                                 No. of      No. of DNA    No. of     No. of DNA
                                                                     subjects    adducts/108   subjects   adducts/108
                                                                     nucleotides                          nucleotides
                                                                                                                                           

    Aluminium production
    Aluminum plant, prebake                      32P-Postlabelling                                                       Van Schooten
    anode process                                                                                                        et al. (1995)
      Anode factory             1.5                                  -           26            -          -
      Pot relining              1.1                                              47            -          -
    Electrode past plant        0.9              32P-Postlabelling   34          11            14         10             Ovrebo et al.
                                                                                                                         (1994)

    Foundries
    Foundry                     0.02             -                   -           7.4           -          -              Perera et al.
                                                                                                                         (1994)
    Iron foundry                < 0.005-0.06     Competitive         67          4.4-9.6       -          -              Santella et al.
                                ELISA                                                                                    (1993)
    Iron foundry                < 0.005-0.06     32P-Postlabelling   67          1.9-2.5       -          -              Perera et al.
                                                                                                                         (1994)
    Iron foundry                < 0.05-> 0.2     Fluorescent         35          0.8-21        10         2.2            Perera et al.
                                                 ELISA                                                                   (1988)
    Iron foundry                < 0.05           32P-Postlabelling   19          7.3           4          4              Szyfter et al.
                                0.005-0.2        -                   63          19            -          -              (1994)
                                > 0.2            -                   6           29            -          -
                                                                                                                                           

    ND, not detected; ELISA, enzyme-linked immunosorbent assay
    a  Median or mean values; ranges are from means or medians of several measurements of groups of exposed persons
    b  In original publication given as fmol/µg DNA. Number of adducts per 108 nucleotides = fmol/µg DNA × 33.2


        Table 101. Comparison of methods for measuring exposure to polycyclic aromatic
    hydrocarbons in an aluminium plant

                                                                                       

    Exposure          Benzo[a]pyrene   Pyrene     1-Hydroxypyrene       DNA adducts
                      (µg/m3)a         (µg/m3)a   in urine (µmol/mol    in leukocytes
                                                  creatinine)b          (adducts/108
                                                  ± SD                  nucleotides)
                                                                        ± SD
                                                                                       

    Bake oven         0.35             1.5        3.65 ± 2.11           30.1 ± 42.1
    Anode factory     1.51             5.6        3.25 ± 1.89           26.2 ± 15.0
    Pot relining      1.05             32.3       6.20 ± 8.44           47.3 ± 39.1
    Electrolysis      0.03             0.12       0.48 ± 0.27           12.8 ± 10.0
    Foundry           0.02             0.04       0.47 ± 0.20           7.4 ± 9.6
                                                                                       

    From van Schooten et al. (1995)
    a Geometric mean
    b Arithmetic mean


    Significant correlations were found in most studies between the
    estimated or measured exposure to PAH and adduct levels (Herbert et
    al., 1990a,b; Ovrebo et al., 1990, 1992; Assennato et al., 1993a;
    Perera et al., 1994; Szyfter et al., 1994; van Schooten et al., 1995),
    but no such correlation was found in others (Herbert et al., 1990a,b;
    Kriek et al., 1993; Mumford et al., 1993, Ovrebo et al., 1994; Schoket
    et al., 1995).

    As shown with 1-hydroxypyrene concentrations in urine, the DNA adduct
    concentrations in certain workers may correlate better with dermal
    exposure than with PAH concentrations in air (Herbert et al.,
    1990a,b).

     (a)  General population

    The levels of DNA adduct in control subjects range from 0.2 to about
    10 adducts per 108 nucleotides in leukocytes (Dell'Omo & Lauwerys,
    1993). DNA adducts were also found in 43% of placentas and in 27% of
    liver samples and 42% of lung specimens from 15 spontaneously aborted
    human fetuses. As there was only 60% concordance between placenta and
    fetal lung or liver with regard to the presence of detectable adducts,
    DNA adducts in the placenta are not a good indicator of adduct
    formation in fetal organs. Although several of the mothers were
    smokers, none of the fetal samples containing DNA adducts were from
    women who smoked during pregnancy, indicating that smoking is unlikely
    to have caused adduct formation (Hatch et al., 1990).

    Conflicting results have been obtained concerning the effects of
    tobacco (cigarette) smoking on DNA adduct levels in peripheral blood
    cells. Most investigations of human peripheral lymphocytes have found
    no remarkable effect of smoking in control or exposed persons, in
    contrast to those of lung and bronchial tissue (Hemminki et al.,
    1990a; Herbert et al., 1990a,b; Dell'Omo & Lauwerys, 1993; Binková et
    al., 1995; van Schooten et al., 1995; Yang et al., 1996). Some
    publications, however, report maximal differences in DNA adduct levels
    of about threefold between tobacco smokers and nonsmokers among
    controls and exposed individuals (Savela & Hemminki, 1991; Kriek et
    al., 1993; Santella et al., 1993; Rojas et al., 1995; van Schooten et
    al., 1995). Granulocytes from smokers and nonsmokers showed no
    difference in DNA adduct levels, but threefold increases were observed
    in T lymphocytes, which have a much longer life than granulocytes
    (Savela & Hemminki, 1991).

    A synergistic effect of tobacco smoking and occupational exposure to
    PAH was reported in two studies (Rojas et al., 1995; van Schooten et
    al., 1995). It was hypothesized that tobacco smoke induces AHH in
    lymphocytes, resulting in increased formation of benzo [a]pyrene-DNA
    adducts in smokers. The large interindividual differences may be due
    to the presence of both non-inducible and highly inducible variants in
    human lymphocytes (Rojas et al., 1995).

    Elevated DNA adduct levels have been detected in the general
    populations of industrialized areas in Poland (Silesia) and the Czech
    Republic (Teplice) (Hemminki et al., 1990a,b; Perera et al., 1992;
    Binková et al., 1995), with levels up to 13 (Hemminki et al., 1990a;
    Motykiewicz, 1995) and 5 adducts per 108 nucleotides (Binková et al.,
    1995). Levels of 8 adducts per 108 nucleotides were found in
    leukocytes from women exposed to high PAH concentrations from burning
    smoky coal in China. Although DNA adducts were also detected in
    placenta, no dose-response relationships were found between exposure
    to benzo [a]pyrene and placental DNA adduct level or the percentage
    of samples with detectable DNA adducts (Mumford et al., 1993).

    The consumption of charcoal-grilled foods leads to elevated DNA adduct
    levels (Rothman et al., 1993; Kang et al., 1995), and such food may
    represent a major dietary source of PAH for some populations. Eating
    charcoal-grilled beef resulted in a 1.9-3.8-fold increase above the
    individual baseline adduct levels in four of 10 subjects (Kang et al.,
    1995).

    Psoriatic patients undergoing coal-tar treatment had a DNA adduct
    level of about 8 per 108 nucleotides (Pavanello & Levis, 1994;
    Santella et al., 1995), and levels up to 13 per 108 were found in
    skin biopsy samples obtained from patients who had received treatment
    with coal-tar ointment. There was no correlation of the adduct levels
    after different treatments. No information was given on controls
    (Phillips et al., 1990).

     (b)  Occupational exposure

    Workers exposed to PAH had elevated mean levels of adducts and a
    higher percentage of positive samples (measured concentrations above
    the detection limit) than controls. Elevated DNA adduct levels have
    been detected in leukocytes from workers exposed in coke-oven plants
    (Assennato et al., 1993a,b; Dell'Omo & Lauwerys, 1993; Harris et al.,
    1985; Haugen et al., 1986; Hemminki et al., 1990a,b; Ovrebo et al.,
    1992; Kriek et al., 1993a,b; Rojas et al., 1995), aluminium
    manufacture (Dell'Omo & Lauwerys, 1993; Kriek et al., 1993a,b; Schoket
    et al., 1995; van Schooten et al., 1995), and foundries (Perera et
    al., 1988; Dell'Omo & Lauwerys, 1993; Santella, 1993; Santella et al.,
    1993; Perera et al., 1994) and among firefighters (Dell'Omo &
    Lauwerys, 1993) and roofers (Herbert et al., 1990a,b; Dell'Omo &
    Lauwerys, 1993).

    In cases of high exposure, for example at coke ovens, 5-70 adducts per
    108 nucleotides have been measured. Significant correlations with
    exposure concentrations have been found, although the level was no
    more than threefold greater than in controls (Hemminki et al.,
    1990a,b; Ovrebo et al., 1990; Assennato et al., 1993a).

    8.3.5.3  Suitability as a biomarker

    DNA adduct levels in the lung may not a reliable indicator of human
    cancer risk, although Phillips et al. (1988) found a correlation
    between cigarette smoking and DNA adducts in the human lung. Weston et
    al. (1993) observed no correlation between lung DNA adduct levels and
    a measure of recent tobacco smoking, serum cotinine. Tissue samples
    taken from different portions of the same lung showed variations in
    DNA adduct levels

    The use of lymphocytes as a surrogate for lung cells has also been
    questioned, because no correlation has been found between PAH-DNA
    adduct levels in human lung and leukocytes (van Schooten et al.,
    1992). In studies on rats exposed to coke-oven emissions, the DNA
    adduct levels were lower in leukocytes than in lung tissues; in
    addition, several types of adducts observed in lung tissue were not
    present in leukocytes (Binková et al., 1994). Granulocytes, which form
    the majority of peripheral leukocytes, have a relatively short life,
    < 24 h, in contrast to lung cells; therefore, adducts are probably
    lost within a few days (Savela & Hemminki, 1991; Dell'Omo & Lauwerys,
    1993). This can be avoided by using the subfraction of T lymphocytes
    which have a half-life of several years. The adduct levels in T
    lymphocytes were three times higher than in granulocytes (Savela &
    Hemminki, 1991).

    DNA adducts are much less sensitive for assessing exposure than
    excretion of 1-hydroxypyrene in urine. Additionally, because of the
    large interindividual differences in control and exposed groups,
    adduct levels can be compared only on a group basis. Thus, PAH-DNA
    adducts can be used as a qualitative biomarker of exposure to
    combustion emissions but to only a limited extent as a quantitative

    marker. This method may, however, allow identification of subjects who
    are highly susceptible to the DNA-damaging properties of PAH and are
    therefore predisposed to lung cancer. This was seen in one
    investigation of lung cancer patients with a family history of lung
    cancer. Monocytes from these patients treated  in vitro with PAH
    showed a slight but significant enhancement of formation of
    benzo [a]pyrene-DNA adducts in comparison with controls (Nowak et
    al., 1992). It is not yet known whether metabolism in leukocytes is
    identical to that in lung cells.

    8.3.6  Antibodies to DNA adducts

    Antibodies to DNA adducts in leukocytes of exposed workers have also
    been found (Harris et al., 1985; Haugen et al., 1986; Vähäkangas et
    al., 1992; Santella et al., 1995). In a study of coal-tar-treated
    patients, elevated levels were also found in controls (Santella et
    al., 1995). Since the initial antigenic stimulus could have occurred
    several years previously, antibodies to benzo [a]pyrene-DNA adducts
    are considered general indicators of past exposure to PAH.

    8.3.7  Protein adducts

    Because genotoxic compounds can bind to haemoglobin and serum protein,
    the assessment of PAH-blood protein adducts has also been considered
    as a possible marker of exposure to PAH or even as a surrogate for the
    evaluation of adduct concentrations at the level of the target organs.
    This approach has several advantages. Relatively large amounts of
    haemoglobin and albumin can be obtained easily from a small volume of
    human blood. As the lifetime of haemoglobin in humans is about 120
    days and that of albumin 20-24 days, exposure days and weeks
    previously can be measured. Albumin is synthesized in the liver, where
    PAH are metabolized. Therefore, reactive metabolites may easily gain
    access to the proteins. Finally, there may be lower interindividual
    variation, because there is no repair, as in the case with DNA
    (Dell'Omo & Lauwerys, 1993).

    The benzo [a]pyrene-albumin adduct concentrations were similar in
    foundry workers and controls, both smokers and nonsmokers (Omland et
    al., 1994), and in patients with psoriasis treated with coal-tar
    (Santella et al., 1995). Minor effects were detected in foundry
    workers and roofers (Lee et al., 1991). No pronounced differences in
    haemoglobin adduct levels were detected in workers in steel foundries
    and in one graphite electrode producing plant (Ferreira et al.,
    1994a,b). In another study, however, significantly increased
    benzo [a]pyrene binding was detected in serum proteins from smoking
    and non-smoking foundry workers (Sherson et al., 1990).

    As protein adducts have been used in relatively few studies, no
    conclusion can be drawn about the usefulness of this biomarker.

    8.3.8  Activity of cytochrome P450

    Increased mRNA levels of the  CYP1A1 gene, which belongs to the
    P4501A1 family responsible for the metabolism of PAH, including
    benzo [a]pyrene, have been proposed as biomarkers for exposure to PAH
    (Cosma et al., 1992; Van den Heuvel et al., 1993; see also Section 6).
    Although the basal levels were not increased, 3-methylcholanthrene
    caused greater induction in lymphocytes from railroad workers exposed
    to creosote in cell culture (Cosma et al., 1992).

    The activity of the cytochrome P450 CYP 1A2 was also determined by
    measuring caffeine metabolites in urine. There were significant
    differences between tobacco smokers and nonsmokers, but there was no
    difference between nonsmoking and smoking foundry workers and the
    respective controls (Sherson et al., 1992).

    8.3.9  Differentiation antigens on the surface of lung cells

    Lung epithelial cells from sputum have been tested for antigens that
    indicate neoplastic transformation (Assennato et al., 1993b). One of
    23 coke-oven workers who had differentiation antigens on the cell
    surface was a smoker who had severe airways obstruction and moderate
    dysplasia of bronchial epithelium cells.

    8.3.10  Oncogene proteins

    Since oncogene activation may be an early step in the carcinogenic
    process, its detection may be a useful marker for identifying
    individuals at risk for the development of malignancy. Plasma levels
    of  ras oncogene-related p21 proteins were elevated in a sample of
    male residents of the highly industrialized Silesian region of Poland.
    They also had elevated DNA adduct levels in their leukocytes (Perera
    et al., 1992). Three of 18 foundry workers screened for the oncogene
    proteins sis, fes ß-TGF, int-1, myb, src, myc, mos, and ras in serum
    had elevated levels of ras and fes; however, two were smokers. No
    unexposed individuals had abnormal serum oncogene protein expression.
    The levels of ras and fes proteins were also increased in the serum of
    lung cancer patients (Brandt-Rauf et al., 1990).

    9.  EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND THE FIELD

     Appraisal

    Data on toxicity are available mainly for naphthalene, phenanthrene,
    and fluoranthene and are scarce for other polycyclic aromatic
    hydrocarbons (PAH). Both metabolism and photooxidation can alter the
    toxicity of PAH in the environment, photooxidation tending to increase
    toxicity.

    At low concentrations, PAH can stimulate the growth of microorganisms
    and algae. The highest values for the no-observed-effect concentration
    (NOEC) were determined for naphthalene (3100 µg/litre in  Anabaena
     flos-aquae) and acenaphthene (> 4600 µg/litre in  A. flos-aquae). 
    The NOEC values for fluorene, phenanthrene, fluoranthene, and pyrene
    were about one order of magnitude lower. Benz [a]anthracene and
    chrysene were the most toxic towards algae (NOEC, < 10 µg/litre). The
    effective concentration that caused a 50% change (EC50) was between 5
    µg/litre for benzo [a]pyrene and 54 000 µg/litre for fluoranthene.

    For invertebrates like crustaceans, insects, molluscs, polychaetes,
    and echinoderms, naphthalene is least toxic, with a 48-h median lethal
    concentration (LC50) of 700-23 000 µg/litre. For three-ring PAH, the
    LC50 values ranged between < 1 and 3000 µg/litre. Anthracene may be
    more toxic than the other three-ring PAH, with 24-h LC50 values
    between < 1 and 260 µg/litre. The values for most four- and five-ring
    PAH are between 0.7 and 1800 µg/litre and 0.4-120 µg/litre,
    respectively. For six-ring PAH, only one LC50 is available: 0.2
    µg/litre for benzo [ghi]perylene. The values for the NOEC are
    slightly lower than those for the LC50. The lowest NOEC reported for
    benzo[a]pyrene is 0.14 µg/litre.

    Naphthalene, acenaphthene, and fluorene are the least toxic for
    vertebrates like fish and amphibians, with 96-h LC50 values of 110 to
    > 10 000 µg/litre; for phenanthrene and fluoranthene, the LC50
    values are 30-4000 µg/litre. Most of the LC50 values for anthracene
    were between 2.8 and 360 µg/litre. For four- and five-ring PAH, the
    LC50 values were 0.7-26 µg/litre. The lowest NOEC reported for
    benzo [a]pyrene in fish was 2.4 µg/litre. In tests with
    sediment-dwelling organisms, LC50 values of 3-15 mg/kg dry weight
    were determined for fluoranthene.

    In earthworms, an LC50 value for growth was 170-200 mg/kg dry weight
    for fluorene, and an LC50 value for reproduction was 150 mg/kg dry
    weight for phenanthrene. At 180 mg/kg dry weight, chrysene,
    benzo [k]fluoranthene, and benzo [a]pyrene did not affect
    reproduction by the earthworm Folsoma candida.

    9.1  Laboratory experiments

    Data on the toxicity of individual PAH to members of different
    taxonomic groups are presented in Tables 102-104; data on the toxicity
    of PAH metabolites are not included. The use of solvents in laboratory
    tests for toxicity often results in unrealistically high
    concentrations of PAH, which exceed their maximum water solubility.
    Only data from tests with concentrations that did not exceed 10 times
    the estimated solubility were used.

    9.1.1  Microorganisms

    9.1.1.1  Water

    The effects of several three-, four-, and five-ring, unsubstituted PAH
    on the growth of the bacterium  Escherichia coli were studied at
    concentrations of 10-5, 10-6, and 10-7 mol/litre in the growth medium
    (Hass & Applegate, 1975). Benz [a]anthracene,
    dibenz [a,h]anthracene, and benzo [a]pyrene promoted bacterial
    growth; pyrene and phenanthrene had slight promoting effects at low
    concentrations (10-7 and 10-6, respectively) and inhibitory effects
    at higher concentrations, whereas anthracene and chrysene inhibited
    bacterial growth at all concentrations.

    The effects of dissolved PAH on the growth rate, lag time before
    initiation of growth, and the number of cells at the end of the log
    growth phase, measured as maximum light absorbance, were determined in
    two species of marine bacteria,  Serratia marinorubra and  Vibrio
     parahaemolyticus. Most of the PAH tested increased the lag time and
    decreased the growth rate and cell yield; pyrene, however, increased
    the growth rate. The extent of inhibition of growth was a function of
    both the concentration of PAH and their inherent toxic properties,
    which decreased with solubility. Thus, the toxicity of naphthalene at
    a concentration of 13 mg/litre was similar to that of benzo [a]pyrene
    at 5 µg/litre (Calder & Lader, 1976).

    PAH at concentrations of 5-20 µg/litre stimulated the growth of the
    freshwater algae  Chlorella vulgaris, Scenedesmus obliquus, and
     Ankistrodesmus orauntic (Gräf & Nowak, 1966) and of the marine
    dinoflagellate  Gyrodinium sp. (Ishio et al., 1977). The growth of
    sporelings of the marine algae  Antithamnium plumula was
    progressively inhibited after exposure to 10-300 µg/litre of
    benz [a]anthracene.

    The growth of the blue-green alga  A. flos-aquae was inhibited by
    16-50% in comparison with controls after exposure to 5-29 µg/litre
    benz [a]anthracene for 14 days. In the same study, 14 days' exposure
    to fluoranthene at concentrations of 38-1100 µg/litre inhibited growth
    by 19-65%. The NOEC values ranged from 1 µg/litre for benzo [a]pyrene
    to > 4600 for acenaphthene (Bastian & Toetz, 1982). Other data for
    cyanobacteria are listed in Table 102.


        Table 102. Results of tests for the toxicity of polycyclic aromatic hydrocarbons (PAH) towards algae and plants

                                                                                                                                            

    Compound, species          Test conditions           Duration   Effect    Concentration   End-point              Reference
                                                                              (µg/litre)
                                                                                                                                            

    Aromatic two-ring PAH
    Acenaphthene
    Anabaena flos-aquae        A S   Contnuous light     2 h        NOEC      > 4600          Nitrogen fixation,     Bastian & Toetz (1985)
                                     no solvent                                               acetylene reduction
                                     250 × 103 cells/ml                                       activity
    Selenastrum                                          96 h       EC50      520             Cell number            US Environmental
    capricornutum                                                                                                    Protection Agency
                                                                                                                     (1978a)a

    Fluorene
    Anabaena flos-aquae        A S   Continuous light,   2 h        NOEC      260             Nitrogen fixation      Bastian & Toetz (1985)
                                     no solvent
                                     250 × 103 cells/ml
    Dunaliella bioculata       N S   Continuous light,   72 h       EC50      15 500          Growth rate            Heldal et al. (1984)
                                     solvent methanol
                                     250 × 103 cells/ml

    Naphthalene
    Anabaena flos-aquae        A S   Continuous light,   < 14 d     NOEC      3100            Growth                 Bastian & Toetz (1985)
                                     250 × 103 cells/ml

    Chlamydomonas                                        24 h       LC61      34 400b                                US Environmental
    angulosa                                                                                                         Protection Agency
                                                                                                                     (1986d)
    Chlorella vulgaris                                   48 h       LC61      33 000b         Cell number            Kauss & Hutchinson
                                                                                                                     (1975)
    Champia parvula            N R   Solvent,TEG         11-14d     MATC      < 695           Female growth          Thursby et al. (1985)
                                                                                              Number cystocarps
    Nitzchia palea             A S   No solvent          4 h        EC50      2820            Assimilation rate      Millemann et al. (1984)
    Selenastrum                A S   Solvent, methanol   4 h        EC50      2960            Assimilation rate      Millemann et al. (1984)
    capricornutum

    Table 102. (continued)

                                                                                                                                            

    Compound, species          Test conditions           Duration   Effect    Concentration   End-point              Reference
                                                                              (µg/litre)
                                                                                                                                            

    Aromatic three-ring PAH
    Anthracene
    Chlamydomonas              N S   5 × 104 cells/ml    3 h        EC50      239b            Photosynthesis         Hutchinson et al.
    angulosa (log phase)                                                                      inhibition             (1980)
    Chlorella vulgaris         N S   20 × 104 cells/ml   3 h        EC50      535b            Photosynthesis         Hutchinson et al.
    (log phase)                                                                               inhibition             (1980)
    Selenastrum                N R   Solvent, acetonec   28 h       EC50      3.9-37          Growth rate            Gala & Giesy (1992)
    capricornutum              (8 h) nitrile UV-A cont.c            EC10      1.5-7.8         Growth rate
                               1 × 105 cell/ml
    Selenastrum                      Cool-white light               EC30      40 000d         Growth                 US Environmental
    capricornutum                                                                                                    Protection Agency
                                                                                                                     (1987b)
    Selenastrum                      Gold fluorescent    NOEC       8000d     Growth          US Environmental
    capricornutum                    light                                                    Protection Agency
                                                                                              (1987b)

    Fluoranthene
    Anabaena flos-aquae        A S   Continuous light,   2 h        LOEC      230             Nitrogen fixation      Bastian & Toetz (1982)
                                     no solvent
    Scenedesmus                N S   Solvent, acetone    96 h       EC10      1.6             Growth                 Kordel et al. (1981)
    subspicatus                                          96 h       EC50      12
    Selenastrum                                          96 h       EC50      54 400d         Cell number            US Environmental
    capricornutum                                                                                                    Protection Agency
                                                                                                                     (1978b)
    Selenastrum                                          96 h       EC50      54 600d         Chlorophylla           US Environmental
    capricornutum                                                                                                    Protection Agency
                                                                                                                     (1978b)
    Skeletonema costatum                                 96 h       EC50      45 000d         Chlorophyla            US Environmental
                                                                                                                     Protection Agency
                                                                                                                     (1978b)
    Skeletonema costatum                                 96 h       EC50      45 600d         Cell number            US Environmental
                                                                                                                     Protection Agency
                                                                                                                     (1978b)

    Table 102. (continued)

                                                                                                                                            

    Compound, species          Test conditions           Duration   Effect    Concentration   End-point              Reference
                                                                              (µg/litre)
                                                                                                                                            

    Phenenthrene
    Anabaena flos-aquae        A S   Continuous light,   2 h        NOEC      130             Nitrogen fixation      Bastian & Toetz (1985)
                                     no solvent,
                                     250 × 103 cells/ml
    Nitzschia palea            A S   No solvent          4 h        EC50      870             Assimilation rate      Millemann et al. (1984)
    Selenastrum                A S   No solvent          4 h        EC50      940             Inhibition of          Millemann et al. (1984)
    capricornutum                                                                             photosynthesis

    Aromatic four-ring PAH
    Benz[a]anthracene
    Anabaena flos-aquae        A S   Continuous light    < 14 d     NOEC      1               Growth                 Bastian & Toetz (1982)
    Anabaena flos-aquae        A S   Continuous light,   2 h        NOEC      19b             Acetylene reduction    Bastian & Toetz (1985)
                                     no solvent
                                     250 × 103 cells/ml
    Anabaena flos-aquae        A S   Continuous light    < 14 d     EC        18-29b          Growth                 Bastian & Toetz (1982)
                                                                    16-48%
    Antithamnium plumula                                 -          EC 17%    10              Cell production level  Boney & Corner (1962)
                                                                                              in algal medium

    Chrysene
    Anabaena flos-aquae        A S   Continuous light,   2 h        NOEC      5b              Nitrogen fixation      Bastian & Toetz (1985)
                                     no solvent,
                                     250 × 103 cells/ml
    Anabaena flos-aquae        A S   Continuous light    14 d       EC35      62-96%          Growth                 Bastian & Toetz (1982)
                                                                              saturation

    Pyrene
    Anabaena flos-aquae        A S   Continuous light    < 14 d     NOEC      < 100           Growth                 Bastian & Toetz (1982)
    Chlamydomonas              N S   5 × 104 cells/ml    3 h        EC50      202b            Inhibition of          Hutchinson et al.
    angulosa (log phase)                                                                      photosynthesis         (1980)
    Chlorella vulgaris         N S   20 × 104 cell/ml    3 h        EC50      332b            Inhibition of          Hutchinson et al.
    (log phase)                                                                               photosynthesis         (1980)

    Table 102. (continued)

                                                                                                                                            

    Compound, species          Test conditions           Duration   Effect    Concentration   End-point              Reference
                                                                              (µg/litre)
                                                                                                                                            

    Aromatic five-ring PAH
    Benzo[a]pyrene
    Anabaena flos-aquae        N S   500 × 103 cells/ml  72 h       EC50      > 4000d         Growth                 Schoeny et al. (1988)
    Antithamnium plumula                                 96 h       EC 49%    10b             Cell production        Boney & Corner (1962)
                                                         96 h       EC 54%    100d            increase
    Chlamydomonas              N S   500 × 103 cells/ml  72 h       EC50      > 4000d         Growth                 Schoeny et al. (1988)
    reinhardtii
    Euglena gracilis           N S   500 × 103 cells/ml  72 h       EC50      > 4000d         Growth                 Schoeny et al. (1988)
    Porphyra tenera                                      80-320     EC        1000d           Cell size decrease     Boney (1974)
                                                         min
    Poteriochromonas           N S   500 × 103 cells/ml  72 h       EC50      > 4000d         Growth                 Schoeny et al. (1988)
    malhamensis
    Scenedasmus acutus         N S   500 × 103 cells/ml  72 h       EC50      5b              Growth                 Schoeny et al. (1988)
    Scenedesmus                N S   Solvent, acetone    20 h       EC        300d            Chlorophyll content    Zachleder et al. (1983)
    quadracanda
    Scenedesmus                N S   Solvent, acetone    20 h       EC        300d            Biomass                Zachleder et al. (1983)

    Perylene
    Scenedesmus                N S   Solvent acetone     96 h       EC10      0.0066          Growth                 Kordel et al. (1981)
    subspicatus                                          96 h       EC50      > 0.32
                                                                                                                                            

    A, analysed concentration; N, nominal concentration; S, static system; F, flow-through system; R (0.5 d), system with renewal
       (each half day)
    NOEC, no-observed-effect concentration; EC, effect concentration; LC, lethal concentration; MATC, maximum acceptable toxicant
    concentration; LOEC, lowest-observed-effect concentration; TEG, triethylene glycol
    a  From Cairns & Nebeker (1982)
    b  Concentration higher than solubility but not exceeding it by 10 times
    c  Explicitly mentioned that organisms were tested for phototoxicity of test substance either by sunlight or artificial UV radiation
    d  Concentration 10 times higher than the solubility


    Naphthalene had no detectable effect on the rate of respiration of
    yeast at concentrations up to its maximum solubility (31 mg/litre)
    (Haubenstricker et al., 1990).

    9.1.1.2  Soil

    Few data are available on the toxicity of PAH to microbial communities
    in the soil. Application of 500 mg/kg dry weight naphthalene did not
    reduce soil microbial respiration or nitrogen mineralization, and 90%
    was degraded within 10-20 days (Kirchmann et al., 1991).

    9.1.2  Aquatic organisms

    9.1.2.1  Plants

    For many PAH, the dose that is toxic for algae exceeds the maximum
    solubility in water (Table 102). Benz [a]anthracene (four-ring) and
    benzo [a]pyrene (five-ring) are considered to be the most toxic PAH,
    with EC50 values of 29 µg/litre and 5-15 µg/litre, respectively. The
    EC50 values for three-ring PAH are 240-940 µg/litre. Naphthalene and
    fluorene (two-ring) are considered to be the least toxic, with EC50
    values of 2800-15 000 µg/litre. The ranges of EC50 values are 200-330
    for four-ring compounds and 5-> 4000 µg/litre for five-ring PAH.

    9.1.2.2  Invertebrates

    Data on the toxicity of two- to six-ring PAH are available for
    invertebrates such as crustaceans, insects, molluscs, polychaetes, and
    echinoderms (Table 103). The data include the results of both
    phototoxicity and non-phototoxicity tests, which are poorly comparable
    because of the dynamic character of the ultraviolet radiation-induced
    oxidation products and the often short exposure time.

    Phenanthrene, fluorene, and triphenylene did not cause photoinduced
    toxicity to  Daphnia and did not absorb light. Benzo [a]fluorene,
    benzo [k]-fluorene, and chrysene were considered to be moderately
    toxic to  Daphnia, whereas anthracene, fluoranthene, pyrene,
    benz [a]anthracene, benzo [k]-fluoranthene, benzo [a]pyrene,
    benzo [e]pyrene, perylene, dibenz [a]anthracene, and
    benzo [ghi]perylene were very toxic and absorbed more energy.
    Toxicity was also correlated with the phosphorescence lifetime and
    energetic state of the molecule. The authors stated that the
    photodynamic response was due to the PAH assimilated into organisms
    rather than to external photoproducts. Phototoxicity occurs as a
    result of energy transfer from activated (triplet) PAH to ground-state
    oxygen. Singlet oxygen is a reactive chemical that can denature
    biomolecules within aquatic organisms. The authors estimated that the
    internal concentration of PAH that caused the death of 50% of the
     Daphnia was 77 nmol/g wet weight in continuous light. No toxic
    effects were seen in the absence of light. The phototoxicity of
    anthracene was confirmed by experiments with
     Daphnia pulex (Newsted & Giesy, 1987).


        Table 103. Results of tests for the toxicity of polycyclic aromatic hydrocarbons (PAH) towards invertebrates

                                                                                                                                              

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                              

    PROTOZOANS
    Aromatic two-ring PAH
    Acenaphthylene
    Tetrahymena                                                      24 h        EC50       6300a          Population      Yoshioka et al.
    puryformis                                                                   growth                                    (1986)

    Aromatic three-ring PAH
    Anthracene
    Paramecium aurelia    10 000           N S  Dark                 1.5 h       NOEC       1000b          Mortality       Joshi & Misra
                          cells/litre           0.75 h sunc          0.75 h      EC 100%    100a           Mortality       (1986)

    Paramecium                                                       1 h         LC90       1000b                          US Environmental
    caudatum                                                                                                               Protection
                                                                                                                           Agency (1987b)

    Aromatic five-ring PAH
    Benzo[a]pyrene
    Gyrodinium sp.        Log phase        N S  Solvent acetone      12 d        EC 20%     5a             Cell division   Ishio et al. (1977)
                                                                                                           period
                                                                                                           increase

    INSECTS
    Aromatic two-ring PAH
    Fluoranthene
    Chironomus riparius   Larvae           N S l/d = 16/8            48 h        EC50       2350           Reproduction    Finger et al.
                                           A IF 30 d                 NOEC        142        Emergence      (1985)
    Hexagenia bilineata                    N S                       96 h        LC50       5800

    Naphthalene
    Chironomus            4th instar       A F  Solvent, ethanol     Chronic     LOEC       500            Physiology      Darville & Wilhm
    attenuatus                                                                   LC50       1300                           (1984)

    Table 103. (continued)

                                                                                                                                              

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                              

    Chironomus tentans    Larvae           A S  Solvent, methanol    48 h        LC50       2,810                          Millemann et al.
                                                                                                                           (1984)
    Somatochlora          Nymph            - S  21°C                 96 h        LC50       1000-                          Correa & Coler
    cingulata                                                                               2500                           (1983)
    Tanytarsus dissimilas Life cycle       A F  Solvent, ethanol     Chronic     LOEC       500            Physiology      Darville & Wilhm
                                                                                 LC50       1300                           (1984)

    Anthracene
    Aedes aegypti         3rd-4th instar   N S  Solvent DMSO         1 d         LC50       < 1.0                          Borovsky et al.
                                                6 h sun, 18 h darkc                                                        (1987)
    Aedes aegypti         < 8 h old        N S  1 h UVc              12 h        LC50       150a                           Kagan et al.
                                                                                                                           (1985)
    Aedes                 3rd-4th instar   N S  Solvent, DMSO        1 d         LC50       260a                           Borovsky et al.
    taeniorrhynchus                             6 h sun, 18 h darkc                                                        (1987)
    Culex                 3rd-4th instar   N S  Solvent, DMSO        1 d         LC50       37                             Borovsky et al.
    quinquefasciatus                       6 h sun, 18 h darkc                                                             (1987)
    Culex sp.                                                        24 h        LC50       26.8                           US Environmental
                                                                                                                           Protection Agency
                                                                                                                           (1987b)

    Fluoranthene
    Aedes aegypti         3rd-4th instar   N S  Solvent, DMSO        24 h        LC50       10                             Borovsky et al.
                                                6 h sun, 18 h darkc                                                        (1987)
    Aedes aegypti         < 8-h old        N S  1 h sunc             12 h        LC50       12                             Kagan et al.
                                                                                                                           (1985)
    Aedes                 3-4 instar       N S  Solvent, DMSO        24 h        LC50       48                             Borovsky et al.
    taeniorrhynchus                             6 h sun, 18 h dark,                                                        (1987)
    Culex                 3rd-4th instar   N S  Solvent, DMSO        24 h        LC50       45                             Borovsky et al.
    quinquefasciatus                            6 h sun, 18 h darkc                                                        (1987)

    Phenanthrene
    Chironomus tentans    Larvae           A S  Solvent, methanol    48 h        LC50       490                            Millemann et al.
                                                                                                                           (1984)

    Table 103. (continued)

                                                                                                                                              

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                              

    Aromatic four-ring PAH
    Pyrene
    Aedes aegypti         1st instar       N S  1 h UVc              11 d        EC 18%     0.9            Adult           Kagan & Kagan
                                                                     7 d         NOEC       0.9            emergence       (1986)
                                           N S  Dark                 11 d        NOEC       30
                          < 8-h old        N S  1 h UVc              12 h        LC50       20                             Kagan et al. (1985)
    Aedes aegypti         3rd-4th instar   N S  Solvent, DMSO        24 h        LC50       35                             Borovsky et al.
                                                6 h sun, 8 h darkc                                                         (1987)
    Aedes                 3rd-4th instar   N S  Solvent, DMSO        24 h        LC50       60                             Borovsky et al.
    aeniorrhynchus                              6 h sun, 8 h darkc                                                         (1987)
    Culex                 3rd-4th instar   N S  Solvent, DMSO        24 h        LC50       37                             Borovsky et al.
    quinquefasciatus                            6 h sun, 8 h darkc                                                         (1987)

    Aromatic five-ring PAH
    Benzo[a]pyrene
    Aades aegypti         1st instar       N S  30 min UVc           11 d        NOEC       0.14           Adult           Kagan & Kagan
                          1st instar       N S  Dark                 11 d        NOEC       0.9            emergence       (1986)
                          4th instar       N S  Dark                 7d          NOEC       6700b
                          4th instar       N S  30 min UVc           7 d         NOEC       30a
                          4th instar       N S  30 min UVc           7 d         LC50       120b

    POLYCHAETES
    Aromatic two-ring PAH
    Fluorene
    Neanthes              Immature         A S  Solvent, acetone     96 h        LC50       1000                           Rossi & Neff
    arenacoendata         adult                 artificial seawater                                                        (1978)

    Naphthalene
    Neanthes              Immature         A S  Solvent, acetone     96 h        LC50       3800                           Rossi & Neff
    arenacoendata         adult                 artificial seawater                                                        (1978)

    Table 103. (continued)

                                                                                                                                              

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                              

    Aromatic three-ring PAH
    Fluoranthene
    Neanthes              Immature         A S  Solvent, acetone     96 h        LC50       500a                           Rossi & Neff
    arenacoendata         adult                 artificial seawater                                                        (1978)

    1-Methylphenanthrene
    Neanthes              Immature         A S  Solvent, acetone     96 h        LC50       300b                           Rossi & Neff
    arenacoendata         adult                 artificial seawater                                                        (1978)

    Phenanthrene
    Neanthes              Immature         A S  Solvent, acetone     96 h        LC50       600                            Rossi & Neff
    arenacoendata         adult                 artificial seawater                                                        (1978)

    Aromatic four-ring PAH
    Benz[a]anthracene
    Nereis virens                          A S  Sediment             6 d         NOEC       14.4           Oxygen          McElroy (1985)
                                                                                            mg/kg          consumption
                                                                                 NOEC       14.4           Ammonia
                                                                                            mg/kg          extraction
                                                                                 NOEC       14.4           Microsomal
                                                                                            mg/kg          AHH activity

    Chrysene
    Neanthes              Immature         A S  Solvent, acetone     96 h        NOEC       > 1000b        Mortality       Rossi & Neff
    arenacoendata         adult                 artificial seawater                                                        (1978)

    Aromatic five-ring PAH
    Benzo[a]pyrene
    Neanthes              Adult            A S  Solvent, acetone     96 h        NOEC       > 1000b        Mortality       Rossi & Neff
    arenaceodentata                                                                                                        (1978)

    Table 103. (continued)

                                                                                                                                              

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                              

    Dibenz[a,h]anthracene
    Neanthes              Immature         A S  Solvent, acetone     96 h        NOEC       > 1000b        Mortality       Rossi & Neff
    aranacoendata         adult                 artificial seawater                                                        (1978)

    MOLLUSCS
    Aromatic two-ring PAH
    Acenaphthene
    Aplexa hypnorum       Adult            A F  Solvent,             6 h         LC50       > 2040                         Holcombe et al.
                                                isopropanol          9                                                     (1983)

    Fluorane
    Mudalia potosensis                     N S                       96 h        LC50       5600a                          Finger et al.
                                                                                                                           (1985)

    Naphthalene
    Physa gyrina          Adult            A S  No solvent           48 h        LC50       5020                           Millemann et al.
                                                                                                                           (1984)

    Aromatic three-ring PAH
    Fluoranthene
    Mytilus edulis        40-50-mm         A S  Solvent, acetone     9 d         EC50       80             Feeding rate    Donkin et al.
                          shell                                                                                            (1989)

    Aromatic five-ring PAH
    Benzo[a]pyrene
    Mercenaria                             A F  Columns              1-15        EC         < 0.001        Haemocyte       Anderson et al.
    mercenaria                                                       weeks                                 lysozome        (1981)
                                                                                                           concentration
                                                                                                           increase
                                                                     8 weeks     EC         < 0.001        Bacterial
                                                                                                           clearance

    Table 103. (continued)

                                                                                                                                              

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                              

    Mytilus californianus                                            24 h        EC 20%     10 000b        Oxygen          Sabourin & Tullis
                                                                                                           consumption     (1981)
                                                                                 EC 10%     1000b          Oxygen
                                                                                                           consumption

    ECHINODERMS
    Aromatic five-ring PAH
    Benzo[a]pyrene
    Strongylocentrotus    Gametes          S N  Solvent, ethanol     30-45       NOEC       0.5            Cytological     Hose (1985)
    purpuratus,                                                      min                                   abnormality
                                                                                 LOEC       0.5            Mitoses/embryo
                                                                                 NOEC       50b            Fertilization
                                                                                                           success
    Psammechinus          Eggs             N S  Artificial seawater  100 min     NOEC       2000b          Development     Bresch et al.
    miliaris              (fertililized                                                                                    (1972)
                          30 min)

    CRUSTACEANS

    Aromatic two-ring PAH
    Acenaphthene
    Daphnia magna                          N S  Solvent              48 h        LC50       41 000b                        LeBlanc (1980)
                                                                                 NOEC       600            Mortality       LeBlanc (1980)

    Fluorene
    Daphnia magna                          A R (0.5 d) No solvent    2 d         NOEC       17.0           Mortality       Newsted & Giesy
                                                -UV:1 d; +UV:1 dc                                                          (1987)
    Daphnia magna                          A IF l/d = 16/8           21 d        NOEC       62.5           Reproduction    Finger et al.
                                                                     21 d        LOEC       125            Reproduction    (1985)
                                           N S  270 mg.l CaCO3       49 h        EC50       430            Immobilization
                                                Solvent, acetone

    Table 103. (continued)

                                                                                                                                              

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                              

    Daphnia pulex                          N S  Solvent, acetone     48 h        EC50       212            Immobilization  Smith et al. (1988)
    Gammurmus                              N S                       96 h        LC50       600                            Finger et al.
    pseudolimnaeus                                                                                                         (1985)

    Naphthalene
    Daphnia magna         < 24 h           N S  Solvent              48 h        NOEC       600            Mortality       LeBlanc (1980)
    Daphnia magna         Adult            N    Solvent, ethanol     4 h         LOEC       1000           Behaviour       Whitman & Miller
                                                                                                                           (1982)
    Daphnia magna                          A S  No solvent           48 h        LC50       2160                           Millemann et al.
                                                                                                                           (1984)
    Daphnia magna                          N S                       48 h        EC50       4700           Immobilization  Smith et al. (1988)
    Daphnia magna         < 24 h           S                         48 h        EC50       4100                           Crider et al. (1982)
    Daphnia magna                          N S  Solvent              48 h        LC50       8600                           LeBlanc (1980)
    Daphnia magna         4-6 d            N S  No solvent           48 h        LC50       16 000                         Bobra et al. (1983)
    Daphnia magna                          N S  Solvent, acetone     48 h        LC50       22 600                         Eastmond et al.
                                                + triton-X-100                                                             (1984)
    Daphnia pulex         24-h old         A R  Filtered crystals    Chronic     NOEC       330            Increased       Geiger & Buikema
                                                                                                           lifespan &      (1982)
                                                                                                           reproduction
                                                                     Chronic     LOEC       600            Growth
    Daphnia pulax         1.9-2.1 mm       N S  No solvent           96h         LC50       1000                           Trucco et al.
                                                                                                                           (1983)
    Daphnia pulex                          N S                       48 h        LC50       3400                           Geiger & Buikema
                                                                                                                           (1981)
    Daphnia pulex                          N S  Solvent, acetone     48 h        EC50       4660           Immobility      Smith et al. (1988)
    Elasmopus sp.         Adult            - S  22°C (closed         24 h        LC50       5000                           Lee & Nicol
                                                bottles)                                                                   (1978)
    Gammarus minus                         A S                       48 h        LC50       3930                           Millemann et al.
                                                                                                                           (1984)

    Table 103. (continued)

                                                                                                                                              

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                              

    Hemigrapsus                            A F  Seawater             8 d         LC50       2800           Mortality and   Gharrett & Rice
    nudus                                       4 h water/8 h air    18 d        EC50       700            locomotion      (1987)
                                           A F  Seawater             8 d         LC50       2200           Mortality and
                                                8 h water/4 h air    18 d        EC50       2000           locomotion
                                           A F  Seawater             8 d         LC50       1100           Mortality and
                                                12 h water/0 h air   18 d        EC50       800            locomotion
    Neomysis                               A F  Artificial sea-      96 h        LC50       850                            Smith &
    americana                                   water, 25°C                                                                Hargreaves
                                           A F  Artificial sea-      96 h        LC50       1280                           (1983)
                                                water, 15°C
    Palaemonetes          -                - -  -                    24 h        LC50       2500                           Anderson et al.
    penaeus                                                                                                                (1974)
    Pandalus              -                - S  12°C                 96 h        LC50       970                            Korn et al. (1979)
    goniurus                                 S  8°C                  96 h        LC50       1020
                                             S  4°C                  96 h        LC50       2200
    Parhyale              Adult            - S  22°C                 24 h        LC50       6000                           Lee & Nicol
    hawaiaensis                                                                                                            (1978)

    Aromatic three-ring PAH
    Anthracene
    Artemia salina        1 d              N S  1 h UVc              3 h         LC50       20                             Kagan et al.
                                                                                                                           (1985)
    Artemia salina                         N S  Darkc                24 h        LC50       > 50                           Abernethy et al.
                                                                                                                           (1986)
    Daphnia magna                          - -  UV-A=0               21 d        NOEC       2.2            Population      Foran et al. (1991)
                                                UV-A=31c             21 d        NOEC       2.2            growth
                                                UV-A=60c             21 d        NOEC       2.2
                                                UV-A=117c            21 d        NOEC       1.9
    Daphnia magna         Adult            N S  1 h UVc              2 h         LC50       20                             Kagan et al.
                                                                                                                           (1985)
    Daphnia magna                          A R (0.5d) No solvent     1.21 d      LC50       15                             Newsted & Giesy
                                                -UV:1 d;                                                                   (1987)
                                                +UV:0.21 dc

    Table 103. (continued)

                                                                                                                                              

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                              

    Daphnia magna         4-6 d            N S  Dark                 48 h        LC50       35.6                           Abernethy et al.
                                                                                                                           (1986)
    Daphnia magna         4-6 d            N S  No solvent           48 h        LC50       3030b                          Bobra et al. (1983)
    Daphnia magna         < 24 h             S                       48 h        LC0        < 500b                         Eastmond et al.
                                                                                                                           (1984)
    Daphnia pulex                          A S  0.25 h sun,          24.25 h     EC50       1.2            Immobility      Allred & Giesy
                                                1 d darkc                                                                  (1985)
                                           A S  0.17 h sun,          24.17 h     EC100      9.6
                                                1 d darkc
                                           A S  0.75 h filtered      24.75 h     NOEC       12.7
                                                sun, 1 d darkc                   EC 75%     26.4
    Daphnia pulex                          N S  Solvent, acetone     48h         EC50       754b           Immobility      Smith et al. (1988)

    Benzo[a]fluorene
    Daphnia magna                          A R (0.5 d) No solvent    1.96 d      LC50       4.8                            Newsted & Giesy
                                                -UV:1 d; +UV:0.96 dc                                                       (1987)
    Benzo[b]fluorine
    Daphnia magna                          A R (0.5 d) No solvent    1.93 d      LC50       2.2                            Newsted & Giesy
                                                -UV:1 d; +UV:0.93 dc                                                       (1987)

    Fluoranthene
    Artemia salina                         N S 1 h sunc              3 h         LC50       40                             Kagan et al.
                                                                                                                           (1985)
    Daphnia magna         Adult            N S 1 h sunc              2 h         LC50       4                              Kagan et al.
                                                                                                                           (1985)
    Daphnia magna                          A R (0.5 d) No solvent    1.45 d      LC50       9.0                            Newsted & Giesy
                                                -UV:1 d; +UV:0.45 dc                                                       (1987)
    Daphnia magna                          N S                       48 h        LC50       325 000b                       US Environmental
                                                                                                                           Protection Agency
                                                                                                                           (1978b)
    Daphnia magna         < 24 h           N S Solvent               48 h        LC50       320 000b                       LeBlanc (1980)
                                                                                 NOEC       < 8800b        Mortality

    Table 103. (continued)

                                                                                                                                              

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                              

    Mysidopsis bahia                                                 96 h        LC50       40                             US Environmental
                                                                                                                           Protection Agency
                                                                                                                           (1978b)

    Phenanthrene
    Artemia salina                         N S  Dark                 24 h        LC50       677                            Abernethy et al.
                                                                                                                           (1986)
    Daphnia magna                          A S                       48 h        LC50       700                            Millemann et al.
                                                                                                                           (1984)
    Daphnia magna                          N S  Solvent, acetone     48 h        LC50       840                            Eastmond et al.
                                                + triton-X-100                                                             (1984)
    Daphnia magna         4-6 d            N S  No solvent           48 h        LC50       1160                           Bobra et al. (1983)
    Daphnia magna                          A R (0.5 d) No solvent    2 d         NOEC       40.1           Immobility      Newsted & Giesy
                                                -UV:1 d; +UVA dc                                                           (1987)
    Daphnia magna                          A F  Glass column         21 d        LC50       130                            Hooftman &
                                                                     21 d        EC50       50             Reproduction    Evers-de Ruiter
                                                                     21 d        NOEC       21             Reproduction    (1992a)
                                                                     21 d        NOEC       66             Mortality
                                                                     21 d        NOEC       38             Growth,
                                                                                                           condition,
                                                                                                           behaviour
                                           A R  Glass column         21 d        EC50       180            Reproduction
                                                                     21 d        NOEC       100            Reproduction
    Daphnia magna         4-6 d            N S  Dark                 48 h        LC50       207                            Abernethy et al.
                                                                                                                           (1986)
    Daphnia pulex         1.9-2.1 mm       N S  No solvent           96 h        LC50       100                            Trucco et al.
                                                                                                                           (1983)
    Daphnia pulex                          N S  Solvent, acetone     48 h        EC50       350            Immobility      Smith et al. (1988)
    Daphnia pulex                          N S                       48 h        EC50       734            Immobility      Passino & Smith
                                                                                                                           (1987)

    Table 103. (continued)

                                                                                                                                              

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                              

    Daphnia pulex                                                    48 h        LC50       960-                           Geiger & Buikema
                                                                                 1280                                      (1982)
                          24 h             A R  (1 d) No solvent     approx.     NOEC       110            Reproduction,
                                                                     50 d                                  growth

    Daphnia pulex                          N R  (2-3 d) 97% A.I.     21 d        LC33-73%   130                            Savino & Tanabe
                                                Solvent, acetone                 LOEC       60             Reproduction,   (1989)
                                                                                                           growth
    Gammarus minus                         A S                       48 h        LC50       460                            Millemann et al.
                                                                                                                           (1984)

    Aromatic four-ring PAH
    Benz[a]anthracene
    Daphnia magna                          A R  (0.5 d) No solvent   1.52 d      LC50       1.8                            Newsted & Giesy
                                                -UV: 1 d; +UV:0.52 dc                                                      (1987)
    Daphnia pulex         1.9-2.1 mm       N S  No solvent           96 h        LC50       10                             Trucco et al.
                                                photo period: 12 h                                                         (1983)

    Chrysene
    Daphnia magna                          A R  (0.5 d) No solvent   2 d         LC50       0.7                            Newsted & Giesy
                                                -UV:1 d; +UV:1 dc                                                          (1987)
    Daphnia magna         Juvenile         N S  Solvent, acetone     2 d         NOEC       288b           Mortality       Eastmond et al.
                          + adult               l/d = 16 h/8 h                                                             (1984)

    Pyrene
    Artemis salina        1 d              N S  1 h UVc              3 h         LC50       8                              Kagan et al.
                                                                                                                           (1985)
    Artemia salina                         N S  Dark                 24 h        LC50       > 99                           Abernethy et al.
                                                                                                                           (1986)
    Daphnia magna         Adult            N S  1 h UVc              2 h         LC50       4                              Kagan et al.
                                                                                                                           (1985)
    Daphnia magna                          A R  (0.5 d) No solvent   1.14 d      LC50       5.7                            Newsted & Giesy
                                                -UV: 1 d; +UV:O. 14 dc                                                     (1987)

    Table 103. (continued)

                                                                                                                                              

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                              

    Daphnia magna         4-6 d old        N S  Dark                 48 h        LC50       91                             Abernethy et al.
                                                                                                                           (1986)
    Daphnia magna         4-6 d old        N S  no solvent           48 h        LC50       1820b                          Bobra et al. (1983)

    Triphenylene
    Daphnia magna                          A R  (15 d) No solvent    2 d         NOEC       1.7            Mortality       Newsted & Giesy
                                                -UV:1 d; +UV:1 dc                                                          (1987)

    Aromatic five-ring PAH
    Benzo[a]pyrene
    Artemia salina        Eggs                                       48 h        NOEC       10 000b        Viability       Kuwabara et al.
                                                                                                                           (1980)
    Calanus               Adult                                      -           LC         4              Mortality       Lee et al. (1972)
    heigolandicus
    Calanus                                                          7 d         EC         50b            AHH activity    Walters et al.
    heigolandicus                                                                                                          (1979)
    Daphnia magna                          A R  (0.5 d) No solvent   1.19 d      LC50       1.5            Stimulation     Newsted & Giesy
                                                -UV:1 d; +UV:0.19 dc                                                       (1987)
    Daphnia pulex         1.9-2.1 mm       N S  No solvent           96 h        LC5O       5a                             Trucco et al.
                                                photo period: 12 h                                                         (1983)

    Benzo[e]pyrene
    Daphnia magna                          A R (0.5 d) No solvent    1.64 d      LC50       0.7                            Newsted & Giesy
                                                -UV:1 d; +UV:0.64 dc                                                       (1987)

    Benzo[k]fluoranthene
    Daphnia magna                          A R  (0.5 d) No solvent   1.54 d      LC50       1.4a                           Newsted & Giesy
                                                -UV: 1 d; +UV:0.54 dc                                                      (1987)

    Dibenz[a,h]anthracene
    Daphnia magna                          A R  (0.5d) No solvent    1.13 d      LC50       0.4a                           Newsted & Giesy
                                                -UV:1 d; +UV:0.13 dc                                                       (1987)

    Table 103. (continued)

                                                                                                                                              

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                              

    Perylene
    Daphnia magna                          A R  (0.5 d) No solvent   1.76 d      LC50       0.6a                           Newsted & Giesy
                                                -UV:1 d; +UV:0.76 dc                                                       (1987)
    Aromatic six-ring PAH
    Benzo[ghi]perylene
    Daphnia magna                          A R  (0.5 d) No solvent   1.58 d      LC50       0.2                            Newsted & Giesy
                                                -UV:1 d; +UV:0.58 dc                                                       (1987)
                                                                                                                                              

    A, analysed concentration; N, nominal concentration; S, static system; F, flow-through system; IF, intermittent flow;
    R(0.5 d), system with renewal (each half day); S\F, first period in a static system followed by a period in a flow-through system;
    l/d, light/dark; +UV, with UV radiation; -UV, without UV radiation; DMSO, dimethyl sulfoxide; EC, exposure concentration;
    NOEC, no-observed-effect concentration; LC, lethal concentration; LOEC, lowest-observed-effect concentration

    a Concentration higher than solubility but not exceeding it by 10 times
    b Concentration 10 times higher than the solubility
    c Explicitly mentioned that organisms were tested for phototoxicity of test substance either in sunlight or artificial UV radiation
    d From Cairns & Nebeker (1982)


    PAH-polluted elutriates derived from polluted sediments were highly
    toxic to  Daphnia magna when combined with either sunlight or 354-nm
    near-ultraviolet radiation, whereas none of the elutriates was toxic
    in the absence of light (Davenport & Spacie, 1991).

    A 50% decrease in feeding rate was reported in the mussel
     Mytilus edulis after nine days' exposure to 80 µg/litre fluoranthene
    (Donkin et al., 1989). When  Mercenaria mercenaria clams were exposed
    in flow-through tanks, in which seawater was pumped through sand
    columns adsorbing 50 mg benzo [a]pyrene, the concentrations in the
    water were generally below the detection limit (< 0.001 µg/litre),
    whereas the tissue concentrations were 2-4 µg/kg (0.15 µg/kg in
    control clams). This resulted in an increased intrahaemocytic lysozyme
    concentration and significantly impaired ability to clear bacteria.
    Thus, resistance to bacterial infection is decreased by PAH (Anderson
    et al., 1981).

    The 96-h LC50 values in the marine polychaete  Neanthes 
     arenaceodentate were 3800 µg/litre for the two-ring PAH naphthalene
    and 1000 µg/litre for fluorene, 600 µg/litre for phenanthrene, and 300
    µg/litre for 1-methyl-phenanthrene (three-ring). None of the four- and
    five-ring PAH were toxic up to the highest concentration tested, 1000
    µg/litre, except fluoranthene, which had a 96-h LC50 of 500 µg/litre
    (Rossi & Neff, 1978).

    9.1.2.3  Vertebrates

    Data on toxicity to vertebrates like fish and amphibians are available
    for two- to five-ring PAH (Table 104). Most of the data are derived
    from phototoxicity tests.

    As discussed in Section 4, fish can metabolize PAH into intermediates
    that may have teratogenic, mutagenic, or carcinogenic properties and
    are associated with hepatic tumours in free-living fish. In addition,
    certain PAH can cause physiological changes that affect the growth,
    reproduction, swimming performance, and respiration of fish. The
    effect of environmental carcinogens on fish populations depends on the
    exposure received at each susceptible life stage, the ability at each
    stage to absorb and metabolize the carcinogen and repair the ensuing
    damage, and the consequences of tumour induction in vital organs at
    each life stage. Additional factors that influence carcinogenicity are
    the stage of organism development, the route of exposure, genetic
    variation, and cytochrome P450 mixed-function oxygenase activity
    (Bailey et al., 1989).

    Several PAH can produce cancer-like growths and are teratogenic and
    mutagenic to fish. In  Oncorhynchus mykiss (former name for
     Salmo gairdneri), the liver was the primary target after exposure to
    benzo [a]pyrene in the diet and by intraperitoneal injection.
    Administration by the latter route, while not directly relevant to
    environmental exposure, also produced a fibrosarcoma and a stomach
    papilloma in one individual, along with tumours, indicating that the
    route of exposure is of some importance in fish (Hendricks et al.,
    1985).


        Table 104. Results of tests for the toxicity of polycyclic aromatic hydrocarbons (PAH) towards vertebrates

                                                                                                                                             

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                             

    FISH
    Aromatic two-ring PAH
    Acenaphthene
    Cyprinodon            Juvenile         N S                       96 h        LC50       2200                           Heitmuller et al.
    variegatus                                                                                                             (1981)
    Ictalurus punctatus                    A F  solvent              96 h        LC50       1720                           Holcombe et al.
                                                                                                                           (1983)
    Lepomis macrochirus   0.32-1.2 g       N S  solvent              96 h        LC50       1700                           Buccafusco et al.
                                                                                                                           (1981)
    Pimephales promelas   Juvenile (32 d)  A F  solvent              96 h        LC50       1600                           Holcombe et al.
                                                                                                                           (1983)
    Pimephales promelas   Embryo-          A F  l/d = 16/8 h         32 d        NOEC       509            Survival        Cairns & Nebeker
                          juvenile         Glass column              96 h        LC50       608                            (1982)
                                           Solvent, DMF
    Oncorhynchus mykiss   Juvenile         A F  Solvent,             96 h        LC50       670                            Holcombe et al.
                                                isopropanol          48 h        LC50       1130                           (1983)
    Salmo trutta          Juvenile         A F  Solvent,             69 h        LC50       580                            Holcombe et al.
                                                isopropanol          48 h        LC50       650                            (1983)

    Acenaphthylene
    Oryzias latipes                                                  48 h        LG50       11 000                         Yoshioka et al.
                                                                                                                           (1986)

    Fluorene
    Lepomis macrochirus                    A F                       30 d        NOEC       19             Predating prey  Finger et al.
                                                                                 NOEC       42             Growth          (1985)
                                                                                 NOEC       49             Mortality
                                           N S                       96 h        LC50       910
    Oncorhynchus mykiss                    N S                       96 h        LC50       820
    Pimephales promelas                    N S                       96 h        LC50       > 100 000a

    Table 104. (continued)

                                                                                                                                             

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                             

    Naphthalene
    Abramis bramana       1 year           N R                       96 h        LC50       10 000                         Frumin et al. (1992)
    Fundulus heteroclitus                                            30 d        NOEC       1600                           US Environmental
                                                                                                                           Protection Agency
                                                                                                                           (1986d)
    Micropterus salmoides Eggs and         A F  No solvent           7 d         NOEC       28             Survival        Black et al. (1983)
                          larvae (to 4 d                                         LC8-35     28-239
                          posthatch
                          Embryo-larva     A F  No solvent           7 d         LC50       510
                          (to 4 d
                          posthatch)
    Micropterus salmoides Eggs-larvae      A F  No solvent           7 d         LC50       680                            Millemann et al.
                                                                                                                           (1984)
    Oncorhynchus          Fry              - S  4-12°C               96 h        LC50       1370-1240                      Korn et al. (1979)
    gorbuscha
    Oncorhynchus kisutch  1 g              A F                       96 h        LC50       770            Parasitized     Moles (1980)
    Oncorhynchus kisutch  1 g              A F                       40 d        EC         670-           Growth          Moles et al. (1981)
                                                                                            1400
    Oncorhynchus kisutch  1 g              A F                       96 h        LC50       2100                           Moles (1980)
    Oncorhynchus kisutch  1 g              A F                       96 h        LC50       3220           Unparasitized   Moles (1980)
    Oncorhynchus mykiss   Eggs-larvae      A F  No solvent           23 d        NOEC       15             Hatching        Black et al. (1983)
                          (to 4 d post-                              27 d        NOEC       15             Survival
                          hatch)                                                 LC50       110
    Oncorhynchus mykiss   Eggs-larvae      A F  No solvent           27 d        NOEC       120            Survival,       Millemann et al.
                                                                                                           teratogenity    (1984)
    Oncorhynchus mykiss   Adult            A F                       96 h        LC50       1600                           DeGraeve et al.
                                                                                                                           (1982)
    Oncorhynchus mykiss   13-21 d          N S  Solvent,             96 h        LC50       4500                           Edsall (1991)
                                                acetone
    Oncorhynchus mykiss                    A F                       96 h        LC50       2300                           DeGraeve et al.
                                                                                                                           (1980)

    Table 104. (continued)

                                                                                                                                             

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                             

    Pimephales promelas   Embryo-larva     A F                       30 d        NOEC       450            Growth,         DeGraeve et al.
                                                                                 EC         850            hatching        (1982)
                                                                     Subchronic  LOEC       850            Reproduction

    Pimephales promelas   Juvenile         A S  No solvent           96 h        LC50       1990                           Millemann et al.
                                                                                                                           (1984)
    Pimephales promelas                    A F                       96 h        LC50       4900           Reproduction    DeGraeve et al.
                                                                                                                           (1980)
    Pimephales promelas                    A F                       96 h        LC50       6140                           Geiger et al. (1985)
    Pimephales promelas                    A F                       96 h        LC50       6080                           Holcombe et al.
                                                                                                                           (1984)
    Pimephales promelas   Adult            A F                       96 h        LC50       7900                           DeGraeve et al.
                                                                                                                           (1982)
    Pimephales promelas                    A F                       96 h        LC50       8900                           DeGraeve et al.
                                                                                                                           (1980)
    Tilapia oreochromis                    N R                       96 h        LC50       22 400                         Frumin et al.
                                                                                                                           (1992)

    Aromatic three-ring PAH
    Anthracene
    Lepomis macrochirus   1-1.5 g          N F  24 h UV,             200 h       NOEC       1.2            Mortality       Oris & Giesy
                                                0 h darkb                                                                  (1986)
    Lepomis sp.           Juvenile         A F  Low UV               96 h        LC50       2.78                           Oris & Giesy
                          (2-3 cm)              intensityb                                                                 (1985)
    Lepomis macrochirus   1-1.5 g          N F  24 h UVb             125 h       LC50       4.5                            Oris & Giesy
                                                                     96 h        LC50       4.5                            (1986)
    Lepomis macrochirus                                              96 h        LC50       11.9                           US Environmental
                                                                                                                           Protection Agency
                                                                                                                           (1987b)
    Lepomis sp.           Juvenile         A F  High UV              96 h        LC50       11.9                           Oris & Giesy
                          (2-3 cm)              intensityb                                                                 (1985)

    Table 104. (continued)

                                                                                                                                             

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                             

    Lepomis macrochirus                    A F  Shadowb,             144 h       LC0        12.7                           Bowling et al.
                                           microcosm + sediment                                                            (1983)
                                                2 h sunb             25 h        LC50       12.7
                                                12 h sunb            72 h        LC100      12.7
    Lepomis macrochirus   1-1.5 g          N F  12 h UV,             200 h       NOEC       15             Mortality       Oris & Giesy
                                                12 h darkb                                                                 (1986)
    Lepomis sp.           Juvenile         A F  Medium UV            96 h        LC50       18.2                           Oris & Giesy
                          (2-3 cm)              intensityb                                                                 (1985)
                                                Low UV               96 h        LC50       26.5
                                                intensityb
    Lepomis macrochirus   1-1.5 g          N F  6h UV,               96 h        LC50       46                             Oris & Giesy
                                                18 h darkb                                                                 (1986)
    Pimephales promelas                    A R  (0.5 d) No           1.6d        LC50       5.4                            Oris & Giesy
                                                solvent; dark:                                                             (1987)
                                                1 d; +UV:16 hb
                                                Dark                 4 d         NOEC       5.4            Mortality
    Pimephales promelas   Adult            A F  No sun               9 weeks     LOEC       6.6            Egg production  Hall & Oris (1991)
                          F1               A R  No sun                           NOEC       6.6            Deformities
                                                No sun                           NOEC       > 12           Survival and
                                                Sunb                             LOEC       12             hatching
    Pimephales promelas   0.8g             N S  0.5 h sunb           24 h        LC50       360c           Hatching        Kagan et al. (1985)

    Fluoranthene
    Brachydanio rerio     Eggs-larvae      A F  Yellow light         41 d        NOEC       4.8            Growth          Hooftman & Evers-
                                                Solvent, TBA         41 d        NOEC       48             Mortality       de Ruiter (1992b)
    Cyprinodon variegatus Juvenile         N S                       96 h        LC0        560 000a                       Heitmuller et al.
                                                                                                                           (1981)
    Lepomis macrochirus                    N S                       96 h        LC50       3980a                          US Environmental
                                                                                                                           Protection Agency
                                                                                                                           (1978b)
    Lepomnis macrochirus  0.32-1.2 g       N S  Solvent              96 h        LC50       4000a                          Buccafusco et al.
                                                                                                                           (1981)
    Pimephales promelas   0.8 g            N S  0.5 h sunb           24 h        LC50       200                            Kagan et al. (1985)

    Table 104. (continued)

                                                                                                                                             

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                             

    Phenanthrene
    Brachydanio redo      Eggs-larvae      A R  Yellow light         28 d        NOEC       28             Growth          Hooftman & Evers-
                          (2 d)                 solvent, TBA         28 d        LOEC       49                             de Ruiter (1992d)
    Gambusia affinis                                                 24 h        LC50       150                            Neff (1979)
    Micropterus salmoides Eggs-larvae      A F                       7 d         LC50       180                            Black et al. (1983)
    Micropterus salmoides Eggs-larvae      A F  No solvent           7 d         LC50       250                            Millemann et al.
                                                                                                                           (1984)
    Oncorhynchus mykiss   Eggs-larvae      A F  No solvent           23 d        NOEC       4              Hatching        Black et al. (1983)
                                                                     27 d        NOEC       4              Survival
    Oncorhynchus mykiss   Eggs-larvae      A F  No solvent           27 d        LC50       30                             Millemann et al.
                                                                                                                           (1984)
    Oncorhynchus mykiss   Eggs-larvae      A F                       7 d         LC50       40                             Black et al. (1983)
    Oncorhynchus mykiss                    N S  Solvent,             96 h        LC50       3200c                          Edsall (1991)
                                                acetone
    Pimephales promelas                    A R  (0.5 d) No           5 d         NOEC       10             Mortality       Oris & Giesy
                                                solvent; dark:                                                             (1987)
                                                1 d; +UV:4 db
                                           Dark                      5 d         NOEC       10

    Aromatic four-ring PAH
    Benz[a]anthracene
    Pimephales promelas                    A R (0.5 d) No            3.7 d       LC50       1.8                            Oris & Giesy
                                                solvent; dark:                                                             (1987)
                                                1 d; +UV:4 db
                                           Dark                      5 d         NOEC       1.8            Mortality
    Poecilia formosa                         F  Injection            9 months    EC         23c            Thyroid         Woodhead et al.
                                                                                                           morphology      (1982)

    Benzo[k]fluoranthene
    Brachydanio rerio     Eggs-larvae      N F  Yellow light         42 d        LC50       0.68                           Hooftman & Evers-
                                                solvent, TBA         42 d        NOEC       0.23           Growth          de Ruiter (1992c)
                                                                     42 d        NOEC       0.40           Mortality

    Table 104. (continued)

                                                                                                                                             

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                             

    Poecilia formosa                         F  Injection            9 months    EC         23c            Spleen          Woodhead et al.
                                                                                                           morphology      (1982)

    Chrysene
    Brachydanio rerio     Eggs-larvae      A R  (2 d) Yellow         28 d        NOEC       > 0.9          Growth,         Hooftman & Evers-
                                                light, glass                                               mortality,      de Ruiter (1992b)
                                                column                                                     hatching

    Pyrene
    Pimephales promelas                    A R  (0.5 d) No           1.13 d      LC50       25.6                           Oris & Giesy
                                                solvent; dark:                                                             (1987)
                                                1 d; +UV:0.13 db
                                           Dark                      4 d         NOEC       25.6           Mortality
    Pimephales promelas                    N S  Solvent,             24 h        NOEC       > 10 000a      Mortality       Kagan et al.
                                                DMSO                                                                       (1987)

    Aromatic five-ring PAH
    Benzo[a]pyrene
    Brachydanio rerio     Eggs-larvae      A R (2 d) Yellow          28 d        NOEC       > 4            Growth,         Hooftman & Evers-
                                                light, glass                                               mortality,      de Ruiter (1992b)
                                                column                                                     hatching
    Fundulus grandis                         F  Injection            7 d         EC 18%     30 mg/         Liver weight    Melius et al. (1980)
                                                                                            kg bw          increase

    Hippoglossoides       Adult                 Food                 5 h         EC 21%     8 mg/kg        Hatching        Hose et al. (1981)
    elassodan                                                                                              success
    Ictalurus punctatus   Juvenile                                   7-10        EC         1.0            Skeletal        Martin (1980)
                                                                     months                                structure,
                                                                                                           pigmentation
    Leuresthes tenuis     Embryo           A S  Solvent,             14 d        NOEC       7.0c           Hatching        Winkler et al.
                                                acetone                                                    success         (1983)
                                                                     14 d        EC 12%     7.0c           Larval
                                                                                                           morphology

    Table 104. (continued)

                                                                                                                                             

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                             

    Leuresthes tenuis     Larvae                                     -           EC         100a           Growth          Puffer et al. (1979)
                                                                                 EC         100a           Development
    Micropogonias         Adult                 Oral                 30 d        NOEC       5.7            Behaviour,      Thomas (1988)
    undulatus             45-60 g                                                           mg/kg          growth,
                                                                                            (fresh wt)     respiration,
                                                                                                           locomotion
                                                                                 EC 34%     5.7            Ovarian growth,
                                                                                            mg/kg          hormone level
                                                                                            (fresh wt)
    Oryzias latipes       6-10 d           A R  0.5 mg/litre         2 × 0.25d   NOEC       47+11a,c       Neoplastic      Hawkins et al.
                                                DMF                  2 × 0.25e   NOEC       47+11a,c       lesions         (1988,1990)
                                                                     2 × 0.25f   NOEC       < 47+11a,c
    Oncorhynchus kisutch  Embryos          N S\F0.1 mmol/litre       24 hg       NOEC       11 000a        Emergence       Ostrander et al.
                          1 d after             DMSO                                                                       (1988)
                          fertilization
                          1 week before                                          NOEC       10 000a        Emergence
                          hatching
                          1 d after                                              NOEC       < 10 000a      Orientation
                          fertilization
                          1 week before                                          NOEC       < 10 000a      Orientation
                          hatching
    Oncorhynchus mykiss   Eggs             Injection                 EC          4.5 mg/    Carcino-       Black et al.
                                                                                 egg        genicity       (1988)
    Oncorhynchus mykiss   Embryo-larva     A R  Column               36 d        NOEC       2.4c           Morphology      Hannah et al.
                                                                     36 d        LOEC       6.7c           Morphology      (1982)
    Parophyrus vetulus    Eggs-larvae      A S  Solvent,             5 d         NOEC       > 2.1          Development     Hose et al.
                                                ethanol                                                                    (1982)
    Pimephales promelas                    A R  (0.5 d) No           2.7 d       LC50       5.6c                           Oris & Giesy
                                                solvent; dark:                                                             (1987)
                                                1 d; +UV:40 hb
                                           Darkb                     4 d         NOEC       5.6            Mortality

    Table 104. (continued)

                                                                                                                                             

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                             

    Poecilia reticulata   6-10 d           A S  0.5 mg/litre         2 × 0.25e   NOEC       32+8           Neoplastic      Hawkins et al.
                                                DMF; darkb           2 × 0.25f   NOEC       32+8           lesions         (1988, 1990)
    Poeciliopsis lucida                    A S  Solvent,             1 d/6       LC 70%     3750a          Lethal effects  Goddard et al.
    Poeciliopsis lucida                         acetone              months      NOEC       1250a          Lethal effects  (1987)
    Psettichtys           Embryo           A F  Solvent,             5 d         EC 50%     0.1            Hatching        Hose et al.
    melanostAicatus                             ethanol                                                    success         (1982)
                                                                     7 d         EC         0.1            Development

    Benzo[a]pyrene
    Pimephales promelas                    A R  (0.5 d) No           5 d         NOEC       2.9            Mortality       Oris & Giesy
                                                solvent; dark:                                                             (1987)
                                                1 d; +UV:4 db
                                                Dark                 5 d         NOEC       2.9            Mortality

    Dibenz[a,h]anthracene
    Pimephales promelas   Larvae           A R  (0.5 d) No           5 d         NOEC       0.15           Mortality       Oris & Giesy
                                                solvent; dark:                                                             (1987)
                                                1 d; +UV:4 db
                                           Dark                      5 d         NOEC       0.15           Mortality

    Perylene
    Pimephales promelas   Larvae           A R  (0.5 d) No           5 d         NOEC       1.7c           Mortality       Oris & Giesy
                                                solvent; dark:                                                             (1987)
                                                1 d; +UV:4 db
                                           Dark                      5 d         NOEC       1.7c           Mortality

    Aromatic six-ring PAH
    Benzo[ghi]perylene
    Brachydanio rerio     Eggs-larvae      A R (2 d) Yellow          28 d        NOEC       > 0.16         Growth,         Hooftman & Evers-
                                                light, glass                                               mortality,      de Ruiter (1992d)
                                                column                                                     hatching

    Table 104. (continued)

                                                                                                                                             

    PAH, species          Life stage       Test conditions           Duration    Effect     Concentration  End-point       Reference
                                                                                            (µg/litre)
                                                                                                                                             

    Pimephales promelas   Larvae           A R  (0.5 d) No           5 d         NOEC       0.15           Mortality       Oris & Giesy
                                                solvent; dark:                                             (1987)
                                                1 d; +UV:4 db
                                           Dark                      5d          NOEC       0.15           Mortality

    AMPHIBIANS
    Aromatic two-ring PAH
    Naphthalene
    Xenopus laevis        Larvae           F    Fluorescent          96 h        LC50       2100                           Edmisten &
                          (3 weeks)             light                6 h         EC50       1700-          Absence of      Bantle (1982)
                                                                                            2300           swimming

    Aromatic three-ring PAH
    Anthracene
    Rana pipiens          Embryo           Sunb                      24 h        LC50       110c                           Kagan et al.
                                                                                                                           (1985)
    Rana pipiens                                                     5 h         LC50       25                             US Environmental
                                                                                                                           Protection Agency
                                                                                                                           (1987b)

    Fluoranthene
    Rana pipiens                           N S  1 h sunb             24 h        LC50       90                             Kagan et al;
                                                                                                                           (1985)

    Aromatic four-ring PAH
    Pyrene
    Rana pipiens          Embryo           Sunb                      24 h        LC50       140c                           Kagan et al.
                                                                                                                           (1985)
                                                                                                                                             

    Table 104 (continued)

    A, analysed concentration; N, nominal concentration; S, static system; F, flow-through system; IF, intermittent flow; R (0.5 d),
    system with renewal (each half day); S\F, first period in a static system, second in a flow-through system; l/d, light/dark;
    UV, with UV radiation; -UV, without UV radiation; TBA, tertiary butyl alcohol; DMF, dimethylformamide; DMSO, dimethyl sulfoxide;
    LC, lethal concentration; NOEC, no-observed-effect concentration; EC, effect concentration; LOEC, lowest-observed-effect
    concentration
    a Concentration 10 times higher than solubility
    b Explicitly mentioned that organisms were tested for phototoxicity of test substance either by sunlight or artificial UV radiation
    c Concentration higher than solubility but not exceeding it by 10 times
    d Exposure followed by 168 d depuration
    e Exposure was followed by 252 d depuration
    f Exposure followed by 365 d depuration
    e Exposure followed by 62 d depuration


    Painting of benzo [a]pyrene and 3-methylcholanthrene onto the skin of
    three freshwater fish twice a week for three to six months caused
    epitheliomas in  Gasterosteus aculetus (stickleback) and  Rhodeus 
     amarus (bitterling) but not in  Cyprinus carpio (carp). In the same
    study, 10 injections of 10 mg benzo [a]pyrene in glycerol to  G. 
     aculetus produced injection-site necrosis but no tumours (Ermer,
    1970).

    The phototoxic potential of PAH in fish is influenced by the amount of
    ultraviolet radiation and light absorbed. Adult fathead minnows
     (Pimephales promelas) were exposed in the absence of artificial
    ultraviolet radiation to 0.6 or 12 µg/litre anthracene for six weeks,
    the dose being increased to 20 µg/litre for three weeks in two groups.
    Eggs were collected daily, placed in clean water, and exposed or
    unexposed to ultraviolet radiation, until 96 h after hatching. All
    fish showed impaired egg production. The lethal concentration in eggs
    was estimated to be 19 µg/g (Hall & Oris, 1991).

    Exposure of the spot  Leiostomus xanthurus to PAH-contaminated
    sediment derived from a river station resulted in death, with fin
    erosion, ulceration of the lateral body surface, and several lesions
    of internal organs. The total concentration of the 21 PAH analysed in
    the sediment was 21 000 mg/kg dry weight. The 28-day LC50 was
    estimated to be 3.2% of contaminated sediment (Roberts et al., 1989).

    9.1.2.4  Sediment-dwelling organisms

    The 10-day LC50 values for fluoranthene in sediment were 11 mg/kg dry
    weight for the marine amphipod  Eohaustorius estuarius, 5.1 mg/kg for
    the marine amphipod  Rhepoxynius abronius, and 15 mg/kg for the
    freshwater amphipod  Hyalella azteca. The sensitivity of
     E. estuarius was not influenced by salinity (DeWitt et al., 1989).

    The toxicity of a sediment containing 46% fines and 0.9% total organic
    carbon and artificially supplemented with solutions of fluoranthene,
    phenanthrene, benz [a]anthracene, benzo [a]pyrene,
    2,6-dimethylnaphthalene, 1-methylnaphthalene, and 2-methylnaphthalene
    was tested in the amphipod  Rhepoxynius abronius. Significant
    mortality occurred among amphipods exposed for 10 days to nominal
    concentrations of 15, 10, 10, 5, 0.5, 0.5, and 0.5 mg/kg dry weight of
    the seven PAH, respectively, whereas at levels five times lower no
    toxic effects were observed (Plesha et al., 1988).

    The ability of an amphipod species to metabolize xenobiotic compounds
    to reactive intermediates appears to influence its sensitivity to
    chemical contaminants. Contaminated sediments are generally more toxic
    to  R. abronius than  E. washingtonianus (Plesha et al., 1988).  R.
     abronius and  E. washingtonianus  exposed to sediment-associated,
    radiolabelled benzo [a]pyrene accumulated similar concentrations of
    radiolabel in their tissues after seven days of exposure, but the
    proportions of metabolites and the amount of radiolabel bound to
    cellular macromolecules were greater in  R. abronius than in

     E. washingtonianus. One explanation for the greater sensitivity of
     R. abronius might therefore be a greater tendency to form reactive
    metabolites that are more acutely toxic than the parent compound
    (Reichert et al., 1985).

    The toxicity of fluoranthene in sediment to the marine amphipods
     R. abronius and  Corophium spinicorne was determined by equilibrium
    partitioning. Toxicity was determined in well-sorted, fine sands
    containing organic carbon at 0.18, 0.31, or 0.48% of dry weight. The
    epibenthic tube-dwelling  C. spinicorne was less sensitive than the
    free-burrowing  R. abronius, possibly because of different routes of
    exposure. The 10-day LC50 values for  R. abronius were 3.4, 6.5, and
    10.7 mg/kg dry weight in sediments with increasing organic carbon. A
    10-day LC50 value for  C. spinicorne could be determined only in the
    sediment with the lowest organic carbon level, at 5.1 mg/kg dry
    weight. An LC50 of 24 µg/litre was calculated on the basis of
    equilibrium partitioning. In another experiment, a 10-day LC50 of 4.2
    mg/kg dry weight was determined for  R. abronius in sediment with
    0.26% organic carbon (Swartz et al., 1988).

     Diporeia sp. were exposed to a sediment artificially contaminated
    with a mixture of labelled phenanthrene and pyrene and nine unlabelled
    PAH at total concentrations of 21, 41, 120, and 330 µmol/kg dry
    sediment. The amphipods avoided the sediment containing the highest
    dose during the first six days; the estimated LC50 at day 26 was
    estimated to be 600 mmol/kg dry sediment. Deaths occurred after 26
    days' exposure to the two highest concentrations. The concentration of
    PAH required to elicit 38% mortality at day 19 was 2.9 mmol/kg
    organism. The authors concluded that PAH probably have a non-polar
    narcotic mode of action and suggested that their effect is additive,
    which is supported by the observation that exposure of  Diporeia for
    31 days to pyrene resulted in an LD50 of 5.8 mmol/kg organism
    (Landrum et al., 1991).

    9.1.2.5  Toxicity of combinations of PAH

    In the concentration addition model, additive effects were found for
    phenanthrene, anthracene, naphthalene, and acenaphthene in  Daphnia 
     magna (Muñoz & Tarazona, 1993). Although the toxic effects of
    combined PAH to  Brachydanio rerio were also found to be additive,
    the concentrations tested were close to the maximum solubility of the
    PAH (Hooftman et al., 1993).

    9.1.3  Terrestrial organisms

    9.1.3.1  Plants

    The effects of anthracene on emergence were tested in three native
    Australian plant species, heath banksia  (Banksia ericifolia), 
    she-oak  (Casuarina distyla), and yellow bloodwood  (Eucalyptus 
     eximia), and in three crop species, oat  (Avena sativa), cucumber  
    (Cucumis sativus), and soya bean  (Glycine max). A. sativa and
     C. sativus were sensitive, with EC50 values of 30 and 720 mg/kg,

    respectively; the the other plants were not sensitive up to the
    highest concentration tested (1000 mg/kg dry weight) (Mitchell et al.,
    1988).

    9.1.3.2  Invertebrates

     Porcellio scaber and  Oniscus asellus showed little difference in
    their sensitivity to benzo [a]pyrene. The growth of both species was
    affected after exposure for nine weeks to 100 and 316 mg/kg dry
    weight. The only difference in response was that the lipid pool was
    reduced in  O. asellus and the protein pool was reduced in
     P. scaber. No effects were observed at 32 mg/kg dry weight (Van
    Brummelen & Stuijfzand, 1993).

    The LC50 values for fluorene in four earthworm species,
     Allolobophora tuberculata, Eisenia foetida, Eudrilus eugenia, and
     Perionyx excavatus, in an artificial soil were 210, 17, 200, and 170
    mg/kg dry weight, respectively, after two weeks' exposure in soil. In
    the contact test, the LC50 values were 120, 170, 47, and 78 µg/m2,
    respectively (Neuhauser et al., 1986). Fluorene at 750 mg/kg dry
    weight significantly reduced the reproduction of  E. foetida, but no
    deaths occurred (Neuhauser & Callahan, 1990).

    Benzo [a]pyrene was incorporated in the food of the wood louse
     Porcellio scaber, and respiration, growth, and food consumption were
    measured for four weeks. Consumption was not affected by
    concentrations up to 125 mg/kg, but at the highest dose, male isopods
    showed significantly greater assimilation (34%) than controls (26%)
    due to an active mechanism, which was not observed in females. Growth
    varied considerably between individuals. At the highest
    concentrations, however, the growth efficiency of males was
    significantly decreased. At 25 mg/kg, no significant effects were
    found (Van Straalen & Verweij, 1991).

    The toxicity of PAH to the earthworm  E. foetida and the springtail
     Folsoma candida was studied in a standard soil. As phenanthrene at a
    concentration of 1000 mg/kg dry weight appeared to be removed almost
    completely from the soil after 14 days' exposure, the soil was renewed
    regularly. The 28-day LC50 of phenanthrene in  F. candida was 150
    mg/kg dry weight, the EC50 was 120 mg/kg, and the NOEC for
    reproduction was 75 mg/kg dry weight. The 21-day EC50 for
    reproduction of  E. foetida was 240 mg/kg dry weight. No effect on
    the survival or reproduction of  F. candida was seen after 28 days'
    exposure to chrysene, benzo [k]fluoranthene, or benzo [a]pyrene at
    180 mg/kg dry weight, and no effect on the reproduction or survival of
     E. foetida was seen after 14 days' exposure to chrysene at 1000
    mg/kg dry weight (Bowmer et al., 1993).

    Ingestion of naphthalene, anthracene, benz [a]anthracene, pyrene, or
    benzo [a]pyrene at 1000 mg/kg food per day for 18 days caused
    significant increases in mortality among  Acheta domesticus crickets.
    Naphthalene caused 50% mortality within 12 days, and anthracene,

    benz [a]anthracene, pyrene, and benzo [a]pyrene caused 39, 26, 23,
    and 32% mortality, respectively, after 18 days (Walton, 1980).

    9.1.3.3  Vertebrates

    Benzo [a]pyrene and chrysene dissolved in oil and covering less than
    10% of the surface of duck eggs reduced hatching and had teratogenic
    and embryotoxic effects (Hoffmann & Gay, 1981). The 72-h LD50 values
    for chick embryos were 14 µg/kg egg for benzo [k]fluoranthen, 39
    µg/kg for dibenz [a,h]anthracene, and 79 µg/kg for
    benz [a]anthracene (Brunström et al., 1991). The LD50 values for
    acenaphthene, anthracene, phenanthrene, and fluorene in red-winged
    blackbirds were > 100 mg/kg (Schafer et al., 1983).

    9.2  Field observations

    9.2.1  Microorganisms

    9.2.1.1  Water

    The effects on a benthic community were determined in the sediment of
    a stream in which a gradient of PAH concentrations was found, with
    total PAH contents at four sites of 0, 3100, 39 000, and 49 000 mg/kg
    dry weight. Detrital accumulation and the redox potentials increased
    with PAH level. Removal of fungi at the polluted sites was probably
    the major factor in detrital accumulation, and a reduction in
    bacterial biomass was thought to be the primary cause of the increased
    redox potentials (Catallo & Gambrell, 1987).

    Addition of 1000 mg/kg dry weight naphthalene to anaerobic salt marsh
    sediments resulted in significant inhibition of methanogenesis,
    sulfate reduction, and evolution of carbon dioxide. Phenanthrene at
    the same concentration had no significant effect on these activities,
    whereas the same dose of naphthalene inhibited methanogenesis and then
    stimulated it relative to controls; however, the sulfate reduction was
    sustained. Carbon dioxide evolution was reduced in only one of the
    three experiments (Kiene & Capone, 1984).

    9.2.1.2  Soil

    No data were available

    9.2.2  Aquatic organisms

    9.2.2.1  Plants

    No data were available

    9.2.2.2  Invertebrates

    In the study of Catallo & Gambrell (1987), described in section
    9.2.1.1, the population densities of nematodes, oligochaetes, and
    other benthic invertebrates were significantly decreased at the site
    with a total PAH content of 3100 mg/kg and were eradicated at the
    other two sites.

    Ecosystem responses were tested in small, multispecies, aquatic
    systems (Leffler microcosm) exposed once to fluorene dissolved in
    acetone at a concentration of 0.12, 0.50, 2, 5, or 10 mg/litre. The
    estimated half-life was 2.1 days. The LOEL for respiration in the dark
    (Rni) and the ratio of net productivity:Rni was 0.12 mg/litre in all
    four communities, suggesting that the responses of these microcosms
    were not completely independent of their source communities. At 5 and
    10 mg/litre, the zooplankton populations were almost eliminated (Stay
    et al., 1988).

    9.2.2.3  Vertebrates

    PAH metabolites were found in English sole  (Parophrys vetulus) with
    hepatic tumours collected from Puget Sound, Washington, USA (Malins,
    1982; Malins et al., 1984). Detectable levels of similar organic free
    radicals were found only when microsomes were incubated with the PAH
    fraction of extracts of sediment from this area and not after
    incubation with the alkane or aromatic polychlorinated biphenyl
    fractions (Collier et al., 1992).

    A consistent, statistically significant association was found between
    the prevalence of hepatic tumours in free-living  P. vetulus and the
    levels of PAH in bottom sediment from sites where the fish were
    captured, in a series of studies conducted over seven years in Puget
    Sound. The strongest relationships were found for four categories of
    hepatic lesion. Other contaminants such as trace metals,
    polychlorinated biphenyls, pesticides, and chlorinated butadienes were
    measured in all studies, but the strongest associations with liver
    lesions were found with PAH. The concentrations of total PAH in the
    sediment ranged from 0.005 mg/kg dry weight at an uncontaminated site
    to 540 mg/kg at the most polluted location (Landahl et al., 1990).

    9.2.3  Terrestrial organisms

    9.2.3.1  Plants

    No data were available.

    9.2.3.2  Invertebrates

    Application of naphthalene at 200 g/m2 to four soils resulted in a
    significant reduction in soil arthropods such as  Collembola. At 10
    g/m2, the densities of most arthropods increased (Best et al., 1978).

    9.2.3.3  Vertebrates

    No data were available.

    10. EVALUATION OF RISKS TO HUMAN HEALTH AND EFFECTS ON THE ENVIRONMENT

    10.1  Human health

    10.1.1  Exposure

    Polycyclic aromatic hydrocarbons (PAH) are released into the
    environment as a result of incomplete combustion of organic materials,
    especially during industrial processes, incineration of refuse, and
    fossil fuel combustion. They are released mainly into the atmosphere,
    adsorbed onto particulate matter, which is deposited in the aquatic
    and terrestrial environments. Direct contamination may also occur
    from, e.g. creosote-preserved wood and deposition of contaminated
    refuse such as sewage sludge and fly ash.

    Owing to their long-range transport, PAH, and particularly those with
    high molecular masses, are ubiquitous in the environment. The levels
    in ambient air vary considerably, ranging from several picograms per
    cubic metre to < 1 µg/m3, although phenanthrene has been found at
    levels of several micrograms per cubic metre.

    10.1.1.1  General population

    Humans are exposed to various complex mixtures of PAH in the air,
    food, water, and soil. The main sources of human exposure are
    emissions from the combustion of coal, diesel, petrol, kerosene, wood,
    biomass, and synthetic chemicals such as plastics. PAH account for a
    significant portion of the carcinogenicity of some mixtures, such as
    coal-tar soot, but not of others such as cigarette smoke, diesel
    emissions, and urban aerosol. The levels of selected PAH of
    toxicological significance in various environmental media are given in
    Tables 105 and 106.

    Pollution of indoor air by PAH is due mainly to tobacco smoking,
    residential heating, and PAH from outdoor ambient air (Table 107).
    Extremely high values (e.g. 15 000 ng/m3 benzo [a]pyrene) were found
    in unvented rooms with open fireplaces, especially those in which soft
    coal was used for cooking and heating. High concentrations have also
    been reported in wood-heated saunas.

    The predominant sources of PAH pollution in urban areas are motor
    vehicle traffic (both petrol- and diesel-fuelled) and residential
    heating, especially with wood, coal, and biomass. The concentrations
    are up to one order of magnitude higher in winter than in summer. Such
    differences may limit the validity of sampling campaigns performed
    during only part of the year for the purpose of estimating mean human
    exposure in urban areas.

    No conclusion can be drawn about the relative PAH emissions from
    petrol-fuelled engines (without catalytic converters) and
    diesel-fuelled engines, given the limited number of studies in which
    emissions were compared under the same conditions of sampling and
    analysis.


        Table 105. Reported levels of selected polycyclic aromatic hydrocarbons (PAH) in various media

                                                                                                                      

    Compound               Ambient air    Drinking-water   Surface water   Soil         Soil near     Sediment
                           (ng/m3)        (ng/litre)       (ng/litre)a     (µg/kg)      industrial    (µg/kg)b
                                                                                        sources
                                                                                        (mg/kg)
                                                                                                                      

    Acenaphthenec          0.06-370       0.02-14          0.08-1200       1-21         1-5100        0.04-3800
    Anthracene             0.004-61       0.5-9.7          0.01-930        0.2-70       0.2-140       0.06-27 000
    Benzo[a]pyrene         0.002-780      0.04-2.0         0.03-910        0.8-3200     0.8-38        0.004-110 000
    Chrysened              0.01-260       No data          10-1100         2.1-2700     2.1-1200      0.04-21 000
    Dibenzo[a,l]pyrene     0.05-1.5       No data          No data         No data      No data       No data
    Fluoranthene           0.03-810       0.58-3400        0.4-6400        0.3-3700     0.3-340       0.1-610 000
    Fluorene               0.02-420       0.008-21         0.33-2500       1-14         1-8600        0.5-6500
    Naphthalenec           0.03-940       0.38-8.8         0.4-2100        3-60         3-5.2         0.7-44 000
    Phenanthrene           0.002-1800     2.2-90           0.24-5700       17-1700      17-20 000     0.06-65 000
    Pyrene                 0.002-540      0.3-40           0.12-3100       0.1-4500     0.1-1600      0.1-410 000
                                                                                                                      

    Only detected values are given, owing to the variability of limits of detection; data obtained from studies of
    road tunnels were excluded even though short-term exposure to such high levels may contribute significantly to
    overall daily exposure.
    a Concentration may exceed solubility in water owing to presence of particulates in sample
    b Highest values usually determined in harbour sediments
    c Probably underestimated because of shortcomings in sampling and analytical procedures; data were not provided
      from laboratories that found high values for three- to six-ring PAH.
    d Most measurements performed with gas chromatography, so that actual levels are overestimates due to analytical
      interference by triphenylene.

    Table 106. Reported levels (µg/kg) of selected polycyclic aromatic hydrocarbons (PAH) in food

                                                                                                                                 

    Compound              Meat and          Fish and          Dairy products    Oil, fats, and    Vegetables        Cereals
                          meat products     seafooda                            margarine         and fruit
                                                                                                                                 

    Acenaphthene          No data           0.9-500           No data           0.02-0.45         No data           0.6-0.7
    Anthracene            0.9-31            0.05-240          No data           0.02-460          0.09-0.4b         0.5-1.3
    Benzo[a]pyrene        0.01-42 (130c)    0.003-290         0.08-1.3          0.02-140          0.05-6.2b         0.1-0.8
    Chrysened             0.15-0.6          0.03-210          1.3-1.5           0.1-120           0.5-69b           0.77
    Dibenzo[a,l]pyrene    No data           No data           No data           No data           No data           No data
    Fluoranthene          0.48-100          0.1-1800          0.01-4.2 (8.0e)   0.02-460          0.93-120b         0.3-28
    Fluorene              No data           0.2-370           No data           0.02-200          No data           1.3-2.7
    Naphthalenec          No data           0.8-210           No data           No data           No data           No data
    Phenanthrene          3-64              0.1-2700          0.56-0.72         0.09-1400         0.47-17b          9.9-29
    Pyrene                0.55-63           0.03-1500         0.04-2.7 (4.8e)   0.02-330          0.83-70b          0.22-21
                                                                                                                                 

    a Data from industrially polluted areas included as food items from those areas enter the market
    b Values detected in vegetables grown on contaminated soil are excluded
    c Exceptionally high values found in processed foods, but PAH not determined in these studies
    d Most measurements performed with gas chromatography, so that actual levels are overestimates due to analytical
      interference by triphenylene.
    e Found in infant food



    Table 107. Ranges of indoor concentrations of
    selected polycyclic aromatic hydrocarbons

                                                      

    Compound                  Concentration
                              (ng/m3)
                                                      

    Acenaphthene              2.5-1650
    Anthracene                1-410
    Fluoranthene              5-270
    Naphthalene               300-2300
    Pyrene                    3.6-32
    Benzo[a]pyrene            0.04-370a
    Phenanthrene              3-550
    Chrysene                  0.6-110
                                                      

    a Levels up to 14 700 ng/m3 found in Chinese
      houses with open fires


    Drinking-water generally contains low levels of individual PAH, up to
    some hundreds of nanograms per litre, depending on the compound. The
    levels of PAH in beverages, including alcoholic drinks, are usually
    < 0.01 µg/kg.

    10.1.1.2  Occupational exposure

    The concentrations in air to which workers are exposed depend on the
    type of industry. The levels in coke ovens, where the highest exposure
    may occur, are up to several hundred micrograms per cubic metre. Table
    108 shows some levels of occupational exposure.

    10.1.2  Toxic effects

    10.1.2.1  Bioavailability

    Owing to the high lipophilicity of this class of compounds, their
    bioavailability after ingestion and inhalation must be considered to
    be significant. Dermal adsorption appears to depend on the PAH being
    studied and the species evaluated: 3% of an applied dose of
    benzo [a]pyrene was absorbed by human skin and 10% by mouse skin
    within 24 h.

    10.1.2.2  Acute toxicity

    Values for the median lethal dose (LD50) indicate that PAH have
    moderate to low acute toxicity. For example, the oral LD50 of
    benzo [a]pyrene is > 1600 mg/kg in mice, and the oral LD50 of
    naphthalene is 350-700 mg/kg bw in mice but 500-9000 mg/kg bw in rats.

    Table 108. Ranges of occupational exposure to selected
    polycyclic aromatic hydrocarbons

                                                                   

    Compound          Concentration (µg/m3)
                                                                   

    Acenaphthene      0.44 in oil refining to 135 in aluminium
                      smelting
    Anthracene        0.028 in oil refining to 405 in coke ovens
    Fluoranthene      0.085 in oil refining to 191 in coke ovens
    Naphthalene       0.22 in roofing to 2900 in food smoke-houses
    Pyrene            0.11 in oil refining to 333 in coke ovens
    Benzo[a]pyrene    0.09 in chimney sweeping to 137 in coke
                      ovens
    Phenanthrene      0.085 in road paving to 1167 in coke ovens
    Chrysenea         0.085 in oil refining to 191 in coke ovens
                                                                   

    a Most measurements performed by gas chromatography, so that the
      actual levels may be overestimates due to analytical
      interference by triphenylene


    Case reports have shown that exposure to naphthalene results in
    haemolytic anaemia, and lethal doses of 2-3 g for children and 5-25 g
    for adults have been reported. There appears to be no cause for
    concern about any acute toxicity of occupational exposure or exposure
    of the general population, with the exception of accidental ingestion.

    10.1.2.3  Irritation and allergic sensitization

    Anthracene, benzo [a]pyrene, and naphthalene are primary irritants.
    Anthracene and benzo [a]pyrene were reported to be sensitizers,
    whereas phenanthrene did not induce contact sensitivity.

    10.1.2.4  Medium-term toxicity

    Oral administration resulted in no-observed-adverse-effect levels of
    175 mg/kg bw per day acanaphthene for hepatotoxicity; 125 mg/kg bw per
    day fluoranthene for nephropathy, increased relative liver weights,
    and haematological and clinical effects; 125 mg/kg bw per day fluorene
    for altered haematological parameters; and 75 mg/kg bw per day pyrene
    for nephropathy. Anthanthrene at 1000 mg/kg bw per day had no effect.

    The daily uptake of PAH by humans is estimated to be 3.7 µg,
    corresponding to about 0.05 µg/kg bw per day (70 kg bw). Human
    exposure is thus six orders of magnitude lower than the concentrations
    administered in studies in mice. There is thus no cause for concern
    about any medium-term toxic effects in humans for the PAH tested so
    far.

    10.1.2.5  Carcinogenicity

    The carcinogenicity of individual PAH and PAH-containing mixtures in
    experimental animals has been well studied. Virtually no data exist on
    the carcinogenicity of individual PAH in humans, although a limited
    database on the carcinogenicity of PAH-containing mixtures is
    available: these have been shown to increase the incidence of cancer
    in exposed human populations. The finding that a number of individual
    PAH are carcinogenic to experimental animals indicates that they are
    potentially carcinogenic to humans. PAH can produce tumours both at
    the site of contact and distantly, and the carcinogenic potency of PAH
    may vary with the route of exposure.

     (a)  Experimental models

    Benzo [a]pyrene is the best-studied PAH. It has been tested in
    multiple species and by various routes, including orally, by
    inhalation, and by skin painting for dermal carcinogenesis. It has
    been shown to be carcinogenic by all routes tested in a number of
    animal species. Those species in which no tumours were found are
    suspected to have been tested at inadequate doses or observed for an
    insufficient portion of their life span.

    Other PAH have been assayed for dermal carcinogenicity as either
    complete carcinogens or as initiators in initiation-promotion models.
    Assays used commonly include tests for lung adenomas in newborn mice
    treated by intraperitoneal, intrapulmonary, or subcutaneous injection.
    There are insufficient data to determine whether other PAH are
    carcinogenic.

     (b)  Epidemiology

    Numerous epidemiological studies have been reported of groups of
    workers exposed to environments that contain mixtures of PAH, all of
    which also contained chemicals other than PAH. Cases of respiratory
    diseases such as pneumoconiosis, respiratory tuberculosis, pneumonia,
    and bronchitis and diseases of the circulatory system were reported in
    these studies, but these effects are not considered to be specific to
    PAH because of simultaneous exposure to agents that cause similar
    effects. Thus, exposure in iron and steel foundries entails exposure
    not only to PAH but also to other potentially carcinogenic materials
    such as nickel, chromium, silica, soot, asbestos, and benzene. The
    working environment of aluminium smelters is unlikely to include
    nickel or chromium but includes alumina, aluminium fluoride, and
    aromatic amines. If each of these materials occurred in a separate
    location in a factory, classical epidemiological techniques would have
    little difficulty in identifying the agent responsible for a
    statistically significant cancer excess. This is not the situation,
    and, while epidemiological studies have produced convincing evidence
    that cancers occur in workers exposed to PAH, the attribution of
    exposure to PAH as the cause of these excesses can only be based on
    information from animal models.

    Studies of workers exposed to mixtures of PAH indicate that the lung
    is the target organ after inhalation. Confounding by cigarette smoking
    cannot explain the effects observed. Studies of workers at gas and
    coke ovens, at aluminium smelters, in iron and steel foundries, and
    with bitumen and asphalt consistently show excess risks for lung
    cancer. Coke-oven workers are probably exposed to the highest
    concentrations, and studies of these populations have provided
    evidence of dose-response effects. In a comparison of the mortality of
    5321 coke-oven workers with that of 10 497 steel workers at the same
    plants, a monotonic positive trend was shown in the relationship
    between the risk for lung cancer and the estimated level of cumulative
    exposure to coal-tar pitch volatiles, the benzene-soluble fraction of
    particulate matter. With a risk of unity for the unexposed group, the
    risk increased from 1.2 for those with exposure of 1-49 mg/m3 ×
    months to 3.1 for the group with the heaviest exposure of > 650
    mg/m3 × months. Analysis of the relative risks and the numbers of
    deaths from lung cancer on which they were based resulted in the
    conclusion that 124 deaths occurred among these coke-oven workers over
    a period of 30 years that can be attributed to exposure to coal-tar
    pitch volatiles, i.e. 2.3% of the cohort. Earlier findings from this
    study were used by others to estimate a unit risk coefficient of 8.7 ×
    10-2 for exposure to benzo [a]pyrene, i.e. the absolute lifetime
    risk of lung cancer from a working lifetime exposure to 1 µg/m3 of
    benzo [a]pyrene. Given the large number of cancers that occurred in
    this cohort, this risk coefficient is probably the best estimate
    currently available. It should be recognized, however, that the
    reports on which this estimate is based gave relatively little
    information on exposure levels, no data on time trends in the level of
    exposure, and no data on benzo [a]pyrene levels in the participating
    plants.

    There is also good evidence that urinary bladder cancer has occurred
    in cohorts of aluminium smelters and gas and coke workers, although
    the overall findings are not as consistent as those for lung cancer.
    In a study of aluminium smelters, a positive trend was observed
    between the risk for urinary bladder cancer and the estimated level of
    cumulative exposure to benzene-soluble matter. PAH cannot be assumed
    to be responsible for this trend, however, because the known bladder
    carcinogen 2-naphthylamine and other aromatic amino and nitro
    compounds were present in the working environment. Similarly, the
    excess of urinary bladder cancer in gas workers is more likely to be a
    consequence of exposure to 2- and 1-naphthylamines.

    PAH are almost certainly one of the carcinogenic agents responsible
    for lung cancers in cigarette smokers, although the role of PAH in the
    many other diseases caused by cigarette smoking, including
    nonmalignant diseases of the respiratory system, is unknown. Studies
    on the rates of mortality from lung cancer in relation to indoor
    burning of coal or wood in open fires for cooking and heating add to
    the body of evidence that links PAH and the risk for lung cancer.
    Workers exposed to diesel or petrol fumes had relatively low exposure
    to PAH, and studies of these exposure are not likely to assist in
    quantification of the risks for cancer associated with exposure to
    PAH.

    Quantitative risk assessments were not made for PAH, either
    individually or as mixtures; however, Appendix I gives some
    comparative features of three approaches to quantitative risk
    assessment that have been used and which have been at least partly
    validated.

    10.1.2.6  Reproductive toxicity

     (a)  Developmental studies

    There are no studies in humans. Embryotoxic effects have been
    described in experimental animals exposed to PAH such as
    benz [a]anthracene, benzo [a]pyrene, and naphthalene. In mice
    treated intraperitoneally with benzo [a]pyrene, increased numbers of
    stillborn and resorbed fetuses, decreased fetal weight, and increased
    incidences of congenital anomalies were seen at a minimum dose of 50
    mg/kg bw per day. In mice given benzo [a]pyrene in the diet,
    malformations were found after administration of 120 mg/kg bw per day
    on days 2-10 of gestation. In another study in mice fed the compound
    during most of the period of gestation, no treatment-related
    embryotoxic effects were found after doses up to 133 mg/kg bw per day.

    In mice, 1 mg benzo [a]pyrene per gram of food would result in
    consumption of 5 g/day. In humans, the total median intake from food,
    air, water, and soil for a 70-kg person would be 0.05 µg/kg bw per
    day. In view of the inter- and intraspecies differences, there is at
    present no reason for concern about effects on development.

     (b)  Fertility

    There are no studies in humans. In mice fed diets containing
    benzo [a]pyrene at doses up to 133 mg/kg bw per day, no
    treatment-related effects on fertility were seen, again indicating no
    concern about effects of PAH on fertility in humans.

    10.1.2.7  Immunotoxicity

    At least one immunotoxic PAH will probably be present in any mixture
    of PAH. Thus, when such mixtures are evaluated for their potential
    effects on human health, the immune system should be considered a
    primary target organ. Benzo [a]pyrene caused immunosuppression in
    mice after dermal application for 28 days at doses as low as 625 µg/kg
    bw. In a study in which the immune status of coke-oven workers was
    evaluated, suppressed immune status was found, as indicated by
    decreased serum antibody levels and functional impairment.

    The mechanisms of immunosuppressive action that have been proposed
    include formation of active metabolites (including diol epoxides),
    alterations in cytokine levels, disruption of membrane fluidity,
    interaction with the Ah receptor, and alterations in calcium ion flux.

    10.1.2.8  Genotoxicity

    PAH have repeatedly been shown to have genotoxic effects both in
     in vivo in rodents and  in vitro in mammalian (including human)
    cell lines and prokaryotes. Some PAH, however, appear not to be
    genotoxic. Most of the unsubstituted PAH categorized as genotoxic are
    not genotoxic  per se but require metabolism to intermediates which
    react with DNA to form DNA adducts and induce genotoxic damage.
    Genotoxic events are postulated to be a required step in the
    carcinogenic process.

    10.2  Environment

    10.2.1  Environmental levels and fate

    Concentrations of up to 100 µg/kg of individual PAH have been detected
    in soil, although higher concentrations of pyrene, phenanthrene,
    chrysene, and benzo [a]pyrene have been found. The concentrations in
    soil near industrial sources of PAH are up to three orders of
    magnitude higher.

    Concentrations of up to 6 µg/litre have been reported for individual
    PAH in surface water, including polluted rivers. High concentrations
    have also been reported in sediment, which acts as a sink for PAH. The
    concentrations in sediment from rivers, lakes, and seas are generally
    < 30 mg/kg dry weight. Concentrations up to 655 mg/kg dry weight have
    been reported in sediment from harbours. The individual PAH compounds
    detected in environmental samples vary according to their source and
    any degradative processes. Phenanthrene is the PAH found in highest
    concentrations in aquatic samples. Those that occur at the highest
    concentrations in sediment include phenanthrene, fluoranthene, pyrene,
    benz [a]anthracene, benzo [b]fluoranthene, benzo [k]fluo-ranthene,
    and indeno[1,2,3- cd]pyrene.

    PAH are sparingly soluble in water and therefore have affinity for
    sediment, soil, and biota. They may be removed from the environment by
    biodegradation or photodegradation. The rates of degradation vary and
    generally decrease with increasing numbers of aromatic rings. PAH are
    inherently biodegradable, and low-molecular-mass compounds can be
    completely degraded by acclimated microorganisms. In surface waters
    with low numbers of unacclimated microorganisms, PAH can persist for
    longer periods of time.

    10.2.2  Ecotoxic effects

    10.2.2.1  Terrestrial organisms

    Few data are available on the effects of PAH on terrestrial organisms,
    and none are available on plants, wild mammals, or birds. The values
    for the concentration causing 50% lethality (LC50) reported for
    earthworm species are 150 mg/kg dry weight for phenanthrene and
    170-210 mg/kg for fluorene. The no-observed-effect level for the
    survival and reproduction of earthworm species was 180 mg/kg dry soil

    for chrysene, benzo [k]fluoranthene, and benzo [a]pyrene. PAH in
    soil are unlikely to exert toxic effects on terrestrial invertebrates,
    except when the soil is highly contaminated.

    10.2.2.2  Aquatic organisms

    The toxicity of naphthalene, phenanthrene, and fluoranthene on aquatic
    organisms has been well studied in the laboratory, but that of other
    PAH has not. The toxicity of PAH to aquatic organisms is affected by
    metabolism and photo-oxidation, and they are generally more toxic in
    the presence of ultraviolet light. Naphthalene is the least toxic to
    invertebrates, with 48-h LC50 values of 700-23 000 µg/litre. The LC50
    values for three-ring PAH range from < 1 to 3000 µg/litre, anthracene
    being more toxic than the others, with 24-h LC50 values of < 1 to
    260 µg/litre. Four-, five-, and six-ring PAH have 48-h LC50 values of
    0.2-1800 µg/litre, their toxicity increasing with molecular mass. The
    96-h values for acute toxicity in fish were 110 to > 10 000 µg/litre
    for naphthalene, 30-4000 µg/litre for three-ring PAH (those for
    anthracene being 2.8-360 µg/litre), and 0.7-26 µg/litre for four- and
    five-ring PAH.

    The no-observed-effect and lowest-observed-effect levels for
    invertebrates were 300-1000 µg/litre for naphthalene, 2-600 µg/litre
    for three-ring PAH, 5-290 µg/litre for four-ring PAH, and 0.1-50
    µg/litre for five-ring PAH. The long-term treatment doses resulting in
    toxicity in fish were 15-1600 µg/litre for naphthalene, 1.2-510
    µg/litre for three-ring PAH, 0.9-26 µg/litre for four-ring PAH, and
    0.15-7 µg/litre for five-ring PAH. Higher no-observed-effect
    concentrations have been reported, but in studies in which the PAH
    were present at more than than 10 times their maximum aqueous
    solubility; these have therefore been ignored. As the concentrations
    of PAH reported in surface water are usually in the range of nanograms
    per litre, they are unlikely to exert adverse effects on aquatic
    organisms, except in cases of heavy exposure, as with creosote.

    The LC50 values reported for sediment-dwelling organisms were 3.4-15
    mg/kg dry sediment for fluoranthene, 10 mg/kg for phenanthrene, 10
    mg/kg for benz [a]anthracene, and 5 mg/kg for benzo [a]pyrene. Since
    sediment acts as a sink for PAH, sediment-dwelling organisms may be
    adversely affected.

    PAH may induce neoplastic effects in aquatic organisms. Tumour
    development has been reported in fish exposed to benzo [a]pyrene and
    3-methyl-cholanthrene after oral, dermal, or intraperitoneal
    administration. Hepatic tumours have been found in wild fish living in
    water with sediment containing PAH at a concentration of 250 mg/kg.
    Although the levels of PAH in sediment are generally an order of
    magnitude lower than this value, the possibility that tumours might be
    formed at lower concentrations cannot be excluded. The ecological
    significance of the carcinogenic effects of PAH in fish has not been
    assessed.

    11.  RECOMMENDATIONS FOR THE PROTECTION OF HUMAN HEALTH AND THE ENVIRONMENT

    11.1  General recommendations

    *    International agreement on analytical procedures and
         interlaboratory quality control studies is strongly recommended.
         Sampling strategies and analytical procedures should be optimized
         and standardized before surveys of exposure to polycyclic
         aromatic hydrocarbons (PAH) are undertaken.

    *    Emissions and effluents of PAH from both point and diffuse
         sources should be monitored and inventories compiled.

    *    Concentrations of individual PAH should be given rather than
         'total PAH'. When PAH are designated as 'not detected', the
         relevant limits of detection should be given.

    *    PAH emissions and effluents should be reduced by:

         -    filtration and scrubbing of industrial emissions,

         -    treatment of effluents, and

         -    use of catalytic converters and particle traps on motor
              vehicles.

    11.2  Protection of human health

    *    Owing to their proven immunotoxic effects, coal-tar shampoos
         should be used for anti-dandruff therapy only if no other
         treatment is available.

    *    In view of the proven immunotoxic and carcinogenic effects of PAH
         in coke-oven workers, exposure to PAH in occupational settings
         should be eliminated or minimized by reducing emissions to the
         extent possible or, when they cannot be sufficiently reduced, by
         providing effective personal protection.

    *    Public education about the sources and health effects of exposure
         to PAH should be improved.

    *    Use of unvented indoor fires, as in many developing countries,
         should be discouraged, and they should be replaced by more
         efficient, well-vented combustion devices.œ

    *    The risk of exposure to PAH from passive smoking should be
         stressed and measures taken to avoid it.

    *    Urban air pollution should be monitored all year round and not
         only seasonally.

    11.3  Recommendations for further research

    11.3.1  General

         -    Investigate the suitability of benzo [a]pyrene as an
              indicator of the effects of PAH on human health and the
              environment and examine the use of other PAH as surrogates.

    11.3.2  Protection of human health

         -    More data should be collected on the human body burden of
              PAH and on biomarkers for these compounds.

         -    The reproductive effects of PAH should be studied further.

         -    More studies on dermal absorption are required.

         -    The contribution of the high-molecular-mass PAH to the
              overall carcinogenic potential of PAH should be studied.

    11.3.3  Environmental protection

         -    The toxic effects of PAH to plants and earthworms should be
              studied.

         -    The body burdens and possible toxic effects of PAH in wild
              mammals and birds should be investigated, as most of these
              species can metabolize PAH.

         -    The extent to which higher-molecular-mass PAH are absorbed
              by sediments and serve as a sink and the effects of
              disturbing sediment, e.g. by dredging, on aquatic organisms
              should be investigated.

         -    The environmental significance of the tumours that have been
              found in fish exposed to PAH must be addressed.

         -    Reliable data should be collected on environmentally
              relevant PAH like dibenzo [a,l]pyrene, particularly with
              regard to noncarcinogenic end-points such as effects on the
              immune system.

    11.3.4  Risk assessment

         -    Quantitative estimates of the risks presented by PAH should
              be compared using various approaches and exposure scenarios,
              both for human health and ecological protection.

         -    The risk estimates obtained by the various approaches to
              risk assessment based on data on human exposure should be
              compared.

         -    Risk assessment procedures that allow integrated assessment
              of the risks due to inhalation and to oral and dermal
              exposure should be developed and validated.

         -    Comparative risk assessment methods for evaluating
              immunotoxicity and other noncancer risks associated with
              exposure to PAH should be improved.

         -    The use of the results of alternative tests, such as those
              for genotoxicity and other short-term effects, in assessing
              risks due to PAH should be evaluated.

         -    Human exposure to alkylated PAH in a variety of situations
              should be investigated further and data acquired on the
              mutagenicity and experimental carcinogenicity of these
              compounds.

    12. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

    12.1  International Agency for Research on Cancer

    Polycyclic aromatic hydrocarbons (PAH) have been evaluated by a number
    of working groups convened by IARC. The evaluations made between 1973
    and 1983 and summarized in Supplement 7 to the  IARC Monographs
    (IARC, 1987) are shown in Table 109.

    12.2  WHO Water Quality Guidelines

    PAH have been assessed in the  WHO Guidelines for Drinking-water 
     Quality (WHO, 1984, 1996). A quantitative risk assessment was
    conducted using the two-stage birth-death mutation model. The
    resulting guidelines for benzo [a]pyrene in drinking-water
    corresponding to excess lifetime risks for gastric cancer of 10-4,
    10-5, and 10-6 are 7, 0.7, and 0.07 µg/litre.

    The data are insufficient to derive guidelines for other PAH, but the
    following recommendations are made for the group:

    *    Because of the close association between PAH and suspended
         solids, treatment to achieve the recommended level of turbidity,
         when necessary, will ensure that the PAH levels are reduced to a
         minimum.

    *    Water should not be contaminated with PAH during water treatment
         or distribution. The use of coal-tar-based and similar materials
         for pipe linings and coatings on storage tanks should therefore
         be discontinued. It is recognized that it may be impracticable to
         remove coal-tar linings from existing pipes, and research is
         needed on methods of minimizing the leaching of PAH from such
         materials.

    *    In monitoring levels of PAH, the use of specific compounds as
         indicators for the group as a whole is recommended. The choice of
         indicator compound will vary in each situation. PAH should be
         monitored regularly in order to determine background levels,
         against which any changes can be assessed and remedial action
         taken, if necessary.

    *    When drinking-water is known to have been contaminated by PAH,
         the specific compounds present and the source of the
         contamination should be identified, as the carcinogenic potential
         of PAH varies.

    12.3  FAO/WHO Joint Expert Committee on Food Additives

    Benzo [a]pyrene was assessed at a meeting of this Committee in June
    1990 (WHO, 1991). The Committee concluded that, for the purpose of
    evaluation, the most significant toxicological effect of
    benzo [a]pyrene is its carcinogenicity. It was recognized that

    benzo [a]pyrene is only one member of a class of more than 100
    compounds and that they should be considered as a class.

    The Committee was unable to establish a tolerable intake for
    benzo [a]pyrene on the basis of the available data. Nevertheless, the
    large difference between the estimated human intake of
    benzo [a]pyrene and the doses that induce tumours in animals suggests
    that any effects on human health are likely to be small. Despite this,
    the considerable uncertainties in risk estimation require that efforts
    be made to minimize human exposure to benzo [a]pyrene as far as is
    practicable.

    The Committee acknowledged the complexity of reducing exposure to
    benzo [a]pyrene and other PAH. Furthermore, it noted that exposure to
    benzo [a]pyrene constitutes only a fraction of consumers' exposure to
    these compounds and that some other members of this class, not
    evaluated at the meeting, have toxicological properties similar to
    those of benzo [a]pyrene and may thus contribute to the overall
    carcinogenic risk. In this regard, strategies to minimize exposure to
    benzo [a]pyrene would also be effective in reducing overall exposure
    to PAH. These include practices that consumers can effect, such as
    washing fruits and vegetables thoroughly to remove any surface
    contamination, trimming excess fat prior to barbecuing meats to
    minimize 'flare-ups', and cooking in a fashion that prevents contact
    of food with flames. Measures that can be taken by the food industry
    include use of indirect heating for drying foods, switching to
    non-coal-fired roasters (e.g. for roasting coffee beans), using
    protective coverings (e.g. cellulose casing) when smoking foods
    conventionally, and ensuring compliance with the limits for PAH in
    food additives specified by national and international bodies. The
    Committee urged application of these measures in order to minimize
    contamination of food with PAH, including benzo [a]pyrene.

    12.4  WHO Regional Office for Europe Air Quality Guidelines

    PAH have been assessed as atmospheric pollutants by the WHO Regional
    Office for Europe (WHO, 1987). No guideline was set, but the group
    concluded that no safe level of PAH could be recommended, owing to
    their carcinogenicity. There is no known threshold for the induction
    of cancer by benzo [a]pyrene, the most thoroughly studied PAH, nor is
    there an ambient mixture of PAH that does not contain benzo [a]pyrene
    and other substances for which there is sufficient evidence of
    carcinogenicity in animals.

    A number of estimates have been made of the risk presented by PAH,
    based primarily on studies in which benzo [a]pyrene was used as the
    index compound. The US Environmental Protection Agency (1984d)
    proposed an upper-bound lifetime cancer risk of 62 per 100 000 exposed
    people per microgram of benzene-soluble coke-oven emission per cubic
    metre of ambient air. Assuming a 0.71% content of benzo [a]pyrene in
    these emissions, it can be estimated that nine out of 100 000 people
    exposed to 1 ng/m3 benzo [a]pyrene over a lifetime would be at risk
    of developing cancer.

        Table 109. Degree of evidence for carcinogenicity in humans and in experimental animals
    and overall evaluations of carcinogenicity to humans for agents evaluated in IARC
    Monographs

                                                                                        

    Compound                  Degree of evidence     Overall       IARC Monographs
                              for carcinogenicity    evaluationa   volume (year)
                                                 
                              Human      Animal
                                                                                        

    Anthanthrene              ND         L           3             32(1983)
    Anthracene                ND         I           3             32(1983)
    Benz[a]anthracene         ND         S           2A            3 (1973); 32 (1983)
    Benzo[b]fluoranthene      ND         S           2B            3 (1973); 32 (1983)
    Benzo[j]fluoranthene      ND         S           2B            3 (1973); 32 (1983)
    Benzo[k]fluoranthene      ND         S           2B            32(1983)
    Benzo[ghi]fluoranthene    ND         I           3             32(1983)
    Benzo[a]fluorene          ND         I           3             32(1983)
    Benzo[b]fluorene          ND         I           3             32(1983)
    Benzo[ghi]perylene        ND         I           3             32(1983)
    Benzo[c]phenanthrene      ND         I           3             32(1983)
    Benzo[a]pyrene            ND         S           2A            3 (1973); 32 (1983)
    Benzo[e]pyrene            ND         I           3             3 (1973); 32 (1983)
    Chrysene                  ND         L           3             3 (1973); 32 (1983)
    Coronene                  ND         I           3             32(1983)
    Cyclopenta[cd]pyrene      ND         L           3             32(1983)
    Dibenz[a,h]anthracene     ND         S           2A            3 (1973); 32 (1983)
    Dibenzo[a,e]pyrene        ND         S           2B            3 (1973); 32 (1983)
    Dibenzo[a,h]pyrene        ND         S           2B            3 (1973); 32 (1983)
    Dibenzo[a,i]pyrene        ND         S           2B            3 (1973); 32 (1983)
    Dibenzo[a,l]pyrene        ND         S           2B            3 (1973); 32 (1983)
    Fluoranthene              ND         I           3             32(1983)
    Fluorene                  ND         I           3             32(1983)
    Indeno[1,2,3-cd]pyrene    ND         S           2B            3 (1973); 32 (1983)
    5-Methylchrysene          ND         S           2B            32(1983)
    1-Methylphenanthrene      ND         I           3             32(1983)
    Perylene                  ND         I           3             32(1983)
    Phenanthrene              ND         I           3             32(1983)
    Pyrene                    ND         I           3             32(1983)
    Triphenylene              ND         I           3             32(1983)
                                                                                        

    Adapted from IARC (1987)
    ND, no adequate data; I, inadequate evidence; L, limited evidence; S, sufficient
    evidence
    a Group 1, the compound is carcinogenic to human; Group 2A, the compound is
      probably carcinogenic to humans; Group 2B, the compound is possibly carcinogenic
      to humans; Group 3, the compound is not classifiable as to its carcinogenicity
      to humans

    APPENDIX I

    SOME APPROACHES TO RISK ASSESSMENT FOR POLYCYCLIC AROMATIC
    HYDROCARBONS

    I.1  Introduction

    Various environmental and technical problems hinder assessment of the
    risk posed by mixtures containing polycyclic aromatic hydrocarbons
    (PAH), particularly for carcinogenicity. Ambient environments contain
    a wide range of PAH, some of which are highly carcinogenic, while
    others are probably not (Table AI.1). Both anthropogenic and natural
    sources may contribute to the ambient levels of these compounds, such
    as in the air over industrial towns (see Section 3).

    As PAH undergo transformation in the environment (see Section 4), it
    cannot be taken for granted that the composition of ambient mixtures
    is similar to that of the source. No data are available to assess the
    potency of individual PAH in humans, but the carcinogenicity of
    several mixtures containing PAH has been estimated in epidemiological
    studies (Albert et al., 1983). Mixtures of a similar type, such as
    from coke ovens, may not always present the same risk, however, even
    when the fuel used and the operating conditions are similar.
    Furthermore, PAH are often not the only contributors to the
    carcinogenic risk presented by a given mixture: other chemicals and
    particulate matter (Heinrich, 1995) may also contribute. The basis for
    quantification and the way in which the quantity of a mixture is
    expressed are also important. Should the levels be expressed in terms
    of the total mass of extractable material or as a surrogate? If the
    concentration of a chosen surrogate is used as an indicator of the
    quantity of the mixture and its toxicity, the surrogate selected must
    be predictive of the toxicity of the mixture.

    Estimating the risk conferred by exposure to PAH has further problems.
    As humans are exposed to mixtures of PAH and other compounds and not
    to pure PAH, experimental data must be used to estimate the risk for
    exposure to individual PAH and the result extrapolated to the low
    doses to which humans are exposed. Such extrapolation is problematic,
    because species may differ in the enzymes that activate PAH (Michel et
    al., 1995) and in their susceptibility to the tumorigenic effects of
    PAH; these differences may otherwise be a simple reflection of
    differences in weight, surface area, basal metabolic rate, or
    respiratory volume. The degree to which species differences affect
    extrapolated human risks is unknown.

    Another set of problems stems from the large number of PAH that are
    typically found in a complex mixture. Only a small percentage of the
    environmentally relevant PAH has been investigated for carcinogenicity
    in experimental animals, and the toxicity of most of the PAH in
    complex mixtures remains unknown. About a dozen PAH of known toxicity
    are monitored in most programmes, and these contribute only a small
    proportion of the risk represented by PAH fractions extracted from
    complex mixtures (Thorslund & Farrar, 1990a). It is therefore likely

    Table AI.1. Evaluations of the carcinogenicity of some polycyclic
    aromatic hydrocarbons
                                                                          

    Compound                  IARC      US Environmental    Task Groupb
                              (1987)a   Protection Agency
                                        (1993)a
                                                                          
    Acenaphthene                        D                   Questionable
    Acenaphthylene                      Dc
    Anthanthrene                                            Positive
    Anthracene                3         Dc                  Negative
    Benz[a]anthracene         2A        B2c                 Positive
    Benzo[b]fluoranthene      2B        B2c                 Positive
    Benzo[j]fluoranthene      2B        B2                  Positive
    Benzo[ghi]fluoranthene                                  (Negative)
    Benzo[k]fluoranthene      2B        B2c                 Positive
    Benzo[a]fluorene                                        Questionable
    Benzo[b]fluorene                                        Questionable
    Benzo[ghi]perylene        3         Dc                  Negative
    Benzo[c]phenanthrene                                    (Positive)
    Benzo[a]pyrene            2A        B2c                 Positive
    Benzo[e]pyrene            3         C                   Questionable
    Chrysene                  3         B2c                 Positive
    Coronene                                                Questionable
    Cyclopenta[cd]pyrene                B2                  Positive
    Dibenz[a,h]anthracene               B2c                 Positive
    Dibenzo[a,e]pyrene                  B2                  Positive
    Dibenzo[a,h]pyrene                  B2                  Positive
    Dibenzo[a,i]pyrene                  B2                  Positive
    Dibenzo[a,l]pyrene                  B2                  Positive
    Dibenzo[e,l]pyrene                  D
    Dibenzo[a,e]fluoranthene            B2
    Dibenzo[a,h]fluoranthene            B2
    Dibenzo[a,i]fluoranthene            B2
    Dibenzo[a,l]fluoranthene            B2
    Fluoranthene              3         Dc                  (Positive)
    Fluorene                  3         Dc                  Negative
    Indeno[1,2,3-cd]pyrene              B2c                 Positive
    5-Methylchrysene                                        Positive
    1-Methophenanthrene                                     (Negative)
    Naphthalene                         Dc/C                Questionable
    Perylene                                                (Negative)
    Phenanthrene              3         Dc                  Questionable
    Pyrene                              Dc                  Questionable
    Triphenylene                                            (Negative)
                                                                          

    a Based on the results of studies in humans and experimental animals
    b Based on the results of studies in experimental animals
    c Consensus position of the US Environmental Protection Agency;
      others have been presented at scientific meetings (Schoeny et al.,
      1994; McClure & Schoeny, 1995).

    that summing the risks posed by individual PAH of known toxicity does
    not accurately reflect the contribution of all the PAH in a mixture.

    I.2  Approaches to risk assessment

    Three of the most popular approaches for assessing dose-response
    relationships for PAH are presented, with their strengths and
    weaknesses. These approaches are toxicity equivalence factors,
    comparative potency, and use of benzo [a]pyrene as a surrogate.

    I.2.1  Toxicity equivalence factors and related approaches

    Several approaches to quantification may be considered for assessing
    the risks posed by mixtures of agents. When there are sufficient data,
    they can be used as a basis for quantitative estimates of risk.
    Relatively few mixtures containing PAH have been tested under
    conditions that are acceptable for risk assessment. For some
    processes, e.g. coal coking, the data on human exposure are
    sufficiently complete to allow quantitative estimates of risk;
    however, changes in the parameters of the combustion process, such as
    temperature and amount of oxygen feedstock, may result in variations
    in the types, amounts, and physical status of PAH in the mixture.
    These variations may be sufficient to alter the risk posed by the
    mixture. One way of resolving the uncertainty inherent in differences
    in the composition of mixtures is to base quantitative estimates on
    considerations of individual components; this alternative is explored
    below.

    I.2.1.1  Principle

    The approaches are based on an assumption of additive risk, which
    leads, in principle, to an estimate of the risk associated with
    identified PAH. In practice, the risks attributable to individual PAH
    are summed, or the risk posed by individual PAH is expressed relative
    to that for benzo [a]pyrene, and then the levels of these equivalents
    are summed. The latter process is the toxicity equivalence factor
    approach.

    The first step is to estimate the potency of a single PAH, which
    serves as a standard against which the potency of other compounds is
    later derived. In practice, this compound is usually benzo [a]pyrene.
    Since no data from studies in humans are available that are suitable
    for assessing the potency of individual PAH, the potency of
    benzo [a]pyrene in humans is estimated from the results of studies in
    animal models. The uncertainty associated with this extrapolation is
    discussed above.

    The second step is to estimate the potency of the PAH relative to that
    of benzo [a]pyrene, in order to obtain a benzo [a]pyrene equivalent.
    The estimate is based on the relative potencies of benzo [a]pyrene
    and other PAH in experimental animals. The key assumption is that the
    relative potency of two PAH in an animal model is the same or similar
    to that of the same compounds in humans. This comparative potency

    approach has been used in relation to chlorinated
    dibenzo- para-dioxins and dibenzofurans (US Environmental Protection
    Agency, 1987) and for PAH and PAH-rich mixtures (Albert et al., 1983;
    Clement Associates, 1988). Further evidence supports the assumption
    made in this approach (Albert et al., 1983; Lewtas, 1985a,b; Nesnow,
    1990).

    The third step involves summation of risks, which can be done either
    by summing the benzo [a]pyrene equivalents and multiplying by the
    potency of benzo [a]pyrene or by estimating the potency of each PAH
    in humans (risk for cancer) and then adding them. The underlying
    assumption is that the individual estimates of risk are additive.
    Although there may be interactions between PAH, the risks appear to be
    approximately additive, especially at low, environmentally relevant
    doses (Krewski et al., 1989; Nesnow et al., 1995). In the absence of
    information to the contrary, additivity is assumed.

    The toxicity equivalence factor approach is feasible if at least two
    pieces of information are available:

    -    the amount of each PAH in the mixture, or the amount of each
         'major bioactive PAH', and

    -    a quantitative estimate of the risk associated with each
         identified PAH.

    For the first requirement, good data on the composition of mixtures of
    PAH can be generated with existing analytical techniques (see Section
    2), although such analyses can be resource-intensive. Quantitative
    risk estimates for individual PAH are generally not available, as the
    data are insufficient. The deficiencies include the following:

    -    the data relate to exposures that are not typically used in
         deriving quantitative estimates of risk after oral or inhalation
         exposure,

    -    the study populations were inappropriately small,

    -    the studies involved only one dose,

    -    dose-response relationships were not reported, and/or

    -    different PAH were tested in different studies with different
         designs.

    Environmental mixtures contain many more PAH than can be monitored
    feasibly or practically. Furthermore, the toxicity of most
    environmentally relevant PAH has not yet been quantified. As the
    toxicity equivalence factor approach assumes additivity of the risks
    posed by PAH in a mixture, the question remains of the extent to which
    the risk of one PAH is representative of the risk of all of those in
    the mixture.

    I.2.1.2  Development and validation

    I.2.1.2.1  Derivation of the potency of benzo [a]pyrene

    Quantitative risk estimation is problematic for even the best-studied
    PAH, namely benzo [a]pyrene. The risk for carcinogenicity is best
    estimated on the basis of data from long-term, usually lifetime,
    assays in which several doses are tested in large groups of animals.
    The data on benzo [a]pyrene are less than optimal: few lifetime
    assays have been conducted with exposure other than dermal and
    generally few doses were tested.

    Krewski et al. (1989) calculated the probability of occurrence of a
    tumour at a specified time after continuous exposure to a mixture of
    PAH. The dose of the PAH mixture was described as a benzo [a]pyrene
    equivalent dose  d as follows:

                          d  = S  Ridi +  do                     (1)

    where  Ri is the relative carcinogenicity of the  ith PAH in
    comparison with that of benzo [a]pyrene,  di is the dose of the
     ith PAH, and  do is the dose of benzo [a]pyrene.

    The tumour probability,  P(d), was calculated from a two-stage birth-
    death mutation model. For the mixture as a whole,  P(d) is given by
    the equation:

                         P (d) = 1-exp (- A( 1 +  bd)2)           (2)

    where the unknown values  A and  b were estimated from bioassays
    with benzo [a]pyrene as  A = 0.00616 and  b = 3.52 µg-1 for
    lifetime exposure.

    The US Environmental Protection Agency (1993) made a quantitative risk
    estimate for oral exposure to benzo [a]pyrene that consisted of a
    range of values, from 4.5 to 11.7 per (mg/kg)/day, with a geometric
    mean of   7.3 per (mg/kg)/day. These estimates were obtained by using
    three methods of determining an upper bound on a linear low-dose term
    from data on the incidence of gastrointestinal tumours in mice exposed
    to benzo [a]pyrene in the diet (Neal & Rigdon, 1967). The models used
    were a form of the two-stage Moolgavkar, Venzon, and Knudson model
    (Moolgavkar & Venzon, 1979; Moolgavkar & Knudson, 1981) and a
    Weibull-type model (Rees & Hattis, 1994). The total numbers of tumours
    in male and female rats exposed in the diet (Brune et al., 1981) were
    used in a linearized multistage procedure to derive an upper bound on
    the low-dose term (slope factor), shown in Table AI.2.

    The potency of benzo [a]pyrene in humans exposed by inhalation has
    been assessed on the basis of extrapolations from the results for
    rodents, sometimes exposed other than by respiration. Since the
    sensitivity to PAH is likely to differ with the route of exposure,
    assessments made on the basis of exposure by inhalation are
    preferable; some of these are shown in Table AI.3.

    Table AI.2. Slope factors for humans based on the results of
    studies in which benzo[a]pyrene was fed to rodents in the diet

                                                                              

    Study           Slope factor         Comments
                    (per [mg/kg]/day)
                                                                              

    Neal & Rigdon        5.9             Two-stage, conditional upper bound
    (1967)               9.0             Two-stage, slope from 10% response
                         4.5             Weilbull-type model

    Brune at al.         11.7            Linearized multistage procedure
    (1981)                               applied to oesophageal, laryngeal,
                                         and forestomach tumours in males
                                         and females
                                                                              

    From US Environmental Protection Agency (1992b, 1993)


    The commonest method of extrapolation is based on the relative surface
    areas or body weights of experimental animals and humans, assuming
    that these are good predictors of the relative potency of PAH in two
    species. While such scaling factors have been validated for other
    compounds (Chappell, 1989) and have been used in the case of PAH
    (Thorslund & Farrar, 1990b; Collins et al., 1991; Collins & Alexeeff,
    1993), this relationship may not hold for PAH. Muller et al. (1995a,b,
    1996) compared the actual and extrapolated doses required to produce a
    tumorigenic effect of a given magnitude in a particular rodent
    species, on the basis of the assumption that if extrapolations based
    on surface area and/or body weight hold between rodents to humans, the
    same extrapolation should hold even more closely for closely related
    rodents. The extrapolated dose was estimated from that required to
    induce a similar response in another rodent species under matching
    experimental conditions and by extrapolating to the target rodent
    species. Examples of the analysis are shown in Tables AI.4 and AI.5.
    The extrapolated and actual doses differed by much as two orders of
    magnitude, even though mice and rats are closely related, of similar
    sizes, and with similar diets, and, furthermore, laboratory rodents
    are placed in similar habitats. It would be expected that
    extrapolation from one rodent to another is more justified than
    extrapolation from rodents to humans, but these analyses indicate that
    extrapolation from rodents to humans may lead to even larger errors.
    Although some of the discrepancies may be due to methodological
    problems, much of the difference is due to the low predictive value of
    the two extrapolations. Extrapolations based on surface area or body
    weight further imply that species differences in the metabolism of the
    parent compound to the primary carcinogen are functions of body weight
    or surface area. This assumption is not supported by the available
    pharmacokinetic data for PAH (Michel et al., 1995).


        Table AI.3. Estimated carcinogenic potency of benzo[a]pyrene in humans exposed by inhalation, on the basis of
    extrapolations from the results of studies in experimental animals

                                                                                                                                   

    Risk          Species      Route of exposure      Assumptions                     Data source     UCL/     Assessor
    (ng/m3)                                                                                           MLE
                                                                                                                                   

    1.7 × 10-6a   Hamster      Inhalation on salt     Risk proportional to            Thyssen et      UCL      US Environmental
                               particulate            (body weight)2/3 and            al. (1981)               Protection Agency
                                                      inhalation rate = 0.037 m3/d                             (1984a); Collins &
                                                                                                               Alexeeff (1993)

    1.1 × 10-6    Hamster      Inhalation on salt     Risk proportional to            Thyssen et      UCL      Collins & Alexeeff
                               particulate            (body welght)2/3 and            al. (1991)               (1993)
                                                      inhalation rate = 0.063 m3/d

    4.7 × 10-6    Hamster      Intratracheal          Risk proportional to            Saffiotti at    UCL      Collins & Alexeeff
                               instillation with      (body weight)2/3                al. (1972)               (1993)
                               ferric oxide

    4.4 × 10-6    Hamster      Intratracheal          Risk proportional to            Feron et al.    UCL      Collins & Alexeeff
                               instillation with      (body weight)2/3                (1973)                   (1993)
                               ferric oxide

    2.0 × 10-8    Rat          Inhalation of          Risk equal to that of humans    Heinrich at     UCL      Heinrich et al.
                               coal-tar/pitch         and hamsters at same air        al. (1994c)              (1994c)
                               condensation           level of benzo[a]pyrene,
                               aerosolb               corrected for rat lifetime
                                                      (2 years)

    7.0 × 10-9    Hamster                             Risk proprotional to body       Thyssen at      MLE      Clement Associates
                                                      weight                          al. (1981)               (1990)

    3.6 × 10-8    Hamster                             Risk proprotional to body       Thyssen et      MLE      Clement Associates
                                                      weight3/4                       al. (1981)               (1990)

    6.2 × 10-8    Hamster                             Risk proprotional to body       Thyssen et      MLE      Clement Associates
                                                      weight2/3                       al. (1981)               (1990)

    Table AI.3. (continued)

                                                                                                                                   

    Risk          Species      Route of exposure      Assumptions                     Data source     UCL/     Assessor
    (ng/m3)                                                                                           MLE
                                                                                                                                   

    3.9 × 10-8    Hamster                             Risk equal to that of humans    Thyssen et      MLE      Clement Associates
                                                      and hamsters at same air        al. (1981)               (1990)
                                                      level of benzo[a]pyrene
                                                                                                                                   

    UCL, upper confidence limit; MLE, maximum likelihood estimate
    a Recalculated from 6.11 mg/kg bw per day using the assumptions of the US Environmental Protection Agency for humans:
      70 kg, 20 m3/d
    b Other active polycyclic aromatic hydrocarbons present in the administered aerosol

    Table AI.4. Comparison of actual and extrapolated doses of 3-methylcholanthrene and benzo[a]pyrene required to obtain observed
    tumour incidence; topical administration

                                                                                                                                  

    Species          Compound                  Actual dose (mg)     Extrapolated dose (mg)    Extrapolated/   Reference
                                                                                              actual dose
                                               Surface    Body      Surface    Body
                                               area       weight    area       weight
                                                                                                                                  

    Rat              3-Methylcholanthrene      58         9.0       20         0.16           0.35            Cavalieri et al.
                                                                                                              (1978)a; Zackheim
                                                                                                              (1964)

    Hamster          3-Methylcholanthrene      5.0b       0.048     0.074      0.0096         0.015           Cavalieri et al.
                                                                                                              (1978)a; Bernfeld &
                                                                                                              Homburger (1983)

    Hamster          Benzo[a]pyrene            5.0b       0.019     0.028      0.0038         0.056           Cavalieri et al.
                                                                                                              (1978)a; Bernfeld &
                                                                                                              Homburger (1983)
                                                                                                                                  

    a Data for mouse
    b No tumours induced at dose tested; assumed 1% response rate

    Table AI.5. Comparison of actual and extrapolated doses of 3-methylcholanthrene and benzo[a]pyrene required to obtain observed tumour
    incidence; respiratory exposure

                                                                                                                                        

    Species          Compound                  Actual dose (mg)     Extrapolated dose (mg)    Extrapolated/   Reference
                                                                                              actual dose
                                               Surface    Body      Surface    Body
                                               area       weight    area       weight
                                                                                                                                        

    Rat              3-Methylcholanthrene      0.50a      7.0a      15a        14a            30a             Nettesheim & Hammons
                                                                                                              (1971)b; Hirano et al.
                                                                                                              (1974)

    Hamster          3-Methylcholanthrene      0.7a       4.7a      7.1        6.7a           10a             Nettesheim & Hammons
                                                                                                              (1971)b; Hammond et al.
                                                                                                              (1987)

    Rat              Benzo[a]pyrene            15         31        33         2.1            2.2             Furst et al. (1979)b;
                                                                                                              Ishinishi et al. (1976)

    Hamster          Benzo[a]pyrene            30         33        222        1.1            0.73            Furst et al. (1979)b;
                                                                                                              Saffiotti et al. (1972)
                                                                                                                                        

    a Nettesheim & Hammons (1971) used intratracheal instillation, while Hirano et al. (1974) used intrapulmonary pellets to
      administer 3-methylcholanthrene to rats. Hammond et al. (1987) applied intrabronchial pellets to hamsters. The fact that
      instillation is considered to be less effective in inducing tumours than implantation is considered to be the likely
      explanation for the apparent discrepancy between the actual and the extrapolated doses.
    b Data for mouse


    Some risk assessments are based on extrapolation of the results of
    studies in which the compound was deposited directly onto or in close
    proximity to the tissues where tumours were later observed. Since the
    dose delivered to these tissues is direct and not a reflection of body
    weight or surface, it may well be argued that extrapolations based on
    body weight or surface area are not appropriate.

    It is likely, therefore, that the estimates of the potency of PAH in
    humans based on such extrapolations would lead to substantial errors.
    It is therefore preferable to use other approaches, like the relative
    potency approach, in order to estimate human risk.

    I.2.1.2.2  Derivation of relative potencies of PAH other than
    benzo [a]pyrene

    Some quantitative risk estimates for mixtures of PAH are based on the
    assumption that all PAH (or all carcinogenic PAH) have the same
    potency as benzo [a]pyrene and that the carcinogenic effect of the
    mixture can be estimated by summing the effects of each PAH. Some PAH
    are less carcinogenic in animal models than benzo [a]pyrene, and a
    few are more active. In order to provide more reasonable estimates of
    the carcinogenicity of PAH mixtures, schemes have been devised that
    are similar to the toxicity equivalence factor approaches of the US
    Environmental Protection Agency and NATO for evaluating chlorinated
    dibenzodioxins and dibenzofurans, which are based on a general or
    specific hypothesis of relative potency.

    In a provisional quantitative risk assessment of PAH, the US
    Environmental Protection Agency (1993) used benzo [a]pyrene as a
    standard and derived the relative potencies of individual PAH in
    increments of order of magnitude by comparison. Only the results of
    carcinogenicity bioassays were considered, and these were limited to
    those in which benzo [a]pyrene and other PAH were assayed by the same
    protocol and within the same time frame. The studies involved various
    routes of exposure, including skin painting, intraperitoneal and
    subcutaneous injection, and lung implantation (see section 7.7.2).
    Maximum likelihood estimates from a two-stage model were used for
    comparison, and ranges of estimates were presented. These values for
    the results of complete carcinogenesis assays in mouse skin are shown
    in Table AI.6. The US Environmental Protection Agency (1993)
    considered that the data on PAH did not meet all of the requirements
    for application of the toxicity equivalence factor approach and
    recommended that the values be applied only to carcinogenicity and not
    to other end-points. In order to differentiate between these values
    and a toxicity equivalence factor meant for use in evaluating all
    types of toxicity, the relative potencies were designated 'estimated
    orders of potential potency'. The US Environmental Protection Agency
    (1993) further recommended that these values not be used for
    evaluating inhaled PAH mixtures, for the following reasons:

    -    The US Environmental Protection Agency currently has no consensus
         value for an inhalation unit risk.

    Table AI.6. Estimated orders of potency of selected polycyclic aromatic
    hydrocarbons in mouse skin carcinogenesis
                                                                            

    Compound                  Relative potencya    Reference
                                                                            

    Benzo[a]pyrene            1.0        1.0
    Benz[a]anthracene         0.145      0.1       Bingham & Falk (1969)
    Benzo[b]fluoranthene      0.167      0.1       Habs et al. (1980)
    Benzo[k]fluoranthene      0.020      0.01      Habs et al. (1980)
    Chrysene                  0.004      0.001     Wynder & Hoffmann
                                                   (1959)
    Dibenz[a,h]anthracene     1.11       1.0       Wynder & Hoffmann
                                                   (1959)
    Indeno[1,2,3-cd]pyrene    0.055b     0.1       Habs et al. (1980);
                                                   Hoffmann & Wynder (1966)
                                                                            

    a Model was P(d) = 1-exp[-A(1 + bd)2] for all except
      indeno[1,2,3-cd]-pyrene. Actual figures (left) and rounded to
      order of 10 (right)
    b Simple mean of relative potencies (0.021 and 0.089), the latter
      being derived with the one-hit model


    -    There is no basis for assuming that the relative order of potency
         for PAH is the same after oral and inhalation exposure.

    -    The co-carcinogenic potential of particulate carriers in the lung
         has not been sufficiently elucidated.

    Improvements to the estimated orders of potential potency have been
    published (McClure & Schoeny, 1995). As the two-stage model requires
    estimation of several parameters in the absence of data, other models
    were investigated. It was shown that the model used had little effect
    on the values when applied consistently; however, the assay type and
    data set used could alter the values by orders of magnitude. It was
    proposed, therefore, that data from all available appropriate assays
    should be modelled and that a central tendency estimate, rounded to
    powers of 10, would give a more realistic value. The list of PAH for
    which estimated orders of potential potency were estimated was
    expanded from that of US Environmental Protection Agency (1993) to
    include several more that could be considered probable human
    carcinogens (Table AI.7).

    In a preliminary validation exercise based on published data on
    PAH-containing mixtures, McClure & Schoeny (1995) used the values in
    Table AI.7 to estimate the carcinogenicity of two synthetic mixtures
    of PAH (Pfeiffer, 1973), both as a sum of their components and as
    whole mixtures. A good correlation was found between the two
    measurements of potency. These results indicate that the components of
    a defined mixture have additive risks.

    Table AI.7. Estimated order of carcinogenic potency for 13
    polycyclic aromatic hydrocarbons in Group B2 as compared with
    benzo[a]pyrene

                                                                    

    Compound                     Estimated order   No. of estimates
                                 of potency
                                                                    

    Benzo[a]pyrene               1.0
    Benz[a]anthracene            0.1               4
    Benzo[b]fluoranthene         0.1               8
    Benzo[j]fluoranthene         0.1               7
    Benzo[k]fluoranthene         0.1               7
    Chrysene                     0.1               5
    Cyclopenta[cd]pyrene         0.1               4
    Dibenz[a,h]anthracene        1.0               3
    Dibenzo[a,e]fluoranthenea    1.0               3
    Dibenzo[a,e]pyrene           1.0               3
    Dibenzo[a,h]pyrene           1.0               2
    Dibenzo[a,i]pyrene           0.1               3
    Dibenzo[a,l]pyrene           100               2
    Indeno[1,2,3-cd]pyrene       0.1               4
                                                                    

    Adapted from McClure & Schoeny (1995)
    a Not evaluated by the Task Group


    The additivity of the potency of mixtures of five PAH was investigated
    in the mouse lung adenoma model (Nesnow et al., 1995). Different
    combinations of PAH with different biological and chemical properties
    were tested. Some interaction was found in which the potency of the
    compounds was more or less than additive. The differences were no more
    than twofold and, therefore, would not be large enough to alter
    significantly the outcome of risk assessments, in which uncertainty of
    an order of magnitude is not seen as excessive.

    Complex environmental mixtures differ from defined synthetic mixtures
    in that they contain not only PAH of known carcinogenicity but also
    hundreds of PAH and other potentially carcinogenic non-PAH compounds
    for which carcinogenicity has not been established. The risk
    attributed to a PAH for which data on exposure and carcinogenic
    potency exist would be similar to that for the entire mixture only if
    the PAH for which the potency is unknown contributed little or nothing
    to the potency of the mixture as a whole. McClure & Schoeny (1995)
    reported that the carcinogenic activity of a coal liquefaction
    material (Mahlum et al., 1984) was similar to that estimated by adding
    benzo [a]pyrene equivalents derived from estimated orders of
    potential potency for several measured PAH. Similar estimates for coal
    flue gas, petrol-engine exhaust, and diesel exhaust, however, resulted

    in underestimates of two to three orders of magnitude of the risks
    presented by the PAH fractions when the results of studies by either
    lung implantation or dermal application in rodents were used for the
    calculation (Grimmer et al., 1984; Thorslund & Farrar, 1990a; see
    Table AI.8).

    Other strategies for risk assessment based on the toxicity equivalence
    factor approach for individual PAH have been published. The resulting
    estimates are compared in Table AI.9. Krewski et al. (1989) analysed
    the published values and derived a new set based largely on estimates
    from a two-stage model (Clement Associates, 1988). Applications of
    their toxicity equivalence factors to the results of bioassays wth PAH
    mixtures (Pfeiffer, 1977; Schmähl et al., 1977) indicated that their
    values would be unlikely to underestimate the carcinogenic risk posed
    by whole mixtures.

    A set of toxicity equivalence factors was derived for the 17 PAH
    commonly measured at hazardous waste sites, and a new list (see column
    2 of Table AI.9) was calculated on the basis of older work and the
    primary literature (Nisbet & LaGoy, 1992). The values tend to
    overestimate the carcinogenic risks of mixtures.

    The relative potency values in 14 publications were used to classify
    PAH into categories of high, medium, low, and very low risk (column 3
    of Table AI.9), and 'environmental assessment levels' were calculated
    on the basis of the highest potency for a PAH, rounded to an order of
    magnitude, relative to that of benzo [a]pyrene (Malcom & Dobson,
    1994).

    Kalberlah et al. (1995) and others adopted the approach of the US
    Environmental Protection Agency Office of Pesticides, Pollution
    Prevention and Toxic Substances to determine the relative potencies of
    PAH. A panel of five experts made independent reviews of the existing
    data on about 150 PAH and scored them as having high, moderate,
    marginal, or slight potential carcinogenicity. The panel considered
    data from studies of skin painting in mice, the induction of lung and
    liver adenomas in newborn mice, mammary tumours in rats, studies by
    oral administration, studies of genotoxicity, and structure-activity
    relationships. Their evaluation, converted to powers of 10 to
    represent levels of concern, is presented in column 4 of Table AI.9.

    Columns 5 and 6 of Table AI.9 show the values of the US Environmental
    Protection Agency (1993) and McClure & Schoeny (1995), discussed
    previously. The results of the six toxicity equivalence factor
    approaches show a reasonable degree of agreement for PAH that are
    generally considered to be carcinogenic. In all of them,
    dibenz [a,h]anthracene appears to be equipotent or somewhat more
    potent than benzo [a]pyrene; and, in most, the benzofluoranthenes and
    benzanthracene were about 10% as potent as benzo [a]pyrene. The
    greatest variation in the estimated relative potency is observed for
    chrysene, although all agree that chrysene is not as potent a
    carcinogen as benzo [a]pyrene.


        Table AI.8. Comparison of the carcinogenic potency of the polycyclic aromatic
    hydrocarbon (PAH) fraction of PAH-rich mixtures with the integrated potency
    of the eight PAH found in the fraction

                                                                                    

    Method of estimating risk          Potency relative to that of benzo[a]pyrene
                                                                                    
                                       Flue gas    Diesel-engine    Petrol-engine
                                                   exhaust          exhaust
                                                                                    

    Fraction of mixture containing     0.38        0.28             0.67
    PAH with > three rings

    Sum of risk for eight PAH          0.0011      0.0018           0.0007

    Fraction/sum                       340         150              950
                                                                                    

    From Thorslund & Farrar (1990a)

    Table AI.9. Relative potencies of indicator polycyclic aromatic hydrocarbons

                                                                                                    
    Compound                    [1]       [2]       [3]       [4]       [5]       [6]       [7]
                                                                                                    

    1-Methylphenanthrene                            0.001
    Acenaphthene                          0.001     0.001     0.001     0
    Acenaphthylene                        0.001     0.001     0.01
    Anthanthrene                0.320                                                       0.28
    Anthracene                            0.01      0.01      0.01
    Benz[a]anthracene           0.145     0.1       0.1       0.1       0.1       0.1       0.014
    Benzo[a]pyrene              1.0       1.0       1.0       1.0       1.0       1.0       1.0
    Benzo[b]fluoranthene        0.141     0.1       0.1       0.1       0.1       0.1       0.11
    Benzo[e]pyrene              0.004               0.01                                    0
    Benzo[ghi]perylene          0.022     0.01      0.01      0.01                          0.012
    Benzo[j]fluoranthene                                      0.1                 0.1       0.045
    Benzo[k]fluoranthene        0.061     0.1       0.1       0.1       0.01      0.1       0.037
    Chrysene                    0.0044    0.01      0.01      0.01      0.001     0.1       0.026
    Coronene                              0.001
    Cyclopenta[cd]pyrene        0.023     0.1                                     0.1       0.012
    Dibenzo[a,e]pyrene                                                            1.0
    Dibenz[a,c]anthracenea                0.1
    Dibenz[a,h]anthracene       1.11      5         1.0       1.0       1.0       1.0       0.89
    Dibenzo[a,l]pyrene                                                            100       100
    Dibenzo[a,e]fluoranthenea                                                               1.0
    Dibenzo[a,h]pyrene                                                            1.0       1.2
    Dibenzo[a,i]pyrene                                                            0.1
    Fluoranthene                          0.001     0.001     0.01
    Fluorene                              0.001     0.001     0
    Indeno[1,2,3-cd]pyrene      0.232     0.1       0.1       0.1       0.1       0.1       0.067
    Naphthalene                           0.001     0.001
    Perylene                                        0.001
    Phenanthrene                          0.001     0.001     0                             0.00064
    Pyrene                      0.81      0.001     0.001     0.001                         0
                                                                                                    

    Table AI.9 (continued)

    [1] Krewski et al. (1989);
    [2] Nisbet& LaGoy (1992);
    [3] Malcolm & Dobson (1994);
    [4] Kalberlah et al. (1995);
    [5] US Environmental Protection Agency (1993);
    [6] McClure & Schoeny (1995);
    [7] Muller et al. (1995a,b, 1996)
    a Not evaluated by the Task Group


    I.2.1.3  Application

    Application of the toxicity equivalence factor approach to assessing
    the risk posed by dibenzodioxins and dibenzofurans involves the
    following steps:

    (1)  analytical determination of the agents in the environmental
         sample;

    (2)  multiplication of the concentrations of congeners in the sample
         by the toxicity equivalence factors to express the concentration
         in terms of the standard agent (e.g. benzo [a]pyrene)
         equivalents;

    (3)  summation of the products in step (2) to obtain the equivalents
         of the standard agent in the sample;

    (4)  determination of human exposure to the mixture in question,
         expressed in terms of standard chemical equivalents; and

    (5)  combination of the exposure derived in step 4 with information on
         the toxicity (here, carcinogenic potency) of the standard
         chemical in order to estimate the risks associated with exposure
         to the mixture.

    These steps were followed for PAH, using one or more of the toxicity
    equivalence factors given in Table AI.9 and benzo [a]pyrene as the
    standard.

    I.2.2  Comparative potency approach

    I.2.2.1  Principle

    The comparative potency approach is used to estimate the potency of
    the PAH in mixtures without having to identify or quantify the
    individual compounds. The carcinogenic potency of an unknown mixture
    in humans is estimated from the potency of the mixture in a bioassay
    and from the potency of another mixture(s) in the same bioassay and in
    humans. It is assumed that the relationship (ratio) between the
    potency of a mixture in a bioassay and human cancer risk is constant
    for different (PAH-rich) mixtures. The relationship is expressed in
    equation (3):

          Human risk carcinogen1/ Bioassay potency carcinogen1

          = Human risk carcinogen2/ Bioassay potency carcinogen2      (3)

                          =  k

    The carcinogenic risk to humans due to exposure to a mixture can
    readily be derived by a rearrangement of terms.

    The potency in the bioassay and the risk to humans are expressed in
    terms of the mass of extractable organic compounds contained in the
    mixture. Although this method is intended to predict human risks due
    to PAH, in practice it estimates the risk due to all organic compounds
    present. This discrepancy may not be significant when estimating the
    carcinogenic risk of mixtures rich in polycyclic organic matter, such
    as coal-tar, but may be important when estimating the risk of exposure
    to cigarette smoke or ambient air, in which PAH do not necessarily
    play a major role.

    I.2.2.2  Development and validation

    The comparative potency approach was initially proposed as part of an
    approach to assessing the carcinogenic risk of PAH in diesel emissions
    (Albert et al., 1983; Lewtas, 1985a,b; Nesnow, 1990). For source
    mixtures such as coal-tar, coke-oven emissions, and diesel and petrol
    emissions tested both for skin tumorigenicity in mice (Nesnow et al.,
    1982a,b) and in short-term bioassays (Lewtas, 1985a), there was
    generally good agreement (Lewtas, 1985a). Furthermore, there appears
    to be a good correlation between the potency of mixtures in bioassays
    and in humans, although this correlation is based on limited
    epidemiological data of good quality (Nesnow, 1990; Lewtas, 1993).
    Thus, risk assessments of relatively high quality are currently
    available only for cigarette smoke, coke-oven emissions, and coal-tar.
    Although the concept of comparative potency has been extensively
    validated, some outstanding issues remain, which are discussed below.

    I.2.2.3  Key implicit and explicit assumptions

    The comparative approach assumes that several distinct sources
    contribute PAH to the environment at a given location in an ambient
    environment. For example, in an industrial city in winter, the sources
    of PAH may include emissions from steel manufacture, from cars,
    lorries, and transport from other locations, and from home heating.
    Each source is assumed to make a specific contribution to the overall
    risk for lung cancer due to PAH. The proportion of the total risk
    attributable to each source depends on its potency (risk per unit mass
    of organic compounds) and the overall contribution to the mass of
    organic compounds in the ambient air. The total risk can be expressed
    as follows:

             Total risk = (unit risk source1 × mass of organic
             compounds source1) + (unit risk source2 × mass of
             organic compounds source2) + (unit risk source3           (4)
             × mass of organic compounds source3) ...

    The unit risks for some sources are listed in Table AI.10.

    Table AI.10. Potency of some source mixtures expressed as average
    dose causing 50% papilloma incidence in male and female Sencar
    mice

                                                                          

    Source mixture                       Organic compounds (mg)
                                                                          

    Coke-oven main                       0.14
    Coke-oven topside                    0.16
    Roofing tar                          2.0
    Nissan diesel emission               1.6
    Volkswagen Rabbit diesel emission    Tumour incidence did not reach
                                         50% with tested doses

                                                                          

    From Nesnow et al. (1982a,b)


    Implicit in this approach are the assumptions that the composition of
    the organic compounds emitted from each source (such as diesel
    engines) is constant and that the potency (unit risk) of a given
    source mixture is constant. If the potency and composition of the
    organic compounds within mixtures from the same source vary widely,
    the standard mixture may not accurately represent other mixtures from
    a similar source. There is some evidence, however, that mixtures from
    similar sources have substantially different compositions. Thus, the
    benzo [a]pyrene content of the emissions from four diesel engines
    varied over a 600-fold range (Nesnow et al., 1982a,b; see Table
    AI.11). Significant differences in the potency of the four mixtures
    were also seen. Nevertheless, the potency of the mixtures appears to
    correlate reasonably well with their benzo [a]pyrene content (see
    Table AI.11), so that the comparative potency approach may be viable
    in principle but may not be appropriate for expressing the potency of
    the mixtures in terms of the mass of the organic content. A possible
    alternative is to express the potency in terms of the level of
    benzo [a]pyrene present in the mixture. If this solution is used, the
    comparative potency approach becomes essentially the benzo [a]pyrene
    surrogate approach discussed in section I.2.3.

    The levels of PAH in ambient air may be influenced by multiple
    sources, and some PAH may be transformed in the environment. In order
    to estimate the carcinogenic risk due to exposure to an ambient
    mixture, the contribution of individual sources to the ambient air
    levels must be estimated, because contributing sources differ in their
    carcinogenicity. Making reliable estimates of the contribution of
    individual sources to ambient air levels is still a difficult,
    non-routine process.

    Table AI.11. Benzo[a]pyrene content of organic fraction extracted from
    diesel-engine emissions

                                                                            

    Source               Benzo[a]pyrene             % Mice with tumours/ng
                         (ng/mg organic fraction)   benzo[a]pyrenea
                                                                            

    Nissan               1200                       0.024
    Oldsmobile           2.0                        NS
    Caterpillar          2.0                        NS
    Volkswagen Rabbit    26                         0.11
                                                                            

    From Nesnow et al. (1982a,b); NS, no significant response observed over
    the range of doses tested
    a Calculated by Muller et al. (1995a,b, 1996)


    I.2.2.4  Application

    In order to use the comparative potency approach, the carcinogenicity
    of the major source mixtures that contribute to a given ambient
    environment must be established. The potency of a number of the
    mixtures has been estimated (see Table AI.10), and the potency of
    source mixtures that affect air has been expressed in terms of risk
    per mass of organic compounds per cubic metre. The levels of each
    source mixture must then be estimated for a given ambient environment.
    The total risk is calculated as shown in equation (4).

    I.2.3  Benzo [a]pyrene as a surrogate for the PAH fraction of
    complex mixtures

    I.2.3.1  Principle

    The third approach assumes that the risk due to the PAH component of
    complex mixtures and the levels of individual PAH in the mixtures are
    proportional to those of benzo [a]pyrene in the mixture and vary
    proportionately. Using this approach, the risk due to the PAH
    component of mixtures can be estimated as the product of the
    environmental levels of benzo [a]pyrene and the estimate of the risk
    attributable to mixtures per unit amount of benzo [a]pyrene.

    In general, the approach does not predict the potency of an ambient
    complex mixture as a whole but merely its PAH component. There is no
    reason to believe that benzo [a]pyrene is a good indicator of
    chlorinated compounds such as dioxins and dibenzofurans or volatile
    organic compounds such as benzene and 1,3-butadiene, which may be
    present in some ambient complex mixtures. The contribution of non-PAH
    to the overall risk of exposure to complex mixtures must thus be
    assessed separately.

    I.2.3.2  Development and validation

    Benzo [a]pyrene was initially favoured as an indicator of all urban
    pollution, and in a number of assessments based primarily (or
    entirely) on studies of the general population exposed to ambient air
    benzo [a]pyrene was used as an index of exposure to a wider mixture
    of materials (Nisbet et al., 1985). There is evidence, however, that
    benzo [a]pyrene cannot serve as an indicator of the toxicity of whole
    mixtures. Various factors may influence the relative contents of PAH
    and other contaminants of ambient air. For instance, the relative
    proportions of benzo [a]pyrene and other PAH in ambient urban air has
    been declining over the years, while the levels of volatile organic
    compounds and others have been rising. In some mixtures, such as
    cigarette smoke condensate, PAH probably play only a minor role in
    overall toxicity. Pott & Heinrich (1992) showed that mixtures
    containing large amounts of carcinogenic compounds other than PAH,
    such as cigarette smoke, are much more potent at a given level of
    benzo [a]pyrene than mixtures that owe much of their carcinogenicity
    to PAH, such as coke-oven emissions. Nisbet et al. (1985) argued
    convincingly that benzo [a]pyrene cannot serve as a general indicator
    of all pollutants in the ambient air, although it may be a suitable
    indicator for the carcinogenic risk posed by four- to seven-ring,
    unsubstituted PAH in the mixture.

    Muller et al. (1995a,b, 1996) examined the PAH profiles of a wide
    range of mixtures from many sources and found that they were generally
    similar (see also section I.2.3.3). Furthermore, those mixtures rich
    in PAH and in which PAH are likely to contribute a significant
    proportion of the risk of the mixture are very similar in potency
    expressed per unit amount of benzo [a]pyrene. This observation is
    consistent with the notion that the PAH components of these mixtures
    are approximately equipotent. (Establishment of the potency of
    mixtures is discussed in section I.2.3.4.)

    These findings do not imply that all mixtures are similar. Differences
    in the PAH profiles of the same mixture have been analysed in order to
    establish markers for mixtures from a particular source (Gordon &
    Bryan, 1973; Greenberg et al., 1981; Vogt et al., 1987). The levels of
    some substituted PAH are clearly not related to the levels of
    benzo [a]pyrene in the mixture (Albert et al., 1983). The differences
    in the profile of four- to seven-ring, unsubstituted PAH in various
    mixtures are probably too small to alter the estimated risks of the
    PAH component of the mixtures significantly.

    I.2.3.3  PAH profiles of complex mixtures

    Information on the levels of PAH in various source mixtures is
    provided in Section 5. The levels of PAH in environmental mixtures
    used in the following analysis were derived mainly from monitoring in
    Canada (Muller et al., 1995a,b, 1996). About 100 mixtures were
    classified into different types, such as diesel emissions, coke-oven
    emissions, ambient air particulate, soils, and sediments, to
    facilitate the analysis, and the profiles of the 15 PAH most commonly

    tested in mixtures were compared. The results are expressed as the
    ratios of the levels of each PAH relative to benzo [a]pyrene; the
    geometric mean, the upper and lower 95% confidence limits, and the
    confidence range were calculated for each PAH ratio for a mixture
    type. The confidence range was determined by dividing the upper
    confidence limit by the lower confidence limit and used as a measure
    of the range of the means of the relative levels a given PAH will
    assume about 95 times out of 100.

    The PAH profiles for petrol exhaust emissions are provided as an
    example in Table AI.12. It can be seen that the confidence range for
    each PAH is less than 5.0, and many are less than 2.0, indicating that
    the levels of these PAH, relative to benzo [a]pyrene, are very stable
    and vary little among the sources. They also indicate that any
    variation among samples is probably not large enough to alter the
    estimated risk. The low variation also means that the level of
    benzo [a]pyrene is a good predictor of the levels of the other PAH
    that may be present in a given mixture from petrol engines.

    The confidence ranges for all types of combustion mixture and all of
    the PAH considered are presented in Table AI.13. The confidence ranges
    were < 50 for more than 90% of all entries and < 6 for 50% of all
    entries. Given the degree of uncertainty usually associated with risk
    assessment, the uncertainty presented by the variation in PAH profile
    is relatively small. In addition, while some compounds in a given
    mixture may be found at higher levels than expected, those of other
    compounds may be lower than expected, and there may therefore be
    little difference between the estimates of risk based on chemical
    analysis and those based on the predicted composition of a mixture.
    The ambient mixtures appear to be less variable than the combustion
    emission mixtures. For example, Table AI.14 shows that the confidence
    ranges for most types of ambient air are similar. The corresponding
    levels of PAH relative to benzo [a]pyrene are shown in Table AI.15.

    Samples of ambient air were collected in 1982-86 at point sources in
    Hamilton, Ontario, Canada, on days when the wind was blowing from
    nearby steel-mill operations 50% or more of the time. Mobile sources
    and home heating also contributed, but the urban levels of PAH were
    much lower on days when the wind was not blowing from the direction of
    the steel mills. The average level of benzo [a]pyrene was about 1.8
    ng/m3. Samples of ambient air from mobile sources were collected in
    Toronto, Ontario, during the summer near the intersection of two busy
    multi-lane highways in 1988-92. The average level of benzo [a]pyrene
    was about 0.17 ng/m3. The highway intersection is surrounded by
    residential areas, and the samples of ambient air associated with home
    heating were collected in the same location as the mobile sources by
    the same collection and analytical protocol, but in winter. The
    average level of benzo [a]pyrene was 0.41 ng/m3. Home heating and
    mobile emisions are considered to be the main sources of PAH. In
    samples of ambient air collected on Wallpole Island, Ontario, a rural
    location with little traffic and no industrial source, the average
    levels of benzo [a]pyrene was about 0.093 ng/m3 (T. Dann, personal
    communication).

        Table AI.12. Confidence ranges for petrol engine exhaust (relative to
    benzo[a]pyrene

                                                                              

    Compound                    Mean     95% confidence
                                                                              
                                         Lower limit   Upper limit   Interval
                                                                              

    Anthracene                  7.0      9.3           5.3           1.8
    Phenanthrene                25       38            17            2.3
    Fluoranthene                7.3      14            4.0           3.5
    Pyrene                      9.5      19            4.7           4.0
    Benz[a]anthracene           0.81
    Perylene                    0.27     0.60          0.12          4.8
    Benzo[e]pyrene              1.1      1.4           0.79          1.8
    Benzo[ghi]perylene          2.6      3.5           2.0           1.7
    Dibenz[a,h]anthracene       0.072
    Coronene                    2.0      2.7           1.4           1.9
    Indeno[1,2,3-cd]pyrene      0.80     1.1           0.60          1.8
    Anthanthrene                0.38     0.55          0.27          2.1
    Chrysene and triphenylene   3.0      4.6           1.9           2.4
    Benzofluoranthenes          1.1      1.5           0.85          1.7
                                                                              

    From Muller (1995a,b, 1996), based on data from Hoffmann & Wynder
    (1962), Grimmer & Hildebrandt (1975), Grimmer & Bohnke (1978),
    Alsberg et al. (1985), and Hagemann et al. (1982)


        Table AI.13. Confidence ranges for polycyclic aromatic hydrocarbons in various combustion mixtures (relative to
    benzo[a]pyrene

                                                                                                                                           

    Compound                    Combustion mixture
                                                                                                                                           
                                Coke    Coal-tar  Coal-fired    Coal    Open burning    Wood     Diesel      Petrol     Roofing   Paving
                                ovens             power plants  stoves  and fireplaces  stoves   emissions   emissions  asphalt   asphalt
                                                                                                                                           

    Anthracene                  3.2     440       830                                   7.6                  1.8
    Phenanthrene                1.3     32        27                                    2.7                  2.3
    Fluoranthene                2.7     4.5       3.2           43      4.9             1.4      6.1         3.5        5.7       5.2
    Pyrene                      2.6     280       37            18      5.6             1.5      5.3         4.0        19        2.7
    Benz[a]anthracene           19                2.8           32      160             2.0      9.0                    130       8.5
    Perylene                    2.3     27                      23      8.2             31                   4.8        4.6       5.9
    Benzo[e]pyrene              1.3     5.5       3.3           35      1.6             1.5      22          1.8
    Benzo[ghi]perylene          8.8                             12      32              2.7      8.9         1.7        5.1       2.8
    Dibenz[a,h]anthracene                                       310     3.2                      2.4
    Coronene                    7.8                             7.1     730                      3.2         1.9
    Indeno[1,2,3-cd]pyrene                                      7.4     1.9             7.0      1.8
    Anthanthrene                8.7                                                                          2.1
    Chrysene and                2.1     12        430           42      25              4.3      7.3         2.4        23        6.1
    triphenylene
    Benzofluoranthenes          5.7               2.0           28      7.1             5.0      3.4         1.7        7.7       120
    Incidence of confdence      0       2         2             1       2               0        0           0          1         1
     range > 50
                                                                                                                                           


    Table AI.14. Confidence ranges for particulates extracted from ambient
    air (relative to benzo[a]pyrene)

                                                                             

    Compound                 Point    Near     Home     Transport   Geometric
                             source   mobile   heating              mean
                                      source
                                                                             

    Anthracene               2.8      5.7      6.7      2.0         20
    Phenanthrene             2.3      1.7      2.6      1.4         13
    Fluoranthene             2.2      1.5      1.7      1.4         8.1
    Pyrene                   2.4      1.4      1.7      1.4         6.7
    Benz[a]anthracene        2.0      1.4      1.5      1.2         2.3
    Perylene                 2.7      1.3      1.2      1.9         1.7
    Benzo[e]pyrene           2.8      1.3      1.6      1.1         1.3
    Benzo[ghi]perylene       2.5      1.5      1.6      1.2         2.4
    Indeno[1,2,3-cd]pyrene   1.3      1.4      1.8      1.2         1.2
    Anthanthrene             2.0      3.4      1.8      41          1.9
    Chrysene and             2.1      1.3      2.0      1.3         1.4
    triphenylene
    Benzofluoranthenes       2.5      1.3      1.9      1.3         1.7
                                                                             


    Table AI.16. Mean profiles of polycyclic aromatic hydrocarbons in
    ambient air (relative to benzo[a]pyrene)

                                                                             

    Compound                 Point    Near     Home     Transport   Geometric
                             source   mobile   heating              mean
                                      source
                                                                             

    Anthracene               5.5      7.6      1.0      1.8         2.9
    Phenanthrene             38       200      39       43          60
    Fluoranthene             14       48       12       13          18
    Pyrene                   9.3      28       11       7.1         12
    Benz[a]anthracene        1.4      0.82     1.0      0.78        0.97
    Perylene                 0.33     0.25     0.22     0.24        0.26
    Benzo[e]pyrene           1.5      1.3      1.6      1.4         1.4
    Benzo[ghi]perylene       1.4      1.5      2.4      1.3         1.6
    Indeno[1,2,3-cd]pyrene   1.5      1.3      1.5      1.4         1.4
    Anthanthrene             0.19     0.15     0.13     0.20        0.17
    Chrysene and             3.0      2.7      3.5      2.9         3.0
    triphenylene
    Benzofluoranthenes       3.6      2.9      3.6      4.4         3.6
                                                                             

    Table AI.16 presents the average PAH profiles of the combustion
    emissions, ambient air particulates, soils, and sediments and the
    average profile of the four types of mixture. The confidence ranges
    indicate that the four mixtures had fairly similar PAH profiles.

    On the basis of this analysis, Muller et al. (1995a,b, 1996) concluded
    that a wide variety of mixtures have fairly similar profiles of
    commonly assayed PAH. They assumed that the PAH fraction of all
    sources of environmental mixtures have profiles similar to the
    average, as shown in the sixth column of Table AI.16. This conclusion
    does not include substituted PAH, as there is strong evidence that
    different mixtures contain different levels of substituted PAH. It
    does not imply that there are no real differences due to the source of
    the mixture, the type of fuel, and the pyrolysis conditions that
    produced it. Furthermore, aerial transport of PAH, degradation in
    sunlight or by soil microorganisms, and other factors may alter the
    PAH profile. These factors are, however, unlikely to generate large
    enough differences in the PAH profiles of mixtures to significantly
    alter the estimate of risk for a given mixture.

    I.2.3.4  Potency of complex mixtures

    If benzo [a]pyrene is a suitable indicator of the carcinogenic
    potency of the PAH in a mixture, then the potency of a mixture
    expressed as the tumour incidence per nanogram of its benzo [a]pyrene
    content should be numerically similar for all mixtures in which PAH
    are expected to be the major cause of tumorigenic effects. Nesnow et
    al. (1982b) tested a number of PAH-rich mixtures in a
    tumour-initiation assay in mouse skin. The different types of mixture
    were roughly equipotent when the potency was expressed in terms of
    benzo [a]pyrene content (Table AI.17).

    I.2.3.5  Key implicit and explicit assumptions

    The approach assumes that the levels of individual PAH relative to
    benzo [a]pyrene are relatively stable from mixture to mixture. It
    also assumes that the risk attributable to PAH in any given mixture is
    proportional to the risk due to benzo [a]pyrene. In other words, the
    level of benzo [a]pyrene is sufficient to estimate the risk of the
    PAH fraction in a mixture.

    Differences in the composition of mixtures from different sources have
    been used to estimate the contribution of those sources to the ambient
    levels of PAH (see Gordon & Bryan, 1973; Greenberg et al., 1981; Vogt
    et al., 1987). Other authors have reported transformation of PAH in
    the environment. Since some compounds are more photosensitive than
    others, the proportion of PAH in ambient air will change over time as
    a result of the different transformation rates of different compounds
    (Van Cauwenberghe, 1985). Muller et al. (1995a,b, 1996) examined a
    wide variety of mixtures from different combustion sources and ambient
    mixtures and concluded that the differences in the profiles of four-
    to seven-ring unsubstituted PAH relative to the benzo [a]pyrene
    content are not large enough to affect the risk posed by the mixtures


        Table AI.16. Average profiles for combustion-derived mixtures, ambient air, soil, and sediment
    (relative to benzo[a]pyrene)

                                                                                                         

    Compound                    Source      Ambient     Soil        Sediment    Geometric   Confidence
                                mixtures    air                                 mean        range
                                                                                                         

    Anthracene                  3.9         2.9         0.85        0.47        1.6         24
    Phenanthrene                18          60          2.8         3.6         4.3         23
    Fluoranthene                4.9         18          2.5         3.2         3.8         1.8
    Pyrene                      4.5         12          3.1         2.4         2.8         2.9
    Benz[a]anthracene           1.8         0.97        1.4         1.4         1.2         2.6
    Perylene                    0.51        0.26        0.34        1.4         0.45        17
    Benzo[e]pyrene              1.0         1.4                     1.4         1.1         7.4
    Benzo[ghi]perylene          0.98        1.6         1.4         0.96        1.0         1.4
    Dibenz[a,h]anthracene       0.35                    0.45        0.30        0.28        4.2
    Coronene                    0.35                                0.45        0.34        3.9
    Indeno[1,2,3-cd]pyrene      0.51        1.4         0.95        1.2         0.86        4.7
    Anthanthrene                0.49        0.17                    0.19                    0.31
    Chrysene and                2.3         3.0         1.4         1.2         2.0         3.3
    triphenylene
    Benzofluoranthenes          1.6         3.6         1.7         2.4         2.5         11
                                                                                                         


    Table A1.17. Potency of various mixtures in an
    assay for tumour initiation

                                                  

    Source mixture            Incidence per ng
                              benzo[a]pyrene
                                                  

    Coke-oven main            9.4 × 10-2
    Coke-oven topside         7.6 × 10-2
    Smoky coal                7.8 × 10-2
    Smokeless coal            2.8 × 10-2
    Roofing tar               1.1 × 10-2
    Wood smoke                5.8 × 10-2
    Diesel engine exhaust     2.5 × 10-2
    Petrol engine exhaust     5.6 × 10-2
    Max/min                   8.6
                                                  

    Calculated from data of Nesnow et al. (1982b)


    significantly. The PAH profile of a tested mixture may deviate from
    the average profile by about an order of magnitude (up or down). Since
    the levels of some PAH may be above and those of others below the
    expected levels, these differences would tend to cancel each other
    out, leading to an error of much less than one order of magnitude.
    Such small differences are below the resolution of the risk assessment
    process.

    I.2.3.6  Application

    The first step is to estimate the carcinogenic risk due to exposure to
    the PAH present in a typical mixture, and this estimate is used for
    all subsequent assessments. WHO (1987) estimated that the risk for
    lung cancer due to lifelong exposure to PAH in mixtures by inhalation
    was 8.7 × 10-5/ng benzo [a]pyrene per m3. This estimate was based
    on the assessment of the risk for lung cancer of coke-oven workers
    conducted by the US Environmental Protection Agency (1984d), which
    generated an upper bound risk estimate expressed in terms of
    benzene-extractable material. WHO (1987) converted the US
    Environmental Protection Agency estimate into benzo [a]pyrene levels
    by assuming that the benzene extract contained 0.71% benzo [a]pyrene.
    Sloof et al. (1989) in the Netherlands estimated the risk for lung
    cancer to be 1.0 × 10-4/ng benzo [a]pyrene per m3 on the basis of
    the estimate of WHO and the assessments of Pike (1983) and Tuomisto &
    Jantunen (1987). That of Pike (1983) was based on the mortality from
    lung cancer of gas workers, and that of Tuomisto & Jantunen (1987) was
    based on the exposure of Chinese women to smoky coal smoke. Muller et
    al. (1995a,b, 1996) proposed 2.3 × 10-5/ng benzo [a]pyrene per m3
    as the risk for lung cancer from lifelong exposure to PAH in ambient
    mixtures on the basis of the study of the US Environmental Protection

    Agency (1984d) on coke-oven workers and assuming that benzo [a]pyrene
    represents 1.7 ng/µg of benzene-extractable material from coke-oven
    emissions. Rather than the upper bound, Muller et al. used a maximum
    likelihood estimate, calculated from the US Environmental Protection
    Agency study, of 3.9 × 10-5/µg of benzene-extractable per m3.

    The next step is to estimate the environmental levels of
    benzo [a]pyrene. In a simplified situation, in which the population
    is exposed to a fixed level of environmental benzo [a]pyrene, the
    lifetime cancer risk is estimated as the product of the potency of a
    typical mixture (expressed as risk per nanogram of benzo [a]pyrene
    per cubic metre in the case of air) and the level of benzo [a]pyrene
    (expressed as ng/m3) in the environment. For example, using the risk
    estimate proposed by Muller et al. (1995a,b, 1996) and assuming that a
    population is exposed over a lifetime to benzo [a]pyrene at 0.5
    ng/m3, the risk of the population is about 1.2 × 10-5. In other
    words, about one person in 100 000 would be expected to develop lung
    cancer in his or her lifetime as a result of exposure to PAH in air.

    I.3  Comparison of the three procedures

    Each approach has its advantages and disadvantages (Table AI.18):

    I.3.1  Individual PAH approach

     Main advantages:

    *    Clearly defined chemical species are assessed.

    *    A good body of scientific literature is available to evaluate it.

    *    Not affected by variability in the composition of mixtures

    *    Relatively easy to apply in ambient environments affected by many
         sources

    *    Regulatory experience exists.

     Main disadvantages:

    *    May underestimate risk due to all PAH by considering only a few
         compounds

    *    Depends on extrapolation from animal models to humans

    *    Resource-intensive, as monitoring and analysis are required

    I.3.2  Comparative potency approach

     Main advantages:

    *    The risk of whole mixtures, rather than only a few components, is
         estimated.


        Table AI.18. Features and properties of three approaches to risk assessment for mixtures containing polycyclic aromatic
    hydrocarbons (PAH)

                                                                                                                                           

    Property or feature              Individual PAH approach            Comparative potency              Benzo[a]pyrene (BaP)
                                                                        approach                         surrogate approach
                                                                                                                                           

    Portion of mixture for which     Selected PAH in complex            Entire complex mixture           Unsubstituted PAH component
    cancer risk is estimated         mixtures account for only                                           of complex mixtures
                                     portion of risk of PAH fraction

    PAH included in assessment       Relatively few PAH out of          All PAH                          Most PAH, except PAH for which
                                     hundreds in environment                                             levels do not correlate well with
                                                                                                         those of BaP, e,g. substituted
                                                                                                         PAH

    Other toxicants included         None                               Toxicants present in source      Some, e.g. those present in
                                                                        mixture                          coke-oven emissions

    Assumption of additivity of      Yes: good evidence that            No: assumption not required      No: assumption not required
    components of mixture            risks of ill health due to
                                     exposure to PAH are
                                     approximately additive;
                                     little known about additivity
                                     of risks due to PAH and
                                     other compounds

    Incorporates directly            No: requires extrapolation         Yes: requires data from          Yes: potency derived from data
    available data on human          from animal models to              animal models to estimate        on potency of coke-oven
    cancer risk                      estimate potency of all PAH        potency of some mixtures         emissions in humans

    Assumption that mixtures         No: not applicable                 Yes: assumes mixtures from       Yes: assumes mixtures from
    from similar sources are                                            similar sources are about        similar sources are about
    about equipotent                                                    equipotent when expressed        equipotent when expressed
                                                                        in terms of mass of organic      in terms of mass of BaP;
                                                                        extractable material; basis      assumption supported by
                                                                        for assumption equivocal         available data

    Table AI.18. (continued)

                                                                                                                                           

    Property or feature              Individual PAH approach            Comparative potency              Benzo[a]pyrene (BaP)
                                                                        approach                         surrogate approach
                                                                                                                                           

    Assumption that mixtures         No: assumption not required        No: assumption not required      Yes: evidence from studies of
    from different sources are                                                                           animal models supports the
    about equipotent                                                                                     assumption; human data are
                                                                                                         equivocal and inadequate to
                                                                                                         validate the approach

    Assumption that environmental    No: assumption not required        Yes: evidence that PAH           Yes: evidence that PAH profile
    transformation                                                      profile relative to BaP does     relative to BaP does not vary
    processes do not change the                                         not vary enough to affect the    enough to affect estimated risk
    PAH profile enough to affect                                        estimated risk significantly     significantly
    the overall cancer risk
    significantly

    Assumption that the PAH          No: assumption not required        No: assumption not required      Yes: good evidence to
    profile of various mixtures is                                                                       support this assumption
    roughly comparable

    Suitable for ambient             Yes                                Requires apportioning of         Yes
    environments affected by                                            ambient mixture to multiple
    multiple sources                                                    sources

    Monitoring requirements          Selected PAH                       Organic extractable matter       BaP
                                                                        (this information is not
                                                                        usually reported and methods
                                                                        not standardized)

    Regulatory use                   Yes                                No                               Yes
                                                                                                                                           


    *    A good body of scientific literature is available to evaluate it.

    *    Takes advantage of existing data on human carcinogenicity

    *    Simple and requires inexpensive monitoring

     Main disadvantages:

    *    Does not define the contribution of PAH to estimated overall
         risk.

    *    Difficult to use for assessing speciated components of a mixture.

    *    Risk estimates require estimates of the contributions of
         individual sources to the levels of organic compounds in the
         ambient environment.

    *    The assumption that mixtures from the same source are associated
         with similar risks may not be supported by the available data.

    *    The levels of compounds extractable in organic solvents are not
         usually reported, and the analytical methods are not
         standardized.

    I.3.3  Benzo [a]pyrene surrogate approach

     Main advantages:

    *    Can be used to estimate risk of entire PAH component of a mixture

    *    Simple and based on a few testable assumptions

    *    Well supported by the available data

    *    Relatively easy and inexpensive to apply for regulatory purposes

    *    Regulatory experience exists.

     Main disadvantages:

    *    May result in overestimate of the risk of PAH within a mixture

    *    Some PAH, such as substituted ones, are not well represented by
         benzo [a]pyrene and must be considered separately.

    APPENDIX II

    SOME LIMIT VALUES

    Regulatory decisions about chemicals taken in a country can be fully
    understood only within the framework of the legislation of that
    country.  Furthermore, the regulations and guidelines of all countries
    are subject to change and should always be verified with the
    appropriate regulatory authorities before application.

    II.1  Exposure of the consumer

    The concentrations of some components of polycyclic aromatic
    hydrocarbons (PAH), especially benzo[a]pyrene, in air, water, and food
    and the use of PAH-containing technical products are regulated by law
    in many countries.  The available limit values are listed in Table
    AII.1.

    II.2  Occupational exposure

    Regulations for limits in the air at different workplaces are compiled
    in Table AII.2.  Only values for individual substances are given.  For
    some occupations, e.g. roofers and asphalt workers, limit values are
    not given for individual compounds but for the mixture of organic
    vapours released, e.g. bitumen fumes, coal-pitch, and coal-tar
    volatiles, that are soluble in benzene or hexane.  These limit values
    were not taken into account.

    II.3  Classification

    Only classifications based on a toxicological end-point are given
    here.  Those relevant to exposure in the workplace are shown in Table
    AII.3.  Especially in industrialized countries, classifications also
    exist for industrial emissions into air, water, and soil.  As these
    are special regulations, which differ from country to country, they
    are not included.

    Some classifications refer to technical mixtures with a high PAH
    content:

    II.3.1  European Union

    *    A maximum of 50 mg/kg benzo[a]pyrene will render coal-tar derived
         products carcinogenic (Directive 94/69/EC: European Economic
         Community, 1994a).

    *    For lubricant base oils analyzed by the legally defined method,
         the cut-off to define carcinogenicity is 3% of the extract
         containing mainly PAH, equivalent to 0.5-1 mg/kg benzo[a]pyrene
         (CONCAWE, 1994).


        Table AII.1. Limit values for consumer exposure to individual polycyclic aromatic hydrocarbons (PAH) in various countries

                                                                                                                              

    Country, year                      Compound                                       Limit value       Reference
                                                                                                                              

    Ambient air
    Italy                                                                                               EEC (1994)
       01.01.1996 to 31.12.1998        Benzo[a]pyrene                                 2.5 ng/m3
       From 01.01.1999                 Benzo[a]pyrene                                 1 ng/m3
    Former USSR, 1985                  Benzo[a]pyrene                                 1 ng/m3           Khesina (1994); UNEP
                                                                                                        (1994)
    Ambient water
    USA, 1984                          Sum of benzo[a]pyrene, benz[a]anthracene,      0.2 µg/litre      Slooff et al. (1989)
                                       benzofluoranthenes, chrysene, fluoranthene,
                                       indeno[1,2,3-cd]pyrene, anthracene, pyrene,
                                       dibenz[a]anthracene

    Former USSR, 1990                  Benzo[a]pyrene                                 0.005 µg/litre    UNEP (1994)
    EEC, 1980                          Sum of fluoranthene, benzo[b]fluoranthene,     1.2 µg/litre      Slooff et al. (1989)
                                       benzo[k]fluoranthene, benzo[a]pyrene,
                                       benzo[ghi]perylene, indeno[1,2,3-cd]pyrene

    Drinking-water
    WHO guideline, 1995                Benzo[a]pyrene                                 0.7 µg/litre      WHO (1996)

    EEC, 1980 (adopted by most         Sum of fluoranthene, benzo[b]fluoranthene,     0.2 µg/litre      EEC (1980)
    Member States and numerous         benzo[k]fluoranthene, benzo[a]pyrene,
    other European countries)          benzo[ghi]perylene, indeno[1,2,3-cd]pyrene

    Former Czechoslovakia, 1991        Sum of PAH expressed as fluoranthene           40 µg/litre       UNEP (1994)
                                       Benzo[a]pyrene                                 0.01 µg/litre

    Canada, 1991                       Benzo[a]pyrene                                 0.01 µg/litre     UNEP (1994)

    Netherlands, 1989                  Sum of fluoranthene, benzo[b]fluoranthene,     0.1 µg/litre      Slooff et al. (1989)
                                       benzo[k]fluoranthene, benzo[a]pyrene,
                                       benzo[ghi]perylene, indeno[1,2,3-cd]pyrene

    Table AII.1. (continued)

                                                                                                                              

    Country, year                      Compound                                       Limit value       Reference
                                                                                                                              

    Soil
    USSR, 1985                         Benzo[a]pyrene                                 0.02 mg/kg        UNEP (1994)

    Food
    EEC, 1991: use of flavourings      Benzo[a]pyrene                                 0.03 µg/kg        European Economic
    in food                                                                                             Community (1991)

    Germany, 1988: meat and meat       Benzo[a]pyrene                                 1 µg/kg           EEC (1988)
    products

    Italy, 1988: food and beverages    Benzo[a]pyrene                                 0.03 µg/kg        Anon. (1988)

    Other
    EEC, 1994: tar-oil products        Benzo[a]pyrene                                 50 mg/kg          Appendix I, No. 32 of
    for wood preservation                                                                               guideline 94/60/EG dated
                                                                                                        20.12.1994

    Germany, 1994: products for        Benzo[a]pyrene                                 5 mg/kg           Appendix to s1 of German
    wood preservation                                                                                   Chemicals Prohibition
                                                                                                        Directive (1994)
                                                                                                                              

    Former Czechoslovakia, 1991        Benzo[a]pyrene                                 Prohibited in     UNEP (1994)
                                                                                      cosmetics

    *    Any substance containing benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[j]fluoranthene, benzo[a]pyrene, or
         dibenz[a,h]anthracene at a concentration > 0.1% is regarded as carcinogenic (Annex I of Directive 67/548/EEC).
         It therefore cannot be supplied to the general public in the European Union (Directive 94/60/EC) but only to
         professional users (Von Meyerinck, 1995).

    Table AII.2. Limit values for individual polycyclic aromatic hydrocarbons at various workplaces

                                                                                                                             

    Country, year             Workplace or             Compound            Limit value             Reference
                              emission source
                                                                                                                             

    Finland, 1989             NR skin                  Benzo[a]pyrene      10 µg/m3 (TWA)          UNEP (1994)
                              absorption
    France, 1988              Production of carbon     Benzo[a]pyrene      0.15 µg/m3              Lafontaine et al.
                              electrodes                                                           (1990b)

    Germany, 1989             Cokeries, oven area      Benzo[a]pyrene      5 µg/m3                 German Federal
                                                                                                   Department for
                                                                                                   Worker Safety (1989)
                              Other workplaces         Benzo[a]pyrene      2 µg/m3                 German Federal
                                                                                                   Department for
                                                                                                   Worker Safety (1989)
    Sweden,1993               NR                       Benzo[a]pyrene      2 µg/m3 (LLV)           Swedish National
                                                                           20 µg/m3 (STV);         Board of Occupational
                                                                                                   Safety & Health (1994)
    Former USSR, 1990         NR                       Benzo[a]pyrene      0.15 µg/m3 (MAC)        UNEP (1994)
    Argentina, 1991           NR                       Naphthalene         50 mg/m3 (TWA; MPC)     UNEP (1994)
                                                                           75 mg/m3 (STEL; MPC)
    Bulgaria, 1985            NR                       Naphthalene         20 mg/m3 (MPC)          UNEP (1994)
    Canada, 1991              NR                       Naphthalene         50 mg/m3 (TWA; TLV)     UNEP (1994)
                                                                           75 mg/m3 (STEL; TLV)
    Germany, 1993             NR                       Naphthalene         50 mg/m3 (MAK)          American Conference of
                                                                                                   Governmental Industrial
                                                                                                   Hygienists (1995)
    Hungary, 1985             NR                       Naphthalene         20 mg/m3 (TWA; MAC)     UNEP (1994)
                                                                           100 mg/m3 (STEL: MAC)
    Italy, 1991               NR                       Naphthalene         50 µg/m3                EEC (1991)
    Mexico, 1991              NR                       Naphthalene         50 mg/m3 (TWA; MXL)     UNEP (1994)
                                                                           75 mg/m3 (STEL; MXL)
    Poland, 1985              NR                       Naphthahne          20 mg/m3 (TWA; MPC)     UNEP (1994)
    Romania, 1985             NR                       Naphthalene         30 mg/m3 (TWA; MPC)     UNEP (1994)
                                                                           40 mg/m3 (MPC)

    Table AII.2. (continued)

                                                                                                                             

    Country, year             Workplace or             Compound            Limit value             Reference
                              emission source
                                                                                                                             

    Sweden, 1991              NR; skin                 Naphthalene         0.2 mg/m3 (TWA; HLV)    UNEP (1994)
                              absorption                                   0.6 mg/m3 (STEL; HLV)
    Switzerland, 1987         NR                       Naphthalene         50 mg/m3 (TWA; MAK)     UNEP (1994)
    United Kingdom, 1992      NR                       Naphthalene         50 mg/m3 (TWA; OES)     UNEP (1994)
                                                                           75 mg/m3 (STEL; OES)
    USA, 1993                 NR                       Naphthalene         52 mg/m3 (TWA)          American Conference of
                                                                           79 mg/m3 (STEL)         Governmental Industrial
                                                                                                   Hygienists (1995)
    Former USSR, 1993         NR                       Naphthalene         20 mg/m3                American Conference of
                                                                                                   Governmental Industrial
                                                                                                   Hygienists (1995)
    Former Yugoslavia,1985    NR                       Naphthalene         50 mg/m3 (TWA; MAC)     UNEP (1994)
    USA, 1993                 Cokeries, oven area      Phenylene           0.1 mg/m3 (TWA)         American Conference of
                                                                                                   Governmental Industrial
                                                                                                   Hygienists (1995)
    Former USSR, 1989         NR                       Phenylene           0.8 mg/m3 (MAC)         UNEP (1994)
    USA, 1993                 NR                       Pyrene              0.1 mg/m3 (TWA)         American Conference of
                                                                                                   Governmental Industrial
                                                                                                   Hygienists (1995)
    Former USSR, 1989         NR                       Pyrene              0.03 mg/m3 (MAC)        UNEP (1994)
                                                                                                                             

    NR, not reported; HLV, hygienic limit value; LLV, level limit value; MAC, maximum allowable concentration; MAK, maximum
    workpace concentration; MPC, maximum permissible concentration; MXL, maximum limit; OES, occupational exposure standard;
    TWA, time-weighted average; STEL, short-time exposure level; STV, short-term value; TLV, threshold limit value

    Table AII.3. Toxicological classifications of polycyclic aromatic hydrocarbons with regard to exposure in
    the workplace

                                                                                                               

    Compound                   ACGIHa (TLV)                  IARCb      EUc                           German
                                                             MAKd
                               TWA (8 h)    STEL (15 min)
                                                                                                               

    Benz[a]anthracene          A2           A2               2A         Carcinogenic, category 2      A2
    Benzo[b]fluoranthene       A2           A2               2B         Carcinogenic, category 2      A2
    Benzo[j]fluoranthene                                     2B         Carcinogenic, category 2      A2
    Benzo[k]fluoranthene                                     2B         Carcinogenic, category 2      A2
    Benzo[a]pyrene             A2                            2A         Carcinogenic, category 2      A2
    Chrysene                   A2           A2               3          Carcinogenic, category 2      A2
    Dibenz[a,h]anthracene                                    2A         Carcinogenic, category 2      A2
    Dibenzo[a,e]pyrene                      2B                                                        A2
    Dibenzo[a,h]pyrene                      2B                                                        A2
    Dibenzo[a,i]pyrene                      2B                                                        A2
    Dibenzo[a,l]pyrene                      2B                                                        A2
    Indeno[1,2,3-cd]pyrene                  2B                                                        A2
    5-Methylchrysene                        2B
                                                                                                               

    a American Conference of Governmental Industrial Hygienists (1995)
    b IARC (1987) see Section 12
    c EU-Rili (Appendix I)
    d German Dangerous Chemicals Directive (1995)


    II.3.2  USA

    *    Coal-tar and coal-pitch volatiles, which are mixtures of organic
         vapours with high PAH levels, are classified as A1, confirmed
         human carcinogens (American Conference of Governmental Industrial
         Hygienists, 1995).

    *    Diesel exhaust is considered to be a suspected human carcinogen
         (A2), but notice has been given of intended changes (American
         Conference of Governmental Industrial Hygienists, 1995).


    13.  REFERENCES

    Aamot E, Krane J, & Steiness E (1987) Determination of trace amounts
    of polycyclic aromatic hydrocarbons in soil. Fresenius Z Anal Chem,
    328: 569-571.

    Abarzua AS, Jonas L, Putzke HP, & Wittenburg E (1983) [Influence of
    3,4-benzopyrene on the ultrastructure of the green alga  Scenedesmus
    quadricauda.] Arch Protistenk, 127: 103-113 (in German).

    Abbott DW, Moody RL, Mann RM, & Vo-Dinh T (1986) Synchronous
    luminescence screening for polynuclear aromatic compounds in
    environmental samples collected at a coal gasification process
    development unit. Am Ind Hyg Assoc J, 47: 379-385.

    Abdo KM, Eustis SL, McDonald M, Jokinen MP, Adkins B, & Haseman JK
    (1992) Naphthalene: A respiratory tract toxicant and carcinogen for
    mice. Inhal Toxicol, 4: 393-409.

    Abe S & Sasaki M (1977a) Studies on chromosomal aberrations and sister
    chromatid exchanges induced by chemicals. Proc Jpn Acad, 53: 46-49.

    Abe S & Sasaki M (1977b) Chromosome aberrations and sister chromatid
    exchanges in Chinese hamster cells exposed to various chemicals. J
    Natl Cancer Inst, 58: 1635-1641.

    Abe S, Nemoto N, & Sasaki M (1983a) Sister-chromatid exchange
    induction by indirect mutagens/carcinogens, aryl hydrocarbon
    hydroxylase activity and benzo [a]pyrene metabolism in cultured human
    hepatoma cells. Mutat Res, 109: 83-90.

    Abe S, Nemoto N, & Sasaki M (1983b) Comparison of aryl hydrocarbon
    hydroxylase activity and inducibility of sister-chromatid exchanges by
    polycyclic aromatic hydrocarbons in mammalian cell lines. Mutat Res,
    122: 47-51.

    Abell CW & Heidelberger C (1962) Interaction of carcinogenic
    hydrocarbons with tissues. VIII. Binding of tritium-labelled
    hydrocarbons to the soluble proteins of mouse skin. Cancer Res, 22:
    931-946.

    Abernethy S, Bobra AM, Shiu WY, Wells PG, & Mackay D (1986) Acute
    lethal toxicity of hydrocarbons and chlorinated hydrocarbons to two
    planktonic crustaceans: The key role of organism-water partitioning.
    Aquat Toxicol, 8: 163-174.

    Abramson MJ, Wlodarczyl JH, Saunders NA, & Hensley MJ (1989) Does
    aluminum smelting cause lung disease? Am Rev Respir Dis, 139:
    1042-1057.

    Achard S, Perderiset M, & Jaurand MC (1987) Sister chromatid exchanges
    in rat pleural mesothelial cells treated with crocidolite,
    attapulgite, or benzo 3-4 pyrene. Br J Ind Med, 44: 281-283.

    Acheson MA, Harrison RM, Perry R, & Wellings RA (1976) Factors
    affecting the extraction and analysis of polynuclear aromatic
    hydrocarbons in water. Water Res, 10: 207-212.

    Adamson RH & Sieber SM (1983) Chemical carcinogenesis studies in
    nonhuman primates. In: Langenbach R, Nesnow S, & Rice JM ed. Organ and
    species specificity in chemical carcinogenesis. New York, Plenum
    Press, pp 129-156.

    Adkins B Jr, van Stee EW, Simmons JE, & Eustis SL (1986) Oncogenic
    response of strain A/J mice to inhaled chemicals. J Toxicol Environ
    Health, 17: 311-322.

    Adler ID & Ingwersen I (1989) Evaluation of chromosomal aberration in
    bone marrow of 1C3F1 mice. Mutat Res, 224: 343-345.

    Adler ID, Kliesch U, & Kiefer F (1989) Clastogenic effects of
    benzo [a]pyrene in postimplantation embryos with different genetic
    background. Teratog Carcinog Mutag, 6: 383-392.

    Adlkofer F, Scherer G, Von Maltzan C, Von Meyerinck L, Jarczyk L,
    Martin F, & Grimmer G (1990) Dietary influences on urinary excretion
    of hydroxyphenanthrenes, thioethers and mutagenicity in man. In:
    Vainio H, Sorsa M, & McMichael AJ ed. Complex mixtures and cancer
    risk. Lyon, International Agency for Research on Cancer, pp 415-420
    (IARC Scientific Publications No. 104).

    Agarwal R & Mukhtar H (1991) Metabolism of benzo [a]pyrene and
    benzo [a]pyrene 7,8-dihydrodiol catalyzed by human and rodent
    epidermal lipoxygenase. Proc Am Assoc Cancer Res, 32: 117.

    Agarwal SK, Sayer JM, Yeh HJC, Pannell LK, Hilton BD, Pigott MA,
    Dipple A, Yagi H, & Jerina DM (1987) Chemical characterization of DNA
    adducts derived from the configurationally isomeric
    benzo [c]phenanthrene-3,4-diol 1,2-epoxides. J Am Chem Soc, 109:
    2497-2504.

    Agarwal R, Medrano EE, Khan IU, Nordlund JJ, & Mukhtar H (1991)
    Metabolism of benzo(a)pyrene by human melanocytes in culture.
    Carcinogenesis, 12: 1963-1966.

    Agency for Toxic Substances and Disease Registry (1990) Toxicological
    profile for polycyclic aromatic hydrocarbons. Atlanta, Georgia, US
    Department of Health and Human Services, 231 pp (Report No. TP-90-20).

    Agrelo C & Amos H (1981) DNA repair in human fibroblasts. In: de
    Serres FJ & Ashby J ed. Evaluation of short-term tests for
    carcinogens. Report of the international collaborative programme. New
    York, Elsevier North Holland, pp 528-532 (in Mutation Research, Volume
    1).

    Ahland E & Mertens H (1980) [PAH emissions from coal fires -
    Collection, analysis, results. Air pollution from polycyclic aromatic
    hydrocarbons - Registration and evaluation.] Düsseldorf, VDI-Verlag
    GmbH, pp 107-111 (VDI Report No. 358) (in German).

    Ahland E, Borneff J, Brune H, Grimmer G, Habs M, Heinrich U, Hermann
    P, Misfeld J, Mohr U, Pott F, Schmähl D, Thyssen J, & Timm J (1985)
    [Air pollution and cancer. Investigation of hazardous constituents
    from various emission sources and their carcinogenic impact.] Münch
    Med Wochenschr, 127: 218-221 (in German).

    Aitio A (1974) Different elimination and effect on mixed function
    oxidase of 20-methylcholanthrene after intragastric and
    intraperitoneal administration. Res Commun Chem Pathol Pharmacol, 9:
    701-710.

    Albaiges J, Bayona JM, Fernandez P, Grimalt J, Rosell A, & Simo R
    (1991) Vaporparticle partitioning of hydrocarbons in western
    Mediterranean urban and marine atmospheres. Mikrochim Acta, 2: 13-27.

    Alben K (1980) Coal tar coatings of storage tanks. A source of
    contamination of the potable water supply. Environ Sci Technol, 14:
    468-470.

    Albert RE, Lewtas J, Nesnow S, Thorslund TW, & Anderson E (1983)
    Comparative potency method for cancer risk assessment: Application to
    diesel particulate emissions. Risk Anal, 3: 101-117.

    Albert RE, Miller ML, Cody TE, Andringa A, Shukla R, & Baxter CS
    (1991a) Benzo [a]pyrene-induced skin damage and tumor promotion in
    the mouse. Carcinogenesis, 12: 1273-1280.

    Albert RE, Miller ML, Cody TE, Barkley W, & Shukla R (1991b) Cell
    kinetics and benzo [a]pyrene DNA adducts in mouse skin tumorigenesis.
    In: Butterworth BE ed. Chemically induced cell proliferation:
    Implications for risk assessment. New York, Wiley-Liss, Inc., pp 115-
    122 (Progress in Clinical and Biological Research, Volume 369).

    Albini A, Colacci A, Melchiori A, Carlone S, Nanni P, Lollini PL, de
    Giovanni C, Nicoletti G, Grilli S, & Parodi S (1991) Chemical
    carcinogens in tumor progression. Induction of invasive and metastatic
    potential in 3T3 cells by benzo [a]pyrene transformation. Proc Am
    Assoc Cancer Res, 32: 153.

    Alden RW III & Butt AJ (1987) Statistical classification of the
    toxicity and polynuclear aromatic hydrocarbon contamination of
    sediments from a highly industrialized seaport. Environ Toxicol Chem,
    6: 673-684.

    Aldis H, Osborn J, & Wolf F (1983) Investigation of soil and water
    contamination at Western Processing, King County, Washington. In:
    National Conference of Management of Uncontrolled Hazardous Waste
    Sites, Silver Spring, 31 October-2 November 1982, Washington DC,
    Hazardous Materials Control Research Institute, pp. 43-53.

    Alfheim I & Ramdahl T (1984) Contribution of wood combustion to indoor
    air pollution as measured by mutagenicity in  Salmonella and
    polycyclic aromatic hydrocarbon concentration. Environ Mutagen, 6:
    121-130.

    Alfheim I & Wikström L (1984) Air pollution from aluminium smelting
    plants. I. The emission of polycyclic aromatic hydrocarbons and of
    mutagens from an aluminium smelting plant using the Söderberg process.
    Toxicol Environ Chem, 8: 55-72.

    Alfheim I, Becher G, Hongslo JK, & Ramdahl T (1984) Mutagenicity
    testing of high performance liquid chromatography fractions from wood
    stove emission samples using a modified Salmonella assay requiring
    smaller sample volumes. Environ Mutagen, 6: 91-102.

    Allen JA & Coombs MM (1980) Covalent binding of polycyclic aromatic
    hydrocarbons to mitochondrial and nuclear DNA. Nature, 287: 244-245.

    Allen-Hoffmann BL & Rheinwald JG (1984) Polycyclic aromatic
    hydrocarbon mutagenesis of human epidermal keratinocytes in culture.
    Proc Natl Acad Sci USA, 81: 7802-7806.

    Allred PM & Giesy JP (1985) Solar radiation-induced toxicity of
    anthracene to  Daphnia pulex. Environ Toxicol Chem, 4: 219-226.

    Alsberg T, Stenberg U, Westerholm R, Strandell M, Rannug U, Sundvall
    A, Romert L, Bernson V, Pettersson B, Toftgard R, Franzen B, Jansson
    M, Gustafsson JC, Egebäck KE & Tejle G (1985) Chemical and biological
    characterization of organic material from gasoline exhaust particles.
    Environ Sci Technol, 19: 43-50.

    Al-Yakoob S, Saeed T, & Al-Hashash H (1993) Polycyclic aromatic
    hydrocarbons in edible tissue of fish from the Gulf after 1991 oil
    spill. Mar Pollut Bull, 27: 297-301.

    Alzieu P, Cassand P, Colin C, Grolier P, & Narbonne JF (1987) Effect
    of vitamins A, C and glutathione on the mutagenicity of
    benzo [a]pyrene mediated by S9 from vitamin A-deficient rats. Mutat
    Res, 192: 227-231.

    Amacher DE & Paillet SC (1982) Hamster hepatocyte-mediated activation
    of procarcinogens to mutagens in the L5178Y/TK mutation assay. Mutat
    Res, 106: 305-316.

    Amacher DE & Paillet SC (1983) The activation of procarcinogens to
    mutagens by cultured rat hepatocytes in the L5178Y/TK mutation assay.
    Mutat Res, 113: 77-88.

    Amacher D & Turner GN (1980) Promutagen activation by rodent-liver
    postmitochondrial fractions in the L5178Y/TK cell mutation assay.
    Mutat Res, 74: 485-501.

    Amacher DE, Paillett SC, Turner GN, Ray VA, & Salsburg DS (1980) Point
    mutations at the thymidine kinase locus in L5178Y mouse lymphoma
    cells. II. Test validation and interpretation. Mutat Res, 72: 447-474.

    American Conference of Governmental Industrial Hygienists (1995) 1995-
    1996 Threshold Limit Values (TLVs) for chemical substances and
    physical agents and Biological Exposure Indices (BEIs). Cincinnati,
    Ohio, 138 pp.

    Amin S, Hecht SS, LaVoie E, & Hoffmann D (1979) Synthesis and
    mutagenicity of 5,11-dimethylchrysene and some methyl-oxidized
    derivatives of 5-methylchrysene. J Med Chem, 22: 1336-1340.

    Amin S, Juchatz A, Furuya K, & Hecht SS (1981) Effects of fluorine
    substitution on the tumor initiating activity and metabolism of
    5-hydroxymethylchrysene, a tumorigenic metabolite of 5-methylchrysene.
    Carcinogenesis, 2: 1027-1032.

    Amin S, Huie K, & Hecht SS (1985a) Mutagenicity and tumor-initiating
    activity of methylated benzo [b]fluoranthenes. Carcinogenesis, 6:
    1023-1025.

    Amin S, Huie K, Melikian AA, Leszczynska JM, & Hecht SS (1985b)
    Comparative metabolic activation in mouse skin of the weak carcinogen
    6-methylchrysene and the strong carcinogen 5-methylchrysene. Cancer
    Res, 45: 6406-6412.

    Amin S, Huie K, Balanikas G, Hecht SS, Pataki J, & Harvey RG (1987)
    High stereoselectivity in mouse skin metabolic activation of
    methylchrysenes to tumorigenic dihydrodiols. Cancer Res, 47:
    3613-3617.

    Amin S, Hecht SS, DiRaddo P, & Harvey RG (1990) Comparative tumor
    initiating activities of cyclopentano and methyl derivatives of
    5-methylchrysene and chrysene. Cancer Lett, 51: 17-20.

    Amin S, Weyand EH, Huie K, Boger E, Neuber E, Hecht SS, & Lavoie EJ
    (1991a) Effects of fluorine substitution on benzo(b)fluoranthene
    tumorgenicity and DNA adduct formation in mouse skin. In: Cooke M,
    Loening K, & Merritt J ed. Polynuclear aromatic hydrocarbons:
    Measurements, means and metabolism. Columbus, Ohio, Battelle Press, pp
    25-35.

    Amin S, Misra B, Braley J, & Hecht SS (1991b) Comparative
    tumorigenicity in newborn mice of chrysene and
    5-alkylchrysene-1,2-diol-3,4-epoxides. Cancer Lett, 58: 115-118.

    Amin S, Desai D, & Hecht SS (1992) Comparative tumorigenicity of
    dimethylchrysenes in mouse skin. Chem Res Toxicol, 5: 237-241.

    Amin S, Desai D, & Hecht SS (1993) Tumor-initiating activity on mouse
    skin of bay region diol-epoxides of 5,6-dimethylchrysene and
    benzo(c)phenanthrene. Carcinogenesis, 14: 2033-2037

    Andelman JB & Suess MJ (1970) Polynuclear aromatic hydrocarbons in the
    water environment. Bull World Health Organ, 43: 479-508.

    Anderson JW, Neff JM, Cox BA, Tatem ME, & Hightower GM (1974) The
    effects of oil on estuarine animals: Toxicity, uptake and depuration,
    respiration. In: Vernberg FJ & Vernberg WB ed. Pollution and
    physiology of marine organisms. New York, Academic Press, pp 285-310.

    Anderson R, Giam CS, Ray LE, & Tripp MR (1981) Effects of
    environmental pollutants on immunological competency of the clam
     Mercenaria mercenaria: Impaired bacterial clearance. Aquat Toxicol,
    1: 187-195.

    Anderson LM, Priest LJ, Deschner EE, & Budinger JM (1983) Carcinogenic
    effects of intracolonic benzo [a]pyrene in b-naphthoflavone-induced
    mice. Cancer Lett, 20: 117-123.

    Anderson JW, Neff JM, & Boehm PD (1986) Sources, fates and effects of
    aromatic hydrocarbons in the Alaskan marine environment with
    recommendations for monitoring strategies. Sequim, Washington,
    Battelle Pacific Northwest Laboratories, 230 pp (Report No.
    EPA/600/3-86-018).

    Andersson K, Levin J-O, & Nilsson C-A (1983) Sampling and analysis of
    particulate and gaseous polycyclic aromatic hydrocarbons from coal tar
    sources in the working environment. Chemosphere, 12: 197-207.

    Andjelkovich DA, Mathew RM, Richardson RB, & Levine RJ (1990)
    Mortality of iron foundry workers: I. Overall findings. J Occup Med,
    32: 529-540.

    Andrews AW, Thibault LH, & Lijinsky W (1978) The relationship between
    carcinogenicity and mutagenicity of some polynuclear hydrocarbons.
    Mutat Res, 51: 311-318.

    Andrews FJ, Halliday GM, & Muller HK (1991) A role for prostaglandins
    in the suppression of cutaneous cellular immmunity and tumor
    development in benzo(a)pyrene- but not
    dimethylbenz(a)anthracene-treated mice. Clin Exp Immunol, 85: 9-13.

    Andrianova MM (1971) Transplacental action of 3-methylcholanthrene and
    benz [a]pyrene on four generations of mice. Bull Exp Biol Med, 71:
    677-680.

    Anziulewicz JA, Dick HJ, & Chiarulli EE (1959) Transplacental
    naphthalene poisoning. Am J Obstet Gynecol, 9: 519-521.

    Aoyama T, Gonzalez FJ, & Gelboin HV (1989) Human cDNA-expressed
    cytochrome P450 1A2: Mutagen activation and substrate specificity. Mol
    Carcinog, 2: 192-198.

    Arce GT, Allen JW, Doerr CL, Elmore E, Hatch GG, Moore MM, Sharief Y,
    Grunberger D, & Nesnow S (1987) Relationships between benzo(a)pyrene-
    DNA adduct levels and genotoxic effects in mammalian cells. Cancer
    Res, 47: 3388-3395.

    Arey J, Zielinska B, Atkinson R, & Winer AM (1987) Polycyclic aromatic
    hydrocarbon and nitroarene concentrations in ambient air during a
    wintertime high-NOx episode in the Los Angeles basin. Atmos Environ,
    21: 1437-1444.

    Arey J, Zielinska B, Atkinson R, & Winer AM (1991) Analysis of PAH and
    their nitroderivates in ambient air. In: Cooke M, Loening K, & Merritt
    J ed. Polynuclear aromatic hydrocarbons: Measurement, means, and
    metabolism. Columbus, Ohio, Battelle Press, pp 51-67.

    Armstrong B, Tremblay C, Baris D, & Thériault G (1994) Lung cancer
    mortality and polynuclear aromatic hydrocarbons: A case-cohort study
    of aluminum production workers in Arvida, Québec, Canada. Am J
    Epidemiol, 139: 250-262.

    Ashby J & Kilbey B (1981) Summary report on the performance of
    bacterial repair, phage induction, degranulation, and nuclear
    enlargement assays. In: de Serres FJ & Ashby J ed. Evaluation of
    short-term tests for carcinogens. Report of the international
    collaborative programme. New York, Elsevier North Holland, pp 33-48
    (Progress in Mutation Research, Volume 1).

    Assennato G, Ferri GM, Foà V, Strickland P, Poirier M, Pozzoli L, &
    Cottica D (1993a) Correlation between PAH airborne concentration and
    PAH-DNA adducts levels in coke-oven workers. Int Arch Occup Environ
    Health, 65: S143-S145.

    Assennato G, Ferri GM, Tockman MS, Poirier MC, Schoket B, Porro A,
    Corrado V, & Strickland PT (1993b) Biomarkers of carcinogen exposure
    and cancer risk in a coke plant. Environ Health Perspectives, 99: 237-
    239.

    Association of Rhine and Meuse Water Supply Companies (1976) Annual
    Report, Part A, The Rhine, Amsterdam, 82 pp.

    Association of Rhine and Meuse Water Supply Companies (1977) Annual
    Report, Part A, The Rhine, Amsterdam, 54 pp.

    Association of Rhine and Meuse Water Supply Companies (1978) Annual
    Report, Part A, The Rhine, Amsterdam, 55 pp.

    Association of Rhine and Meuse Water Supply Companies (1979) Annual
    Report, Part A, The Rhine, Amsterdam, 60 pp.

    Association of Rhine and Meuse Water Supply Companies (1987-88) Annual
    Report, Part A, The Rhine, Amsterdam, 164 pp.

    Association of Rhine and Meuse Water Supply Companies (1989) Annual
    Report, Part A, The Rhine, Amsterdam, 108 pp.

    Association of Rhine and Meuse Water Supply Companies (1990) Annual
    Report, Part A, The Rhine, Amsterdam, 92 pp.

    Atkinson R (1987) Structure-activity relationship for the estimation
    of rate constants for the gas-phase reactions of OH radicals with
    organic compounds. Int J Chem Kinet, 19: 799-828.

    Atkinson, R (1989) Kinetics and mechanisms of the gas-phase reactions
    of the hydroxyl radical with organic compounds (26) naphthalene. J
    Phys Chem Ref Data Monogr, 1: 237.

    Atkinson R & Arey J (1994) Atmospheric chemistry of gas-phase
    polycylic aromatic hydrocarbons: Formation of atmospheric mutagens.
    Environ Health Perspectives, 102 (suppl 4): 117-126.

    Atkinson R & Carter WPL (1984) Kinetics and mechanisms of gas-phase
    ozone reaction with organic compounds under atmospheric conditions.
    Chem Rev, 84: 437-470.

    Atkinson R, Arey J, Zielinska B, & Winer AM (1991) Atmospheric loss
    processes for PAH and formation of nitroarenes. In: Cooke M, Loening
    K, & Merritt J ed. Polynuclear aromatic hydrocarbons: Measurement,
    means, and metabolism. Columbus, Ohio, Batelle Press, pp 69-88.

    Autrup H (1979) Separation of water-soluble metabolites of
    benzo [a]pyrene formed by cultured human colon. Biochem Pharmacol,
    28: 1727-1730.

    Autrup JL & Autrup H (1986) Metabolism of tobacco specific carcinogens
    in cultured rat buccal mucosa epithelial cells. Acta Pharmacol
    Toxicol, 59: 339-344.

    Autrup H & Harris CC (1983) Metabolism of chemical carcinogens by
    human tissues. In: Harris CC & Autrup H ed. Human carcinogenesis. New
    York, Academic Press, pp 169-194.

    Autrup H, Harris CC, Stoner GD, Selkirk JK, Schafer PW, & Trump B
    (1978a) Metabolism of [3H]benzo [a]pyrene by cultured human bronchus
    and cultured human pulmonary alveolar macrophages. Lab Invest, 38:
    217-224.

    Autrup H, Harris CC, Trump B, & Jeffrey AM (1978b) Metabolism of
    benzo [a]pyrene and identification of the major benzo [a]pyrene-DNA
    adducts in cultured human colon. Cancer Res, 38: 3689-3696.

    Autrup H, Harris CC, Schafer PW, Trump B, Stoner GD, & Hsu IC (1979)
    Uptake of benzo [a]pyrene-ferric oxide particulates by human
    pulmonary macrophages and release of benzo [a]pyrene and its
    metabolites. Proc Soc Exp Biol Med, 161: 280-284.

    Autrup H, Wefald FC, Jeffrey AM, Tate H, Schwartz RD, Trump B, &
    Harris CC (1980) Metabolism of benzo [a]pyrene by cultured
    tracheobronchial tissues from mice, rats, hamsters, bovines and
    humans. Int J Cancer, 25: 293-300.

    Awogi T & Sato T (1989) Micronucleus test with benzo [a]pyrene using
    a single peroral administration and intraperitoneal injection in males
    of the MS/Ae and CDl-1 mouse strains. Mutat Res, 223: 353-356.

    Ayrton AD, McFarlane M, Walker R, Neville S, & Ioannides C (1990) The
    induction of P450 I proteins by aromatic amines may be related to
    their carcinogenic potential. Carcinogenesis, 11: 803-810.

    Babich H, Sardana MK, & Borenfreund E (1988) Acute cytotoxicities of
    polynuclear aromatic hydrocarbons determined  in vitro with the human
    liver tumor cell line, HepG2. Cell Biol Toxicol, 4: 295-309.

    Babson JR, Russo-Rodriguez SE, Rastetter WR, & Wogan GG (1986a)
     In vitro DNA-binding of microsomally-activated fluoranthene:
    Evidence that the major product is a fluoranthrene N2-deoxyguanosine
    adduct. Carcinogenesis, 7: 859-865.

    Babson JR, Russo-Rodriguez SE, Wattley RV, Bergstein PL, Rastetter WH,
    Liber HL, Andon BM, Thilly WG, & Wogan GN (1986b) Microsomal
    activation of fluoranthene to mutagenic metabolites. Toxicol Appl
    Pharmacol, 85: 355-366.

    Bachmann S, Stolz W, Kantor W, & Kuhnt G (1994) [Texte 6:
    Implementation of the soil information system for a survey of forest
    soils in Germany.] Berlin, Ministry of the Environment, 445 pp (UBA
    Report No. 93-147) (in German)

    Backer JM & Weinstein IB (1980) Mitochondrial DNA is a major cellular
    target for a dihydrodiol-epoxide derivative of benzo [a]pyrene.
    Science, 209: 297-299.

    Badger GM, Cook JW, Hewett CL, Kennaway EL, Kennaway NM, Martin RH, &
    Robinson AM (1940) The production of cancer by pure hydrocarbons. Part
    V. Proc R Soc Med, 129: 439-474.

    Badger GM, Cook JW, Hewett CL, Kennaway EL, Kennaway NM, & Martin RH
    (1942) The production of cancer by pure hydrocarbons. VI. Proc R Soc
    Lond, 131: 170-182.

    Baek SO, Field RA, Goldstone ME, Kirk PW, Lester JN, & Perry R (1991)
    A review of atmospheric polycyclic aromatic hydrocarbons: Sources,
    fate and behavior. Water Air Soil Pollut, 60: 279-300.

    Baek SO, Goldstone ME, Kirk PWW, Lester JN, & Perry R (1992)
    Concentrations of particulate and gaseous polycyclic aromatic
    hydrocarbons in London air following a reduction in the lead content
    of petrol in the United Kingdom. Sci Total Environ, 111: 169-199.

    Bagg J, Smith D, & Maher WA (1981) Distribution of polycyclic aromatic
    hydrocarbons in sediments from estuaries of south-eastern Australia.
    Aust J Mar Freshwater Res, 32: 65-73.

    Bailey GS, Goeger DE, & Hendricks J (1989) Factors influencing
    experimental carcinogenesis in laboratory fish models. In: Varanasi U
    ed. Metabolism of polycyclic aromatic hydrocarbons in the aquatic
    environment. Boca Raton, Florida, CRC Press, pp 253-268.

    Baird WM & Diamond L (1978) Metabolism and DNA binding of polycyclic
    aromatic hydrocarbons by human diploid fibroblasts. Int J Cancer, 22:
    189-195.

    Baird WM, Salmon CP, & Diamond L (1984) Benzo(e)pyrene-induced
    alterations in the metabolic activation of benzo(a)pyrene and
    7,12-dimethylbenz(a)anthracene by hamster embryo cells. Cancer Res,
    44: 1445-1452.

    Baker JE & Eisenreich SJ (1990) Concentrations and fluxes of
    polycyclic aromatic hydrocarbons and polychlorinated biphenyls across
    the air-water interface of Lake Superior. Environ Sci Technol, 24:
    342-352.

    Baker RSU, Bonin AM, Stupans I, & Holder GM (1980) Comparison of rat
    and guinea pig as sources of the S9 fraction in the
    Salmonella/mammalian microsome mutagenicity test. Mutat Res, 71: 43-
    52.

    Bakke J, Struble C, Gustafsson JA, & Gustafsson B (1983) Enterohepatic
    circulation and catabolism of mercapturic acid pathway metabolites of
    naphthalene. In: Rydstrom J, Montelius J, & Bengtsson M. ed.
    Extrahepatic drug metabolism and chemical carcinogenesis. Amsterdam,
    Elsevier Science Publishers, pp 257-266.

    Baranova LN, Shendrikova IA, Aleksandrov VA, Likhachev AY,
    Ivanov-Galitsin MN, Dikun PP, & Napalkov NP (1976) [On the mechanism
    of penetration of carcinogenic polycyclic hydrocarbons through the
    placenta of rats and mice.] Dokl Akad Nauk SSSR, 228: 733-736 (in
    Russian).

    Barat F (1991) [Measures for clean air at the workplace.]
    Staub-Reinhalt Luft, 51: 243-246 (in German).

    Barbieri O, Ognio E, Rossi O, Astigiano S, & Rossi L (1986)
    Embryotoxicity of benzo(a)pyrene and some of its synthetic derivatives
    in Swiss mice. Cancer Res, 46: 94-98.

    Barfknecht TR, Andon BM, Thilly WG, & Hites RA (1981) Soot and
    mutation in bacteria and human cells. In: Cooke M & Dennis AJ ed.
    Polynuclear aromatic hydrocarbons: Chemical analysis and biological
    fate. Columbus, Ohio, Battelle Press, pp 231-242.

    Barfknecht TR, Hites RA, Cavaliers EL, & Thilly WG (1982) Human cell
    mutagenicity of polycyclic aromatic hydrocarbon components of diesel
    emissions. Dev Toxicol Environ Sci, 10: 277-294.

    Barnsley EA (1975) The bacterial degradation of fluoranthene and
    benzo [a]pyrene. Can J Microbiol, 21: 1004-1008.

    Barratt RW & Tatum EL (1958) Carcinogenic mutagens. Ann NY Acad Sci,
    71: 1072-1084.

    Barrows ME, Petrocelli SR, Macek KJ, & Carroll JJ (1980)
    Bioconcentration and elimination of selected water pollutants by
    bluegill sunfish  Lepomis macrochirus. In: Dynamic, exposure, hazard
    assessment of toxic chemicals. Michigan, Ann Arbor Science Publishers,
    pp 379-392.

    Barry G & Cook CW (1934) A comparison of the action of some polycyclic
    aromatic hydrocarbons in producing tumours of connective tissue. Am J
    Cancer, 20: 58-69.

    Barry G, Cook JW, Haslewood AD, Hewett CL, Hieger I, & Kennaway EL
    (1935) The production of cancer by pure hydrocarbons. Part III. Proc R
    Soc Med, 117: 318-351.

    Bartczak AW, Sangaiah S, Ball LM, Warren SH, & Gold A (1987) Synthesis
    and bacterial mutagenicity of the cyclopenta oxides of the four
    cyclopenta-fused isomers of benzanthracene. Mutagenesis, 2: 101-105.

    Bartle KD (1985) Recent advances in the analysis of polycyclic
    aromatic compounds by gas chromatography. In: Bjorseth A & Ramdahl T
    ed. Handbook of polycyclic aromatic hydrocarbons. Volume 2. Emission
    sources and recent progress in analytical chemistry. New York, Marcel
    Dekker, pp 193-236.

    Bartosek I, Guaitani A, Modica R, Fiume M, & Urso R (1984) Comparative
    kinetics of oral benz(a)anthracene, chrysene und triphenylene in rats:
    Study with hydrocarbon mixtures. Toxicol Lett, 23: 333-339.

    Bartsch H, Malaveille C, Camus AM, Martel-Planche G, Brun G,
    Hautefeuille A, Sabadie N, Barbin A, Kuroki T, Drevon C, Piccoli C, &
    Montesano R (1980) Validation and comparative studies on 180 chemicals
    with  S. typhimurium strains and V79 Chinese hamster cells in the
    presence of various metabolizing systems. Mutat Res, 76: 1-50.

    Basler A, Herbold B, Peter S, & Röhrborn G (1977) Mutagenicity of
    polycyclic hydrocarbons. II. Monitoring genetical hazards of chrysene
     in vitro and  in vivo. Mutat Res, 48: 249-254.

    Bastian MV & Toetz DW (1982) Effect of eight polynuclear hydrocarbons
    on growth of  Anabaena flos aquae. Bull Environ Contam Toxicol, 29:
    531-538.

    Bastian MV & Toetz DW (1985) Effect of polynuclear hydrocarbons on
    algal nitrogen fixation (acetylene reduction). Bull Environ Contam
    Toxicol, 35: 258-265.

    Basu DK & Saxena J (1978a) Monitoring of polycyclic aromatic
    hydrocarbons in water. II. Extraction and recovery of six
    representative compounds with polyurethane foams. Environ Sci Technol,
    12: 791-795.

    Basu DK & Saxena J (1978b) Polynuclear aromatic hydrocarbons in
    selected US drinking water and their raw water sources. Environ Sci
    Technol, 12: 795-798.

    Basu DK, Saxena J, Stoss FW, Santodonato J, Neal MW, & Kopfler FC
    (1987) Comparison of drinking water mutagenicity with leaching of
    polycyclic aromatic hydrocarbons from water distribution pipes.
    Chemosphere, 16: 2595-2612.

    Batiste-Alentorn M, Xamena N, Creus A, & Marcos R (1991) Genotoxicity
    studies with the unstable zeste-white (UZ) system of  Drosophila
    melanogaster: Results with ten carcinogenic compounds. Environ Mol
    Mutag, 18: 120-125.

    Bauer L, Gräf W, & Mueller LG (1985) The phototoxic effect of
    polycyclic aromatic hydrocarbons (PAH) on human fibroblastic cultures.
    Zentralbl Bakteriol Hyg I Abt Orig B, 181: 281-294.

    Bauer E, Guo Z, Ueng Y-F, Bell LC, Zeldin D, & Guengerich FP (1995)
    Oxidation of benzo [a]pyrene by recombinant human cytochrome P450
    enzymes. Chem Res Toxicol, 8: 136-142.

    Baumung H, Huber L, & Kalbfus W (1985) [Testing of selected components
    of wastewater from filling stations and fuel storage depots.] Erdöl
    Kohle Erdgas Petrochem, 38: 558-559 (in German).

    Bayer U (1978)  In vivo induction of sister chromatid exchanges by
    three polyaromatic hydrocarbons. Carcinogenesis, 3: 423-428.

    Bayona JM, Fernandez P, Porte C, Tolosa I, Valls M, & Albaiges J
    (1991) Partitioning of urban wastewater organic microcontaminants
    among coastal compartments. Chemosphere, 23: 313-326.

    Beach AC & Gupta RC (1991) Analysis of cyclopenta(CP)-fused and
    'pseudo-CP' polycyclic aromatic hydrocarbon (PAH)-DNA adducts by
    32P-postlabeling. Proc Am Assoc Cancer Res, 32: 98.

    Beach AC & Gupta RC (1992) Human biomonitoring and the 32
    P-postlabeling assay. Carcinogenesis, 13: 1053-1074.

    Beach AC & Gupta RC (1994) DNA adducts of the ubiquitous contaminant
    cyclopenta (cd)pyrene. Carcinogenesis, 15: 1065-1072.

    Beach AC, Agarwal SC, Lamberg GR, Nesnow S, & Gupta RC (1993) Reaction
    of cyclopenta (c,d)pyrene-3,4-epoxide with DNA and desoxynucleotides.
    Carcinogenesis, 14: 767-771.

    Becher G & Bjorseth A (1983) Determination of exposure to polycyclic
    aromatic hydrocarbons by analysis of human urine. Cancer Lett, 17:
    301-311.

    Becher G, Haugen A, & Bjorseth A (1984) Multimethod determination of
    occupational exposure to polycyclic aromatic hydrocarbons in an
    aluminium plant. Carcinogenesis, 5: 647-651.

    Behn U, Kaschani DT, Lützke K, Rentel S, & Burk HD (1985) [PAH
    sampling systems for industrial plants.] Erdöl Kohle Erdgas Petrochem,
    38: 131 (in German).

    Behymer TD & Hites RA (1985) Photolysis of polycyclic aromatic
    hydrocarbons adsorbed on simulated atmospheric particulates. Environ
    Sci Technol, 19: 1004-1006.

    Behymer TD & Hites RA (1988) Photolysis of polycyclic aromatic
    hydrocarbons adsorbed on fly ash. Environ Sci Technol, 22: 1311-1319.

    Beilstein Institute for Organic Chemistry (1993) Data base.
    Benzo(c)phenanthrene. Frankfurt, 2 pp.

    Bender ME & Huggett RJ (1988) Polynuclear aromatic hydrocarbon
    residues in shellfish: Species variations and apparent intraspecific
    differences. In: Kaiser HE ed. Cancer growth and progression. Volume
    5: Comparative aspects of tumor development. Dordrecht, Kluwer
    Academic Publishers, pp 226-234.

    Bender MA, Leonard RC, White O Jr, Costantino JP, & Redmond CK (1988)
    Chromosomal aberrations and sister-chromatid exchanges in lymphocytes
    from coke oven workers. Mutat Res, 206: 11-16.

    Benfield JR & Hammond WG (1992) Bronchial and pulmonary carcinogenesis
    at focal sites in dogs and hamsters. Cancer Res, 52: 2687-2693.

    Beniashvili DSH (1978) [A comparative study on the action of some
    carcinogens inducing transplacental blastomogenesis in rabbits.] Vopr
    Onkol, 24: 77-83 (in Russian with English abstract).

    Benner BA Jr, Gordon GE, & Wise SA (1989) Mobile sources of
    atmospheric polycyclic aromatic hydrocarbons: A roadway tunnel study.
    Environ Sci Technol, 23: 1269-1278.

    Benner BA Jr, Bryner NP, Wise SA, Mulholland GW, Lao RC, & Fingas MF
    (1990) Polycyclic aromatic hydrocarbon emissions from the combustion
    of crude oil on water. Environ Sci Technol, 24: 1418-1427.

    Berbee RPM (1992) PAH in the aquatic environment: Sources and
    emissions. Summary. Proceedings of the workshop on polycyclic aromatic
    hydrocarbons (PAH), Oslo, 11-13 November 1991 (Report TA-816). Oslo,
    State Pollution Control Authority, Norwegian Food Control Authority.

    Berenblum I & Haran H (1955) The influence of croton oil and of
    polyethylene glycol-400 on carcinogenesis in the forestomach of the
    mouse. Cancer Res, 15: 510-516.

    Berenblum I & Schoental R (1943) The metabolism of 3,4-benzpyrene in
    mice and rats. The isolation of a hydroxy and a quinone derivative and
    a consideration of their biological significance. Cancer Res, 3: 145-
    150.

    Berenblum I & Shubik P (1947) The role of croton oil applications,
    associated with a single painting of a carcinogen in tumour induction
    of the mouse skin. Br J Cancer, 1: 379-382.

    Berglind L (1982) Determination of polycyclic aromatic hydrocarbons in
    industrial discharges and other aqueous effluents (Nordic PAH
    Project). Oslo, Central Institute for Industrial Research, 21 pp
    (Report No. 16).

    Bernfeld P & Homburger F (1983) Skin painting studies in Syrian
    hamsters. Prog Exp Tumor Res, 26: 128-153.

    Best GR, Nabholz JV, Ojasti J, & Crossley DA Jr (1978) Response of
    micro arthropod populations to naphthalene in three contrasting
    habitats. Pedobiologia, 18: 189-201.

    Bhatia AL, Tausch, H & Stehlik G (1987) Mutagenicity of chlorinated
    polycyclic aromatic compounds. Ecotoxicol Environ Saf, 14: 48-55.

    Bhatt TS & Coombs MM (1990) The carcinogenicity of
    cyclopenta [a]phenanthrene and chrysene derivatives in the Sencar
    mouse. Polycyclic Aromat Compd, 1: 51-58.

    Bhattacharyya KK, Brake PB, Eltom SE, Otto SA, & Jefcoate CR (1995)
    Identification of a rat adrenal cytochrome P450 active in polycyclic
    hydrocarbon metabolism as rat CYP1B1; demonstration of a unique
    tissue-specific pattern of hormonal and aryl hydrocarbon
    receptor-linked regulation. J Biol Chem, 270: 11595-11602.

    Bieniek G (1994) The presence of 1-naphthol in the urine of industrial
    workers exposed to naphthalene. Occup Environ Med, 51: 357-359.

    Bieri RH, Hein C, Huggett RJ, Shou P, Slone H, Smith C, & Su C (1986)
    Polycyclic aromatic hydrocarbons in surface sediments from the
    Elizabeth River subestuary. Int J Environ Anal Chem, 26: 97-113.

    Biermann HW, MacLeod H, Atkinson R, Winer AM, & Pitts JN Jr (1985)
    Kinetics of the gas-phase reactions of the hydroxyl radical with
    naphthalene, phenanthrene and anthracene. Environ Sci Technol, 19:
    244-248.

    Bingham E & Falk HL (1969) Environmental carcinogens. The modifying
    effect of cocarcinogens on the threshold response. Arch Environ
    Health, 19: 779-783.

    Binková B, Dobiás L, Wolff T, & Srám RJ (1994) 32P-Postlabeling
    analysis of DNA adducts in tissues of rats exposed to coke-oven
    emissions. Mutat Res, 307: 355-363.

    Binková B, Lewtas J, Misková I, Lenrcek J, & Srám R (1995) DNA adducts
    and personal air monitoring of carcinogenic polycyclic aromatic
    hydrocarbons in an environmentally exposed population. Carcinogenesis,
    16: 1037-1046.

    Bjorseth A (1979) Determination of polycyclic aromatic hydrocarbons in
    sediments and mussels from Saudafjord, west Norway, by glass capillary
    gas chromatography. Sci Total Environ, 13: 71-86.

    Bjorseth A (1983) Appendix: List of dicyclic and polycyclic aromatic
    hydrocarbons, their structure, molecular weight, melting and boiling
    points. In: Bjorseth A ed. Handbook of polycyclic aromatic
    hydrocarbons. New York, Marcel Dekker, pp 709-718.

    Bjorseth A & Becher G (1986) PAH in work atmospheres: Occurrence and
    determination. Florida, Boca Raton, CRC Press, pp 57-62.

    Bjorseth A & Lunde G (1979) Long-range transport of polycyclic
    aromatic hydrocarbons. Atmos Environ, 13: 45-53.

    Bjorseth A & Olufsen S (1983) Long transport of polycyclic aromatic
    hydrocarbons. In: Bjorseth A ed. Polycyclic aromatic hydrocarbons. New
    York, Marcel Dekker, pp 507-524.

    Bjorseth A & Ramdahl T (1985) Sources and emissions of PAH. In:
    Bjorseth A & Ramdahl T ed. Handbook of polycyclic aromatic
    hydrocarbons: Volume 2: Emission sources and recent progress in
    analytical chemistry. New York, Marcel Dekker, pp 1-20.

    Black JJ, Hart TF Jr, & Evans E (1981) HPLC studies of PAH pollution
    in a Michigan trout stream. In: Cooke M & Dennis A ed. Polynuclear
    aromatic hydrocarbons: Chemical analysis and biological fate.
    Columbus, Ohio, Battelle Press, pp 343-355.

    Black JA, Birge WJ, Westerman AG, & Francis PC (1983) Comparative
    aquatic toxicology of aromatic hydrocarbons. Fundam Appl Toxicol, 3:
    353-358.

    Black JJ, Maccubin AE, & Johnston CJ (1988) Carcinogenicity of
    benzo [a]pyrene in rainbow trout resulting from embryo micro
    injection. Aquat Toxicol, 13: 297-308.

    Blanton RH, Lyte M, Myers MJ, & Bick PH (1986) Immunomodulation by
    polyaromatic hydrocarbons in mice and murine cells. Cancer Res, 46:
    2735-2739.

    Bobra A, Shiu WY, & Mackay (1983) A predictive correlation for the
    acute toxicity of hydrocarbons and chlorinated hydrocarbons to the
    water flea  Daphnia magna. Chemosphere, 12: 1121-1129.

    Bock FG (1964) Early effects of hydrocarbons on mammalian skin. Progr
    Exp Tumor Res, 4: 126-168.

    Bock FG & Dao TL (1961) Factors affecting the polynuclear hydrocarbon
    level in rat mammary glands. Cancer Res, 21: 1024-1029.

    Bock FG & King DW (1959) A study of the sensitivity of the mouse
    forestomach toward certain polycyclic hydrocarbons. J Natl Cancer
    Inst, 23: 833-838.

    Bock FG & Mund R (1958) A survey of compounds for activity in
    suppression of mouse sebaceous glands. Cancer Res, 18: 887-892.

    Boehm PD & Fiest DL (1983) Ocean dumping of dredged material in the
    New York Bight: Organic chemistry studies. In: Kester DR, Ketchum H,
    Bostwick I, & Duedal IW ed. Wastes in the ocean. Volume 2:
    Dredged-material disposal in the ocean. New York, John Wiley & Sons,
    pp 151-169.

    Boldrin B, Tiehm A, & Fritzsche C (1993) Degradation of phenanthrene,
    fluorene, fluoranthene, and pyrene by a  Mycobacterium sp. Appl
    Environ Microbiol, 59: 1927-1930.

    Bolling H (1964) [Carcinogenic substances in cereals dried by
    combustion gas.] Tech Monit Pinerolo, 15: 137-142 (in Italian).

    Bolonova LN (1967) [Action of naphthalene and its methyl derivatives
    on the ammonia content in rat brain.] Farmakol Toksikol, 30: 484-486
    (in Russian).

    Boney AD (1974) Aromatic hydrocarbons and the growth of marine algae.
    Mar Pollut Bull, 5: 185-186.

    Boney AD & Corner EDS (1962) On the effects of some carcinogenic
    hydrocarbons on the growth of sporelings of marine red algae. J Mar
    Biol Assoc, 42: 579-585.

    Bonfanti L, Cioni M, Belli R, & Cappiello A (1988) Determination of
    trace organic compounds in effluents from a coal-fired power plant.
    Biomed Mass Spectrom, 16: 175-178.

    Boogaard PJ & van Sittert NJ (1994) Exposure to polycyclic aromatic
    hydrocarbons in petrochemical industries by measurement of urinary
    1-hydroxypyrene. Occup Environ Med, 51: 250-258.

    Boogaard PJ & van Sittert NJ (1995) Urinary 1-hydroxypyrene as
    biomarker of exposure to polycyclic aromatic hydrocarbons in workers
    in petrochemical industries: Baseline values and dermal uptake. Sci
    Total Environ, 163: 203-209.

    Boom A & Marsalek J (1988) Accumulation of polycyclic aromatic
    hydrocarbons (PAHs) in an urban snowpack. Sci Total Environ, 74: 133-
    148.

    Boom MM (1987) The determination of polycyclic aromatic hydrocarbons
    in indigenous and transplanted mussels  (Mytilus 
     edulis L) along the Dutch coast. Int J Environ Anal Chem, 31: 251-
    261.

    Booth J & Boyland E (1949) Metabolism of polycyclic compounds. 5.
    Formation of 1,2-dihydroxy-1,2-dihydronaphthalene. Biochem J, 44: 361-
    365.

    Booth J, Keysell GR, Pal K, & Sims P (1974) The metabolism of
    polycyclic hydrocarbons by cultured human lymphocytes. FEBS Lett, 43:
    341-344.

    Borchert J & Westendorf J (1994) [Kinetics of uptake and metabolism of
    sediment-bound benzo(a)pyrene in sediment-inhabiting invertebrates.]
    Ber Zent Meeres Klimaforsch, 7: 75-55 (in German).

    Borneff J & Kunte H (1964) [Carcinogenic substances in water and soil.
    XVI. Determination of polycyclic aromatics in water samples by direct
    extraction.] Arch Hyg, 148: 585-597 (in German).

    Borneff J & Kunte H (1965) [Carcinogenic substances in water and soil.
    XVII. Source and evaluation of polycyclic aromatic hydrocarbons in
    water.] Arch Hyg, 149: 226-243 (in German).

    Borneff J & Kunte H (1979) Method 1. Analysis of polycyclic aromatic
    hydrocarbons in water using thin layer chromatography and
    spectrofluorometry. In: Egan H, Castegnaro M, Bogovski P, Kunte H, &
    Walker EA ed. Environmental carcinogens: Selected methods of analysis.
    Volume 3: Analysis of polycyclic aromatic hydrocarbons in
    environmental samples. Lyon, International Agency for Research on
    Cancer, pp 129-139 (IARC Scientific Publications No. 29).

    Borneff J & Kunte H (1983) Polycyclic aromatic hydrocarbons in river
    and lake water, biota, and sediments. In: Bjorseth A ed. Handbook of
    polycyclic aromatic hydrocarbons. New York, Marcel Dekker, pp 629-652.

    Boroujerdi M, Kung HC, Wilson AGE, & Anderson MW (1981) Metabolism and
    DNA binding of benzo [a]pyrene  in vivo in the rat. Cancer Res, 41:
    951-957.

    Borovsky D, Linley JR, & Kagan J (1987) Polycyclic aromatic compounds
    as phototoxic mosquito larvicides. J Am Mosq Control Assoc, 3: 246-
    250.
    Bos RP, Prinsen WJC, van Rooy JGM, Jongeneelen FJ, Theuws JLG, &
    Henderson PT (1987) Fluoranthene, a volatile mutagenic compound,
    present in creosote and coal tar. Mutat Res, 187: 119-125.

    Bos RP, Theuws JLG, Jongeneelen FJ, & Henderson PT (1988) Mutagenicity
    of bi-,tri- and tetra-cyclic aromatic hydrocarbons in the 'taped-plate
    assay' and in the conventional  Salmonella 
    mutagenicity assay. Mutat Res, 204: 203-206.

    Bossert ID & Bartha R (1986) Structure-biodegradability relationships
    of polycyclic aromatic hydrocarbons in soil. Bull Environ Contam
    Toxicol, 37: 490-495.

    Bossert I, Kachel WM, & Bartha R (1984) Fate of hydrocarbons during
    oily sludge disposal in soil. Appl Environ Microbiol, 47: 763-767.

    Bottomley AC & Twort CC (1934) The carcinogenicity of chrysene and
    oleic acid. Am J Cancer, 21: 781-786.

    Bourcart J & Mallet L (1965) [Coastal marine pollution in the central
    region of the Tyrrhenian Sea (Bay of Naples) by polyaromatic
    hydrocarbons of the benzo-3,4-pyrene type.] C R Acad Sci Paris, 260:
    3729-3734 (in French).

    Bourguet CC, Checkoway H, & Hulka BS (1987) A case-control study of
    skin cancer in the tire and rubber manufacturing industry. Am J Ind
    Med, 11: 461-473.

    Bourne MC & Young L (1934) The metabolism of naphthalene in rabbits.
    Biochem J, 28: 803-808.

    Bowling J, Leversee G, Landrum PF, & Giesy JP (1983) Acute mortality
    of anthracene-contaminated fish exposed to sunlight. Aquat Toxicol, 3
    :79-90.

    Bowmer CT, Roza P, Henzen L, & Degeling C (1993) The development of
    chronic toxicological tests for PAH contaminated soils using the
    earthworm  Eisenia fetida and the springtail  Folsomia candida. 
    Delft, TNO Institute of Environmental Sciences, 49 pp (TNO Report No.
    IMW-R 92/387).

    Boyland E & Burrows H (1935) The experimental production of sarcoma in
    rats and mice by a colloidal aqueous solution of
    1:2:5:6-dibenzanthracene. J Pathol Bacteriol, 41: 231-238.

    Boyland E & Levi AA (1935) Metabolism of polycyclic compounds. I.
    Production of dihydroxydihydroanthracene from anthracene. Biochem J,
    29: 2679-2683.

    Boyland E & Levi AA (1936a) Metabolism of polycyclic compounds. II.
    Production of dihydroxydihydroanthracene glycuronic acid from
    anthracene. Biochem J, 30: 728-731.

    Boyland E & Levi AA (1936b) Metabolism of polycyclic compounds. III.
    Anthrylmercapturic acid. Biochem J, 30: 1225-1227.

    Boyland E & Sims P (1958) Metabolism of polycyclic compounds. 12. An
    acid-labile precursor of 1-naphthylmercapturic acid and naphthol: An
    N-acetyl-S-(1,2-dihydro-hydroxynaphthyl) L-cysteine. Biochem J, 68:
    440-447.

    Boyland E & Sims P (1962a) Metabolism of polycyclic compounds. 20. The
    metabolism of phenanthrene in rabbits and rats: Mercapturic acids and
    related compounds. Biochem J, 84: 564-570.

    Boyland E & Sims P (1962b) Metabolism of polycyclic compounds. 21. The
    metabolism of phenanthrene in rabbits and rats: Dihydrodihydroxy
    compounds and related glucosiduronic acids. Biochem J, 84: 571-582.

    Boyland E & Sims P (1964a) Metabolism of polycyclic compounds. 23. The
    metabolism of pyrene in rats and rabbits. Biochem J, 90: 391-398.

    Boyland E & Sims P (1964b) Metabolism of polycyclic compounds. 24. The
    metabolism of benz [a]anthracene. Biochem J, 91: 493-506.

    Boyland E & Sims P (1967) The carcinogenic activities in mice of
    compounds related to benz [a]anthracene. Int J Cancer, 2: 500-504.
    Boyland E & Weigert F (1947) Metabolism of carcinogenic compounds. Br
    Med Bull, 4: 354-359.

    Boyland E & Wolf G (1950) Metabolism of polycyclic compounds. 6.
    Conversion of phenanthrene into dihydroxydihydrophenanthrene. Biochem
    J, 47: 64-69.

    Boyland E, Levi AA, Mawson EH, & Roe E (1941) Metabolism of polycyclic
    compounds. 4. Production of a dihydroxy-1,2,5,6-dibenzanthracene.
    Biochem J, 35: 184-191.

    Boyland E, Kimura M, & Sims P (1964) Metabolism of polycyclic
    compounds. 26. The hydroxylation of some aromatic hydrocarbons by the
    ascorbic acid model hydroxylating system and by rat liver microsomes.
    Biochem J, 92: 631-638.

    Bozicevic Z, Cvitas T, Curic M, Klasinc L, & Pecina P (1987) Airborne
    polycyclic aromatic hydrocarbons in the city of Zagreb, Yugoslavia.
    Sci Total Environ, 66: 127-136.

    Brandt-Rauf PW, Smith S, Perera FP, Niman HL, Yohannan W, Hemminki K,
    & Santella RM (1990) Serum oncogene proteins in foundry workers. J Soc
    Occup Med, 40: 11-14.

    Brasser LJ (1980) [Polycyclic aromatic hydrocarbon concentration in
    the Netherlands. Air pollution from polycyclic aromatic hydrocarbons:
    Collection and evaluation.] Düsseldorf, VDI-Verlag GmbH, pp 171-180
    (VDI Report No. 358) (in German).

    Bresch H, Spielhoff R, Mohr U, & Barkemeyer H (1972) Use of the sea
    urchin egg for quick screen testing of the biological activities of
    substances. I. Influence of fractions of a tobacco smoke condensate on
    early development. Proc Soc Exp Biol Med, 141: 747-752.

    Bridges BA, Zeiger E, & McGregor DB (1981) Summary report on the
    performance of bacterial mutation assays. In: de Serres FJ & Ashby J
    ed. Evaluation of short-term tests for carcinogens. Report of the
    international collaborative programme. New York, Elsevier North
    Holland, pp 49-67 (Progress in Mutation Research, Volume 1).

    Brockhaus A & Tomingas R (1976) [Emission of polycyclic hydrocarbons
    during burning processes in small heating installations and their
    concentration in the atmosphere.] StaubReinhalt Luft, 36: 96-101 (in
    German).

    Broddin G, Van Vaeck L, & Van Cauwenberghe K (1977) On the size
    distribution of polycyclic aromatic hydrocarbon containing particles
    from a coke oven emission source. Atmos Environ, 11: 1061-1064.

    Broman D, Colmjö A, & Näf C (1987) Characterization of the PAC profile
    in settling particulates from the urban waters of Stockholm. Bull
    Environ Contam Toxicol, 38: 1020-1028.

    Broman D, Naf C, Rolff C, & Zebuhr Y (1990) Occurrence and dynamics of
    polychlorinated dibenzo-p-dioxins and dibenzofurans and polycyclic
    aromatic hydrocarbons in the mixed surface layer of remote coastal and
    offshore water of the Baltic. Environ Sci Technol, 25: 1850-1864.

    Brooke DN, Dobbs AJ & Williams N (1986) Octanol:water partition
    coefficients (P): Measurement, estimation and interpretation,
    particularly for chemicals with P > 105. Ecotoxicol Environ Saf, 11:
    251-260.

    Brookes P & Lawley PD (1964) Evidence of the binding of polynuclear
    aromatic hydrocarbons to the nucleic acids of mouse skin: Relation
    between carcinogenic power of hydrocarbons and their binding to
    deoxyribonucleic acid. Nature, 202: 781-784.

    Brookes P, Ellis MV, Pataki J, & Harvey RG (1986) Mutation in
    mammalian cells by isomers of 5-methylchrysene diolepoxide.
    Carcinogenesis, 7: 463-466.

    Bruce WR & Heddle JA (1979) The mutagenic activity of 61 agents as
    determined by the micronucleus,  Salmonella, and sperm abnormality
    assays. Can J Genet Cytol, 21: 319-334.

    Bruggeman WA, Van der Steen J, & Hutzinger O (1982) Reversed-phase
    thin-layer chromatography of polynuclear aromatic hydrocarbons and
    chlorinated biphenyls. Relationship with hydrophobicity as measured by
    aqueous solubility and octanol-water partition coefficient. J
    Chromatogr, 238: 335-346

    Brune K, Kalin H, Schmidt R, & Hecker E (1978) Inflammatory, tumor
    initiating and promoting activities of polycyclic aromatic
    hydrocarbons and diterpene esters in mouse skin as compared with their
    prostaglandin releasing potency  in vitro. Cancer Lett, 4: 333-342.

    Brune H, Deutsch-Wenzel RP, Habs M, Ivankovic S, & Schmähl D (1981)
    Investigation of the tumorigenic response to benzo [a]pyrene in
    aqeous caffeine solution applied orally to Sprague-Dawley rats. J
    Cancer Res Clin Oncol, 102: 153-157.

    Brunström B, Hakansson H, & Lundberg K (1991) Effects of a technical
    PCB preparation and fractions thereof on ethoxyresorufin O-deethylase
    activity, vitamin A levels and thymic development in the mink  Mustela
    vison. Pharmacol Toxicol, 69: 421-426.

    Bryan WR & Shimkin MB (1943) Quantitative analysis of dose-response
    data obtained with three carcinogenic hydrocarbons in strain C3H male
    mice. J Natl Cancer Inst, 3: 503-531.

    Bryant MF, Erexson GL, Kwanyuen P, Atwater AL, & Kligerman AD (1990)
    Sister chromatid exchange and micronucleus analyses in rat peripheral
    blood lymphocytes following  in vivo exposure to
    dibenz(a,h)anthracene (Abstract 30). Environ Mol Mutag, 15 (suppl 17):
    10-11.

    Bryant MF, Kwanyuen P, Atwater AL, Erexson GL, & Kligerman AD (1991)
    Cytogenetic effects of benzo-b-fluoranthene in Sprague-Dawley rat
    peripheral blood lymphocytes after  in vivo 
    exposure (Abstract 33). Environ Mol Mutag, 17 (suppl 19): 13.

    Bryla P & Weyand EH (1991) Role of activated oxygen species in
    benzo [a]pyrene:DNA adduct formation  in vitro. Free Radicals Biol
    Med, 11: 17-24.

    Buccafusco RJ, Ells SJ, & LeBlanc GA (1981) Acute toxicity of priority
    pollutants to bluegill  (Lepomis macrochirus). Bull Environ Contam
    Toxicol, 26: 446-452.

    Buchet JP, Gennart JP, Mercado-Calderon F, Delavignette JP, Cupers L,
    & Lauwerys R (1992) Evaluation of exposure to polycyclic aromatic
    hydrocarbons in a coke production and a graphite electrode
    manufacturing plant: Assessment of urinary excretion of
    1-hydroxypyrene as a biological indicator of exposure. Br J Ind Med,
    49: 761-768.

    Buck M (1983) [Immission measurements of polycyclic aromatic
    hydrocarbons (PAH) in the Rhein-Ruhr-Gebiet.] Schriftenr Landesanst
    Immissionsschutz Landes Nordrhein-Westfalen. 57: 37-45 (in German).

    Buck M (1991) [Methods and results of the measurement of carcinogenic
    polycyclic aromatic hydrocarbons.] In: [Carcinogenic compounds in the
    environment: Sources, measurement, risk, reduction.] Dusseldorf,
    VDI-Verlag, pp 49-70 (VDI Report No. 888) (in German).

    Buck M, Ixfeld H, & Ellermann K (1989) [Report on the results of
    discontinuous sulfur dioxide and multiple component measurements taken
    in the Rhine-Ruhr area in the period from 1 January to 31 December
    1988.] In: Summaries of reports, 1988. A series from the State of
    North-Rhine Westfalia Pollution Control Office. Düsseldorf, Cornelsen
    Verlag Schwann-Girardet, pp 69-130 (in German with English summary)

    Buckley TJ & Lioy PJ (1992) An examination of the time course from
    human dietary exposure to polycyclic aromatic hydrocarbons to urinary
    elimination of 1-hydroxypyrene. Br J Ind Med, 49: 113-124.

    Buckpitt AR & Franklin RB (1989) Relationship of naphthalene and
    2-methylnaphthalene metabolism to pulmonary bronchiolar epithelial
    cell necrosis. Pharmacol Ther, 41: 393-410.

    Budavari S, O'Neil MJ, Smith A, & Heckelman PE (1989) The Merck Index:
    An encyclopedia of chemicals, drugs, and biologicals, 11th ed. Rahway,
    New Jersey, Merck & Co., pp 108, 350, 650, 1008, 1139, 1266.

    Buening MK, Levin W, Karle JM, Yagi H, Jerina DM, & Conney AH (1979)
    Tumorigenicity of bay-region epoxides and other derivatives of
    chrysene and phenanthrene in newborn mice. Cancer Res, 39: 5063-5068.

    Buening MK, Levin W, Wood AW, Chang RL, Lehr RE, Taylor CW, Yagi H,
    Jerina DM, & Conney AH (1980) Tumorigenicity activity of
    benzo(e)pyrene derivatives on mouse skin and in newborn mice. Cancer
    Res, 40: 203-206.

    Bui QQ, Tran MB, & West WL (1986) A comparative study of the
    reproductive effects of methadone and benzo [a]pyrene in the pregnant
    and pseudopregnant rat. Toxicology, 42: 195-204.

    Bulay OM (1970) The study of development of lung and skin tumors in
    mice exposed in utero to polycyclic hydrocarbons. Acta Med Turk, 7: 3-
    38.

    Bulay OM & Wattenberg LW (1971) Carcinogenic effects of polycyclic
    hydrocarbon carcinogen administration to mice during pregnancy on the
    progeny. J Natl Cancer Inst, 46: 397-402.

    Bulman TL, Lesage S, Fowlie P, & Webber MD (1987) The fate of
    polynuclear aromatic hydrocarbons in soil. In: Vandermeulan JH &
    Hurley SE ed. Oil in fresh water: chemistry, biology, countermeasure
    technology. New York, Pergamon Press, pp 231-251.

    Burchiel SW, Hadley WM, Barton SL, Fincher RH, Lauer LD, & Dean JH
    (1988) Persistent suppression of humoral immunity produced by
    7,12-dimethylbenz [a]anthracene (DMBA) in B6C3F1 mice: Correlation
    with changes in spleen cell surface markers detected by flow
    cytometry. Int J Immunopharmacol, 10: 369-376.

    Burchiel SW, De Davis AP, Gomez MP, Montano RM, Barton SL, & Seamer LC
    (1990) Inhibition of lymphocyte activation in splenic and
    gut-associated lymphoid tissues followig oral exposure of mice to
    7,12-dimethylbenz [a]anthracene. Toxicol Appl Pharmacol, 105:
    434-442.

    Burchiel SW, Thompson TA, & Davis DP (1991) Alterations in
    mitogen-induced calcium mobilization and intracellular free calcium
    produced by 7,12-dimethylybenz(a)-anthracene in the Jurkat human T
    cell line. Int J Immunopharmacol, 13: 109-115.

    Burgaz S, Borm PJA, & Jongeneelen F (1992) Evaluation of urinary
    excretion of 1-hydroxypyrene and thioethers in workers exposed to
    bitumen fumes. Int Arch Occup Environ Health, 63: 397-401.

    Burnham K & Rahman M (1992) Effects of petrochemicals and ultraviolet
    radiation on epidermal IA expression  in vitro. J Toxicol Environ
    Health, 35: 175-185.

    Busby WF, Goldman ME, Newberne PM, & Wogan GN (1984) Tumorigenicity of
    fluoranthene in a newborn mouse lung adenoma bioassay. Carcinogenesis,
    5: 1311-1316.

    Busby WF Jr, Stevens EK, Kellenbach ER, Cornelisse J, & Lugtenburg J
    (1988) Dose-response relationships of the tumorigenicity of
    cyclopenta [c,d]pyrene, benzo [a]pyrene and 6-nitrochrysene in a
    newborn mouse lung adenoma bioassay. Carcinogenesis, 9: 741-746.

    Busby WF Jr, Stevens EK, Martin CN, Chow FL, & Garner RC (1989)
    Comparative lung tumorigenicity of parent and mononitro-polynuclear
    aromatic hydrocarbons in the BLU: Ha newborn mouse assay. Toxicol Appl
    Pharmacol, 99: 555-563.

    Butler JD & Crossley P (1979) An appraisal of relative airborne
    suburban concentrations of polycyclic aromatic hydrocarbons monitored
    indoors and outdoors. Sci Total Environ, 11: 53-58.

    Butler JD & Crossley P (1981) Reactivity of polycyclic aromatic
    hydrocarbons adsorbed on soot particles. Atmos Environ, 15: 91-94.

    Butler JD & Crossley P (1982) Predicting polycyclic aromatic
    hydrocarbon concentrations in urban aerosols by linear multiple
    regression analysis. Environ Pollut, B3: 109-123.

    Butler JD, Butterworth V, Kellow SC, & Robinson HG (1984) Some
    observations on the polycyclic aromatic hydrocarbon (PAH) content of
    surface soils in urban areas. Sci Total Environ, 33: 75-85.

    Butlin HT (1892) Cancer of the scrotum in chimney-sweeps and others.
    Br Med J, ii: 66-71.

    Buu-Hoi NP (1964) New developments in chemical carcinogenesis by
    polycyclic hydrocarbons and related heterocycles: A review. Cancer
    Res, 24: 1511-1523.

    Cairns MA & Nebeker AV (1982) Toxicity of acenaphthene and isophorone
    to early life stages of fathead minnows. Arch Environ Contam Toxicol,
    11: 703-707.

    Calder JA & Lader JH (1976) Effect of dissolved aromatic hydrocarbons
    on the growth of marine bacteria in batch culture. Appl Environ
    Microbiol, 32: 95-101.

    Callahan MA, Slimak MW, Gabel NW, May IP, & Fowler CF (1979)
    Water-related environmental fate of 129 priority pollutants. Vol II.
    Halogenated aliphatic hydrocarbons, halogenated ethers, monocyclic
    aromatics, phthalate esters, polycyclic aromatic hydrocarbons,
    nitrosamines and miscellaneous compounds Report EPA-440/4-79-029b;
    PB80 204381). Washington DC, US Environmental Protection Agency, 673
    pp.

    Capel PD, Leuenberger C, & Giger W (1991) Hydrophobic organic
    chemicals in urban fog. Atmos Environ, 25: 1335-1346.

    Carmichael PL, Jacob J, Grimmer G, & Phillips DH (1990) Analysis of
    the polycyclic aromatic hydrocarbon content of petrol and diesel
    engine lubricating oils and determination of DNA adducts in topically
    treated mice by 32P-postlabelling. Carcinogenesis, 11: 2025-2032.

    Carmichael PL, Platt KL, Ni She M, Lecoq S, Oesch F, Phillips DH, &
    Grover PL (1993) Evidence for the involvement of a bis-diol-epoxide in
    the metabolic activation of dibenz [a,h]anthracene to DNA-binding
    species in mouse skin. Cancer Res, 53: 944-948.

    Carstensen U, Alexandrie AK, Högstedt B, Rannug A, Bratt I, & Hagmar L
    (1993) B- and T-lymphocyte micronclei in chimney sweeps with respect
    to genetic polymorphism for CIP1A1 and GST1 (class Mu). Mutat Res,
    289: 187-195.

    Carver JH, Machado ML, & MacGregor JA (1986) Application of modified
     Salmonella/microsome prescreen to petroleum-derived complex mixtures
    and polynuclear aromatic hydrocarbons (PAH). Mutat Res, 174: 247-253.

    Casserly DM, Davis EM, Downs TD, & Guthrie RK (1983) Sorption of
    organisms by  Selenastrum capricornutum. Water Res, 17: 1591-1594.

    Casto BC (1973) Enhancement of adenovirus transformation by treatment
    of hamsters with ultraviolet irradiation, DNA base analogs, and
    dibenz(a,h)anthracene. Cancer Res, 33: 402-407.

    Casto BC (1979) Polycyclic hydrocarbons and Syrian hamster embryo
    cells: Cell transformation, enhancement of viral transformation and
    analysis of DNA-damage. In: Jones PW & Leber P ed. Polynuclear
    aromatic hydrocarbons. Ann Arbor, Michigan, Ann Arbor Science
    Publishers, pp 51-66.

    Casto BC, Janosko N, & DiPaolo JA (1977) Development of a focus assay
    model for transformation of hamster cells  in vitro by chemical
    carcinogens. Cancer Res, 37: 3508-3515.

    Catallo WJ III & Gambrell RP (1987) The effects of high levels of
    polycyclic aromatic hydrocarbons on sediment physicochemical
    properties and benthic organisms in a polluted stream. Chemosphere,
    16: 1053-1064.

    Catoggio JA, Succar SD, & Roca AE (1989) Polynuclear aromatic
    hydrocarbon content of particulate matter suspended in the atmosphere
    of La Plata, Argentina. Sci Total Environ, 79: 43-58.

    Cautreels W & van Cauwenberghe K (1977) Comparison between the organic
    fraction of suspended matter at a background and an urban station. Sci
    Total Environ, 8: 79-88.

    Cavalieri E & Rogan E (1985) Role of radical cations in aromatic
    hydrocarbon carcinogenesis. Environ Health Perspectives, 64: 69-84.
    Cavalieri E, Mailander P, & Pelfrene A (1977) Carcinogenic activity of
    anthanthrene on mouse skin. Z Krebsforsch, 89: 113-118.

    Cavalieri E, Roth R, Althoff J, Grandjean C, Patil K, Marsh S, &
    McLaughlin D (1978) Carcinogenicity and metabolic profiles of
    3-methylcholanthrene oxygenated derivatives at the 1 and 2 positions.
    Chem-Biol Interactions, 22: 69-81.

    Cavalieri E, Rogan E, & Thilly WG (1981a) Carcinogenicity,
    mutagenicity and binding studies of the environmental contaminant
    cyclopenteno [c,d]pyrene and some of its derivatives. In: Cooke M &
    Dennis AJ ed. Polynuclear aromatic hydrocarbons: Chemical analysis and
    biological fate. Columbus, Ohio, Battelle Press, pp 487-499.

    Cavalieri E, Rogan E, Toth B, & Munhall A (1981b) Carcinogenicity of
    the environmental pollutants cyclopenteno(c,d)pyrene and
    cyclopentano(c,d)pyrene in mouse skin. Carcinogenesis, 2: 277-281.

    Cavalieri E, Rogan E, & Sinha D (1988a) Carcinogenicity of aromatic
    hydrocarbons directly applied to rat mammary gland. Cancer Res Clin
    Oncol, 114: 3-9.

    Cavalieri E, Rogan E, Cremonesi P, Higginbotham S, & Salmasi S (1988b)
    Tumorigenicity of 6-halogenated derivatives of benzo [a]pyrene in
    mouse skin and rat mammary gland. J Cancer Res Clin Oncol, 114: 10-15.

    Cavalieri EL, Rogan EG, Higginbotham S, Cremonesi P, & Salmasi S
    (1989) Tumor-initiating activity in mouse skin and carcinogenicity in
    rat mammary gland of dibenzo[a]pyrenes: The very potent environmental
    carcinogen dibenzo(a,l)pyrene. J Cancer Res Clin Oncol, 115: 67-72.

    Cavalieri EL, Higginbotham S, Ramakrishna NVS, Devanesan PD, Todorovic
    R, Rogan EG, & Salmasi S (1991) Comparative dose-response
    tumorigenicity studies of dibenzo [a,l]pyrene versus
    7,12-dimethylbenz [a]anthracene, benzo [a]pyrene and two
    dibenzo [a,l]pyrene dihydrodiols in mouse skin and rat mammary gland.
    Carcinogenesis, 12: 1939-1944.

    Cavalieri EL, Rogan EG, Ramakrishna NVS, & Devanesan PD (1993)
    Mechanisms of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene
    activation: Qualitative aspects of the stable and depurination DNA
    adducts obtained from radical cations and diol epoxides. In: Garrigues
    P & Lamotte M ed. Polycyclic aromatic compounds: Synthesis,
    properties, analytical measurements, occurrence and biological
    effects. Bordeaux, Gordon & Breach Science Publishers, pp 725-732.

    Cenni A, Sciarra G, Sartorelli P, & Pappalardo F (1993) Environmental
    and biological monitoring of polycyclic aromatic hydrocarbons (PAHs)
    in coke plants and other workplaces. Med Lav, 84: 379-386.

    Cerniglia CE (1984) Microbial metabolism of polycyclic aromatic
    hydrocarbons. In: Cerniglia CE ed. Advances in applied microbiology,
    Volume 30. Jefferson, Arkansas, Academic Press, pp 31-71.

    Chakraborti D, Van Vaeck L, & Van Espen P (1988) Calcutta pollutants:
    Part II. Polynuclear aromatic hydrocarbon and some metal concentration
    on air particulates during winter 1984. Int J Environ Anal Chem, 32:
    109-120.

    Chaloupka K, Santosstefano M, Goldfarb IS, Liu G, Myers MJ, Tsyrolv
    IB, Gelboin HV, Krishnan V, & Safe S (1994) Aryl hydrocarbon (ah)
    receptor-independent induction of Cyp1a2 gene expression by
    acenaphthylene and related compounds in B6C3F1 mice. Carcinogenesis,
    15: 2835-2840.

    Chang RL, Levin W, Wood AW, Lehr RE, Kumar S, Yagi H, Jerina DM, &
    Conney AH (1981) Tumorigenicity of the diastereomeric bay-region
    benzo(e)pyrene 9,10-diol-11,12-epoxides in newborn mice. Cancer Res,
    41: 915-918.

    Chang RL, Levin W, Wood AW, Lehr RE, Kumar S, Yagi H, Jerina DM, &
    Conney AH (1982) Tumorigenicity of bay-region diol-epoxides and other
    benzo-ring derivatives of dibenzo[a,h]pyrene and dibenzo[a,i]pyrene on
    mouse skin and newborn mice. Cancer Res, 42: 25-29.

    Chang RL, Levin W, Wood AW, Yagi H, Tada M, Vyas KP, Jerina DM, &
    Conney AH (1983) Tumorigenicity of enantiomers of chrysene
    1,2-dihydrodiol and of the diastereomeric bay-region chrysene
    1,2-diol-3,4-epoxides on mouse skin and in newborn mice. Cancer Res,
    43: 192-196.

    Chang SC, Chang KT, Keng, YF Lan CF, Hsiao HC, Hsen SH, & Wei YH
    (1988) Mutagenicity and polycyclic aromatic hydrocarbons analysis of
    airborne particulate matters from Taipei city. Proc Natl Sci Counc
    Taiwan, 12: 129-139.

    Chappell WR (1989) Interspecific scaling of toxicity data: A question
    of interpretation. Risk Anal, 9: 13-14.

    Chasseaud LF (1979) The role of glutathione and glutathione
    S-transferases in the metabolism of chemical carcinogens and other
    electrophilic agents. Adv Cancer Res, 29: 175-274.

    Chau N, Bertrand JP, Mur JM, Figueredo A, Patris A, Moulin JJ, & Pham
    QT (1993) Mortality in retired coke oven plant workers. Br J Ind Med,
    50: 127-135..

    Chemical Abstracts Service (1988) Ring systems handbook. Ring Systems
    File I RF 1-RF 27595. Columbus, Ohio, American Chemical Society.

    Chemical Abstracts Service (1990) Index guide. Part 1, pp. 1-1470;
    Part 2, pp 1471-2446. Columbus, Ohio, American Chemical Society.

    Chen TT & Heidelberger C (1969) Quantitative studies on the malignant
    transformation of mouse prostate cells by carcinogenic hydrocarbons
     in vitro. Int J Cancer, 4: 166-178.

    Chen PHS, Shieh HH, & Gaw JM (1980) Determination of polycyclic
    aromatic hydrocarbons in airborne particulates at various sites in
    Taipei city by GC/MS and glass capillary GC. Proc Natl Sci Counc
    Taiwan, 4: 280-284.

    Chen PHS, Chuang CY Lu YD, & Chung KT (1981) Gas chromatography/mass
    spectrometric determination of polycyclic aromatic hydrocarbons in
    airborne particulates at various sites in Kaohsiung area. Proc Natl
    Sci Counc Taiwan, 5: 262-267.

    Chiazze L Jr, Watkins DK, & Amsel J (1991) Asphalt and risk of cancer
    in man. Br J Ind Med, 48: 538-542.

    Chipman JK (1982) Bile as a source of potential reactive metabolites.
    Toxicology, 25: 99-111.

    Chipman JK, Hirom PC, Frost GS, & Millburn P (1981) The biliary
    excretion and enterohepatic circulation of benzo [a]pyrene and its
    metabolites in the rat. Biochem Pharmacol, 30: 937-944.

    Chiu CH, Howes PS, Li KC, Poole GK, & Lao RC (1991) The determination
    and measurement of PAH in municipal incinerator samples. In: Cooke M,
    Loening K, & Merritt J ed. Polynuclear aromatic hydrocarbons:
    Measurement, means, and metabolism. Columbus, Ohio, Battelle Press, pp
    195-211.

    Chladek E & Marano RS (1984) Use of bonded phase silica sorbents for
    the sampling of priority pollutants in wastewaters. J Chromatogr Sci,
    22: 313-320.

    Chorazy M, Szeliga J, Strozyk M, & Cimander B (1994) Ambient air
    pollutants in Upper Silesia: Partial chemical composition and
    biological activity. Environ Health Perspectives, 102: 61-66.

    Chu EW & Malmgren RA (1965) An inhibitory effect of vitamin A on the
    induction of tumors of forestomach and cervix in the Syrian hamster by
    carcinogenic polynuclear hydrocarbons. Cancer Res, 25: 884-895.

    Chuang JC, Hannan SW, & Wilson NK (1987) Field comparison of
    polyurethane foam and XAD-2 resin for air sampling for polynuclear
    aromatic hydrocarbons. Environ Sci Technol, 21: 798-804.

    Chuang JC, Mack GA, Kuhlman MR, & Wilson NK (1991) Polycyclic aromatic
    hydrocarbons and their derivatives in indoor and outdoor air in an
    eight-home study. Atmos Environ, 25B: 369-380.

    Chuang JC, Wise SA, Cao S, & Mumford JL (1992) Chemical
    characterization of mutagenic fractions of particles from indoor coal
    combustion: A study of lung cancer in Xuan Wie, China. Environ Sci
    Technol, 26: 999-1004.

    Chuang JC, Callahan PJ, Menton RG, & Gordon SM (1995) Monitoring
    methods for polycyclic aromatic hydrocarbons and their distribution in
    house dust and track-in soil. Environ Sci Technol, 29: 494-500.

    Clayson DB, Pringle JAS, Bonser GM, & Wood M (1968) The technique of
    bladder implantation: Further results and an assessment. Br J Cancer,
    22: 825-832.

    Clayton P, Davis BJ, Jones K, & Jones P (1992) Toxic organic
    micropollutants in urban air. Stevenage, Hertfordshire, Warren Spring
    Laboratory, 122 pp (Report No LR 904 [PA]).

    Clement Associates (1988) Comparative potency approach for estimating
    the cancer risk associated with exposure to mixtures of polycyclic
    aromatic hydrocarbons. Interim final report. Fairfax, Virginia, 125 pp
    (Report No. 68-02-4403).

    Clement Associates (1990) Development of a dose-response model for
    inhaled B[a]P. Fairfax, Virginia, 28 pp (prepared for US EPA under
    contract No. 68-02-4601).

    Clive D, Johnson KO, Spector AG, & Brown MMM (1979) Validation and
    characterization of the L5178Y/TK+/- mouse lymphoma mutagen assay
    system. Mutat Res, 59: 61-108.

    Clonfero E, Venier P, Toffolo D, Busi L, & Gava C (1984) Mutagenesis
    test on urine of workers exposed to polycyclic aromatic hydrocarbons
    in an anode plant. Med Lav, 75: 275-281.

    Clonfero E, Zordan M, Venier P, Paleologo M, Levis AG, Cottica D,
    Pozzoli L, Jongeneelen FJ, Bos RP, & Anzion RBM (1989) Biological
    monitoring of human exposure to coal tar. Urinary excretion of total
    polycyclic aromatic hydrocarbons, 1-hydroxypyrene and mutagens in
    psoriatic patients. Int Arch Occup Environ Health, 61: 363-368.

    Clonfero E, Jongeneelen F, Zordan M, & Levis AG (1990) Biological
    monitoring of human exposure to coal tar. Urinary mutagenicity assays
    and analytical determination of polycyclic aromatic hydrocarbon
    metabolites in urine. In: Vainio H, Sorsa M, & McMichael AJ ed.
    Complex mixtures and cancer risk. Lyon, International Agency for
    Research on Cancer, pp 215-222 (IARC Scientific Publications No. 104).

    Clonfero E, Granella M, Marchioro M, Leopardi Barra E, Nardini B,
    Ferri G, & Foà V (1995) Urinary excretion of mutagens in coke oven
    workers. Carcinogenesis, 16: 547-554.

    Coates JT, Elzerman AW, & Garrison AW (1986) Extraction and
    determination of selected polycyclic aromatic hydrocarbons in plant
    tissues. J Assoc Off Anal Chem, 69: 110-114.

    Cody T, Radike M, & Warshawsky D (1984) The phototoxicity of
    benzo [a]pyrene in the green algea  Selenastrum capricornutum. 
    Environ Res, 35: 122-132.

    Cohen GM, Haws SM, Moore BP, & Bridges JW (1976) Benzo [a]pyren-3-yl
    hydrogen sulphate, a major ethyl acetate-extractable metabolite of
    benzo [a]pyrene in human, hamster and rat lung cultures. Biochem
    Pharmacol, 25: 2561-2570.

    Collier TK, Singh SV, Awasthi YC, & Varanasi U (1992) Short
    communication. Hepatic xenobiotic metabolizing enzymes in two species
    of benthic fish showing different prevalences of
    contaminant-associated liver neoplasms. Toxicol Appl Pharmacol, 113:
    319-324.

    Collin G & Höke H (1985) Anthracene. In: Elvers B, Hawkins S, & Schulz
    G ed. Ullmann's encyclopedia of industrial chemistry, 5th ed.,Volume
    A2: Weinheim, Verlagsgesellschaft , pp 343-345.

    Collin G & Höke H (1991) Naphthalene and hydronaphthalene. In: Elvers
    B, Hawkins S, & Schulz G ed. Ullmann's encyclopedia of industrial
    chemistry, 5th ed., Volume A17: Weinheim, Verlagsgesellschaft, pp 1-8.

    Collins JF & Alexeeff G (1993) Benzo [a]pyrene as a toxic air
    contaminant. Part B: Health effects of benzo [a]pyrene. Berkeley,
    California, California Environmental Protection Agency, Office of
    Environmental Health Hazard Assessment, 69 pp.

    Collins JF, Brown JP, Dawson SV, & Marty MA (1991) Risk assessment for
    benzo [a]pyrene. Regul Toxicol Pharmacol, 13: 170-184.

    Colmsjö A, Zebühr YU, & Ostman CE (1986a) Polynuclear aromatic
    compounds in flue gases and ambient air in the vicinity of a municipal
    incineration plant. Atmos Environ, 20: 2279-2282.

    Colmsjö AL, Zebühr YU, & Ostman CE (1986b) Polynuclear aromatic
    compounds in the ambient air of Stockholm. Chemosphere, 15: 169-182.

    Combet E, Jarosz J, Martin-Bouyer M, Paturel L, & Saber A (1993)
    [Shpol'skii spectrofluorimetric measurement of unit emissions of PAH
    from 30 petrol and diesel light vehicles  in eight representative
    cycles.] Sci Total Environ, 134: 147-160 (in French).

    Community Bureau of Reference (1992) Reference materials. Brussels,
    Commission of the European Communities, 2 pp.

    Compaan H & Laane RW (1992) Polycyclic aromatic hydrocarbons (PAH) in
    the North Sea: An inventory. Delft, TNO Institute of Environmental
    Sciences, 130 pp (TNO Report IMW-R 92/392).

    CONCAWE  (The Oil Companies' European Organization for Environment,
    Health and Safety) (1992) The chemical composition of diesel
    particulate emissions (Report No. 92/51). The Hague, 24 pp.

    CONCAWE  (The Oil Companies' European Organization for Environment,
    Health and Safety) (1994) Motor vehicle emission regulations and fuel
    specifications. 1994 update (Report 4/94). The Hague, 234 pp.

    Conney AH (1982) Induction of microsomal enzymes by foreign chemicals
    and carcinogenesis by polycyclic aromatic hydrocarbons: G.H.A. Clowes
    memorial lecture. Cancer Res, 42: 4875-4917.

    Coombs MM & Bhatt TS ed. (1987) Cyclopenta(a)phenanthrenes. Polycyclic
    aromatic compounds structurally related to steroids. Cambridge,
    Cambridge University Press, 265 pp.

    Coombs MM, Dixon C, & Kissonerghis A-M (1976) Evaluation of the
    mutagenicity of compounds of known carcinogenicity, belonging to the
    benz [a]anthracene, chrysene, and cyclopenta [a]phenanthrene series,
    using Ames' test. Cancer Res, 36: 4525-4529.

    Cooper JA (1980) Environmental impact of residential wood combustion
    emissions and its implications. J Air Pollut Control Assoc, 30: 855-
    861.

    Cooper CS, Hewer A, Ribeiro O, Grover PL, & Sims P (1980) The
    enzyme-catalysed conversion of a non-'bay-region' diol-epoxide of
    benz(a)anthracene into a gluthathione conjugate. FEBS Lett, 118: 39-
    42.

    Cooper CS, Grover PL, & Sims P (1983) The metabolism and activation of
    benzo [a]pyrene. Drug Metab, 7: 295-396.

    Coover MP & Sims RC (1987) The effect of temperature on polycyclic
    aromatic hydrocarbon persistence in an unacclimated agricultural soil.
    Hazard Waste Hazard Mater, 4: 69-82.

    Cope VW & Kalkwarf DR (1987) Photooxidation of selected polycyclic
    aromatic hydrocarbons and pyrenequinones coated on glass surfaces.
    Environ Sci Technol, 21: 643-648.

    Corner EDS & Young L (1954) Biochemical studies of toxic agents. 7.
    The metabolism of naphthalene in animals of different species. Biochem
    J, 58: 647-655.

    Corner EDS, Billett FS, & Young L (1954) Biochemical studies of toxic
    agents. 6. The conversion of naphthalene into
    1,2-dihydro-2-hyroxy-l-naphthyl glucosiduronic acid in the rabbit.
    Biochem J, 56: 270-274.

    Correa M & Coler R (1983) Enhanced oxygen uptake rates in dragonfly
    nymphs  Somatochlora cingulata as an indication of stress from
    naphthalene. Environ Contam Toxicol, 30: 269-276.

    Cosma GN, Toniolo P, Currie D, Pasternack BS, & Seymour JG (1992)
    Expression of the CYP1A1 gene in peripheral lymphocytes as a marker of
    exposure to creosote in railroad workers. Cancer Epidemiol Biomarkers
    Prev, 1: 137-142.

    Costantino JP, Remond CK, & Bearden A (1995) Occupationally related
    cancer risk among coke oven workers: 30 years of follow-up. J Occup
    Environ Med, 37: 597-604.

    Cottini GB & Mazzone GB (1939) The effects of 3:4-benzpyrene on human
    skin. Am J Cancer, 37: 186-195.

    Coutant RW, Brown L, Chuang JC, Riggin RM, & Lewis RG (1988) Phase
    distribution and artifact formation in ambient air sampling for
    polynuclear aromatic hydrocarbons. Atmos Environ, 22: 403-409.

    Coutant RW, Callahan PJ, & Chuang JC (1992) Efficiency of
    silicone-grease-coated denuders for collection of polynuclear aromatic
    hydrocarbons. Atmos Environ, 26A: 2831-2834.

    Creasia DA, Poggenburg JK Jr, & Nettesheim P (1976) Elution of
    benzo [a]pyrene from carbon particles in the respiratory tract of
    mice. J Environ Health, 1: 967-975.

    Crespi CL & Thilly WG (1984) Assay for gene mutation in a human
    lymphoblast line, AHH-1, competent for xenobiotic metabolism. Mutat
    Res, 128: 221-230.

    Crespi CL, Liber HL, Behymer TD, Hites RA, & Thilly WG (1985) A human
    cell line sensitive to mutation by particle-born chemicals. Mutat Res,
    157: 71-75.

    Cretney JR, Lee HL, & Wright GJ (1985) Analysis of polycyclic aromatic
    hydrocarbons in air particulate matter from a lightly industrialized
    urban area. Environ Sci Technol, 19: 397-404.

    Crider JY, Wilhm J, & Harmon HJ (1982) Effects of naphthalene on the
    hemoglobin concentration and oxygen uptake of  Daphnia 
     magna. Bull Environ Contam Toxicol, 28: 52-57.

    Crocker TT, Chase JE, Wells SA, & Nunes LL (1970) Preliminary report
    on experimental squamous carcinoma of the lung in hamsters and in a
    primate  (Galago Crassicauda Tus.). San Diego, California, Office of
    the County Veterinarian, pp 317-328 (Symposium Series No. 21).

    Croisy-Delcey M, Ittah Y, & Jerina DM (1979) Synthesis of
    benzo [c]phenanthrene dihydrodiols. Tetrahedr Lett, 31: 2849-2852.

    Crosby NT, Hunt DC, Philp LA, & Patel I (1981) Determination of
    polynuclear aromatic hydrocarbons in food, water and smoke using
    high-performance liquid chromatography. Analyst, 106: 135-145.

    Crössmann G & Wüstemann M (1992) [Loadings in domestic gardens and
    allotments by anorganic and organic substances with damaging
    potential: Actual documentation. Part I: Soils and garden wastes and
    Part II: Vegetables and fruits.] Berlin, Ministry of Environment, pp
    40-42, 108-124 (in German).

    Crow KD, Alexander E, Buck WHL, Johnson BE, Magnus IA, & Porter AD
    (1961) Photosensitivity due to pitch. Br J Dermatol, 73: 220-232.

    Csaba G & Inczefi-Gonda A (1992) Benzopyrene exposure at 15 days of
    prenatal life reduces the binding capacity of thymic glucocorticoid
    receptors in adulthood. Gen Pharmacol, 23: 123-124.

    Csaba G, Inczefi-Gonda A, & Szeberenyi S (1991) Lasting impact of a
    single benzpyrene treatment in pre-natal and growing age on the thymic
    glucocorticoid receptors of rats. Gen Pharmacol, 22: 815-818.

    Culp SJ, Gaylor DW, Sheldon WG, Goldstein LS, & Beland FA (1996) DNA
    adduct measurements in relation to tumor incidence during the chronic
    feeding of coal tar or benzo(a)pyrene to mice. Polycyclic Aromat Compd
    11: 161-168.

    Cummings DA, Lin ELC, Daniel FB, Klaunig JE, & Schut, HAJ (1991)  In
    vivo and  in vitro binding of benzo [a]pyrene to tissue DNA and
    circulating macromolecules in the mouse, monkey and human. Proc Am
    Assoc Cancer Res, 32: 159.

    Dahl AR, Coslett DC, Bond JA, & Hesseltine GR (1985) Metabolism of
    benzo [a]pyrene on the nasal mucosa of Syrian hamsters: Comparison to
    other extrahepatic tissues and possible role of nasally produced
    metabolites in carcinogenesis. J Natl Cancer Inst, 75: 135-139.

    Dai Q (1980) Researches on chemical carcinogens and mechanism of
    chemical carcinogenesis. DI-region theory: A quantitative molecular
    orbital model of carcinogenic activity for polycyclic aromatic
    hydrocarbons. Sci Sin, 23: 453-470.

    Daisey JM (1983) Analysis of polycyclic aromatic hydrocarbons by
    thin-layer chromatography. In: Bjorseth A ed. Handbook of polycyclic
    aromatic hydrocarbons. New York, Marcel Dekker, pp 397-437.

    Daisey JM & Gundel LA (1993) Method 20: Determination of extractable
    particulate organic matter and selected polycyclic aromatic
    hydrocarbons. In: Seifert B, van de Wiel HJ, Dodet B, & O'Neill IK ed.
    Environmental carcinogens. Methods of analysis and exposure
    measurement: Volume 12. Indoor air. Lyon, International Agency for
    Research on Cancer, pp 314-327 (IARC Scientific Publications No 109).

    Daisey JM, McCaffrey RJ, & Gallagher RA (1981) Polycyclic aromatic
    hydrocarbons and total extractable particulate organic matter in the
    arctic aerosol. Atmos Environ, 15: 1353-1361.

    Daisey JM, Cheney JL, & Lioy PH (1986) Profiles of organic particulate
    emissions from air pollution sources: Status and needs for receptor
    source apportionment modeling. J Air Pollut Control Assoc, 36: 17-33.

    Daisey JM, Spengler JD, & Kaarakka P (1989) A comparison of the
    organic chemical composition of indoor aerosols during woodburning and
    non-woodburning periods. Environ Int, 15: 435-442.

    Danz M, Hartmann A, Otto M, & Blaszyk H (1991) Hitherto unknown
    additive growth effects of fluorene and 2-acetylaminofluorene on bile
    duct epithelium and hepatocytes in rats. Arch Toxicol, 14 (suppl): 71-
    74.

    Darby FW, Willis AF, & Winchester RV (1986) Occupational health
    hazards from road construction and sealing work. Ann Occup Hyg, 30:
    445-454.

    Darville RG & Wilhm JL (1984) The effect of naphthalene on oxygen
    consumption and hemoglobin concentration in  Chironomus 
    attenuatus and on oxygen consumption and life cycle of  Tanytarsus
    dissimilis. Environ Toxicol Chem, 3: 135-142.

    Davenport R & Spacie A (1991) Acute phototoxicity of harbor and
    tributary sediments from lower Lake Michigan. J Great Lakes Res, 17:
    51-56.

    Davidson GE & Dawson GWP (1976) Chemically induced presumed somatic
    mutations in the mouse. Mutat Res, 38: 151-154.

    Davies IW, Harrison RM, Perry R, Ratnayaka D, & Wellings RA (1976)
    Municipal incinerator as source of polynuclear aromatic hydrocarbons
    in environment. Environ Sci Technol, 10: 451-453.

    Davies GM, Hodkinson A, & DiVetta P (1986) Measurement and analysis of
    occupational exposures to coke oven emissions. Ann Occup Hyg, 30: 51-
    62.

    Davis WW, Krahl ME, & Clowes GHA (1942) Solubility of carcinogenic and
    related hydrocarbons in water. J Am Chem Soc, 64: 108-110.

    Davis BR, Whitehead JK, Gill ME, Lee PN, Butterworth AD, & Roe FJR
    (1975) Response of rat lung to 3,4-benzpyrene administered by
    intratracheal instillation in infusine with or without carbon black.
    Br J Cancer, 31: 443-452.

    Davis CS, Fellin P, & Otson R (1987) A review of sampling methods for
    polyaromatic hydrocarbons in air. J Am Pollut Control Assoc, 37: 1397-
    1408.

    Deal CL (1995) The role of metabolic activation in B[a]P-induced
    suppression of the humoral immune response. Richmond, Virginia,
    Virginia Commonwealth University, Medical College of Richmond, 120 pp
    (Doctoral Thesis).

    Dean BJ (1981) Activity of 27 coded compounds in the RL, chromosome
    assay. In: De Serres FJ & Ashby J ed. Evaluation of short-term tests
    for carcinogens. Report of the international collaborative programme.
    New York, Elsevier North-Holland, pp 570-579 (Progress in Mutation
    Research, Volume 1).

    Dean RG, Bynum G, Jacobson-Kram D, & Hadley E (1983a) Activation of
    polycyclic hydrocarbons in Reuber H4-II-E hepatoma cells. An
     in vitro system for the induction of SCEs. Mutat Res, 11: 419-427.

    Dean JH, Luster MI, Boorman GA, Lauer LD, & Leubke RW (1983b)
    Selective immunosuppression resulting from exposure to the
    carcinogenic congener benzopyrene in B6C3F1 mice. Clin Exp Immunol,
    52: 199-206.

    Dean JH, Ward EC, Murray MJ, Lauer LD, House RV, Stillman W, Hammilton
    TA, & Adams DO (1986) Immunosupression following
    7,12-dimethylbenz [a]anthracene exposure in B6C3F1 mice. II. Altered
    cell-mediated imunity and tumor resistance. Int J Immunopharmacol, 8:
    189-198.

    De Fré R, Bruynseraede P, & Kretzschmar JG (1994) Air pollution
    measurements in traffic tunnels. Environ Health Perspectives, 102: 31-
    37.

    DeGraeve GM, Geiger DL, Meyer JS, & Bergman HL (1980) Acute and
    embryo-larval toxicity of phenolic compounds to aquatic biota. Arch
    Environ Contam Toxicol, 9: 557-568.

    DeGraeve GM, Elder RG, Woods DC, & Bergman HL (1982) Effects of
    naphthalene and benzene on fathead minnows and rainbow trout. Arch
    Environ Contam Toxicol, 11: 487-490.

    DeLeon IR, Byrne CJ, Peuler EA, Antoine SR, Schaeffer J, & Murphy RC
    (1986) Trace organic and heavy metal pollutants in the Mississippi
    River. Chemosphere, 15: 795-805.

    Dell'Omo M & Lauwerys RR (1993) Adducts of macromolecules in the
    biological monitoring of workers exposed to polycyclic aromatic
    hydrocarbons. Crit Rev Toxicol, 23: 111-126.

    Den Hollander H, Van de Meent D, Van Noort P, & Wondergem E (1986) Wet
    deposition of polycyclic aromatic hydrocarbons in the Netherlands. Sci
    Total Environ, 52: 211-219.

    Dennis MJ, Massey RC, McWeeny DJ, Knowles ME, & Watson D (1983)
    Analysis of polycyclic aromatic hydrocarbons in UK total diets. Food
    Chem Toxicol, 21: 569-574

    Dennis MJ, Massey RC, Cripps G, Venn I, Howarth N, & Lee G (1991)
    Factors affecting the polycyclic aromatic hydrocarbons content of
    cereals, fats and other food products. Food Addit Contam, 8: 517-530.

    DePierre JW & Ernster L (1978) The metabolism of polycyclic
    hydrocarbons and its relationship to cancer. Biochim Biophys Acta,
    473: 149-186.

    De Raat WK, Schulting FL, Burghardt E, & De Meijere FA (1987a)
    Application of polyurethane foam for sampling volatile mutagens from
    ambient air. Sci Total Environ, 63: 175-189.

    De Raat WK, Kooijman SALM, & Gielen JWJ (1987b) Concentrations of
    polycyclic aromatic hydrocarbons in airborne particles in the
    Netherlands and their correlation with mutagenicity. Sci Total
    Environ, 66: 95-114.

    De Raat WK, Bakker GL, & De Meijere FA (1990) Comparison of filter
    materials used for sampling of mutagens and polycyclic aromatic
    hydrocarbons in ambient airborne particles. Atmos Environ, 24A: 2875-
    2887.

    DeSalvia R, Meschini R, Fiore M, Polani S, Palitti F, Carluccio MA, &
    Turchi G (1988) Induction of sister-chromatid exchanges by
    procarcinogens in metabolically competent Chinese hamster epithelial
    liver cells. Mutat Res, 207: 69-75.

    De Serres FJ & Ashby J ed. (1981) Evaluation of short-term tests for
    carcinogens. Report of the international collaborative programme. New
    York, Elsevier North Holland, 813 pp (Progress in Mutation Research,
    Volume 1).

    De Serres FJ & Hoffman GR (1981) Summary report on the performance of
    yeast assays. In: de Serres FJ & Ashby J ed. Evaluation of short-term
    tests for carcinogens. Report of the international collaborative
    programme. New York, Elsevier North Holland, pp 68-76 (Progress in
    Mutation Research, Volume 1).

    Desideri PG, Lepri L, Heimler D, Giannessi S, & Checchini L (1984)
    Concentration, separation and determination of hydrocarbons in sea
    water. J Chromatogr, 284: 167-178.

    Desideri PG, Lepri L, Canovaro M, & Checcini L (1988) Recovery,
    identification and determination of organic compounds in marine
    sediments. Stud Environ Sci, 34: 317-331.

    Deutsch-Wenzel RP (1983) Experimental studies on the carcinogenicity
    of five nitrogen containing polynuclear aromatic compounds directly
    injected into rat lungs. Cancer Lett, 20: 97-101.

    Deutsch-Wenzel RP, Brune H, Grimmer G, Dettbarn G, & Misfeld J (1983)
    Experimental studies in rat lungs on the carcinogenicity and dose-
    response relationships of eight frequently occuring environmental
    polycyclic aromatic hydrocarbons. J Natl Cancer Inst, 71: 539-544.

    Devanesan PD, Cremonesi P, Nunnally JE, Rogan EG, & Cavalieri EL
    (1990) Metabolism and mutagenicity of dibenzo [a,e]pyrene and the
    very potent environmental carcinogen dibenzo [a,l]pyrene. Chem Res
    Toxicol, 3: 580-586.
    263-268.

    De Wiest F (1978) Any factors influencing the dispersion and the
    transport of heavy hydrocarbons associated with airborne particles.
    Atmos Environ, 12: 1705-1711.

    DeWitt TH, Swartz RC, & Lamberson JO (1989) Measuring the acute
    toxicity of estuarine sediments. Environ Toxicol Chem, 8: 1035-1048.

    Diamond L, Kruszewski F, Aden DP, Knowles BB, & Baird WM (1980)
    Metabolic activation of benzo [a]pyrene by a human hepatoma cell
    line. Carcinogenesis, 1: 871-875.

    Dickerson RL, Hooper MJ, Gard NW, Cobb GP, & Kendall RJ (1994)
    Toxicological foundations of ecological risk assessment: Biomarker
    development and interpretation based on laboratory and wildlife
    species. Environ Health Perspectives, 102 (suppl 12): 65-69.

    Diercxsens P & Tarradellas J (1987) Soil contamination by some organic
    micropollutants related to sewage sludge spreading. Int J Environ Anal
    Chem, 28: 143-159.

    DiGiovanni J, Diamond L, Pritchett WP, Fisher EP, & Harvey RG (1985)
    Tumor-initiating activity of the 9,10-dihydrodiol- and
    9,10-dihydrodiol-7,8-epoxide of 3-methylcholanthrene in Sencar mice.
    Cancer Lett, 28: 223-228.

    Dikun PP (1967) [Detection of polycyclic aromatic hydrocarbons in
    atmospheric contamination and other materials with quasi-linear
    fluorescence spectra.] Zh Prikl Spektrosk, 6: 202-209 (in Russian).
    DiMichele L & Taylor M (1978) Histopathological and physiological
    responses of  Fundulus heteroclitus to naphthalene exposure. J Fish
    Res Board Can, 35: 1060-1066.

    DiPaolo JA & Casto BC (1976)  In vitro transformation: Interaction of
    chemical carcinogens with viruses and physical agents. In: Montesano
    R, Bartsch, H, & Tomatis L ed. Screening tests in chemical
    carcinogenesis. Lyon, International Agency for Research on Cancer, pp
    415-432 (IARC Scientific Publications No. 12).

    DiPaolo JA, Donovan JP, & Nelson RL (1969) Quantitative studies of  in
    vitro transformation by chemical carcinogens, J Natl Cancer Inst 42:
    867-874.

    DiPaolo JA, Donovan PJ, & Nelson RL (1971) Transformation of hamster
    cells  in vitro by polycyclic hydrocarbons without cytotoxicity. Proc
    Natl Acad Sci USA, 68: 2958-2961.

    DiPaolo JA, Takano K, & Popescu NC (1972) Quantitation of chemically
    induced neoplastic transformation of BALB/3T3 cloned cell lines.
    Cancer Res, 35: 2686-2695.

    DiPaolo JA, Nelson RL, Donovan PJ, & Evans CH (1973) Host-mediated  in
    vivo-in vitro assay for chemical carcinogenesis. Arch Pathol, 95:
    380-385.

    DiPaolo JA, Doniger J, Evans CH, & Popescu NC (1985) Enhancement and
    inhibition of transformation of Syrian hamster embryo cells.
    Carcinogenesis, 8: 319-328.

    Dipple A, Moschel RC, & Bigger CAH (1984) Polynuclear aromatic
    carcinogens. In: Searle CE ed. Chemical carcinogenesis, 2nd ed.
    Washington DC, American Chemical Society, Vol 1ume, pp 41-163.

    Dipple A, Pigott MA, Agarwal SK, Yagi H, Sayer JM, & Jerina DM (1987)
    Optically active benzo [c]phenanthrene diol epoxides bind extensively
    to adenine in DNA. Nature, 327: 535-536.

    Dipple A, Cheng SC, & Bigger CA (1990) Polycyclic aromatic hydrocarbon
    carcinogens. Prog Clin Biol Res, 347:109-127.

    Dobriner K, Rhoads CP, & Lavin GI (1939) Conversion of
    1,2,5,6-dibenzanthracene by rabbits, rats and mice. Significance in
    carcinogenesis of this conversion. Proc Soc Exp Biol Med, 41: 67-69.

    Dock L, Waern F, Martinez M, Grover PL, & Jernstrom B (1986) Studies
    on the further activation of benz [a]pyrene diol epoxides by rat
    liver microsomes and nuclei. Chem-Biol Interactions, 58: 301-318.

    Doll R, Vessey MP, Buckley AR, Fear EC, Gammon EJ, Gunn W, Hughes GO,
    Lee K, & Norman-Smith B (1972) Mortality of gasworkers. Final report
    of a prospective study. Br J Med, 29: 394-406.

    Dong MW & Greenberg A (1988) Liquid chromatographic analysis of
    polynuclear aromatic hydrocarbons with diode array detection. J Liq
    Chromatogr, 11: 1887-1905.

    van Dongen (1987) [Leaching characteristics of pre-impregnated wood
    during storage, Parts 1 and 2.]. Zeist, Organisation for Applied
    Science (TNO), 170 pp (Report No. HI 87.1178) (in Dutch).

    Donkin P, Widdows J, Evans SV, Worrall CM, & Carr M (1989)
    Quantitative structure-activity relationships for the effect of
    hydrophobic organic chemicals on rate of feeding by mussels  Mytilus
    edulis. Aquat Toxicol, 14: 277-293.

    Doremire ME, Harmon GE, & Pratt DE (1979) 3,4-Benzopyrene in charcoal
    grilled meats. J Food Sci, 44: 622-623.

    DouAbdul AAZ, Abaychi JK, Al-Edanee TE, Ghani AA, & Al-Saad HT (1987)
    Polynuclear aromatic hydrocarbons (PAHs) in fish from the Arabian
    Gulf. Bull Environ Contam Toxicol, 38: 546-552.

    Dragoescu C & Friedlander S (1989) Dynamics of the aerosol products of
    incomplete combustion in urban atmospheres. Aerosol Sci Technol, 10:
    249-257.

    Draudt HN (1963) The meat smoking process: A review. Food Technol, 17:
    85-90.

    Dreier F, Siles S, Buchs M, Gülacar FO, & Buchs A (1985) [Polycyclic
    aromatic hydrocarbons in sediments of Léman Lake.] Arch Sci Genève,
    38: 215-224 (in French).

    Druckrey H & Schmähl D (1955) [Carcinogenic effect of anthracene.]
    Naturwissen-schaften, 42: 159-160 (in German).

    Dunkel VD, Pienta RJ, Sivak A, & Traul KA (1981) Comparative
    neoplastic transformation responses of Balb/3T3 cells, Syrian hamster
    embryo cells, and Rauscher murine leukemia virus-infected Fischer 344
    rat embryo cells to chemical carcinogens. J Natl Cancer Inst, 67:
    1303-1315.

    Dunkel VC, Zeiger E, Brusick D, McCoy E, McGregor D, Mortelmans K,
    Rosenkranz HS, & Simmon VF (1984) Reproducibility of microbial
    mutagenicity assays: 1. Tests with  Salmonella typhimurium and
     Escherichia coli using a standardized protocol. Environ Mutag, 6
    (suppl 2): 1-39.

    Dunkel VC, Schechtmann LM, Tu AS, Sivak A, Lubet RA, & Cameron TP
    (1988) Intralaboratory evaluation of the C3H/10T1/2 cell
    transformation assay. Environ Mol Mutag, 12: 21-31.

    Dunlap CE & Warren S (1943) The carcinogenic activity of some new
    derivatives of aromatic hydrocarbons. I. Compounds related to
    chrysene. Cancer Res, 3: 606-607.

    Dunn BP & Douglas GR (1991) DNA adducts in cells treated with
    1-methylphenanthrene. Proc Am Assoc Cancer Res, 32: 93.

    Duus U, Ahlborn J, & Andersson J (1994) Toxic oil in rubber tyres.
    Solna, National Chemicals Inspectorate, 4 pp.

    Eadie B, Landrum PF, & Faust W (1982) Polycyclic aromatic hydrocarbons
    in sediments pore water and the amphipod
     Pontoporeia hoyi from Lake Michigan, USA. Chemosphere, 11: 847-858.

    Eadie BJ, Morehead NR, & Landrum PF (1990) Three-phase partitioning of
    hydrophobic organic compounds in Great Lakes waters. Chemosphere, 20:
    161-178.

    Eastmond D, Booth G, & Lee M (1984) Toxicity accumulation and
    elimination of polycyclic aromatic sulfur heterocycles in
     Daphnia magna. Arch Environ Contam Toxicol, 13: 105-112.

    Edes TE, Gysbers DG, Buckley CS, & Thornton WH Jr (1991) Exposure to
    the carcinogen benzopyrene depletes tissue vitamin A: b-Carotene
    prevents depletion. Nutr Cancer, 15: 159-166.

    Edmisten G & Bantle J (1982) Use of  Xenopus laevis larvae in 96
    hour, flow-through toxicity tests with naphthalene. Bull Environ
    Contam Toxicol, 29: 392-399.

    Edsall CC (1991) Acute toxicities to larval rainbow trout of
    representative compounds detected in Great Lakes fish. Bull Environ
    Contam Toxicol, 46: 173-178.

    Edwards NT (1983) Polycyclic hydrocarbons (PAHs) in the terrestrial
    environment. A review. J Environ Qual, 12: 427-441.

    Edwards NT (1986) Uptake translocation and metabolism of anthracene in
    bush bean  Phaseolus vulgaris. Environ Toxicol Chem, 5: 659-666.

    Egan-Baum E, Miller BA, & Waxweiler RJ (1981) Lung cancer and other
    mortality patterns among foundrymen. Scand J Work Environ Health, 7
    (suppl 4): 147-155.

    Ehrlich HW & Beevers CA (1956) The crystal structure of
    2:13-benzfluoranthene. Acta Crystal, 9: 602-606.

    Eiceman GA, Clement RE, & Karasek FW (1979) Analysis of fly ash from
    municipal incinerators for trace organic compounds. Anal Chem, 51:
    2343-2350.

    Eisenhut W, Friedrich F, & Reinke M (1990) Coking plant environment in
    West-Germany. Coke Making Int, 1: 74-77.

    Eisenstadt E & Gold A (1978) Cyclopenta [c,d]pyrene: A highly
    mutagenic polycyclic aromatic hydrocarbon. Proc Natl Acad Sci USA, 75:
    1667-1669.

    El-Bayoumy K, Amin S, & Hecht SS (1986) Effects of 6-nitro
    substitution on 5-methylchrysene tumorigenicity, mutagenicity and
    metabolism. Carcinogenesis, 7: 673-676.

    Elgjo K (1968) Growth kinetics of the mouse epidermis after a single
    application of 3,4-benzopyrene, croton oil, or 1,2-benzopyrene. Acta
    Pathol Microbiol Scand, 73: 183-190.

    Eling TE & Curtis JF (1992) Xenobiotic metabolism by prostaglandin H
    synthase. Pharmacol Ther, 53: 261-273.

    Eling T, Curtis J, Battista J, & Marnett LJ (1986) Oxidation of
    (+)-7,8-dihydroxy-7,8-dihydrobenzo [a]pyrene by mouse keratinocytes:
    Evidence for peroxyl radical- and monoxygenase-dependent metabolism.
    Carcinogenesis, 12: 1957-1963.

    Ellwardt PC (1976) [German Society for Moor and Peat. Determination of
    polycyclic aromatic hydrocarbons with and without carcinogenic effect
    in peat in comparison with their occurrence in soils and composts].
    Ber Dtsch Ges Moor Torfkunde Hanover, 6: 135-144 (in German).

    Elmets CA, Khan WA, Klemme JC, & Mukhtar H (1988) Impaired
    immunological surveillance by 7,12-dimethylbenz [a]anthracene
    augments its skin tumorigenicity in C3H mice. Biochem Biophys Res
    Commun, 151: 148-152.

    Elovaara E, Heikkilä P, Pyy L, Muranen P, & Riihimäki V (1995)
    Significance of dermal and respiratory uptake in creosote workers:
    Exposure to polycyclic aromatic hydrocarbons and urinary excretion of
    1-hydroxypyrene. Occup Environ Med, 52: 196-203.

    Emerole GO, Uwaifo AO, Thabarew MI, & Bababunmi EA (1982) The presence
    of aflatoxin and some polycyclic aromatic hydrocarbons in human foods.
    Cancer Lett, 15: 123-129.

    Emura M, Richter-Reichhelm HB, Schneider P, & Mohr U (1980)
    Sensitivity of Syrian golden hamster fetal lung cells to
    benzo [a]pyrene and other polycyclic hydrocarbons  in vitro. 
    Toxicology, 17: 149-155.

    Emura M, Mohr U, Riebe M, Aufderheide M, & Dungworth DL (1987)
    Predispostion of cloned fetal hamster lung epithelial cells to
    transformation by a precarcinogen, benzo(a)pyrene, using growth
    hormone supplementation and collagen gel substratum. Cancer Res, 47:
    1155-1160.

    Engelbreth-Holm J (1941) Acceleration of the development of mammary
    carcinomas in mice by methylcholanthrene. Cancer Res, 1: 109-112.

    Engewald W, Knobloch T, & Efer J (1993) [Volatile organic compounds in
    emissions from brown-coal-fired residential stoves.] Z Umweltchem
    Okotox, 5: 303-308 (in German).

    Engholm G, Englund A, & Linder B (1991) Mortality and cancer incidence
    in Swedish road paving asphalt workers and roofers. Eur Asphalt Mag,
    1: 62-67.

    Environment Agency, Japan (1993) Chemicals in the environment: Summary
    of the result of environmental survey for chemical substances 1974 to
    1991. Tokyo, 5 pp.

    Environment Canada (1994) Canadian Environmental Protection Act.
    Priority substances list assessment report: Polycyclic aromatic
    hydrocarbons. Ottawa, Ministry of Supply and Services, 61 pp.

    Epler JL, Rao TK, & Guerin MR (1979) Evaluation of feasibility of
    mutagenic testing of shale oil products and effluents. Environ Health
    Perspectives, 30: 179-184.

    Epstein S (1968) Chemical mutagens in the human environment. Nature,
    219: 385-387.

    Ermer M (1970) [Studies with carcinogens in short-lived fish species.]
    Zool Anz, 184: 175-193 (in German).

    Ernst W, Eder G, Goerke H, Weber K, Weigelt S, & Weigelt V (1986)
    [Organic environmental chemicals in German estuaries and coastal
    waters: Origin, biotransfer, degradation.] Bremerhaven, Federal
    Ministry for Research and Technology, Institute for Oceanography, 78
    pp (Report No. M/86-001) (in German).

    European Aluminium Association, Environment, Health and Safety
    Secretariat (1990) Polycyclic aromatic hydrocarbons. Oslo, 51 pp
    (Report of the Working Group on PAH No. ALUM./TEKN.-HYG.UTV No.
    80-90).

    European Economic Community (1967) Council Directive 67/548/EEC, of 27
    June 1967 on the approximation of laws, regulations and administrative
    provisions relating to the classification, packaging and labelling of
    dangerous substances. Off J Eur Communities, L196: 234-237

    European Economic Community (1980) Council Directive 80/778/EEC, of 15
    July 1980, relating to the quality of water intended for human
    consumption. Off J Eur Communities, L229: 11-29.

    European Economic Community (1983) Council Directive of 16 June 1983
    amending Council Directive 70/220/EEC on the approximation of the laws
    of the Member States relating to measures to be taken against air
    pollution by gases from positive ignition engines of motor vehicles
    (83/351/EEC). Off J Eur Communities, L 197(I): 1.

    European Economic Community (1988) Council Directive, of 22 June 1988,
    on the approximation of the laws of member states relating to
    flavourings for use in foodstuffs and to source materials for their
    production (88/388/EEC). Off J Eur Communities,  L184: 61-65.

    European Economic Community (1991) Council Directive, of 29 May 1991,
    on establishing indicative values by implementing Council Directive
    80/1107/EEC on the protection of workers from the risks related to
    exposure to chemical, physical and biological agents at work
    (91/322/EEC). Off J Eur Communities, L177: 22-24.

    European Economic Community (1994a) Council Directive 94/69/EC, of 19
    December 1994 adapting to technical progress for the twenty-first time
    Council Directive 67/548/EEC on the approximation of laws, regulations
    and administrative provisions relating to the classification,
    packaging and labelling of dangerous substances. Off J Eur
    Communities, L381: 1-241.

    European Economic Community (1994b) Council Directive 94/60/EC, of 25
    November 1994 updating technical norms for concentration limits, and
    attention and alarm levels for atmospheric pollution in urban areas
    and provisions for certain pollutants referred to in the ministerial
    decree of 15 April 1994. Off J Eur Communities, L290: 1-32.

    Evans CH & DiPaolo JA (1975) Neoplastic transformation of guinea pig
    fetal cells in culture induced by chemical carcinogens. Cancer Res,
    35: 1035-1044.

    Evans MS & Landrum PF (1989) Toxicokinetics of DDE, benzo [a]pyrene,
    and 2,4,5,2',4',5'-hexachlorobiphenyl in  Pontoporeia hoyi and  Mysis
    relicta. J Great Lakes Res, 15: 589-600.

    Evans EL & Mitchell AD (1981) Effects of 20 coded chemicals on sister
    chromatid exchange frequencies in cultured Chinese hamster cells. In:
    De Serres FJ & Ashby J ed. Evaluation of short-term tests for
    carcinogens. Report of the international collaborative programme. New
    York, Elsevier North Holland, pp 538-550 (Progress in Mutation
    Research, Volume 1).

    Fabacher DL, Besser JM, Schmitt CJ, Harshbarger JC, Peterman PH, &
    Lebo JA (1991) Contaminated sediments from tributaries of the Great
    Lakes: Chemical characterization and carcinogenic effects in medaka
     (Oryzias latipes). Arch Environ Contam Toxicol, 21: 17-34.

    Fahmy OG & Fahmy MJ (1973) Oxidative activiation of
    benz [a]anthrazene and methylated derivatives in mutagenesis and
    carcinogenesis. Cancer Res, 33: 2354-2361.

    Fahmy MJ & Fahmy OG (1980) Altered control of gene acitivity in the
    soma by carcinogens. Mutat Res, 72: 165-172.

    Falk HL, Kotin P, & Markul I (1958) The disappearance of carcinogens
    from soot in human lungs. Cancer, 11: 482-489.

    Falk HL, Kotin P, Lee SS, & Nathan A (1962) Intermediary metabolism of
    benzo [a]pyrene in the rat. J Natl Cancer Inst, 28: 699-724.

    Fallon ME & Horvath FJ (1985) Preliminary assessment of contaminants
    in soft sediments of the Detroit River. J Great Lakes Res, 11: 373-
    378.

    Fanburg SJ (1940) Exfoliative dermatitis due to naphthalene: Report of
    an eruption resembling  Mycosis fungoides. Arch Dermatol Syphilol,
    42: 53-58.

    Faoro RB & Manning JA (1981) Trends in benzo(a)pyrene, 1966-77. J Air
    Pollut Control Assoc, 31: 62-64.

    Farrington JW (1991) Biochemical processes governing exposure and
    uptake of organic pollutant compounds in aquatic organisms. Environ
    Health Perspectives, 90: 75-84.

    Fazio T (1990) 48. Food additives. Indirect: Polycyclic aromatic
    hydrocarbons and benzo [a]pyrene in food. Spectrophotometric method
    (No. 973.30). In: Helrich K ed. Official methods of analysis of the
    Association of Official Analytical Chemists (AOAC), 15th ed.
    Arlington, Virginia, Association of Official Analytical Chemists,
    Volume 2, pp 1176-1178.

    Fedorak PM, Foght JM, & Westlake DWS (1982) A method for monitoring
    mineralization of 14C-labeled compounds in aqueous samples. Water
    Res, 16: 1285-1290.

    Fendinger NJ, Radway JC, Tuttle JH, & Means JC (1989) Characterization
    of organic material leached from coal by simulated rainfall. Environ
    Sci Technol, 23: 170-177.

    Feron VJ, de Jong D, & Emmelot P (1973) Dose-response correlation for
    the induction of respiratory-tract tumors in Syrian golden hamsters by
    intratracheal instillations of benzo(a)pyrene. Eur J Cancer, 9: 387-
    390.

    Ferraro S, Lee I, Ozretich R, & Specht D (1990) Predicting
    bioaccumulation potential. A test of a fugacity-based model. Arch
    Environ Contam Toxicol, 3: 386-394.

    Ferreira MJ Jr, Buchet JP, Burrion JB, Moro J, Cupers L, Delavignette
    JP, Jacques J, & Lauwerys R (1994a) Determinants of urinary
    thioethers, D-glucaric acid and mutagenicity after exposure to
    polycyclic aromatic hydrocarbons assessed by air monitoring and
    measurement of 1-hydroxypyrene in urine: A cross-sectional study in
    workers of coke and graphite-electrode-producing plants. Int Arch
    Occup Environ Health, 65: 329-338.

    Ferreira M Jr, Tas S, Dell'Omo M, Goormans G, Buchet JP, & Lauwerys R
    (1994b) Determinants of benzo(a)pyrene diol epoxide adducts to
    haemoglobin in workers exposed to polycyclic aromatic hydrocarbons.
    Occup Environ Med, 51: 451-455.

    Feunekes FDJR, Jongeneleen FJ, van der Laan H, & Schoonhof FHG (1997)
    Uptake of polycyclic aromatic hydrocarbons among trainers in a
    fire-fighting training facility. Am Ind Hyg Assoc J, 58: 23-28.

    Finger SE, Little EF, Henry MG, Fairchild JF, & Boyle TP (1985)
    Comparison of laboratory and field assessment of fluorene. Part I:
    Effects of fluorene on the survival, growth, reproduction, and
    behavior of aquatic organisms in laboratory tests. In: Boyle TP ed.
    Validation and predictability of laboratory methods for assessing the
    fate and effects of contaminants in aquatic ecosystems. Philadelphia,
    Pennsylvania, American Society for Testing and Materials, pp 120-133
    (ASTM STP No. 865).

    Flesher JW & Myers SR (1990) Bioalkylation of benz(a)anthracene as a
    biochemical probe for carcinogenic activity. Drug Metab Disposition,
    18: 163-167.

    Flesher JW & Myers SR (1991) Rules of molecular geometry for
    predicting carcinogenic activity of unsubstituted polynuclear aromatic
    hydrocarbons. Teratog Carcinog Mutag, 11: 41-54.

    Florin I, Rutberg L, Curvall M, & Enzell CR (1980) Screening of
    tobacco smoke constituents for mutagenicity using the Ames' test.
    Toxicology, 18: 219-232.

    Flury F & Zernik F (1935) [List of the toxic and lethal doses for the
    most common poisons in experimental animals.] In: Abderhalden E ed.
    [Handbook of biological methods.] Berlin, Urban & Schwarzenberg, pp
    12289-14222 (in German).

    Foran JA, Holst LL, & Giesy JP (1991) Effects of photoenhanced
    toxicity of anthracene on ecological and genetic fitness of  Daphnia
    magna: A reappraisal. Environ Toxicol Chem, 10: 425-427.

    Forbes PD, Davies RE, & Urbach F (1976) Phototoxicity and
    photocarcinogenesis: Comparative effects of anthracene and
    8-methoxypsoralen in the skin of mice. Food Cosmet Toxicol, 14: 303-
    306.

    Foster GD, Baksi SM & Means JC (1987) Bioaccumulation of trace organic
    contaminants from sediment by Baltic clams  (Macoma 
     balthica) and soft-shell clams  (Mya arenaria). Environ Toxicol
    Chem, 6: 969-976.

    Fox MA & Staley SW (1976) Determination of polycyclic aromatic
    hydrocarbons in atmospheric particulate matter by high pressure liquid
    chromatography coupled with fluorescence techniques. Anal Chem, 48:
    992-998.

    Fox CH, Selkirk JK, Price FM, Croy RG, Sandord KK, & Cottler-Fox M
    (1975) Metabolism of benzo [a]pyrene by human epithelial cells
     in vitro. Cancer Res, 35: 3551-3557.

    Fox M, Lutz H-J, Gassman E, & Yoshikawa S (1988) Chemical economics
    handbook (CEH): Product review for naphthalene. Menlo Park,
    California, SRI International, 31 pp.

    Franck HG & Stadelhofer JW (1987) [Industrial aromatic chemistry. Raw
    products, processes, products.] Berlin, Springer-Verlag, pp 308-380
    (in German).

    Frank AP, Landrum PF, & Eadie BJ (1986) Polycyclic aromatic
    hydrocarbon: Rates of uptake, depuration, and biotransformation by
    Lake Michigan  (Stylodrilus heringianus). Chemosphere, 15: 317-330.

    Freeman AE, Weisburger EK, Weisburger JH, Wolford RG, Maryak JM &
    Huebner RJ (1973) Transformation of cell cultures as an indication of
    the carcinogenic potential of chemicals. J Natl Cancer Inst, 51: 799-
    807.

    Freitag DL, Ballhorn L, Geyer H, & Korte F (1985) Environmental hazard
    profile of organic chemicals. An experimental method for the
    assessment of the behaviour of organic chemicals in the ecosphere by
    means of simple laboratory tests with 14C labelled chemicals.
    Chemosphere, 14: 1589-1616.

    Fritz W (1971) [The extent of sources of contamination of our food
    with carcinogenic hydrocarbons.] Ernährungsforschung, 16: 547-557 (in
    German).

    Fritz W (1972) [Contamination of food with carcinogenic hydrocarbons
    during processing and cooking.] Arch Geschwulstforsch, 40: 81-90 (in
    German).

    Fritz W (1983) [Analysis and assessment of carcinogenic polycyclic
    aromatic hydrocarbons from the food hygiene. Toxicology point of view.
    A review]. Nahrung, 27: 965-973 (in German).

    Frölich A & Würgler FE (1990) Drosophila wing-spot test: Improved
    detectability of genotoxicity of polycyclic aromatic hydrocarbons.
    Mutat Res, 234: 71-80.

    Frumin G, Chuiko G, Pavlov D, & Menzykova O (1992) New rapid method to
    evaluate the median effect concentrations of xenobiotics in
    hydrobionts. Bull Environ Contam Toxicol, 49: 361-367.

    Fujikawa K, Fort FL, Samejima K, & Sakamoto Y (1993) Gentoxic potency
    in  Drosophila melanogaster of selected aromatic amines and
    polycyclic hydrocarbons as assayed in the DNA repair test. Mutat Res,
    290: 175-182.

    Fukuda K, Inagaki Y, Maruyama T, Kojima HI, & Yoshida T (1988) On the
    photolysis of alkylated naphthalenes in aquatic systems. Chemosphere,
    17: 651-659.

    Funcke W, König J, Henze W, & Umland F (1986) Determination of
    polycyclic aromatic hydrocarbons in mainstream cigarette smoke with
    respect to particle size. In: Cooke M & Dennis AJ ed. Polynuclear
    aromatic hydrocarbons: Chemistry, characterization and carcinogenesis.
    Columbus, Ohio, Battelle Press, pp 333-341.

    Funcke W, König J, & Balfanz E (1988) Determination of polycyclic
    aromatic hydrocarbons in flue gases from coal-fired power plants. In:
    Cooke M & Dennis AJ ed. Polynuclear aromatic hydrocarbons: A decade of
    progress. Columbus, Ohio, Battelle Press, pp 277-284.

    Furlong ET, Carter DS, & Hites, RA (1988) Organic contaminants in
    sediments from the Trenton Channel of the Detroit River, Michigan. J
    Great Lakes Res, 14: 489-501.

    Furst A, Kolff B, & Dempsey DA (1979) Pulmonary tumor induction: Three
    hydrocarbons compared. Proc West Pharmacol Soc, 22: 269-271.

    Gaines TB (1969) Acute toxicity of pesticides. Toxicol Appl Pharmacol,
    14: 515-534.

    Gala WR & Giesy JP (1992) Photo-induced toxity of anthracene to the
    green algae,  Selenastrum capricornutum. Arch Environ Contam Toxicol,
    23: 316-323.

    Gamper HB, Tung ASC, Straub K, Bartholomew JC, & Calvin M (1977) DNA
    strand scission by benzo [a]pyrene diol epoxides. Science, 197: 671-
    674.

    Gamper HB, Bartholomew JC, & Calvin M (1980) Mechanism of
    benzo(a)pyrene diol epoxide induced deoxyribonucleic acid strand
    scission. Biochemistry, 19: 3948-3956.

    Gardiner K, Hale KA, Calvert IA, Rice D, & Harrington JM (1992) The
    suitability of the urinary metabolite 1-hydroxypyrene as an index of
    polynuclear aromatic hydrocaarbon bioavailability from workers exposed
    to carbon black. Ann Occup Hyg, 36: 681-688.

    Garg A, Beach A, & Gupta RC (1991) DNA-reactive metabolites (DRM)
    detected in the serum of benzo [a]pyrene (BP)-treated rodents by
    32P-postlabeling. Proc Am Assoc Cancer Res, 32: 122.

    Garrigues P & Ewald M (1987) High resolution emission spectroscopy
    (Shpol'skii effect): A new analytical technique for the analysis of
    polycyclic aromatic hydrocarbons (PAH) in the environmental samples.
    Chemosphere, 16: 485-494.

    Garrigues P, Soclo HH, Marniesse MP, & Ewald M (1987) Origin of
    polycyclic aromatic hydrocarbons (PAH) in recent sediments from the
    continental shelf of the 'Golfe de Gascogne' (Atlantic Ocean) and in
    the Gironde estuary. Int J Environ Anal Chem, 28: 121-131.

    Gauthier TD, Shane EC, Guerin WF, Seltz WR, & Grant CL (1986)
    Fluorescence quenching method for determining equilibrium constants
    for polycyclic aromatic hydrocarbons binding to dissolved humic
    materials. Environ Sci Technol, 20: 1162-1166.

    Gaydos RM (1981) Naphthalene. In: Kirk-Othmer encyclopedia of chemical
    technology, 3rd ed. New York, John Wiley & Sons, Volume 15, pp 698-
    719.

    Geacintov NE (1988) Mechanisms of reaction of polycyclic aromatic
    epoxide derivatives with nucleic acids. In: Yang SK & Silverman BD ed.
    Polycyclic aromatic hydrocarbon carcinogenesis: Structure-activity
    relationships. Boca Raton, Florida, CRC Press, Volume 2, pp 181-206.

    Geahchan A, Le Gren I, Chambon P, & Chambon R (1991) Improved method
    for determination of polynuclear aromatic hydrocarbons in
    pharmacopoeial paraffin and mineral oils. J Assoc Off Anal Chem, 74:
    968-973.

    Geddie JE, Amin S, Huie K, & Hecht SS (1987) Formation and
    tumorigenicity of benzo [b]fluoranthene metabolites in mouse
    epidermis. Carcinogenesis, 8: 1579-1584.

    Gehly EB, Landolph JR, Heidelberger C, Nagasawa H, & Little JB (1982)
    Induction of cytotoxicity, mutation, cytogenetic changes and
    neoplastic transformation by benzo(a)pyrene and derivatives in C3H/10T
    1/2 clone 8 mouse fibroblasts. Cancer Res, 42: 1866-1875.

    Geiger JG Jr & Buikema AL Jr (1981) Oxygen consumption and filtering
    rate of  Daphnia pulex after exposure to water-soluble fractions of
    naphthalene, phenanthrene, No. 2 fuel oil, and coal-tar creosote.
    Environ Contam Toxicol, 27: 783-789.

    Geiger JG Jr & Buikema AL Jr (1982) Hydrocarbons depress growth and
    reproduction of  Daphnia pulex (Cladocera). J Fish Aquat Sci, 39:
    830-836.

    Geiger DL, Northcott CE, Call DJ, & Brooke LT ed. (1985) Acute
    toxicities of organic chemicals to fathead minnows  Pimephales 
     promelas. Superior, Wisconsin, University of Wisconsin, Center for
    Lake Superior Environmental Studies, Volume 2, pp 211-212.

    Gelboin HV & Ts'o POP (1978) Polycyclic hydrocarbons and cancer.
    Volume 2: Metabolism and cell biology. New York, Academic Press, 441
    pp.

    Gendimenico GJ & Kochevar IE (1984) Degranulation of mast cells and
    inhibition of the response to secretory agents by phototoxic and
    ultraviolet radiation. Toxicol Appl Pharmacol, 76: 374-382

    Generoso WM, Cain KT, Hellwig CD, & Cacheiro NLA (1982) Lack of
    association between induction of dominant-lethal mutations and
    induction of heritable translocations with benzo(a)pyrene in
    postmeiotic germ cells of male mice. Mutat Res, 94: 155-163.

    Genevois C, Brandt HCA, Bartsch H, Wild CP & Castegnaro M (1995)
    Formation of DNA adducts in skin, lung and lymphocytes after skin
    painting of rats with undiluted coaltar and bitumen vapor/particulates
    condensates. In: Fifteenth international symposium on polycyclic
    aromatic compounds: Chemistry, biology and environmental impact,
    Belgirate, Italy, 19-22 September 1995. Ispra, Joint Research Centre
    European Commission, pp 54-55.

    Gensler HL (1988) Enhancement of chemical carcinogenesis in mice by
    systemic effects of ultraviolet irradiation. Cancer Res, 48: 620-623.

    Gerarde HW (1960) Toxicology and biochemistry of aromatic
    hydrocarbons. In: Browning E ed. Elsevier monographs on toxic agents.
    Amsterdam, Elsevier Publishing Co., pp 240-321.

    Gerhart E & Carlson R (1978) Hepatic mixed-function oxidase activity
    in rainbow trout exposed to several polycyclic aromatic compounds.
    Environ Res, 17: 284-295.

    German Federal Department for Worker Safety (1989) [23.TRK-Wert for
    benzo(a)pyrene.] In:[Bundesarbeitsblatt 10.] Dortmund, pp 58-61 (in
    German).

    German Federal Office for Sea Navigation and Hydrography (1993)
    [Monitoring of the sea. Report for the year 1990. Part II: Data.]
    Hamburg, pp 79-94 (in German).

    German Ministry of Environment (1979) [Air quality criteria for
    selected polycyclic aromatic hydrocarbons. PAH as an environmental
    carcinogen.] Berlin, Erich Schmidt Verlag, 270 pp (Report No.
    UBA-1/79) (in German).

    German Ministry of Environment (1993) [Environmental sample bank.
    Annual report 1991.] Berlin, 139 pp (Report No. UBA-7/93) (in German).

    German Research Commission (1991) Polycyclic aromatic hydrocarbons
    (PAH) (particle-bound). In: Kettrup A ed. Commission for the
    investigation of health hazards of chemical compounds in the work air,
    working group on analytical chemistry: Analyses of hazardous
    substances in air. Weinheim, VCH Publishers, Volume 1, pp 41-52.

    German Society for Mineral-oil and Coal Chemistry (1984)
    [Investigations into the contents of wastewater from oil refineries.]
    Hamburg, 95 pp (Report No. 283) (in German).

    Gershbein LL (1975) Liver regeneration as influenced by the structure
    of aromatic and heterocyclic compounds. Res Commun Chem Pathol
    Pharmacol, 11: 445-466.

    Gerstle RW, Cuffe ST, Orning AA, & Schwartz CH (1965) Air pollution
    emissions from coal-fired power plants. Report No. 2. J Air Pollut
    Control Assoc, 15: 59-64.

    Geyer H, Politzki G, & Freitag D (1984) Prediction of ecotoxicological
    behaviour of chemicals: Relationship between  n-octonal/water
    partition coefficient and bioaccumulation of organic chemicals by
     Alga chlorella. Chemosphere, 13: 269-284.

    Gharrett JA & Rice SD (1987) Influence of simulated tidal cycles on
    aromatic hudrocarbon uptake and elimination by the shore crab
     Hemigrapsus nudus. Mar Biol, 95: 365-370.

    Gibbs GW (1985) Mortality of aluminum reduction plant workers, 1950
    through 1977. J Occup Med, 27: 761-770.

    Gibbs GW & Horowitz I (1979) Lung cancer mortality in aluminum
    reduction plant workers. J Occup Med, 21: 347-353.

    Gibson TL (1982) Nitro derivates of polynuclear aromatic hydrocarbons
    in airborne and source particulate matter. Atmos Environ, 16: 2037-
    2040.

    Gibson ES, Martin RH, & Lockington JN (1977) Lung cancer mortality in
    a steel foundry. J Occup Med, 19: 807-812.

    Giger W & Schaffner C (1978) Determination of polycyclic aromatic
    hydrocarbons in the environment by glass capillary gas chromatography.
    Anal Chem, 50: 243-249.

    Gill RD, Butterworth BE, Nettikumara AN, & Digiovanni J (1991)
    Relationship between DNA adduct formation and unscheduled DNA
    synthesis (UDS) in cultured mouse epidermal keratinocytes. Environ Mol
    Mutag, 18: 200-206.

    Ginsberg GL & Atherholt TB (1989) Transport of DNA-adducting
    metabolites in mouse serum following benzo(a)pyrene administration.
    Carcinogenesis, 10: 673-679.

    Gjessing E, Lygren E, Berglind L, Gulbrandsen T, & Skaane R (1984)
    Effect of highway runoff on lake water quality. Sci Total Environ, 33:
    245-257.

    Glatt H, Bücker M, Platt KL, & Oesch F (1985) Host-mediated
    mutagenicity experiments with benzo [a]pyrene and two of its
    metabolites. Mutat Res, 156: 163-169.

    Glatt H, Seidel A, Bochnitschek W, Marquardt H, Marquardt H, Hodgson
    RM, Grover PL, & Oesch F (1986) Mutagenic and cell-transforming
    activities of triol-epoxides as compared to other chrysene
    metabolites. Cancer Res, 46: 4556-4565.

    Glatt H, Seidel A, Ribeiro O, Kirkhy C, Ilirom P, & Oesch F (1987)
    Metabolic activation to a mutagen of
    3-hydroxy- trans-7,8-dihydroxy-7,8-dihydrobenzo [a]pyrene, a
    secondary metabolite of benzo [a]pyrene. Carcinogenesis, 8:
    1621-1627.

    Glatt H, Harvey RG, Phillips DH, Hewer A, & Grover PL (1989) Influence
    of the alkyl substituent on mutagenicity and covalent DNA binding of
    bay region diol-epoxides of 7-methyl- and 7-ethylbenz [a]anthracene
    in  Salmonella and V79 Chinese hamster cells. Cancer Res, 49: 1778-
    1782.

    Goddard KA, Schultz RJ, Stegeman JJ, Schultz RJ, & Stegemann JJ (1987)
    Uptake, toxicity and distribution of benzo [a]pyrene and
    monooxygenase induction in the top minnows  Poeciliopsis monacha 
    and  Poeciliopsis lucida. Drug Metab Disposition, 15: 449-455.

    Göen T, Gündel J, Schaller KH, & Angerer J (1995) The elimination of
    1-hydroxypyrene in the urine of the general population and workers
    with different occupational exposures to PAH. Sci Total Environ, 163:
    195-201.

    Gold A & Eisenstadt E (1980) Metabolic activation of
    cyclopenta(cd)pyrene to 3,4-epoxycyclopenta(cd)pyrene by rat liver
    microsomes. Cancer Res, 40: 3940-3944.

    Gold A, Nesnow S, Moore M, Garland H, Curtis G, Howard B, Graham D, &
    Eisenstadt E (1980) Mutagenesis and morphological transformation of
    mammalian cells by a nonbay-region polycyclic cyclopenta(cd)pyrene and
    its 3,4-oxide. Cancer Res, 40: 4482-4484.

    Goldschmidt BM, Katz C, & Van Duuren BL (1973) The cocarcinogenic
    activity of noncarcinogenic aromatic hydrocarbons. Proc Am Assoc
    Cancer Res, 14: 84.

    Gollahon L (1991) Chromosomal damage to preimplantation mouse embryos
     in vitro by naphthalene and aflatoxin B1. Diss Abstr Int B, 52: 694-
    695.

    Gollahon LS, Iyer P, Martin JE, & Irvin TR (1990) Chromosomal damage
    to preimplantation embryos  in vitro by naphthalene. Toxicologist,
    10: 274.

    Gonzalez FJ & Gelboin HV (1994) Role of human cytochromes P450 in the
    metabolic activation of chemical carcinogens and toxins. Drug Metab
    Rev, 26: 165-183.

    Gonzalez-Vila FJ, Lopez JL, & Martin F (1988) Determination of
    polynuclear aromatic compounds in composted municipal refuse and
    compost-amended soils by a simple cleanup procedure. Biomed Environ
    Mass Spectrom, 16: 423-425.

    Gordon RJ (1976) Distribution of airborne polycyclic aromatic
    hydrocarbons throughout Los Angeles. Environ Sci Technol, 10: 370-373.

    Gordon RJ & Bryan RJ (1973) Patterns in airborne polynuclear
    hydrocarbon concentrations at four Los Angeles sites. Environ Sci
    Technol, 7: 1050-1053.

    Gorelova ND & Cherepanova AI (1970) [Possibility of accumulation of
    3,4-benzpyrene in tissues and organs of cows and calves and in milk
    when this carcinogen is present in food.] Vopr Onkol, 16: 69-73 (in
    Russian).

    Gorelova ND, Dikun PP, Solinek VA, & Emshanova AV (1960) [Content of
    3,4-benzpyrene in fish smoked by different methods.] Vopr Onkol, 6:
    33-37 (in Russian).

    Götz R (1984) [Investigations into leakage water from the refuse dump
    Georgswerder in Hamburg. Results of analyses up to 1982 inclusive.]
    Müll Abfall, 12: 349-356 (in German).

    Grachev MA, Baram GI, Hodgher, TV, Gorshow AG, Vodiannikova NI, &
    Bartz MP (1994) Determination of the concentration of PAHs in the
    atmosphere of the south part of the Lake Baikal coast. Irkutsk,
    Limnological Institute, Russian Academy of Sciences (unpublished
    report).

    Gräf W (1970) Levels of 3,4-benzopyrene in human organs of different
    ages. Second communication. Arch Hyg, 154: 331-335.

    Gräf W & Nowak W (1966) [Promotion of growth in lower and higher
    plants by carcinogenic polycyclic aromatics.] Arch Hyg, 150: 513-528
    (in German).

    Gräf W, Eff H, & Schormair S (1975) Levels of carcinogenic, polycyclic
    aromatic hydrocarbons in human and animal tissues. Third
    communication. Zentralbl Bakteriol Hyg Abt Orig B, 161: 85-103.

    Graffi A (1940a) [Cellular accumulation of carcinogenic hydrocarbons.]
    Z Krebsforschung, 49: 477-495 (in German).

    Graffi A (1940b) [Intracellular benzopyrene accumulation in living
    normal and tumor cells.] Z Krebsforschung, 50: 196-219 (in German).

    Graffi A (1940c) [Some observations on the aetiology of tumors, in
    particular on the nature of the active agent in cell-free transferable
    chicken tumours.] Z Krebsforschung, 50: 501-551 (in German).

    Graffi A, Vlamynck E, Hoffmann F, & Schulz I (1953) [Studies on the
    tumor producing effects of different chemicals in combination with
    croton oil.] Arch Geschwulstforsch, 5: 110-126 (in German).

    Grant G & Roe FJC (1963) The effect of phenanthrene on tumour
    induction by 3,4-benzopyrene administered to newly born mice. Br J
    Cancer, 17: 261-265.

    Greb W, Strobel R & Röhrborn G (1980) Transformation of BHK 21/CL 13
    cells by various polycyclic aromatic hydrocarbons using the method of
    Styles. Toxicol Lett, 7: 143-148.

    Greenberg A, Bozzelli JW, Cannova F, Forstner F, Giorgio P, Stout D, &
    Yokoyama R (1981) Correlations between lead and coronene
    concentrations at urban, suburban, and industrial sites in New Jersey.
    Environ Sci Technol, 15: 566-570.

    Greenberg A, Darack F, Harkov R, Lioy P, & Daisey J (1985) Polycyclic
    aromatic hydrocarbons in New Jersey: A comparison of winter and summer
    concentrations over a two-year period. Atmos Environ, 19: 1325-1339.

    Greife AL & Warshawsky D (1993) Influence of the dose levels of
    carcinogen ferric oxide on the metabolism of benzo(a)pyrene by
    pulmonary alveolar macrophages in suspension culture. J Toxicol
    Environ Health, 38: 399-417.

    Greife A, Schoeny R, & Warshawsky D (1988) Effect of the cocarcinogen
    ferric oxide on benzo(a)pyrene metabolism by hamster alveolar
    macrophages. In: Cooke M & Dennis A ed. Polycyclic aromatic
    hydrocarbons: Chemical and biological effects. Columbus, Ohio,
    Battelle Press, pp 317-327.

    Griesbaum K, Behr A, Biedenkapp D, Voges HW, Garbe D, Paetz C, Collin
    G, Mayer D, & Höke H (1989) Hydrocarbons. In: Ullmann's encyclopedia
    of industrial chemistry, 5th ed. Volume A13. Weinheim, Verlag Chemie,
    pp 227-281.

    Griest WH (1980) Multicomponent polycyclic aromatic hydrocarbon
    analysis of inland water and sediment. Environ Sci Res, 16: 173-183.

    Griest WH & Caton JE (1983) Extraction of polycyclic aromatic
    hydrocarbons for quantitative analysis. In: Bjorseth A ed. Handbook of
    polycyclic aromatic hydrocarbons. New York, Marcel Dekker, pp 95-148.

    Griest WH, Maskarinec MP, Herbes SE, & Southworth GR (1981)
    Multicomponent methods for the identification and quantification of
    polycyclic aromatic hydrocarbons in the aqueous environment. In:
    Jackson LP & Wright CC ed. Analysis of waters associated with
    alternative fuel production. Philadelphia, Pennsylvania, American
    Society for Testing and Materials, pp 167-178 (ASTM STP No. 720).

    Grifoll M, Casellas M, Bayona JM, & Solanas AM (1992) Isolation and
    characterization of a fluorene-degrading bacterium: Identification of
    ring oxidation and ring fission products. Appl Environ Microbiol, 58:
    2910-2917.

    Grimmer G (1979) Sources and occurrence of polycyclic aromatic
    hydrocarbons. In: Egan H, Castegnaro M, Bogovski P, Kunte H, & Walker
    EA ed. Environmental carcinogens: Selected methods of analysis. Volume
    3. Analysis of polycyclic hydrocarbons in environmental samples. Lyon,
    International Agency for Research on Cancer, pp 31-54 (IARC Scientific
    Publications No. 29).

    Grimmer G (1980) [Analysis and comparison of PAH profile from
    environmental samples.] Düsseldorf, VDI-Verlag, pp 39-50 (VDI Report
    No. 358) (in German).

    Grimmer G (1983a) Chemistry. In: Grimmer G ed. Environmental
    carcinogens: Polycyclic aromatic hydrocarbons. Boca Raton, Florida,
    CRC Press, pp 27-60.

    Grimmer G (1983b) Profile analysis of polycyclic aromatic hydrocarbons
    in air. In: Bjorseth A ed. Handbook of polycyclic aromatic
    hydrocarbons. New York, Marcel Dekker, pp 149-191.

    Grimmer G (1993) [Environmental-toxicological evaluation of PAH in
    soil.] Altlasten Spectrum, 2: 85-92 (in German).

    Grimmer G & Böhnke H (1975) Profile analysis of polycyclic aromatic
    hydrocarbons and metal content in sediment layers of a lake. Cancer
    Lett, 1: 75-84.

    Grimmer G & Böhnke H (1978) The tumor producing effect of automobile
    exhaust condensate and fractions thereof. Part 1: Chemical studies. J
    Environ Pathol Toxicol, 1: 661-667.

    Grimmer G & Böhnke H (1979a) Method 4: Gas chromatographic profile
    analysis of polycyclic aromatic hydrocarbons in (i) high protein
    foods, (ii) fats and vegetable oils and (iii) plants, soils and sewage
    sludge. In: Egan H, Castegnaro M, Bogovski P, Kunte H, & Walker EA ed.
    Environmental carcinogens: Selected methods of analysis. Volume 3.
    Analysis of polycyclic aromatic hydrocarbons in environmental samples.
    Lyon, International Agency for Research on Cancer, pp 163-173 (IARC
    Scientific Publications No. 29).

    Grimmer G & Böhnke H (1979b) Method 3: Gas chromatographic profile
    analysis of polycyclic aromatic hydrocarbons in lubricating oil,
    cutting oil and fuel. In: Egan H, Castegnaro M, Bogovski P, Kunte H, &
    Walker EA ed. Environmental carcinogens: Selected methods of analysis.
    Volume 3. Analysis of polycyclic aromatic hydrocarbons in
    environmental samples. Lyon, International Agency for Research on
    Cancer, pp 155-162 (IARC Scientific Publications No. 29).

    Grimmer G & Düvel D (1970) [Investigation of biosynthetic formation of
    polycyclic hydrocarbons in higher plants.] Z Naturforsch, 256: 1171-
    1175 (in German with English summary).

    Grimmer G & Hildebrandt A (1965) [The content of polyaromatic
    hydrocarbons in various vegetables.] Dtsch Lebensm Rundsch, 61: 237-
    239 (in German).

    Grimmer G & Hildebrandt A (1975) Investigations on the carcinogenic
    burden by air pollution in man. XIII. Assessment of the contribution
    of passenger cars to air pollution by carcinogenic polycyclic aromatic
    hydrocarbons. Zentralbl Bakteriol Hyg I Orig B, 161: 104-124.

    Grimmer G, Jacob J, & Hildebrandt A (1972) [Hydrocarbons in the human
    environment. 9. Content of polycyclic hydrocarbons in Icelandic soil.]
    Z Krebsforsch, 78: 65-72 (in German).

    Grimmer G, Hildebrandt A, & Böhnke H (1979) Method 2: Gas
    chromatographic profile analysis of polycyclic aromatic hydrocarbons
    in automobile exhaust gas condensate. In: Egan H, Castegnaro M,
    Bogovski P, Kunte H, & Walker EA ed. Environmental carcinogens:
    Selected methods of analysis. Volume 3. Analysis of polycyclic
    aromatic hydrocarbons in environmental samples. Lyon, International
    Agency for Research on Cancer, pp 141-154 (IARC Scientific
    Publications No. 29).

    Grimmer G, Hilge G, & Niemitz W (1980) [Comparison of the profile of
    polycyclic aromatic hydrocarbons of sewage sludge samples from 25
    filter plants.] Vom Wasser, 54: 255-272 ( in German).

    Grimmer G, Jacob J, & Naujack KW (1981a) Profile of the polycyclic
    aromatic hydrocarbons from lubricating oils. Inventory by GCGC/MS. PAH
    in environmental materials, Part 1. Fresenius Z Anal Chem, 306: 347-
    355.

    Grimmer G, Schneider D, & Dettbarn G (1981b) [The load of different
    rivers in the Federal Republic of Germany by PAH (PAH-profiles of
    water surface)]. Vom Wasser, 56: 131-144 (in German).

    Grimmer G, Naujack K-W, & Schneider D (1981c) Comparison of the
    profiles of polycyclic aromatic hydrocarbons in different areas of a
    city by glass-capillary-gas chromatography in the nanogram range. Int
    J Environ Chem, 10: 265-276.

    Grimmer G, Naujack K-W, & Schneider D (1982) Profile analysis of
    polycyclic aromatic hydrocarbons by glass capillary gas chromatography
    in atmospheric suspended particulate matter in the nanogram range
    collecting 10 m3 of air. Fresenius Z Anal Chem, 311: 475-484.

    Grimmer G, Jacob J, & Naujack KW (1983) Profile of the polycyclic
    aromatic compounds from crude oils. Inventory by GCGC/MS. PAH in
    environmental materials, part 3. Fresenius Z Anal Chem, 314: 29-36.

    Grimmer G, Brune H, Deutsch-Wenzel R, Dettbarn G, & Misfeld J (1984)
    Contribution of polycyclic aromatic hydrocarbons to the carcinogenic
    impact of gasoline engine exhaust condensate evaluated by implantation
    into the lungs of rats. J Natl Cancer Inst, 72: 733-739.

    Grimmer G, Jacob J, Dettbarn G, & Naujack KW (1985) Determination of
    polycyclic aromatic hydrocarbons, azaarenes, and thiaarenes emitted
    from coal-fired residential furnaces by gas chromatography/mass
    spectrometry. Fresenius Z Anal Chem, 322: 595-602.

    Grimmer G, Naujack KW, & Dettbarn G (1987) Gas chromatographic
    determination of polycyclic aromatic hydrocarbons, aza-arenes,
    aromatic amines in the particle and vapor phase of mainstream and
    sidestream smoke of cigarettes. Toxicol Lett, 35: 117-124.

    Grimmer G, Jacob J, Dettbarn G, & Naujack K-W (1988a) Effect of the
    pH-value of diesel exhaust on the amount of filter-collected
    nitro-PAH. In: Cooke M & Dennis AJ ed. Polynuclear aromatic
    hydrocarbons: A decade of progress.  Columbus, Ohio, Battelle Press,
    pp 341-351.

    Grimmer G, Brune H, Dettbarn G, Heinrich U, Jacob J, Mohtashamipur E,
    Norpoth K, Pott F, & Wenzel-Hartung R (1988b) Urinary and faecal
    excretion of chrysene and chrysene metabolites by rats after oral,
    intraperitoneal, intratracheal or intrapulmonary application. Arch
    Toxicol, 62: 401-405.

    Grimmer G, Brune H, Dettbarn G, Naujack K-W, Mohr U, & Wenzel-Hartung
    R (1988c) Contribution of polycyclic aromatic compounds to the
    carcinogenicity of sidestream smoke of cigarettes evaluated by
    implantation into lungs of rats. Cancer Lett, 43: 173-177.

    Grimmer G, Brune H, Dettbarn G, Jacob J, Mohtashamipur E, Norpoth K, &
    Wenze-Hartung R (1991a) Urinary and fecal excretion of phenanthrene
    and phenanthrols by rats following oral, intraperitoneal, or
    intrapulmonary application. Polycyclic Aromat Compd, 2: 39-47.

    Grimmer G, Brune H, Dettbarn G, Jacob J, Misfeld J, Mohr U, Naujack
    K-W, Timm J, & Wenzel-Hartung R (1991b) Relevance of polycyclic
    aromatic hydrocarbons as environmental carcinogens. Fresenius J Anal
    Chem, 339: 792-795.

    Grimmer G, Dettbarn G, & Naujack KW (1991c) A method for the
    determination of phenanthrene and five isomeric hydroxyphenanthrenes
    in urine of man and rat. In: Cooke M, Loening K, & Merritt J ed.
    Polynuclear aromatic hydrocarbons: Measurements, means, and
    metabolism. Columbus, Ohio, Battelle Press, pp 389-403.

    Grimmer G, Dettbarn G, & Jacob J (1993) Biomonitoring of polycyclic
    aromatic hydrocarbons in highly exposed coke plant workers by
    measurement of urinary phenanthrene and pyrene metabolites (phenols
    and dihydrodiols). Int Arch Occup Environ Health, 65: 189-199.

    Grimmer G, Dettbarn G, Naujack KW, & Jacob J (1994) Relationship
    between inhaled PAH and urinary excretion of phenanthrene, pyrene and
    benzo [a]pyrene metabolites in coke plant workers. Polycyclic Aromat
    Compd, 5: 269-277.

    Grob K & Grob G (1974) Organic substances in potable water and in its
    precursor. Part II: Applications in the area of Zürich. J Chromatogr,
    90: 303-313.

    Groenewegen D & Stolp H (1976) [Microbial breakdown of polycyclic
    aromatic hydrocarbons.] Zentralbl Bakteriol Parasitenkd Infektionskr
    Hyg Abt 1 Orig B, 161: 225-232 (in German).

    Grosjean D (1983) Polycyclic aromatic hydrocarbons in Los Angeles air
    from samples collected on teflon, glass and quartz filters. Atmos
    Environ, 17: 2565-2573.

    Grosser RJ, Warshawsky D, & Vestal JR (1995) Mineralization of
    polycyclic and N-heterocyclic aromatic compounds in
    hydrocarbon-contaminated soils. Environ Toxicol Chem, 14: 375-382.

    Grover PL & Sims P (1968) Enzyme-catalysed reactions of polycyclic
    hydrocarbons with deoxyribonucleic acid and protein  in vitro. 
    Biochem J, 110: 159-160.

    Grover PL, Sims P, Huberman E, Marquardt H, Kuroki T, & Heidelberger C
    (1971)  In vitro transformation of rodent cells by K-region
    derivatives of polycyclic hydrocarbons. Proc Natl Acad Sci USA, 68:
    1098-1101.

    Grover PL, Sims P, Mitchel BCU, & Roe FJ (1975) The carcinogenicity of
    polycyclic hydrocarbon epoxides in newborn mice. Br J Cancer, 31: 182-
    188.

    Grover PL, MacNicoll AD, Sims P, Easty GC, & Neville AM (1980)
    Polycyclic hydrocarbon activation and metabolism in epithelial cell
    aggregates prepared from human mammary tissue. Int J Cancer, 26: 467-
    475.

    Gückel W, Synnatschke R, & Rittig R (1973) A method for determining
    the volatility of active ingredients used in plant protection. Pestic
    Sci, 4: 137-147.

    Guengerich FP & Shimada T (1991) Oxidation of toxic and carcinogenic
    chemicals by human cytochrome P-450 enzymes. Chem Res Toxicol, 4: 391-
    407.

    Guenther FR, Chesler SN, Gordon GE, & Zoller WH (1988) Residential
    wood combustion: A source of atmospheric polycyclic aromatic
    hydrocarbons. J High Resol Chromatogr Chromatogr Commun, 11: 761-766.

    Guerin MR (1977) Energy sources of polycyclic aromatic hydrocarbons.
    Oak Ridge, Tennessee, Oak Ridge National Laboratory, Analytical
    Chemistry Division, pp 1-78 (EPA Conf/Doc. 770-130-2).

    Guerin MR, Epler JL, Griest WH, Clark BR, & Rao TK (1978) Polycyclic
    aromatic hydrocarbons from fossil fuel conversion processes. In: Jones
    PW & Freudenthal RI ed. Carcinogenesis. Volume 3: Polynuclear aromatic
    hydrocarbons. New York, Raven Press, pp 21-33.

    Guggenberger J, Krammer G, & Lindenmüller W (1981) [Contribution to
    the determination of the emission of polycyclic aromatic hydrocarbons
    from large capacity furnaces.] Staub-Reinhalt Luft, 41: 339-344 (in
    German).

    Guicherit R & Schulting FL (1985) The occurrence of organic chemicals
    in the atmosphere of the Netherlands. Sci Total Environ, 43: 193-219.

    Guillemin MP, Herrera H, Huynh CK, Droz PO, & Vu Duc T (1992)
    Occupational exposure of truck drivers to dust and polynuclear
    aromatic hydrocarbons: A pilot study in Geneva, Switzerland. Int Arch
    Occup Environ Health, 63: 439-447.

    Gupta RS & Goldstein S (1981) Mutagen testing in the human fibroblasts
    diphtheria toxin resistance (HF Dipr) system. In: De Serres FJ & Ashby
    J ed. Evaluation of short-term tests for carcinogens. Report of the
    international collaborative programme. New York, Elsevier North
    Holland, pp 614-625 (Progress in Mutation Research, Volume 1).

    Gupta RS & Singh B (1982) Mutagenic responses of five independent
    genetic loci in CHO cells to a variety of mutagens. Development and
    characteristics of a mutagen screening system based on selection for
    multiple drug-resistant markers. Mutat Res, 94: 449-466.

    Gupta RC, Earley K, & Sharma S (1988) Use of human peripheral blood
    lymphocytes to measure DNA binding capacity of chemical carcinogens.
    Proc Natl Acad Sci USA, 85: 3513-3517.

    Gurtoo HL, Vaught JB, Marinello AJ, Paigen B, Gessner T, & Bolanowska
    W (1980) High-pressure liquid chromatographic analysis of
    benzo [a]pyrene metabolism by human lymphocytes from donors of
    different aryl hydrocarbon hydroxylase inducibility and antipyrine
    half-lives. Cancer Res, 40: 1305-1310.

    Gustavsson P (1989) Cancer and ischemic heart disease in occupatioal
    groups exposed to combustion products. Solna, National Institute of
    Occupational Health, pp 1-28 (World and Health series No. 21).

    Gustavsson P & Reuterwall C (1990) Mortality and incidence of cancer
    among Swedish gas workers. Br J Ind Med, 47: 169-174.

    Gustavsson P, Fellenius E, & Hogstedt C (1987) Possible causes of
    increased lung cancer incidence among butchers and slaughterhouse
    workers. Scand J Work Environ Health, 13: 518-523.

    Gustavsson P, Gustavsson A, & Hogstedt C (1988) Excess of cancer in
    Swedish chimney sweeps. Br J Ind Hyg, 45: 777-781.

    Habs M, Schmähl S, & Misfeld J (1980) Local carcinogenicity of some
    environmentally relevant polycyclic aromatic hydrocarbons after
    lifelong topical application to mouse skin. Geschwulstforschung, 50:
    266-274.

    Habs M, Jahn SAA, & Schmähl D (1984) Carcinogenic activity of
    condensate from coloquint seeds  (Citrullus colocynthis) after
    chronic epicutaneous administration to mice. J Cancer Res Clin Oncol,
    108: 154-156.

    Haddow A, Scott CM, & Scott JD (1937) The influence of certain
    carcinogenic and other hydrocarbons on body growth in the rat. Proc R
    Soc Ser B, 122: 477-507.

    Hagemann R, Virelizier H, Gaudin D, & Pesneau A (1982) Polycyclic
    aromatic hydrocarbons in exhaust particles emitted from gasoline and
    diesel automobile engines. Toxicol Environ Chem, 5: 227-236.

    Hall M & Grover PL (1990) Polycyclic aromatic hydrocarbons:
    Metabolism, activation and tumour initiation. In: Cooper CS & Grover
    PL ed. Handbook of experimental pharmacology. Berlin, Springer-Verlag,
    Volume 94/I, pp 327-372.

    Hall AT & Oris JT (1991) Anthracene reduces reproductive potential and
    is maternally transferred during long-term exposure in fathead
    minnows. Aquat Toxicol, 19: 249-264.

    Hall M, Forrester LM, Parker DK, Grover PL, & Wolf CR (1989) Relative
    contribution of various forms of cytochrome P450 to the metabolism of
    benzo [a]pyrene by human liver microsomes. Carcinogenesis, 10: 1815-
    1821.

    Halsall CJ, Coleman PJ, Davies BJ, Burnett V, Waterhouse KS,
    Harding-Jones P, & Jones KC (1994) Polycyclic aromatic hydrocarbons in
    UK urban air. Environ Sci Technol, 28: 2380-2386.

    Hambrick GA, Delaume RD, & Patrick WH Jr (1980) Effects of estuarine
    sediment, pH and oxidation-reduction potential on microbial
    hydrocarbon degradation. Appl Environ Microbiol, 40: 365-369.

    Hamburg Environment Office (1993) [Report on an investigation into
    polycyclic aromatic hydrocarbons (PAHs) in Hamburg's waters.] Hamburg,
    63 (Report 42/93 13-16) (in German).

    Hammond WG, Gabriel A, Paladugu RR, Azumi N, Hill RL, & Benfield JR
    (1987) Differential susceptibility to bronchial carcinogenesis in
    syngeneic hamsters. Cancer Res, 47: 5202-5206.

    Hampton CV, Pierson WR, Schuetzle D, & Harvey TM (1983) Hydrocarbon
    gases emitted from vehicles on the road. 2. Determination of emission
    rates from diesel and spark ignition vehicles. Environ Sci Technol,
    17: 699-708.

    Hannah JB, Hose JE, Landolt ML, Miller BS, Felton SP, & Iwaoka WT
    (1982) Benzo [a]pyrene-induced morphologic and developmental
    abnormalities in rainbow trout  Salmo gairdneri Richardson. Arch
    Environ Contam Toxicol, 11: 727-734.

    Hansen ES (1989) Cancer incidence in an occupational cohort exposed to
    bitumen fumes. Scand J Work Environ Health, 15: 101-105.

    Hansen ÅM, Olsen IB, Holst E, & Poulsen OM (1991a) Validation of a
    high-performance liquid chromatography/fluorescence detection method
    for the simultaneous quantification of fifteen polycyclic aromatic
    hydrocarbons. Ann Occup Hyg, 35: 603-611.

    Hansen ÅM, Poulsen OM, & Christensen JM (1991b) Correlation of levels
    of volatile versus carcinogenic particulate polycyclic aromatic
    hydrocarbons in air samples from smokehouses. Int Arch Occup Environ
    Health, 63: 247-252.

    Hansen ÅM, Olsen IB, & Poulsen OM (1992) Polycyclic aromatic
    hydrocarbons in air samples of meat smokehouses. Sci Total Environ,
    126: 17-26.

    Hansen ÅM, Omland œ, Poulsen OM, Sherson D, Sigsgaard T, Christensen
    JM, & Overgaard E (1994) Correlation between work process-related
    exposure to polycyclic aromatic hydrocarbons and urinary levels of
    a-naphthol, b-naphthylamine and 1-hydroxypyrene in iron foundry
    workers. Int Arch Occup Environ Health, 65: 385-394.

    Hansen AM, Christensen JM, & Sherson D (1995) Estimation of reference
    values for urinary 1-hydroxypyrene and a-naphthol in Danish workers.
    Sci Total Environ, 163: 211-219.

    Hardin BD, Bond GP, Sikov MR, Andrew FD, Beliles RP, & Niemeier RW
    (1981) Testing of selected workplace chemicals for teratogenic
    potential. Scand J Work Environ Health, 7: 66-75.

    Hardin BD, Schuler RL, Burg JR, Booth GM, Hazelden KP, MacKenzie KM,
    Piccirillo VJ, & Smith KN (1987) Evaluation of 60 chemicals in a
    preliminary developmental toxicity test. Teratog Carcinog Mutag, 7:
    29-48.

    Harkov R & Greenberg A (1985) Benzo(a)pyrene in New Jersey. Results
    from a twenty-seven-site study. J Air Pollut Control Assoc, 35: 238-
    243.

    Harkov R, Greenberg A, Darack F, Daisey JM, & Lioy PJ (1984)
    Summertime variations in polycyclic aromatic hydrocarbons at four
    sites in New Jersey. Environ Sci Technol, 18: 187-291.

    Harper KH (1957) The metabolism of pyrene. Br J Cancer, 11: 499-507.

    Harper KH (1958a) The intermediary metabolism of pyrene. Br J Cancer,
    12: 116-120.

    Harper KH (1958b) The intermediary metabolism of 3,4-benzpyrene. Br J
    Cancer, 12: 121-128.

    Harper KH (1958c) The intermediary metabolism of 3,4-benzyprene: The
    biosynthesis and identification of the X1 and X2 metabolites. Br J
    Cancer, 12: 645-660.

    Harper KH (1959a) The intermediary metabolism of polycyclic
    hydrocarbons. Br J Cancer, 13: 718-731.

    Harper KH (1959b) Metabolism of 1,2-benzanthracene in the rabbit. Br J
    Cancer, 13: 746-750.

    Harper BL & Legator MS (1987) Pyridine prevents the clastogenicity of
    benzene but not of benzo [a]pyrene or cyclophosphamide. Mutat Res,
    179: 23-31.

    Harper BL, Sadagopa Ramanujam VM, Gad-El-Karim MM & Legator MS (1984)
    The influence of simple aromatics on benzene clastogenicity. Mutat
    Res, 128: 105-114.

    Harris CC, Autrup H, Connor R, Barrett LA, McDowell EM, & Trump BF
    (1976) Interindividual variation in binding of benzo [a]pyrene to DNA
    in cultured human bronchi. Science, 194: 1067-1069.

    Harris CC, Autrup H, Stoner G, Yang SK, Leutz JC, Gelboin HV, Selkirk
    JK, Conner RJ, Barrett LA, Jones RT, McDowell E, & Trump BF (1977)
    Metabolism of benzo [a]pyrene and 7,12-dimethylbenz [a]anthracene in
    cultured human bronchus and pancreatic duct. Cancer Res, 37: 3349-
    3355.

    Harris CC, Hsu IC, Stoner GD, Trump BF, & Selkirk JK (1978a) Human
    pulmonary alveolar macrophages metabolise benzo [a]pyrene to
    proximate and ultimate mutagens. Nature, 272: 633-634.

    Harris CC, Autrup H, & Stoner G (1978b) Metabolism of benzo [a]pyrene
    in cultured human tissues and cells. In: Gelboin HV & Ts'o POP ed.
    Polycyclic hydrocarbons and cancer. New York, Academic Press, Volume
    2, pp 331-342.

    Harris CC, Autrup H, Stoner GD, Trump BF, Hillman E, Schafer PW, &
    Jeffrey AM (1979) Metabolism of benzo [a]pyrene,
     N-nitrosodimethylamine, and  N-nitrosopyrrolidine and
    identification of the major carcinogen-DNA adducts formed in cultured
    human esophagus. Cancer Res, 39: 4401-4406.

    Harris CC, Grafstom RC, Shamsuddin AM, Sinopoli NT, Trump BF, & Autrup
    H (1984) Carcinogen metabolism and carcinogen-DNA adducts in human
    tissues and cells. In: Greim H, Jung R, Kramer M, Marquardt H, & Oesch
    F ed. Biochemical basis of chemical carcinogenesis. New York, Raven
    Press, pp 123-135.

    Harris CC, Vahakangas K, Newman MJ, Trivers GE, Shamsuddin A, Sinopoli
    N, Mann DL, & Wright WE (1985) Detection of benzo [a]pyrene diol
    epoxide-DNA adducts in peripheral blood lymphocytes and antibodies to
    the adducts in serum from coke oven workers. Proc Natl Acad Sci USA,
    82: 6672-6676.

    Hart KM & Pankow JF (1994) High-volume air sampler for particle and
    gas sampling. 2. Use of backup filters to correct for the adsorption
    of gas-phase polycyclic aromatic hydrocarbons to the front filter.
    Environ Sci Technol, 28: 655-661.

    Hartung H & Koch D (1991) [Environmental research plan from the
    Federal Ministry for Environment and Reactor Safety (Research Project
    103 03 220/01): Waste disposal: Quantity, recycling and disposal of
    used motor tyres in the Federal Republic of Germany.] Berlin, Ministry
    of the Environment, pp 73-74 (Report No. UBA-FB 89-149, Text 52/91)
    (in German).

    Harvey RG (1996) Mechanisms of carcinogenesis of polycyclic aromatic
    compounds. Polycyclic Aromat Compd, 9: 1-23.

    Häsänen E, Pohjola V, Pyysalo H, & Wickström K (1983) Polycyclic
    aromatic hydrocarbons in the Finnish wood-heated sauna. Kemia Kemi,
    10: 27-29.

    Haseltine WA, Lo KM, & D'Andrea AD (1980) Preferred sites of strand
    scission in DNA modified by  anti-diol epoxide of benzo [a]pyrene.
    Science, 209: 929-931.

    Hass BS & Applegate HG (1975) The effects of unsubstituted polycyclic
    aromatic hydrocarbons on the growth of  Escherichia 
     coli. Chem-Biol Interactions, 10: 265-268.

    Hatch MC, Warburton D, & Santella RM (1990) Polycyclic aromatic
    hydrocarbon-DNA adducts in spontaneously aborted fetal tissue.
    Carcinogenesis, 11: 1673-1675.

    van Hattum B, Cofino WP, & Feenstra JF (1993) Environmental aspects of
    produced water discharges from oil and gas production on the Dutch
    continental shelf: Part II. A literature review of characteristics of
    produced water from offshore platforms. Amsterdam, Oil and Gas
    Exploitation and Production Association, 64 pp.

    Haubenstricker ME, Meier PG, Mancy KH, & Brabec MJ (1990) Rapid
    toxicity testing based on yeast respiratory activity. Bull Environ
    Contam Toxicol, 44: 669-674.

    Haudenschild R, Poffer J, Schott T, & Deuber A (1990) [Application of
    corrosion inhibitor in a bus garage.] Illus Z Arb Sicherheitstech, 37:
    6-8 (in German).

    Haugen A, Becher G, Benestad C, Vahakangas K, Trivers GE, Newman MJ, &
    Harris CC (1986) Determination of polycyclic aromatic hydrocarbons in
    the urine, benzo(a)pyrene diol epoxide-DNA adducts in lymphocyte DNA,
    and antibodies to the adducts in sera from coke oven workers exposed
    to measured amounts of polycyclic aromatic hydrocarbons in the work
    atmosphere. Cancer Res, 46: 4178-4183.

    Hawkins WE, Walker WW, Overstreet RM, Lytle TF, & Lytle JS (1988)
    Dose-related carcinogenic effects of water-borne benzo [a]pyrene on
    livers of two small fish species. Ecotoxicol Environ Saf, 16: 219-231.

    Hawkins WE, Walker WW, Overstreet RM, Lytle JS, & Lytle TF (1990)
    Carcinogenic effects of some polycyclic aromatic hydrocarbons on the
    Japanese medaka and guppy in waterborne exposures. Sci Total Environ,
    94: 155-167.

    Hawley G (1987) Hawley's condensed chemical dictionary, 11th rev ed.
    New York, Van Nostrand Reinhold Co., p 6.

    Hawley-Fedder RA, Parsons ML, & Karasek FW (1984a) Products obtained
    during combustions of polymers under simulated incinerator conditions:
    I. Polyethylene. J Chromatogr, 314: 263-273.

    Hawley-Fedder RA, Parsons ML, & Karasek FW (1984b) Products obtained
    during combustions of polymers under simulated incinerator conditions:
    II. Polystyrene. J Chromatogr, 315: 201-210.

    Hawley-Fedder RA, Parsons ML, & Karasek FW (1984c) Products obtained
    during combustions of polymers under simulated incinerator conditions:
    III. Polyvinyl chloride. J Chromatogr, 315: 211-221.

    Hawley-Fedder RA, Parsons ML, & Karasek FW (1987) Identification of
    organic compounds produced during combustion of a polymer mixture. J
    Chromatogr, 387: 207-221.

    Hawthorne SB & Miller DJ (1987) Extraction and recovery of polycyclic
    aromatic hydrocarbons from environmental solids using supercritical
    fluids. Anal Chem, 59: 1705-1708.

    Hawthorne SB, Krieger MS, & Miller DJ (1989a) Supercritical carbon
    dioxide extraction of polychlorinated biphenyls, polycyclic aromatic
    hydrocarbons, heteroatom-containing polycyclic aromatic hydrocarbons,
    and  n-alkanes from polyurethane foam sorbents. Anal Chem, 61: 736-
    740.

    Hawthorne SB, Miller DJ, & Krieger MS (1989b) Coupled SFE-GC: A rapid
    and simple technique for extracting, identifying, and quantitating
    organic analytes from solid and sorbent resins. J Chromatogr Sci, 27:
    347-354.

    Hawthorne SB, Miller DJ, Langenfeld JJ, & Krieger MS (1992) PM-10
    high-volume collection and quantitation of semi- and nonvolatile
    phenols, methoxylated phenols, alkanes, and polycyclic aromatic
    hydrocarbons from winter urban air and their relationship to wood
    smoke emissions. Environ Sci Technol, 26: 2251-2262.

    He S & Baker R (1991) Micronuclei in mouse skin cells following
     in vivo exposure to benzo [a]pyrene,
    7,12-dimethylbenz [a]anthracene, chrysene, pyrene and urethane.
    Environ Mol Mutag, 17: 163-168.

    Heaton DM, Bartle, KD, Clifford AA, Meyers P, & King BW (1994) Rapid
    separation of polycyclic aromatic hydrocarbons by packed column
    supercitical fluid chromatography. Chromatographia, 39: 607-611.

    Hecht SS, Bondinell WE, & Hoffmann D (1974) Chrysene and
    methylchrysenes: Presence in tobacco smoke and carcinogenicity. J Natl
    Cancer Inst, 53: 1121-1133.

    Hecht SS, Loy M, Maronpot RR, & Hoffmann D (1976a) A study of chemical
    carcinogenesis: Comparative carcinogenicity of 5-methylchrysene,
    benzo(a)pyrene, and modified chrysenes. Cancer Lett, 1: 147-153.

    Hecht SS, Loy M, & Hoffmann D (1976b) On the structure and
    carcinogenicity of the methylchrysenes. In: Freudenthal R & Jones PW
    ed. Carcinogenesis: A comprehensive survey. Volume 1: Polynuclear
    aromatic hydrocarbons chemistry, metabolism, and carcinogenesis. New
    York, Raven Press, pp 325-340.

    Hecht SS, Loy M, Mazzarese R, & Hoffmann D (1978) On the
    carcinogenicity of 5-methylchrysene: Structure-activity studies and
    metabolism. Polycyclic Hydrocarbons Cancer, 1: 119-130.

    Hecht SS, Grabowski W, & Groth K (1979) Analysis of faeces for
    benzo [a]pyrene after consumption of charcoal-broiled beef by rats
    and humans. Food Cosmet Toxicol, 17: 223-227.

    Hecht SS, LaVoie E, Amin S, Bedenko V, & Hoffmann D (1980) On the
    metabolic activation of the benzofluoranthenes. In: Bjorseth A &
    Dennis AJ ed. Polynuclear aromatic hydrocarbons: Chemistry and
    biological effects. Columbus, Ohio, Battelle Press, pp 417-433.

    Hecht SS, LaVoie EJ, Bedenko V, Hoffmann D, Sardella DJ, Boger E, &
    Lehr RE (1981) On the metabolic activation of dibenzo [a,i]pyrene and
    dibenzo [a,h]pyrene. In: Cooke M & Dennis AJ ed. Polynuclear aromatic
    hydrocarbons: Chemical analysis and biological fate. Columbus, Ohio,
    Battelle Press, pp 43-45.

    Hecht SS, Radok L, Amin S, Huie K, Melikian AA, Hoffmann D, Pataki J,
    & Harvey RG (1985) Tumorigenicity of 5-methylchrysene dihydrodiols and
    dihydrodiol epoxides in newborn mice and on mouse skin. Cancer Res,
    45: 1449-1452.

    Hecht SS, Melikian AA, & Amin S (1986) Methylchrysenes as probes for
    the mechanism of metabolic activation of carcinogenic methylated
    polynuclear aromatic hydrocarbons. Acc Chem Res, 19: 174-180.

    Hecht SS, Amin S, Huie K, Melikian AA, & Harvey RG (1987) Enhancing
    effect of a bay region methyl group on tumorigenicity in newborn mice
    and mouse skin of enantiomeric bay region diol epoxides formed
    stereoselectively from methylchrysenes in mouse epidermis. Cancer Res,
    47: 5310-5315.

    Hecht SS, El-Bayoumy K, Rivenson A, & Amin S (1994) Potent mammary
    carcinogenicity in female CD rats of a fjord region diol-epoxide of
    benzo(c)phenanthrene compared to a bay region diol-epoxide of
    benzo(a)pyrene. Cancer Res, 54: 21-24.

    Hecht SS, Amin S, Lin J-M, Rivenson A, Kurtzke C, & El-Bayoumy K
    (1995) Short communication. Mammary carcinogenicity in female CD rats
    of a diol epoxide metabolite of fluoranthene, a commonly occurring
    environmental pollutant. Carcinogenesis, 16: 1433-1435.

    Heeschen WH (1985) [Scientific working group on chemicals in human
    milk.] Arch Gynekol, 238: 199-216 (in German).

    Heflich RH, Thornton-Manning JR, Kinouchi T, & Beland FA (1990)
    Mutagenicity of oxidized microsomal metabolites of 1-nitropyrene in
    Chinese hamster ovary cells. Mutagenesis, 5: 151-157.

    Heidelberger C & Davenport GR (1961) Local functional components of
    carcinogenesis. Acta Unio Int Contra Cancrum, 17: 55-63.

    Heidelberger C & Jones HB (1948) The distribution of radioactivity in
    the mouse following administration of dibenzanthracene labeled in the
    9 and 10 positions with carbon 14*. Cancer, 1: 252-260.

    Heidelberger C & Weiss SM (1951) The distribution of radioactivity in
    mice following administration of 3,4-benzpyrene-5-C14 and
    1,2,5,6-dibenzanthracene-9,10-C14. Cancer Res, 11: 885-891.

    Heikkilä PR, Hämeilä M, Pyy L, & Rauni P (1987) Exposure to creosote
    in the impregnation and handling of impregnated wood. Scand J Work
    Environ Health, 13: 431-437.

    Heinrich U (1989) Exhaust-specific carcinogenic effects of polycyclic
    aromatic hydrocarbons and their significance for the estimation of the
    exhaust exposure-related lung cancer risk. In: Mohr U, Bates DV,
    Dungworth DL, Lee PN, McClellan RO, & Roe FJC ed. Assessment of
    inhalation hazards: Integration and extrapolation using diverse data.
    Berlin, Springer-Verlag, pp 301-313.

    Heinrich U (1995) Do PAH contribute to the lung tumor response in
    diesel engine exhaust-exposed rats? In: Fifteenth international
    symposium on polycyclic aromatic compounds: Chemistry, biology and
    environmental impact, Belgirate, Italy, 19-22 September 1995. Ispra,
    Joint Research Centre European Commission, p 150.

    Heinrich U, Pott F, Mohr U, Fuhst R, & König J (1986a) Lung tumours in
    rats and mice after inhalation of PAH-rich emissions. Exp Pathol, 29:
    29-34.

    Heinrich U, Pott F, & Rittinghausen S (1986b) Comparison of chronic
    inhalation effects in rodents after long-term exposure to either coal
    oven flue gas mixed with pyrolysed pitch or diesel engine exhaust. In:
    Ishinishi N, Koizumi A, McClellan RO, & Stöber W ed. Carcinogenic and
    mutagenic effects of diesel engine exhaust. Amsterdam, Elsevier
    Science Publishers, pp 441-457.

    Heinrich U, Peters L, Creutzenberg O, Dasenbrock C, & Hoymann HG
    (1994a) Inhalation exposure of rats to tar/pitch condensation aerosol
    or carbon black alone or in combination with irritant gases. In: Mohr
    U, Dungworth DL, Mauderly JL, & Oberdörster G ed. Toxic and
    carcinogenic effects of solid particles in the respiratory tract.
    Washington DC, International Life Sciences Institute Press, pp 433-
    441.

    Heinrich U, Dungworth DL, Pott F, Peters L, Dasenbrock C, Levsen K,
    Koch W, Creutzenberg O, & Schulte A (1994b) The carcinogenic effects
    of carbon black particles and tar-pitch condensation aerosol after
    inhalation exposure of rats. Ann Occup Hyg, 38 (suppl): 351-356.

    Heinrich U, Roller M, & Pott F (1994c) Estimation of a lifetime unit
    lung cancer risk for benzo [a]pyrene based on tumor rates in rats
    exposed to coaltar/pitch condensation aerosol. Toxicol Lett, 72: 155-
    161.

    Heit M (1985) The relationship of a coal fired power plant to the
    levels of polycyclic aromatic hydrocarbons (PAH) in the sediment of
    Cayuga Lake. Water Air Soil Pollut, 24: 41-61.

    Heit M, Klusek CS, & Miller KM (1980) Trace element, radionuclide, and
    polynuclear aromatic hydrocarbon concentrations in Unionidae mussels
    from northern Lake George. Environ Sci Technol, 14: 465-468.

    Heitkamp MA, Freeman JP, Miller DW, & Cerniglia CE (1988) Pyrene
    degradation by a  Mycobacterium sp.: Identification of ring oxidation
    and ring fission products. Appl Environ Microbiol, 54: 2556-2565.

    Heitmuller PT, Hollister TA, & Parrish PR (1981) Acute toxicity of 54
    industrial chemicals to sheepshead minnows  Cyprinodon 
     variegatus. Bull Environ Contam Toxicol, 27: 596-604.

    Heldal M, Norland S, Lien T, Knutsen G, Tjessem K, & Aarberg A (1984)
    Toxic responses of the green alga  Dunaliella bioculata 
    (Chlorophycea, Volvocales) to selected oxidised hydrocarbons. Environ
    Pollut, A34: 119-132.

    Helfrich J & Armstrong DE (1986) Polycyclic aromatic hydrocarbons in
    sediments of the southern basin of Lake Michigan. J Great Lakes Res,
    12: 192-199.

    Hembrock-Heger A & König W (1990) Occurrence and transfer of
    polycyclic aromatic hydrocarbons in soil and plants.] Düsseldorf,
    VDI-Verlag, pp 815-830 (VDI Report No. 837) (in German).

    Hemminki K & Vainio H (1979) Preferential binding of benzo [a]pyrene
    into nuclear matrix fraction. Cancer Lett, 6: 167-173.

    Hemminki K, Grzybowska E, Chorazy M, Twardowska-Saucha K, Srczynski
    JW, Putman KL, Randerath K, Phillips DH, Hewer A, Santella RM, &
    Perera FP (1990a) DNA adducts in humans related to occupational and
    environmental exposure to aromatic compounds. In: Vainio H, Sorsa M, &
    McMichael AJ ed. Complex mixtures and cancer risk. Lyon, International
    Agency for Research on Cancer, pp 181-192 (IARC Scientific
    Publications No. 104).

    Hemminki K, Grzybowska E, Chorazy M, Twardowska-Saucha K, Sroczynski
    JW, Putman KL, Randerath, Phillips DH, & Hewer A (1990b) Aromatic DNA
    adducts in white blood cells of coke workers. Int Arch Occup Environ
    Health, 62: 467-470.

    Hendricks JP, Meyers TR, Shelton DW, Casteel JL, & Bailey GS (1985)
    Hepatocarcinogenicity of benzo [a]pyrene to rainbow trout by dietary
    exposure and intraperitoneal injection. J Natl Cancer Inst, 74: 839-
    851.

    Henry MC & Kaufman DG (1973) Clearance of benzo [a]pyrene from
    hamster lungs after administration on coated particles. J Natl Cancer
    Inst, 51: 1961-1964.

    Henry MC, Port CD & Kauhman DG (1975) Importance of physical
    properties of benzo (a)pyrene-ferric oxide mixtures in lung tumor
    induction. Cancer Res, 35: 207-217.

    Herbert R, Marcus M, Wolff MS, Perera FP, Andrews L, Godbold JH,
    Rivera M, Stefanidis M, Lu XQ, Landrigan PJ, & Santella RM (1990a)
    Detection of adducts of deoxyribonucleic acid in white blood cells of
    roofers by 32P-postlabeling. Scand J Work Environ Health, 16: 135-
    143.

    Herbert R, Marcus M, Wolff MS, Perera FP, Andrews L, Godbold JH,
    Rivera M, Stefanidis M, Lu XQ, Landrigan PJ, & Santella RM (1990b) A
    pilot study of detection of DNA adducts in white blood cells of
    roofers by 32P-postlabelling. In: Vainio H, SorsaM, & McMichael AJ
    ed. Complex mixtures and cancer risk. Lyon, International Agenca for
    Research on Cancer, pp 205-214 (IARC Scientific Publications No. 104).

    Herbes SE (1981) Rates of microbial transformation of polycyclic
    aromatic hydrocarbons in water and sediments in the vicinity of
    coal-coking waste water discharge. Appl Environ Microbiol, 41: 20-28.

    Herbes SE, Southworth GR, Shaeffer DL, Griest WH, & Maskarinec MP
    (1980) Critical pathways of polycyclic aromatic hydrocarbons in
    aquatic environments. In: Witschi H ed. The scientific basis of
    toxicity assessment.Amsterdam, Elsevier Biomedical Press, pp 113-128.

    Herlan A (1982) Content of polycyclic aromatics in middle distillates.
    Zentralbl Bakteriol Hyg I Abt Orig B, 176: 249-268.

    Hermann M (1981) Synergistic effects of individual polycyclic aromatic
    hydrocarbons on the mutagenicity of their mixtures. Mutat Res, 90:
    399-409.

    Hermann M, Durand JP, Charpentier JM, Chaude O, Hofnung M, Petroff N,
    Vandecasteele JP, & Weill N (1980) Correlations of mutagenic activity
    with polynuclear aromatic hydrocarbon content of various mineral oils.
    In: Cooke M & Dennis AJ ed. Polynuclear aromatic hydrocarbons:
    Chemical analysis and biological fate. Columbus, Ohio, Battelle Press,
    pp 899-916.

    Heussner JC, Ward JB, & Legator MS (1985) Genetic monitoring of
    aluminium workers exposed to coal tar pitch volatiles. Mutat Res, 155:
    143-155.

    Hinoshita F, Hardin JA, & Sherr DH (1992) Fluoranthene induces
    programmed cell death and alters growth of immature B cell populations
    in bone marrow cultures. Toxicology, 73: 203-218.

    Hirano T, Stanton M, & Layard M (1974) Measurement of epidermoid
    carcinoma development induced in the lungs of rats by
    3-methylcholanthrene-containing beeswax pellets. J Natl Cancer Inst,
    53: 1209-1215.

    Hirom PC, Chipman JK, Millburn P, & Pue MA (1983) Enterohepatic
    circulation of the aromatic hydrocarbons benzo(a)pyrene and
    naphthalene. In: Rydstrom J, Montelius J, & Bengtsson M ed.
    Extrahepatic drug metabolism and chemical carcinogenesis. Amsterdam,
    Elsevier Science Publishers, pp 275-281.

    Hites RA (1981) Sources and fates of atmospheric polycyclic aromatic
    hydrocarbons. In: Macias ES & Hopke PK ed. Atmospheric aerosol,
    source/air quality relationships (ACS Symposium Series 167).
    Washington DC, American Chemical Society, pp 187-196.

    Hites RA (1989) Mass spectrometry of polycyclic aromatic compounds.
    In: Vo-Dinh T ed. Chemical analysis of polycyclic aromatic compounds.
    New York, John Wiley & Sons, pp 219-261.

    Hites RA, LaFlamme JW, & Farrington JW (1977) Sedimentary polycyclic
    aromatic hydrocarbons: The historical record. Science, 198: 829-831.

    Hites RA, LaFlamme RE, & Windsor JG Jr (1980) Polycyclic aromatic
    hydrocarbons in marine/aquatic sediments: Their ubiquity. In: Petrakis
    L & Weiss FT ed. Petroleum in the marine environment (Advances in
    Chemistry Series No. 185). Washington DC, American Chemical Society,
    pp 289-311.

    Ho CH, Clark BR, Guerin MR, Barkenbus BD, Rao TK, & Epler JL (1981)
    Analytical and biological analyses of test materials from the
    synthetic fuel technologies: IV. Studies of chemical
    structure-mutagenic activity relationships of aromatic nitrogen
    compounds relevant to synfuels. Mutat Res, 85: 335-345.

    Hoch-Ligeti C (1941) Studies on the changes in the lymphoid tissue of
    mice treated with carcinogenic and noncarcinogenic hydrocarbons.
    Cancer Res, 1: 484-488.

    Hodgson RM, Weston A, & Grover PL (1983) Metabolic activation of
    chrysene in mouse skin: Evidence for the involvement of a
    triol-epoxide. Carcinogenesis, 4: 1639-1643.

    Hodson J & Williams NA (1988) The estimation of the adsorption (Koc)
    for soils by high performance liquid chromatography. Chemosphere, 17:
    67-77.

    Hoff RM & Chan KW (1987) Measurement of polycyclic aromatic
    hydrocarbons in the air along the Niagara River. Environ Sci Technol,
    21: 556-561.

    Hoffmann K (1993) [Risk assessment and restoration concept for
    PAH-contaminated soil.] Altlasten-Spektrum, 2: 93-99 (in German).

    Hoffmann DJ & Gay ML (1981) Embryotoxic effects of benzo [a]pyrene,
    chrysene, and 7,12-dimethylbenz [a]anthracene in petroleum
    hydrocarbon mixtures in mallard ducks. J Toxicol Environ Health, 7:
    775-787.

    Hoffmann D & Wynder EL (1962) Analytical and biological studies on
    gasoline engine exhaust. Natl Cancer Inst Monogr, 9: 91-110.

    Hoffmann D & Wynder EL (1966) [Carcinogenic effect of dibenzopyrenes.]
    Z Krebsforsch, 68: 137-149 (in German).

    Hoffmann D, Rathkamp G, Nesnow S, & Wynder EL (1972) Fluoranthenes:
    Quantitative determination in cigarette smoke, formation by pyrolysis,
    and tumor-initiating activity. J Natl Cancer Inst, 49: 1165-1175.

    Hoffmann D, Schmeltz I, Hecht SS, & Wynder EL (1978) Tobacco
    carcinogenesis. In: Gelboin HV & Ts'o POP ed. Polycyclic hydrocarbons
    and cancer, Volume 1. New York, Academic Press, pp 85-117.

    Hoffman EJ, Mills GL, Latimer JS, & Quinn JG (1984) Urban runoff as a
    source of polycyclic aromatic hydrocarbons to coastal waters. Environ
    Sci Technol, 18: 580-587.

    Hoffman EJ, Latimer JS, Hunt CD, Mills GL, & Quinn JG (1985)
    Stormwater runoff from highways. Water Air Soil Pollut, 25: 349-364

    Holcombe GW, Phipps GL, & Fiandt JT (1983) Toxicity of selected
    priority pollutants to various aquatic organisms. Ecotoxicol Environ
    Saf, 7: 400-409.

    Holcombe GW, Phipps GL, Knuth ML, & Felhaber T (1984) The acute
    toxicity of selected substituted phenols, benzenes and benzoic acid
    esters to fathead minnows  Pimephales promelas. Environ Pollut, A35:
    367-381.

    Holder G, Yagi H, Dansette P, Jerina DM, Levin W, Lu AYH, & Conney AH
    (1974) Effects of inducers and epoxide hydrase on the metabolism of
    benzo [a]pyrene by liver microsomes and a reconstituted system:
    Analysis by high pressure liquid chromatography. Proc Natl Acad Sci
    USA, 71: 4356-4360.

    Hollstein M, McCann J, Angelosanto FA, & Nichols WW (1979) Short-term
    tests for carcinogens and mutagens. Mutat Res, 65: 133-226.

    Holman A, Karlsson A, Bratt I, Raihle G, & Hogstedt B (1994) Increased
    frequency of micronuclei in lymphocytes of Swedish chimney sweeps. Int
    Arch Occup Environ Health, 66: 185-187.

    Holoubek I, Housková L, Seda Z, Holoubkova I, Korínek P, Bohácek Z, &
    Cáslavsk J (1990) Project TOCOEN. The fate of selected organic
    pollutants in the environment. III. Water and sediments 1988. Toxicol
    Environ Chem, 29: 29-35.

    Homburger F, Russfield AB, Baker JR, & Tregier A (1962) Experimental
    chemotherapy in chemically induced mouse tumors and their transplants.
    Cancer Res, 22: 368-375.

    Honda T, Kiyozumi M, & Kojima S (1990) Alkylnaphthalene: XI. Pulmonary
    toxicity of naphthalene, 2-methylnaphthalene, and
    isopropylnaphthalenes in mice. Chem Pharm Bull, 38: 3130-3135.

    Honkakoski P & Lang MA (1989) Mouse liver phenobarbital-inducible P450
    system: Purification, characterization, and differential inducibility
    of four cytochrome P450 isozymes from the D2 mouse. Arch Biochem
    Biophys, 273: 42-57.

    Hooftman RJ & Evers-de Ruiter A (1992a) Investigations into aquatic
    toxicity of phenanthrene (cover-report for reproduction tests with the
    waterflea  Daphnia magna and an early life stage test with the zebra
    fish  Brachydanio rerio. Delft, The Netherlands, TNO Institute of
    Environmental Science, 23 pp (TNO Report No. IMW-R 92/290).

    Hooftman RJ & Evers-de Ruiter A (1992b) The toxicity and uptake of
    fluoranthene in  Brachidanio rerio in an early life stage test.
    Delft, TNO Institute of Environmental Science, 36 pp (TNO Report No.
    IMW-R 92/207).

    Hooftman RJ & Evers-de Ruiter A (1992c) The toxicity and uptake of
    benzo[k]fluoranthene using  Brachidanio rerio in an early life stage
    test. Delft, The Netherlands, TNO Institute of Environmental Science,
    33 pp (TNO Report No. IMW-R 92/218).

    Hooftman RJ & Evers-de Ruiter A (1992d) Early life stage tests with
     Brachidanio rerio and several polycyclic aromatic hydrocarbons using
    an intermittent flow-through system. Delft, TNO Institute of
    Environmental Science, 35 pp (TNO Report No. IMW-R 92/210).

    Hooftman RN, Henzen L, & Roza P (1993) The toxicity of a polycyclic
    aromatic mixture in an early stage toxicity test carried out in an
    intermittent flow-through system. Delft, TNO Institute of
    Environmental Science, 41 pp (TNO Report No. IMW-R 93/253).

    Hopia A, Pyysalo H, & Wickström K (1986) Margarines, butter and
    vegetable oils as sources of polycyclic aromatic hydrocarbons. J Am
    Oil Chem Soc, 63: 889-893.

    Horikawa K, Sera N, Otofuji T, Murakami K, Tokiwa H, Hwagawa M, Izumi
    K, & Otsuka H (1991) Pulmonary carcinogenicity of 3,9- and
    3,7-dinitrofluoranthene, 3-nitrofluoranthene and benzo [a]pyrene in
    F344 rats. Carcinogenesis, 12: 1003-1008.

    Horton AW & Christian GM (1974) Cocarcinogenic versus incomplete
    carcinogenic activity among aromatic hydrocarbons: Contrast between
    chrysene and benzo [b]-triphenylene. J Natl Cancer Inst, 53:
    1017-1020.

    Hose JE (1985) Potential uses of sea-urchin embryos for identifying
    toxic chemicals: Description of a bioassay incorporating cytologic,
    cytogenetic and embryologic endpoints. J Appl Toxicol, 5: 245-254.

    Hose JE, Hannah JB, Landolt ML, Miller BS, Felton SP, & Iwaoka WT
    (1981) Uptake of benzo [a]pyrene by gonadal tissue of flatfish family
    Plueronectidae and its effects on subsequent egg development. J
    Toxicol Environ Health, 11: 991-1000.

    Hose JE, Hannah JB, DiJulio D, Landolt ML, Miller BS, Iwaoka WT, &
    Felton SP (1982) Effects of benzo [a]pyrene on early development of
    flatfish. Arch Environ Contam Toxicol, 11: 167-171.

    Hoshino K, Hayashi Y, Takehira Y, & Kameyama Y (1981) Influences of
    genetic factors on the teratogenicity of environmental pollutants:
    Teratogenic susceptibility to benzo [a]pyrene and Ah locus in mice.
    Congenital Anomalies, 21: 97-103.

    House RV, Pallardy MJ, Burleson GR, & Dean JH (1988)
    7,12-Dimethylbenz [a]-anthracene-induced modulation of cytokines
    involved in cytotoxic T-lymphocyte induction. In Vitro Toxicol, 2:
    267-278.

    House RV, Pallardy MJ, & Dean JH (1989) Suppression of murine
    cytotoxic T-lymphocyte induction following exposure to
    7,12-dimethylbenz [a]anthracene: Dysfunction of antigen recognition.
    Int J Immunopharmacol, 2: 207-215.

    Houser WH, Raha A, & Vickers M (1992) Induction of CYP1A1 gene
    expression in H4II-E rat hepatoma cells by benzo [e]pyrene. Mol
    Carcinog, 5: 232-237.

    Howard J (1979) Method 5: Analysis of benzo [a]pyrene and other
    polycyclic aromatic hydrocarbons in foods. In: Egan H, Castegnaro M,
    Bogovski P, Kunte H, & Walker EA ed. Environmental carcinogens:
    Selected methods of analysis. Volume 3. Analysis of polycyclic
    aromatic hydrocarbons in environmental samples. Lyon, International
    Agency for Research on Cancer, pp 175-191 (IARC Scientific
    Publications No. 29).

    Howard JW & Fazio T (1980) Review of polycyclic aromatic hydrocarbons
    in foods. Analytical methodology and reported findings of polycyclic
    aromatic hydrocarbons in foods. J Assoc Off Anal Chem, 63: 1077-1104.

    Howard PH, Boethling RS, Jarvis WF, Meylan WM, & Michalenko EM (1991)
    In: Printup HT ed. Handbook of environmental degradation rates.
    Chelsea, Michigan, Lewis Publishers, 725 pp.

    Hradec J, Seidel A, Platt KL, Glatt HR, Oesch F, & Koblyakov V (1990)
    The initiator tRNA acceptance assay as a short-term test for
    carcinogens. 6. Results with 78 polycyclic aromatic compounds.
    Carcinogenesis, 11: 1921-1926.

    Huberman E (1975) Mammalian cell transformation and cell-mediated
    mutagenesis by carcinogenic polycyclic hydrocarbons. Mutat Res, 29:
    285-291.

    Huberman E (1978) Cell transformation and mutability of different
    genetic loci in mammalian cells by metabolically activated
    carcinogenic polycyclic hydrocarbons. In: Gelboin HV & Ts'O POP ed.
    Polycyclic hydrocarbons and cancer: Molecular and cell biology, Volume
    2. New York, Academic Press, pp 161-174.

    Huberman E & Sachs L (1976) Mutability of different genetic loci in
    mammalian cells by metabolically activated carcinogenic polycyclic
    hydrocarbons. Proc Natl Acad Sci USA, 73: 188-192.

    Huberman E, Kuroki T, Marquardt H, Selkirk JK, Heidelberger C, Grover
    PL & Sims P (1972) Transformation of hamster embryo cells by epoxides
    and other derivatives of polycyclic hydrocarbons. Cancer Res, 32:
    1391-1396.

    Huberman E, McKeown CK, Jones CA, Hoffman DR, & Murao S (1984)
    Induction of mutations by chemical agents at the hypoxanthine-guanine
    phosphoribosyl transferase locus in human epithelial teratoma cells.
    Mutat Res, 130: 127-137.

    Huggett RJ, deFur PO, & Bieri RH (1988) Organic compounds in
    Chesapeake Bay sediments. Mar Pollut Bull, 19: 454-458.

    Huggins C & Yang NC (1962) Induction and extinction of mammary cancer.
    Science, 137: 257-262.

    Huggins C, Morii S, & Grand LC (1961) Mammary cancer induced by a
    single dose of polynuclear hydrocarbons: Routes of administration. Ann
    Surg, 154: 315-318.

    Hughes TW & DeAngelis DG (1982) Emissions from coal-fired residential
    combustion equipment. In: Proceedings of the International Conference
    on Residues of Solid Fuels: Environmental Impacts/ Solutions. Dayton,
    Ohio, Monsanto Research Corporation, pp 333-348.

    Hughes NC & Phillips DH (1991) Dependence on dose of initial and
    persistant levels of benzo(a)pyrene and dibenzo(a,e)pyrene DNA adducts
    in mouse tissues. Proc Am Assoc Cancer Res, 32: 98.

    Hughes MM, Natusch DFS, Taylor DR, & Zeller MV (1980) Chemical
    transformations of particulate polycyclic organic matter. In: Bjorseth
    A & Dennis AJ ed. Polynuclear aromatic hydrocarbons: Chemistry and
    biological effects. Columbus, Ohio, Battelle Press, pp 1-8.

    Hughes MF, Chamulitrat W, Mason RP, & Eling TE (1989) Epoxidation of
    7,8-dihydroxy-7,8-dihydrobenzo [a]pyrene via a
    hydroperoxide-dependent mechanism catalyzed by lipoxygenases.
    Carcinogenesis, 10: 2075-2080.

    Huh N, Nemoto N, & Utakoji T (1982) Metabolic activation of
    benzo [a]pyrene, aflatoxin B1, and dimethylnitrosamine by a human
    hepatoma cell line. Mutat Res, 94: 339-348.

    van Hummelen P, Gennart JP, Buchete JP, Lauwerys R, & Kirsch-Volders M
    (1993) Biological markers in PAH exposed workers and controls. Mutat
    Res, 300: 231-239.

    Hungspreugs M, Silpipat S, Tonapong C, Lee RF, Windom HL, & Tenore KR
    (1984) Heavy metals and polycyclic hydrocarbon compounds in benthic
    organisms of the upper Gulf of Thailand. Mar Pollut Bull, 15: 213-218.

    Hurley JF, Archibald RMcL, Collins PL, Fanning DM, Jacobsen M, &
    Steele RC (1983) The mortality of coke workers in Britain. Am J Ind
    Med, 4: 691-704.

    Husgafvel-Pursiainen K, Sorsa M, Mœller M, & Benestad C (1986)
    Genotoxicity and polynuclear aromatic hydrocarbon analysis of
    environmental tobacco smoke samples from restaurants. Mutagenesis, 1:
    287-292.

    Hutchinson TC, Hellebust JA, Tam D, Mackay D, Mascarenhas RA, & Shiu
    WY (1980) The correlation of the toxicity to algae of hydrocarbons and
    halogenated hydrocarbons with their physical-chemical properties. In:
    Afghan BK & Mackay D ed. Hydrocarbons and halogenated hydrocarbons in
    the aquatic environment. New York, Plenum Press, pp 577-586.

    IARC (1973) Certain polycyclic aromatic hydrocarbons and heterocyclic
    compounds. Lyon, International Agency for Research on Cancer, p 178
    (IARC Monographs on the Evaluation of the Carcinogenic Risk of
    Chemicals to Man, Volume 13).

    IARC (1983) Polynuclear aromatic compounds. Part 1: Chemical,
    environmental and experimental data. Lyon, International Agency for
    Research on Cancer, 477 pp (IARC Monographs on the Evaluation of the
    Carcinogenic Risk of Chemicals to Humans, Volume 32).

    IARC (1984a) Polynuclear aromatic hydrocarbons. Part 2: Carbon blacks,
    mineral oils (lubricant base oils and derived products) and some
    nitroarenes. Lyon, International Agency for Research on Cancer, 365 pp
    (IARC Monographs on the Evaluation of the Carcinogenic Risk of
    Chemicals to Humans, Volume 33).

    IARC (1984b) Polynuclear aromatic compounds. Part 3: Industrial
    exposures in aluminium production, coal gasification, coke production,
    and iron and steel founding. Lyon, International Agency for Research
    on Cancer, 219 pp (IARC Monographs on the Evaluation of the
    Carcinogenic Risk of Chemicals to Humans, Volume 34).

    IARC (1985) Polynuclear aromatic compounds. Part 4: Bitumens,
    coal-tars and derived products, shale-oils and soots. Lyon,
    International Agency for Research on Cancer, 271 pp (IARC Monographs
    on the Evaluation of the Carcinogenic Risk of Chemicals to Humans,
    Volume 35).

    IARC (1986) Tobacco smoking. Lyon, International Agency for Research
    on Cancer, 139 pp (IARC Monographs on the Evaluation of the
    Carcinogenic Risk of Chemicals to Humans, Volume 38).

    IARC (1987) Overall evaluations of carcinogenicity: An updating of
     IARC Monographs Volumes 1 to 42. Lyon, International Agency for
    Research on Cancer, 403 pp (IARC Monographs on the Evaluation of the
    Carcinogenic Risk of Chemicals to Humans, Supplement 7).

    IARC (1989a) Diesel and gasoline engine exhausts and some nitroarenes.
    Lyon, International Agency for Research on Cancer, 322 pp (IARC
    Monographs on the Evaluation of Carcinogenic Risk of Chemicals to
    Humans, Volume 46).

    IARC (1989b) Occupational exposures in petroleum refining: Crude oil
    and major petroleum fuels. Lyon, International Agency for Research on
    Cancer, 283 pp (IARC Monographs on the Evaluation of the Carcinogenic
    Risk of Chemicals to Man, Volume 45).

    Ichinotsubo K, Mower HF, Settliff J, & Mandel M (1977) The use of rec-
     bacteria for testing of carcinogenic substances. Mutat Res, 46: 53-
    61.

    Ilnitsky AP, Mischenko VS, & Shabad LM (1977) New data on volcanoes as
    natural sources of carcinogenic substances. Cancer Lett, 3: 227-230.

    Ingram AJ & Phillips JC (1993) The dermal bioavailability of
    radiolabelled benzo(a)pyrene from acetone or from oils of differing
    viscosity, assessed by DNA and protein binding. J Appl Toxicol, 13:
    25-32.

    Ingram LL Jr, McGinnis GD, Gjovik LR, & Roberson G (1982) Migration of
    creosote and its components from treated piling sections in a marine
    environment. In: Proceedings of the Seventy-eighth Annual Meeting of
    the American Wood-preservers' Association, New Orleans, Louisiana, 2-5
    May 1982. Bethesda, Maryland, American Wood-preservers' Association,
    Volume 78, pp 120-128.

    Ingram AJ, Lee R, & Phillips JC (1995) Factors affecting the
    bioavailability of benzo(a)pyrene from oils in mouse skin: Oil
    viscosity, grooming, activity and its prevention. J Appl Toxicol, 15:
    175-182.

    Inokuchi H & Nakagaki M (1959) The density of the polycyclic aromatic
    compounds. Bull Chem Soc Jpn, 32: 65-67.

    International Programme on Chemical Safety (1993) Environmental health
    criteria 155: Biomarkers and risk assessment: Concepts and principles.
    Geneva, World Health Organization, 82 pp.

    International Union of Pure and Applied Chemistry (1979) Nomenclature
    of organic chemistry. Sections A, B, C, D, E, F and H. Oxford,
    Pergamon Press, pp 20-31.

    International Union of Pure and Applied Chemistry (1987) Recommended
    method for a thin-layer-chromatographic screening method for the
    determination of benzo(a)pyrene in smoked food. Pure Appl Chem, 59:
    1735-1738.

    Iosifidou HG, Kilikidis SD, & Kamarianos AP (1982) Analysis for
    polycyclic aromatic hydrocarbons in mussels  (Mytilus 
     galloprovincialis) from the Thermaikos Gulf, Greece. Bull Environ
    Contam Toxicol, 28: 535-541.

    Ishidate M & Odashima S 81977) Chromosome tests with 134 compounds on
    Chinese hamster cells  in vitro: A screening for chemical
    carcinogens. Mutat Res, 48: 337-354.

    Ishinishi N, Kodema Y, Kunitake E, Nobutomo K & Fukushima Y (1976) The
    carcinogenicity of dusts collected from an open-hearth furnace for the
    smelting of iron: A preliminary experimental study. In: Nordberg GF,
    ed. Effects and dose-response relationships of toxic metals.
    Amsterdam, Elsevier Scientific Publishers, pp 480-488.

    Ishio S, Chen JC, & Kawasaki Y (1977) Cell division of
     Gyrodinium sp. and mitotic delay induced by causal substances of
    algal tumor and carcinogens. Jpn Soc Sci Fish, 43: 507-516.

    Iyer P, Gollahon LS, Martin JE, & Irvin TR (1990) Evaluation of the
     in vitro growth of rodent preimplantation embryos exposed to
    naphthalene  in vivo. Toxicologist, 10: 274.

    Iyer P, Martin JE, & Irvin TR (1991) Role of biotransformation in  in
    vitro preimplantation embryotoxicity of naphthalene. Toxicology, 66:
    257-270.

    Jacob J (1996) Mammalian organism - Cell cultures - Enzymes. A
    comparison of  in vivo and  in vitro systems. In: Mohr M, Adler K,
    Dungworth D, Harris C, Plopper C, & Saracci R ed. Correlations between
     in vitro and  in vivo investigations in inhalation toxicology.
    Washington DC, International Life Sciences Institute Press, pp 279-
    297.

    Jacob J & Grimmer G (1979) Extraction and enrichment of polycyclic
    aromatic hydrocarbons (PAH) from environmental matter. In: Egan H,
    Castegnaro M, Bogovski P, Kunte H, & Walker EA ed. Environmental
    carcinogens: Selected methods of analysis. Volume 3: Analysis of
    polycyclic aromatic hydrocarbons in environmental samples. Lyon,
    International Agency for Research on Cancer, pp 79-89 (IARC Scientific
    Publications No. 29).

    Jacob J & Grimmer G (1992) Organic analytical approaches. In: Rossbach
    M, Schladot JD, & Ostapczuk P ed. Specimen banking. Berlin,
    SpringerVerlag, pp 93-113.

    Jacob J & Grimmer G (1994) [Environmental sample bank. PAH analysis in
    different matrices. Annual Report 1993.] Grosshansdorf, Biochemical
    Institute for Environmental Carcinogens, 50 pp (in German).

    Jacob J & Grimmer G (1995) [Environmental sample bank. PAH analysis in
    environmental samples. Annual Report 1994.] Grosshansdorf, Biochemical
    Institute for Environmental Carcinogens, 50 pp (in German).

    Jacob J, Grimmer G, & Schmoldt A (1981a) The influence of polycyclic
    aromatic hydrocarbons as inducers of monooxygenases on the metabolic
    profile of benz [a]anthracene in the rat liver microsomes. Cancer
    Lett, 14: 175-185.

    Jacob J, Schmoldt A, & Grimmer G (1981b) Glass-capillary-gas
    chromatography/mass spectrometry data of mono- and polyhydroxylated
    benz(a)anthracene. Comparison with benz(a)anthracene metabolites from
    rat liver microsomes. Hoppe-Seyler's Z Physiol Chem, 362: 1021-1030.

    Jacob J, Schmoldt A, & Grimmer G (1982a) Influence of monooxygenase
    inducers on the metabolic profile of phenanthrene in rat liver
    microsomes. Toxicology, 25: 333-343.

    Jacob J, Schmoldt A, & Grimmer G (1982b) Formation of carcinogenic and
    inactive chrysene metabilites by rat liver microsomes of various
    monooxygenase activities. Arch Toxicol, 51: 255-265.

    Jacob J, Schmoldt A & Grimmer G (1983) Benzo(e)pyrene metabolism in
    rat liver microsomes: Dependence of the metabolite profile on the
    pretreatment of rats with various monooxygenase inducers.
    Carcinogenesis, 4: 905-919.

    Jacob J, Brune H, Dettbarn G, Grimmer D, Heinrich U, Mohtashamipur E,
    Norpoth K, Pott F, & Wenzel-Hartung R (1989) Urinary and faecal
    excretion of pyrene and hydroxypyrene by rats after oral,
    intraperitoneal, intratracheal or intrapulmonary application. Cancer
    Lett, 46: 15-20.

    Jacob J, Grimmer G, & Schneider D (1990a) Sampling and analysis of
    polycyclic aromatic hydrocarbons present in particulate matter and in
    semivolatiles (b.p. > 130°C) of ambient air. Fresenius' J Anal Chem,
    37: 73.

    Jacob J, Brune H, Grimmer G, Heinrich U, Mohtashamipur E, Norpoth K,
    Pott F, & Wenzel-Hartung R (1990b) Urinary and faecal excretion of
    metabolites after various modes of administration of polycyclic
    aromatic hydrocarbons (PAH) to rats. In: Seemayer NH & Hadnagy W ed.
    Environmental hygiene II. Berlin, Springer-Verlag, pp 87-90.

    Jacob J, Grimmer G, Mohr U, Emura M, Riebe-Imre M, & Raab G (1992) The
    metabolism of chrysene and benzo(a)pyrene in hamster, rat and human
    lung cells in culture. In: Seemeyer NH & Hadnagy W ed. Environmental
    hygiene III. Berlin, Springer-Verlag, pp 87-90.

    Jacob J, Grimmer G, & Hildebrandt A (1993a) Correlation between PAH
    concentrations measured in air, biological passive samplers and in
    corresponding soil samples in Germany. In: Garrigues P & Lamotte M ed.
    Polycyclic aromatic compounds: Synthesis, properties, analytical
    measurements, occurrence and biological effects. Bordeaux, Gordon &
    Breach Science Publishers, pp 427-433.

    Jacob J, Grimmer G, & Hildebrandt A (1993b) The use of passive
    samplers for monitoring polycyclic aromatic hydrocarbons in ambient
    air. Sci Total Environ, 139/140: 307-321.

    Jacob J, Grimmer G, Mohr U, Emura M, Riebe-Imre M, Raab G, & Knebel J
    (1993c) Metabolic activation of chrysene and benzo [a]pyrene in
    hamster, rat and human  in vitro lung cell cultures. In: Garrigues P
    & Lamotte M ed. Polycyclic aromatic compounds: Synthesis, properties,
    analytical measurements, occurrence and biological effects. Bordeaux,
    Gordon & Breach Science Publishers, pp 1175-1182.

    Jacob J, Grimmer G, Hanssen HP, & Hildebrand A (1994) Extractability
    and bioavailability of PAH from soil and air particulate matter.
    Polycyclic Aromat Compd, 5: 209-217.

    Jacob J, Doehmer J, Grimmer G, Soballa V, Raab G, Seidel A, & Greim H
    (1996) Metabolism of phenanthrene, benz(a)anthracene, benzo(a)pyrene
    and benzo(c)-phenanthrene by eight cDNA-expressed human and rat
    cytochromes P450. Polycyclic Aromat Compd 10: 1-9.

    Jacobs BW & Billings CE (1985) Characterization and temperature
    dependence of PAH emissions from a simulated rubber combustion
    operation. Am Ind Hyg Assoc J, 46: 547-554.

    Jahn CL & Litman GW (1977) Distribution of covalently bound
    benzo [a]pyrene in chromatin. Biochem Biophys Res Commun, 76:
    534-540.

    Jahn CL & Litman GW (1979) Accessibility of deoxyribonucleic acid in
    chromatin to the covalent binding of the chemical carcinogen
    benzo [a]pyrene. Biochemistry, 18: 1442-1449.

    Jaklin J & Krenmayr P (1985) A routine method for the quantitative
    determination of polycyclic aromatic hydrocarbons (PAHs) in urban air.
    Int J Environ Anal Chem, 21: 33-42.

    Jaklin J, Krenmayr P, & Varmuza K (1988) [Polycyclic aromatic
    compounds in the atmosphere of Linz (Austria).] Fresenius' Z Anal
    Chem, 331: 479-485 (in German).

    James MO (1989) Biotransformation and disposition of PAH in aquatic
    invertebrates. In: Varanasi U ed. Metabolism of polycyclic aromatic
    hydrocarbons in the aquatic environment. Boca Raton, Florida, CRC
    Press, pp 69-91.

    Janini GM, Johnston K, & Zielinski WL Jr (1975) Use of nematic liquid
    crystal for gas-liquid chromatographic separation of polyaromatic
    hydrocarbons. Anal Chem, 47: 670-674.

    Janini GM, Muschik GM, Schroer JA, & Zielinski WL Jr (1976) Gas-liquid
    chromatographic evaluation and gas-chromatography/mass spectrometric
    application of new high-temperature liquid crystal stationary phases
    for polycyclic aromatic hydrocarbon separations. Anal Chem, 48: 1879-
    1883.

    Janssen O (1980) [Brief review of investigations on PAH in vehicle
    exhaust, round robin tests on profile analysis, role of fuels and
    lubricants, field studies. Air pollution from polycyclic aromatic
    hydrocarbons. Registration and evaluation.] Düsseldorf, VDI-Verlag, pp
    69-79 (VDI Report No. 358) (in German).

    Japanese Ministry of International Trade and Industry (1992)
    Biodegradation and accumulation, data of existing chemicals based on
    the CSCL Japan. Tokyo: Japan Chemical Industry Ecology-toxicology and
    Information Center, 467 pp.

    Japenga J, Wagenaar WJ, Smedes F, & Salomons W (1987) A new, rapid
    clean-up procedure for the simultaneous determination of different
    groups of organic micropollutants in sediments. Application in two
    European estuarine sediment studies. Environ Technol Lett, 8: 9-20.

    Jeffrey AM, Jennette KW, Blobstein SH, Weinstein IB, Beland FA, Harvey
    RG, Kasai H, Miura, & Nakananishi K (1976) Benzo [a]pyrene-nucleic
    acid derivative found  in vivo: Structure of a benzo[-]pyrene
    tetrahydrodiol epoxide-guanosine adduct. J Am Chem Soc, 98: 5714-5715.

    Jennette KW, Jeffrey AM, Blobstein SH, Beland FA, Harvey RG, &
    Weinstein IB (1977) Nucleoside adducts from the  in vitro reaction of
    benzo [a]pyrene-7,8-dihydrodiol 9,10-oxide or benzo [a]pyrene
    4,5-oxide with nucleic acids. Biochemistry, 16: 932-938.

    Jerina DM, Lehr RE, Yagi H, Hernandez O, Dansette PM, Wislocki PG,
    Wood AW, Chang RI, Levin W, & Conney AH (1976) Mutagenicity of
    benzo [a]pyrene derivatives and the description of a quantum
    mechanical model which predicts the ease of carbonium ion formation
    from diol epoxides. In: De Serres FJ, Fouts JR, & Bend JR ed.
     In vitro metabolic activation in mutagenesis testing. New York,
    Elsevier North Holland, pp 159-178.

    Jernström B & Gräslund A (1994) Covalent binding of benzo(a)pyrene
    7,8-dihydrodiol 9,10-epoxides to DNA: Molecular structures, induced
    mutations and biological consequences. Biophys Chem, 49: 185-199.

    Jernström B, Vadi H, & Orrennius S (1978) Formation of DNA-binding
    products from isolated benzo(a)pyrene metabolites in rat liver nuclei.
    Chem-Biol Interactions, 20: 311-321.

    Jernström B, Martinez M, Meyer DJ, & Ketterer B (1985) Glutathione
    conjugation of the carcinogenic and mutagenic electrophile
    (±)-7b,8a-dihydroxy-9a,10a-oxy-7,8,9,10-tetra hydrobenzo [a]pyrene
    catalyzed by purified rat liver glutathione transferases.
    Carcinogenesis, 6: 85-89.

    Ji C & Marnett LJ (1992) Oxygen radical-dependent epoxidation of
    (7 S,8 S)-dihyroxy-7,8-dihydrobenzo [a]pyrene in mouse skin
     in vivo. J Biol Chem, 267: 17842-17848.

    Jimenez BD, Cirmo CP, & McCarthy JF (1987) Effects of feeding and
    temperature on uptake, elimination and metabolism of benzo(a)pyrene in
    the bluegill sunfish  (Lepomis macrochirus). Aquat Toxicol, 10: 41-
    57.

    Jockers R, Patalas N, Schacht S, Rehm H-J, & Freier D (1988)
    [Development of biotechnological processes for the treatment of
    wastewater from coal refinement: Final report.] Essen,
    Bergbau-Forschung, 158 pp (Report No. BMFT FKZ 03 E-6284-A) (in
    German).

    Joe FL Jr, Salemme J, & Fazio T (1984) Liquid chromatographic
    determination of trace residues of polynuclear aromatic hydrocarbons
    in smoked foods. J Assoc Off Anal Chem, 67: 1076-1082.
    Johnke B (1992) [Waste incineration as dioxin source or sink.]
    ENTSORGA-Mag Entsorg.wirtsch, 9: 59-66 (in German).

    Johnsen S, Kukkonen J, & Grande M (1989) Influence of natural aquatic
    humic substances on the bioavailability of benzo(a)pyrene to Atlantic
    salmon. Sci Total Environ, 81/82: 691-702.

    Johnson S (1968) Effect of thymectomy on the induction of skin tumours
    by dibenzanthracene, and of breast tumours by dimethylbenzanthracene
    in mice of the IF strain. Br J Cancer, 22: 755-761.

    Johnson AC, Larsen PF, Gadbois DF, & Humason AW (1985) The
    distribution of polycyclic aromatic hydrocarbons in the superficial
    sediments of Penobscot Bay (Maine, USA) in relation to possible
    sources and to other sites worldwide. Mar Environ Res, 15: 1-16.

    Jones PW, Giammar RD, Strup PE, & Stanford TB (1976) Efficient
    collection of polycyclic organic compounds from combustion effluents.
    Environ Sci Technol, 10: 806-810.

    Jones KC, Stratford JA, Waterhouse KS, & Johnston AE (1987)
    Polynuclear aromatic hydrocarbons in UK soils: Long-term temporal
    trends and current levels. In: Hemphill DD ed. Trace substances in
    environmental health. XXI. Proceedings of the University of Missouri's
    21st Annual Conference on Trace Substances in Environmental Health, St
    Louis, Missouri, 25-28 May 1987. Columbia, Missouri, University of
    Missouri, pp 140-148.

    Jones KC, Stratford JA, Waterhouse, & Vogt NB (1989a) Organic
    contaminants in Welsh soils: Polynuclear aromatic hydrocarbons.
    Environ Sci Technol, 23: 540-550.

    Jones KC, Grimmer G, Jacob J, & Johnston AE (1989b) Changes in the
    polynuclear aromatic hydrocarbon content of wheat grain and pasture
    grassland over the last century from one site in the UK. Sci Total
    Environ, 78: 117-130.

    Jones KC, Stratford JA, Waterhouse KS, Furlong ET, Giger W, Hites RA,
    Schaffner C, & Johnston AE (1989c) Increases in the polynuclear
    aromatic hydrocarbon content of an agricultural soil over the last
    century. Environ Sci Technol, 23: 95-101.

    Jongeneelen FJ (1992) Biological exposure limit for occupational
    exposure to coal tar pitch volatiles at coke ovens. Int Arch Occup
    Environ Health, 63: 511-516.

    Jongeneelen FJ (1994) Biological monitoring of environmental exposure
    to polycyclic aromatic hydrocarbons: 1-Hydroxypyrene in urine of
    people. Toxicol Lett, 72: 205-211.

    Jongeneelen FJ, Bos RP, Anzion RBM, Theuws JLG, & Henderson PT (1986)
    Biological monitoring of polycyclic aromatic hydrocarbons: Metabolites
    in urine. Scand J Work Environ Health, 12: 137-143.

    Jongeneelen FJ, Scheepers PTJ, Groenendijk A, Van Aerts LAGJM, Anzion
    RBM, Bos RP, & Veenstra SJ (1988a) Airborne concentrations, skin
    contamination, and urinary metabolite excretion of polycyclic aromatic
    hydrocarbons among paving workers exposed to coal tar derived road
    tars. Am Ind Hyg Assoc J, 49: 600-607.

    Jongeneelen FJ, Anzion RBM, Scheepers PTJ, Bos RP, Henderson PT,
    Nijenhuis EH, Veenstra SJ, Brouns RME, & Winkes A (1988b)
    1-Hydroxypyrene in urine as a biological indicator of exposure to
    polycyclic aromatic hydrocarbons in several work environments. Ann
    Occup Hyg, 32: 35-43.

    Jongeneelen FJ, van Leeuwen FE, Oosterink S, Anzion RBM, van der Loop
    F, Bos RP, & van Veen HG (1990) Ambient and biological monitoring of
    coke oven workers: Determinants of the internal dose of polycyclic
    aromatic hydrocarbons. Br J Ind Med, 47: 454-461.

    Joshi PL & Misra RB (1986) Evaluation of chemically-induced
    phototoxicity to aquatic organism using  Paramecium as a model.
    Biochem Biophys Res Commun, 139: 79-84.

    Jotz MM & Mitchell AD (1981) Effects of 20 coded chemicals on the
    forward mutation frequency at the thymidine kinase locus in L5178Y
    mouse lymphoma cells. In: De Serres FJ & Ashby J ed. Evaluation of
    short-term tests for carcinogens. Report of the international
    collaborative programme. New York, Elsevier North Holland, pp 580-593
    (Progress in Mutation Research, Volume 1).

    Junk GA, Richard JJ, Avery MJ, Vick RD, & Norton GA (1986) Organic
    compounds from coal combustion. Am Chem Soc Symp Ser, 319: 109-123.

    Jury WA, Russo D, Streile G, & El Abd H (1990) Evaluation of
    volatilization by organic chemicals residing below the soil surface.
    Water Res, 26: 13-26.

    Kadar R, Nagy K, & Frimstad D (1980) Determination of polycyclic
    aromatic hydrocarbons in industrial waste water at the ng/ml level.
    Talanta, 27: 227-230.

    Kaden DA, Hites RA, & Thilly WG (1979) Mutagenicity of soot and
    associated polycyclic aromatic hydrocarbons to  Salmonella 
     typhimurium. Cancer Res, 39: 4152-4159.

    Kagan J & Kagan ED (1986) The toxicity of benzo(a)pyrene and pyrene in
    the mosquito  Aedes aegypti, in the dark and in the presence of
    ultraviolet light. Chemosphere, 15: 243-251.

    Kagan J, Kagan ED, Kagan IA, Kagan PA, & Quigley S (1985) The
    phototoxicity of non-carcinogenic polycyclic aromatic hydrocarbons in
    aquatic organisms. Chemosphere, 14: 1829-1834.

    Kagan J, Sinnott D, & Kagan E (1987) The toxicity of pyrene in the
    fish  Pimephales promelas. Synergism by piperonyl butoxide and by
    ultraviolet light. Chemosphere, 16: 2291-2298.

    Kagan J, Tuveson RW, & Gong HH (1989) The light-dependent cytotoxicity
    of benzo [a]pyrene: Effect on human erythrocytes,  Escherichia coli
    cells, and  Haemophilus influenzae transforming DNA. Mutat Res, 216:
    231-242.

    Kagi R, Alexander R, & Cumbers M (1985) Polycyclic aromatic
    hydrocarbons in rock oysters: A baseline study. Int J Environ Anal
    Chem, 22: 135-153.

    Kaidbey KH & Nonaka S (1984) Action spectrum for anthracene-induced
    photosensitization of human skin. Photochem Photobiol, 39: 375-378.

    Kakunaga T (1973) A quantitative system for assay of malignant
    transformation by chemical carcinogens using a clone derived from
    BALB/3T3. Int J Cancer, 12: 463-473.

    Kalberlah F, Frijus-Plessen N, & Hassauer M (1995) [Toxicological
    criteria for the risk assessment of polyaromatic hydrocarbons (PAH) in
    existing chemicals. Part 1: The use of equivalency factors.]
    Altlasten-Spektrum, 5: 231-237 (in German).

    Kallistratos G & Pfau A (1971) [Effect of 3,4-benzopyrene on large
    mammals.] Naturwissenschaften, 58: 222 (in German).

    Kamens RM, Zhishi G, Fulcher JN, & Bell D (1986a) The influence of
    temperature on the daytime PAH decay on atmospheric soot particles.
    Proceedings of the 79th Air Pollution Control Association Annual
    Meeting, 23-27 June (No. 86-77-2), pp 1-19.

    Kamens RM, Fulcher JN, & Zhishi G (1986b) Effects of temperature on
    wood soot PAH decay in atmospheres with sunlight and low Nox
    nitrogen oxides. Atmos Environ, 20: 1579-1587.

    Kamens RM, Guo Z, Fulcher JN, & Bell DA (1988) Influence of humidity,
    sunlight and temperature on the daytime decay of polyaromatic
    hydrocarbons on atmospheric soot particles. Environ Sci Technol, 22:
    103-108.

    Kamens RM, Zhishi G, Fulcher JN, & Bell DA (1991) The influence of
    humidity on the daytime decay of PAH on atmospheric soot particles.
    In: Cooke M, Loening K, & Merrit J ed. Polynuclear aromatic
    hydrocarbons: Measurement, means and metabolism. Columbus, Ohio,
    Battelle Press, pp 435-451.

    Kang DH, Rothman N, Poirier, MC, Greenberg A, Hsu CH, Schwartz BS,
    Baser ME, Groopman JD, Weston A, & Strickland PT (1995)
    Interindividual differences in the concentration of
    1-hydroxypyrene-glucuronide in urine and polycyclic aromatic
    hydrocarbon-DNA adducts in peripheral white blood cells after
    charbroiled beef consumption. Carcinogenesis, 16: 1079-1085.

    Kanij JBW (1987) The emission of polycyclic aromatic hydrocarbons by
    coal-fired power stations in the Netherlands. Kema Sci Tech Rep, 5:
    83-91.

    Kanoh T, Fukuda M, Onozuka H, Kinouchi T, & Ohnishi Y (1993) Urinary
    1-hydroxypyrene as a marker of exposure to polycyclic aromatic
    hydrocarbons in environment. Environ Res, 62: 230-241.

    Kao J, Patterson FK, & Hall J (1985) Skin penetration and metabolism
    of topically applied chemicals in six mammalian species, including
    man: An  in vitro study with benzo [a]pyrene and testosterone.
    Toxicol Appl Pharmacol, 81: 502-516.

    Kappeler T & Wuhrmann K (1978) Microbial degradation of water soluble
    fraction of gas oil. Water Res, 12: 327-333.

    Karcher W (1988) Spectral atlas of polycyclic aromatic compounds,
    Volume 2. Dordrecht, Kluwer Academic Publishers, pp 16-18, 55.

    Karcher W, Dubois J, Fordham RJ, Glaude P, Barale R, & Zucconi D
    (1984) Molecular spectra and mutagenic activity of some nitrogen
    containing heterocyclic aromatic compounds. In: Cooke M & Dennis AJ
    ed. Mechanisms, methods and metabolism: Polynuclear aromatic
    hydrocarbons. Columbus, Ohio, Battelle Press, pp 685-696

    Karcher W, Fordham R, Dubois JJ, Glaude PGJM, & Ligthart JAM (1985)
    Spectral atlas of polycyclic aromatic compounds including data on
    occurrence and biological activity. Dordrecht, D Reichel Publishing
    Co., 818 pp.

    Karcher W, Devillers J, Garrigues P, & Jacob J (1991) Spectral atlas
    of polycyclic aromatic compounds.Dordrecht, Kluwer Academic
    Publishers, p 21.

    Karickhoff SW (1981) Semi-empirical estimation of sorption of
    hydrophobic pollutants on natural sediments and soils. Chemosphere,
    10: 833-846.

    Karickhoff SW & Morris KR (1985) Sorption dynamics of hydrophobic
    pollutants in sediment suspensions. Environ Toxicol Chem, 4: 469-479.

    Karickhoff SW, Brown DS, & Scott TA (1979) Sorption of hydrophobic
    pollutants on natural sediments. Water Res, 13: 241-248.

    Karlehagen S, Andersen A, & Ohlson CG (1992) Cancer incidence among
    creosote-exposed workers. Scand J Work Environ Health, 18: 26-29.

    Karlesky DL, Ramelow G, Ueno Y, Warner IM, & Ho C-N (1987) Survey of
    polynuclear aromatic compounds in oil refining areas. Environ Pollut,
    43: 195-207.

    Katz M, Heddle JA, & Salamone MF (1981) Mutagenic activity of
    polycyclic aromatic hydrocarbons and other environmental pollutants.
    Columbus, Ohio, Battelle Press, pp 519-528.

    Kauss PB & Hutchinson TC (1975) The effects of water-soluble petroleum
    components on the growth of  Chlorella vulgaris 
    Beijerinck. Environ Pollut, 9: 157-174.

    Kawabata TT & White KL (1987) Suppression of the  in vitro humoral
    immune response of mouse splenocytes by benzo(a)pyrene metabolites and
    inhibition of benzo(a)pyrene-induced immunosuppression by
    alpha-naphthoflavone. Cancer Res, 47: 2317-2322.

    Kawabata TT & White KL (1990) Effects of naphthalene and naphthalene
    metabolites on the  in vitro humoral immune response. J Toxicol
    Environ Health, 30: 53-67.

    Kawai M (1979) [Review of toxicological and occupational aspects of
    naphthalene.] Aromatics, 31: 168-181 (in Japanese).

    Kawamura K & Kaplan IR (1986) Compositional change of organic matter
    in rainwater during precipitation events. Atmos Environ, 20: 527-535.

    Kawamura Y, Kamata E, Ogawa Y, Kaneko T, Uchiyama S, & Saito Y (1988)
    The effect of various foods on the intestinal absorption of
    benzo(a)pyrene in rats. J Food Hyg Soc Jpn, 29: 21-25.

    Kayal SI & Connell DW. (1990) Partitioning of unsubstituted polycyclic
    aromatic hydrocarbons between surface sediments and the water column
    in the Brisbane River estuary. Aust J Mar Freshwater Res, 41: 443-456.

    Kebbekus B, Greenberg A, Horgan L, Bozzelli J, Darack F, Eveleens C, &
    Stangeland L (1983) Concentration of selected vapor and
    particulate-phase substances in the Lincoln and Holland tunnels. J Air
    Pollut Control Assoc, 33: 328-330.

    Keller CD & Bidleman TF (1984) Collection of airborne polycyclic
    aromatic hydrocarbons and other organics with a glass fiber
    filter-polyurethane foam system. Atmos Environ, 18: 837-845.

    Kelman BJ & Springer DL (1982) Movements of benzo [a]pyrene across
    the hemochorial placenta of the guinea pig (41307). Proc Soc Exp Biol
    Med, 169: 58-62.

    Kemena A, Norpoth KH, & Jacob J (1988) Differential induction of the
    monooxygenase isoenzymes in mouse liver microsomes by polycyclic
    aromatic hydrocarbons. In: Cooke M & Dennis AJ ed. Polynuclear
    aromatic hydrocarbons: A decade of progress. Columbus, Ohio, Battelle
    Press, pp 449-460.

    Kennaway FL (1924) On the cancer-producing factor in tar. Br Med J, i:
    564-567.

    Kennaway EL (1930) Further experiments on cancer-producing substances.
    Biochem J, 24: 497-504.

    Kensler TW, Egner PA, Moore KG, Taffe BG, Twerdok LE, & Trush MA
    (1987) Role of inflammatory cells in the metabolic activation of
    polycyclic aromatic hydrocarbons in mouse skin. Toxicol Appl
    Pharmacol, 90: 337-346.

    Ketkar M, Green V, Schneider P, & Mohr U (1979) Investigations on the
    carcinogenic burden by air pollution in man. Intratracheal
    instillation studies with benzo(a)pyrene in a mixture of Tris buffer
    and saline in Syrian golden hamsters. Cancer Lett, 6: 279-284.

    Khalili NR, Scheff PA, & Holsen TM (1995) PAH source fingerprints for
    coke ovens, diesel and gasoline engines, highway tunnels, and wood
    combustion emissions. Atmos Environ, 29: 533-542.

    Khesina AY (1994) Urban air pollution by carcinogenic and genotoxic
    polyaromatic hydrocarbons in the former USSR. Environ Health Perspect,
    102 (suppl 4): 49-53.

    Kicinski HG, Adamek S, & Kettrup A (1989) Trace enrichment and HPLC
    analysis of polycyclic aromatic hydrocarbons in environmental samples,
    using solid phase extraction in connection with UV/VIS diode-array and
    fluorescence detection. Chromatographia, 28: 203-208.

    Kiene R & Capone D (1984) Effects of organic pollutants on
    methanogenesis, sulfate reduction and carbon dioxide evolution in salt
    marsh sediments. Mar Environ Res, 13: 141-160.

    Kimber I, Jones K, & Vignali DAA (1986) The influence of
    7,12-dimethybenzanthracene on natural killer (NK) cell function in
    rats. J Clin Lab Immunol, 20: 193-198.

    Kincannon DF & Lin YS (1985) Microbial degradation of hazardous wastes
    by land treatment. In: Proceedings of the 40th Industrial Waste
    Conference, Purdue University, West Lafayette, Indiana, 14-16 May,
    1985. Boston, Butterworth Press, pp 607-619.

    King HWS, Osborne MR, & Brookes P (1979) The  in vitro and
     in vivo reaction at the N7 position of guanine of the ultimate
    carcinogen derived from benzo [a]pyrene. Chem-Biol Interactions, 24:
    345-353.

    Kirchmann H, Aström H, & Jönsäll G (1991) Organic pollutants in sewage
    sludge. 1. Effect of toluene, naphthalene, 2-methylnaphthalene,
    4-n-nonylphenol and di-2-ethylhexyl phthalate on soil biological
    processes and their decomposition in soil. Swed J Agric Res, 21: 107-
    113.

    Kishi H, Kogure N, & Hashimoto Y (1990) Contribution of soil
    constituents in adsorption coefficient of aromatic compounds,
    halogenated alicyclic and aromatic compounds to soil. Chemosphere, 21:
    867-876.

    Kjuus H, Andersen A, Langard S, & Knudsen KE (1986) Cancer incidence
    among workers in the Norwegian ferroalloy industry. Br J Ind Med, 43:
    227-236.

    Klassert A (1993) [Demonstration plant for adsorptive purification of
    waste water from basic chemical industry.] Berlin, Ministry of
    Environment, 93 pp (Report No. UBA 20441-5/2) (in German).

    Klein M (1960) A comparison of the initiating and promoting actions of
    9,10-dimethyl-1,2-benzanthracene and 1,2,5,6-dibenzanthracene in skin
    tumorigenesis. Cancer Res, 20: 1179-1183.

    Klein M (1963) Susceptibility of strain B6AF1/J hybrid infant mice to
    tumorigenesis with 1,2-benzanthracene, deoxycholic acid, and
    3-methylcholanthrene. II. Tumours called forth by painting the skin
    with dibenzpyrene. Cancer Res, 23: 1701-1707.

    Kleinenberg HE (1939) [Investigations on the blastomogenic effect of
    3:4:8:9- dibenzpyrene and some of its derivatives.] Arch Biol Nauk,
    56: 39-47 (in Russian).

    Klemme JC, Mukhtar H, & Elmets CA (1987) Induction of contact
    hypersensitivity to dimethylbenz(a)anthracene and benzo(a)pyrene in
    C3H/HeN mice. Cancer Res, 47: 6074-6078.

    Kliesch U, Roupova I, & Adler ID (1982) Induction of chromosome damage
    in mouse bone marrow by benzo [a]pyrene. Mutat Res, 102: 265-273.

    Klingenberg H, Schürmann D, & Lies K-H (1992) Specific air pollutants
    from passenger cars: Emission and ambient air concentrations. In:
    Toxic air pollutants from mobile sources: Emissions and health
    effects. Proceedings of an International Specialty Conference.
    Pittsburgh, Pennsylvania, Air & Waste Management Association, pp 82-
    93.

    Klöpffer W, Rippen G, & Frische R (1982) Physicochemical properties as
    useful tools for predicting the environmental fate of organic
    chemicals. Ecotoxicol Environ Saf, 6: 294-301.

    Klug A (1950) The crystal and molecular structure of triphenylene,
    C18H12. Acta Crystallogr, 3: 165-175.

    Knaap AGAC, Goze C, & Simons JWIM (1981) Mutagenic activity of seven
    coded samples in V79 Chinese hamster cells. In: De Serres FJ & Ashby J
    ed. Evaluation of short-term tests for carcinogens. Report of the
    international collaborative programme. New York, Elsevier/North
    Holland, pp 608-613 (Progress in Mutation Research, Volume 1).

    Knake E (1956) [Weak tumor-inducing effect of naphthalene and
    benzene.] Virchows Arch, 329: 141-116 (in German).

    Knecht U & Woitowitz H-J (1990) [Cancer risk from use of tar bitumen
    in road building.] Bremerhaven, Wirtschaftsverlag NW Verlag für neue
    Wissenschaft GmbH, 47 pp (in German).

    Knecht U, Elliehausen H-J, & Woitowitz H-J (1986) Gaseous and adsorbed
    PAH in an iron foundry. Br J Ind Med, 43: 834-838.

    Knecht U, Elliellausen HJ, Judas W, & Woitowitz HJ (1987) Polycyclic
    aromatic hydrocarbons (PAH) in abraded particles of brake and clutch
    linings. Int J Environ Anal Chem, 28: 227-236.

    Knecht U, Bolm-Audorff U, & Woitowitz HJ (1989) Atmospheric
    concentrations of polycyclic aromatic hydrocarbons during chimney
    sweeping. Br J Ind Med, 46: 479-481.

    Knight CV & Humphreys MP (1985) Polynuclear aromatic hydrocarbons in
    indoor residential air resulting from use of conventional and
    catalytic wood heaters in a weatherized home. In: Cooke M & Dennis AJ
    ed. Mechanisms, methods and metabolism: Polynuclear aromatic
    hydrocarbons. Columbus, Ohio, Battelle Press, pp 725-737.

    Knutzen J & Sortland B (1982) Polycyclic aromatic hydrocarbons (PAH)
    in some algae invertebrates from moderately polluted parts of the
    coast of Norway. Water Res, 16: 421-428.

    Kochevar IE, Armstrong RB, Einbinder J, Walther RR, & Harber LC (1982)
    Coal tar phototoxicity: Active compounds and action spectra. Photochem
    Photobiol, 36: 65-69.

    Konar NR, Roy HK, & De MN (1939) Naphthalene poisoning. Indian Med
    Gaz, 74: 723-725.

    Kongerud J, Boe J, Soyseth V, Naalsund A, & Magnus P (1994) Aluminium
    potroom asthma: The Norwegian experience. Eur Respir J, 7: 165-172.

    König W, Hembrock-Heger A, & Wilkens (1991) [Persistent organic
    chemicals in soil - routes of entry and occurrence]. Umweltwissensch
    Schadstoff-Forsch, 3: 33-36 (in German).

    Kootstra A & Slaga TJ (1979) Differential accessibility of (±)
     trans-7b,8a-dihydroxy-9a,10a-epoxy-7,8,9,10-tetrahydrobenzo [a]
    pyrene to histone proteins. FEBS Lett, 108: 321-325.

    Kootstra A & Slaga TJ (1980) Binding of isomers of benzo [a]pyrene
    diol-epoxide to chromatin. Biochem Biophys Res Commun, 93: 954-959.

    Kootstra A, Slaga TJ, & Olins DE (1979) Interaction of
    benzo [a]pyrene diol-epoxide with nuclei and isolated chromatin.
    Chem-Biol Interactions, 28: 225-236.

    Kördel W, Schoene K, Bruckert J, Pfeiffer U, Schreiber G, Rittmann D,
    Hochrainer D, Otto F, Spiegelberg T, Fingerhut R, Kuhnen-Clausen D, &
    König J (1981) [Test for chemicals: Study on the feasibility of the EC
    regulatory test methods.] Hanover, Fraunhofer Institute for Toxicology
    and Aerosol Research, Volume 1, p 553 (in German).

    Koreeda M, Moore PD, Wislocki PG, Levin W, Conney AH, Yagi H, & Jerina
    DM (1978) Binding of benzo[a]pyrene 7,8-diol 9,10-epoxides to DNA,
    RNA, and protein of mouse skin occurs with high stereoselectivity.
    Science, 199: 778-780.

    Korhonen K & Mulari K (1983) Airborne pollutants in ties workers.
    Lappeenrannan, Finnish Institute of Occupational Health, 23 pp.

    Korn S, Moles D, & Rice SD (1979) Effects of temperature on the median
    tolerance limit of pink salmon and shrimp exposed to toluene,
    naphthalene, and Cook Inlet crude oil. Bull Environ Contam Toxicol,
    21: 521-525.

    Kotin P, Falk HL, & Busser R (1959) Distribution, retention, and
    elimination of C14-3,4-benzpyrene after administration to mice and
    rats. J Natl Cancer Inst, 23: 541-555.

    Kouri RE, Connolly GM, Nebert DW, & Lubet RA (1983) Association
    between susceptibility to dibenzanthracene induced fibrosarcoma
    formation and the Ah locus. Int J Cancer, 32: 765-768.

    Krahn DF & Heidelberger C (1977) Liver homogenate-mediated mutagenesis
    in Chinese hamster V79 cells by polycyclic aromatic hydrocarbons and
    aflatoxins. Mutat Res, 46: 27-44.

    Krämer M, Bimboes D, & Greim H (1974)  Salmonella typhimurium and  E.
    coli to detect chemical mutagens. Arch Pharmacol, 284: R46.

    Krewski D, Thorslund T, & Withey J (1989) Carcinogenic risk assessment
    of complex mixtures. Toxicol Ind Health, 5: 851-867.

    Kriek E, Van Schooten FJ, Hillebrand MJX, Van Leeuwen FE, Den Engelse
    L, De Looff AJA, & Dijkmans APG (1993) DNA adducts as a measure of
    lung cancer risk in humans exposed to polycyclic aromatic
    hydrocarbons. Environ Health Perspectives, 99: 71-75.

    Kröber B & Häckl M (1989) [Report on orientation measurements on
    dangerous, organic compounds in wastewater pipes, sewage works and
    waters in the Federal State of Hessen (1985-1988)] .Wiesbaden, Hessen
    State Office for the Environment, pp 225-288 (Report 96) (in German).

    Krokje Å (1989) Mutagenicity of expectorate from workers in a coke
    plant. Mutat Res, 223: 213-219.

    Krokje Å, Tiltnes A, Mylius E, & Gullvå B (1988) Testing for mutagens
    in an aluminium plant. The results of  Salmonella 
     typhimurium tests on urine from exposed workers. Mutat Res, 204:
    163-172.

    Krolewski B, Nagasawa H, & Little JB (1986) Effect of aliphatic amides
    on oncogenic transformation, sister chromatid exchanges, and mutations
    induced by cyclopenta [cd]-pyrene. Carcinogenesis, 7: 1647-1650.

    Kronberger H & Weiss J (1944) Formation and structure of some organic
    molecular compounds. Part III. The dielectric polarisation of some
    solid crystalline molecular compounds. J Chem Soc, 146: 464-469.

    Kruber O (1937) [Some new constituents of coal tar pitch.] Chem Ber,
    70: 1556-1564 (in German).

    Kruber O & Grigoleit G (1954) [New compounds isolated from coal tar
    pitch.] Chem Ber, 87: 1895-1905 (in German).

    Kruber O & Marx A (1938) [The anthracene oil of coal tar.] Chem Ber,
    71: 2478-2484 (in German).

    Kubasiewicz M, Starzynski Z, & Szymczak W (1991) Case-referent study
    on skin cancer and its relation to occupational exposure to polycyclic
    aromatic hydrocarbons. II. Study results. Pol J Occup Med Environ
    Health, 4: 141-147.

    Kunstler K (1983) Failure to induce tumors by intratracheal
    instillation of automobile exhaust condensate and fractions thereof in
    Syrian golden hamsters. Cancer Lett, 18: 105-108.

    Kuroki T & Heidelberger C (1972) Determination of the h-protein in
    transformable and transformed cells in culture. Biochemistry, 11:
    2116-2124.

    Kuroki T, Nemoto N, & Kitano Y (1980) Metabolism of benzo [a]pyrene
    in human epidermal keratinocytes in culture. Carcinogenesis, 1: 559-
    565.

    Kushwaha SC, Clarkson SG & Mehkeri KA (1985) Polycyclic aromatic
    hydrocarbons in barbecue briquets. J Food Saf, 7: 177-201.

    Kuwabara K, Nakamura A, & Kashimoto T (1980) Effect of petroleum oil,
    pesticides, PCBs and other environmental contaminants on the
    hatchability of  Artemia salina dry eggs. Environ Contam Toxicol, 25:
    69-74.

    Kveseth K, Sortland B, & Bokn T (1982) Polycyclic aromatic
    hydrocarbons in sewage, mussels and tap water. Chemosphere, 11: 623-
    639.

    La Budde JA & Heidelberger C (1958) The synthesis of the mono- and
    dihydroxy derivatives of 1,2,5,6-dibenzanthracene excreted by the
    rabbit and of other hydroxylated dibenzanthracene derivatives. J Am
    Chem Soc, 80: 1225-1236.

    Lacassagne A, Buu-Hoi NP, & Zajdela F (1958) [Relationship between
    molecular structure and carcinogenic activity in three series of
    hexacyclic aromatic hydrocarbons.] C R Acad Sci Paris, 245: 1477-1481
    (in French).

    Lacassagne A, Buu-Hoi NP, Zajdela F, Lavit-Lamy D, & Chalvet O (1963a)
    [Carcinogenic activity of fluoranthene-based polycyclic aromatic
    hydrocarbons.] Acta Unio Int Contra Cancrum, 19: 490-496 (in French).

    Lacassagne A, Buu-Hoi NP, Zajdela F, & Lavit-Lamy D (1963b) [High
    carcinogenic activity of 1,2:3,4-dibenzopyrene and
    1,2:4,5-dibenzopyrene.] C R Acad Sci Paris, 256: 2728-2731 (in
    French).

    Lacassagne A, Buu-Hoi NP, Zajdela F, & Vingiello FA (1968a) The true
    dibenzo [a,l]pyrene, a new, potent carcinogen. Naturwissenschaften,
    55: 43.

    Lacassagne A, Buu-Hoi NP, & Zajdela F (1968b) [Absence of sarcomagenic
    property in dibenz [a,c]anthracene; clear activity of its 10-methyl
    derivative.] Eur J Cancer, 4: 123-127 (in French).

    Ladics GS & White KL (1996) Immunotoxicity of polyaromatic
    hydrocarbons. In: Smialowicz RJ & Holsapple MP ed. Experimental
    immunotoxicology. Boca Raton, Florida, CRC Press, pp 331-349.

    Ladics GS, Kawabata TT, & White KL Jr (1991) Suppression of the
     in vitro humoral immune response of mouse splenocytes by
    7,12-dimethylbenz(a)anthracene metabolites and inhibition of
    immunosuppression by a-naphthoflavone. Toxicol Appl Pharmacol, 110:
    31-44.

    Ladics GS, Kawabata TT, Munson AE, & White KL Jr (1992a) Generation of
    7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene by murine
    splenic macrophages. Toxicol Appl Pharmacol, 115: 72-79.

    Ladics GS, Kawabata TT, Munson AE, & White KL Jr (1992b) Metabolism of
    benzo [a]pyrene by murine splenic cell types. Toxicol Appl Pharmacol,
    116: 248-257.

    Lafontaine M, Attenont H, Hubert G, Taiclet A, & Truy S (1990a)
    [Emission of polycyclic aromatic hydrocarbons in foundries.] Cah Notes
    Doc, 141: 799-807 (in French).

    Lafontaine M, Attenont H, & Truy S (1990b) [Exposure to polycyclic
    aromatic hydrocarbons in the electrode-producing industry]. Cah Notes
    Doc, 132: 453-455.

    Lahmann E, Seifert B, Zhao L, & Bake D (1984) [Immission of polycyclic
    aromatic hydrocarbons in Berlin (West).] Staub-Reinhalt Luft, 44: 149-
    157 (in German).

    Lake RS, Kropko ML, Pezzutti MR, Shoemaker RH, & Igel HJ (1978)
    Chemical induction of unscheduled DNA synthesis in human skin
    epithelial cell cultures. Water Res, 38: 2091-2098.

    Lampe V, Puettmann W, & Kasig W (1991) Analysis of the PAH load of
    river sediments from the Aachen area. Contribution to the
    determination of emission/immission pathways. Wiss Umwelt, 1: 51-62.

    Landahl JT, McCain BB, Myers MS, Rhodes LD, & Brown DW (1990)
    Consistent associations between hepatic lesions in English sole
     (Parophrys vetulus) and polycyclic aromatic hydrocarbons in bottom
    sediment. Environ Health Perspectives, 89: 195-203.

    Landrum PF (1982) Uptake, depuration and biotransformation of
    anthracene by the scud  Pontoporeia hoyi. Chemosphere, 11: 1049-1057.

    Landrum PF (1988) Toxicokinetics of organic xenobiotics in the
    amphipod  Pontoporeia hoyi: Role of physiological and environmental
    variables. Aquat Toxicol, 12: 245-271.

    Landrum PF & Poore R (1988) Toxicokinetics of selected xenobiotics in
     Heagenia limbata. J Great Lakes Res, 14: 427-437.

    Landrum PF & Scavia D (1983) Influence of sediment on anthracene
    uptake, depuration, and biotransformation by the amphipod
     Hyalella azteca. Can J Fish Aquat Sci, 40: 298-305.

    Landrum PF, Bartell SM, Giesy JP, Leversee GJ, Bowling JW, Haddock J,
    LaGory K, Gerould S, & Bruno M (1984a) Fate of anthracene in an
    artificial stream: A case study. Ecotoxicol Environ Saf, 8: 183-201.

    Landrum PF, Nihart SR, Edie BJ, & Gardner WS (1984b) Reverse-phase
    separation method for determining pollutant binding to Aldrich humic
    acid and dissolved organic carbon of natural waters. Environ Sci
    Technol, 18: 187-192.

    Landrum PF, Eadie BJ, & Faust WR (1991) Toxicokinetics and toxicity of
    a mixture of sediment-associated polycyclic aromatic hydrocarbons to
    the amphipod  Diporeia sp. Environ Toxicol Chem, 10: 35-46.

    Lane DA (1989) The fate of polycyclic aromatic compounds in the
    atmosphere and during sampling. In: Vo-Dinh T ed. Chemical analysis of
    polycyclic aromatic compounds. New York, John Wiley & Sons, pp 31-58.

    Lane DA & Katz M (1977) The photomodification of benzo [a]pyrene,
    benzo [b]-fluoranthene, and benzo [k]fluoranthene under simulated
    atmospheric conditions. Adv Environ Sci Technol, 8: 137-154.

    Langenfeld JL, Hawthorne SB, Miller DJ, & Pawliszyn J (1993) Effects
    of temperature and pressure on supercritical fluid extraction
    efficiencies of polycyclic aromatic hydrocarbons and polychlorinated
    biphenyls. Anal Chem, 65: 338-344.

    Lao RC, Thomas RS, Oja H, & Dubois L (1973) Application of a gas
    chromatograph-mass spectrometer-data processor combination to the
    analysis of the polycyclic aromatic hydrocarbon content of airborne
    pollutants. Anal Chem, 45: 908-915.

    Larssen S (1985) Automotive emission factors: An indirect measurement
    method applied to polycyclic aromatic hydrocarbon and lead emissions.
    In: Proceedings of the Air Pollution Control Association, 77th Annual
    Meeting, San Francisco, 24-29 June 1984. Houston, Texas, Air Pollution
    Control Association, pp 1-18.

    Larsson BK (1982) Polycyclic aromatic hydrocarbons in smoked fish. Z
    Lebensm Untersuch Forsch, 174: 101-107.

    Larsson B (1986) Polycyclic aromatic hydrocarbons in Swedish foods:
    Aspects on analysis, occurrence and intake. Uppsala, Swedish
    University of Agricultural Sciences, 60 pp (Doctoral Thesis).

    Larsson B & Sahlberg G (1982) Polycyclic aromatic hydrocarbons in
    lettuce. Influence of a highway and an aluminium smelter. In: Cooke M
    & Fisher AJ ed. Polynuclear aromatic hydrocarbons: Physical and
    biological chemistry. Columbus, Ohio, Battelle Press, pp 417-426.

    Larsson BK, Sahlberg GP, Eriksson AT, & Busk LA (1983) Polycyclic
    aromatic hydrocarbons in grilled food. J Agric Food Chem, 31: 867-873.

    Larsson BK, Eriksson AT, & Cervenka M (1987) Polycyclic aromatic
    hydrocarbons in crude and deodorized vegetable oils. J Am Oil Chem
    Soc, 64: 365-370.

    Laskin S, Kuschner M, & Drew RT (1970) Studies in pulmonary
    carcinogenesis. In: Hanna MG, Nettesheim P, & Gilbert J ed. Inhalation
    carcinogenesis. Oak Ridge, Tennessee, US Atomic Energy Commission,
    Division of Technical Information, pp 321-351 (AEC Symposium Series
    No. 18).

    Lasnitzki A & Woodhouse DL (1944) The effect of
    1:2:5:6-dibenzanthracene on the lymph nodes of the rat. J Anat, 78:
    121-128.

    LaVoie EJ, Bedenko V, Hirota N, Hecht SS, & Hoffmann D (1979) A
    comparison of the mutagenicity, tumor-initiating activity and complete
    carcinogenicity of polynuclear aromatic hydrocarbons. In: Jones PW &
    Leber P ed. Polynuclear aromatic hydrocarbons. Ann Arbor, Michigan,
    Ann Arbor Science Publishers, pp 705-721.

    LaVoie EJ, Tulley L, Bedenko V, & Hoffmann D (1980) Mutagenicity,
    tumor initiating activity, and metabolism of tricyclic polynuclear
    aromatic hydrocarbons. In: Bjorseth A & Dennis AJ ed. Polynuclear
    aromatic hydrocarbons: Chemistry and biological effects. Columbus,
    Ohio, Battelle Press, pp 1041-1057.

    LaVoie EJ, Tulley L, Bedenko V, & Hoffmann D (1981a) Mutagenicity of
    methylated fluorenes and benzofluorenes. Mutat Res, 91: 167-176.

    LaVoie EJ, Tulley-Freiler L, Bedenko V, & Hoffmann D (1981c)
    Mutagenicity, tumor-initiating activity and metabolism of
    methylphenanthrenes. Cancer Res, 41: 3441-3447.

    LaVoie EJ, Tulley-Freiler L, Bedenko V, Girach Z, & Hoffmann D (1981c)
    Comparative studies on the tumor initiating activity and metabolism of
    methylfluorenes and methylbenzofluorenes. In: Cooke M & Dennis AJ ed.
    Chemical analysis and biologicalfate: Polynuclear aromatic
    hydrocarbons. Columbus, Ohio, Battelle Press, pp 417-427.

    La Voie EJ, Hecht SS, Bedenko V, & Hoffmann D (1982a) Identification
    of the mutagenic metabolites of fluoranthene, 2-methylfluoranthene,
    and 3-methylfluoranthene. Carcinogenesis, 3: 841-846.

    La Voie EJ, Amin S, Hecht SS, Furuya K, & Hoffmann D (1982b) Tumour
    initiating activity of hydrodiols of benzo [b]fluoranthene,
    benzo [j]fluoranthene, and benzo [k]-fluoranthene. Carcinogenesis,
    3: 49-53.

    LaVoie EJ, Coleman DT, Tonne RL, & Hoffmann D (1983a) Mutagenicity,
    tumor initiating activity and metabolism of methylated anthracenes.
    In: Cooke M & Dennis AJ ed. Polynuclear aromatic hydrocarbons.
    Columbus, Ohio, Battelle Press, pp 785-798.

    LaVoie EJ, Tulley-Freiler L, Bedenko V, & Hoffmann D (1983b)
    Mutagenicity of substituted phenanthrenes in  Salmonella 
     typhimurium. Mutat Res, 116: 91-102.

    LaVoie EJ, Coleman DT, Rice JE, Geddie NG & Hoffmann D (1985)
    Tumor-initiating activity, mutagenicity, and metabolism of methylated
    anthracenes. Carcinogenesis, 6: 1483-1488.

    LaVoie EJ, Braley J, Rice JE, & Rivenson A (1987) Tumorigenic activity
    of non-alternant polynuclear aromatic hydrocarbons in newborn mice.
    Cancer Lett, 34: 15-20.

    LaVoie EJ, Cai ZW, Meschter CL, & Weyand EH (1994) Tumorigenic
    activity of fluoranthene, 2-methylfluoranthene in newborn CD-1 mice.
    Carcinogenesis, 15: 2131-2135.

    Lawrence JF & Weber DF (1984) Determination of polycyclic aromatic
    hydrocarbons in Canadian samples of processed vegetable and dairy
    products by liquid chromatography with fluorescence detection. J Agric
    Food Chem, 32: 794-797.

    Leach JM, Otson R, & Armstrong V (1987) Airborne contaminants in two
    small Canadian coal liquefaction pilot plants. Am Ind Hyg Assoc J, 48:
    693-697.

    Leadon SA, Stampfer MR, & Bartley J (1988) Production of oxidative DNA
    damage during the metabolic activation of benzo [a]pyrene in human
    mammary epithelial cells correlates with cell killing. Proc Natl Acad
    Sci USA, 85: 4365-4368.

    LeBlanc GA (1980) Acute toxicity of priority pollutants to water flea
     (Daphnia magna). Environ Contam Toxicol, 24: 684-691.

    Lecoq S, Perin F, Plessis MJ, Strapelias H, & Duquesne M (1989)
    Comparison of the  in vitro metabolisms and mutagenicities of
    dibenz [a,c]anthracene, dibenz [a,h]anthrancene, and
    dibenz [a,j]anthrancene: Influence of norharman. Carcinogenesis, 10:
    461-469.

    Lecoq S, Ni She M, Hewer A, Grover PL, Platt KL, Oesch F, & Phillips
    DH (1991) The metabolic activation of dibenz [a,h]anthracene in mouse
    skin examined by 32P-postlabelling: Minor contribution of the
    3,4-diol 1,2-oxides to DNA binding. Carcinogenesis, 12: 1079-1083.

    Lecoq S, Pfau W, Grover PL, & Phillips DH (1992) HPLC separation of
    32P-postlabelled DNA adducts formed from dibenz [a,h]anthracene in
    skin. Chem-Biol Interactions, 85: 173-185.

    Lee RF (1977) Fate of petroleum components in estuarine water of
    southeastern United States. In: Proceedings of the oil spill
    conference: Prevention, behavior, control, cleanup, New Orleans, 8-10
    March 1997. Washington DC, American Petroleum Institute, pp 611-616
    (API Publication No. 4284).

    Lee RF & Andersen JW (1977) Fate and effect of naphthalenes:
    Controlled ecosystem pollution experiment. Bull Mar Sci, 27: 127-134.

    Lee H & Lin JY (1988) Antimutagenic activity of extracts from
    anticancer drugs in Chinese medicine. Mutat Res, 204: 229-234.

    Lee WY & Nicol JAC (1978) The effect of naphthalene on survival and
    activity of the amphipod  Parhyale hawaiensis. Bull Environ Contam
    Toxicol, 20: 233-240.

    Lee RF & Ryan C (1976) Biodegradation of petroleum hydrocarbons by
    marine microbes. In: Sharpley JM & Kaplan AM ed. Biodeterioration of
    materials. Milton Keynes, Essex, Applied Science Publishers, pp 119-
    125.

    Lee FSC & Schuetzle D (1983) Sampling, extraction, and analysis of
    polycyclic aromatic hydrocarbons from internal combustion engines. In:
    Bjorseth A ed. Handbook of polycyclic aromatic hydrocarbons. New York,
    Marcel Dekker, pp 27-94.

    Lee RF, Sauerheber R, & Dobbs G (1972) Uptake, metabolism and
    discharge of polycyclic aomatic hydrocarbons by marine fish. Mar Biol,
    17: 201-208.

    Lee ML, Novotny M, & Bartle KD (1976a) Gas chromatography/mass
    spectrometric and nuclear magnetic resonance determination of
    polynuclear aromatic hydrocarbons in airborne particulates. Anal Chem,
    48: 1566-1572.

    Lee ML, Novotny M, & Bartle KD (1976b) Gas chromatography/mass
    spectrometric and nuclear magnetic resonance spectrometric studies of
    carcinogenic polynuclear aromatic hydrocarbons in tobacco and
    marijuana smokes condensates. Anal Chem, 48: 405-416.

    Lee FS-C, Harvey TM, Prater TJ, Paputa MC, & Schuetzle D (1980)
    Chemical analysis of diesel particulate matter and an evaluation of
    artifact formation. In: Sampling and analysis of toxic organics in the
    atmosphere. Philadelphia, Pennsylvania, American Society for Testing
    and Materials, pp 92-110 (ASTM STP 721).

    Lee ML, Novotny MV, & Bartle KD (1981) Analytical chemistry of
    polycyclic aromatic compounds. New York, Academic Press, pp 35-40, 78-
    122, 156-289.

    Lee MD, Wilson JT, & Ward CH (1984) Microbial degradation of selected
    aromatics in a hazardous waste site. Dev Ind Microbiol, 25: 557-565.

    Lee PM, Baoyun Y, Herbert R, Hamminki K, Perera FP, & Santella RM
    (1991) Immunologic measurement of polycyclic aromatic
    hydrocarbon-albumin adducts in foundry workers and roofers. Scand J
    Work Environ Health, 17: 190-194.

    de Leeuw JW, de Leer EWB, Sinninghe Damsté JS, & Schuyl PJW (1986)
    Screening of anthropogenic compounds in polluted sediments and soils
    by flash evaporation/pyrolysis gas chromatography-mass spectrometry.
    Anal Chem, 58: 1852-1857.

    Legraverend C, Harrison DE, Ruscetti FW, & Nebert DW (1983) Bone
    marrow toxicity induced by oral benzo [a]pyrene: Protection resides
    at the level of the intestine and liver. Toxicol Appl Pharmacol, 70:
    390-401.

    Legraverend C, Guenthner TM, & Nebert DW (1984) Importance of the
    route of administration for genetic differences in
    benzo [a]pyrene-induced in utero toxicity and teratogenicity.
    Teratology, 29: 35-47.

    Lehmann EJ, Auffarth J, Häger J, Rentel KH, & Altenburg H (1986)
    [Concentration profiles of selected PAH in coal-tar derived products.]
    Staub-Reinhalt Luft, 46: 128-131 (in German).

    Lei ZM (1993) The relationship between concentration of B(a)P in
    blood, urine, and immune function of coking workers. Chung Hua Yu Fang
    I. Hsueh Tsa Chih, 27: 212-214 (in Chinese).

    Leinster P & Evans MJ (1986) Factors affecting the sampling of
    airborne polycyclic aromatic hydrocarbons. A review. Ann Occup Hyg,
    30: 481-495.

    Lenin K (1994) Contamination with polycyclic aromatic hydrocarbons
    through sewage irrigation. Doctoral thesis submitted to the Jawaharlal
    Nehru University, Delhi, India, 22 pp.

    Leo A, Hansch C, & Elkins D (1971) Partition coefficients and their
    uses. Chem Rev, 71: 525-616.

    Leoni V, Puccetti G, & Grella A (1975) Preliminary results on the use
    of Tenax(R) for the extraction of pesticides and polynuclear
    aromatic hydrocarbons from surface and drinking waters for analytical
    purposes. J Chromatogr, 106: 119-124.

    Lepperhoff G (1981) [The PAH emissions of spark ignition engines. Part
    I.] Wiss Umwelt, 2: 72-87 (in German).

    Lesage J, Perrault G, & Durand P (1987) Evaluation of worker exposure
    to polycyclic aromatic hydrocarbons. Am Ind Hyg Assoc J, 48: 753-759.

    Leslie TJ, Dickson KL, Jordan JA, & Hopkins DW (1987) Effects of
    suspended solids on the water column biotransformation of anthracene.
    Arch Environ Contam Toxicol, 16: 637-642.

    Leversee GJ, Landrum PJ, Bartell S, Gerould S, Bruno M, Spacie A,
    Bowling J, Haddock J, & Fannin T (1981) Disposition of
    benzo [a]pyrene in aquatic system components:  Periphyton, 
     Chironomids, Daphnia, fish. In: Cooke M & Dennis AJ ed. Polynuclear
    aromatic hydrocarbons: Chemical analysis and biological fate.
    Columbus, Ohio, Battelle Press, pp 357-367.

    Levin W, Wood AW, Chang RL, Yagi H, Mah HD, Jerina DM, & Conney AH
    (1978) Evidence for bay region activation of chrysene 1,2-dihydrodiol
    to an ultimate carcinogen. Cancer Res, 38: 1831-1834.

    Levin W, Wood AW, Chang RL, Ittah Y, Croisy-Delcey M, Yagi H, Jerina
    DM, & Conney AH (1980) Exceptionally high tumor-initiating activity of
    benzo(c)phenanthrene bay-region diol-epoxides on mouse skin. Cancer
    Res, 40: 3910-3914.

    Levin W, Wood A, Chang R, Ryan D, Thomas P, Yagi H, Thakker D, Vyas K,
    Boyd C, Chu S-Y, Conney A, & Jerina D (1982) Oxidative metabolism of
    polycyclic aromatic hydrocarbons to ultimate carcinogens. Drug Metab
    Rev, 13: 555-580.

    Levin W, Chang RL, Wood AW, Yagi H, Thakker DR, Jerina DM, & Conney AH
    (1984) High stereoselectivity among the optical isomers of the
    diastereomeric bay-region diolepoxides of benz(a)anthracene in the
    expression of tumorigenic activity in murine tumor models. Cancer Res,
    44: 929-933.

    Levin W, Chang RL, Wood AW, Thakker DR, Yagi H, Jerina DM, & Conney AH
    (1986) Tumorigenicity of optical isomers of the diastereomeric
    bay-region 3,4-diol-1,2-epoxides of benzo [c]phenanthrene in murine
    tumor models. Cancer Res, 46: 2257-2261.

    Levin JO, Rhén M, & Sikström E (1995) Occupational PAH exposure:
    Urinary 1-hydroxypyrene levels of coke oven workers, aluminium smelter
    pot-room workers, roadpavers, and occupationally non-exposed persons
    in Sweden. Sci Total Environ, 193: 169-177.

    Levsen K (1988) The analysis of diesel particulate. Fresenius' Z Anal
    Chem, 331: 467-478.

    Levsen K, Behnert S, Priess B, & Winkeler HD (1991) The contamination
    of precipitation in Hannover by hydrocarbons. Vom Wasser, 76: 109-126.

    Lewis WM (1975) Polynuclear aromatic hydrocarbons in water. Water
    Treat Exam, 23: 243-277.

    Lewis RJ Sr (1992) Sax's dangerous properties of industrial materials,
    8th ed. New York, Van Nostrand Reinhold Co., 1245 pp.

    Lewtas J (1985a) Development of a comparative potency method for
    cancer risk assessment of complex mixtures using short-term
     in vivo and  in vitro bioassays. Toxicol Ind Health, 4: 193-203.

    Lewtas J (1985b) Combustion emissions: Characterization and comparison
    of their mutagenic and carcinogenic activity. In: Stich HF ed.
    Carcinogens and mutagens in the environment, Volume V: The workplace:
    Source of carcinogens. Boca Raton, Florida, CRC Press, pp 59-74.

    Lewtas J (1993) Complex mixtures of air pollutants: Characterizing the
    cancer risk of polycyclic organic matter. Environ Health Perspectives,
    100: 211-218.

    Lewtas J, Mumford J, Everson RB, Hulka B, Wilcosky T, Kozumbo W,
    Thompson C, George M, Dobiàs L, Sràm R, Li X, & Gallagher J (1993)
    Comparison of DNA adducts from exposure to complex mixtures in various
    human tissues and experimental systems. Environ Health Perspectives,
    99: 89-97.

    Li Y, Xu H, Song Y, Yang X, & Li Z (1991) [A study on the relationship
    between urinary BaP and SCE frequency in rats.] Zhongguo Huanjing
    Kexue, 11: 361-364 (in Chinese with English abstract).

    Liao W, Smith WD, Chiang TC, & Williams LR (1988) Rapid, low-cost
    cleanup procedure for determination of semivolatile organic compounds
    in human and bovine adipose tissues. J Assoc Off Anal Chem, 71: 742-
    747.

    Lide DR ed. (1991) CRC handbook of chemistry and physics, 72nd ed.
    Boca Raton, Florida, CRC Press, pp 22-35.

    Liem AKD, Baumann RA, de Jong APJM, van der Velde EG, & van Zoonen P
    (1992) Analysis of organic micropollutants in the lipid fraction of
    foodstuffs. J Chromatogr, 624: 317-339.

    Lies KH, Hartung A, Postulka A, Gring H, & Schulze J (1986)
    Composition of diesel exhaust with particular reference to particle
    bound organics including formation of artifacts. Dev Toxicol Environ
    Sci, 13: 65-82.

    Ligocki MP & Pankow JF (1989) Measurements of the gas/particle
    distributions of atmospheric organic compounds. Environ Sci Technol,
    23: 75-83.

    Ligocki MP, Leuenberger C, & Pankow JF (1985) Trace organic compounds
    in rain. II. Gas scavening of neutral organic compounds. Atmos
    Environ, 19: 1609-1617.

    Lijinsky W & Garcia H (1972) Skin carcinogenesis tests of hydrogenated
    derivatives of anthanthrene and other polynuclear hydrocarbons. Z
    Krebsforsch, 77: 226-230.

    Lijinsky W & Ross AE (1967) Production of carcinogenic polynuclear
    hydrocarbons in the cooking of food. Food Cosmet Toxicol, 5: 343-347.

    Lijinsky W & Saffiotti U (1965) Relationships between structure and
    skin tumorigenic activity among hydrogenated derivates of several
    polycyclic aromatic hydrocarbons. Ann It Dermatol Clin Sper, 19: 34-
    44.

    Lijinsky W & Shubik P (1964) Benzo(a)pyrene and other polynuclear
    hydrocarbons in charcoal-broiled meat. Science, 145: 53-55.

    Lijinsky W & Shubik P (1965) Polynuclear hydrocarbon carcinogens in
    cooked meat and smoked food. Ind Med Surg, 34: 152-154.

    Lijinsky WH, Garcia B, & Terrracini B (1965) Tumorigenic activity of
    hydrogenated derivatives of dibenz [a,h]anthracene. J Natl Cancer
    Inst, 34:1-6.

    Likhachev AJ, Beniashvili DS, Bykov VJ, Dikun PP, Tyndyk ML,
    Savochkina IV, Yermilov VB, & Zabezhinski MA (1992) Biomarkers for
    individual susceptibility to carcinogenic agents: Excretion and
    carcinogenic risk of benzo [a]pyrene metabolites. Environ Health
    Perspectives, 98: 211-214.

    Linder G & Bergman H (1984) Periodic depuration of anthracene
    metabolites by rainbow trout  Salmo gairdneri. Trans Am Fish Soc,
    113: 513-520.

    Linder G, Bergman H, & Meyer J (1985) Anthracene bioconcentration in
    rainbow-trout during single-compound and complex-mixture exposures.
    Environ Toxicol Chem, 4: 549-558.

    Lindquist B & Warshawsky D (1985) Identification of the
    11,12-dihydro-11,12-dihydroxybenzo [a]pyrene as a major metabolite
    produced by the green alga,  Selenastrum capriconutum. Biochem
    Biophys Res Commun, 130: 7.

    Lindskog A, Brorström-Lundén E, Alfheim I, & Hagen I (1987) Chemical
    transformation of PAH on airborne particles by exposure to NO2 during
    sampling: A comparison between two filter media. Sci Total Environ,
    61: 51-57.

    Lindstedt G & Sollenberg J (1982) Polycyclic aromatic hydrocarbons in
    the occupational environment - with special reference to
    benzo [a]pyrene measurements in Swedish industry. Scand J Work
    Environ Health, 3: 1-19.

    Lindström-Seppä P, Hänninen O, Tuominen J, & Pyysalo H (1989)
    Polycyclic aromatic hydrocarbons in perch  (Perca fluviatilis) 
    following an oil-spill in Vaasa Archipelago, Finland. Toxicol Environ
    Chem, 19: 83-86.

    Lintas C, De Matthaeis MC, & Merli F (1979) Determination of
    benzo(a)pyrene in smoked, cooked and toasted food products. Food
    Cosmet Toxicol, 17: 325-328.

    Liotti FS, Pelliccia C, & Pezzetti F (1988) Different response of
    chicken embryo fibroblasts and hepatocytes to the interference of
    certain antioxidants on the binding of [G3H]benzo [a]pyrene to DNA.
    Cancer Lett, 41: 235-242.

    Lioy PL, Waldman JM, Greenberg A, Harkov R, & Pietarinen C (1988) The
    total human environmental exposure study (THEES) to benzo(a)pyrene:
    Comparison of the inhalation and food pathways. Arch Environ Health,
    43: 304-312.

    Little JB & Vetrovs H (1988) Studies of ionizing radiation as a
    promoter of neoplastic transformation  in vitro. Int J Radiat Biol,
    53: 661-666.

    Liu D, Maguire RJ, Pacepavicius GJ, & Nagy E (1992) Microbial
    degradation of polycyclic aromatic hydrocarbons and polycyclic
    aromatic nitrogen heterocyclics. Environ Toxicol Water Qual, 7: 355-
    372.

    Lo MT & Sandi E (1978) Polycyclic aromatic hydrocarbons (polynuclear)
    in foods. Res Rev, 69: 35-85.

    Loening KL & Merritt JE (1990) Some aids for naming polycyclic
    aromatic hydrocarbons and their heterocyclic analogs. In: Loening K,
    Merritt J, Later D, & Wright W ed. Polynuclear aromatic hydrocarbons:
    Nomenclature guide. Columbus, Ohio, Battelle Press, pp 1-25.

    Löfroth G, Toftgard R, Nilsson L, Agurell E, & Gustafsson JA (1984)
    Short-term bioassays of nitro derivatives of benzo [a]pyrene and
    perylene. Carcinogenesis, 5: 925-930.

    Lovell WW & Sanders DJ (1992) Phototoxicity testing in guinea-pigs.
    Food Chem Toxicol, 30: 155-160.

    Lowenthal DH, Zielinska B, Chow JC, Watson JG, Gautman M, Ferguson DH,
    Neuroth GR, & Stevens KD (1994) Characterizitation of heavy-duty
    diesel vehicle emissions. Atmos Environ, 28: 731-743.

    Lu PY, Metcalf RL, Plummer N, & Mandel D (1977) The environmental fate
    of three carcinogens: Benzo [a]pyrene, benzidine, and vinyl chloride
    evaluated in laboratory model ecosystems. Arch Environ Contam Toxicol,
    6: 129-142.

    Lubet RA, Kiss E, Gallagher MM, Dively C, Konri R, & Schechtman LM
    (1983a) Induction of neoplastic transformation and DNA single-strand
    breaks in C3H/10T1/2 clone 8 cells by polycyclic hydrocarbons and
    alkylating agents. J Natl Cancer Inst, 71: 991-997.

    Lubet RA, Connelly GM, & Nebert DW (1983b)
    Dibenz [a,h]anthracene-induced subcutaneous tumors in mice. Strain
    sensitivity and the role of carcinogen metabolism. Carcinogenesis, 4:
    513-517.

    Lubet RA, Brunda MJ, & Lemaira B (1984a) Polycyclic hydrocarbon
    induced immunotoxicity in mice: Role of the Ah locus. In: Cooke M &
    Dennis AJ ed. Polycyclic aromatic hydrocarbons: Mechanisms, methods
    and metabolism. Columbus, Ohio, Battelle Press, pp 843-858.

    Lubet RA, Brunda MJ, Taramelli D, Dansie D, Nebert DW, & Kouri RE
    (1984b) Induction of immunotoxicity by polycyclic hydrocarbons: Role
    of the Ah locus. Arch Toxicol, 56: 18-24.

    Lubet RA, Kouri RE, Curren RA, Putman DL, & Schechtman LM (1990)
    Induction of mutagenesis and transformation in BALB/c-3T3 clone A31-1
    cells by diverse chemical carcinogens. Environ Mol Mutag, 16: 13-20.

    Luijten JA & Piet GJ (1983) Identity and sources of organic chemicals
    in groundwater. In: Proceedings of the 1st Atlantic Workshop,
    Nashville, Tennessee. Denver, Colorado, American Water Works
    Association, pp 7-18.

    van Luin AB & van Starkenburg W (1984) Hazardous substances in waste
    water. Water Sci Technol, 17: 843-853.

    Lunde G (1976) Long-range aerial transmission of organic
    micropollutants. Ambio, 5: 207-208.

    Lunde G & Bjorseth A (1977) Polycyclic aromatic hydrocarbons in
    long-range transported aerosols. Nature, 268: 518-519.

    Luther M, Moriske HJ, & Rüden H (1990) [Indoor air levels of
    polycyclic aromatic hydrocarbons from the use of asphalt floor tiles.]
    Forum Städte-Hyg, 41: 95-103 (in German).

    Lutz WK & Schlatter J (1992) Chemical carcinogens and overnutrition in
    diet-related cancer. Carcinogenesis, 13: 2211-2216.

    Lyall RJ, Hooper MA, & Mainwaring SJ (1988) Polycyclic aromatic
    hydrocarbons in the Latrobe Valley. Atmos Environ, 22: 2549-2555.

    Lygren E, Gjessing E, & Berglind L (1984) Pollution transport from a
    highway. Sci Total Environ, 33: 147-159.

    Lyman WJ, Reehl WF, & Rosenblatt DH ed. (1982) Handbook on chemical
    property estimation methods, environmental behavior of organic
    compounds. New York, McGrawHill, 960 pp.

    Lyon JL, Klauber MR, Graff W, & Chiu G (1981) Cancer clustering around
    point sources of pollution. Assessment by a case control methodology.
    Environ Res, 25: 29-34.

    Lyte Ml, Blanton RH, Myers MJ, & Bick PH (1987) Effect of
     in vivo administration of carcinogen benzo(a)pyrene on interleukin-2
    and interleukin-3 production. Int J Immunopharmacol, 9: 307-312.

    Maccubbin AE, Black P, Trzeciak L, & Black JJ (1985) Evidence for
    polynuclear aromatic hydrocarbons in the diet of bottom-feeding fish.
    Bull Environ Contam Toxicol, 34: 876-882.

    Machado ML, Beatty PW, Fetzer JC, Glickman AH, & McGinnis EL (1993)
    Evaluation of the relationship between PAH content and mutagenic
    activity of fumes from roofing and paving asphalts and coal tar pitch.
    Fundam Appl Toxicol, 21: 492-499.

    Mackay D & Leinonen PJ (1975) Rate of evaporation of low-solubility
    contaminants from water bodies to atmosphere. Environ Sci Technol, 9:
    1178-1180.

    Mackay D & Shiu WY (1977) Aqueous solubility of polynuclear aromatic
    hydrocarbons. J Chem Eng Data, 22: 399-402.

    Mackay D & Shiu WY (1981) A critical review of Henry's law constants
    for chemicals of environmental interest. J Phys Chem Ref Data, 10:
    1175-1199.

    Mackay D, Shiu WY, & Sutherland RP (1979) Determination of air-water
    Henry's law constants for hydrophobic pollutants. Environ Sci Technol,
    13: 333-337.

    Mackay D, Shiu WY, & Ma KC (1992) Illustrated handbook of physical-
    chemical properties and environmental fate for organic chemicals.
    Volume II: Polynuclear aromatic hydrocarbons, polychlorinated dioxins
    and dibenzofurans. Boca Raton, Florida, Lewis Publishers, pp 1-367.

    Mackell JV, Rieders F, Brieger H, & Bauer EL (1951) Acute hemolytic
    anemia due to ingestion of naphthalene moth balls. Pediatrics, 7: 722-
    728.

    MacKenzie KM & Angevine DM (1981) Infertility in mice exposed in utero
    to benzo(a)pyrene. Biol Reprod, 24: 183-191.

    Maclaren WM & Hurley JF (1987) Mortality of tar distillation workers.
    Scand J Work Environ Health, 13: 404-411.

    MacNicoll AD, Easty GC, Neville AM, Grover PL, & Sims P (1980)
    Metabolism and activation of carcinogenic polycyclic hydrocarbons by
    human mammary cells. Biochem Biophys Res Commun, 95: 1599-1606.

    Madhavan ND& Naidu KA ( 1995) Polycyclic aromatic hydrocarbons in
    placenta, maternal blood, umbilical cord blood and milk of Indian
    women. Hum Exp Toxicol, 14: 503-506.

    Maga JA (1986) Polycyclic aromatic hydrocarbon (PAH) composition of
    mesquite  (Prosopis fuliflora) smoke and grilled beef. J Agric Food
    Chem, 34: 249-251.

    Mager R, Huberman E, Yang SK, Gelboin HV, & Sachs L (1977)
    Transformation of normal hamster cells by benzo(a)pyrene diol-epoxide.
    Int J Cancer, 19: 814-817.

    Mahlum D, Wright CW, Chess EK, & Wilson BW (1984) Fractionation of
    skin tumor initiating activity in coal liquids. Cancer Res, 44: 5176-
    5181.

    Maisin J & Coolen M-L (1936) [Carcinogenic potency of
    methylcholanthrene.] Comp Soc Biol, 123: 159-160 (in French).

    Malaiyandi M, Benedek A, Holko AP, & Bancsi JJ (1986) Measurement of
    potentially hazardous polynuclear aromatic hydrocarbons from
    occupational exposure during roofing and paving operations. In: Cooke
    M, Dennis AJ, & Fisher GL ed. Polynuclear aromatic hydrocarbons:
    Physical and biological chemistry. Columbus, Ohio, Battelle Press, pp
    471-489.

    Malcolm HM & Dobson S (1994) The calculation of an environmental
    assessment level (EAL) for atmospheric PAHs using relative
    potencies.London, Department of the Environment, 34 pp (Report No.
    DoE/HMIP/RR/94/041).

    Malins DC (1982) Alterations in the cellular and subcellular structure
    of marine teleosts and invertebrates exposed to petroleum in the
    laboratory and field: A critical review. Can J Fish Aquat Sci, 39:
    877-889.

    Malins DC, McCain BB, Brown DW, Chan S-L, Myers MS, Landahl JT,
    Prohaska PG, Friedman AJ, Rhodes LD, Burrows DG, Gronlund WD, &
    Hodgins HO (1984) Chemical pollutants in sediments and diseases of
    bottom-dwelling fish in Puget Sound, Washington. Environ Sci Technol,
    18: 705-713.

    Malins DC, Krahn MM, Brown DW, Rhodes LD, Myers MS, McCain BB, & Chan
    SL (1985) Toxic chemicals in marine sediment and biota from Mukilteo,
    Washington: Relationships with hepatic neoplasms and other hepatic
    lesions in English sole  (Parophrys vetulus). J Natl Cancer Inst, 74:
    487-494.

    Mallet WG, Mosebrook DR, & Trush MA (1991) Activation of
    (±)- trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene to diolepoxides by
    human polymorphonuclear leukocytes or myeloperoxidase. Carcinogenesis,
    12: 521-524.

    Mamber SW, Bryson V, & Katz SE (1983) The  Escherichia coli 
    WP2/WP100 rec assay for detection of potential chemical carcinogens.
    Mutat Res, 119: 135-144.

    Mamber SW, Bryson V, & Katz SE (1984) Evaluation of the  Escherichia
    coli K12 inductest for detection of potential chemical carcinogens.
    Mutat Res, 130: 141-151.

    Mane SS, Purnell DM, & Hsu IC (1990) Genotoxic effects of five
    polycyclic aromatic hydrocarbons in human and rat mammary epithelial
    cells. Environ Mol Mutagen, 15: 78-82.

    Manilal VB & Alexander M (1991) Factors affecting the microbial
    degradation of phenanthrene in soil. Appl Microbiol Biotechnol, 35:
    410-405.

    Mannschreck C, Gündel J, & Angerer K (1996) Occupational exposure to
    PAH. Biological monitoring of hydroxylated metabolites. Polycyclic
    Aromat Compd 11: 11-18.

    Manz A, Berger J, & Waltsgott H (1983) [Occupational cancer in gas
    industry workers.] Bremerhaven, German Federal Department for Worker
    Safety and Accident Research  pp 1-131 (Wirtschaftsverlag NW, Report
    No. 352) (in German).

    Marcomini A, Pavoni B, Donazzolo R, & Orio AA (1986) Combined
    preparative and analytical use of normal-phase and reversed-phase
    high-performance liquid chromato-graphy for determination of aliphatic
    and polycyclic aromatic hydrocarbons in sediments of the Adriatic Sea.
    Mar Chem, 18: 71-84.

    Marcus JM & Stokes TP (1985) Polynuclear aromatic hydrocarbons in
    oyster tissue around three coastal marinas. Bull Environ Contam
    Toxicol, 35: 835-844.

    Marcus JM, Swearingen GR, Williams AD, & Heizer DD (1988) Polynuclear
    aromatic hydrocarbon and heavy metal concentrations in sediments at
    coastal South Carolina marinas. Arch Environ Contam Toxicol, 17: 103-
    113.

    Marino DJ (1987) Evaluation of Pluronic(R) Polyol F17 as a vehicle
    for petroleum hydrocarbons in the Salmonella/microsomal assay. Environ
    Mutagen, 9: 307-316.

    Marnett LJ, Reed GA, & Dennison DJ (1978) Prostaglandin synthetase
    dependent activation of 7,8-dihydro-7,8-dihydroxy-benzo(a)pyrene to
    mutagenic derivatives. Biochem Biophys Res Commun, 82: 210-216.

    Marquardt H & Heidelberger C (1972) Influence of 'feeder cells' and
    inducers and inhibitors of microsomal mixed-function oxidases on
    hydrocarbon-induced malignant transfromation of cells derived from C3H
    mouse prostate. Cancer Res, 32: 721-725.

    Marquardt H, Kuroki T, Huberman E, Selkirk JK, Heidelberger C, Grover
    PL, & Sims P (1972) Malignant transformation of cells derived from
    mouse prostate by epoxides and other derivatives of polycyclic
    hydrocarbons. Cancer Res, 32: 716-720.

    Marshall MV, McLemore TL, Martin RR, Jenkins WT, Snodgrass DR, Corson
    MA, Arnott MS, Wray NP, & Griffin AC (1979) Patterns of
    benzo [a]pyrene metabolism in normal human pulmonary alveolar
    macrophages. Cancer Lett, 8: 103-109.

    Martel L, Gagnon MJ, Masse R, Leclerc A, & Tremblay L (1986)
    Polycyclic aromatic hydrocarbons in sediments from the Saguenay Fjord,
    Canada. Bull Environ Contam Toxicol, 37: 133-140.

    Martin BJ (1980) Effects of petroleum compounds on estuarine fishes.
    Gulf Breeze, Florida, US Environmental Protection Agency, 43 pp
    (EPA-600/3-80-019; PB 80-141310).

    Martin CN & McDermid AC (1981) Testing of 42 coded compounds for their
    ability to induce unscheduled DNA repair synthesis in HeLa cells. In:
    DeSerres FJ & Ashby J ed. Evaluation of short-term tests for
    carcinogens. Report of the international collaborative programme. New
    York, Elsevier North Holland, pp 533-537 (Progress in Mutation
    Research, Volume 1).

    Martin CN, McDermid AC, & Garner RC (1978) Testing of known
    carcinogens and noncarcinogens for their ability to induce unscheduled
    DNA synthesis in HeLa cells. Cancer Res, 38: 2621-2627.

    Martin F, Hoepfner I, Scherer G, Adlkofer F, Dettbarn G, & Grimmer G
    (1989) Urinary excretion of hydroxy-phenanthrenes after intake of
    polycyclic aromatic hydrocarbons. Environ Int, 15: 41-47.

    Masclet P, Nikolaou K, & Mouvier G (1984) [Identification of sources
    of particular polycyclic aromatic hydrocarbons in the urban
    atmosphere.] In: Versino B & Angeletti ed. Physico-chemical behavior
    of atmospheric pollutants. Dordrecht: Reidel Publishing Co., pp 616-
    625 (in French).

    Mass MJ, Rodgers NT, & Kaufman DG (1981) Benzo [a]pyrene metabolism
    in organ culture of human endometrium. Chem-Biol Interactions, 33:
    195-205.

    Massie LC, Ward AP, & Davies JM (1985) The effects of oil exploration
    and production in the northern North Sea: Part 1. The levels of
    hydrocarbons in water and sediments in selected areas, 1978-1981. Mar
    Environ Res, 15: 165-213.

    Masuda Y & Kagawa R (1972) A novel synthesis and carcinogenicity of
    dibenzo [a,l]pyrene. Chem Pharm Bull, 20: 2736-2737.

    Matsumoto H & Kashimoto T (1985) Average daily respiratory intake of
    polycyclic aromatic hydrocarbons in ambient air determined by
    capillary gas chromatography. Bull Environ Contam Toxicol, 34: 17-23.

    Matsuoka A, Hayashi M, & Ishidate MJ (1979) Chromosomal aberration
    tests on 29 chemicals combined with S9 mix  in vitro. Mutat Res, 66:
    277-290.

    Matsuoka A, Sofuni I, Miyata N, & Ishidate M Jr (1991) Clastogenicity
    of 1-nitropyrene, dinitropyrenes, fluorene and mononitrofluorenes in
    cultered Chinese hamster cells. Mutat Res, 259: 103-110.

    Mattison DR & Nightingale MR (1980) The biochemical and genetic
    characteristics of murine ovarian aryl hydrocarbon (benzo [a]pyrene)
    hydroxylase activity and its relationship to primordial oocyte
    destruction by polycyclic aromatic hydrocarbons. Toxicol Appl
    Pharmacol, 56: 399-408.

    Mattison DR, White NB, & Nightingale MS (1980) The effect of
    benzo(a)pyrene on fertility, primordial oocyte number, and ovarian
    response to pregnant mare's serum gonadotropin. Pediatr Pharmacol, 1:
    143-151.

    Mattison DR, Singh H, Takizawa K, & Thomford PJ (1989) Ovarian
    toxicity of benzo(a)pyrene and metabolites in mice. Reprod Toxicol, 3:
    115-125.

    Matzner E (1984) Annual rates of deposition of polycyclic aromatic
    hydrocarbons in different forest ecosystems. Water Air Soil Pollut,
    21: 425-434.

    Matzner B, Hübner D, & Thomas W (1981) Content and storage of
    polycyclic aromatic hydrocarbons in two forested ecosystems in
    northern Germany. Z Pflanzenernähr Bodenkd, 144: 283-288.

    Mavournin KH, Blakey DH, Cimino MC, Salamone MF, & Heddle JA (1990)
    The  in vivo micronucleus assay in mammalian bone marrow and
    peripheral blood. A report of the US Environmental Protection Agency
    Gene-Tox Program. Mutat Res, 239: 29-80.

    May WE, Wasik SP, & Freeman DH (1978) Determination of the aqueous
    solubility of polynuclear aromatic hydrocarbons by a coupled column
    liquid chromatographic technique. Anal Chem, 50: 175-179.

    McCann J, Choi E, Yamasaki E, & Ames BN (1975a) Detection of
    carcinogens as mutagens in the Salmonella/microsome test: Assay of 300
    chemicals. Proc Natl Acad Sci USA, 72: 5135-5139.

    McCann J, Spingarn NE, Kobori J, & Ames BN (1975b) Detection of
    carcinogens as mutagens: Bacterial tester strains with R factor
    plasmids. Proc Natl Acad Sci USA, 72: 979-983.

    McCarroll NE, Keech BH, & Piper CE (1981) A microsuspension adaptation
    of the  Bacillus subtilis 'rec' assay. Environ Mutag, 3: 607-616.

    McCarthy JF & Jimenez BD (1985) Reduction in bioavailability to
    bluegills of polycyclic aromatic hydrocarbons bound to dissolved humic
    material. Environ Toxicol Chem, 4: 511-521.

    McCarthy JF, Jimenez BD, & Barbee T (1985) Effect of dissolved humic
    material on accumulation of polycyclic aromatic hydrocarbons:
    Structure-activity relationships. Aquat Toxicol, 7: 15-24.

    McClure P & Schoeny R (1995) Evaluation of a component-based relative
    potency approach to cancer risk assessment for exposure to PAH. In:
    Fifteenth international symposium on polycyclic aromatic compounds:
    Chemistry, biology and environmental impact, Belgirate, Italy, 19-22
    September 1995. Ispra, Joint Research Centre European Commission, p
    161.

    McCormick DL, Burns FJ, & Albert RE (1981) Inhibition of
    benzo(a)pyrene-induced mammary carcinogenesis by retinyl acetate. J
    Natl Cancer Inst, 66: 559-564.

    McElroy AE (1985)  In vivo metabolism of benz(a)anthracene by the
    polychaete  Nereis virens. Mar Environ Res, 17: 133-136.

    McElroy AE & Sisson JP (1989) Trophic transfer of benzo [a]pyrene
    metabolites between benthic marine organisms. Mar Environ Res, 28:
    265-269.

    McFall JA, Antoine SR, & DeLeon IR (1985) Base-neutral extractable
    organic pollutants in biota and sediments from Lake Pontchartrain.
    Chemosphere, 14: 1561-1569.

    McGill AS, Mackie PR, Parsons E, Bruce C, & Hardy R (1982) The
    polynuclear aromatic hydrocarbon content of smoked foods in the United
    Kingdom. In: Cooke M, Dennis AJ, & Fisher GL ed. Polynuclear aromatic
    hydrocarbons: Physical and biological chemistry. Columbus, Ohio,
    Battelle Press, pp 491-499.

    McGill AS, Mackie PR, Howgate P, & McHenery JG (1987) The flavour and
    chemical assessment of dabs  (Limanda limanda) caught in the vicinity
    of the Beatrice oil platform. Mar Pollut Bull, 18: 186-189.

    McIntyre AE, Perry R & Lester JN (1981) Analysis of polynuclear
    aromatic hydrocarbons in sewage sludges. Anal Lett, 14: 291-309.

    McKay S, Phillips DH, Hewer AJ, & Grover PL (1988) Metabolic
    activation of 7-ethyl- and 7-methylbenz [a]anthracene in mouse skin.
    Carcinogenesis, 9: 141-145.

    McLeese DW & Burridge LE (1987) Comparative accumulation of PAHs in
    four marine invertebrates. In: Capuzzo IM & Kester DR ed. Oceanic
    processes in marine pollution. Malabar, Florida, Kirger RE, pp
    109-118.

    McMahon CK & Tsoukalas SN (1978) Polynuclear aromatic hydrocarbons in
    forest fire smoke. In: Jones PW & Freudenthal RI ed. Carcinogenesis.
    Volume 3: Polynuclear aromatic hydrocarbons. New York, Raven Press, pp
    61-73.

    McVeety BD & Hites RA (1988) Atmospheric deposition of polycyclic
    aromatic hydrocarbons to water surfaces: A mass balance approach.
    Atmos Environ, 22: 511-536.

    Means JC, Hassett JJ, Wood SG, & Banwart WL (1979) Sorption properties
    of energy-related pollutants and sediments. In: Jones PW & Leber P ed.
    Polynuclear aromatic hydrocarbons. Ann Arbor, Michigan, Ann Arbor
    Science Publishers, pp 327-340.

    Means JC, Wood SG, Hassett JJ, & Banwart WL (1980) Sorption of
    polynuclear aromatic hydrocarbons by sediments and soils. Environ Sci
    Technol, 14: 1524-1528.

    Mehta R, Meredith-Brown M, & Cohen GM (1979) Metabolism and covalent
    binding of benzo [a]pyrene in human peripheral lung. Chem-Biol
    Interactions, 28: 345-358.

    Melancon M & Lech J (1978) Distribution and elimination of naphthalene
    and 2-methylnaphthalene in rainbow trout during short- and long-term
    exposures. Arch Environ Contam Toxicol, 7: 207-220.

    Melikian AA, LaVoie EJ, Hecht SS, & Hoffmann D (1983) 5-Methylchrysene
    metabolism in mouse epidermis  in vivo, diol epoxide-DNA adduct
    persistence, and diol epoxide reactivity with DNA as potential factors
    influencing the predominance of 5-methylchrysene-1,2-diol-3,4-epoxide-
    DNA adducts in mouse epidermis. Carcinogenesis, 4: 843-849.

    Melikian AA, Amin S, Huie K, Hecht SS, & Harvey G (1988) Reactivity
    with DNA bases and mutagenicity toward  Salmonella typhimurium of
    methylchrysene diol epoxide enantiomers. Cancer Res, 48: 1781-1787.

    Melikian AA, Prahalad AK, Amin SG, & Hecht SS (1991) Comparative DNA
    binding of benzo(a)pyrene, 5-methylchrysene, 6-methylchrysene and
    their corresponding bay-region dihydrodiol epoxides in newborn mouse
    lung and liver  in vivo. Proc Am Assoc Cancer Res, 32: 96.

    Melius P, Elan D, Kilgore M, Tan B, & Schoor WP (1980) Mixed function
    oxidase inducibility and polyaromatic hydrocarbon metabolism in the
    mullet, sea catfish and Gulf killifish. In: Bjorseth A & Dennis AJ ed.
    Polynuclear aromatic hydrocarbons: Chemistry and biological effects.
    Columbus, Ohio, Battelle Press, pp 1059-1075.

    Menichini E (1992a) Urban air pollution by polycyclic aromatic
    hydrocarbons: Levels and sources of variability. Sci Total Environ,
    116: 109-135.

    Menichini E (1992b) Opinion adopted by the Italian National Advisory
    Toxicological Committee on polycyclic aromatic hydrocarbons. Rome,
    Istituto Superiore di Sanità, 69 pp (Serie Relazioni 92/4).

    Menichini E, Bonanni L, & Merli F (1990) Determination of polycyclic
    aromatic hydrocarbons in mineral oils and oil aerosols in glass
    manufacturing. Toxicol Environ Chem, 28: 37-51.

    Menichini E, di Domenico A, Bonanni L, Corradetti E, Mazzanti L, &
    Zucchetti G (1991a) Reliability assessment of a gas chromatographic
    method for polycyclic aromatic hydrocarbons in olive oil. J
    Chromatogr, 555: 211-220.

    Menichini E, Bocca A, Merli F, Ianni D, & Monfredini F (1991b)
    Polycyclic aromatic hydrocarbons in olive oils on the Italian market.
    Food Addit Contam, 8: 363-369.

    Merriman JC (1988) Distribution of organic contaminants in water and
    suspended solids of the Rainy River. Water Pollut Res J Can, 23: 590-
    600.

    Mersch-Sundermann V, Mochayedi S, & Kevekordes S (1992) Genotoxicity
    of polycyclic aromatic hydrocarbons in
     Escherichia coli PQ37. Mutat Res, 278: 1-9.

    Meyer JP & Grimmer G (1974) [The influence of PCA-containing and
    PCA-free fuel on the emission of polycyclic aromatic hydrocarbons from
    a motor vehicle with spark-ignition engine in the Europe test cycle.]
    Hamburg, German Society for Mineral-oil and Coal Chemistry, 22 pp
    (BMI-DGMK joint project 4547, Part 1) (in German).

    Meyer H-P, Grimmer G, & Behn U (1980) [PAH from oil heating:
    Collection, analysis, results. Air pollution from polycylic aromatic
    hydrocarbons. Registration and evaluation.] Düsseldorf, VDI-Verlag, pp
    101-105 (VDI Report No. 358) (in German).

    Meyers MJ, Blanton RH, & Bick PH(1988) Inhibition of IL-2
    responsiveness following exposure to benzo(a)pyrene is due to
    alterations in accessory cell function. Int J Immunopharmacol, 10:
    177-186.

    Michel X, Bani MH, & Narbonne JF (1995) Regio-selective metabolism of
    benzo [a]pyrene by microsomes from 5 vertebrate species. In:
    Fifteenth international symposium on polycyclic aromatic compounds:
    Chemistry, biology and environmental impact, Belgirate, Italy, 19-22
    September 1995. Ispra, Joint Research Centre European Commission, p
    78.

    Middaugh DP, Thomas RL, Lantz SE, Heard CS, & Mueller JG (1994) Field
    scale testing of a hyperfiltration unit for removal of creosote and
    pentachlorophenol from groundwater: Chemical and biological
    assessment. Arch Environ Contam Toxicol, 26: 309-319.

    Mielzynska D & Snit M (1992) Urine mutagenicity in workers directly
    employed in coke production. Pol J Occup Med, 5: 363-371.

    Miescher G (1942) [Experimental studies on the formation of tumours by
    photosensitization.] Schweiz Med Wochenschr, 72: 1082-1984 (in
    German).

    Milano JC & Vernet JL (1988) [Size of the contribution of carcinogenic
    polyaromatic hydrocarbons by the Rhône.] Oceanis, 14: 133-140 (in
    French).

    Milano JC, Fache B, & Vernet JL (1985) [Contamination of the Cortiou
    site by polyaromatic hydrocarbons in wastewater from the city of
    Marseille (western Mediterranean, France).] J Rech Oceanogr, 10: 36-38
    (in French).

    Milano JC, Fache B, & Vernet JL (1986) [Pollution of the sediment,
    fauna and flora by polyaromatic hydrocarbons at Cap Sicié at the
    emission site of the city of Toulon  (French Mediterranean coast).] J
    Rech Oceanogr, 11: 93-96 (in French).

    Mill T & Mabey W (1985) Photochemical transformations. In: Neely WB &
    Blau GE ed. Environmental exposure from chemicals, Volume 1. Boca
    Raton, Florida, CRC Press, pp 175-216.

    Mill T, Mabey WR, Lan BY, & Baraze A (1981) Photolysis of polycyclic
    aromatic hydrocarbons in water. Chemosphere, 10: 1281-1290.

    Millemann RE, Birge WJ, Black JA, Cushman RM, Daniels KL, Franco PJ,
    Giddings JM, McCarthy JF, & Stewart AJ (1984) Comparative acute
    toxicity of aquatic organisms of components of coal derived synthetic
    fuels. Trans Am Fish Soc, 113: 74-85.

    Miller EC (1951) Studies on the formation of protein-bound derivatives
    of 3,4-benzpyrene in the epidermal fraction of mouse skin. Cancer Res,
    11: 100-108.

    Miller JA & Miller EC (1953) The carcinogenic aminoazo dyes. Adv
    Cancer Res, 1: 339-396.

    Miller JA & Miller EC (1963) The carcinogenicities of fluoro
    derivatives of 10-methyl- 1,2-benzanthracene. II. Substitution of the
    K region and the 3'- 6-, and 7-positions. Cancer Res, 23: 229-239.

    Miller JA & Miller (1977) Ultimate chemical carcinogens as reactive
    mutagenic electrophiles In: Hiatt HH, Watson JD, & Winston JA ed.
    Origins of human cancer, Book B, Mechanisms of carcinogenesis. Cold
    Spring Harbor, New York, Cold Spring Harbor Laboratory, pp 605-627.

    Miller MM, Wasik SP, Huang G-L, Shiu W-Y, & Mackay D (1985)
    Relationships between octanol-water partition coefficient and aqueous
    solubility. Environ Sci Technol, 19: 522-529.

    Miller MM, Plowchalk DR, Weitzman GA,, London SN & Mattison DR (1992)
    The effect of benzo(a)pyrene on murine ovarian and corpora lutea
    volumes. Am J Obstet Gynecol, 166: 1535-1541.

    Milo GE, Blakeslee J, Yohn DS, & DiPaolo JA (1978) Biochemical
    activiation of aryl hydrocarbon hydroxylase activity, cellular
    distribution of polynuclear hydrocarbon metabolites, and DNA damage by
    polynuclear hydrocarbon products in human cells  in vitro. 
    Cancer Res, 38: 1638-1644.

    Miralis JC, Tyson CK, & Butterworth BE (1982) Detection of genotoxic
    carcinogens in the  in vivo-in vitro hepatocyte DNA repair assay.
    Environ Mutag, 4: 553-562.

    Mishra NK, Wilson CM, Pant KJ, & Thomas FO (1978) Simultaneous
    determination of cellular mutagenesis and transformation by chemical
    carcinogens in Fischer rat embryo cells. J Toxicol Environ Health, 4:
    79-91.

    Mitchell CE (1982) Distribution and retention of benzo [a]pyrene in
    rats after inhalation. Toxicol Lett, 11: 35-42

    Mitchell RL, Burchett MD, Pulkownik A, & McCluskey L (1988) Effects of
    environmentally hazardous chemicals on the emergence and early growth
    of selected Australian plants. Plant Soil, 112: 195-199.

    Mix MC & Schaffer RL (1983) Concentrations of unsubstituted polycyclic
    aromatic hydrocarbons in softshell clams from Coos Bay, Oregon, USA.
    Mar Pollut Bull, 14: 94-97.

    Mohr U (1969) [Studies on the carcinogenic properties of
    3.4,-10.11-,12.13- tribenzofluoranthene by mice.] Arch Hyg, 153: 495-
    510 (in German).

    Mohr U (1971) [Carcinogenicity of diethylnitrosamine.] Fortschr Med,
    89: 251-253 (in German).

    Moles A (1980) Sensitivity of parasitized Coho salmon fry to crude
    oil, toluene, and naphthalene. Am Fish Soc, 109: 293-297.

    Moles A, Bates S, Rice SD, & Korn S (1981) Reduced growth of Coho
    salmon fry exposed to two petroleum components, toluene and
    naphthalene, in fresh water. Am Fish Soc, 110: 430-436.

    Monarca S, Pasquini R, Scassellati Sforzolini G, Savino A, Bauleo FA,
    & Angeli G (1987) Environmental monitoring of mutagenic/carcinogenic
    hazards during road paving operations with bitumens. Int Arch Occup
    Environ Health, 59: 393-402.

    Monnerjahn S, Seidel A, Steinberg P, Oesch F, Hinz M, Stezowsky JJ,
    Hewer A, Phillips DH & Glatt HR (1993) Formation of DNA adducts from
    1-hydroxymethylpyrene in liver cells  in vivo and  in 
     vitro. In: Phillips DH, Castegnaro M & Bartsch H ed. Postlabelling
    methods for detection of DNA adducts, Lyon, International Agency for
    Research on Cancer, pp. 189-193 (IARC Scientific Publications No. 124)


    Monteith DK & Gupta RC (1992) Carcinogen-DNA adducts in cultures of
    rat and human hepatocytes. Cancer Lett, 62: 87-93.

    Montizaan GK, Kramers PGH, Janus JA & Posthumus R (1989) Integrated
    criteria document PAH: Effects of 10 selected compounds. Appendix to
    Report No. 758474011. Bilthoven, National Institute of Public Health
    and Environmental Protection, 180 pp (Re-publication in March 1989 of
    addendum to Report No. 758447007).

    Moolgavkar SH & Knudson A (1981) Mutation and cancer: A model for
    human carcinogenesis. J Natl Cancer Inst, 66: 1037-1052.

    Moolgavkar SH & Venzon DJ (1979) Two-event models for carcinogenesis.
    Math Biosci, 47: 55-77.

    Moore BP, Hicks RM, Knowles MA, & Redgrave S (1982) Metabolism and
    binding of benzo(a)pyrene and 2-acetylaminofluorene by short-term
    organ cultures of human and rat bladder. Cancer Res, 42: 642-648.

    Moore MN, Livingstone DR, & Widdows J (1989) Hydrocarbons in marine
    mollusks: Biological effects and ecological consequences. In: Varanasi
    U ed. Metabolism of polycyclic aromatic hydrocarbons in the aquatic
    environment. Boca Raton, Florida, CRC Press, pp 291-329.

    Moriske H-J, Freise R, Schneider C, & Rüden H (1987) [Polar neutral
    organic compounds (POCN) in town aerosols. 2. Communication:
    Measurement of the emissions from homeheating and cars and from
    immission particles in Berlin (West).] Zentralbl Bakteriol Hyg I Abt
    Orig B, 185: 72-104 (in German).

    Morris HP, Velat CA, Wagner BP, Dahlgard M, & Ray FE (1960) Studies of
    carcinogenicity in the rat of derivatives of aromatic amines related
    to N-2-fluorenylacetamide. J Natl Cancer Inst, 24: 149-180.

    Morrison VM, Burnett AK, & Craft JA (1991a) Metabolism of
    7,12-dimethyl-benz [a]anthracene in hepatic microsomal membranes from
    rats treated with isoenzyme-selective inducers of cytochromes P450.
    Biochem Pharmacol, 41: 1505-1512.

    Morrison VM, Burnett AK, Forrester LM, Wolf CR, & Craft JA (1991b) The
    contribution of specific cytochromes P450 in the metabolism of
    7,12-dimethylbenz [a]anthracene in rat and human liver microsomal
    membranes. Chem-Biol Interactions, 79: 179-196.

    Morselli L & Zappoli S (1988) PAH determination in samples of
    environmental interest. Sci Total Environ, 73: 257-266.

    Mossanda K, Poncelet F, Fouassin A, & Mercier A (1979) Short papers.
    Detection of mutagenic polycyclic aromatic hydrocarbons in African
    smoked fish. Food Cosmet Toxicol, 17: 141-143.

    Motykiewicz G (1995) Application of biomarkers in heavily polluted
    industrialized areas of countries of central and eastern Europe.
    Toxicology, 101: 117-123.

    Moulin JJ, Portefaix P, Wild P, Mur JM, Smagghe G, & Mantout B (1990)
    Mortality study among workers producing ferroalloys and stainless
    steel in France. Br J Ind Med, 47: 537-543.

    Moulin JJ, Wild P, Mantout B, Fournier-Betz M, Mur JM, & Smagghe G
    (1993) Mortality from lung cancer and cardiovascular diseases among
    stainless-steel producing workers. Cancer Causes Control, 4: 75-81.
    Muel B & Saguem S (1985) Determination of 23 polycyclic aromatic
    hydrocarbons in atmospheric particulate matter of the Paris area and
    photolysis by sunlight. Int J Environ Anal Chem, 19: 111-131.

    Mueller JG & Lantz SE (1993) Strategy using bioreactors and specially
    selected microorganisms for bioremediation of groundwater contaminated
    with creosote and pentachlorophenol. Environ Sci Technol, 27: 691-698.

    Müller E (1968) [Carcinogenic compounds in water and soil. XX.
    Investigation into the carcinogenic properties of benzo(ghi)perylene.]
    Arch Hyg, 152: 23-36 (in German with English abstract).

    Müller H (1987) Hydrocarbons in the freshwater environment. A
    literature review. Arch Hydrobiol, 24: 1-69.

    Müller G, Grimmer G & Böhnke H (1977) [Sedimentary record of heavy
    metals and polycyclic aromatic hydrocarbons in Lake Constance.].
    Naturwissenschaften, 64: 427-431 (in German).

    Muller P, Leece B & Raha D (1995a) Estimated risk of cancer from
    exposure to PAH fractions of complex mixtures. In: Fifteenth
    international symposium on polycyclic aromatic compounds: Chemistry,
    biology and environmental impact, Belgirate, Italy, 19-22 September
    1995. Ispra, Joint Research Centre European Commission, pp 159-160.

    Muller P, Leece B & Raha D (1995b) Dose-response assessment PAH.
    Ottawa, Ontario Ministry of the Environment and Energy, 197 pp.

    Muller P, Leece B & Raha D (1996) Scientific criteria document for
    multimedia environmental standards development: Polycyclic aromatic
    hydrocarbons (PAH). Part 1. Dose response assessment. Ottawa, Ontario
    Ministry of the Environment and Energy, 203 pp.

    Mumford JL, He XZ, Chapman RS, Cao SR, Harris DB, Li XM, Xian YL,
    Jiang WZ, Xu CW, Chuang JC, Wilson WE, & Cooke M (1987a) Lung cancer
    and indoor air pollution in Xuan Wei, China. Science, 235: 217-235.

    Mumford JL, Chapman RS, Harris DB, He XZ, Cao SR, Xian YL, & Li XM
    (1987b) Lung cancer and indoor air exposure to unvented coal and wood
    combustion emission in Xuan Wie, China. In: Seifert B, Esdorn H,
    Fischer M, Rüden H, & Wegner J ed. Indoor Air '87, Volume 3:
    Developing countries, guaranteeing adequate indoor air quality,
    control measures, ventilation effectiveness, thermal climate and
    comfort, policy and strategies. Berlin, Institute for Water, Soil and
    Air Hygiene, pp 8-14.

    Mumford JL, Helmes CT, Lee X, Seidenberg J, & Nesnow S (1990) Mouse
    skin tumorigenicity studies of indoor coal and wood combustion
    emissions from homes of residents in Xuan Wie, China, with high lung
    cancer mortality. Carcinogenesis, 11: 397-403.

    Mumford JL, Williams RW, Walsh DB, Burton RM, Svensgaard DJ, Chuang
    JC, Houk VS, & Lewtas J (1991) Indoor air pollutants from unvented
    kerosene heater emissions in mobile homes: Studies on particles,
    semivolatile organics, carbon monoxide, and mutagenicity. Environ Sci
    Technol, 25: 1732-1738.

    Mumford JL, Lee X, Lewtas J, Young TL, & Santella RM (1993) DNA
    adducts as biomarkers for assessing exposure to polycyclic aromatic
    hydrocarbons in tissues from Xuan Wei women with high exposure to coal
    combustion emissions and high lung cancer mortality. Environ Health
    Perspectives, 99: 83-87.

    Mumford JL, Li X, Hu F, Lu XB & Chuang JC (1995) Human exposure and
    dosimetry of polycyclic aromatic hydrocarbons in urine from Xuan Wei,
    China, with high lung cancer mortality associated with exposure to
    unvented coal smoke. Carcinogenesis, 16: 3031-3036.

    Munœz MJ & Tarazona JV (1993) Synergistic effect of two- and
    four-component combinations of the polycyclic aromatic hydrocarbons:
    Phenanthrene, anthracene, and acenaphthene on  Daphnia magna. Bull
    Environ Contam Toxicol, 50: 363-368.

    Mur JM, Moulin JJ, Meyer-Bisch C, Massin N, Couplon JP & Loulergue J
    (1987) Mortality of aluminium reduction plant workers in France. Int J
    Epidemiol, 16: 257-264.

    Murison GL (1988) Induction of sister-chromatid exchanges by direct
    and indirect agents in a human teratoma cell line. Mutat Res, 203:
    347-354.

    Murray JJ, Pottie RF, & Pupp C (1974) The vapor pressures and
    enthalpies of sublimation of five polycyclic aromatic hydrocarbons.
    Can J Chem, 52: 557-563.

    Myhr BC & Caspary WJ (1988) Evaluation of the L5178Y mouse lymphoma
    cell mutagenesis assay: Intralaboratory results for sixty-three coded
    chemicals tested at Litton Bionetics, Inc. Environ Mol Mutag, 12
    (suppl 13): 103-194.

    Nagabhushan M, Hussong J, Polverini PJ, & Solt DB (1990) Inhibition of
    hamster buccal pouch epithelial cell replication during  in 
     vitro exposure to polycyclic aromatic hydrocarbons. Proc Am Assoc
    Cancer Res, 31: 86.

    Nagel DL, Stenbäck F, Clayson DB, & Wallcave L (1976) Intratracheal
    installation studies with 7 H-dibenzo [c,g]carbazole in Syrian
    hamster. J Natl Cancer Inst, 57: 119-123.

    Namkung MJ & Juchau MR (1980) On the capacity of human placental
    enzymes to catalyse the formation of diols from benzo [a]pyrene.
    Toxicol Appl Pharmacol, 55: 253-259.

    Natarajan AT & Darroudi F (1991) Use of human hepatoma cells for  in
    vitro metabolic activation of chemical mutagens/carcinogens.
    Mutagenesis, 6: 399-403.

    National Chemicals Inspectorate (1994) [Report on the use of highly
    aromatic oils in tyres in Sweden.] Solna, pp 15-21 (Report No. 6/94)
    (in Swedish with English summary).

    National Institute for Occupational Health and Safety and Occupational
    Safety and Health Administration (1981) Occupational health guideline
    for coal tar pitch volatiles. In: Mackison FW, Stricoff RS, &
    Partridge LJ Jr ed. Occupational health guidelines for chemical
    hazards. Cambridge, Massachusetts, 30 pp [DHHS (NIOSH) Publication No.
    81-123; US NTIS PB83-154609, Part 1 of 3].

    National Institute for Occupational Health and Safety (1994a)
    Polynuclear aromatic hydrocarbons by HPLC: Method No. 5506. In: Eller
    PM & Cassinelli ME ed. NIOSH manual of analytical methods, 4th ed.
    Cincinnati, Ohio, 8 pp (Publication No. 94-113).

    National Institute for Occupational Health and Safety (1994b)
    Polynuclear aromatic hydrocarbons by GC: Method No. 5515. In: Eller PM
    & Cassinelli ME ed. NIOSH manual of analytical methods, 4th ed.
    Cincinnati, Ohio, 7 pp. (Publication No. 94-113).

    National Research Council Canada (1983) Polycyclic aromatic
    hydrocarbons in the aquatic environment: formation, sources, fate and
    effects on aquatic biota. Ottawa, Associate Committee on Scientific
    Criteria for Environmental Quality, pp 32-33 (Report NRCC No. 18981).

    National Toxicology Program (1991) Final study report and appendix:
    Developmental toxicity evaluation of naphthalene (CAS No. 91-20-3)
    administered by gavage to Sprague-Dawley (CD) rats on gestational days
    6 through 15. Research Triangle Park, North Carolina, US Department of
    Health and Human Services, 107 pp (Report TER-91006).
    National Toxicology Program (1992a) Final study report and appendix:
    Development toxicity evaluation of naphthalene (CAS No. 91-20-3)
    administered by gavage to New-Zealand White (NZW) rabbits on
    gestational days 6 through 19. Research Triangle Park, North Carolina,
    US Department of Health and Human Services, 107 pp (Report TER-91021).

    National Toxicology Program (1992b) Toxicology and carcinogenesis
    studies of naphthalene (CAS No. 91-20-3) in B6C3F1 mice (inhalation
    studies). Research Triangle Park, North Carolina, US Department of
    Health and Human Services, 129 pp (NTP TR 410; NIH Publication No.
    92-3141).

    National Toxicology Program (1993) Hazardous substances data bank.
    Bethesda, Maryland, National Library of Medicine, 20 pp.

    Natusch DFS & Tomkins BA (1978) Isolation of polycyclic organic
    compounds by solvent extraction with dimethyl sulfoxide. Anal Chem,
    50: 1429-1434.

    Navarro A, Rosell A, Villanueva J, & Grimalt JO (1991) Monitoring of
    hazardous waste dumps by the study of metals and solvent-soluble
    organic chemicals. Chemosphere, 22: 913-928.

    Naylor LM & Loehr RC (1982) Priority pollutants in municipal sewage
    sludge. Bio-Cycle, 23: 18-22.

    Neal J & Rigdon RH (1967) Gastric tumors in mice fed benzo(a)pyrene: A
    quantitative study. Tex Rep Biol Med, 25: 553-557.

    Nebert DW (1980) Pharmacogenetics: An approach to understanding
    chemical and biological aspects of cancer. J Natl Cancer Inst, 6:
    1279-1290.

    Nebert DW, Levitt RC, Jensen NM, Lambert GS, & Felton JS (1977) Birth
    defects and aplastic anemia: Differences in polycyclic hydrocarbon
    toxicity associated with the Ah locus. Arch Toxicol, 39: 109-132.

    Neff JM (1979) Polycyclic aromatic hydrocarbons in the aquatic
    environment: Sources, fates and biological effects. London, Applied
    Science Publishers, 262 pp.

    Neff JM & Anderson JW (1975) Accumulation, release, and distribution
    of benzo(a)pyrene-C14 in the clam  Rangia cuneata. 
    Proc Conf Prev Control Oil Pollut, 75: 469-471.

    Negishi M, Swan DC, Enquist LW, & Nebert DW (1981) Isolation and
    characterization of a cloned DNA sequence associated with the murine
     Ah locus and a 3-methylcholan-threne-induced form of cytochrome
    P450. Proc Natl Acad Sci USA, 78: 800-801.

    Nelson PF (1989) Combustion-generated polycyclic aromatic hydrocarbons
    in diesel exhaust emissions. Fuel, 68: 283-286.

    Nelson DR, Kamataki T, Waxman DJ, Guengerich FP, Estabrook RW,
    Feyereisen R, Gonzalez FJ, Coon MJ, Gunsalus IC, Gotoh O, Okuda K, &
    Nebert W (1993) The P450 superfamily: Update on new sequences, gene
    mapping, accession numbers, early trivial names of enzymes, and
    nomenclature. DNA Cell Biol, 12: 1-51.

    Nesnow S (1990) Mouse skin tumors and human lung cancer: Relationships
    with complex environmental emissions. In: Vainio H, Sorsa M, &
    McMichael A ed. Complex mixtures and cancer risk. Lyon, International
    Agency for Research on Cancer, pp 44-54 (IARC Scientific Publications
    No. 104).

    Nesnow S & Heidelberger C (1976) The effect of modifiers of microsomal
    enzymes on chemical oncogenesis in cultures of C3H mouse cell lines.
    Cancer Res, 36: 1801-1808.

    Nesnow S, Evans C, Stead A, Creason J, Slaga TJ, & Triplett LL (1982a)
    Skin carcinogenesis studies of emission extracts. In Lewtas J ed.
    Toxicological effects of emissions from diesel engines. Amsterdam,
    Elsevier, 295-320.

    Nesnow S, Triplett L, & Slaga TJ (1982b) Comparative tumor-initiating
    activity of complex mixtures from environmental particulate emissions
    on Sencar mouse skin. J Natl Cancer Inst, 68: 829-834.

    Nesnow S, Leavitt S, Easterling R, Watts R, Toney SH, Claxton L,
    Sangaiah R, Toney GE, Wiley J, Fraher P, & Gold A (1984) Mutagenicity
    of cyclopenta-fused isomers of benz [a]anthracene in bacterial and
    rodent cells and identification of the major rat liver microsomal
    metabolites. Cancer Res, 44: 4993-5003.

    Nesnow S, Easterling RE, Ellis S, Watts R, & Ross J (1988) Metabolism
    of benz [j]aceanthrylene (cholanthrylene) and benz [1]aceanthrylene
    by induced rat liver S9. Cancer Lett, 39: 19-27.

    Nesnow S, Ross J, Mohapatra N, Gupta R, Sangaiah R, & Gold A (1991)
    Genotoxicity and identification of the major DNA-adducts of
    aceanthrylene. In: Cooke M, Loening K, & Merritt J ed. Polynuclear
    aromatic hydrocarbons: Measurements, means, and metabolism. Columbus,
    Ohio, Battelle Press, pp 629-639.

    Nesnow S, Ross J, Beck S, Lasley J, Nelson G, Lamberg G, Platt KL, &
    Agarwal SC (1994) Morphological transformation and DNA adduct
    formation by dibenz [a,h]-anthracene and its metabolites in
    C3H10T1/2Cl8 cells. Carcinogenesis, 15: 2225-2231.

    Nesnow S, Mass MJ, Ross JA, Gennings C, Carter WH Jr, & Stoner GD
    (1995) Lung tumorigenic interactions of five environmental PAH.
    Additivity, synergism and antagonism. In: Fifteenth international
    symposium on polycyclic aromatic compounds: Chemistry, biology and
    environmental impact, Belgirate, Italy, 19-22 September 1995. Ispra,
    Joint Research Centre European Commission, p 151.

    Netherlands' Delegation (1991) The problem of polycyclic aromatic
    hydrocarbons (PAH) in the Rhine. In: Working Group B of International
    Rhine Commission, pp 1-7 (B 5/91 Revision).

    Nettesheim P & Hammons AS (1971) Induction of squamous cell carcinoma
    in the respiratory tract of mice. J Natl Cancer Inst, 47: 697-701.

    Neubert D & Tapken S (1988) Transfer of benzo(a)pyrene into mouse
    embryos and fetuses. Arch Toxicol, 62: 236-239.

    Neuhauser EF & Callahan CA (1990) Growth and reproduction of the
    earthworm  Eisenia fetida exposed to sublethal concentrations of
    organic chemicals. Soil Biol Biochem, 22: 175-179.

    Neuhauser EF, Durkin PR, Malecki MR, & Anatra M (1986) Comparative
    toxicity of ten organic chemicals to four earthworm species. Comp
    Biochem Phys, C83: 197-200.

    Newsted JL & Giesy JP Jr (1987) Predictive models for photoinduced
    acute toxicity of polycyclic aromatic hydrocarbons to  Daphnia 
     magna, Strauss  Cladocera, Crustacea. Toxicol Chem, 6: 445-461.

    Ng KM, Chu I, Bronaugh RL, Franklin CA, & Somers DA (1992)
    Percutaneous absorption and metabolism of pyrene, benzo (a)pyrene,
    and di(2-ethylhexyl)phthalate: Comparison of  in vitro and  in 
     vivo results in the hairless guinea pig. Toxicol Appl Pharmacol,
    115: 216-223.

    Nicholls TP, Perry R, & Lester JN (1979) The influence of heat
    treatment on the metallic and polycyclic aromatic hydrocarbon content
    of sewage sludge. Sci Total Environ, 12: 137-150.

    Nichols DG, Gangwal SK, & Sparacino CM (1981) Analysis and assessment
    of PAH from coal composition and gasification. In: Cooke M & Dennis AJ
    ed. Polynuclear aromatic hydrocarbons: Chemical analysis and
    biological fate. Columbus, Ohio, Battelle Press, 397-406.

    Nielsen T (1984) Reactivity of polycyclic aromatic hydrocarbons toward
    nitrating species. Environ Sci Technol, 18: 157-163.

    Nikonova TV (1977) Transplacental action of benzo(a)pyrene and pyrene.
    Bull Exp Biol Med, 84: 1025-1027.

    Nisbet ICT & LaGoy PK (1992) Toxic equivalency factors (TEFs) for
    polycyclic aromatic hydrocarbons (PAHs). Regul Toxicol Pharmacol, 16:
    290-300.

    Nisbet ICT, Schneiderman MA, Karch NJ, & Siegel DM (1985) Review and
    evaluation of the evidence for cancer associated with air pollution.
    Research Triangle Park, North Carolina, US Environmental Protection
    Agency, 295 pp (NTIS/PB85-142016).

    Nishioka M, Chang H-C, & Lee ML (1986) Structural characteristics of
    polycyclic aromatic hydrocarbon isomers in coal tars and combustion
    products. Environ Sci Technol, 20: 1023-1027.

    Nkedi-Kizza P, Rao PSC, & Hornsby AG (1985) Influence of organic
    cosolvent on sorption of hydrophobic organic chemicals by soils.
    Environ Sci Technol, 19: 975-979.

    Nordholm L, Espensen I-M, Jensen HS, & Holst E (1986) Polycyclic
    aromatic hydrocarbons in smokehouses. Scand J Work Environ Health, 12:
    614-618.

    Norpoth K, Kemena A, Jacob J, & Schümann C (1984) The influence of 18
    environmentally relevant polycyclic aromatic hydrocarbons and Clophen
    A50, as liver monooxygenase inducers, on the mutagenic activity of
    benz [a]anthracene in the Ames test. Carcinogenesis, 5: 747-752.

    Nousiainen U, Törrönen R, & Hänninen O (1984) Differential induction
    of various carboxylesterases by certain polycyclic aromatic
    hydrocarbons in the rat. Toxicology, 32: 243-251.

    Novelli G & Rinaldi A (1979) Further contributions to the study of
    coal dust for foundries. Giesserei, 66: 480-482.

    Nowak D, Meyer A, Schmidt-Preuss U, Gatzemeyer U, Magnussen H, &
    Rüdiger HW (1992) Formation of benzo(a)pyrene-DNA adducts in blood
    monocytes from lung cancer patients with a familial history of lung
    cancer. J Cancer Res Clin Oncol, 118: 67-71.

    Noyes WF (1969) Carcinogen-induced neoplasia with metastasis in a
    South American primate,  Saguinus oedipus (33845). Proc Soc Exp Biol
    Med, 131: 223-225.

    Ny ET, Heederik D, Kromhout H, & Jongeneelen F (1993) The relationship
    between polycyclic aromatic hydrocarbons in air and in urine of
    workers in a Söderberg potroom. Am Ind Hyg Assoc J, 54: 277-284.

    Obana H, Hori S, & Kashimoto T (1981a) Determination of polycyclic
    aromatic hydrocarbons in marine samples by high-performance liquid
    chromatography. Bull Environ Contam Toxicol, 26: 613-620.

    Obana H, Hori S, Kashimoto T, & Kunita N (1981b) Polycyclic aromatic
    hydrocarbons in human fat and liver. Bull Environ Contam Toxicol, 27:
    23-27.

    Oberly TJ, Huffman DM, & Garriott ML (1992) An evaluation of
    chromosomal mutagens in the CHO-AS52 cell line. Environ Mol Mutag, 19
    (suppl 20): 46 (Abstract).

    O'Brien KAF, Smith LL, & Cohen GM (1985) Differences in
    naphthalene-induced toxicity in the mouse and rat. Chem-Biol
    Interactions, 55: 109-122.

    O'Brien KAF, Suverkropp C, Kaqnekal S, Plopper CG, & Buckpitt AR
    (1989) Tolerance to multiple doses of the pulmonary toxicant,
    naphthalene. Toxicol Appl Pharmacol, 99: 487-500.

    Oesch F (1973) Mammalian epoxide hydrases: inducible enzymes
    catalysing the inactivation of carcinogenic and cytotoxic metabolites
    derived from aromatic and olefinic compounds. Xenobiotica, 3: 305-340.

    Oesch F, Bücker M, & Glatt HR (1981) Activation of phenanthrene to
    mutagenic metabolites and evidence for at least two different
    activation pathways. Mutat Res, 81: 110.

    Okano P, Miller HN, Robinson RC, & Gelboin HV (1979) Comparison of
    benzo [a]pyrene and
    (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo [a]pyrene metabolism in
    human blood monocytes and lymphocytes. Cancer Res, 39: 3184-3193.

    Okita T, Yanagihara M, Yoshida K, Iwata M, Tanabe K, & Hara H (1994)
    Measurements of air pollution associated with oil fires in Kuwait by a
    Japanese research team. Atmos Environ, 28: 2255-2259.

    Old LJ, Benacerraf B, & Carswell E (1963) Contact reactivity to
    carcinogenic polycyclic hydrocarbons. Nature, 198: 1215-1216.

    Olufsen SB (1980) Polynuclear aromatic hydrocarbons in Norwegian
    drinking water resources. In: Bjorseth A & Dennis AJ ed. Polynuclear
    aromatic hydrocarbons: Chemistry and biological effects. Columbus,
    Ohio, Battelle Press, pp 333-343.

    Olufsen SB & Bjorseth A (1983) Analysis of polycyclic aromatic
    hydrocarbons by gas chromatography. In: Bjorseth A ed. Handbook of
    polycyclic aromatic hydrocarbons. New York, Marcel Dekker, pp 257-300.

    Omland O, Sherson D, Hansen AM, Sigsgaard T, Autrup H, & Overgaard E (
    1994) Exposure of iron foundry workers to polycyclic aromatic
    hydrocarbons: benzo(a)pyrene-albumin adducts and 1-hydroxypyrene as
    biomarkers for exposure. Occup Environ Med, 51: 513-518.

    Oris JT & Giesy JP Jr (1985) The photoenhanced toxicity of anthracene
    to juvenile sunfish  (Lepomis spp.). Aquat Toxicol, 6: 133-146.

    Oris JT & Giesy JP (1986) Photoinduced toxicity of anthracene to
    juvenile bluegill sunfish  (Lepomis macrochirus Rafinesque):
    Photoperiod effects and predictive hazard evaluation. Environ Toxicol
    Chem, 5: 761-768.

    Oris JT & Giesy JP Jr (1987) The photo-induced toxicity of polycyclic
    aromatic hydrocarbons to larvae of the fathead minnow  (Pimephales
    promelas). Chemosphere, 16: 1395-1404.

    Oris JT, Hall AT, & Tylka JD (1990) Humic acids reduce the
    photo-induced toxicity of anthracene to fish and  Daphnia. Environ
    Toxicol Chem, 9: 575-584.

    Osborn JF, Santhanam S, Davidson CI, Flotard RD, & Stetter JR (1984)
    Characterization of airborne trace metal and trace organic species
    from coal gasification. Environ Monit Assess, 4: 317-333.

    Osborne MR & Crosby NT (1987a) Binding to proteins and nucleic acids.
    In: Benzopyrenes. Cambridge, Cambridge University Press, pp 137-176
    (Cambridge Monographs on Cancer Research).

    Osborne MR & Crosby NT (1987b) Benzo [e]pyrene. In: Benzopyrenes.
    Cambridge, Cambridge University Press, pp 229-250 (Cambridge
    Monographs on Cancer Research).

    Osborne MR, Harvey RG, & Brookes P (1978) The reaction of
     trans-7,8-dihydroxy- anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo
     [a]pyrene with DNA involves attack at the N7-position of guanine
    moieties. Chem-Biol Interactions, 20: 123-130.

    Osborne MR, Brookes P, Lee H, & Harvey RG (1986) The reaction of a
    3-methylcholan-threne diol epoxide with DNA in relation to the binding
    of 3-methylcholanthrene to the DNA of mammalian cells. Carcinogenesis,
    7: 1345-1350.

    Oshiro Y, Balwierz PS, Soelter SG, Guzzie PJ, & Rohrbacher E (1992)
    Evaluation of mouse peripheral blood micronucleus assay. Environ Mol
    Mutag, 19 (suppl 20): 47 (Abstract).

    Ostman C, Nilsson U, Carlsson H, Andersson I, & Fahlgren L (1991)
    [Polycyclic aromatic compounds (PAC) in work environment. I. PAC in
    Stockholm street air: An introductory study.] Solna, Swedish National
    Institute of Occupational Health, 16 pp (Research Report No. 21) (in
    Swedish).

    Ostman C, Nilsson U, Carlsson H, Andersson I, & Fahlgren L (1992a)
    [Polycyclic aromatic compounds (PAC) in work environment. II. PAC in
    Stockholm street air: Content of PAH in two busy streets.] Solna,
    Swedish National Institute of Occupational Health, 41 pp (Research
    Report No. 34) (in Swedish with English summary).

    Ostman C, Nilsson U, Carlsson H, Andersson I, & Fahlgren L (1992b)
    [Polycyclic aromatic compounds (PAC) in work environment. III. PAC in
    Stockholm street air: Content of PAH before and after a traffic
    diversion.] Solna, Swedish National Institute of Occupational Health,
    Division of Analytical Chemistry, 31 pp (Research Report No. 35) (in
    Swedish with English summary).

    Ostrander GK, Landolt ML, & Kocan RM (1988) The ontogeny of Coho
    salmon  (Oncorhynchus kisutch) behavior following embryonic exposure
    to benzo [a]pyrene. Aquat Toxicol, 13: 325-346.

    Oueslati R, Alexandrov K, Chouikha M, & Chouroulinkov I (1992)
    Formation and persistence of DNA adducts in epidermal and dermal mouse
    skin exposed to benzo(a)pyrene  in vivo. In Vivo, 6: 231-236.

    Ovrebo S, Hewer A, Phillips DH, & Haugen A (1990) Polycyclic aromatic
    hydrocarbon-DNA adducts in coke-oven workers. In: Vainio H, Sorsa M, &
    McMichael AJ ed. Complex mixtures and cancer risk. Lyon, International
    Agency for Research on Cancer, pp 193-198 (IARC Scientific
    Publications No. 104).

    Ovrebo S, Haugen A, Phillips DH, & Hewer A (1992) Detection of
    polycyclic aromatic hydrocarbon-DNA adducts in white blood cells from
    coke oven workers: Correlation with job catagories. Cancer Res, 52:
    1510-1514.

    Ovrebo S, Haugen A, Fjeldstad PE, Hemminki K, & Szyfter K (1994)
    Biological monitoring of exposure to polycyclic aromatic hydrocarbon
    in an electrode paste plant. J Occup Med, 36: 303-310.

    Ovrebo S, Fjeldstad PE, Grzybowska E, Kure EH, Chorazy M, & Haugen A
    (1995) Biological monitoring of polycyclic aromatic hydrocarbon
    exposure in a highly polluted area of Poland. Environ Health
    Perspectives, 103: 838-843.

    Pahlman R & Pelkonen O (1987) Mutagenicity studies of different
    polycyclic aromatic hydrocarbons: The significance of enzymatic
    factors and molecular structure. Carcinogenesis, 8: 773-778.

    Paika IJ, Beauchesne MT, Randall M, Schreck RR, & Latt SA (1981)  In
    vivo SCE analysis of 20 coded compounds. In: De Serres FJ & Ashby J
    ed. Evaluation of short-term tests of carcinogens. Report of the
    international collaborative programme. New York, Elsevier
    North-Holland, pp 672-681 (Progress in Mutation Research, Volume 1).

    Pal K (1981) The induction of sister-chromatid exchanges in Chinese
    hamster ovary cells by K-region epoxides and some dihydrodiols derived
    from benz [a]anthracene, dibenz [a,c]anthracene and
    dibenz [a,h]anthracene. Mutat Res, 84: 389-398.

    Pal K, Grover PL, & Sims P (1975) The metabolism of carcinogenic
    polycyclic hydrocarbons by tissues of the respiratory tract. Biochem
    Soc Trans, 3: 174-175.

    Palitti F, Cozzi R, Fiore M, Palombo F, Polcaro C, Perez G, & Possagno
    E (1986) An  in vitro and  in vivo study on mutagenic activity of
    fluoranthene: Comparison between cytogenetic studies and HPLC
    analysis. Mutat Res, 174: 125-130.

    Pallardy MJ, House RV, & Dean JH (1989) Molecular mechanism of
    7,12-dimethylbenz(a)anthracene induced immunosuppression: Evidence for
    action via the interleukin-2 pathway. Mol Pharmacol, 36: 128-133.

    Pallardy M, Mishal Z, Lebrec H, & Bohuon C (1992) Immune modification
    due to chemical interference with transmembrane signalling:
    Application to polycyclic aromatic hydrocarbons. Int J
    Immunopharmacol, 14: 377-381.

    Palmer WG & Scott WD (1981) Lung cancer in ferrous foundry workers: A
    review. Am Ind Hyg Assoc J, 42: 329-340.

    Palmork KH, Wilhelmsen S, & Neppelberg T (1973) International Council
    for Exploration of the Sea. The contribution of polycyclic aromatic
    hydrocarbons (PAH) to the marine environment from different
    industries. Bergen, Institute of Marine Research, pp 1-21 (Report No.
    C M 1973/E:33).

    Pancirov RJ, Searl TD, & Brown RA (1980) Methods of analysis for
    polynuclear aromatic hydrocarbons in environmental samples. Adv Chem
    Ser, 185: 123-142.

    Pankow JF, Isabelle LM, & Asher WE (1984) Trace organic compounds in
    rain. 1. Sampler design and analysis by adsorption/thermal desorption
    (ATD). Environ Sci Technol, 18: 310-318.

    Park KS, Sims RC, Dupont RR, Doucette WJ, & Matthews JE (1990) Fate of
    PAH compounds in two soil types: Influence of volatilization, abiotic
    loss and biological activity. Environ Toxicol Chem, 9: 187-195.

    Parkinson EK & Newbold RF (1980) Benzo [a]pyrene metabolism and DNA
    adduct formation in serially cultivated strains of human epidermal
    keratinocytes. Int J Cancer, 26: 289-299.

    Parrott MC, Kawabata TT, & White KL Jr (1989) Suppression of humoral
    immunity following dermal exposure to benzo(a)pyrene in B6C3F1 mice.
    Toxicologist, 9: 201 (Abstract 801).

    Partanen T & Boffetta P (1994) Cancer risk in asphalt workers and
    roofers: Review and meta-analysis of epidemiologic studies. Am J Ind
    Med, 26: 721-740.

    Paschke A, Herbel W, Steinhard H, Franke S, & Francke W (1992)
    Determination of mono- to tetracyclic aromatic hydrocarbons in
    lubricating oil. J High Res Chromatogr, 15: 827-833.

    Passino DRM & Smith SB (1987) Acute bioassays and hazard evaluation of
    representative contaminants detected in Great Lakes fish. Environ
    Toxicol Chem, 6: 901-907.

    Pataki J & Huggins C (1969) Molecular site of substituents of
    benz(a)anthracene related to carcinogenicity. Cancer Res, 29: 506-509.

    Pathirana S, Connell W, & Vowles PD (1994) Distribution of polycyclic
    aromatic hydrocarbons (PAHs) in an urban roadway system. Ecotoxicol
    Environ Saf, 28: 256-269.

    Pavanello S & Levis AG (1994) Human peripheral blood lymphocytes as a
    cell model to evaluate the genotoxic effect of coal tar treatment.
    Environ Health Perspectives, 102: 95-99.

    Pavoni B, Sfriso A, & Marcomini A (1987) Concentration and flux
    profiles of PCBs, DDTs and PAHs in a dated sediment core from the
    lagoon of Venice. Mar Chem, 21: 25-35.

    Payne JF (1977) Mixed function oxidases in marine organisms in
    relation to petroleum hydrocarbon metabolism and detection. Mar Pollut
    Bull, 8: 112-116.

    Pelkonen O & Nebert DW (1982) Metabolism of polycyclic aromatic
    hydrocarbons: Etiologic role in carcinogenesis. Pharmacol Rev, 34:
    189-222.

    Pelkonen O & Saarni H (1980) Unusual patterns of benzo [a]pyrene
    metabolites and DNA-benzo [a]pyrene adducts produced by human
    placental microsomes  in vitro. Chem-Biol Interactions, 30: 287-296.

    Pelkonen O, Sotaniemi E, & Mokka R (1977) The  in vitro oxidative
    metabolism of benzo [a]pyrene in human liver measured by different
    assays. Chem-Biol Interactions, 16: 13-22.

    Pellizzari ED, Castillo NP, Willis S, Smith D, & Bursey JT (1979)
    Identification of organic components in aqueous effluents from
    energy-related processes. In: Van Hall CE ed. Measurement of organic
    pollutants in water and wastewater. Philadelphia, Pennsylvania,
    American Society for Testing and Materials, pp 256-274 (ASTM STP 686).

    PPenman BW, Kaden DA, Liber HL, Skopek TR, & Thilly WG (1980) Perylene
    is a more potent mutagen than benzo [a]pyrene for  Salmonella
    typhimurium. Mutat Res, 77: 271-277.

    Perera FP, Hemminki K, Young TL, Brenner D, Kelly G, & Santella RM
    (1988) Detection of polycyclic aromatic hydrocarbon-DNA adducts in
    white blood cells of foundry workers. Cancer Res, 48: 2288-2291.

    Perera FP, Hemminki K, Gryzbowska E, Motykiewicz G, Michalska J,
    Santella RM, Young T, Dickey C, Brandt-Rauf P, DeVivo I, BlanerW, Tsai
    W, & Chorazy M (1992) Molecular and genetic damage in humans from
    environmental pollution in Poland. Nature, 360: 256-258.

    Perera FP, Tang DL, O'Neill JPO, Bigbee WL, Albertini RJ, Santella R,
    Ottman R, Tsai WY, Dickey C, Mooney LA, Savela K, & Hemminki K (1993)
    HPRT and glycophorin A mutations in foundry workers: Relationship to
    PAH exposure and to PAH-DNA adducts. Carcinogenesis, 14: 969-973.

    Perera FP, Dickey C, Santella R, O'Neill JP, Albertini RJ, Ottman R,
    Tsai WY, Mooney LA, Savela K, & Hemminki K (1994) Carcinogen-DNA
    adducts and gene mutation in foundry workers with low-level exposure
    to polycyclic aromatic hydrocarbons. Carcinogenesis, 15: 2905-2910.

    Perfetti GA, Nyman PJ, Fisher S, Joe FL Jr, & Diachenko GW (1992)
    Determination of polynuclear aromatic hydrocarbons in seafood by
    liquid chromatography with fluorescence detection. J Assoc Off Anal
    Chem, 75: 872-877.

    Perin-Roussel O, Saguem S, Ekert B, & Zajdela F (1983) Binding to DNA
    of bay-region and pseudo bay region diol-epoxides of
    dibenzo [a,e]fluoranthene and comparison with adducts obtained with
    dibenzo [a,e]fluoranthene or its dihydrodiols in the presence of
    microsomes. Carcinogenesis, 4: 27-32.

    Perin-Roussel O, Croisy A, Ekert B, & Zajdela F (1984) The metabolic
    activation of dibenzo(a,e)fluoranthene  in vitro. 
    Evidence that its bay-region and pseudo-bay-region diolepoxides react
    preferentially with guanosine. Cancer Lett, 22: 289-298.

    Perry PE & Thomson EJ (1981) Evaluation of the sister chromatid
    exchange method in mammalian cells as a screening system for
    carcinogens. In: De Serres FJ & Ashby J ed. Evaluation of short-term
    tests for carcinogens. Report of the international collaborative
    programme. New York, Elsevier North-Holland, pp 560-569 (Progress in
    Mutation Research, Volume 1).

    Peter S, Palme GE, & Röhrborn G (1979) Mutagenicity of polycyclic
    hydrocarbons. III. Monitoring genetic hazards of benz(a)anthracene.
    Acta Morphol Acad Sci Hung, 27: 199-204.

    Peters JA, DeAngelis DG, & Hughes TW (1981) An environmental
    assessment of POM emissions from residential wood-fired stoves and
    fireplaces. In: Cooke M & Dennis AJ ed. Polynuclear aromatic
    hydrocarbons: Chemical analysis and biological fate. Columbus, Ohio,
    Battelle Press, pp 571-581.

    Peterson AR, Landolph JR, Peterson H, Spears CP, & Heidelberger C
    (1981) Oncogenic transformation and mutation of C3H/10T1/2 clone 8
    mouse embryo fibroblasts by alkylating agents. Cancer Res, 41: 3095-
    3099.

    Petridou-Fischer J, Whaley SL, & Dahl AR (1988)  In vivo 
    metabolism of nasally instilled benzo [a]pyrene in dogs and monkeys.
    Toxicology, 48: 31-40.

    Petry TH, Schmid P, & Schlatter CH (1994) Exposure to polycyclic
    aromatic hydrocarbons (PAHs) in two different silicon carbide plants.
    Ann Occup Hyg, 38: 741-752.

    Pezzuto JM, Lea MA, & Yang CS (1976) Binding of metabolically
    activated benzo(a)pyrene to nuclear macromolecules. Cancer Res, 36:
    3647-3653.

    Pezzuto JM, Lea MA, & Yang CS (1977) The role of microsomes and
    nuclear envelope in the metabolic activation of benzo [a]pyrene
    leading to binding with nuclear macro-molecules. Cancer Res, 37: 3427-
    3433.

    Pfannhauser W (1991) [Polycyclic aromatic hydrocarbons (PAH) in food
    and selected vegetables in Austria.] Mitt Geb Lebensmittelunters Hyg,
    82: 66-79 (in German).

    Pfau W, Hughes NC, Grover PL, & Phillips DH (1992) HPLC separation of
    32P-postlabelled benzo [b]fluoranthene-DNA adducts. Cancer Lett, 65:
    159-167.

    Pfeffer HU (1994) Ambient air concentrations of pollutants at
    traffic-related sites in urban areas of North Rhine-Westphalia,
    Germany. Sci Total Environ, 146/147: 263-273.

    Pfeiffer EH (1973) Investigation on the carcinogenic burden by air
    pollution in man. VII. Studies on the oncogenic interaction of
    polycyclic aromatic hydrocarbons. Zentralbl Bakteriol Hyg Abt. Orig B,
    158: 69-83.

    Pfeiffer EH (1977) Oncogenic interaction of carcinogenic and
    non-carcinogenic polycyclic aromatic hydrocarbons. In: Mohr V, Schmähl
    D, & Tomatis L eds. Air pollution and cancer in man. Lyon,
    International A gency for Research on Cancer, pp 69-77 (IARC
    Scientific Publications No. 16).

    Pflock H, Georgii HW, & Müller J (1983) [Particulate polycyclic
    aromatic hydrocarbons (PAH) in polluted and in clean areas.]
    Staub-Reinhalt Luft, 43: 230-234 (in German).

    Phillips DH (1990) Modern methods of DNA adduct determination. In:
    Cooper CS & Grover PL ed. Handbook of experimental pharmacology,
    Volume 94/1. Berlin, Springer-Verlag, pp 503-546.

    Phillips DH (1991) DNA-adduct analysis by 32P-postlabeling in the
    study of human exposure to carcinogens. In: Groopman JD & Skipper PL
    ed. Molecular dosimetry and human cancer. Chapter 9: Analytical,
    epidemiological, and social considerations. Boca Raton, Florida, CRC
    Press, pp 151-170.

    Phillips DH & Alldrick AJ (1994) Tumorigenicity of a combination of
    psoriasis therapies. Br J Cancer, 69: 1043-1045.

    Phillips DH & Castegnaro M (1993) Results of an interlaboratory trial
    of 32P-postlabelling. In: Phillips DH, Castegnaro M & Bartsch H ed.
    Postlabelling methods for detection of DNA adducts. Lyon,
    International Agency for Research on Cancer, pp 35-49 (IARC Scientific
    Publications No. 124)

    Phillips DH, Hewer A, Martin CN, Garner RC, & King MM (1988)
    Correlation of DNA adduct levels in human lung with cigerette smoking.
    Nature, 336: 790-792.

    Phillips DH, Schoket B, Hewer A, & Grover PL (1990) DNA adduct
    formation in human and mouse skin by mixtures of polycyclic aromatic
    hydrocarbons. In: Vainio H, Sorsa M, & McMichael AJ ed. Complex
    mixtures and cancer risk. Lyon, International Agency for Research on
    Cancer, pp 223-229 (IARC Scientific Publications No. 104).

    Phillips DH, Hewer A, Seidel A, Steinbrecher T, Schrode R, Oesch F, &
    Glatt H (1991) Relationship between mutagenicity and DNA adduct
    formation in mammalian cells for fjord- and bay-region diol-epoxides
    of polycyclic aromatic hydrocarbons. Chem-Biol Interactions, 80: 177-
    186.

    Phillips DH, Castegnaro M & Bartsch H ed. (1993) Postlabelling methods
    for detection of DNA adducts. Lyon, International Agency for Research
    on Cancer, 388 pp (IARC Scientific Publications No. 124).

    Pienta RJ, Poiley JA, & Lebherz WB III (1977) Morphological
    transformation of early passage golden Syrian hamster embryo cells
    derived from cryopreserved primary cultures as a reliable  in 
     vitro bioassay for identifying diverse carcinogens. Int J Cancer,
    19: 642-655.

    Pike MH (1944) Ocular pathology due to organic compounds. J Mich State
    Soc, 43: 581-584.

    Pike MC (1983) Human cancer risk assessment. Polynuclear aromatic
    hydrocarbons: Evaluation of sources and effects. Report by the
    Committee on Pyrene and Selected Analogues, the Board on Toxicology
    and Environmental Health Hazards, the Commission on Life Sciences and
    the National Research Council. Washington DC, National Academic Press,
    pp C1-C28.

    Pischinger F & Lepperhoff G (1980) [Influence of air-fuel ratio on the
    PAH emissions from Otto motor engines. Air pollution from polycylic
    aromatic hydrocarbons. Registration and evaluation.] Düsseldorf,
    VDI-Verlag, pp 59-63 (VDI Report No. 358) (in German).

    Pistikopoulos P, Masclet P, & Mouvier G (1990) A receptor model
    adapted to reactive species: Polycyclic aromatic hydrocarbons:
    Evaluation of source contributions in an open urban site. I. Particle
    compounds. Atmos Environ, 24: 1189-1197.

    Plasterer MR, Bradshaw WS, Booth GM, Carter MW, Schuler RL, & Hardin
    BD (1985) Developmental toxicity of nine selected compounds following
    prenatal exposure in the mouse: Naphthalene, p-nitrophenol, sodium
    selenite, dimethyl phthalate, ethylenethiourea, and four glycol ether
    derivatives. J Toxicol Environ Health, 15: 25-38.

    Platt KL, Pfeiffer E, Petrovic P, Friesel H, Beermann D, Hecker E, &
    Oesch F (1990) Comparative tumorigenicity of picene and
    dibenz [a,h]anthracene in the mouse. Carcinogenesis, 11: 1721-1726.

    Plesha P, Stein J, Schiewe M, McCin B, & Varanasi U (1988) Toxicity of
    marine sediments supplemented with mixtures of selected chlorinated
    and aromatic hydrocarbons to the infaunal amphipod
     Rhepoxynius-abronius. Mar Environ Res, 25: 85-98.

    Plopper CG, Suverkropp C, Morin D, Nishio S, & Buckpitt A (1992)
    Relationship of cytochrome P-450 activity to Clara cell cytotoxicity.
    I. Histopathologic comparison of the respiratory tract of mice, rats
    and hamsters after parenteral administration of naphthalene. J
    Pharmacol Exp Ther, 261: 353-363.

    Podoll RT, Irwin KC, & Parish HJ (1989) Dynamic studies of naphthalene
    sorption on soil from aqueous solution. Chemosphere, 18: 2399-2412.

    Poirier MC (1994) Human exposure monitoring, dosimetry, and cancer
    risk assessment: The use of antisera specific for carcinogen-DNA
    adducts and carcinogen-modified DNA. Drug Metab Rev, 26: 87-109.

    Poirier MC & Beland FA (1992) DNA adduct measurement and tumor
    incidence during chronic carcinogen exposure in animal models:
    Implications for DNA adduct-based human cancer risk assessment. Chem
    Res Toxicol, 5: 749-755.

    Pollia JA (1941) Investigation on the possible carcinogenic effect of
    anthracene and chrysene and some of their compounds. II. The effect of
    subcutaneous injection in rats. J Ind Hyg Toxicol, 223: 449-451.

    Poncelet F, Massanda K, Fouassin A, & Mercier M (1978) Mutagenic study
    of some polycyclic aromatic hydrocarbons present in smoked fishes from
    Africa. Arch Int Phys Biochem, 86: 954-955.

    Popescu NC, Turnbull D, & DiPaolo JA (1977) Sister chromatid exchange
    and chromosome aberration analysis with the use of several carcinogens
    and noncarcinogens: Brief communication. J Natl Cancer Inst, 59: 289-
    293.

    Pothuluri JV, Freeman JP, Evang FE, & Cerniglia CE (1993)
    Biotransformation of fluorene by the fungus  Cunninghamella 
     elegans. Appl Environ Microbiol, 59: 1977-1980.

    Pott P (1775) Chirurgical observations relative to the cataract, the
    polypus of the nose, the cancer of the scrotum, the different kinds of
    ruptures, and the mortification of the toes and feet. London, Hawes,
    Clark & Collins, pp 63-68.

    Pott F & Heinrich U (1992) [Dust and dust components / polycyclic
    aromatic hydrocarbons (PAH).] In: Wichmann HE, Schlipköter HW, &
    Fülgraff G ed. [Handbook of environmental medicine, 2nd ed.]
    Landsberg, Lech Ecomed mbH, pp 1-23 (in German).

    Pott F, Brockhaus A, & Huth F (1973) [Tests on the production of
    tumours in animal experiments with polycyclic aromatic hydrocarbons.]
    Zentralbl Bakteriol Hyg I Abt Orig B, 157: 34-43 (in German).

    Pott F, Mohr U, & Brockhaus A (1978) [Studies on the combined effects
    of benzopyrene and dibenz [a]anthracene with SO2 and NO2 inhalation
    on the golden hamster.] In: Rothe H ed. [Air hygiene and silicosis
    research.] Essen, Girardet, pp 224-226 (in German).

    Pott F, Ziem U, Reiffer FJ, Huth F, Ernst H, & Mohr U (1987)
    Carcinogenicity studies on fibres, metal compounds, and some other
    dusts in rats. Exp Pathol (Jena), 32: 129-152.

    Potthast K (1980) [Recent results on the benzo [a]pyrene content of
    meat products.] Fleischwirtschaft, 60: 1941-1949 (in German).

    Potvin RR, Adamek EG, & Balsillie D (1980) Ambient PAH levels near a
    steel mill in northern Ontario. In: Cooke M & Dennis AJ ed.
    Polynuclear aromatic hydrocarbons: Chemical analysis and biological
    fate. Columbus, Ohio, Battelle Press, pp 741-753.

    Prasanna P, Jacobs MM, & Yang Sk (1987) Selenium inhibition of
    benzo [a]pyrene, 3-methylcholanthrene, and 3-methylcholanthrylene
    mutagenicity in  Salmonella typhimurium strains TA98 and TA100. Mutat
    Res, 190: 101-105.

    Prinsen AJ & Kennedy WBH (1977) [Quantity of alpha-benzopyrene in
    smoked foods.] In: [Aroma and flavouring substances.] Bilthoven,
    National Institute of Public Health and Environmental Protection, pp
    1-11 (Report No. 11) (in Dutch).

    Prinsen AJ & Kennedy WBH (1978) [Quantity of alpha benzopyrene in
    various tea samples.] In: [Aroma and flavouring substances.]
    Bilthoven, National Institute of Public Health and Environmental
    Protection, pp 1-5 (Report No. 12) (in Dutch).

    Probst GS, McMahon RE, Hill LE, Thompson CZ, Epp JK, & Neal SB (1981)
    Chemically-induced unscheduled DNA synthesis in primary rat hepatocyte
    cultures: A comparison with bacterial mutagenicity using 218
    compounds. Environ Mutagen, 3: 11-32.

    Prough RA, Patrizi VW, Okita RT, Masters BSS, & Jakobsson SW (1979)
    Characteristics of benzo [a]pyrene metabolism by kidney, liver, and
    lung microsomal fractions from rodents and humans. Cancer Res, 39:
    1199-1206.

    Pruell RJ, Hoffmann EJ, & Quinn JG (1984) Total hydrocarbons,
    polycyclic aromatic hydrocarbons and synthetic organic compounds in
    the hard shell clam,  Mercenaria mercenaria, purchased at commercial
    seafood stores. Mar Environ Res, 11: 163-181.

    Pruess-Schwartz D, Baird WM, Yagi H, Jerina DM, Pigott MA, & Dipple A
    (1987) Stereochemical specificity in the metabolic activation of
    benzo [c]phenanthrene to metabolites that covalently bind to DNA in
    rodent embryo cell cultures. Cancer Res, 47: 4032-4037.

    Puffer H, Duncan K, Von Hofe E, Brewer G, & Mondal S (1979)
    Benz(a)pyrene: Studies of the effects of this ubiquitous pollutant on
    fishes. Ocean, 79: 398-400.

    Pullman A (1945) [On an electronic theory of the carcinogenic action
    of condensed aromatic hydrocarbons.] C R Séance Soc Biol Fil, 139:
    1056-1058 (in French).

    Pullman A (1947) [Contribution to the study of the electronic
    structure of organic molecules. Special study on carcinogenic
    hydrocarbons.]. Ann Chim, 2: 7-71 (in French).

    Purchase IFH, Longstaff E, Ashby J, Styles JA, Anderson D, Lefevre PA,
    & Westwood FR (1976) Evaluation of six short term tests for detecting
    organic chemical carcinogens and recommendations for their use.
    Nature, 264: 624-627.

    Pussemier L, Szabo G, & Bulman RA (1990) Prediction of the soil
    adsorption coefficient Koc for aromatic pollutants. Chemosphere, 21:
    1199-1212.

    Pyysalo H, Tuominen J, Wickström K, Skyttä E, Tikkanen L, Salomaa S,
    Sorsa M, Nurmela T, Mattila T, & Pohjola V (1987) Polycyclic organic
    material (POM) in urban air. Fractionation, chemical analysis and
    genotoxicity of particulate and vapour phases in an industrial town in
    Finland. Atmos Environ, 21: 1167-1180.

    Quaghebeur D, De Wulf E, Ravelingien MC, & Janssens G (1983)
    Polycyclic aromatic hydrocarbons in rainwater. Sci Total Environ, 32:
    35-54.

    Quarles JM, Sega MW, Schenley CK, & Lijinsky W (1979) Transformation
    of hamster fetal cells by nitrosated pesticides in a transplacental
    assay. Cancer Res, 39: 4525-4533.

    Quilliam MA & Sim PG (1988) Determination of polycyclic aromatic
    compounds by high-performance liquid chromatography with simultaneous
    mass spectrometry and ultraviolet diode array detection. J Chromatogr
    Sci, 26: 160-167.

    Quinlan R, Kowalczyz G, Gardiner K, Calvert I, Hale K, & Walton S
    (1995a) Polycyclic aromatic hydrocarbon exposure in coal liquefaction
    workers: The value of urinary 1-hydroxypyrene excretion in the
    development of occupational hygiene control strategies. Ann Occup Hyg,
    39: 329-346.

    Quinlan R, Kowalczyk G, Gardiner K, Hale K, Walton S, & Calvert I
    (1995b) Urinary 1-hydroxypyrene: A biomarker for polycyclic aromatic
    hydrocarbon exposure in coal liquefaction workers. Occup Med, 45: 63-
    68.

    Quinlan R, Kowalczyk G, Gardiner K, & Calvert I (1995c) Exposure to
    polycyclic aromatic hydrocarbons in coal liquefaction workers: Impact
    of a workwear policy on excretion of urinary 1-hydroxypyrene. Occup
    Environ Med, 52: 600-605.

    Radian Corp (1991) Asphalt industry cross sectional exposure
    assessment study. Final Report. Sacramento, California, 200 pp.

    Raha CR (1972) Metabolism of benzo [a]pyrene at the 4,5-position. Ind
    J Biochem Biophys, 9: 105-110.

    Rahman A, Barrowman JA, & Rahimtula A (1986) The influence of bile on
    the bioavailability of polynuclear aromatic hydrocarbons from the rat
    intestine. Can J Physiol Pharmacol, 64: 1214-1218.

    Rainio K, Linko RR, & Ruotsila L (1986) Polycyclic aromatic
    hydrocarbons in mussel and fish from the Finnish archipelago sea. Bull
    Environ Contam Toxicol, 37: 337-343.

    Raiyani CV, Jani JP, Desai NM, Shah JA, & Kashyap SK (1993a) Levels of
    polycyclic aromatic hydrocarbons in ambient environment of Ahmedabad
    City. Indian J Environ Prot, 13: 206-215.

    Raiyani CV, Jani JP, Desai NM, Shah JA, Shah PG, & Kashyap SK (1993b)
    Assessment of indoor exposure to polycyclic aromatic hydrocarbons for
    urban poor using variuos types of cooking fuels. Bull Environ Contam
    Toxicol, 50: 757-763.

    Ramdahl T & Mœller M (1983) Chemical and biological characterization
    of emissions from a cereal straw burning furnace. Chemosphere, 12: 23-
    34.

    Ramdahl T, Alfheim I, Rustad S, & Olsen T (1982) Chemical and
    biological characterization of emissions from small residential stoves
    burning wood and charcoal. Chemosphere, 11: 601-611.

    Rao KSM, Phadke KM, & Muthal PI (1987) Estimation of carcinogenic
    polycyclic aromatic hyrocarbon concentrations on the top of coke
    ovens. Res Ind, 43: 276-281.

    Rastetter WH, Nachbar RB, Russo-Rodriguez S, Wattley RV, Thilly WG,
    Andon BM, Jorgensen WL, & Ibrahim M (1982) Fluoranthene: Synthesis and
    mutagenicity of fluor diol epoxides. J Org Chem, 47: 4873-4878.

    Ratajczak EA, Ahland E, Grimmer G, & Dettbarn G (1984) [Reduction of
    PAH emissions from hard coal briquettes containing bitumen instead of
    pitch binder.] Staub-Reinhalt Luft, 44: 505-509 (in German).

    Raunio H & Pelkonen O (1994) Cancer genetics: Genetic factors in the
    activation and inactivation of chemical carcinogens. In: Ioannides C
    ed. Drugs, diet and disease. Volume 1: Mechanistic approaches to
    cancer. New York, Simon & Schuster International, pp 229-258.

    Raveh D, Slaga TJ, & Huberman E (1982) Cell-mediated mutagenesis and
    tumor-initiating activity of the ubiquitous polycyclic hydrocarbon,
    cyclopenta [c,d]pyrene. Carcinogenesis, 3: 763-766.

    Readman JW, Preston MR, & Mantoura RFC (1986) An integrated technique
    to quantify sewage, oil and PAH pollution in estuarine und coastal
    environments. Mar Pollut Bull, 17: 298-308.

    Reardon DB, Prakash AS, Hilton BD, Roman JM, Pataki J, Harvey RG, &
    Dipple A (1987) Characterization of
    5-methylchrysene-1,2-dihydroidiol-3,4-epoxide-DNA adducts.
    Carcinogenesis, 8: 1317-1322.

    Reddy MV, Gupta RC, Randerath E, & Randerath K (1984)
    32P-Postlabeling test for covalent DNA binding of chemicals
     in vivo: Application to a variety of aromatic carcinogens and
    methylating agents. Carcinogenesis, 5: 231-243.

    Reddy MV, Olson JA, Stober GR, & Daniel FB (1991) Induction of nuclear
    anomalies in the gastrointestinal tract by polycyclic aromatic
    hydrocarbons. Cancer Lett, 56: 215-224.

    Redmond CK (1983) Cancer mortality among coke oven workers. Environ
    Health Perspectives, 52: 67-73.

    Reed L (1983) Health hazard evaluation: Anchor Hocking Glass Company
    Roofing Site, Lancaster, Ohio, January 1983. Cincinnati, Ohio,
    National Institute for Occupational Safety and Health, pp 1-9 (Report
    HETA 82-067-1253; PB 84-173046).

    Reed GA, Layton ME, & Ryan MJ (1988) Metabolic activation of
    cyclopenteno [c,d]pyrene by peroxyl radicals. Carcinogenesis, 9:
    2291-2295.

    Rees DC & Hattis D (1994) Developing quantitative strategies for
    animal to human extrapolation. In: Hayes AW ed. Principles and methods
    of toxicology, 3rd Ed, New York, Raven Press, pp 275-315.

    Rees ED, Mandelstam P, Lowry JQ, & Lipscomb H (1971) A study of the
    mechanism of intestinal absorption of benzo [a]pyrene. Biochem
    Biophys Acta, 225: 96-107.

    Rees RW, Brice AJ, Carlton JB, Gilbert PJ & Mitchell I de G (1989)
    Optimization of metabolic activation for four mutagens in a bacterial,
    fungal and two mammalian cell mutagenesis assays. Carcinogenesis, 4:
    335-342.

    Regional Office for Water and Waste Disposal (1986) [Water report
    1985.] Düsseldorf, Northrhine-Westphalia, pp 24-27 (in German).

    Regional Office for Water and Waste Disposal (1988) [Water report
    1987] Düsseldorf, Northrhine-Westphalia, Table 10, p 29 (in German).

    Regional Office for Water and Waste Disposal (1989) [Water report
    1988.] Düsseldorf, Northrhine-Westphalia, pp 28, i-viii (in German).

    Regional Office for Water and Waste Disposal (1990) [Water report
    1989.] Düsseldorf, Northrhine-Westphalia, pp 25-29 (in German).

    Reichert WL, Eberhart BTL, & Varanasi U (1985) Exposure of two species
    of deposit-feeding amphipods to sediments-associated
    3H-benzo [a]pyrene: Uptake, metabolism and covalent binding to
    tissue macromolecules. Aquat Toxicol, 6: 45.

    Reinhard M, Goodman NL, & Barker JF (1984) Occurrence and distribution
    of organic chemicals in two landfill leachate plumes. Environ Sci
    Technol, 18: 953-961.

    Renwick AG & Drasar BS (1976) Environmental carcinogens and large
    bowel cancer. Nature, 263: 234-235.

    Reuterwall C, Aringer L, Elinder CG, Rannung A, Levin JO, Juringe L, &
    Onfelt A (1991) Assessment of genotoxic exposure in Swedish coke-oven
    work by different methods of biological monitoring. Scand J Work
    Environ Health, 17: 123-132.

    Reznikoff CA, Bertram JS, Brankow DW, & Heidelberger C (1973)
    Quantitative and qualitative studies of chemical transformation of
    cloned C3H mouse embryo cells sensitive to postconfluence inhibition
    of cell division. Cancer Res, 33: 3239-3249.

    Rhee K & Bratzler LJ (1970) Benzo(a)pyrene in smoked meat products. J
    Food Sci, 35: 146-149.

    Rhett RG, Simmers JW, & Lee CR (1988)  Eisenia foetida used as a
    biomonitoring tool to predict the potential bioaccumulation of
    contaminants from contaminated dredged material. In: Edwards CA &
    Neuhauser EF ed. Earthworms in waste and environmental management. The
    Hague, SPB Academic Publishers, pp 321-328.

    Rhoads CP, Smith WE, Cooper NS & Sullivan RD (1954) Early changes in
    the skin or several species including man, after painting with
    carcinogenic materials. Proc Am Assoc Cancer Res, 1: 40.

    Rice JE, Hosted TJ Jr, & LaVoie EJ (1984) Fluoranthene and pyrene
    enhance benzo [a]pyrene-DNA adduct formation  in vivo in mouse skin.
    Cancer Lett, 24: 327-333.

    Rice JE, Coleman DT, Hosted TJ, LaVoie EJ, McCaustland DJ, & Wiley JC
    (1985) Identification of mutagenic metabolites of
    indeno[1,2,3- cd]pyrene formed  in vitro with rat liver enzymes.
    Cancer Res, 45: 5421-5425.

    Rice JE, Hosted TJ Jr, DeFloria MC, LaVoie EJ, Fischer DL, & Wiley JC
    Jr (1986) Tumor-initiating activity of major  in vivo 
    metabolites of indeno[1,2,3- cd]pyrene on mouse skin. Carcinogenesis,
    7: 1761-1764.

    Rice JE, Weyand EH, Geddie NG, DeFloria MC, & LaVoie EJ (1987)
    Identification of tumorigenic metabolites of benzo [j]fluoranthene
    formed  in vivo in mouse skin. Cancer Res, 47: 6166-6170.

    Rice JE, Geddie NG, Defloria MC, & LaVoie EJ (1988a) Structural
    requirements favoring mutagenic activity among methylated pyrenes in
     S. typhimurium. In: Cooke M & Dennis AJ ed. Polynuclear aromatic
    hydrocarbons: A decade of progress. Columbus, Ohio, Battelle Press, pp
    773-785.

    Rice JE, Jordan K, Little P, & Hussain N (1988b) Comparative
    tumor-initiating activity of methylene-bridged and bay-region
    methylated derivatives of benz [a]anthracene and chrysene.
    Carcinogenesis, 9: 2275-2278.

    Rice JE, Weyand EH, Burrill C, & Lavoie EJ (1990) Fluorine probes for
    investigating the mechanism of activation of indeno [1,2,3- cd]pyrene
    to a tumorigenic agent. Carcinogenesis, 11: 1971-1974.

    Riebe-Imre, M, Peiser, D, Emura M, Aufderheide M, Jacob J, Grimmer G,
    & Raab G (1993) Passage-dependent characteristics of PAH-metabolism
    and PAH-induced transformation in airway epithelial cells  in vitro.
    In: Garrigues P & Lamotte M ed. Polycyclic aromatic compounds:
    Synthesis, properties, analytical measurements, occurrence and
    biological effects. Bordeaux, Gordon & Breach Science Publishers, pp
    849-856.

    Riegel B, Wartman WB, Hill WT, Reeb BB, Shubik P, & Stanger DW (1951)
    Delay of methylcholanthrene skin carcinogenesis in mice by
    1,2,5,6-dibenzofluorene. Cancer Res, 11: 301-306.

    Riess MH & Wefers H (1994) [Ecotoxicological evaluation of chlorine
    and phosphorous organics as well as PAH in sediments of Bremen
    waters.] Bremen, Institute for Environmental Chemistry, pp 9-10 (in
    German).

    Rigdon RH & Neal J (1965) Effects of feeding benzo [a]pyrene on
    fertility, embryos, and young mice. J Natl Cancer Inst, 34: 297-305.

    Rigdon RH & Neal J (1966) Gastric carcinomas and pulmonary adenomas in
    mice fed benzo(a)pyrene. Tex Rep Biol Med, 24: 195-207.

    Rigdon RH & Neal J (1969) Relationship of leukemia to lung and stomach
    tumors in mice fed benzo(a)pyrene. Proc Soc Exp Biol Med, 130: 146-
    148.

    Riley RT, Shirazi MA, & Swartz RC (1981) Transport of naphthalene in
    the oyster O  streaedulis. Mar Biol, 63: 325-330

    Rimatori V, Sperduto B, & Iannaccone A (1983) Environmental oil
    aerosol. J Aerosol Sci, 14: 253-256.

    Rippe RM & Pott F (1989) [Carcinogenicity studies into nitro-PAH
    (nitroarenes) in view of their importance in the cancer-inducing
    effects of diesel motor emissions.] In: Environmental Hygiene, Volume
    21. Düsseldorf, Stefan W Albers Verlag, pp 65-89 (Society for Research
    on Air Hygiene and Silicosis,  Medical Institute for Environmental
    Hygiene, Annual Report 1988/1989) (in German).

    Risch HA, Burch JD, Miller AB, Hill GB, Steele R, & Howe GR (1988)
    Occupational factors and the incidence of cancer of the bladder in
    Canada. Br J Ind Med, 45: 361-367.

    Robbins WK, Searl TD, Wasserstrom DH, & Boyer GT (1981) Determination
    of polynuclear aromatic hydrocarbons in wastewater from coal
    liquefaction processes by the gas chromatography-ultraviolet
    spectrometry technique. In: Jackson LP & Wright CC ed. Analysis of
    waters associated with alternative fuel production. Philadelphia,
    Pennsylvania, American Society for Testing and Materials, pp 149-166
    (ASTM STP 720).

    Roberts MH Jr, Hargis WJ Jr, Strobel CJ, & De Lisle PF (1989) Acute
    toxicity of PAH contaminated sediments to the estuarine fish,
     Leiostomus xanthurus. Bull Environ Contam Toxicol, 42: 142-149.

    Robertson IGC, Guthenberg C, Mannervik B, & Jernström B (1986)
    Differences in stereoselectivity and catalytic efficiency of three
    human glutathione transferases in the conjugation of glutathione with
    7b, 8a-dihydroxy-9a,10a-oxy-7,8,9,10-tetrahydrobenzo [a]pyrene.
    Cancer Res, 46: 2220-2224.

    Robinson DE & Mitchell AD (1981) Unscheduled DNA synthesis response of
    human fibroblasts, WI-38 cells, to 20 coded chemicals. In: DeSerres FJ
    & Ashby J ed. Evaluation of short-term tests for carcinogens. Report
    of the international collaborative programme. New York, Elsevier North
    Holland, pp 517-527 (Progress in Mutation Research, Volume 1).

    Robinson JR, Felton JS, Levitt RC, Thorgeirsson SS, & Nebert DW (1975)
    Relationship between 'aromatic hydrocarbon responsiveness' and the
    survival times in mice treated with various drugs and environmental
    compounds. Mol Pharmacol, 11: 850-865.

    Rocchi P, Ferreri AM, Borgia R, & Prodi G (1980) Polycyclic
    hydrocarbons induction of diphtheria toxin-resistant mutants in human
    cells. Carcinogenesis, 1: 765-767.

    Rockette HE & Arena VC (1983) Mortality studies of aluminum reduction
    plant workers: Potroom and carbon department. J Occup Med, 25: 549-
    557.

    Rockette HE & Redmond CK (1985) Selection, follow-up, and analysis in
    the coke oven study. Natl Cancer Inst Monogr, 67: 89-94.

    Roe FJC (1962) Effect of phenanthrene on tumour-initiation by
    3,4-benzpyrene. Br J Cancer, 16: 503-506.

    Roe JC & Grant CA (1964) Test of pyrene and phenanthrene for
    incomplete carcinogenic and anticarcinogenic activity. Br Emp Cancer
    Campaign, 41: 59.

    Rogan EG, Cavalieri EL, Ramakrishna NVS, & Devanesan PD (1993)
    Mechanisms of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene
    activation: Quantitative aspects of the stable and depurination DNA
    adducts obtained from radical cations and diol epoxides. In: Garrigues
    P & Lamotte M ed. Polycyclic aromatic compounds: Synthesis,
    properties, analytical measurements, occurrence and biological
    effects. Bordeaux, Gordon & Breach Science Publishers, pp 733-740.

    Rogerson PF (1988) Organic chemical waste characterization for marine
    disposal of Black Rock Harbor dredged materials. In: Lichtenberg JJ,
    Winter JA, Weber CI, & Fradkin L ed. Chemical and biological
    characterization of municipal sludges, sediments, dredge spoils, and
    drilling muds. Philadelphia, Pennsylvania, American Society for
    Testing and Materials, pp 213-222.

    Roggeband R, Van den Berg PTM, Steenwinkel MJST, Van Delft JHM, Van
    der Wulp CJM, & Baan RA (1994a)  In situ detection of different PAH-
    DNA adducts by means of immunofluorescence microscopy. In: Annual
    report on toxicology 1993/1994. Zeist, TNO Nutrition and Food Research
    Institute, pp 79-80.

    Roggeband R, Wolterbeek APM, Van den Berg PTM, & Baan RA (1994b) DNA
    adducts in hamster and rat tracheas exposed to benzo(a)pyrene
     in vitro. Toxicol Lett, 72: 105-111.

    Rojas M, Alexandrov K, Auburtin G, Wastiaux-Denamur A, Mayer L, Mahieu
    B, Sebastien P, & Bartsch H (1995) Anti-benzo(a)pyrene diolepoxide-DNA
    adduct levels in pheripheral mononuclear cells from coke oven workers
    and the enhancing effect of smoking. Carcinogenesis, 16: 1373-1376.

    Roller M, Kamino K, & Rosenbruch M (1992) Carcinogenicity testing of
    bladder carcinogens and other organic compounds by the intraperitoneal
    and intravesical route. In: Seemayer NH & Hadnagy W ed. Environmental
    hygiene. III. Berlin, Springer-Verlag, pp 95-98.

    Ronneberg A & Andersen A (1995) Mortality and cancer morbidity in
    workers from an aluminum smelter with prebaked carbon anodes. Part II:
    Cancer morbidity. Occup Environ Med, 52: 250-254.

    Ronneberg A & Langmark F (1992) Epidemiologic evidence of cancer in
    aluminum reduction plant workers. Am J Ind Med, 22: 573-590.

    Rosenkranz HS & Poirier LA (1979) Evaluation of the mutagenicity and
    DNA-modifying activity of carcinogens and noncarcinogens in microbial
    systems. J Natl Cancer Inst, 62: 873-891.

    Ross J, Nelson G, Erexson G, Kligerman A, Earley K, Gupta RC, & Nesnow
    S (1991) DNA adducts in rat lung, liver, and peripheral blood
    lymphocytes produced by ip administration of benzo [a]pyrene
    metabolites and derivatives. Carcinogenesis, 12: 1953-1955.

    Ross JA, Nelson GB, Holden KL, Kligerman AD, Erexson GL, Bryant MF,
    Earley K, Beach AC, Gupta RC, & Nesnow S (1992) DNA adducts and
    induction of sister chromatid exchanges in the rat following
    benzo (b)fluoranthene administration. Carcinogenesis, 13: 1731-1734.

    Ross JA, Nelson GB, Wilson KH, Rabinowitz JR, Galati A, Stoner GD,
    Nesnow S, & Mass MJ (1995) Adenomas induced by polycyclic aromatic
    hydrocarbons in strain A/J mouse lung correlate with time-integrated
    DNA adduct levels. Cancer Res, 55: 1039-1044.

    Rossi SS & Neff JM (1978) Toxicity of polynuclear aromatic
    hydrocarbons to the polychaete  Neanthes arenaceodentata. Mar Pollut
    Bull, 9: 220-223.

    Rossman TG, Molina M, Meyer L, Boone P, Klein CB, Wang Z, Li F, Lin
    WC, & Kinney PL (1991) Performance of 133 compounds in the lambda
    prophage induction endpoint of the microscreen assay and a comparison
    with  Salmonella typhimurium mutagenicity and rodent carcinogenicity
    assays. Mutat Res, 260: 349-367.

    Rostad CE & Pereira WE (1987) Creosote compounds in snails obtained
    from Pensacola Bay, Florida, near an onshore hazardous-waste site.
    Chemosphere, 16: 2397-2404.

    Roszinsky-Köcher G, Basler A, & Röhrborn G (1979) Mutagenicity of
    polycyclic hydrocarbons. V. Induction of sister-chromatid exchanges
     in vivo. Mutat Res, 66: 65-67.

    Rothman N, Poirier MC, Haas RA, Correa-Villasenor A, Ford P, Hansen
    JA, O'Toole T, & Strickland PT (1993) Association of PAH-DNA adducts
    in peripheral white blood cells with dietary exposure to polyaromatic
    hydrocarbons. Environ Health Perspect, 99: 265-267.

    Ruepert C, Grinwis A, & Govers H (1985) Prediction of partition
    coefficients of unsubstituted polycyclic aromatic hydrocarbons from
    C18 chromatographic and structural properties. Chemosphere, 14: 279-
    291

    Rundell JO, Guntakatta M, & Matthews EJ (1983) Criterion development
    for the application of Balb/c-3T3 cells to routine testing for
    chemical carcinogenic potential. In: Waters MD, Sandhu SS, Lewtas J,
    Claxton L, Chernoff N, & Nesnow S ed. Short-term bioassays in the
    analysis of complex environmental mixtures. III. New York, Plenum
    Press, pp 309-324.

    Russell H (1947) An unsuccessful attempt to induce gliomata in rabbits
    with cholanthrene. J Pathol Bacteriol, 59: 481-483.

    Russell LB (1977) Validation of the  in vivo somatic mutation method
    in the mouse as a prescreen for germinal point mutations. Arch
    Toxicol, 38: 75-85.

    Russell P, Yamada T, Xu GT, Garland D, & Zigler JS Jr (1991) Effects
    of naphthalene metabolites on cultured cells from eye lens. Free
    Radicals Biol Med, 10: 255-261.

    Ryan PA & Cohen Y (1986) Multimedia transport of particle-bound
    organics: Benzo [a]pyrene test case. Chemosphere, 15: 21-47.

    Saber A, Jarosz J, Martin-Bouyer M, Paturel L, & Vial M (1987)
    Analysis of polycyclic aromatic hydrocarbons in lacustral sediments by
    high resolution Shpol'skii spectrofluori-metry at 10 K. Int J Environ
    Anal Chem, 28: 171-184.

    Sabourin TD & Tullis RE (1981) Effect of three aromatic hydrocarbons
    on respiration and heart rates of the mussel,
     Mytilus californianus. Bull Environ Contam Toxicol, 26: 729-736.

    Saed T, Al-Yakoob S, Al-Hashash, & Al-Bahlou M (1995) Preliminary
    exposure assessment for Kuwaiti consumers to polycyclic aromatic
    hydrocarbons in seafood. Environ Int, 21: 255-263.

    Saffiotti U, Cefis F, & Kolb LH (1968) A method for experimental
    induction of bronchogenic carcinoma. Cancer Res, 28: 104-113.

    Saffiotti U, Montesano R, Sellkumar AR, & Kaufman DG (1972)
    Respiratory tract carcinogenesis induced in hamsters by different dose
    levels of benzo [a]pyrene and ferric oxide. J Natl Cancer Inst, 49:
    1199-1204.

    Sagredos AN, Sinha-Roy D, & Thomas A (1988) [Determination, sources
    and composition of polycyclic aromatic hydrocarbons in oils and fats.]
    Fat Sci Technol, 90: 76-81 (in German).

    Saguem S, Mispelter J, Perin-Roussel O, Lhoste JM, & Zajdela F (1983a)
    Multi-step metabolism of the carcinogen dibenzo [a,e]fluoranthene. I.
    Identification of the metabolites from rat microsomes. Carcinogenesis,
    4: 827-835.

    Saguem S, Perin-Roussel O, Mispelter J, Lhoste JM, & Zajdela F (1983b)
    Multi-step metabolism of the carcinogen dibenzo [a,e]fluoranthene.
    II. Metabolism pathways. Carcinogenesis, 4: 837-842.

    Sakai M, Yoshida D, & Mizusaki S (1985) Mutagenicity of polycyclic
    hydrocarbons and quinones on  Salmonella thyphimurium TA97. Mutat
    Res, 156: 61-67.

    Salagovic J, Kalina I, & Dubayová K (1995) Induction of single strand
    DNA breaks in workers professionally exposed to polycyclic aromatic
    hydrocarbons. Neoplasma, 42: 115-118.

    Salaman MH & Roe FJC (1956) Further tests for tumour-initiating
    activity: N,N-Di-(2-chloroethyl)-p-aminophenylbutyric acid (CB1348) as
    an initiator of skin tumor formation in the mouse. Br J Cancer, 10:
    363-378.

    Salamone MF (1981) Toxicity of 41 carcinogens and noncarcinogenic
    analogs. In: De Serres FJ & Ashby J ed. Evaluation of short-term tests
    for carcinogens. Report of the international collaborative programme.
    Amsterdam, Elsevier North-Holland, pp 682-685 (Progress in Mutation
    Research, Volume 1).

    Salamone MF, Heddle JA, & Katz M (1979) The mutagenic activity of
    thirty polycyclic aromatic hydrocarbons (PAH) an oxides in urban
    airborne particulates. Environ Int, 2: 37-43.

    Salamone MF, Heddle JA, & Katz M (1981) Mutagenic activity of 41
    compounds in the  in vivo micronucleus assay. In: De Serres FJ &
    Ashby J ed. Evaluation of short-term tests for carcinogens. Report of
    the international collaborative programme. Amsterdam, Elsevier
    North-Holland, pp 686-697 (Progress in Mutation Research,Volume 1).

    Salomaa S, Tuominen J, & Skyttä E (1988) Genotoxicity and PAC analysis
    of particulate and vapour phases of environmental tobacco smoke. Mutat
    Res, 204: 173-183.

    Sanders CL, Skinner D, & Gelman RA (1986) Percutaneous absorption of
    7,10 14C-benzo(a)pyrene and 7,12 14C-dimethylbenz(a)anthracene in
    mice. J Environ Pathol Toxicol Oncol, 7: 25-34.

    Sandmeyer EE (1981) Aromatic hydrocarbons. In: Clayton GD & Clayton FE
    ed. Patty's industrial hygiene and toxicology, 3rd rev Ed. New York,
    John Wiley & Sons, pp 3333-3339.

    Santella RM (1993) Human DNA and protein adduct dosimetry. Proc Am
    Assoc Cancer Res, 34: 604-605.

    Santella RM, Hemminki K, Tang DL, Paik M, Ottman R, Young TL, Savela
    K, Vodickova L, Dickey C, Whyatt R, & Perera FP (1993) Polycyclic
    aromatic hydrocarbon-DNA adducts in white blood cells and urinary
    1-hydroxypyrene in foundry workers. Cancer Epidemiol Biomarkers Prev,
    2: 59-62.

    Santella RM, Nunes MG, Blaskovic R, Perera FP, Tang D, Beachman A, Lin
    JH, & DeLeo VA (1994) Quantification of polycyclic aromatic
    hydrocarbons, 1-hydroxypyrene, and mutagenicity in urine of coal
    tar-treated psoriasis patients and untreated volunteers. Cancer
    Epidemiol Biomarkers Prev, 3: 137-140.

    Santella RM, Perera FP, Young TL, Zhang YJ, Chiamprasert S, Tang D,
    Wang LW, Beachman A, Lin JH, & DeLeo VA (1995) Polycyclic aromatic
    hydrocarbon-DNA and protein adducts in coar tar treated patients and
    controls and their relationship to glutathione S-transferase genotype.
    Mutat Res, 334: 117-124.

    Santodonato J, Basu D, & Howard PH (1980) Multimedia human exposure
    and carcinogenic risk assessment for environmental PAH. In: Bjorseth A
    & Dennis AJ ed. Polynuclear aromatic hydrocarbons: Chemistry and
    biological effects. Columbus, Ohio, Battelle Press, 435-454.

    Santodonato J, Howard P, & Basu D (1981) In: Lee SD & Grant L ed.
    Health and ecological assessment of polynuclear aromatic hydrocarbons.
    Park Forest South, Illinois, Pathotox Publishers, 364 pp.

    Sardella DJ, Boger E, & Ghoshal PK (1981) Active sites in hexacyclic
    carcinogens probed by the fluorine substitution methodology. Columbus,
    Ohio, Battelle Press, pp 529-538.

    Savas U, Bhattacharyya KK, Christou M, Alexander DL, & Jefcoate CR
    (1994) Mouse cytochrome P450EF, representative of a new 1B subfamily
    of cytochrome P450s. Cloning, sequence determination, and tissue
    expression. J Biol Chem, 269: 14905-14911.

    Savela K & Hemminki K (1991) DNA adducts in lymphocytes and
    granulocytes of smokers and nonsmokers detected by the
    32P-postlabelling assay. Carcinogenesis, 12: 503-508.

    Savino JF & Tanabe LL (1989) Sublethal effects of phenanthrene,
    nicotine, and pinane on  Daphnia pulex. Bull Environ Contam Toxicol,
    42: 778-784.

    Sawicki JT, Moschel RC, & Dipple A (1983) Involvement of both
     syn and  antidihydrodiol-epoxides in the binding of
    7,12-dimethylbenz [a]anthracene to DNA in mouse embryo cell cultures.
    Cancer Res, 43: 3213-3218.

    Sax NI & Lewis JR Sr (1984) Dangerous properties of industrial
    materials, 7th Ed. New York, Van Nostrand Reinhold Co, pp 2451-2452.

    Saxton WL, Newton RT, Rohrberg J, Sutton J, & Johnson LJ (1993)
    Polycyclic aromatic hydrocarbons in seafood from the Gulf of Alaska
    following a major crude oil spill. Bull Environ Contam Toxicol, 51:
    515-522.

    Schafer EW Jr, Bowles WA Jr, & Hurlbut J (1983) The acute oral
    toxicity, repellency, and hazard potential of 998 chemicals to one or
    more species of wild and domestic birds. Arch Environ Contam Toxicol,
    12: 355-381.

    Schaller KH, Angerer J, & Hausmann N (1993) The determination of
    1-hydroxypyrene in urine as a tool for the biological monitoring of
    PAH-exposed persons. Polycyclic Aromat Compd, 3 (suppl): 1023-1030.

    Scheepers PTJ & Bos RP (1992) Combustion of diesel fuel from a
    toxicological perspective 1. Origin of incomplete combustion products.
    Int Arch Occup Environ Health, 64: 149-161.

    Scherer G, Conze C, Von Meyerinck L, Sorsa M, & Adlkofer F (1990)
    Importance of exposure to gaseous and particulate phase components of
    tobacco smoke in active and passive smokers. Int Arch Occup Environ
    Health, 62: 459-466.

    Schimberg RW, Toivonen E, & Tossavainen A (1981) [Polycyclic aromatic
    hydrocarbons and other hazardous agents in foundry moulding sand with
    various hydrocarbon carriers.] Staub-Reinhalt Luft, 41: 221-224 (in
    German).

    Schlede E, Kuntzman R, Haber S, & Conney AH (1970a) Effect of enzyme
    induction on the metabolism and tissue distribution of
    benzo [a]pyrene. Cancer Res, 30: 2893-2897.

    Schlede E, Kuntzman R, & Conney AH (1970b) Stimulatory effect of
    benzo [a]pyrene and phenobarbital pretreatment on the biliary
    excretion of benzo [a]pyrene metabolites in the rat. Cancer Res, 30:
    2898-2904.

    Schmähl D (1955) [Testing of naphthalene and anthracene for
    carcinogenic effects in rats.] Z Krebsforsch, 60: 697-710 (in German).

    Schmähl D, Schmidt KG, & Habs M (1977) Syncarcinogenic action of
    polycyclic hydrocarbons in automobile exhaust gas condensates. In: Air
    pollution and cancer in man. Lyon, International Agency for Research
    on Cancer, pp 53-59 (IARC Scientific Publications No. 16).

    Schmeltz I, Tosk J, Hilfrich J, Hirota N, Hoffmann D, & Wynder EL
    (1978) Bioassays of naphthalene and alkylnaphthalenes for
    co-carcinogenic activity. Relation to tobacco carcinogenesis. In:
    Jones PW & Freudenthal RI ed. Carcinogenesis, Volume 3: Polynuclear
    aromatic hydrocarbons. New York, Raven Press, pp 47-60.

    Schmidt H (1992) [Emissions of polycyclic aromatic hydrocarbons in the
    processsing of bitumen and polymer bitumen street sections.] Bitumen,
    54: 50-53 (in German).

    Schmoldt A, Jacob J, & Grimmer G (1981) Dose-dependent induction of
    rat liver microsomal aryl hydrocarbon monooxygenase by
    benzo [k]fluoranthene. Cancer Lett, 13: 249-257.

    Schnizlein CT, Munson AE, & Rhoades RA (1987) Immunomodulation of
    local and systemic immunity after subchronic pulmonary exposure of
    mice to benzo(a)pyrene. Int J Immunopharmacol, 9: 99-106.

    Schoeny R & Warshawsky D (1983) Mutagenicity of benzo(a)pyrene
    metabolites generated on the isolated perfused lung following
    particulate exposure. Teratog Carcinog Mutag, 151: 151-162.

    Schoeny R, Cody T, Radike M, & Warshawsky D (1985) Mutagenicity of
    algal metabolites of benzo(a)pyrene for  Salmonella typhimurium. 
    Environ Mutag, 7: 839-855.

    Schoeny R, Cody T, Warshawsky D, & Radike M. (1988) Metabolism of
    mutagenic polycyclic hydrocarbons by photosynthetic algal species.
    Mutat Res, 197: 289-302.

    Schoeny R, Lewtas J, McClure P, & Stiteler W (1994) Risk assessment
    for polycyclic aromatic hydrocarbons: Options revisited. Dallas,
    Texas, Society of Toxicology.

    Schoket B, Hewer A, Grover PL, & Phillips DH (1989) 32P-Postlabelling
    analysis of DNA adducts in the skin of mice treated with petrol and
    diesel engine lubricating oils and exhaust condensates.
    Carcinogenesis, 10: 1485-1490.

    Schoket B, Horkay I, Kósa A, Páldeák L, Hewer A, Grover PL, & Phillips
    DH (1990) Formation of DNA adducts in the skin of psoriasis patients,
    in human skin in organ culture, and in mouse skin and lung following
    topical application of coal-tar and juniper tar. J Invest Dermatol,
    94: 241-246.

    Schoket B, Poirier MC, & Vincze I (1995) Biomonitoring of genotoxic
    exposure in aluminium plant workers by determination of DNA adducts in
    human peripheral blood lymphocytes. Sci Total Environ, 163: 153-163.

    van Schooten FJ, Hillebrandt MJX, van Leeuwen FE, van Zandwijk N,
    Janssen HM, den Engelse L, & Kriek E (1992) Polycyclic aromatic
    hydrocarbon-DNA adducts in white blood cells from lung cancer
    patients: No correlation with adduct levels in lung. Carcinogenesis,
    13: 987-993.

    van Schooten FJ, Moonen EJC, Rhijnsburger E, van Algen B, Thijssen
    HHW, & Kleinjans JCS (1994) Dermal uptake of polycyclic aromatic
    hydrocarbons after hairwash with coal-tar shampoo. Lancet, 344: 1505-
    1506.

    van Schooten FJ, Jongeneelen FJ, Hillebrand MJ, van Leeuwen FE, de
    Looff AJ, Dijkmans AP, van Rooij JGM, den Engelse L, & Kriek E (1995)
    Polycyclic aromatic hydrocarbon-DNA adducts in white blood cell DNA
    and 1-hydroxypyrene in the urine from aluminium workers: Relation with
    job category and synergistic effect of smoking. Cancer Epidemiol
    Biomarkers Prev, 4: 69-77.

    Schrimpff E (1983) [Forests dying from high concentrations of
    pollutants in fog.] Staub Reinhalt Luft, 43: 240 (in German).

    Schrimpff E, Thomas W, & Herrmann R (1979) Regional patterns of
    contaminants (PAH, pesticides and trace metals) in snow of northeast
    Bavaria and their relationship to human influence and orographic
    effects. Water Air Soil Pollut, 11: 481-497.

    Schuetzle D (1983) Sampling of vehicle emissions for chemical analysis
    and biological testing. Environ Health Perspectives, 47: 65-80.

    Schuetzle D & Frazier JA (1986) Factors influencing the emission of
    vapor and particulate phase components from diesel engines. In:
    Ishinishi N, Koizumi A, McClellan RO, & Stöber W ed. Carcinogenic and
    mutagenic effects of diesel engine exhaust. Amsterdam, Elsevier
    Science Publishers, pp 41-63.

    Schunk W (1979) [Relationship between exposure to polycyclic
    hydrocarbons and the increased occurrence of cancer cases in two
    chemical companies in Thüringen.] Z Ärztl Fortbild, 73: 84-88 (in
    German).

    Schürch O & Winterstein A (1935) [The cancer inducing effect of
    aromatic hydrocarbons.] Z Physiol Chem, 236: 79-91 (in German).

    Schuyer J, Blom L, & Van Krevelen DW (1953) The molar refraction of
    condensed aromatic compounds. Trans Faraday Soc, 49: 1391-1401.

    Schwarz FP (1977) Determination of temperature dependence of
    solubilities of polycyclic aromatic hydrocarbons in aqueous solutions
    by a fluorescence method. J Chem Eng Data, 22: 273-277.

    Scribner JO (1973) Brief communication: Tumor initiation by apparently
    noncarcinogenic polycyclic aromatic hydrocarbons J Natl Cancer Inst,
    50: 1717-1719.

    Sega GA (1979) Unscheduled DNA synthesis (DNA repair) in the germ
    cells of male mice. Its role in the study of mammalian mutagenesis.
    Genetics, 92: 49-58.

    Segerbäck D & Vodicka P (1993) Recoveries of DNA adducts of polycyclic
    aromatic hydrocarbons in the 32P-postlabelling assay. Carcinogenesis,
    14: 2463-2469.

    Seifert B, Ullrich D, & Schmahl HJ (1983) Occurrence of carcinogenic
    organic substances in kitchen air. In: Proceedings of VIth World
    Congress on Air Quality, Paris, 16-20 May 1983. Paris, SEFIC, pp 177-
    179 (Poster presentation).

    Seifert B, Ullrich D, & Liu ZF (1986) [Inorganic and organic air
    pollutants at a street intersection in West Berlin. Reports of Society
    for Water, Soil, and Air) Schriftenreihe Ver WaBoLu, 67: 211-222 (in
    German).

    Selgrade MK, Daniels MJ, Burleson GR, Lauer LD, & Dean JH (1988)
    Effects of 7,12-dimethylbenz [a]anthracene, benzo [a]pyrene and
    cyclosporin A on murine cytomegalo-virus infections: Studies of
    resistance mechanisms. Int J Immunopharmacol,10: 811-818.

    Selkirk JK, Croy RG, Whitlock JP Jr, & Gelboin HV (1975)  In 
     vitro metabolism of benzo [a]pyrene by human liver microsomes and
    lymphocytes. Cancer Res, 35: 3651-3655.

    Sellakumar A & Shubik P (1974) Carcinogenicity of different polycyclic
    hydrocarbons in the respiratory tract of hamsters. J Natl Cancer Inst,
    53: 1713-1719.

    Serth RW & Hughes TW (1980) Polycyclic organic matter (POM) and trace
    element contents of carbon black vent gas. Environ Sci Technol, 14:
    298-301.

    Shabad LM & Dikun PP (1959) Atmospheric pollution by the carcinogenic
    hydrocarbon 3,4-benzpyrene. Leningrad, Medgiz, 228 pp.

    Sharpe CR, Rochon JE, Adam JM, & Siussa S (1989) Case-control study of
    hydrocarbon exposures in patients with renal cell carcinoma. Can Med
    Assoc J, 140: 1309-1318.

    Shaw GR & Connell DW (1994) Prediction and monitoring of the
    carcinogenicity of polycyclic aromatic compounds (PACs). In: Ware GW
    ed. Reviews of environmental contamination and toxicology. Berlin,
    Springer-Verlag, pp 1-62.

    Shay H, Aegerter EA, Gruenstein M, & Komarov SA (1949) Development of
    adenocarcinoma of the breast in the Wistar rat following the gastric
    instillation of methylcholanthrene. J Natl Cancer Inst, 10: 255-266.

    Shear MJ (1938) Studies in carcinogenesis. V. Methyl derivatives of
    1:2-benzanthracene. Am J Cancer, 33: 499-537.

    Shear MJ & Leiter J (1941) Studies in carcinogenesis. XVI. Production
    of subcutaneous tumors in mice by miscellaneous polycyclic compounds.
    J Natl Cancer Inst, 2: 241-259.

    Shen Z, Wells RL, & Elkind MM (1994) Enhanced cytochrome P450
     (Cyp1b1) expression, aryl hydrocarbon hydroxylase activity,
    cytotoxicity, and transformation of C3H10T1/2 cells by
    dimethylbenz (a)anthracene in conditioned medium. Cancer Res, 54:
    4052-4056.

    Shendrikova IA & Aleksandrov VA (1974) Comparative characteristics of
    penetration of polycyclic hydrocarbons through the placenta in the
    fetus in rats. Bull Exp Biol Med, 77: 77-79.

    Shendrikova IA, Ivanov-Golitsyn MM, Anisimov YN, & Likhachev AYa
    (1973) [Dynamics of transplacental penetration of
    7,12-dimethylbenz [a]anthracene in mice.] Vopr Onkol, 19: 75-79 (in
    Russian with English translation).

    Shendrikova IA, Ivanov-Golitsyn MN, & Likjachev AYa (1974) [The
    transplacental penetration of benzo [a]pyrene in mice.] Vopr Onkol,
    20: 53-56 (in Russian with English abstract).

    Sherson D & Iversen E (1986) Mortality among foundry workers in
    Denmark due to cancer and respiratory and cardiovascular diseases.
    Cancer Res Monogr, 2: 403-414.

    Sherson D, Sabro P, Sigsgaard T, Johansen F, & Autrup H (1990)
    Biological monitoring of foundry workers exposed to polycylic aromatic
    hydrocarbons. Br J Ind Med, 47: 448-453.

    Sherson D, Sigsgaard T, Overgaard E, Luft S, Poulsen H, & Jongenellen
    FJ (1992) Interaction of smoking, PAH uptake and cytochrome P450IA2
    activity among foundry workers. Br J Ind Med, 49:197-202.

    Shiaris MP & Jambard-Sweet D (1986) Polycyclic aromatic hydrocarbons
    in surficial sediments of Boston Harbour, Massachusetts, USA. Mar
    Pollut Bull, 17: 469-472.

    Shimada T, Martin MV, Pruess-Schwartz D, Marnett LJ, & Guengerich FP
    (1989) Roles of individual human cytochrome P450 enzymes in the
    bioactivation of benzo (a)pyrene,
    7,8-dihydroxy-7,8-dihydrobenzo (a)pyrene, and other dihydrodiol
    derivatives of polycyclic aromatic hydrocarbons. Cancer Res, 49: 6304-
    6312.

    Shimada H, Satake S, Itoh S, Hattori C, Hayashi M, & Ishidate M Jr
    (1991) Multiple dosing effects of benzo [a]pyrene in the mouse bone
    marrow micronucleus test. Mutat Res, 252: 107.

    Shimada H, Suzuki H, Itoh S, Hattori C, Matsuura Y, Tada S, & Watanabe
    C (1992) The micronucleus test of benzo(a)pyrene with mouse and rat
    peripheral blood reticulocytes. Mutat Res, 278:165-168.

    Shimkin MB & Stoner GD (1975) Lung tumours in mice: Application to
    carcinogenesis bioassay. In: Klein G & Weinhouse S ed. Advances in
    cancer research, Volume 1. New York, Raven Press, pp 1-58.

    Shopp GM, White KL Jr, Holsapple MP, Barnes DW, Duke SS, Anderson AC,
    Condie LW Jr, Hayes JR, & Borzelleca JF (1984) Naphthalene toxicity in
    CD-1 mice: General toxicology and immunotoxicology. Fundam Appl
    Toxicol, 4: 406-419.

    Shou M, Korzekwa KR, Crespi CL, Gonzalez FJ, & Gelboin HV (1994) The
    role of 12 cDNA-expressed human, rodent, and rabbit cytochromes P450
    in the metabolism of benzo [a]pyrene  trans-7,8-dihydrodiol. Mol
    Carcinog, 1: 159-168.

    Shubik P & Della Porta G (1957) Carcinogenesis and acute intoxication
    with large doses of polycyclic hydrocarbons. Am Med Assoc Arch Pathol,
    64: 691-703.

    Shubik P, Pietra G, & Della Porta G (1960) Studies of skin
    carcinogenesis in the Syrian golden hamster. Cancer Res, 20: 100-105.

    Shum S, Jensen NM, & Nebert DW (1979) The murine Ah locus:
     In utero toxicity and teratogenesis with genetic differences in
    benzo [a]pyrene metabolism. Teratology, 20: 365-376.

    Siebert D, Marquardt H, Friesel H, & Hecker E (1981) Polycyclic
    aromatic hydrocarbons and possible metabolites: Convertogenic activity
    in yeast and tumor initiating activity in mouse skin. J Cancer Res
    Clin Oncol, 102: 127-139.

    Simmon VF (1979)  In vitro mutagenicity assays of chemical
    carcinogens and related compounds with  Salmonella typhimurium. 
    J Natl Cancer Inst, 62: 893-899.

    Simmon VF, Rosenkranz HS, Zeiger E, & Poirier LA (1979) Mutagenic
    activity of chemical carcinogens and related compounds in the
    intraperitoneal host-mediated assay. J Natl Cancer Inst, 62: 911-918.

    Simó R, Colom-Altés M, Grimalt JO, & Albaigés J (1991) Background
    levels of atmospheric hydrocarbons, sulfate and nitrate over the
    western Mediterranean. Atmos Environ, 25A: 1463-1471.

    Simoneit BRT, Sheng G, Chen X, Fu J, Zhang J, & Xu Y (1991) Molecular
    marker study of extractable organic matter in aerosols from urban
    areas of China. Atmos Environ, 25: 2111-2130.

    Sims P (1959) Metabolism of polycyclic compounds. 14. The conversion
    of naphthalene into compounds related to
     trans-1:2-dihydro-1:2-dihydroxynaphthalene by rabbits. Biochem J,
    73: 389-395.

    Sims P (1962) Metabolism of polycyclic compounds. 19. The metabolism
    of phenanthrene in rabbits and rats: Phenols and sulphuric esters.
    Biochem J, 84: 558-563.

    Sims P (1964) Metabolism of polycyclic compounds. 25. The metabolism
    of anthracene and some related compounds in rats. Biochem J, 92: 621-
    631.

    Sims P & Grover PL (1974) Epoxides in polycyclic aromatic hydrocarbon
    metabolism and carcinogenesis. Adv Cancer Res, 20: 165-274.

    Sims P & Grover PL (1981) Involvement of dihydrodiols and diol
    epoxides in the metabolic activation of polycyclic hydrocarbons other
    than benzo [a]pyrene. In: Gelboin HV & Ts'o POP ed. Polycyclic
    hydrocarbons and cancer, Volume 3. New York, Academic Press, pp 117-
    181.

    Sims RC & Overcash MR (1983) Fate of polynuclear aromatic compounds
    (PNAs) in soil plant systems. Res Rev, 88: 1-67.

    Sipal Z, Ahlenius T, Bergstrand A, Rodriquez L, & Jakobsson SW (1979)
    Oxidative biotransformation of benzo [a]pyrene by human lung
    microsomal fractions prepared from surgical specimens. Xenobiotica, 9:
    633-645.

    Sirianni SR & Huang CC (1978) Sister chromatid exchange induced by
    promutagens/carcinogens in Chinese hamster cells cultured in diffusion
    chambers in mice. Proc Soc Exp Biol Med, 158: 269-274.

    Sirota GR & Uthe JF (1981) Polynuclear aromatic hydrocarbon
    contamination in marine shellfish. In: Cooke M & Dennis AJ ed.
    Polynuclear aromatic hydrocarbons: Chemical analysis and biological
    fate. Columbus, Ohio, Battelle Press, pp 329-341.

    Sirota R, Uthe JF, Sreedharan A, Matheson R, Musial J, & Hamilton K
    (1983) Polynuclear aromatic hydrocarbons in lobster  (Homarus 
     americanus) and sediments in the vicinity of a coking facility. In:
    Cooke M & Dennis AJ ed. Polynuclear aromatic hydrocarbons: Formation,
    metabolism and measurement. Columbus, Ohio, Battelle Press, pp 1123-
    1136.

    Sivarajah K, Mukhtar H, & Eling T (1979) Arachidonic acid-dependent
    metabolism of (+) trans-7,8-dihydroxy-7,8-dihydrobenzo [a]pyrene
    (BP-7,8 diol) to 7,10/8,9 tetrols. FEBS Lett, 106: 17-20.

    Skopek TR & Thilly WG (1983) Rate of induced forward mutation at 3
    genetic loci in  Salmonella typhimurium. Mutat Res, 108: 45-56.

    Skopek TR, Liber HL, Kaden DA, Hites RA, & Thilly WG (1979) Mutation
    of human cells by kerosene soot. J Natl Cancer Inst, 63: 309-312.

    Slaga TJ, Hubermann E, Selkirk JK, Harvey RG, & Bracken WM (1978)
    Carcinogenicity and mutagenicity of benz(a)anthracene diols and
    diol-epoxides. Cancer Res, 38: 1699-1704.

    Slaga TJ, Jecker L, Bracken WM, & Weeks CE (1979) The effects of weak
    or noncarcinogenic polycyclic hydrocarbons on
    7,12-dimethylbenz [a]anthracene and benzo [a]pyrene skin
    tumor-initiation. Cancer Lett, 7: 51-59.

    Slaga TJ, Gleason GL, Mills C, Ewald L, Fu PP, Lee HM, & Harvey RG
    (1980) Comparison of the tumour-initiating activities of dihydrodiols
    and diol-epoxides of various polycyclic aromatic hydrocarbons. Cancer
    Res, 40: 1981-1984.

    Slaga TJ, Iyer RP, Lyga W, Secrist A III, Daub GH, & Harvey RG (1981)
    Comparison of the skin tumor-initiating activities of dihydrodiols,
    diol-epoxides, and methylated derivatives of various polycyclic
    aromatic hydrocarbons. In: Cooke M & Dennis AJ ed. Polynuclear
    aromatic hydrocarbons: Chemical analysis and biological fate.
    Columbus, Ohio, Battelle Press, pp 753-769.

    Slooff W, Janus JA, Matthijsen AJCM, Montizaan GK, & Ros JPM (1989)
    Integrated criteria document on PAHs (Report No. 758474011).
    Bilthoven, National Institute of Public Health and Environmental
    Protection, pp 15-36.

    Smith RL & Hargreaves BR (1983) A simple toxicity apparatus for
    continuous flow with small volumes: Demonstration with mysids and
    naphthalene. Bull Environ Contam Toxicol, 30: 406-412.

    Smith SR, Tanaka J, Futoma DJ, & Smith TE (1981) Sampling and
    preconcentration methods for the analysis of polycyclic aromatic
    hydrocarbons in water systems. CRC Crit Rev Anal Chem, 10: 375-425.

    Smith KR, Aggarwal AL, & Dave RM (1983) Air pollution and rural
    biomass fuels in developing countries: A pilot village study in India
    and implications for research and policy. Atmos Environ, 17: 2343-
    2362.

    Smith JD, Bagg J, & Bycroft BM (1984) Polycyclic aromatic hydrocarbons
    in the clam  Tridacna maxima from the Great Barrier Reef, Australia.
    Environ Sci Technol, 18: 353-358.

    Smith JD, Bagg J, & Sin YO (1987) Aromatic hydrocarbons in seawater,
    sediments and clams from Green Island, Great Barrier Reef, Australia.
    Aust J Mar Freshwater Res, 38: 501-510.

    Smith S, Savino J, & Blouin M (1988) Acute toxicity to  Daphnia 
     pulex of six classes of chemical compounds potentially hazardous to
    Great Lakes aquatic biota. J Great Lakes Res, 14: 394-404.

    Smith-Sonneborn J (1983) Use of a ciliated protozoan as a model system
    to detect toxic and carcinogenic agents. In: Kolber AR, Wong TK, Grant
    LD, DeWoskin RS, & Hughes TJ ed.  In vitro toxicity testing of
    environmental agents: Current and future possibilities. Part A: Survey
    of test systems. New York, Plenum Press, pp 113-137.
    Smyth HF, Carpenter CP, Weil CS, Pozzani UC, & Striegel JA (1962)
    Range-finding toxicity data: List VI. Ind Hyg J, March-April: 95-107.

    Snell KC & Stewart HL (1962) Pulmonary adenomatosis induced in DBA/2
    mice by oral administration of dibenz [a,h]anthracene. J Natl Cancer
    Inst, 28: 1043-1049.

    Snider EH & Manning FS (1982) A survey of pollutant emission levels in
    wastewaters and residuals from the petroleum refining industry.
    Environ Int, 7: 237-258.

    Society of German Chemists (Advisory Committee on Existing Chemicals
    of Environ-mental Relevance) (1989) [Naphthalene.] Weinheim, VCH
    Verlagsgesellschaft, 155 pp (Report No. 39) (in German).

    Society of German Engineers (1989) Emission measurement. Measurement
    of polycyclic aromatic hydrocarbons (PAH): Measurement of PAH in the
    exhaust gas from gasoline and diesel engines of passenger cars. Gas
    chromatographic determination. Düsseldorf, Commission for Air Quality
    part 1, 27 pp (VDI Report No. 3872).

    Solt DB, Polverini PJ, & Calderon L (1987) Carcinogenic response of
    hamster buccal pouch epithelium to 4 polycyclic aromatic hydrocarbons.
    J Oral Pathol, 16: 294-302.

    Sonnefeld WJ, Zoller WH, & May WE (1983) Dynamic coupled-column liquid
    chromatographic determination of ambient temperature vapor pressures
    of polynuclear aromatic hydrocarbons. Anal Chem, 55: 275-280.

    Sorahan T & Cooke MA (1989) Cancer mortality in a cohort of United
    Kingdom steel foundry workers: 1946-1985. Br J Ind Med, 46: 74-81.

    Sorrell K, Brass HJ, & Reding R (1980) A review of occurrences and
    treatment of polynuclear aromatic hydrocarbons in water. Environ Int,
    4: 245-254.

    Southworth GR (1977) Transport and tranformations of anthracene in
    natural waters. In: Marking LL & Kimerle RA ed. Aquatic toxicology.
    Philadelphia, Pennsylvania, American Society for Testing and
    Materials, pp 359-380 (ASTM ATP 667).

    Southworth GR (1979) The role of volatilization in removing polycyclic
    aromatic hydrocarbons from aquatic environments. Bull Environ Contam
    Toxicol, 21: 507-514.

    Southworth GR, Beauchamp JJ, & Schmieder PK (1978) Bioaccumulation
    potential of polycyclic aromatic hydrocarbons in  Daphnia pulex. 
    Water Res, 12: 973-977.

    Spacie A, Landrum PF, & Leversee GJ (1983) Uptake, depuration, and
    biotransformation of anthracene and benzo [a]pyrene in bluegill
    sunfish. Ecotoxicol Environ Saf, 7: 330-341.

    Sparnins VL, Mott AW, Baraney G, & Wattenberg LW (1986) Effects of
    allyl methyl trisulfide on glutathione-S-transferase activity and
    BP-induced neoplasia in the mouse. Nutr Cancer, 8: 211-215.

    Speer K, Steeg E, Horstmann P, Kühn TH, & Montag A (1990)
    Determination and distribution of PAH in native vegetable oils, smoked
    fish products, mussels and oysters, and bream from the River Elbe. J
    High Resol Chromatogr, 13: 104-111.

    Spicer CW, Holdren MW, Smith DL, Hughes DP, & Smith MD (1992) Chemical
    composition of exhaust from aircraft turbine engines. J Eng Gas
    Turbines Power, 114: 111-117.

    Spinelli JJ, Band PR, Svirchev LM, & Gallagher RP (1991) Mortality and
    cancer incidence in aluminium reduction plant workers. J Occup Med,
    33: 1150-1155.

    Spitzer T & Dannecker W (1983) Membrane filters as adsorbents for
    polycyclic aromatic hydrocarbons during high-volume sampling of air
    particulate matter. Anal Chem, 55: 2226-2228.

    Spitzer T & Kuwatsuka S (1986) Simple method for determination of
    polynuclear aromatic hydrocarbons in soil by clean-up on XAD-2. J
    Chromatogr, 358: 434-437.

    Sporstœl S, Gjœs N, Lichtenthaler RG, Gustavsen KO, Urdal K, Oreld F,
    & Skei J (1983) Source identification of aromatic hydrocarbons in
    sediments using GC/MS. Environ Sci Technol, 17: 282-286.

    Stahl RG, Liehr JG, & Davis EM (1984) Characterization of organic
    compounds in simulated rainfall runoffs from model coal piles. Arch
    Environ Contam Toxicol, 13: 179-190.

    Stanton MF, Miller E, Wrench C, & Blackwell R (1972) Experimental
    induction of epidermoid carcinoma in the lungs of rats by cigarette
    smoke condensate. J Natl Cancer Inst, 49: 867-877.

    State Chemical Analysis Institute, Freiburg (1995) [Food control and
    the environment: Annual report 1994.] Freiburg, pp 156-160 (in
    German).

    State Committee for Air Pollution Control (1992) [Cancer risk from air
    pollution.] Development of evaluation criteria for carcinogenic
    pollutants. Düsseldorf, Minister for Environment and Agriculture for
    Northrhine-Westfalia, 71 pp (in German).

    State Pollution Control Authority and Norwegian Food Control Authority
    (1992) Recommendations from the workshop on PAH. In: Proceedings of
    the workshop on polyaromatic hydrocarbons (PAH), Oslo, 11-13 November
    1991. Oslo, p 423 (Report No. TA-816/1992).

    Stauffer TB, MacIntyre WG, & Wickman DC (1989) Sorption of nonpolar
    organic chemicals on low-carbon-content aquifer materials. Environ
    Toxicol Chem, 8: 845-852.

    Stavenow L & Pessah-Rasmussen H (1988) Effects of polycyclic aromatic
    hydrocarbons on proliferation, collagen secretion and viability of
    arterial smooth muscle cells in culture. Artery, 15: 94-108.

    Stay FS, Katko A, Rohm CM, Fix MA, & Larsen DP (1988) Effects of
    fluorene on microcosms developed from four natural communities.
    Environ Toxicol Chem, 7: 635-644.

    Steen WC & Karickhoff SW (1981) Biosorption of hydrophobic organic
    pollutants by mixed microbial populations. Chemosphere, 10: 27-32.

    Steiner PF (1955) Carcinogenicity of multiple chemicals simultaneously
    administered. Cancer Res, 15: 632-635.

    Steiner PE & Edgcomb JH (1952) Carcinogenicity of 1,2-benzanthracene.
    Cancer Res, 12: 657-659.

    Steiner PF & Falk HL (1951) Summation and inhibition effects of weak
    and strong carcinogenic hydrocarbons: 1:2-Benzanthracene, chrysene,
    1:2:5:6-dibenzanthracene, and 20-methylcholanthrene. Cancer Res, 11:
    56-63.

    Steinhoff D, Mohr U & Hahnemann S (1991) Carcinogenesis studies with
    iron oxides. Exp Pathol, 43: 189-194.

    Steinig J (1976) 3,4-Benzopyrene contents in smoked fish depending on
    smoking procedure. Z Lebensmittelunters Forsch, 162: 235-242.

    Stenbäck F & Sellakumar A (1974) Lung tumor induction by
    dibenz(a,i)pyrene in the Syrian golden hamster. Z Krebsforsch, 82:
    175-182.

    Stenberg UR (1985) PAH emissions from automobiles. In: Bjorseth A &
    Ramdahl T ed. Handbook of polycyclic aromatic hydrocarbons. Volume 2:
    Emission sources and recent progress in analytical chemistry. New
    York, Marcel Dekker, pp 87-111.

    Stenberg U, Alsberg T, & Westerholm R (1983) Applicability of a
    cryogradient technique for the enrichment of PAH from automobile
    exhausts: Demonstration of methodology and evaluation experiments.
    Environ Health Perspectives, 47: 43-51.

    Stevenson JL & Von Haam E (1965) Carcinogenicity of benz(a)anthracene
    and benzo(c)phenanthrene derivatives. Am Ind Hyg Assoc J, 26: 475-478.

    Stoner GD, Harris CC, Autrup H, Trump BJ, Kingsbury EW, & Myers GA
    (1978) Explant cultures of human peripheral lung. I. Metabolism of
    benzo [a]pyrene. Lab Invest, 38: 685-692.

    Storer JS, DeLeon I, Millikan LE, Laseter JL, & Griffing C (1984)
    Human absorption of crude coal tar products. Arch Dermatol, 120: 874-
    877.

    Stout P & Mamantov G (1989) Recent advances in infrared analysis of
    polycyclic aromatic compounds. In: Vo-Dinh T ed. Chemical analysis of
    polycyclic aromatic compounds. New York, John Wiley & Sons, pp 411-
    432.

    Strandell M, Zakrisson S, Alsberg T, Westerholm R, Winquist L, &
    Rannug U (1994) Chemical analysis and biological testing of a polar
    fraction of ambient air, diesel engine, and gasoline engine
    particulate extracts. Environ Health Perspectives, 102 (suppl 4): 85-
    92.

    Strickland PT, Routledge MN, & Dipple A (1993) Methodologies for
    measuring carcinogen adducts in humans. Cancer Epidemiol Biomarkers
    Prev, 2: 607-619.

    Stuermer DH, Ng DJ, & Morris CJ (1982) Organic contaminants in
    groundwater near underground coal gasification site in northeastern
    Wyoming. Environ Sci Technol, 16: 582-587.

    Suess MJ (1976) The environmental load and cycle of polycyclic
    aromatic hydrocarbons. Sci Total Environ, 6: 239-250.

    Sugiyama T (1973) Chromosomal aberrations and carcinogenesis by
    various benz(a)-anthracene derivatives. Gann, 64: 637-639.

    Sullivan TJ & Mix MC (1983) Pyrolytic deposition of polynuclear
    aromatic hydrocarbons due to slash burning on clear-cut sites. Bull
    Environ Contam Toxicol, 31: 208-215.

    Sullivan TJ & Mix MC (1985) Persistence and fate of polynuclear
    aromatic hydrocarbons deposited on slash burn sites in the Cascade
    Mountains and coast range of Oregon. Arch Environ Contam Toxicol, 14:
    187-192.

    Suntzeff VA, Cowdry EV, & Croninger A (1955) Microscopic visualization
    of the degeneration of sebaceous glands caused by carcinogens. Cancer
    Res, 15: 637-640.

    Surh YS, Liem A, Miller EC, & Miller JA ( 1989) Metabolic activation
    of the carcinogen 6-hydroxymethylbenzo(a)pyrene: Formation of an
    electrophilic sulfuric acid ester and benylic DNA adducts in rat liver
     in vivo and in reactions  in vivo. 
    Carcinogenesis, 10: 1519-1528.

    Surh YJ, Blomquist JC, Liem A, & Miller JA (1990a) Metabolic
    activation of 9-hydroxymethyl-10-methylanthracene and
    1-hydroxymethylpyrene to electrophilic, mutagenic and tumorigenic
    sulfuric acid esters by rat hepatic sulfotransferase activity.
    Carcinogenesis, 11: 1451-1460.

    Surh, YJ, Liem A, Miller EC, & Miller JA (1990b) The strong
    hepatocarcinogenicity of the electrophilic and mutagenic metabolite
    6-sulfooxymethylbenzo(a)pyrene and its formation of benzylic DNA
    adducts in the livers of infant male B6C3F1 mice. Biochem Biophys Res
    Commun, 172: 85-91.

    Süss A (1980) [Basic questions for the solution of environmental
    problems.] FreisingMunich, Bavarian State Department for Soil and
    Horticulture, pp 376-378 (in German).

    Sutter TR, Tang YM, Hayes CL, Wo Y-YP, Jabs EW, Li X, Yin H, Cody CW,
    & Greenlee WF (1994) Complete cDNA sequence of a human
    dioxin-inducible mRNA identifies a new gene subfamily of cytochrome
    P450 that maps to chromosome 2. J Biol Chem, 269: 13092-13099.

    Swaen GMH, Slangen JJM, Volovics A, Hayes RB, Scheffers T, & Sturmans
    F (1991) Mortality of coke plant workers in the Netherlands. Br J Ind
    Med, 48: 130-135.

    Swallow WH & van Noort RW (1985) Occupational exposure to polycyclic
    aromatic hydrocarbons in some New Zealand industries. Wellington,
    Department of Scientific and Industrial Research, 17 pp.

    Swartz RC, Kemp PF, Schults DW, & Lamberson JO (1988) Effects of
    mixtures of sediment contaminants on the marine infaunal amphipod
     Rhepoxynius abronius. Environ Toxicol Chem, 7: 1013-1020.

    Swartz WJ & Mattison DR (1985) Benzo(a)pyrene inhibits ovulation in
    C57Bl/6N mice. Anat Rec, 221: 268-276.

    Swedish National Board of Occupational Safety and Health (1994)
    Occupational exposure limit values, Solna, National Institute of Work
    and Health, p 5.

    Symons RK & Crick I (1983) Determination of polynuclear aromatic
    hydrocarbons in refinery effluent by high-performance liquid
    chromatography. Anal Chim Acta, 151: 237-243.

    Szabo G, Prosser SL, & Bulman RA (1990) Determination of the
    adsorption coefficient (Koc) of some aromatics for soil by RP-HPLC on
    two immobilized humic acid phases. Chemosphere, 21: 777-788.

    Szyfter K, Krüger J, Ericson P, Vaca C, Försti A, & Hemminki K (1994)
    32P-Postlabelling analysis of DNA adducts in humans: Adduct
    distribution and method improvement. Mutat Res, 313: 269-276.

    Tabak HH, Quave SA, Mashni CI, & Barth EF (1981) Biodegradability
    studies with organic priority pollutant compounds. J Water Pollut
    Control Fed, 53: 1503-1518.

    Takada H, Onda T, & Ogura N (1990) Determination of polycyclic
    aromatic hydrocarbons in urban street dusts and their source materials
    by capillary gas chromatography. Environ Sci Technol, 24: 1179-1186.

    Takahashi G (1974) Distribution and metabolism of benzo(a)pyrene in
    fetal mouse. Bull Chest Dis Res Inst Kyoto Univ, 7: 155-160.

    Takahashi G (1978) Distribution and excretion of the hydrocarbon
    3-methylcholanthrene in the animal body. In: Gelboin HV and Ts'o POP,
    ed. Polycyclic hydrocarbons and cancer, Volume 1. New York, Academic
    Press, pp 233-246.

    Takahashi G & Yasuhira K (1972) Excretion and conversion of
    3-methylcholanthrene metabolites in the intestinal tract of the mouse.
    Cancer Res, 32: 710-715.

    Takahashi G & Yasuhira K (1973) Macroautoradiographic and radiometric
    studies on the distribution of 3-methylcholanthrene in mice and their
    fetuses. Cancer Res, 33: 23-28.

    Takatsuki K, Suzuki S, Sato N, & Ushizawa I (1985) Liquid
    chromatographic determination of polycyclic aromatic hydrocarbons in
    fish and shellfish. J Assoc Off Anal Chem, 68: 945-949.

    Tan YL, Quanci JF, Borys RD, & Quanci MJ (1992) Polycyclic aromatic
    hydrocarbons in smoke particles from wood and duff burning. Atmos
    Environ, 26A: 1177-1181.

    Tawfic HN (1965) Studies on ear duct tumors in rats. Part II:
    Inhibitory effect of methylcholanthrene and 1,2-benzanthracene on
    tumor formation by 4-dimethylamino-stilbene. Acta Pathol Jpn, 15: 255-
    260.

    Ten Hulscher ThEM, Van Der Velde LE, & Bruggeman WA (1992) Temperature
    dependence of Henry's law constants for selected chlorobenzenes,
    polychlorinated biphenyls and polycyclic aromatic hydrocarbons.
    Environ Toxicol Chem, 11: 1595-1603.

    Teranishi K, Hamada K, & Watanabe H (1975) Quantitative relationship
    between carcinogencity and mutagenicity of polyaromatic hydrocarbons
    in  Salmonella typhimurium mutants. Mutat Res, 31: 97-102.

    Teta MJ, Ott MG, & Schnatter AR ( 1987) Population based mortality
    surveillance in carbon products manufacturing plants. Br J Ind Med,
    44: 344-350.

    Tetzen D (1989) [Environmentally relevant classification of PKWF and
    Printosol. Classification of printing ink oils.] Verfkroniek, 62: 469-
    472 (in German).

    Theriault G, Tremblay C, Cordier S, & Gingras S (1984) Bladder cancer
    in the aluminium industry. Lancet, i: 947-950.

    Thilly WG, DeLuca JG, Furth EE, Hoppe H IV, Kaden DA, Krolewski JJ,
    Liber HL, Skopek TR, Slapikoff SA, Tizard RJ, & Penman BW (1980)
    Gene-locus mutation assays in diploid human lymphoblast lines. In: De
    Serres FJ & Hollaender A ed. Chemical mutagens: Principles and methods
    for their detection, Volume 6. New York, Plenum Press, pp 331-364.

    Thirman M, Albrecht JH, Krüger MA, Erickson RR, Cherwitz DL, Park SS,
    Gelboin HV, & Holtzmann JL (1994) Induction of cytochrome CYPIA1 and
    formation of toxic metabolites of benzo (a)pyrene by rat aorta: A
    possible role in atherogenesis. Proc Natl Acad Sci USA, 91: 5397-5401.

    Thomas W (1986) Principal component analysis of trace substance
    concentrations in rainwater samples. Atmos Environ, 20: 995-1000.

    Thomas P (1988) Reproductive endocrine function in female Atlantic
    croaker exposed to pollutants. Mar Environ Res, 24: 179-183.

    Thomson BM, Lake RJ, & Lilli RE (1996) The contribution of margarine
    to cancer risk from polycyclic aromatic hydrocarbons in the New
    Zealand diet. Polycyclic Aromat Compd 11: 177-184.

    Thorslund TW & Farrar D (1990a) Development of relative potency
    estimates for PAHs and hydrocarbon combustion product fractions
    compared to benzo(a)pyrene and their use in carcinogenic risk
    assessments. Fairfax, Virginia, Clement Associates, 79 pp.

    Thorslund TW & Farrar D (1990b) Ingestion dose-response model for
    benzo [a]pyrene. Fairfax, Virginia, Clement International Corp, 22 pp
    (Contract 68-02-4601).

    Thorsteinsson T (1969) Polycyclic hydrocarbons in commercially and
    home-smoked food in Iceland. Cancer Lett, 23: 455-457.

    Thrane KE (1987) Deposition of polycyclic aromatic hydrocarbons (PAH)
    in the surroundings of primary aluminium industry. Water Air Soil
    Pollut, 33: 385-393.

    Thrane KE & Mikalsen A (1981) High-volume sampling of airborne
    polycyclic aromatic hydrocarbons using glass fibre filters and
    polyurethane foam. Atmos Environ, 15: 909-918.

    Thrane KE & Wikström L (1984) Monitoring of polycyclic aromatic
    hydrocarbons in ambient air. In: Cooke M & Dennis AJ ed. Polynuclear
    aromatic hydrocarbons: Mechanisms, methods and metabolism. Columbus,
    Ohio, Battelle Press, pp 1299-1314.

    Thruston AD Jr (1978) High pressure liquid chromatography techniques
    for the isolation and identification of organics in drinking water
    extracts. J Chromatogr Sci, 16: 254-259.

    Thurmond LM, Tucker AN, Rickert DE, Lauer LD, & Dean JH (1989)
    Functional and biochemical disposition of
    7,12-dimethylbenz(a)anthracene in murine lymphoid cells. Chem-Biol
    Interactions, 72: 93-104.

    Thursby GB, Steele RL, & Kane ME (1985) Effect of organic chemicals on
    growth on reproduction in the marine red alga  Champia 
     parvula. Environ Toxicol Chem, 4: 797-806.

    Thyssen J, Althoff J, Kimmerle G, & Mohr U (1980) Investigations on
    the carcinogenic burden of air pollution in man. XIX. Effect of
    inhaled benzo(a)pyrene in Syrian golden hamsters: A pilot study.
    Zentralbl Bakteriol Hyg I Abt Orig B, 171: 441-444.

    Thyssen J, Althoff J, Kimmerle G, & Mohr U (1981) Inhalation studies
    with benz [a]pyrene in Syrian golden hamsters. J Natl Cancer Inst,
    66: 575-577.

    Tilgner DJ (1958) [New information about smoking procedures].
    Fleischwirtschaft, 10: 649-653 (in German).

    Tilgner DJ (1968) Carcinogens in food. Food Manuf, 43: 37-39, 42.

    Todorovic R, Devanesan PD, Cavalieri EL, Rogan EG, Park SS, & Gelboin
    HV (1991) A monoclonal antibody to rat liver cytochrome P450 IIC11
    strongly and regiospecifically inhibits constitutive benzo [a]pyrene
    metabolism and DNA binding. Mol Carcinog, 4: 308-314.

    Tokiwa H, Morita K, Takeyoshi H, Takahashi K, & Ohnishi Y (1977)
    Detection of mutagenic activity in particulate air pollutants. Mutat
    Res, 48: 237-248.

    Tola S, Koskela R-S, Hernberg S, & Järvinen E (1979) Lung cancer
    mortality among iron foundry workers. J Occup Med, 21: 753-760.

    Tolos WP, Shaw PB, Lowry LK, MacKenzie BA, Deng J-F, & Markel HL
    (1990) 1-Pyrenol: A biomarker for occupational exposure to polycyclic
    aromatic hydrocarbons. Appl Occup Environ Hyg, 5: 303-309.

    Tomatis L (1973) Transplacental carcinogenesis. In: Raven RW ed.
    Modern trends in oncology. Part 1: Research progress. London,
    Butterworths, pp 99-126.

    Tomingas R, Pott F, & Dehnen W (1976) Polycyclic aromatic hydrocarbons
    in human bronchial carcinoma. Cancer Lett, 1: 189-195.

    Tonelli QJ, Custer RP, & Sorof S (1979) Transformation of cultured
    mouse mammary glands by aromatic amines and amides and their
    derivatives. Cancer Res, 39: 1784-1792.

    Tong C, Laspia MF, Telang S, & Williams GM (1981a) The use of adult
    rat liver cultures in the detection of the genotoxicity of various
    polycyclic aromatic hydrocarbons. Environ Mutag, 3: 477-487.

    Tong C, Brat SV, & Williams GM (1981b) Sister-chromatid exchange
    induction by polycyclic aromatic hydrocarbons in an intact cell system
    of adult rat-liver epithelial cells. Mutat Res, 91: 467-473.

    Tong C, Brat VS, Telang S, Laspia, MF, Fazio M, Reiss B, & Williams GM
    (1983) Effects of genotoxic polycyclic aromatic hydrocarbons in rat
    liver culture systems. In: Cooke M & Dennis AJ ed. Polynuclear
    aromatic hydrocarbons: Formation; metabolism,and measurement.
    Columbus, Ohio, Battelle Press, pp 1189-1203.

    Topham JC (1980) Do induced sperm-head abnormalities in mice
    specifically identify mammalian mutagens rather than carcinogens?
    Mutat Res, 74: 379-387.

    Topping DC, Martin DH, & Nettesheim P (1981) Determination of
    cocarcinogenic activity of benzo [e]pyrene for respiratory tract
    mucosa. Cancer Lett, 11: 315-321.

    Törrönen R, Nousianen U, & Hänninen O (1981) Induction of aldehyde
    dehydrogenase by polycyclic aromatic hydrocarbons in rats. Chem-Biol
    Interactions, 36: 33-44.

    Toth L & Blaas W (1972) [The effect of smoking technology on the
    content of carcinogenic hydrocarbons in smoked meat products.]
    Fleischwirtschaft, 9: 1121-1124 (in German).

    Traynor GW, Apte MG, Carruthers AR, Dillworth JF, Grimsrud DT, &
    Gundel LA (1987) Indoor air pollution due to emissions from
    wood-burning stoves. Environ Sci Technol, 21: 691-697.

    Tremblay C, Armstrong B, Thériault G, & Brodeur J (1995) Estimation of
    risk of developing bladder cancer among workers exposed to coal tar
    pitch volatiles in the primary aluminum industry. Am J Ind Med, 27:
    335-348.

    Trucco RG, Engelhardt FR, & Stacey B (1983) Toxicity accumulation and
    clearance of aromatic hydrocarbons in  Daphnia pulex. Environ Pollut,
    A31: 191-202.

    Tsuchimoto T & Matter BE (1981) Activity of coded compounds in the
    micronucleus test. In: De Serres FJ & Ashby J ed. Evaluation of
    short-term tests for carcinogens. Report of the international
    collaborative programme. New York, Elsevier North-Holland, pp 705-711
    (Progress in Mutation Research, Volume 1).

    Tucci AF (1988) PAH characterization in hazardous waste from coke
    processing plants. In: Cooke M & Dennis AJ ed. Polynuclear aromatic
    hydrocarbons: A decade of progress. Columbus, Ohio, Battelle Press, pp
    865-870.

    Tuominen JP, Pyysalo HS, & Sauri M (1988) Cereal products as a source
    of polycyclic aromatic hydrocarbons. J Agric Food Chem, 36: 118-120.

    Tuomisto J & Jantunen M (1987) A simple way of comparing carcinogenic
    effects of chemical and radioactive emissions. Kuopio, National Public
    Health Institute, 18 pp (Report No. NPHI-A2/1987).

    Tweats DJ (1981) Activity of 42 coded compounds in a differential
    killing test using  Escherichia coli strains WP2, WP67 (uvrA polA),
    and CM871 (uvrA lexA recA). In: De Serres FJ & Ashby J ed. Evaluation
    of short-term tests for carcinogens. Report of the international
    collaborative programme. New York, Elsevier North-Holland, pp 199-209
    (Progress in Mutation Research, Volume 1).

    Tyndyk ML, Zabezhinski MA, Bykoy VJ, Dikun PP, Dymochka LA,
    Nepomnyaschaya OB, Yatsuk OS, Yermilov VB, & Likhachev AJ (1994)
    Individual values of excretion of benzo [a]pyrene metabolites and
    susceptibility to its carcinogenic effect in rats. Cancer Lett, 78:
    163-170.

    UNEP (1994) International register for Potentially Toxic Chemicals, PC
    database

    Urso P & Gengozian N (1980) Depressed humoral immunity and increased
    tumor incidence in mice following  in utero exposure to
    benzo [a]pyrene. J Toxicol Environ Health, 6: 569-576.

    Urso P & Johnson RA (1987) Early changes in T lymphocytes and subsets
    of mouse progeny defective as adults in controlling growth of a
    syngeneic tumor after  in utero insult with benzo(a)pyrene.
    Immunopharmacology, 14: 1-10.

    Urso P & Johnson RA (1988) Quantitative and functional change in T
    cells of primiparous mice following injection of benzo(a)pyrene at the
    second trimester of pregnancy. Immunopharmacol Immunotoxicol, 10: 195-
    217.

    Urso P, Gengozian N, Rossi RM, & Johnson RA (1986) Suppression of
    humoral and cellmediated immune responses  in vitro by
    benzo(a)pyrene. J Immunopharmacol, 8: 223-241.

    Urso P, Ryan MC, & Bennett JS (1988) Changes in peripheral blood cells
    in mice after injection with benzo(a)pyrene during pregnancy.
    Immunopharmacol Immunotoxicol, 10: 179-193.

    US Environmental Protection Agency (1978a) Ambient water quality
    criteria: Naphthalene. Washington DC, p B/6 (PB-296 786).

    US Environmental Protection Agency (1978b) Ambient water quality
    criteria: Acenaphthene. Washington DC, p B/7 (PB-296 782).

    US Environmental Protection Agency (1978c) Ambient water quality
    criteria: Fluoranthene. Washington DC, pp B/5-B/7 (PB-292 433).

    US Environmental Protection Agency (1980) Ambient water quality
    criteria for polynuclear aromatic hydrocarbons. Washington DC, 7 pp
    (EPA 440/5-80-069).

    US Environmental Protection Agency (1984a) Guidelines establishing
    test procedures for the analysis of pollutants under the clean water
    act: Method 610. Polynuclear aromatic hydrocarbons. Fed Reg, 49(209):
    43344-43352 (40 CFR Part 136).

    US Environmental Protection Agency (1984b) Health effects assessment
    for naphthalene. Research Triangle Park, North Carolina, Section 7
    (EPA/540/1-86/014).

    US Environmental Protection Agency (1984c) Health effects assessment
    for polycyclic aromatic hydrocarbons (PAH). Washington DC, Office of
    Emergency and Remedial Response, 49 pp (EPA 540/1-86/013; NTIS
    PB86-134244/AS).

    US Environmental Protection Agency (1984d) Carcinogenic assessment of
    coke oven emissions. Final report. Washington DC, Office of Health and
    Environmental Assessment, 209 pp (EPA 600/6-82-003F; NTIS
    PB84-170182).

    US Environmental Protection Agency (1984e) Health effects assessment
    for benzo(a)pyrene. Cincinnati, Ohio, 43 pp (EPA/540/1-86/022; PB
    86-134335).

    US Environmental Protection Agency (1986a) (I) Method 3510 'Separatory
    funnel liquid-liquid extraction'; (II) Method 3520 'Continuous liquid-
    liquid extraction'; (III) Method 3630 'Silica gel cleanup'; (IV)
    Method 8100 'Polynuclear aromatic hydrocarbons'; (V) Method 8270 'Gas
    chromatography/mass spectrometry for semivolatile organics: Capillary
    column technique'; (VI) Method 8310 'Polynuclear aromatic
    hydrocarbons'. In: Test methods for evaluating solid waste, 3rd Ed,
    Volume IB. Washington DC, 50 pp (EPA-SW-846).

    US Environmental Protection Agency (1986b) (I) Method 3540 'Soxhlet
    extraction'; (II) Method 3550 'Sonication extraction'; (III) Method
    3630 'Silica gel cleanup'; (IV) Method 8100 'Polynuclear aromatic
    hydrocarbons'; (V) Method 8270 'Gas chromatography/mass spectrometry
    for semivolatile organics: Capillary column technique'; (VI) Method
    8310 'Polynuclear aromatic hydrocarbons'. In: Test methods for
    evaluating solid waste, 3rd Ed, Volume IB. Washington DC, 45 pp
    (EPA-SW-846).

    US Environmental Protection Agency (1986c) (I) Method 0010 'Modified
    method 5 sampling train'; (II) Method 0020 'Source assessment sampling
    system (SASS)'. In: Test methods for evaluating solid waste, 3rd Ed,
    Volume II. Washington DC, 86 pp (EPA-SW846).

    US Environmental Protection Agency (1986d) Health and environmental
    effects profile for naphthalene. Cincinnati, Ohio, pp 41-54 (PB
    88-242383).

    US Environmental Protection Agency (1987a) Reference method for the
    determination of particulate matter as PM10 in the atmosphere.
    Appendix J. Fed Reg, 52(126): 24664-24666.

    US Environmental Protection Agency (1987b) Health and environmental
    effects profile for anthracene. Cincinnati, Ohio, pp 43-47, 57, 63, 66
    (PB 89-118319).

    US Environmental Protection Agency (1987c) The risk assessment
    guidelines of 1986. Washington DC, Office of Health and Environmental
    Assessment (EPA/600/8-87/045).

    US Environmental Protection Agency (1988) 13-Week mouse oral
    subchronic toxicity study (fluoranthene). Washington DC, 104 pp (TRL
    Study No. 042-008).

    US Environmental Protection Agency (1989a) Mouse oral subchronic
    toxicity study with acenaphthene. Washington DC, 89 pp.

    US Environmental Protection Agency (1989b) Subchronic toxicity in mice
    with anthracene: Final report. Washington DC, 465 pp (HLA Study No.
    2399-131).

    US Environmental Protection Agency (1989c) Mouse oral subchronic
    toxicity study (fluorene). Washington DC, 38 pp (TRL Study No.
    042010).

    US Environmental Protection Agency (1989d) Mouse oral subchronic
    toxicity of pyrene. Washington DC, 102 pp (TRL Study No. 042-012).

    US Environmental Protection Agency (1990) Method IP-7 'Determination
    of benzo(a)pyrene and other polynuclear aromatic hydrocarbons in
    indoor air'. In: Winberry WT Jr, Forehand L, Murphy NT, Ceroli A,
    Phinney B, & Evans A ed. Compendium of methods for the determination
    of air pollutants in indoor air. Research Triangle Park, North
    Carolina, pp 550-639 (EPA 600/4-90/010; US NTIS PB90-200288).

    US Environmental Protection Agency (1992a) Protection of the
    environment: Chapter 1, part 86, sections 86-109, 86-110. US Code Fed
    Regul, Title 40, Parts 86-99: 377-410.

    US Environmental Protection Agency (1992b) Drinking water criteria
    document for polycyclic aromatic hydrocarbons (PAHs). Washington DC,
    Office of Water, 442 pp.

    US Environmental Protection Agency (1993) Provisional guidance for
    quantitative risk assessment of polycyclic aromatic hydrocarbons.
    Cincinnati, Ohio, Office of Health and Environmental Assessment,
    Environmental Criteria and Assessment Office (EPA/600/R-93/089).

    Uthe JF & Musial CJ (1986) Polycyclic aromatic hydrocarbon
    contamination of American lobster,  Homarus americanus, in the
    proximity of a coal-coking plant. Bull Environ Contam Toxicol, 37:
    730-738.

    Vaessen HAMG, Schuller PL, Jekel AA, & Wilbers AAMM (1984) Polycyclic
    aromatic hydrocarbons in selected foods: Analysis and occurence.
    Toxicol Environ Chem, 7: 297-324.

    Vaessen HAMG, Jekel AA, & Wilbers AAMM (1988) Dietary intake of
    polycyclic aromatic hydrocarbons. Toxicol Environ Chem, 16: 281-294.

    Vähäkangas K, Pyy L, & Yrjänheikki E (1992) Assessment of PAH-exposure
    among coke oven workers. Pharmacogenetics, 2: 304-308

    Vainio H, Uotila P, Hartiala J, & Pelkonen O (1976) The fate of
    intratracheally installed benzo [a]pyrene in the isolated perfused
    rat lung of both control and 20-methylcholanthrene pretreated rats.
    Res Commun Chem Pathol Pharmacol, 13: 259-271.

    Vainiotalo S & Matveinen K (1993) Cooking fumes as a hygienic problem
    in the food and catering industries. Am Ind Hyg Assoc J, 54: 376-382.

    Vaishnav DD & Babeu L (1987) Comparison of occurrence and rates of
    chemical biodegradation in natural waters. Bull Environ Contam
    Toxicol, 39: 237-244.

    Valaes T, Doxiadis SA, & Fessas P (1963) Acute hemolysis due to
    naphthalene inhalation. J. Pediatr, 63: 904-915.

    Valencia R & Houtchens K (1981) Mutagenic acitivity of 10 coded
    compounds in the  Drosophila sex-linked recessive lethal test. In: De
    Serres FJ & Ashby J ed. Evaluation of short-term tests for
    carcinogens. Report of the international collaborative programme.
    Amsterdam, Elsevier North-Holland, pp 652-659 (Progress in Mutation
    Research, Volume 1).

    Valerio F, Bottino P, Ugolini D, Cimberle MR, Tozzi GA, & Frigerio A
    (1984) Chemical and photochemical degradation of polycyclic aromatic
    hydrocarbons in the atmosphere. Sci Total Environ, 40: 169-188.

    Valerio F, Antolini E, & Lazzarotto A (1987) A model to evaluate
    half-lifes of PAHs naturally occurring on airborne particulate. Int J
    Environ Anal Chem, 28: 185-196.

    Valerio F, Pala M, Brescianini C, Lazarrotto A, & Balducci D (1991)
    Effect of sunlight and temperature on concentration of pyrene and
    benzo [a]pyrene adsorbed on airborne particulate. Toxicol Environ
    Chem, 31/32: 113-118.

    Valerio F, Brescianini C, Pala M, Lazzarotto A, Balducci D, & Vincenzo
    F (1992) Sources and atmospheric concentrations of polycyclic aromatic
    hydrocarbons and heavy metals in two Italian towns (Genoa and La
    Spezia). Sci Total Environ, 114: 47-57.

    Van Brummelen TC & Stuijfzand SC (1993) Effects of benzo [a]pyrene on
    survival, growth and energy reserves in terrestrial isopods  Oniscus
    asellus and  Porcellio scaber. Sci Total Environ, Suppl (Part II):
    921-930.

    Van Cauwenberghe KA (1985) Atmospheric reactions of PAH. In: Bjorseth
    A & Ramdahl T ed. Handbook of polycyclic aromatic hydrocarbons, Volume
    2. Emission sources and recent progress in analytical chemistry. New
    York, Marcel Dekker, pp 351-384.

    Van den Heuvel JPP, Clark GC, Thompson CL, McCoy Z, Miller CR, Lucier
    GW, & Bell DA (1993) CYP1A1 mRNA levels as a human exposure biomarker:
    Use of quantitative polymerase chain reaction to measure CYP1A1
    expression in human peripheral blood lymphocytes. Carcinogenesis, 14:
    2003-2006.

    Van der Oost R, Heida H, Opperhuizen A, & Vermeulen (1991)
    Interrelationships between bioaccumulation of organic trace pollutants
    PCBs organochlorine pesticides and PAHs and MFO-induction in fish.
    Comp Biochem Phys, C100: 43-48.

    Van Duuren BL & Goldschmidt BM (1976) Cocarcinogenic and
    tumor-promoting agents in tobacco carcinogenesis. J Natl Cancer Inst,
    56: 1237-1242.

    Van Duuren BL, Sivak A, Segal A, Orris L, & Langseth L (1966) The
    tumor-promoting agents of tobacco leaf and tobacco smoke condensate. J
    Natl Cancer Inst, 37: 519-526.

    Van Duuren BL, Langseth L, Goldschmidt BM & Orris L (1967)
    Carcinogenicity of epoxides, lactones, and peroxy compounds. VI.
    Structure and carcinogenic activity. J Natl Cancer Inst, 39:
    1217-1228.

    Van Duuren BL, Sivak A, Langseth L, Goldschmidt BM, & Segal A (1968)
    Initiators and promoters in tobacco carcinogenesis. Natl Cancer Inst
    Monogr, 28: 173-180.

    Van Duuren BL, Sivak A, Goldschmidt BM, Katz C, & Melchionne S (1970)
    Initiating activity of aromatic hydrocarbons in two-stage
    carcinogenesis. J Natl Cancer Inst, 44: 1167-1173.

    Van Heyningen R & Pirie A (1967) The metabolism of naphthalene and its
    toxic effect on the eye. Biochem J, 102: 842-852.

    Van Noort PCM & Wondergem E (1985a) The isolation of some polynuclear
    aromatic hydrocarbons from aqueous samples by means of reversed-phase
    concentrator columns. Anal Chim Acta, 172: 335-340.

    Van Noort PCM & Wondergem E (1985b) Scavenging of airborne polycyclic
    aromatic hydrocarbons by rain. Environ Sci Technol, 19: 1044-1048.

    Van Rooij JGM, Bodelier-Bade MM, De Looff AJA, Dijkmans AGP, &
    Jongeneelen FJ (1992) Dermal exposure to polycyclic aromatic
    hydrocarbons among primary aluminium workers. Med Lav, 83: 519-529.

    Van Rooij JGM, Bodelier-Bade MM, & Jongeneelen FJ (1993a) Estimation
    of individual dermal and respiratory uptake of polycyclic aromatic
    hydrocarbons in 12 coke oven workers. Br J Ind Med, 50: 623-632.

    Van Rooij JGM, Van Lieshout EMA, Bodelier-Bade MM, & Jongeneelen FJ
    (1993b) Effect of the reduction of skin contamination on the internal
    dose of creosote workers exposed to polycyclic aromatic hydrocarbons.
    Scand J Work Environ Health, 19: 200-207.

    Van Rooij JGM, Veeger MMS, Bodelier-Bade MM, Scheepers PTJ, &
    Jongeneelen FJ (1994a) Smoking and dietary intake of polycyclic
    aromatic hydrocarbons as sources of interindividual variability in the
    baseline excretion of 1-hydroxypyrene in urine. Int Arch Occup Environ
    Health, 66: 55-65.

    Van Rooij JGM, Bodelier-Bade MM, Hopmans PMJ, & Jongeneelen FJ (1994b)
    Reduction of urinary 1-hydroxypyrene excretion in coke-oven workers
    exposed to polycyclic aromatic hydrocarbons due to improved hygienic
    skin protective measures. Ann Occup Hyg, 38: 247-256.

    Van Straalen NM & Verweij RA (1991) Effects of benzo [a]pyrene on
    food assimilation and growth efficiency in  Porcellio scaber 
    (Isopoda). Bull Environ Contam Toxicol, 46: 134-140.

    Van Vaeck L, Broddin G, & Van Cauwenberghe K (1980) On the relevance
    of air pollution measurements of aliphatic and polyaromatic
    hydrocarbons in ambient particulate matter. Biomed Mass Spectrom, 7:
    473-483.

    Van Vaeck L, Van Cauwenberghe K, & Janssens J (1984) The gas-particle
    distribution of organic aerosol constituents: Measurement of the
    volatilisation artefact in hi-vol cascade impactor sampling. Atmos
    Environ, 18: 417-430.

    Varanasi U, Reichert WL, Stein JE, Brown DW, & Sanborn HR (1985)
    Bioavailability and biotransformation of aromatic hydrocarbons in
    benthic organisms exposed to sediment from an urban estuary. Environ
    Sci Technol, 19: 836-841.

    Varanasi U, Stein JE, Reichert WL, Tilbury KL, Krahn MM, & Chan SL
    (1992) Chlorinated and aromatic hydrocarbons in bottom sediments, fish
    and marine mammals in US coastal waters: Laboratory and field studies
    of metabolism and accumulation. In: Walker CH & Livingstone DR ed.
    Persistent pollutants in marine ecosystems. Oxford, Pergamon Press, pp
    82-115.

    Vassilaros DL, Stoker PW, Booth GM, & Lee ML (1982) Capillary gas
    chromatographic determination of polycyclic aromatic compounds in
    vertebrate fish tissue. Anal Chem, 54: 106-112.

    Vaught J & Bresnick E (1976) Binding of polycyclic hydrocarbons to
    nuclear components  in vitro. Biochem Biophys Res Commun, 69:
    587-591.

    Vaught JB, Gurtoo HL, Paigen B, Minowada J, & Sartori P (1978)
    Comparison of benzo [a]pyrene metabolism by human peripheral blood
    lymphocytes and monocytes. Cancer Lett, 5: 261-268.

    Veldre IA & Itra AR (1991) PAH in the water medium of the Estonian SSR
    and their monitoring. In: Cooke M, Loening K, & Merritt J ed.
    Polynuclear aromatic hydrocarbons: Measurement, means, and metabolism.
    Columbus, Ohio, Battelle Press, pp 939-948.

    Venier P, Clonfero E, Cottica D, Gava C, Zordan M, Pozzoli L, & Levis
    AG (1985) Mutagenic activity and polycyclic aromatic hydrocarbon level
    in urine of workers exposed to coal tar pitch volatiles in an anode
    plant. Carcinogenesis, 6: 749-752.

    Verma DK, Julian JA, Roberts RS, Muir DC, Jadon N, & Shaw DS (1992)
    Polycyclic aromatic hydrocarbons (PAHs): A possible cause of lung
    cancer mortality among nickel/copper smelter and refinery workers. Am
    Ind Hyg Assoc J, 53: 317-324.

    Vermorken AJM, Goos CMAA, Roelofs HMJ, Henderson PT, & Bloemendal H
    (1979) Metabolism of benzo [a]pyrene in isolated human scalp hair
    follicles. Toxicology, 14: 109-116.

    Verschueren K (1983) Handbook of environmental data on organic
    chemicals, 2nd Ed. New York, Van Nostrand Reinhold Co, pp 460, 760,
    968.

    Viau C & Vyskocil A (1995) Patterns of 1-hydroxypyrene excretion in
    volunteers exposed to pyrene by the dermal route. Sci Total Environ,
    163: 187-190.

    Viau C, Vyskoçil A, Tremblay C, & Morissette L (1993) Urinary
    excretion of 1-hydroxypyrene in workers exposed to polycyclic aromatic
    hydrocarbon mixtures. J Occup Med Toxicol, 2: 267-276.

    Viau C, Carrier G, Vyskoçil A, & Dodd C (1995) Urinary excretion
    kinetics of 1-hydroxypyrene in volunteers exposed to pyrene by the
    oral and dermal route. Sci Total Environ, 163: 179-186.

    Viras LG, Siskos PA, & Stephanou E (1987) Determination of polycyclic
    aromatic hydrocarbons in Athens atmosphere. Int J Environ Anal Chem,
    28: 71-85.

    Vo-Dinh T (1989) Chemical analysis of polycyclic aromatic compounds.
    New York, John Wiley & Sons, 487 pp.

    Vo-Dinh T, Bruewer TJ, Colovos GC, Wagner TJ, & Jungers RH (1984)
    Field evaluation of a cost-effective screening procedure for
    polynuclear aromatic pollutants in ambient air samples. Environ Sci
    Technol, 18: 477-482.

    Vogel EW, Zijlstra JA, & Blijleven WGH (1983) Mutagenic activity of
    selected aromatic amines and polycyclic hydrobarbons in
     Drosophila melanogaster. Mutat Res, 107: 53-77.

    Vogt NB, Brakstad F, Thrane K, Nordenson S, Krane J, Aamot E, Kolset
    K, Esbensen K, & Steinnes E (1987) Polycyclic aromatic hydrocarbons in
    soil and air: Statistical analysis and classification by the SIMCA
    method. Environ Sci Technol, 21: 35-44.

    Volkswagen AG (1989) Unregulated motor vehicle exhaust gas components.
    Wolfsburg, Research and Development, 128 pp.

    Von Boente L (1955) [Role of coronene in the products of high-pressure
    hydrogenation.] Brennstoff-Chemie, 36: 210-214 (in German).

    Von Meyerinck (1995)

    de Vos (1980)

    de Vos RH, Van Dokkum W, Schouten A, & De Jong-Berkhout P (1990)
    Polycyclic aromatic hydrocarbons in Dutch total diet samples
    (1984-1986). Food Chem Toxicol, 28:

    Vreuls JJ, De Jong GJ, & Brinkman UAT (1991) On-line coupling of
    liquid chromatography, capillary gas chromatography and mass
    spectrometry for the determination and identification of polycyclic
    aromatic hydrocarbons in vegetable oils. Chromatographia, 31: 113-118.

    Vu Duc T & Huynh CK (1981) [Organic  micropolluants in water.
    Preliminary results on polycyclic aromatic haloforms and
    hydrocarbons.] Méd Soc Prév, 26: 315-316 (in French).

    Vu Duc T & Huynh CK (1991) Photodecomposition rates of adsorbed PAH
    and mutagenic activity of irradiated synthetic mixtures. In: Cooke M,
    Loening K, & Merritt J ed. Polynuclear aromatic hydrocarabons:
    Measurement, means and metabolism. Columbus, Ohio, Battelle Press, pp
    979-994.

    Wakeham SG, Schaffner C, & Giger W (1980a) Polycyclic aromatic
    hydrocarbons in recent lake sediments. I. Compounds having
    anthropogenic origins. Geochim Cosmochim Acta, 44: 403-413.

    Wakeham SG, Schaffner C, & Giger W (1980b) Diagenetic polycyclic
    aromatic hydrocarbons in recent sediments: Structural information
    obtained by high performance liquid chromatography. Phys Chem Earth,
    12: 353-363.

    Wakeham SG, Davis AC, & Karas J (1983) Mesocosm experiments to
    determine the fate and persistence of volatile organic compounds in
    coastal seawater. Environ Sci Technol, 17: 611-617.

    Waldman JM, Lioy PJ, Greenberg A, & Butler JP (1991) Analysis of human
    exposure to benzo(a)pyrene via inhalation and food ingestion in the
    Total Human Environment Exposure Study (THEES). J Exposure Anal
    Environ Epidemiol, 1: 193-225.

    Walker JD & Colwell RR (1976) Measuring the potential activity of
    hydrocarbon-degrading bacteria. Appl Environ Microbiol, 31: 189-197.

    Wall KL, Gao W, Te Koppele JM, Kwei GY, Kauffman FC, & Thurman RG
    (1991) The liver plays a central role in the mechanism of chemical
    carcinogenesis due to polycyclic aromatic hydrocarbons.
    Carcinogenesis, 12: 783-786.

    Waller RE (1981) Trends in lung cancer in London in relation to
    exposure to diesel fumes. Environ Int, 5: 479-483.

    Waller RE, Hampton L, & Lawther PJ (1985) A further study of air
    pollution in diesel bus garages. Br J Ind Med, 42: 824-830.

    Walter U, Beyer M, Klein J, & Rehm HJ (1990) Biodegradation of
    polycyclic aromatic hydrocarbons by a bacterial mixed culture.
    Biotechnol Conf, 4: 489-492.

    Walters RW & Luthy RG (1981) Physicochemical behavior of PAH in coal
    conversion liquid effluents. In: Cooke M & Dennis AJ ed. Polynuclear
    aromatic hydrocarbons: Chemical analysis and biological fate.
    Columbus, Ohio, Battelle Press, pp 539-550.

    Walters RW & Luthy RG (1984) Liquid/suspended solid phase partitioning
    of polycyclic aromatic hydrocarbons in coal coking wastewaters. Water
    Res, 18: 795-809.

    Walton B (1980) Influence of route of entry on toxicity of polycyclic
    aromatic hydrocarbons to the cricket  (Acheta 
     domesticus). Bull Environ Contam Toxicol, 25: 289-293.

    Wang DT & Meresz O (1982) Occurrence and potential uptake of
    polynuclear aromatic hydrocarbons of highway traffic origin by
    proximally grown food crops. In: Cooke M, Dennis AJ & Fisher GL ed.
    Polynuclear aromatic hydrocarbons: Physical and biological chemistry.
    Columbus, Ohio, Battelle Press, pp 885-896.

    Wangenheim J & Bolcsfoldi G (1988) Mouse lymphoma L5178Y thymidine
    kinase locus assay of 50 compounds. Mutagenesis, 3: 193-205.

    Waravdekar SS & Ranadive KJ (1958) Biologic testing of
    3,4,9,10-dibenzpyrene. J Natl Cancer Inst, 21: 1151-1159.

    Ward EC, Murray MJ, Lauer LD, House RV, Irons R, & Dean JH (1984)
    Immunosuppres-sion following 7,12-dimethylbenz [a]anthracene exposure
    in B6C3F1 mice. I. Effects on humoral immunity and host resistance.
    Toxicol Appl Pharmacol, 75: 299-308.

    Ward EC, Murray MJ, Lauer LD, House RV, & Dean JH (1986) Persistent
    suppression of humoral and cell-mediated immunity in mice following
    exposure to the polycyclic aromatic hydrocarbon
    7,12-dimethylbenz [a]anthracene. Int J Immunopharmacol, 8: 13-22.

    Warman K (1985) PAH emissions from coal-fired plants. In: Bjorseth A &
    Ramdahl T ed. Handbook of polycyclic aromatic hydrocarbons, Volume 2:
    Emission sources and recent progress in analytical chemistry. New
    York, Marcel Dekker, pp 21-59.

    Warren DL, Brown DR Jr, & Buckpitt AR (1982) Evidence for cytochrome
    P450 mediated metabolism in the bronchiolar damage by naphthalene.
    Chem-Biol Interactions, 40: 287-303.

    Warshawsky D & Barkley W (1987) Comparative carcinogenic potencies of
    7H-dibenzo [c,g]carbazole, dibenz [a,j]acridine and benzo [a]pyrene
    in mouse skin. Cancer Lett, 37: 337-344.

    Warshawsky D, Barkley W, Miller ML, LaDow K, & Andringa A (1994)
    Carcinogenicity of 7H-dibenzo(c,g)carbazole, dibenz(a,j)acridine and
    benzo(a)pyene in mouse skin and liver following topical application.
    Toxicology, 93: 135-149.

    Warshawsky D, Barkley W, Miller ML, LaDow K, & Andringa A (1995)
    Erratum to 'Carcinogenicity of 7H-dibenz(a)pyrene in mouse skin and
    liver following topical application' (Toxicology 93 (1994) 135-149).
    Toxicology, 96: 239-240.

    Wattenberg LW (1978) Inhibitors of chemical carcinogenesis. Adv Cancer
    Res, 26: 197-226.

    Wattenberg LW & Leong JL (1970) Inhibition of the carcinogenic action
    of benzo(a)pyrene by flavones. Cancer Res, 30: 1922-1925.

    Weaver NK & Gibson RL (1979) The US oil shale industry: A health
    perspective. Am Ind Hyg Assoc J, 40: 460-467.

    Wehry EL (1983) Optical spectrometric techniques for determination of
    polycyclic aromatic hydrocarbons. In: Bjorseth A ed. Handbook of
    polycyclic aromatic hydrocarbons. New York, Marcel Dekker, pp 323-396.

    Weigert F & Mottram JC (1946) The biochemistry of benzpyrene. II. The
    course of its metabolism and the chemical nature of the metabolites.
    Cancer Res, 6: 109-120.

    Weinstein IB, Jeffrey AM, Jennette KW, Blobstein SH, Harvey RG, Harris
    C, Autrup H, Kasai H, & Nakanishi K (1976) Benzo [a]pyrene diol
    epoxides as intermediates in nucleic acid binding  in vitro 
    and  in vivo. Science, 193: 592-595.

    Weinstein D, Katz ML, & Kazmer S (1977) Chromosomal effects of
    carcinogens and noncarcinogens on WI-38 after short term exposures
    with and without metabolic acitivation. Mutat Res, 46: 297-304.

    Weinstein IB, Jeffrey AM, Leffler S, Pulkrabek P, Yamasaki H, &
    Grunberger D (1978) Interactions between polycyclic aromatic
    hydrocarbons and cellular macromolecules. In: Gelboin HV & Ts'o POP
    ed. Polycyclic hydrocarbons and cancer, Volume 2. New York, Academic
    Press, pp 3-36.

    Welch RM, Gommi B, Alvares AP, & Conney AH (1972) Effect of
    enzyme-induction on the metabolsim of benzo(a)pyrene and
    3-methyl-4-monomethylaminoazobenzene in the pregnant and fetal rat.
    Cancer Res, 32: 973-978.

    Wells PG, Wilson B, & Lubek BM (1989)  In vivo murine studies on the
    biochemical mechanism of naphthalene cataractogenesis. Toxicol Appl
    Pharmacol, 99: 466-473.

    Wenclawiak B, Rathmann C, & Teuber A (1992) Supercritical-fluid
    extraction of soil samples and determination of polycyclic aromatic
    hydrocarbons (PAHs) by HPLC. Fresenius' J Anal Chem, 344: 497-500.

    Wenzel-Hartung R, Brune H, Grimmer G, Germann P, Timm J, & Wosniok W
    (1990) Evaluation of the carcinogenic potency of four environmental
    polycyclic aromatic compounds following intrapulmonary application in
    rats. Exp Pathol, 40: 221-227.

    West WR, Smith PA, Stoker PW, Booth GM, Smith-Oliver T, Butterworth
    BE, & Lee ML (1985) Analysis and genotoxicity of a PAC-polluted river
    sediment. In: Cooke M & Dennis AJ ed. Polynuclear aromatic
    hydrocarbons: Mechanisms, methods, and metabolism. Columbus, Ohio,
    Battelle Press, pp 1395-1411.

    West WR, Wise SA, Campbell RM, Bartle KD & Lee ML (1986) The analysis
    of polycyclic hydrocarbon minerals curtisite and idrialite by high
    resolution gas and liquid chromatographic techniques. In: Cooke M &
    Dennis AJ ed. Polynuclear aromatic hydrocarbons: Chemistry,
    characterization and carcinogenesis. Columbus, Battelle Press, pp 995-
    1009.

    Wester RC, Maibach HI, Bucks DAW, Sedik L, Melendres J, Liao C, &
    DiZio S (1990) Percutaneous absorption of [14C] DDT and [14C]
    benzo [a]pyrene from soil. Fundam Appl Toxicol, 15: 510-516.

    Westerholm R, Alsberg T, Strandell M, Frommelin Å, Grigoriadis V,
    Hantzaridou A & Maitra G (1986) Chemical analysis and biological
    testing of emissions from a heavy duty diesel truck with and without
    two different particulate traps. Warrendale, Pennsylvania, Society of
    Automotive Engineers, pp 74-82 (SAE Technical Paper Series No.
    860014).

    Westerholm R, Stenberg U, & Alsberg T (1988) Some aspects of the
    distribution of polycyclic aromatic hydroarbons (PAH) between
    particles and gas phase from diluted gasoline exhausts generated with
    the use of a dilution tunnel, and its validity for measurement in
    ambient air. Atmos Environ, 22: 1005-1010.

    Westerholm R, Hang L, Egebäck K-E, & Grägg K (1989) Exhaust emission
    reduction from a heavy duty diesel truck, using a catalyst and a
    particulate trap. Fuel, 68: 856-860.

    Westerholm RN, Almen J, Li H, Rannug JU, Egebäck K-E, & Grägg K (1991)
    Chemical and biological characterization of particulate-,
    semivolatile-, and gas-phase-associated compounds: A comparison of
    three different semivolatile-phase samplers. Environ Sci Technol, 25:
    332-338.

    Weston A (1993) Physical methods for the detection of carcinogen-DNA
    adducts in humans. Mutat Res, 288: 19-29.

    Weston A, Grover PL, & Sims P (1983) Metabolic activation of
    benzo [a]pyrene in human skin maintained in short-term organ culture.
    Chem-Biol Interactions, 45: 359-371.

    Weston A, Bowman ED, Shields PG, Trivers GE, Poirier MC, Santella RM,
    & Manchester DK (1993) Detection of polycyclic aromatic hycrocarbon-
    DNA adducts in human lung. Environ Health Perspectives, 99: 257-259.

    Weyand EH & Bevan DR (1986) Benzo(a)pyrene disposition, and metabolism
    in rats following intratracheal instillation. Cancer Res, 46: 5655-
    5661.

    Weyand EH & Bevan DR (1987) Species differences in disposition of
    benzo [a]pyrene. Drug Metab Disposition, 15: 442-448.

    Weyand EH & LaVoie EJ (1988) Comparison of PAH DNA adduct formation
    and tumor initiating activity in newborn mice. Proc Am Assoc Cancer
    Res, 29: 98.

    Weyand EH, Rice JE, Hussain N, & LaVoie EJ (1987) Detection of DNA
    adducts of tumorigenic nonalternant polycyclic aromatic hydrocarbons
    by 32P-postlabelling. Proc Am Assoc Cancer Res, 28: 102.

    Weyand EH, Patel S, LaVoie EJ, Cho B, & Harvey RG (1990) Relative
    tumor initiating activity of benzo [a]fluoranthene,
    benzo [b]fluoranthene, naphtho[1,2- b]fluoranthene and
    naphtho[2,1- a]fluoranthene on mouse skin. Cancer Lett, 52: 229-233.

    Weyand EH, Bryla P, Wu Y, He Z-M, & LaVoie EJ (1993) Detection of the
    major DNA adducts of benzo(j)fluoranthene in mouse skin: Nonclassical
    dihydrodiol epoxides. Chem Res Toxicol, 6: 117-124.

    White JG (1948) The crystal structure of 1:12-benzperylene: A
    quantitatve X-ray investigation. J Chem Soc, 1: 1398-1408.

    White CM (1986) Prediction of the boiling point, heat of vaporization,
    and vapor pressure at various temperatures for polycyclic aromatic
    hydrocarbons. J Chem Eng Data, 31: 198-203.

    White KL & Holsapple MP (1984) Direct suppression of  in vitro 
    antibody production by mouse spleen cells by the carcinogen
    benzo(a)pyrene but not by the noncarcinogenic congener benzo(e)pyrene.
    Cancer Res, 44: 3388-3393.

    White J & White A (1939) Inhibition of growth of the rat by oral
    administration of methylcholanthrene, benzpyrene, or pyrene and the
    effects of various dietary supplements. J Biol Chem, 131: 149-161.

    White KL, Lysy HH, & Holsapple MP (1985) Immunosuppression by
    polycyclic aromatic hydrocarbons: A structure-activity relationship in
    B6C3F1 and DBA/2 mice. Immunopharmacology, 9: 155-164.

    Whitlock JP (1979) The conformation of the chromatin core particle is
    ionic strength dependent. J Biol Chem, 254: 5684-5689.

    Whitman LJ & Miller RJ (1982) The phototactic behavior of
     Daphnia magna as an indicator of chronic toxicity. Proc Oklahoma
    Acad Sci, 62: 22-33.

    WHO (1971) International drinking-water standards, 3rd Ed, p 55.

    WHO (1984) Guidelines for drinking-water quality, Volume 1:
    Recommendations, pp 66-68; Volume  2: Health criteria and other
    supporting information. Geneva, pp 185-186.

    WHO (1987) Polynuclear aromatic hydrocarbons (PAH). In: Air quality
    guidelines for Europe. Copenhagen, Regional Office for Europe, pp 105-
    117 (WHO Regional Publications, European Series, No. 23).

    WHO (1988) Emissions of heavy metals and PAH from municipal solid
    waste incinerators: Control technology and health impact. Copenhagen,
    Regional Office for Europe, 67 pp (Environmental Health Series, No
    32WHO/FADL).

    WHO (1991) Evaluation of certain food additives and contaminants.
    Thirty-seventh report of the Joint FAO/WHO Expert Committee on Food
    Additives. Geneva, pp 27-29 (WHO Technical Report Series 806).

    WHO (1996) Guidelines for drinking-water quality, Volume 2: Health
    criteria and other supporting information. Geneva, pp 495-505.

    Whong WZ, Stewart JD, Cutler D, & Ong T (1992) Comparative study of
    DNA adduct formation and cytogenic effects of two constituents in coke
    oven emissions with an  in vivo rat lung cell system. Environ Mol
    Mutag, 19 (Suppl 20): 70.

    Whong WZ, Stewart DJ, Cutler D, & Ong T (1994) Induction of  in 
     vivo DNA adducts by 4 industrial by-products in the rat lung-cell
    system. Mutat Res, 312:165-172.

    Wickström K, Pyysalo H, Plaami-Heikkilä S, & Tuominen J (1986)
    Polycyclic aromatic compounds (PAC) in leaf lettuce. Z
    Lebensmittelunters Forsch, 183: 182-185.

    Wielgosz SM, Brauze D, & Pawlak AL (1991) Ah locus-associated
    differences in induction of sister-chromatid exchanges and in DNA
    adducts by benzo [a]pyrene in mice. Mutat Res, 246: 129-137.

    Wienecke J, Kruse H, & Wassermann O (1992) Organic compounds in the
    flue gas from a power station with circulating fluid bed combustion of
    coal. Chemosphere, 25: 1889-1895.

    Wild SR & Jones KC (1993) Biological and abiotic losses of polynuclear
    aromatic hydrocarbons (PAHs) from soils freshly amended with sewage
    sludge. Environ Toxicol Chem, 12: 5-12.

    Wild SR, McGrath SP, & Jones KC (1990) The polynuclear aromatic
    hydrocarbon (PAH) content of archived sewage sludges. Chemosphere, 20:
    703-716.

    Wild SR, Berrow ML, & Jones KC (1991) The persistence of polynuclear
    aromatic hydrocarbons (PAH's) in sewage sludge amended agricultural
    soils. Environ Pollut, 72: 141-157.

    Wild SR, Mitchell DJ, Yelland CM, & Jones KC (1992) Arrested municipal
    solid waste incinerator fly ash as a source of polynuclear aromatic
    hydrocarbons (PAHs) to the environment. Waste Manage Res, 10: 99-111.

    Willems MI, Roggeband R, Baan RA, Wilmer JWGM, De Raat WK, & Lohman
    PHM (1991) Monitoring the exposure of rats to benzo [a]pyrene by the
    determination of mutagenic acitivity in excreta, chromosome
    aberrations and sister chromatid exchanges in peripheral blood cells,
    and DNA adducts in peripheral blood lymphocytes and liver.
    Mutagenesis, 6: 151-158.

    Williams RT (1959) Detoxication mechanisms. The metabolism and
    detoxication of drugs, toxic substances and other organic compounds,
    2nd Ed. London, Chapman & Hall, 768 pp.

    Williams GM (1977) Detection of chemical carcinogens by unscheduled
    DNA synthesis in rat liver primary cell cultures. Cancer Res, 37:
    1845-1851.

    Williams GM, Laspia MF & Dunkel VC (1982) Reliability of the
    hepatocyte primary culture / DNA repair test in testing of coded
    carcinogens and noncarcinogens. Mutat Res, 97: 359-370.

    Williams PT, Abbass MK, Andrews GE, & Bartle KD (1989) Diesel
    particulate emissions: The role of unburned fuel. Combust Flame, 75:
    1-24.

    Wilson NK & Chuang JC (1991) Indoor air levels of polynuclear aromatic
    hydrocarbons and related compounds in an eight-home pilot study. In:
    Cooke M, Loening K, & Merritt J ed. Polynuclear aromatic hydrocarbons:
    Measurements, means and metabolism. Columbus, Ohio, Battelle Press, pp
    1053-1064.

    Wilson NK, Chuang JC, & Kuhlman MR (1991) Sampling polycyclic aromatic
    hydrocarbons and related semivolatile organic compounds in indoor air.
    Indoor Air, 4: 513-521.

    Windsor JG Jr & Hites RA (1978) Polycyclic aromatic hydrocarbons in
    Gulf of Maine sediments and Nova Scotia soils. Geochim Cosmochim Acta,
    41: 27-33.

    Winker N, Weniger P, Klein W, Ott E, Kocsis F, Schoket B, & Korpert K
    (1995) Detection of polycyclic aromatic hydrocarbon exposure damage
    using different methods in laboratory animals. J Appl Toxicol, 15: 59-
    62.

    Winkler DL, Duncan KL, Hose JE, & Puffer HW (1983) Effects of
    benzo(a)pyrene on the early development of California grunion,
     Leuresthes tenuis (Pisces, Atherinidae). Fish Bull, 81: 473-481.

    Wise SA (1983) High-performance liquid chromatography for the
    determination of polycyclic aromatic hydrocarbons. In: Bjorseth A ed.
    Handbook of polycyclic aromatic hydrocarbons, Volume 2: Emission,
    sources and recent progress in analytical chemistry. New York, Marcel
    Dekker, pp 183-256.

    Wise SA (1985) Recent progress in the determination of PAH by high
    performance liquid chromatography. In: Bjorseth A & Ramdahl T ed.
    Handbook of polycyclic aromatic hydrocarbons, Volume 2. New York,
    Marcel Dekker, pp 113-191.

    Wise SA, Bonnett WJ, & May WE (1980) Normal- and reverse-phase liquid
    chromatographic separations of polycyclic aromatic hydrocarbons. In:
    Bjorseth A & Dennis AJ ed. Polynuclear aromatic hydrocarbons:
    Chemistry and biological effects. Columbus, Ohio, Battelle Press, pp
    791-806.

    Wise SA, Bonnett WJ, Guenther FR, & May WE (1981) A relationship
    between reversed-phase C18 liquid cromatographic retention and the
    shape of polycyclic aromatic hydrocarbons. J Chromatogr Sci, 19: 457-
    465.

    Wise SA, Sander LC, & May WE (1993) Determination of polycyclic
    aromatic hydrocarbons by liquid chromatography. J Chromatogr, 642:
    329-349.

    Wislocki PG, Buening MK, Levin W, Lehr RE, Thakkes DR, Jerina DM, &
    Conney AH (1979) Tumorigenicity of the diastereomeric
    benz [a]anthracene 3,4-diol-1,2-epoxides and the (+)-and
    (-)-enantiomers of benz [a]anthracene 3,4-dihydrodiol in newborn
    mice. J Natl Cancer Inst, 63: 201-204.

    Withey JR, Law FCP, & Endrenyi L (1991) Pharmacokinetics and
    bioavailability of pyrene in the rat. J. Toxicol Environ Health, 32:
    429-447.

    Withey JR, Shedden J, Law FPC, & Abedini S (1992) Distribution to the
    fetus and major organs of the rat following inhalation exposure to
    pyrene. J Appl Toxicol, 12: 223-231.

    Withey JR, Law FCP, & Endrenyi L (1993) Percutaneous uptake,
    distribution, and excretion of pyrene in rats. J Toxicol Environ
    Health, 40: 601-612.

    Witte H, Langenohl T, & Offenbächer G (1988) [Investigation of the
    entry of organic pollutants into soils and plants through the use of
    sewage sludge in agriculture. Part A: Organic pollutant load in sewage
    sludge.] Korresp Abwasser, 5: 440-448 (in German).

    Wodinsky I, Helinski A, & Kensler CJ (1964) Susceptibility of Syrian
    hamsters to induction of fibrosarcomas with a single injection of
    3,4,9,10-dibenzpyrene. Nature, 203: 308-309.

    Woidich W, Pfannhauser W, Blaicher G, & Tiefenbacher K (1976)
    [Analysis of polycyclic aromatic hydrocarbons in drinking and utility
    water.] Lebensmittelchem Gerichtl Chem, 30: 141-146 (in German).

    Wojciechowski JP, Kaur P & Sabharwal PS (1981) Comparison of metabolic
    systems required to activate pro-mutagens/carcinogens
     in vitro for sister-chromatid exchange studies. Mutat Res, 88: 89-
    97.

    Wojdani A & Alfred LJ (1984) Alterations in cell-mediated immune
    functions induced in mouse splenic lymphocytes by polycyclic aromatic
    hydrocarbons. Cancer Res, 44: 942-945.

    Wolfe JM & Bryan WR (1939) Effects induced in pregnant rats by
    injection of chemically pure carcinogenic agents. Am J Cancer, 36:
    359-368.

    Wolff MS, Herbert R, Marcus M, Rivera M, Landrigan PJ, & Andrews LR
    (1989) Polycyclic aromatic hydrocarbons (PAH) residues on skin in
    relation to air levels among roofers. Arch Environ Health, 44:
    157-163.

    Wolff RK, Griffith WC, Henderson RF, Hahn FF, Harkema JR, Rebar AH,
    Eidson AF, & McClellan RO (1989) Effects of repeated inhalation
    exposures to 1-nitropyrene, benzo(a)pyrene, Ga203 particles, and
    S02 alone and in combinations of particle clearance, bronchoalveolar
    lavage fluid composition, and histopathology. J Toxicol Environ
    Health, 27: 123-138.

    Wong O, Bailey WJ, & Amsel J (1992) Cancer mortality and incidence in
    mastic asphalt workers. Scand J Work Environ Health, 18: 133-135.

    Wood SC & Holsapple MP (1993) Effects of
    7,12-dimethylbenz [a]anthracene on the superantigen toxic shock
    syndrome toxin (TSST-1)-induced proliferation and antibody secretion
    by human lymphocytes. Fundam Appl Toxicol, 20: 280-287.

    Wood AW, Levin W, Ryan D, Thomas PE, Yagi H, Mah HD, Thakker DR,
    Jerina DM, & Conney AH (1977) High mutagenicity of metabolically
    activated chrysene 1,2-dihydrodiol: Evidence for bay region activation
    of chrysene. Biochem Biophys Res Commun, 78: 847-854.

    Wood AW, Levin W, Thomas PE, Ryan D, Karle JM, Yagi H, Jerina DM, &
    Conney AH (1978) Metabolic activation of dibenzo(a,h)anthracene and
    its dihydrodiols to bacterial mutagens. Cancer Res, 38: 1967-1973.

    Wood AW, Chang RL, Levin W, Ryan DE, Thomas PE, Mah HD, Karle JM, Yagi
    H, Jerina DM, & Conney AH (1979) Mutagenicity and tumorigenicity of
    phenanthrene and chrysene epoxides and diol epoxides. Cancer Res, 39:
    4069-4077.

    Wood AW, Levin W, Chang RL, Huang M-T, Ryan DE, Thomas PE, Lehr RE,
    Kumar S, Koreeda M, & Akagi, H (1980) Mutagenicity and
    tumor-initiating activity of cyclopenta(c,d)pyrene and structurally
    related compounds. Cancer Res, 40: 642-649.

    Wood AW, Chang RL, Levin W, Ryan DE, Thomas PE, Lehr RE, Kumar S,
    Sardella DJ, Boger E, Yagi H, Sayer JM, Jerina DM, & Conney AH (1981)
    Mutagenicity of the bayregion diol-epoxides and other benzo-ring
    derivatives of dibenzo(a,h)pyrene and dibenzo(a,i)pyrene. Cancer Res,
    41: 2589-2597.

    Wood AW, Chang RL, Levin W, Yagi H, Thakker DR, van Bladeren PJ,
    Jerina DM, & Conney AH (1983) Mutagenicity of the enantiomers of the
    diastereomeric bay-region benz [a]anthracene 3,4-diol-1,2-epoxides in
    bacterial and mammalian cells. Cancer Res, 43: 5821-5825.

    Wood AL, Bouchard DC, Brusseau ML, & Rao PSC (1990) Cosolvent effects
    on sorption and mobility of organic contaminants in soil. Chemosphere,
    21: 575-587.

    Woodhead AD, Setlow RB, & Pond V (1982) Effects of polycyclic aromatic
    hydrocarbons on the proliferation of ectopic thyroid tissue in
     Poecilia formosa, the Amazon molly. J Fish Biol, 20: 455-463.

    Wright BW & Smith RD (1989) Capillary supercritical fluid
    chromatography methods. In: Vo-Dinh T ed. Chemical analysis of
    polycyclic aromatic compounds. New York, John Wiley & Sons, pp
    111-149.

    Wu R, Jiang Y-M, Ge N-C, Bai S-M, & Qiao S-J (1985) Determination of
    trace amounts of organic pollutants in the Yellow River by capillary
    column gas chromatography-mass spectrometry. Int J Environ Anal Chem,
    22: 115-126.

    Wu Z, Hearl FJ, Peng K, McCawley MA, Chen A, Palassis J, Dosemeci M,
    Chen J, McLaughlin JK, Rexing SH, & Blot WJ (1992) Occupational
    hygiene around the world: Current occupational exposures in Chinese
    iron and copper mines. Appl Occup Environ Health, 7: 735-743.

    Wynder EL & Hoffmann D (1959a) A study of tobacco carcinogenesis. VII.
    The role of higher polycyclic hydrocarbons. Cancer, 12: 1079-1086.

    Wynder EL & Hoffmann D (1959b) The carcinogenicity of
    benzofluoranthenes. Cancer, 12: 1194-1199.

    Wynder EL, Mabuchi K, & Beattie EJ (1970) The epidemiology of lung
    cancer. Recent trends. J Am Med Assoc, 213: 2221-2228.

    Xu GT, Zigler JS Jr, & Lou MF (1992) The possible mechanism of
    naphthalene cataract in rat and its prevention by an aldose reductase
    inhibitor (AL01576). Exp Eye Res, 54: 63-72.

    Xue B, Lei ZM, Zhao XL, & Yang XH (1991) [Acute immunotoxicity induced
    by benzo(a)pyrene in mice.] Zhonggou Yaolixue Dulixue Zazhi, 5: 221-
    222 (in Chinese with English abstract).

    Yalkowsky SH & Valvani SC (1979) Solubilities and partitioning. 2.
    Relationships between aqueous solubilities, partition coefficients,
    and molecular surface areas of rigid aromatic hydrocarbons. J Chem Eng
    Data, 24: 127-129.

    Yamasaki H, Kuwata K, & Miyamoto H (1982) Effects of ambient
    temperature on aspects of airborne polycyclic aromatic hydrocarbons.
    Environ Sci Technol, 16: 189-194.

    Yamazaki H, Imamura E, Kamei S, Yamauchi A, Kakiuchi Y, & Tai HH
    (1990) Polycyclic aromatic hydrocarbons affect the calcium ionophore
    induced activation of rabbit platelet. Chemosphere, 21: 21-28.

    Yang K, Airoldi L, Pastorelli R, Restano J, Guanci M, & Hemminki K
    (1996) Aromatic DNA adducts in lymphocytes of humans working at high
    and low traffic density areas. Chem-Biol Interactions, 101: 127-136.

    Yoshikawa T, Ruhr LP, Flory W, Banton MJ, Giamalva D, Church DF, &
    Pryor WA (1987) Toxicity of polycyclic aromatic hydrocarbons. III.
    Effects of  beta-naphthoflavone pretreatment on hepatotoxicity of
    compounds produced in the ozonation or NO2-nitration of phenanthrene
    and pyrene in rats. Vet Hum Toxicol, 29: 113-117.

    Yoshioka Y, Nagase H, Ose Y, & Sato T (1986) Evaluation of the test
    method 'activated sludge, respiration inhibition test' proposed by the
    OECD. Ecotoxicol Environ Saf, 12: 209-212.

    You L, Wang D, Galati A, Ross JA, Mass MJ, Nelson GB, Wilson KH, Amin
    S, Stoner JC, Nesnow S, & Stoner GD (1994) Tumor multiplicity, DNA
    adducts and K- ras mutation pattern of 5-methylchrysene in strain A/J
    mouse lung. Carcinogenesis, 15: 2613-2618.

    Young L (1947) The metabolic conversion of naphthalene to
    1:2-dihydronaphthalene-1:2-diol. Biochem J, 41: 417-422.

    Young L (1950) The oxidation of polycyclic hydrocarbons in the animal
    body. Biochem Soc Symp, 5: 27-39.

    Young DR, Gossett RW, Baird RB, Brown DA, Taylor PA, & Miille MJ
    (1983) Wastewater inputs and marine bioaccumulation of priority
    pollutant organics off southern California. Water Chlorination, 4:
    871-884.

    Yrjänheikki E, Pyy L, Hakala E, Lapinlampi T, Lisko A, & Vähäkangas K
    (1995) Exposure to polycyclic aromatic hydrocarbons in a new coking
    plant. Am Ind Hyg Assoc J, 56: 782-787.

    Yun C-H, Shimada T, & Guengerich FP (1992) Roles of human liver
    cytochrome P4502C and 3A enzymes in the 3-hydroxylation of
    benzo (a)pyrene. Cancer Res, 52: 1868-1874.

    Zachleder V, Abarzua S, & Wittenburg E (1983) Effects of
    3,4-benzopyrene on the course of cell cycle events in the chlorococcal
    alga  Scenedesmus quadricauda. Planta, 157: 432-440.

    Zackheim HS (1964) Comparative cutaneous carcinogenesis in the rat.
    Oncologia, 17: 236-246

    Zajdela F, Perin-Roussel O, & Saguem S (1987) Marked differences
    between mutagenicity in  Salmonella and tumour-initiating activities
    of dibenzo [a,e]fluoranthene proximate metabolites; initiation
    inhibiting activity of norharman. Carcinogenesis, 8: 461-464.

    Zander M (1980) [Origins, chemical and physical properties of PAH.]
    In: [Air pollution through polycyclic aromatic hydrocarbons:
    Registration and evaluation.] Düsseldorf, VDI-Verlag, pp 11-21 (VDI
    Report No. 358) (in German).

    Zepp RG & Schlotzhauer PF (1979) Photoreactivity of selected aromatic
    hydrocarbons in water. In: Jones PW & Leber P ed. Polynuclear aromatic
    hydrocarbons. Carcinogenesis and mutagenesis. Ann Arbor, Michigan, Ann
    Arbor Science Publishers, pp 141-158.

    Zey JN & Stephenson R (1986) NIOSH health hazard evaluation: Roofing
    and waterproofing sites, Chicago, Illinois. Cincinnati, Ohio, National
    Institute for Occupational Safety and Health, 29 pp (Report No.
    HETA-85-416-1742; PB 87-174207).

    Zhao Z-H, Quan W-Y, & Tian D (1990) Urinary 1-hydroxypyrene as an
    indicator of human exposure to ambient polycylic aromatic hydrocarbons
    in a coal-burning environment. Sci Total Environ, 92: 145-154.

    Zhao Z-H, Quan WY, & Tian DH (1992) Experiments on the effects of
    several factors on the 1-hydroxypyrene level in human urine as an
    indicator of exposure to polycyclic aromatic hydrocarbons. Sci Total
    Environ, 133: 197-207.

    Zhong BZ, Gu ZW, Stewart J, & Ong T (1995) Micronucleus formation
    induced by three polycyclic aromatic hydrocarbons in rat bone marrow
    and spleen erythrocytes following intratracheal instillation. Mutat
    Res, 326: 147-153.

    Zijlstra JA & Vogel EW (1984) Mutagenicity of
    7,12-dimethylbenz [a]anthracene and some other aromatic mutagens in
     Drosophila melanogaster. Mutat Res, 125: 243-261.

    Zimmermeyer G, Roge G, & Schabronath J (1991) [Reduction of PAH
    emissions: For example, some stationary plants.] In: [Carcinogenic
    compounds in the environment: Sources, measurement, risk, reduction.]
    Düsseldorf, VDI-Verlag, pp 93-115 (VDI Report No. 888) (in German).

    Zinkham WH & Childs B (1958) A defect of glutathione metabolism in
    erythrocytes from patients with a naphthalene-induced hemolytic
    anemia. Pediatrics, 14: 461-471.

    Zuelzer WW & Apt L (1949) Acute hemolytic anemia due to naphthalene
    poisoning. J Am Med Assoc, 141: 185-190.
    

    1.  RÉSUMÉ

    1.1  Choix des composés pour la monographie

    Les hydrocarbures aromatiques polycycliques forment un vaste groupe de
    composés et c'est par centaines qu'ils peuvent être libérés dans
    l'environnement lors de la combustion incomplète ou de la pyrolyse des
    matières organiques, constituant ainsi une source importante
    d'exposition humaine. L'étude des matrices susceptibles d'être
    importantes sur le plan écologique tels que les résidus de combustion
    du charbon, les gaz d'échappement des véhicules à moteur, les huiles
    lubrifiantes usées et la fumée de tabac, montre que leur activité
    cancérogène est essentiellement liée à leur teneur en HAP.

    Les HAP se présentent presque toujours sous la forme de mélanges.
    Etant donné que leur composition est complexe et qu'elle dépend du
    processus qui leur a donné naissance, il n'a pas été possible de
    passer en revue tous les mélanges susceptibles de contenir des
    hydrocarbures aromatiques polycycliques. C'est pourquoi on a choisi 33
    composés (31 composés originaux et 2 dérivés alkylés) en vue d'une
    évaluation sur la base des données pertinentes relatives aux points
    d'aboutissement toxicologiques retenus ou à l'exposition (Tableau 1).
    Toutefois, étant donné que l'on ne disposait d'études épidémiologiques
    que pour les mélanges et que ces études sont indispensables pour
    l'évaluation du risque, les sections 8 et 10 exposent les résultats
    relatifs à des mélanges d'HAP, contrairement au reste de la
    monographie.

    Nombre d'articles et de mises au point ont été publiées au sujet de la
    présence, de la distribution et de la transformation des HAP dans
    l'environnement ainsi que de leurs effets toxicologiques et
    écotoxicologiques. Sauf indication contraire, seules les références
    des 10 à 15 dernières années sont prises en compte dans la
    monographie. En revanche, les mises au point consacrées à des études
    plus anciennes sont citées à titre de complément d'information.

    1.2  Identité, propriétés physiques et chimiques et méthodes d'analyse

    On désigne généralement par hydrocarbures aromatiques polycycliques un
    vaste ensemble de composés contenant un ou plusieurs noyaux
    aromatiques condensés et constitués de carbone et d'hydrogène. Ces
    hydrocarbures sont solides à la température ambiante. Ils ont pour
    caractéristiques communes d'avoir un point de fusion et un point
    d'ébullition élevés, une faible tension de vapeur et d'être très peu
    solubles dans l'eau-d'autant moins que leur masse moléculaire est plus
    élevée. Ils sont solubles dans de nombreux solvants organiques et très
    lipophiles. Chimiquement, ils sont relativement inertes. Les réactions
    intéressantes du point de vue de leur devenir dans l'environnement et
    des possibilités de pertes au cours des prélèvements d'air sont celles
    qui comportent une photodécomposition ou dans lesquelles interviennent
    les oxydes d'azote, l'acide nitrique, les oxydes de soufre, l'acide
    sulfurique, l'ozone et les radicaux hydroxyles.


        Tableau 1. Les hydrocarbures aromatiques polycycliques évalués dans cette monographie

                                                                                                                               

    Nom commun                    Nom CAS                              Synonymea                      No d'enregistrement CAS
                                                                                                                               

    Acenaphthylene                Acenaphthylene                                                      91-20-3
    Acenaphthene                  Acenaphthylene, 1,2-dihydro-                                        208-96-8
    Anthanthrene                  Dibenzo[def,mno]chrysene                                            191-26-4
    Anthracene                    Anthracene                                                          120-12-7
    Benz[a]anthracene             Benz[a]anthracene                    1,2-Benzanthracene,            56-55-3
                                                                       tetraphene
    Benzo[a]fluorene              11H-Benzo[a]fluorene                 1,2-Benzofluorene              238-84-6
    Benzo[b]fluorene              11H-Benzo[b]fluorene                 2,3-Benzofluorene              243-17-4
    Benzo[b]fluoranthene          Benz[e]acephenanthrylene             3,4-Benzofluoranthene          205-99-2
    Benzo[ghi]fluoranthene        Benzo[ghi]fluoranthene               2,13-Benzofluoranthene         203-12-3
    Benzo[j]fluoranthene          Benzo[j]fluoranthene                 10,11-Benzofluoranthene        205-82-3
    Benzo[k]fluoranthene          Benzo[k]fluoranthene                 11,12-Benzofluoranthene        207-08-9
    Benzo[ghi]perylene            Benzo[ghi]perylene                   1,12-Benzoperylene             191-24-2
    Benzo[c]phenanthrene          Benzo[c]phenanthrene                 3,4-Benzophenanthrene          195-19-7
    Benzo[a]pyrene                Benzo[a]pyrene                       3,4-Benzopyreneb               50-32-8
    Benzo[e]pyrene                Benzo[e]pyrene                       1,2-Benzopyrene                192-97-2
    Chrysene                      Chrysene                             1,2-Benzophenanthrene          218-01-9
    Coronene                      Coronene                             Hexabenzobenzene               191-07-1
    Cyclopenta[cd]pyrene          Cyclopenta[cd]pyrene                 Cyclopenteno[cd]pyrene         27208-37-3
    Dibenz[a,h]anthracene         Dibenz[a,h]anthracene                1,2:5,6-Dibenzanthracene       53-70-3
    Dibenzo[a,e]pyrene            Naphtho[1,2,3,4-def]chrysene         1,2:4,5-Dibenzopyrene          192-65-4
    Dibenzo[a,h]pyrene            Dibenzo[b,def]chrysene               3,4:8,9-Dibenzopyrene          189-64-0
    Dibenzo[a,i]pyrene            Benzo[rst]pentaphene                 3,4:9,10-Dibenzopyrene         189-55-9
    Dibenzo[a,l]pyrene            Dibenzo[def,p]chrysene               1,2:3,4-Dibenzopyrene          191-30-0
    Fluoranthene                  Fluoranthene                                                        206-44-0
    Fluorene                      9H-Fluorene                                                         86-73-7
    Indeno[1,2,3-cd]pyrene        Indeno[1,2,3-cd]-pyrene              2,3-o-Phenylenpyrene           193-39-5
    5-Methylchrysene              Chrysene, 5-methyl-                                                 3697-24-3
    1-Methylphenanthrene          Phenanthrene, 1-methyl-                                             832-69-9

    Tableau 1. (cont.)

                                                                                                                               

    Nom commun                    Nom CAS                              Synonymea                      No d'enregistrement CAS
                                                                                                                               

    Naphthalene                   Naphthalene                                                         91-20-3
    Perylene                      Perylene                             peri-Dinaphthalene             198-55-0
    Phenanthrene                  Phenanthrene                                                        85-01-8
    Pyrene                        Pyrene                               Benzo[def]phenanthrene         129-00-0
    Triphenylene                  Triphenylene                         9,10-Benzophenanthrene         217-59-4
                                                                                                                               

    Des listes assez complètes de synonymes ont également été publiées par le CIRC (1989) et par Loening & Merritt (1990).
    a Synonyme commun utilisé dans la littérature
    b On le trouve également sous le nom de benzo(def)chrysène.


    L'échantillonnage dans l'air ambiant s'effectue par recueil de
    matières particulaires sur filtres eu fibre de verre,
    polytétrafluoréthylène, ou fibre de quartz, au moyen
    d'échantillonneras de grand volume ou d'échantillonneurs passifs.
    Comme il y a risque de volatilisation des hydrocarbures de la phase
    gazeuse, qui pourraient s'évaporer des filtres lors de
    l'échantillonnage, on a l'habitude de les piéger par adsorption sur
    mousse de polyuréthane. La variabilité des résultats provient
    essentiellement de ce processus d'échantillonnage.

    Sur les lieux de travail, les prélèvements d'air se font à faible
    débit; les particules sont recueillies sur des filtres de fibre de
    verre ou de polytétrafluoréthylène et la phase gazeuse sur résine
    Amberlite XAD-2. Les collecteurs de gaz de cheminées sont constitués
    de filtres en fibre de verre ou en quartz placés devant un réfrigérant
    destiné à retenir le condensant et une cartouche d'adsorbant (en
    général, de l'XAD-2). Les gaz d'échappement des véhicules à moteur
    sont recueillis au laboratoire, pendant un cycle de fonctionnement
    normalisé simulant les conditions réelles. Les émissions sont
    recueillies telles quelles ou après dilution dans de l'air froid
    filtré.

    De nombreuses techniques d'extraction et de purification ont été
    décrites. En fonction de la matrice, on peut extraire les HAP au
    Soxhlet, par action des ultrasons, par partage liquide-liquide ou,
    après dissolution et digestion alcaline, au moyen d'un solvant
    sélectif. On utilise aussi l'extraction par fluide supercritique pour
    diverses substances solides présentes dans l'environnement.
    L'efficacité de l'extraction dépend largement du solvant et nombre de
    solvants utilisés par le passé se sont révélés inappropriés. Après
    l'extraction, on procède généralement à une purification par
    chromatographie sur colonne - d'alumine, de gel de silice ou de
    sephadex LH-20- mais aussi par chromatographie sur couche mince.

    La recherche et le dosage s'effectuent classiquement par
    chromatographie en phase gazeuse avec détection par ionisation de
    flamme ou encore par chromatographie en phase liquide à haute
    performance avec détection en UV ou fluorescence, généralement en
    série. Pour la chromatographie en phase gazeuse, on utilise des
    colonnes capillaires en silice fondue, avec des polysiloxanes comme
    phase stationnaire (SE-54 et SE-52); pour la chromatographie en phase
    liquide, on utilise couramment des colonnes de gel de silice C-18.
    Pour confirmer l'identité des pics chromatographiques, on couple
    généralement un spectromètre de masse au chromatographie.

    Le choix des HAP à doser dépend de l'objectif de la mesure: étude à
    visée sanitaire, investigation écotoxicologique ou recherche d'une
    source de pollution. La recherche et le dosage de divers groupes de
    composés peuvent être demandés au niveau national ou international.

    1.3  Sources d'exposition humaine et environnementale

    On sait peu de choses sur la production des hydrocarbures aromatiques
    polycycliques et sur les processus auxquels ils peuvent être soumis,
    mais il est probable que ces activités n'entraînent la libération que
    de petites quantités d'hydrocarbures. Ceux que l'on retrouve dans
    l'environnement sont principalement utilisés comme intermédiaires dans
    la préparation du chlorure de polyvinyle et de divers plastifiants
    (naphtalène), de pigments (acénaphtène, pyrène), de colorants
    (anthracène, fluoranthène) et de pesticides (phénanthrène).

    Les émissions les plus importantes d'hydrocarbures aromatiques
    polycycliques sont dues à la combustion incomplète de matières
    organiques lors de divers processus industriels ou d'autres activités
    humaines, notamment:

    -    les diverses opérations effectuées sur la houille, le pétrole
         brut et le gaz naturel, y compris la cokéfaction, la conversion
         de la houille, le raffinage du pétrole et la production de noirs
         de carbone, de créosote, de goudron de houille et de bitume;

    -    la production d'aluminium, de fer et d'acier dans les divers
         ateliers et fonderies;

    -    la génération d'énergie calorifique par les centrales thermiques,
         le chauffage des habitations et la cuisine;

    -    le brûlage des déchets;

    -    la circulation automobile; et

    -    la fumée de tabac dispersée dans l'environnement.

    Les HAP, notamment ceux qui ont une masse moléculaire élevée,
    s'adsorbent sur les particules de matière une fois qu'ils sont libérés
    dans l'environnement par la voie atmosphérique. La pénétration dans
    l'hydrosphère et la géosphère s'effectue ensuite selon un processus de
    dépôt par voie humide ou par voie sèche. La conservation du bois par
    traitement au créosote constitue une autre source de pénétration d'HAP
    dans l'hydrosphère et les dépôts de déchets contaminés, comme par
    exemple les boues d'égout et les cendres volantes, contribuent à
    l'introduction de ces composés dans la géosphère. On possède peu de
    renseignements sur le passage des HAP dans la biosphère. Des
    hydrocarbures aromatiques polycycliques sont présents à l'état naturel
    dans la tourbe, le lignite, la houille et le pétrole brut. La plupart
    de ceux que l'on trouve dans l'anthracite sont fermement liés à la
    structure carbonée et ne peuvent pas en être extraits par lessivage.

    On a pu déterminer le passage d'HAP dans l'environnement en mettant en
    évidence un profil de concentration caractéristique, mais cela n'a été
    possible que dans quelques cas. Le benzo(a)pyrène est fréquemment
    utilisé comme indicateur de la présence d'HAP, notamment dans les
    études un peu anciennes. En général, les chiffres concernant les
    émissions d'HAP ne sont que des estimations basées sur des données
    plus ou moins fiables et elles ne donnent qu'une idée approximative de
    l'exposition.

    Les sources d'HAP les plus importantes sont les suivantes:

     La cokéfaction de la houille: les émissions atmosphériques d'HAP
    résultant de la cokéfaction de la houille ont sensiblement diminué en
    Allemagne au cours des 10 dernières années par suite des améliorations
    techniques apportées aux installations industrielles, à la fermeture
    des anciennes usines et au recul de la production de coke. On pense
    que la situation est à peu près la même dans le reste de l'Europe
    occidentale, au Japon, et aux Etats-Unis, sans toutefois disposer de
    données à ce sujet.

     La production d'aluminium (notamment en raison de l'utilisation
    d'anodes spéciales en graphite),  de fer et d'acier ainsi que les
    liants utilisés en fonderie dans les moules à sable. On ne possède
    guère d'informations à ce sujet.

     Le chauffage collectif ou individuel: les émissions sont
    principalement constituées de phénanthrène, de pyrène et de chrysène.
    Les poëles à bois en émettent 25 à 1000 fois plus que les poëles à
    charbon et dans les régions où l'on se chauffe surtout au bois, la
    majeure partie des émissions atmosphériques d'HAP ont ce mode de
    chauffage pour origine, principalement l'hiver. On considère donc que
    le chauffage des habitations est une source importante d'hydrocarbures
    aromatiques polycycliques dans les pays en développement où l'on brûle
    de la biomasse dans des poëles assez rudimentaires.

     La cuisine: la combustion incomplète des matières combustibles peut
    produire des HAP, de même que le chauffage de l'huile de cuisine et la
    cuisson des denrées alimentaires elles-mêmes.

     La circulation des véhicules à moteur: les principaux hydrocarbures
    rejetés par les véhicules dotés de moteurs à essence sont le
    fluoranthène et le pyrène, tandis que le naphtalène et l'acénaphtène
    prédominent dans les gaz d'échappement des moteurs diesel. Le
    cyclopenta(cd)-pyrène est émis en grande quantité par les moteurs à
    essence mais il est juste au-dessus de la limite de détection dans les
    gaz d'échappement des moteurs diesel. Le taux d'émission, qui dépend
    du composé, du type de véhicule et de l'état de son moteur, de même
    que des conditions dans lesquelles l'essai se déroule, varie de
    quelques nanogrammes par kilomètre à > 1000 mg/km. La pose d'un
    catalyseur réduit de façon spectaculaire les émissions d'HAP par les
    moteurs d'automobiles.

     Les feux de forêt: Dans les pays où la forêt couvre de vases
    étendues de territoire, les feux de forêt peuvent contribuer de façon
    importante à l'émission d'HAP.

     Centrales thermiques à charbon: Les HAP libérés dans l'atmosphère
    par ces centrales sont principalement des composés bi-et tricycliques.
    Dans les zones contaminées, la teneur en HAP de l'air ambiant peut
    être supérieure à celle qui résulte des émission de cheminées.

     Incinération des déchets: les émissions d'HAP dans les gaz de
    cheminée des usines d'incinération sont inférieures à 10 mg/m3 dans
    un certain nombre de pays.

    1.4  Transport, distribution et transformation dans l'environnement

    La destinée des HAP, qu'ils soient seuls ou en mélange, dépend d'un
    certain nombre de processus de distribution et de transformation. Les
    processus de distribution les plus importants sont le partage entre
    l'eau et l'air, entre l'eau et les sédiments et entre l'eau et les
    organismes vivants.

    Comme ces hydrocarbures sont hydrophobes et très peu solubles dans
    l'eau, il n'ont qu'une très faible affinité pour la phase aqueuse;
    toutefois, bien qu'ils soient libérés dans l'environnement par la voie
    atmosphérique, on les retrouve également en concentration importante
    dans l'hydrosphère, du fait que leur constante de Henry est faible.
    Etant donné que leur affinité est plus grande pour la phase organique
    que pour la phase aqueuse, leur coefficient de partage entre les
    solvants organiques- comme l'octanol- et l'eau est élevé. Ils ont
    également une forte affinité pour les fractions organiques des
    sédiments, du sol et des organismes vivants, de sorte qu'ils
    s'accumulent dans les organismes aquatiques et sédimentaires ainsi que
    dans leur nourriture. On ne connaît pas avec certitude l'importance
    relative de leur fixation à partir de la nourriture et de l'eau. Chez
    la daphnie et les mollusques, il y a corrélation positive entre
    l'accumulation d'HAP provenant de l'eau et le coefficient de partage
    entre l'octanol et l'eau (Kow). Par contre, chez les poissons et les
    algues qui sont capables de métaboliser ces hydrocarbures, il n'y a
    pas de corrélation entre la concentration des différents HAP et le
    Kow.

    Le phénomène de bioamplification, c'est-à-dire la concentration d'une
    substance dans l'organisme d'animaux à chaque niveau trophique
    successif de la chaîne alimentaire, n'a pas été observé en milieu
    aquatique et il ne semble pas qu'il puisse se produire, car la plupart
    des organismes sont tout à fait à même de métaboliser les HAP. Ce sont
    les organismes qui occupent les niveaux trophiques les plus élevés qui
    possèdent la plus grande capacité de biotransformation.

    La dégradation des HAP s'opère par photodécomposition, par
    biodégradation microbienne et, chez les organismes supérieurs, par
    métabolisation. Cette dernière voie de transformation n'a guère
    d'influence sur la destinée globale des HAP dans l'environnement, mais

    elle joue néanmoins un rôle biologique important du fait que des
    métabolites cancérogènes sont susceptibles de se former. Comme les HAP
    sont chimiquement stables et dépourvus de groupements réactifs,
    l'hydrolyse n'intervient pas dans leur décomposition. Il n'existe
    guère d'épreuves classiques pour l'étude de la biodégradation des HAP.
    Celle-ci s'opère généralement en aérobiose, la vitesse du processus
    diminuant fortement avec le nombre de cycles aromatiques. En
    anaérobiose, la dégradation est beaucoup plus lente.

    Dans l'air et dans l'eau, les HAP subissent une photo-oxydation en
    présence de radicaux ou molécules sensibilisateurs comme OH, NO3 ou
    O3. Au laboratoire, le temps de demi-réaction avec les radicaux OH
    présents dans l'air est d'environ 1 jour; en revanche la constante de
    vitesse est généralement beaucoup plus faible dans le cas des
    réactions avec NO3 et O3. En principe, l'adsorption des HAP de
    masse moléculaire élevée sur les particules carbonées devrait
    stabiliser leur réaction avec les radicaux OH. La réaction des HAP
    possédant 2 à 4 cycles avec NO3, réaction qui a lieu principalement
    en phase gazeuse, conduit à la nitration de ces hydrocarbures, c'est-
    à-dire à la formation de produits notoirement cancérogènes. Pour
    certains d'entre eux, la photo-oxydation semble être plus rapide dans
    l'eau que dans l'air. Les calculs basés sur la physico-chimie et la
    biodégradabilité de ces hydrocarbures montrent que ceux qui possèdent
    quatre cycles aromatiques ou davantage persistent dans
    l'environnement.

    1.5  Concentrations dans l'environnement et exposition humaine

    Les HAP sont présent dans tout l'environnement et de nombreuses études
    ont permis d'en mettre un certain nombre en évidence dans divers
    compartiments.

    1.5.1  Air

    La concentration des HAP a tendance à être environ 10 fois plus élevée
    l'hiver que l'été. En hiver, la source principale d'hydrocarbures
    aromatiques polycyclique est le chauffage des habitations, alors qu'en
    été, ce sont les gaz d'échappement des véhicules à moteur qui sont les
    principaux responsables. Dans l'air de diverses agglomérations, on a
    mis en évidence, pour un certain nombre d'hydrocarbures aromatiques
    polycycliques, des concentrations moyennes de 1 à 30 ng/m3. Dans
    certains grands centres urbains, où la circulation automobile est très
    intense et où l'on utilise beaucoup la biomasse pour le chauffage des
    habitations, comme Calcutta par exemple, on a trouvé des teneurs
    allant jusqu'à 200 ng/m3 pour divers HAP. Sous les tunnels routiers,
    on a mesuré des concentrations de 1 à 50 ng/m3. Le
    cyclopenta(cd)pyrène et le pyrène étaient présents à des
    concentrations atteignant 100 ng/m3. Dans une station de métro, on a
    mesuré des concentrations allant jusqu'à 20 ng/m3. A proximité de
    sources de pollution d'origine industrielle, la concentration moyenne
    des divers HAP s'étalait de 1 à 10 ng/m3. La concentration du
    phénanthrène pouvait atteindre environ 310 ng/m3.

    La concentration de fond des HAP est d'au moins deux ordres de
    grandeur plus faible qu'à proximité de sources telles que les
    véhicules à moteur. A titre d'exemple, à 1100 m d'altitude, on a
    obtenu des valeurs comprises entre 0,004 et 0,03 ng/m3.

    1.5.2  Eaux superficielles et précipitations

    On pense que la majeure partie des HAP présents dans l'eau y ont été
    entraînés par ruissellement ou résultent de retombées atmosphériques
    (petites particules) ou encore de l'abrasion de l'asphalte (grosses
    particules). Il reste que, pour une étendue d'eau donnée, la majeure
    partie des HAP n'a pas toujours la même origine. Eu général, la
    plupart des échantillons d'eaux superficielles contiennent divers HAP
    à des concentrations pouvant atteindre 50 ng/litre, mais dans des
    cours d'eau extrêmement pollués, on a relevé des concentrations allant
    jusqu'à 6 000 ng/litre. La teneur des eaux souterraine en HAP se situe
    entre 0,02 et 1,8 ng/litre et dans des échantillons d'eau destinée à
    la boisson, on a trouvé des valeurs du même ordre de grandeur. Les HAP
    présents dans l'eau de boisson ont principalement pour origine le
    revêtement d'asphalte des réservoirs et des canalisations.

    Dans l'eau de pluie, on relève des concentrations comprises entre 10
    et 200 ng/litre, et des teneurs allant jusqu'à 1000 ng/litre ont été
    mesurées dans la neige et le brouillard.

    1.5.3  Sédiments

    La concentration des HAP dans les sédiments est généralement 10 fois
    plus forte que dans les précipitations.

    1.5.4  Sol

    Les HAP présents dans le sol proviennent principalement des dépôts
    atmosphériques, de la carbonisation des végétaux et du dépôt de
    particules en suspension dans les effluents ou divers types de
    déchets. L'ampleur de la pollution des sols dépend de facteurs tels
    que le type de cultures auxquels ils sont soumis, la porosité et la
    teneur en substances humiques.

    A proximité des sources industrielles, on a trouvé, pour les divers
    HAP, des concentrations dans le sol pouvant atteindre 1 g/kg. Pour les
    HAP ayant une autre origine, par exemple les gaz d'échappement des
    véhicules à moteur, la concentration dans le sol va de 2 à 5 mg/kg.
    Dans les zones non polluées, la teneur du sol en HAP se situe entre 5
    et 100 µg/kg.

    1.5.5  Denrées alimentaires

    Les denrées alimentaires crues ou plus généralement, non transformées,
    ne contiennent normalement pas de grandes quantités d'HAP, mais il
    peut s'en former lorsqu'on fait rôtir, griller, frire ou que l'on
    prépare d'une manière ou d'une autre, ces produits. Les légumes
    peuvent être contaminés par le dépôt de particules aéroportées ou par

    le sol sur lequel ils ont poussé. D'après diverses mesures, la
    concentration d'un certain nombre d'HAP dans la viande, le poisson,
    les produits laitiers, les légumes, les fruits, les céréales et les
    produits céréaliers, les pâtisseries et confiseries, les boissons
    ainsi que les huiles et graisses animales et végétales, se situe entre
    0,01 et 10 µg/kg. On a trouvé des concentrations supérieures à 100
    µg/kg dans de la viande fumée et pouvant aller jusqu'à 86 µg/kg dans
    du poisson fumé; dans des céréales fumées, les valeurs relevées
    atteignaient 160 µg/kg. Dans de l'huile de coco on en a trouvé jusqu'à
    460 µg/kg. Dans le lait maternel, les mesures ont donné des valeurs
    comprises entre 0,003 et 0,03 µg/kg.

    1.5.6  Organismes aquatiques

    On sait que les organismes marins absorbent et accumulent les HAP
    présents dans l'eau. Le degré de contamination dépend du développement
    industriel et urbain ainsi que du trafic maritime dans la zone. Des
    concentrations allant jusqu'à 7 mg/kg out été mises en évidence dans
    des organismes aquatiques vivant à proximité de points de décharge
    d'effluents industriels et la concentration moyenne d'HAP dans
    l'organisme d'animaux aquatiques prélevés dans des zones contaminées
    s'est révélée comprise entre 10 et 500 µg/kg, avec des pointes à 5
    mg/kg.

    Chez des animaux aquatiques prélevés dans des zones où la pollution
    par des HAP n'avait pas d'origine précise, on a trouvé des valeurs
    moyennes de 1 à 100 µg/kg, mais des valeurs supérieures sont
    possibles, par exemple 1 mg/kg chez des homards du Canada.

    1.5.7  Organismes terrestres

    Chez des insectes, on a relevé des concentrations comprises entre 730
    et 5 500 µg/kg. La teneur en HAP des déjections de lombrics varie
    sensiblement selon le lieu: dans une région fortement industrialisée
    de l'est de l'Allemagne, la teneur en benzo(a)pyrène des déjections de
    lombrics atteignait 2 mg/kg.

    1.5.8  Population générale

    Les principales sources d'exposition non professionnelle sont les
    suivantes: air pollué, fumée de feux et foyers non couverts, fumée de
    tabac dispersée dans l'environnement, denrées alimentaires et eau de
    boisson contaminées, utilisation de produits contaminés par des HAP.
    On peut trouver dans l'air à l'intérieur des habitations des HAP qui
    proviennent du chauffage ou de la présence de fumée de tabac, à des
    concentrations moyennes de 1 à 100 ng/m3, avec des pointes à 2300
    ng/m3.

    On estime que l'apport d'HAP d'origine alimentaire est de 0,10 à 10 µg
    par jour et par personne. La quantité totale de benzo(a)pyrène
    absorbée quotidiennement avec l'eau de boisson est estimée à 0,0002 µg
    par personne. Ce sont les céréales et les produits céréaliers qui

    contribuent le plus à cet apport car ils sont un constituant majeur de
    la ration alimentaire totale.

    1.5.9  Exposition professionnelle

    A proximité d'une batterie de fours à coke, on a relevé des teneurs en
    benzo(a)pyrène allant de <0,1 à 100-200 µg/m3, avec des pointes à
    environ 400 µg/m3. Dans les installations modernes de gazéification
    de la houille, la concentration des HAP est en général de < 1 µg/m3
    et de 30 µg/m3 au maximum. Des échantillons prélevés individuellement
    dans la zone de travail de personnes affectées à divers postes dans
    des raffineries de pétrole, ont révélé une exposition comprise entre
    2,6 et 470 µg/m3. Dans des échantillons d'air prélevés dans des
    ateliers de préparation de bitume, on a obtenu une concentration en
    HAP totaux de 0,004 à 50 µg/m3. Lors de travaux d'enrobage de
    chaussées, on a relevé sur le site des concentrations atmosphériques
    en HAP totaux pouvant atteindre 190 µg/m3, avec une concentration
    moyenne de 0,13 µg/m3. Dans une fonderie d'aluminium, la dosimétrie
    individuelle indiquait des valeurs de 0,05-9,6 µg/m3 pour les HAP
    totaux, mais dans les urines d'ouvriers travaillant dans une unité de
    production d'aluminium, on n'en a relevé que de très petites
    quantités. Dans une fonderie allemande, les échantillons d'air ambiant
    contenaient des HAP à des concentrations pouvant atteindre 5 µg/m3.
    Elles étaient respectivement égales à 3-40 µg/m3 dans des mines de
    fer et à 4-530 µg/m3 dans des mines de cuivre. Dans les vapeurs de
    cuisson d'une usine de produits alimentaires, la concentration en HAP
    était comprise entre 0,07 et 26 µg/m3.

    1.6  Cinétique et métabolisme

    Les HAP sont absorbés au niveau des poumons, des voies digestives et
    par la voie percutanée. La vitesse de résorption au niveau pulmonaire
    dépend de la nature de l'hydrocarbure, de la granulométrie des
    particules sur lesquelles il est adsorbé et de la composition du
    substrat adsorbant. Les hydrocarbures adsorbés sur des particules sont
    éliminés plus lentement des poumons que les hydrocarbures libres. Chez
    les rongeurs, la résorption est rapide dans les voies digestives, mais
    les métabolites, excrétés par la voie biliaire, finissent par
    retourner dans l'intestin. Des études effectuées sur des rongeurs avec
    des mélanges d'HAP ayant subi un postmarquage au 32p ont montré
    qu'après absorption par la voie percutanée, les hydrocarbures
    parvenaient jusqu'aux poumons où ils se liaient à l'ADN. Chez la
    souris, la vitesse d'absorption percutanée dépend de la nature du
    composé.

    Quelle que soit la voie d'administration, les HAP se répartissent dans
    tout l'organisme et on en retrouve dans pratiquement tous les organes
    internes, mais plus particulièrement dans ceux qui sont riches en
    lipides. Après injection intraveineuse à des rongeurs, les HAP sont
    rapidement éliminés du courant sanguin, mais ils sont capables de
    traverser la barrière foeto-placentaire et on en a décelé la présence
    dans les tissus foetaux.

    Les HAP ont un métabolisme complexe. En général, le composé initial
    est époxydé puis transformé en phénol, diol ou tétrol qui peut
    lui-même se conjuguer à l'acide sulfurique ou à l'acide glucuronique
    (sulfuro- ou glucuro-conjugaison) ou encore au glutathion. La plupart
    du temps, la métabolisation d'un hydrocarbure aromatique polycyclique
    entraîne sa détoxication, mais certains d'entre eux subissent une
    activation en composés susceptibles de se lier à l'ADN, principalement
    des époxydes-diols, qui sont capables d'amorcer un processus de
    cancérisation. Les métabolites et leurs conjugués sont excrétés dans
    les urines et les matières fécales, mais les conjugués excrétés dans
    la bile peuvent être hydrolysés par les enzymes de la flore
    intestinale et être ensuite réabsorbés. On peut déduire des données
    disponibles au sujet de la charge totale de l'organisme humain en HAP,
    que ces hydrocarbures ne s'accumulent pas dans l'organisme et qu'ils
    se renouvellent rapidement. Il faut exclure de cette conclusion les
    HAP qui forment des liaisons covalentes avec certain constituants
    tissulaires, notamment les acides nucléiques et que les processus de
    réparation ne permettent pas d'éliminer.

    1.7  Effets sur les mammifères de laboratoire et effets in vitro

    La toxicité aiguë des HAP est faible à modérée. Un HAP bien
    caractérisé, le naphtalène, a donné des valeurs de la DL50 par voie
    orale ou intraveineuse égales à 100-500 mg/kg pc chez la souris et une
    DL50 moyenne par voie orale de 2700 mg/kg pc chez le rat. Pour les
    autres HAP, on a obtenu des valeurs similaires. Du naphtalène
    administré en doses uniques à des souris, des rats et des hamsters, a
    provoqué l'apparition d'une nécrose des bronchioles.

    Des études à court terme ont révélé des anomalies hématologiques, dues
    à une myélotoxicité dans le cas du benzo(a)pyrène et qui, en ce qui
    concerne le dibenz(a,h)anthracène, consistaient en modifications
    hémolymphatiques. Dans le cas du naphtalène, on a constaté une anémie.
    Toutefois, une étude de 7 jours au cours de laquelle on a administré
    du naphtalène à des souris par voie orale et intrapéritonéale, a
    révélé l'existence d'une tolérance aux effets de cet hydrocarbure. On
    n'a que rarement décrit des effets généraux dus à une longue
    exposition à des HAP, car l'effet toxicologique retenu dans la plupart
    des études correspondantes était la cancérisation. Aux doses où se
    déclenche un processus de cancérisation, on observe également des
    effets toxiques importants.

    En étudiant les effets cutanés indésirables des HAP après application
    sur l'épiderme, on a constaté que des hydrocarbures faiblement ou non
    cancérogènes comme le pérylène, le benzo(e)pyrène, le phénanthrène, le
    pyrène, l'anthracène, l'acénaphtène, le fluorène et le fluoranthène
    étaient inactifs, alors que les hydrocarbures cancérogènes comme le
    benz(a) anthracène, le dibenz(a,h)-anthracène et le benzo(a)pyrène
    provoquaient une hyperkératose. Les vapeurs d'anthracène et de
    naphtalène peuvent causer une légère irritation oculaire. Le
    benzo(a)pyrène a provoqué une hypersensibilité de contact chez des
    cobayes et des souris. Le benz(a)anthracène, le benzo(a)pyrène, le
    dibenz(a,h)anthracène et le naphtalène se sont révélés embryotoxiques
    chez la souris et le benzo(a)pyrène a également eu des effets

    tératogènes et des effets sur la reproduction. On a fait de gros
    efforts pour tenter de d'élucider les bases génétiques des effets
    embryotoxiques du benzo(a)pyrène. On n'observe de morts foetales et de
    malformations que si le système des monooxygénases du cytochrome p450
    est inductible, chez la mère (avec migration transplacentaire) ou chez
    l'embryon. On ne peut expliquer tous les effets observés par une
    prédisposition génétique, mais chez la souris et le lapin, cet
    hydrocarbure a une activité transplacentaire qui se traduit par des
    adénomes pulmonaires et des papillomes cutanés dans la descendance des
    animaux traités. On a également observé une diminution de la fécondité
    et la destruction des ovocytes.

    On a également procédé à de nombreuses études sur la génotoxicité des
    HAP et sur leur aptitude à provoquer une transformation cellulaire. La
    plupart des 33 HAP qui font l'objet de cette monographie sont
    génotoxiques ou ont des chances de l'être. Les seuls composés pour
    lesquels on ait obtenu des résultats négatifs dans toutes les épreuves
    sont l'anthracène, le fluorène et le naphtalène. Dans le cas du
    phénanthrène et du pyrène, l'irrégularité des résultats ne permet pas
    de se prononcer avec certitude sur leur génotoxicité.

    Les travaux très complets qui ont été consacrés à la cancérogénicité
    des hydrocarbures aromatiques polycycliques montrent que 26 des 33
    composés qui font l'objet de la présente monographie sont
    effectivement cancérogènes ou soupçonnés de l'être (Tableau 2). Le
    mieux connu de tous est le benzo(a)pyrène, qui a été étudié par toutes
    les méthodes existantes sur sept espèces. Plus d'une douzaine d'études
    ont été consacrées à l'anthracène, à l'anthanthrène, au
    benz(a)anthracène, au chrysène, au dibenz(a,h)anthracène, au
    dibenzo(a,i)pyrène, au 5-méthylehrysène, au phénanthrène et au pyrène.
    Aux études spéciales sur l'immunotoxicité, la phototoxicité et
    l'hépatotoxicité des HAP s'ajoutent un certain nombre d'articles sur
    la toxicité oculaire du naphtalène. L'anthracène, le benzo(a)pyrène et
    un certain nombre d'autres HAP sont phototoxiques pour la peau des
    mammifères ou les cultures cellulaires in vitro, lorsqu'on les
    applique sous rayonnement ultraviolet. D'une façon générale, on
    considère que les HAP ont un effet immunodépresseur. Après
    administration de benzo(a)pyrène à des souris, on a observé une forte
    immunodépression dans la descendance de ces animaux pendant une
    période pouvant atteindre 18 mois. On a également constaté un
    accroissement de la régénération du tissu hépatique et une
    augmentation du poids du foie. La formation de cataractes sous l'effet
    du naphtalène chez des souris appartenant à des souches génétiquement
    différentes, a été attribuée à l'inductibilité du cytochrome P 450.

    Dès les années 30, on a proposé des modèles théoriques prenant en
    compte un grand nombre de résultats expérimentaux, pour tenter de
    prévoir le pouvoir cancérogène des hydrocarbures aromatiques
    polycycliques à partir de leur structure moléculaire. Le premier de
    ces modèles se fondait sur la forte réactivité chimique de certaines
    doubles liaisons (théorie de la région K). Ultérieurement, on a tenté
    une approche systématique du problème basée sur la synthèse chimique
    des divers métabolites possibles et l'étude de leur activité mutagène.

    Tableau 2. Résultats des épreuves de génotoxicité et de cancérogénicité
    effectuées sur les 33 hydrocarbures aromatiques polycycliques étudiés.

                                                                       

    Compound                          Genotoxicity    Carcinogenicity
                                                                       

    Acenaphthene                      (?)             (?)
    Acenaphthylene                    (?)             No studies
    Anthracene                        -               -
    Benz[a]anthracene                 +               +
    Benzo[a]fluorene                  (?)             (?)
    Benzo[a]pyrene                    +               +
    Benzo[b]fluoranthene              +               +
    Benzo[b]fluorene                  (?)             (?)
    Benzo[c]phenanthrene              (+)             +
    Benzo[e]pyrene                    +               ?
    Benzo[ghi]fluoranthene            (+)             (-)
    Benzo[ghi]perylene                +               -
    Benzo[j]fluoranthene              +               +
    Benzo[l]fluoranthene              +               +
    Chrysene                          +               +
    Coronene                          (+)             (?)
    Cyclopenta[cd]pyrene              +               +
    Dibenzo[a,e]pyrene                +               +
    Dibenz[a,h]anthracene             +               +
    Dibenzo[a,h]pyrene                (+)             +
    Dibenzo[a,i]pyrene                +               +
    Dibenzo[a,l]pyrene                (+)             +
    Fluoranthene                      +               (+)
    Fluorene                          -               -
    Indeno[1,2,3-cd]pyrene            +               +
    1-Methylphenanthrene              +               -
    5-Methylchrysene                  +               +
    Naphthalene                       -               ?
    Perylene                          +               -
    Phenanthrene                      (?)             (?)
    Pyrene                            (?)             -
    Triphenylene                      +               -
                                                                       

    +, résultat positif; -, résultat négatif; ?, résultat douteux
    Parenthèses, résultat tiré d'une petite base de données.


    Selon cette théorie, dite de la "région en baie", les époxydes
    adjacents à une région en baie conduisent à la formation d'ions
    carbonium très stables qui peuvent alkyler les bases nucléiques. Parmi
    les autres théories, on peut citer la théorie de la "di-région" et
    celle du "cation radical potentiel".

    De nombreux HAP sont cancérogènes pour l'animal et pourraient
    également l'être pour l'Homme. D'ailleurs, on a montré que
    l'exposition à divers mélanges contenant des HAP augmentait
    l'incidence des cancers dans les populations humaines en cause. Ce qui
    est préoccupant, c'est que les HAP dont l'étude expérimentale a révélé
    l'activité cancérogène chez l'animal, sont probablement aussi
    cancérogènes pour l'Homme. Ces composés font apparaître des tumeurs
    non seulement au point de contact, mais aussi à distance de ce point.
    Le pouvoir cancérogène peut varier avec la voie d'administration. On a
    proposé plusieurs méthodes pour évaluer le risque associé à une
    exposition à ces composés, seuls ou en mélange. Sans se prononcer en
    faveur de telle ou telle méthode, la monographie indique les données
    nécessaires, les hypothèses et les conditions de validité etc. pour
    trois d'entre elles qui ont été plus ou moins validées en vue d'une
    évaluation quantitative du risque.

    1.8  Effets sur l'Homme

    Les HAP sont présents dans l'environnement et sur les lieux de travail
    dans des conditions d'une telle complexité que pour étudier
    l'exposition humaine à chacun de ces composés à l'état pur, on s'est
    limité à des expériences sur des voluntaires, sauf dans le cas du
    naphtalène que l'on utilise comme anti-mite sur les vêtements.

    L'application cutanée d'anthracène, de fluoranthène et de phénanthrène
    provoque des réaction cutanées spécifiques et le benzo(a)pyrène donne
    naissance à des verrues régressives et réversibles que l'on a classées
    comme étant de nature néoplasique. On connaît les effets généraux du
    naphtalène en raison des nombreux cas d'ingestion accidentelle
    auxquels il a donné lieu, notamment chez des enfants. La dose létale
    est de 5 000 à 15 000 mg pour un adulte et de 2 000 mg sur deux jours
    pour un enfant. Après contact cutané ou ingestion, l'intoxication se
    caractérise par une anémie hémolytique aiguë, qui peut également
    toucher le foetus par la voie transplacentaire.

    On sait que le tabagisme est la cause la plus importante de cancers du
    poumon et qu'il accroît également l'incidence des tumeurs de la
    vessie, du bassinet du rein, de la cavité buccale, du pharynx, du
    larynx et de l'oesophage. On estime en revanche que les HAP présents
    dans les denrées alimentaires ne jouent pas un rôle important dans
    l'apparition des cancers chez l'Homme. Dans les zones très
    industrialisées, on a observé un accroissement de la charge de
    l'organisme en HAP par suite de la pollution de l'air ambiant. Les
    malades dont on traite le psoriasis par des applications de goudron,
    sont également exposés à des HAP.

    C'est en 1775 que l'on a, pour la première fois, avancé que
    l'exposition professionnelle à la suie était une cause de cancer du
    scrotum. Par la suite, on a remarqué que l'exposition aux goudrons et
    aux paraffines provoquait des cancers de la peau. Le poumon est
    désormais la principale localisation des cancers dus aux HAP, les
    cancers cutanés étant devenus plus rares par suite des progrès de
    l'hygiène individuelle.

    On a effectué des études épidémiologiques sur l'exposition aux HAP
    chez des ouvriers de fours à coke pendant la cokéfaction et la
    gazéification de la houille, chez des ouvriers d'ateliers de
    préparation d'asphalte, de fonderies, de fours à aluminium ou encore
    chez des travailleurs exposés aux gaz d'échappement de moteurs diesel.
    On a constaté une augmentation des tumeurs pulmonaires dues aux HAP
    chez les ouvriers des fours à coke et des ateliers de préparation de
    l'asphalte, de même que chez ceux qui travaillaient près des cuves de
    réduction électrolytique de l'alumine par le procédé Söderberg. C'est
    chez les ouvriers des fours à coke que l'on a mis en évidence le
    risque le plus élevé, avec un rapport comparatif de mortalité (SMR) de
    195. Plusieurs études ont permis d'établir des relations dose-réponse.
    Dans les usine d'aluminium, on a observé non seulement des cancers de
    la vessie, mais aussi des symptômes asthmatiformes, des anomalies de
    la fonction pulmonaire et des bronchites chroniques. Chez les ouvriers
    des fours à coke, il y avait diminution des taux d'immunoglobulines
    sériques et dépression des fonctions immunitaires. Par ailleurs, ou a
    signalé l'apparition d'une cataracte après cinq ans d'exposition au
    naphtalène.

    On a mis au point un certain nombre de méthodes pour évaluer
    l'exposition interne aux HAP. Dans la plupart de ces études, on a
    procédé au dosage des métabolites urinaires de ces composés:
    thioéthers, 1-naphtol, ß-naphtylamine, hydroxyphénantrènes et
    1-hydroxypyrène. Ce dernier composé est largement utilisé comme
    indicateur biologique d'une exposition à des HAP.

    Les effets génotoxiques des HAP ont été étudiés en recherchant la
    présence de substances mutagènes dans les urines et les matières
    fécales et celle de micronoyaux, d'aberrations chromosomiques et
    d'échanges entre chromatides-soeurs dans les lymphocytes du sang
    périphérique. En outre, on a dosé les adduits du benzo(a)pyrène et de
    l'ADN dans les lymphocytes du sang périphérique et dans d'autres
    tissus, ainsi que ceux que cet HAP forme avec des protéines comme
    l'albumine. On a également procédé au dosage des anticorps dirigés
    contre les adduits de l'ADN.

    Plusieurs études se sont donné pour but de rechercher s'il était
    possible d'utiliser la présence de 1-hydroxypyrène dans l'urine et
    d'adduits de l'ADN dans les lymphocytes comme marqueurs d'une
    exposition à des HAP. Il est plus facile de doser le 1-hydroxypyrène
    urinaire que les adduits de l'ADN. Ce marqueur a en outre l'avantage
    d'être moins sujet aux variations interindividuelles et de permettre
    de repérer des expositions plus faibles. Les deux types de marqueurs
    ont été utilisés pour évaluer l'exposition humaine dans divers
    environnements. Ainsi, on a relevé une augmentation de la
    concentration urinaire de 1-hydroxypyrène sur les divers lieux de
    travail de cokeries, d'usines de production d'aluminium, d'ateliers
    d'imprégnation du bois, de fonderies et d'ateliers de préparation
    d'asphalte. L'exposition la plus forte a été observée chez les
    ouvriers des fours à coke et chez ceux qui travaillent à
    l'imprégnation du bois avec du créosote. Chez ces travailleurs,
    l'exposition est à 95% percutanée, alors que dans le reste de la

    population, les HAP sont absorbés principalement par la voie
    alimentaire et par la voie respiratoire lors de la consommation de
    tabac.

    L'estimation du risque associé à une exposition à des HAP repose sur
    l'évaluation de cette exposition et sur les résultats des études
    épidémiologiques. En ce qui concerne les ouvriers des fours à coke, on
    aboutit à un risque relatif de cancer du poumon égal à 15,7. En
    procédant de la même manière pour la population générale, on trouve
    que le risque, pour un individu donné, de faire un cancer du poumon au
    cours de son existence est de 10-4 à 10-5 par ng de benzo(a)pyrène
    par m3 d'air. En d'autres termes, il y a environ une personne sur 10
    000 ou 100 000 qui va faire un cancer au cours de sa vie par suite de
    la présence de benzo(a)pyrène dans l'air ambiant.

    1.9  Effets sur les autres êtres vivants au laboratoire et dans leur
    milieu naturel

    S'il y a absorption simultanée de lumière UV ou de lumière visible,
    les HAP peuvent provoquer des effets toxiques aigus sur les poissons
    et sur des invertébrés aquatiques comme les daphnies. La toxicité des
    HAP peut être modifiée par dégradation et métabolisation. A faible
    concentration, les HAP peuvent stimuler la croissance des
    microorganismes et des algues. Le composé le plus toxique pour les
    algues est le benz(a)anthracène, un hydrocarbure tétracyclique. La
    valeur de la CE50 pour ce composé (réduction de 50% des paramètres
    vitaux) est égale à 1-29 µg/litre. Dans le cas du benzo(a)pyrène, un
    composé pentacyclique, elle est égale à 5-15 µg/litre. Toujours en ce
    qui concerne les algues, la CE50 pour la plupart des HAP
    tricycliques est égale à 240-290 µg/litre. Le naphtalène, qui est
    bicyclique, est le moins toxique, avec une CE50 de 2 800-34 000
    µg/litre.

    Il n'y a pas de différence de sensibilité bien nette entre les divers
    groupes taxonomiques d'invertébrés tels que les crustacés, les
    insectes, les mollusques, les polychètes et les échinodermes. Le
    naphtalène est le moins toxique avec une CL50 à 96 h de 100 à 2
    300/µg/litre. Pour trois HAP tricycliques, la valeur de ce même
    paramètre varie de <1 à 3 000 µg/litre. L'anthracène pourrait être
    plus toxique que les autres HAP tricycliques avec une CL50 à 24 h
    comprise entre <1 et 260 µg/litre. Pour les composés à quatre, cinq et
    six noyaux aromatiques, la CL50 à 96 h est comprise entre 0,2 et 1
    200 µg/litre. Des effets toxiques aigus (CL50) ont été observés chez
    des poissons à des concentrations de 110 à > 10 000 µg/litre de
    naphtalène, de 30 à 40 000 µg/litre d'HAP tricycliques (anthracène,
    2,8-360 µg/litre) et de 0,7 à 26 µg/litre d'HAP tétra- et
    pentacycliques.

    Chez des poissons vivant à l'état sauvage, on a attribué la présence
    de tumeurs hépatiques à la contamination des sédiments par des HAP à
    la concentration de 250 mg/kg. On a également provoqué l'apparition de
    tumeurs chez des poissons par exposition en laboratoire. L'exposition
    des poissons à certains HAP peut aussi provoquer chez eux des

    anomalies physiologiques et perturber leur croissance, leur
    reproduction, leur locomotion et leur respiration.

    1.  RESUMEN

    1.1  Selección de compuestos para esta monografía

    Los hidrocarburos aromáticos policiclicos (HAP) constituyen una clase
    muy amplia de compuestos, y durante la combustión incompleta o la
    pirolisis de materia orgánica pueden liberarse cientos de sustancias
    distintas, que son una fuente importante de exposición humana. Los
    estudios de diversas matrices aplicables al medio ambiente, como los
    efluentes de la combustión de carbón, los gases de escape de los
    vehículos de motor, el aceite lubricante de motores usados y el humo
    del tabaco, han demostrado que los HAP de esas mezclas son los
    principales responsables de su potencial carcinogénico.

    En las mezclas casi siempre hay presentes HAP. Debido a que la
    composición de tales muestras es compleja y varía con el proceso de
    formación, no es posible examinar con detalle en la presente
    monografía todas las mezclas que contienen HAP. Así pues, se
    seleccionaron 33 compuestos distintos (31 HAP originales y dos
    derivados alquilo) para evaluarlos tomando como base la disponibilidad
    de datos pertinentes sobre los efectos finales toxicológicos y/o la
    exposición (Cuadro 1). Sin embargo, dado que sólo se disponía para las
    mezclas de estudios epidemiológicos, que son imprescindibles para la
    evaluación del riesgo, en las Secciones 8 y 10 se presentan los
    resultados de estudios de mezclas de HAP, en contraposición con el
    resto de la monografía.

    Se han publicado numerosos artículos y reseñas sobre la presencia,
    distribución y transformación de HAP en el medio ambiente y sobre sus
    efectos ecotoxicológicos y toxicológicos. Solamente se citan en la
    presente monografía referencias de los 10-15 últimos años, a menos que
    no se dispusiera de otra información; en relación con los estudios más
    antiguos y con otra información se citan reseñas.

    1.2  Identidad, propiedades físicas y químicas y métodos analíticos

    El término "hidrocarburos aromáticos policíclicos" se refiere en
    general a una clase muy amplia de compuestos orgánicos que contienen
    dos o más anillos aromáticos condensados formados por átomos de
    carbono y de hidrógeno. A temperatura ambiente, los HAP son sólidos.
    Las características comunes de la clase son puntos de fusión y de
    ebullición elevados, presión de vapor baja y solubilidad en agua muy
    baja, que tiende a disminuir con el aumento del peso molecular. Los
    HAP son solubles en muchos disolventes orgánicos y muy lipófilos.
    Desde el punto de vista químico son bastante inertes. Las reacciones
    que tienen interés con respecto a su destino en el medio ambiente y a
    las posibles fuentes de pérdidas durante el muestren atmosférico son
    la fotodescomposición y las reacciones con óxidos de nitrógeno, ácido
    nítrico, óxidos de azufre, ácido sulfúrico, ozono y radicales
    hidroxilo.


        Cuadro 1. Hidrocarburos aromáticos policíclicos evaluados en esta monografía

                                                                                                                      
    Nombre común                Nombre CAS                     Sinónimoa                         No de registro CAS
                                                                                                                      

    Acenaftileno                Acenaftileno                                                     91-20-3
    Acenafteno                  Acenaftileno, 1.2-dihidro-                                       208-96-8
    Antantreno                  Dibenzo[def,mno]criseno                                          191-264
    Antraceno                   Antraceno                                                        120-12-7
    Benz[a]antraceno            Benz[a]antraceno               1,2-Benzantraceno, tetrafeno      56-55-3
    Benzo[a]fluoreno            11H-Benzo[a]fluoreno           1,2-Benzofluoreno                 238-84-6
    Benzo[b]fluoreno            11H-Benzo[b]fluoreno           2,3-Benzofluoreno                 243-17-4
    Benzo[b]fluoranteno         Benz[e]acefenantrileno         3,4-Benzofluoranteno              205-99-2
    Benzo[ghl]fluoranteno       Benzo[ghl]fluoranteno          2,13-Benzofluoranteno             203-12-3
    Benzo[j]fluoranteno         Benzo[j]fluoranteno            10,11-Benzofluoranteno            205-82-3
    Benzo[k]fluoranteno         Benzo[k]fluoranteno            11,12-Benzofluoranteno            207-08-9
    Benzo[ghi]perileno          Benzo[ghi]perileno             1,12-Benzoperileno                191-24-2
    Benzo[c]fenantreno          Benzo[c]fenantreno             3,4-Benzofenantreno               195-19-7
    Benzo[a]pireno              Benzo[a]pireno                 3,4-Benzopirenob                  50-32-8
    Benzo[e]pireno              Benzo[e]pireno                 1.2-Benzopireno                   192-97-2
    Criseno                     Criseno                        1,2-Benzofenantreno               218-01-9
    Coroneno                    Coroneno                       Hexabenzobencano                  191-07-1
    Ciclopenta[cd]pireno        Ciclopenta[cd]pireno           Ciclopenteno[cd]pireno            27208-37-3
    Dibenz[a,h]antraceno        Dibenz[a,h]antraceno           1,2:5.6-Dibenzantraceno           53-70-3
    Dibenzo[a,e]pireno          Naftol[1,2:3,4-def]criseno     1,2:4,5-Dibenzopireno             192-65-4
    Dibenzo[a,h]pireno          Dibenzo[b,def]criseno          3,4:8,9-Dibenzopireno             189-64-0
    Dibenzo[a,i]pireno          Benzo[rsf]pentafeno            3,4:9,10-Dibenzopireno            189-55-9
    Dibenzo[a,l]pireno          Dibenzo[def,p]criseno          1,2:3,4-Dibenzopireno             191-30-0
    Fluoranteno                 Fluoranteno                                                      206-44-0
    Fluoreno                    9H-Fluoreno                                                      86-73-7
    Indeno[1,2,3-cd]pireno      Indeno[1,2,3-cd]pireno         2,3-o-Fenilenpireno               193-39-5
    5-Metilcriseno              Criseno, 5-metil-                                                3697-24-3
    1-Metilfenantreno           Fenantreno, 1-metil-                                             832-69-9
    Naftaleno                   Naftaleno                                                        91-20-3
    Perileno                    Perileno                       peri-Dinaftaleno                  198-55-0
    Penantreno                  Fenantreno                                                       85-01-8
    Pireno                      Pireno                         Benzo[def]fenantreno              129-00-0
    Trifenileno                 Trifenileno                    9,10-Benzofenantreno              217-59-4
                                                                                                                      

    Cuadro 1 (sigue).


    Han notificado listas muy amplias de sinónimos el CIIC (1983) y Loening y Merritt (1990).
    a Sinónimo común que aparece en la bibliografia.
    c También denominado benzo[def]criseno.


    El aire del ambiente se muestrea recogiendo partículas suspendidas en
    filtros de fibra de vidrio, de politetrafluoroetileno o de fibra de
    cuarzo mediante muestreadores de alto volumen o pasivos. Los HAP en
    fase de vapor, que podrían volatilizarse de los filtros durante el
    muestreo, se suelen retener por adsorción en espuma de poliuretano. La
    fase de muestren es con diferencia la fuente más importante de
    variabilidad de los resultados.

    En el lugar de trabajo se toman muestras con tasas de flujo bajas; se
    recogen las partículas en filtros de fibra de vidrio o de
    politetrafluoroetileno y los vapores en resina XAD-2 de amberlita. Los
    dispositivos para el muestren de gases de chimenea constan de un
    filtro de fibra de vidrio o de fibra de cuarzo en la parte frontal de
    un refrigerador para recoger la materia condensable y un cartucho
    adsorbente (por lo general XAD-2). Las muestras de gases de escape de
    los vehículos se toman en condiciones de laboratorio, con ciclos de
    conducción normalizados que simulan las condiciones en carretera. Las
    emisiones se recogen sin diluir o bien una vez diluidas con aire frío
    filtrado.

    Se han descrito numerosas técnicas de extracción y purificación. En
    función de la matriz, los HAP se extraen de las muestras con un
    aparato de Soxhlet, por ultrasonidos, mediante reparto liquido-liquido
    o, tras la disolución o la digestión alcalina de la muestra, con un
    disolvente selectivo. También se ha utilizado la extracción de fluidos
    supercríticos a partir de diversos sólidos del medio ambiente. La
    eficacia de la extracción depende en gran medida del disolvente
    utilizado, y muchos de los que se utilizaban en el pasado no eran
    apropiados. Las muestras extraídas se suelen purificar por
    cromatografía en columna, en particular sobre alúmina, silicagel o
    Sephadex LH-20, pero también por cromatografía en capa fina.

    La identificación y la cuantificación se realizan habitualmente
    mediante cromatografía de gases con detección por ionización de llama
    o mediante cromatografía liquida de alta resolución (HPLC) con
    detección por ultravioleta o fluorescencia, generalmente en serie. En
    la cromatografía de gases se utilizan columnas capilares de sílice
    fundido con polisiloxanos (SE-54 y SE-52) como fases estacionarias; en
    la HPLC se suelen utilizar columnas de sílice-C18. Con frecuencia se
    acopla un detector de espectrometría de masas a una columna de fase
    gaseosa a fin de confirmar la identidad de los picos.

    La elección de los HAP que se han de determinar depende de la
    finalidad de la medición, por ejemplo para estudios orientados a la
    salud o ecotoxicológicos, o bien para investigar las fuentes. Es
    posible que se exija o se recomiende la realización de pruebas para
    distintos conjuntos de compuestos a nivel nacional e internacional.

    1.3  Fuentes de exposición humana y ambiental

    Es poca la información disponible acerca de la producción y
    elaboración de HAP, pero es probable que sólo se desprendan pequeñas
    cantidades como resultado directo de esas actividades. Los HAP que se
    encuentran se utilizan sobre todo como productos intermedios en la
    producción de cloruro de polivinilo y de agentes plastificantes
    (naftaleno), pigmentos (acenafteno, pireno), tintes (antraceno,
    fluoranteno) y plaguicidas (fenantreno).

    Las mayores emisiones de HAP se derivan de la combustión incompleta de
    materia orgánica durante procesos industriales y en otras actividades
    humanas, en particular:

    -    elaboración de carbón, de petróleo crudo y de gas natural,
         incluida la coquificación de carbón, la conversión de carbón, el
         refinado de petróleo y la producción de negro de humo, de
         creosota, de alquitrán de hulla y de betún;

    -    producción de aluminio, de hierro y de acero en fábricas y
         fundiciones;

    -    calefacción en centrales de energía y en residencias y ocinado;

    -    combustión de basuras;

    -    tráfico de vehículos de motor; y

    -    humo de tabaco en el medio ambiente.

    Los HAP, especialmente los de mayor peso molecular, cuando se
    incorporen al medio ambiente a través de la atmósfera se adsorben en
    las partículas en suspensión. La hidrosfera y la geosfera se ven
    afectadas de manera secundaria por la deposición húmeda y seca. La
    madera conservada con creosota es otro fuente de liberación de HAP en
    la hidrosfera, y la deposición de desechos contaminados, como fangos
    de alcantarillado y cenizas en suspensión, contribuye a las emisiones
    de HAP en la geosfera. Hay poca información acerca del paso de HAP a
    la biosfera. Hay HAP presentes naturalmente en la turba, el lignito,
    el carbón y el petróleo crudo. La mayoría de los HAP de las antracitas
    están fuertemente unidos a la estructura del carbón y no se pueden
    lixiviar.

    La liberación de HAP en el medio ambiente se ha determinado mediante
    la identificación de un perfil característico de su concentración,
    pero esto sólo ha sido posible en un pequeño número de casos. Con
    frecuencia se ha utilizado el benzo[a]pireno como indicador de HAP,
    especialmente en estudios más antiguos. En general, las emisiones de
    HAP son solamente estimaciones basadas en datos más o menos fidedignos
    y apenas den una idea general de la exposición.

    Las fuentes más importantes de HAP son las siguientes:

     Coquificación de carbón: Las emisiones de HAP en suspensión en el
    aire procedentes de la coquificación de carbón en Alemania han
    disminuido considerablemente en los 10 últimos años gracias a las
    mejoras técnicas de las instalaciones existentes, al cierre de otras
    antiguas y a la menor producción de coque. Se supone que la situación
    es análoga en el resto de Europa occidental, el Japón y los Estados
    Unidos, pero no se dispone de datos.

     Producción de aluminio (principalmente en ánodos especiales de
    carbón), de hierro y de acero y los aglutinantes utilizados en la
    arena de moldeo de las fundiciones: La información disponible es
    escasa.

     Cocinas y calefacción de viviendas: Los principales componentes que
    se emiten son fenantreno, fluoranteno, pireno y criseno. Las emisiones
    de los hornillos de leña son 25-1000 veces superiores a las que se
    producen en los de carbón, y en las zonas donde predomina el uso de
    leña en las viviendas la mayor proporción de HAP en suspensión puede
    derivarse de esta fuente, especialmente en invierno. Por consiguiente,
    se supone que la liberación de HAP en la calefacción de las viviendas
    es una fuente importante en los países en desarrollo, donde con
    frecuencia se quema biomasa en hornillos relativamente simples.

     Cocinado: Pueden emitirse HAP durante la combustión incompleta de
    los combustibles, del aceite de cocinar y de los alimentos que se
    cocinen.

     Tráfico de vehículos de motor: Los principales compuestos que se
    liberar de los vehículos de gasolina son el fluoranteno y el pireno,
    mientras que en los gases de escape de los vehículos de motor diesel
    abundan el naftaleno y el acenafteno. Aunque los motores de gasolina
    emiten una proporción elevada de ciclopenta[cd]pireno, su
    concentración en los gases de escape de los motores diesel está apenas
    por encima del límite de detección. Las tasas de emisión, que dependen
    de la sustancia, el tipo de vehículo, el estado de su motor y las
    condiciones de la prueba, oscilan entre unos pocos nanogramos por
    kilómetro y > 1000 mg/km. Las emisiones de HAP de los vehículos de
    motor se reducen enormemente con la instalación de catalizadores.

     Incendios forestales: En los países con grandes superficies
    forestales, los incendios pueden contribuir de manera importante a las
    emisiones de HAP.

     Centrales eléctricas de carbón: Los HAP que se liberar en la
    atmósfera a partir de dichas centrales son sobre todo compuestos de
    dos y tres anillos. En las zonas contaminadas, los niveles de HAP en
    el aire pueden ser más elevados que los de los gases de chimenea.

     Incineración de basuras: Las emisiones de HAP en los gases
    procedentes de este tipo de incineración fueron en varios países < 10
    mg/m3.

    1.4  Transporte, distribución y transformación en el medio ambiente

    Son varios los factores de distribución y de transformación de los que
    depende el destino tanto de los HAP por separado como de las mezclas.
    Los procesos de distribución más importantes son el reparto entre el
    agua y el aire, entre el agua y los sedimentos y entre el agua y la
    biota.

    Puesto que los HAP son hidrófobos, con escasa solubilidad en el agua,
    su afinidad por la fase acuática es muy pequeña; sin embargo, a pesar
    del hecho de que la mayoría de los HAP se liberan en el medio ambiente
    a través de la atmósfera, también se encuentran concentraciones
    considerables en la hidrosfera, debido a sus bajas constantes de la
    ley de Henry. Como la afinidad de los HAP por las fases orgánicas es
    mayor que la que tienen por el agua, sus coeficientes de reparto entre
    disolventes orgánicos como el octanol y el agua son elevados. Su
    afinidad por las fracciones orgánicas de los sedimentos, del suelo y
    de la biota es también alta, por lo que se acumulan en los organismos
    del agua y los sedimentos y en sus alimentos. No se conoce con
    claridad la importancia relativa de su ingesta con los alimentos y el
    agua. En  Daphnia y en los moluscos, hay una correlación positiva
    entre la acumulación de HAP procedentes del agua y el coeficiente de
    reparto octanol:agua (Kow). Sin embargo, en los peces y las algas
    capaces de metabolizar los HAP no hay correlación entre las
    concentraciones internas de distintos HAP y el Kow.

    No se ha observado bioamplificación -aumento de la concentración de
    una sustancia en animales de niveles tróficos sucesivos de las cadenas
    alimentarias- en sistemas acuáticos y no cabe prever que se produzca,
    puesto que la mayoría de los organismos tienen un potencial de
    biotransformación elevado para los HAP. El mayor potencial de
    biotransformación se observa en los organismos de los niveles tróficos
    más altos de las cadenas alimentarias.

    Los HAP se descomponen por fotodegradación, biodegradación por
    microorganismos y metabolismo en la biota de niveles más altos. Aunque
    la última rata de transformación tiene escasa importancia para el
    destino global de los HAP en el medio ambiente, es una vía importante
    para la biota, debido a que pueden formarse metabolitos
    carcinogénicos. Dado que los HAP son químicamente estables, sin grupos
    reactivos, la hidrólisis no interviene en su degradación. Hay pocas
    pruebas normalizadas para la biodegradación de los HAP. En general, se
    biodegradan en condiciones aerobias, registrando un fuerte aumento la
    tasa de biodegradación con el número de anillos aromáticos. En
    condiciones anaerobias la degradación es mucho más lenta.

    Los HAP se fotooxidan en el aire y en el agua en presencia de
    radicales sensibilizantes como OH, NO3 y O3. En condiciones de
    laboratorio, la semivida de la reacción con radicales OH presentes en
    el aire es de alrededor de un día, mientras que las reacciones con
    NO3 y O3 suelen tener unas constantes de velocidad mucho más
    bajas. La adsorción de HAP de peso molecular alto en partículas
    carbonosas en el medio ambiente debería estabilizar la reacción con

    radicales OH. La reacción, que tiene lugar sobre todo en la fase
    gaseosa, de HAP de entre dos y cuatro anillos con NO3 da lugar a la
    formación de nitro-HAP, que son conocidos como mutágenos. Parece que
    la fotooxidación de algunos HAP en el agua es más rápida que en el
    aire. Los cálculos basados en parámetros fisicoquímicos y de
    degradación indican que los HAP con cuatro o más anillos aromáticos
    persisten en el medio ambiente.

    1.5  Niveles ambientales y exposición humana

    Los HAP están omnipresentes en el medio ambiente, habiéndose detectado
    en numerosos estudios diversos HAP por separado en distintos
    compartimentos.

    1.5.1  Aire

    Los niveles de cada uno de los HAP tiendan a ser más elevados en
    invierno que en verano por lo menos en un orden de magnitud. La fuente
    predominante durante el invierno es la calefacción de las viviendas y
    la del verano el tráfico urbano de vehículos de motor. Se detectaron
    concentraciones medias de distintos HAP de 1-30 ng/m3 en la
    atmósfera de diversas zonas urbanas. En grandes ciudades con un
    tráfico intenso de vehículos de motor y utilización abundante de
    combustibles a base de biomasa, como Calcuta, se encontraron niveles
    de hasta 200 ng/m3 de distintos HAP. En túneles de carreteras se
    detectaron concentraciones de hasta 1-50 ng/m3. Había
    ciclopenta[cd]-pireno y pireno en concentraciones de hasta 100
    ng/m3. En una estación de metro se midieron concentraciones de HAP
    de hasta 20 ng/m3. En las cercanías de fuentes industriales, las
    concentraciones medias de los distintos HAP oscilaban entre 1 y 10
    ng/m3. Había fenantreno presente hasta un máximo aproximado de 310
    ng/m3.

    Los valores básicos de los HAP son por lo menos uno o dos órdenes de
    magnitud menores que los obtenidos cerca de fuentes como el tráfico de
    vehículos de motor. Por ejemplo, los niveles a 1100 m oscilaban entre
    0,004 y 0,03 ng/m3.

    1.5.2  Agua superficial y precipitación

    La mayor parte de los HAP presentes en el agua proceden al parecer del
    agua de escorrentía urbana, de la precipitación atmosférica
    (partículas más pequeñas) y de la abrasión del asfalto (partículas
    mayores). La principal fuente de HAP, sin embargo, varia para
    distintas masas de agua. En general, la mayoría de las muestras de
    agua superficial contienen distintos HAP en concentraciones de hasta
    50 ng/litro, pero los ríos muy contaminados tenían concentraciones de
    hasta 6000 ng/litro. Los niveles de HAP en el agua freática son del
    orden de 0,02-1,8 ng/litro, y las muestras de agua potable contienen
    concentraciones del mismo orden de magnitud. Las principales fuentes
    de los HAP presentes en el agua potable son los depósitos y las
    tuberías con revestimiento de asfalto.

    Los niveles de HAP por separado en el agua de lluvia oscilaban entre
    10 y 200 ng/litro, mientras que en la nieve y la niebla se detectaron
    concentraciones de hasta 1000 ng/litro.

    1.5.3  Sedimentos

    Las concentraciones de los distintos HAP cm los sedimentos eran por lo
    general un orden de magnitud superiores a las presentes cm la
    precipitación.

    1.5.4  Suelo

    Las principales fuentes de los HAP presentes en el suelo son la
    deposición atmosférica, la carbonización de material vegetal y la
    deposición a partir de aguas residuales y desechos particulados. El
    grado de contaminación del suelo depende de factores como su cultivo,
    su porosidad y su contenido de sustancias húmicas.

    Cerca de fuentes industriales se han encontrado concentraciones de
    distintos HAP de hasta 1 g/kg de suelo. La concentración en el suelo a
    partir de otras fuentes, como los gases de escape de los automóviles,
    son del orden de 2-5 mg/kg. En zonas no contaminadas, los niveles de
    HAP eran de 5-100 µg/kg de suelo.

    1.5.5  Alimentos

    Los alimentos credos no suelen contener niveles elevados de HAP, pero
    se forman al elaborarlos, asados o cocerlos en horno o freírlos. Las
    hortalizas pueden contaminarse por la deposición de partículas de la
    atmósfera o por el crecimiento en suelo contaminado. Las
    concentraciones de los distintos HAP en la carne, el pescado, los
    productos lácteos, las frutas y hortalizas, los cereales y sus
    productos, los dulces, las bebidas y las grasas y los aceites animales
    y vegetales eran del orden de 0,01-10 µg/kg. Se han detectado
    concentraciones de más de 100 µg/kg en carne ahumada y de hasta 86
    µg/kg cm pescado ahumado; los cereales ahumados contenían hasta 160
    µg/kg. En el aceite de coco se encontraron concentraciones de hasta
    460 µg/kg. Los niveles en la leche materna humana eran de 0,003-0,03
    µg/kg.

    1.5.6  Organismos acuáticos

    Se sabe que los organismos marinos adsorben y acumulan HAP del agua.
    El grado de contaminación depende del desarrollo industrial y urbano y
    de los movimientos de transporte marítimo. Se han detectado
    concentraciones de HAP de hasta 7 mg/kg en organismos acuáticos que
    vivían cerca de efluentes industriales, y los niveles medios de HAP en
    los animales acuáticos muestreados en lugares contaminados fueron de
    10-500 µg/kg, aunque también se detectaron niveles de hasta 5 mg/kg.

    Los niveles medios de HAP en animales acuáticos muestreados en
    diversos lugares con fuentes sin especificar de dichos compuestos
    fueron de 1-100 µg/kg, pero se encontraron concentraciones de hasta 1
    mg/kg, por ejemplo en langostas en el Canadá.

    1.5.7  Organismos terrestres

    Las concentraciones de HAP en insectos oscilaban entre 730 y 5500
    µg/kg. El contenido de las heces de las lombrices de tierra depende
    considerablemente del lugar: las de una región muy industrializada de
    Alemania oriental contenían concentraciones de benzo[a]pireno de hasta
    2 mg/kg.

    1.5.8  Población general

    Las principales fuentes de exposición no profesional son las
    siguientes: atmósfera contaminada, humo de fuegos abiertos y del
    cocinado, humo de tabaco en el medio ambiente, alimentos y agua
    potable contaminados y utilización de productos contaminados. Pueden
    encontrarse HAP en el aire de espacios cerrados como consecuencia de
    la calefacción de las viviendas y del humo del tabaco del medio
    ambiente en concentraciones medias de 1-100 ng/m3, con un máximo de
    2300 ng/m3.

    Se ha estimado que la ingesta de distintos HAP con los alimentos es de
    0,10-10 µg/día por persona. La ingesta diaria total de benzo[a]-pireno
    con el agua potable se estimó en 0,0002 µg/persona. Los cereales y
    productos derivados son los que más contribuyen a la ingesta de HAP
    con los alimentos, por ser el principal componente de la alimentación
    total.

    1.5.9  Exposición profesional

    Cerca de una batería de hornos de coque, los niveles de
    benzo[a]-pireno oscilaban entre < 0,1 y 100-200 µg/m3, con un máximo
    aproximado de 400 µg/m3. En los sistemas modernos de gasificación
    del carbón, la concentración de HAP suele ser < 1 µg/m3, con un
    máximo de 30 µg/m3. Las muestras personales tomadas de operadores de
    equipo de refinerías de petróleo mostraron una exposición a 2,6470
    µg/m3. En muestras de aire tomadas cerca de instalaciones de
    elaboración de asfalto en refinerías, los niveles totales de HAP
    fueron de 0,004-50 µg/m3. En las proximidades de obras de
    pavimentación de carreteras, las concentraciones totales de HAP en
    muestras personales de aire eran de hasta 190 µg/m3, con un valor
    medio en las muestras de aire de la zona de 0,13 µg/m3. Los niveles
    de HAP en las muestras personales de aire tomadas en una fundición de
    aluminio eran de 0,059,6 µg/m3, pero las muestras de orina de los
    trabajadores de una fábrica de aluminio contenían niveles muy bajos.
    Las muestras de aire de la zona contenían concentraciones de HAP de
    hasta 5 µg/m3 en una fundición alemana, 3-40 µg/m3 en minas de
    hierro µg/m3 y 4530 µg/m3 en minas de cobre. Las concentraciones
    de HAP en humos de cocinado en una fábrica de productos alimenticios
    oscilaban entre 0,07 y 26 µg/m3.

    1.6  Cinética y metabolismo

    Los HAP se absorben por las vías respiratorias, el aparato digestivo y
    la piel. La tasa de absorción por los pulmones depende del tipo de
    HAP, el tamaño de las partículas sobre las que están adsorbidos y la
    composición del adsorbente. Los HAP adsorbidos sobre partículas se e
    'laminan de los pulmones con mayor lentitud que los hidrocarburos
    libres. En el aparato digestivo se produce una absorción rápida en los
    roedores, pero los metabolitos vuelven al intestino mediante la
    excreción biliar. En estudios de absorción percutánea de mezclas de
    HAP marcados con 32P en roedoras se observó que los componentes de las
    mezclas negaban a los pulmones, donde se unían al ADN. La tasa de
    absorción percutánea en ratones varia en función del compuesto.

    Los HAP se distribuyen ampliamente en todo el organismo tras la
    administración por cualquier vía y se encuentran en casi todos los
    órganos internos, particularmente en los ricos en lípidos. Los HAP
    inyectados por vía intravenosa se eliminan con rapidez de la corriente
    sanguínea en los roedores, pero pueden atravesar la barrera
    placentaria y se han detectado en tejidos fetales.

    El metabolismo de los HAP es complejo. En general, los compuestos
    originales se convierten mediante epóxidos intermedios en fenoles,
    dioles y tetroles, que a su vez pueden conjugarse con los ácidos
    sulfúrico y glucurónico o con el glutatión. El metabolismo produce en
    su mayor parte una desintoxicación, pero algunos HAP se activan a
    especies que se unen al ADN, principalmente diolepóxidos, que pueden
    inducir tumores. Los metabolitos de los HAP y sus cunjugados se
    excretan en la orina y las heces, pero los conjugados que se excretan
    en la bilis pueden hidrolizarse por la acción de enzimas de la flora
    intestinal y reabsorberse. De la información disponible acerca de la
    carga total en el cuerpo humano cabe deducir que los HAP no persisten
    en el organismo y que su ciclo metabólico es rápido. De la deducción
    anterior están excluidos los grupos de HAP que se unen por enlaces
    covalentes a elementos constitutivos de los tejidos, en particular
    ácidos nucleicos, y que no se eliminan por reparación.

    1.7  Efectos en mamíferos de laboratorio y en sistemas de prueba in vitro

    La toxicidad aguda de los HAP parece ser de moderada a baja. Un
    producto bien caracterizado, el naftaleno, mostró valores para la
    DL50 por vía oral e intravenosa de 100-500 mg/kg de peso corporal en
    ratones y una DL50 media por vía oral de 2700 mg/kg de peso corporal
    en ratas. Los valores para otros HAP son semejantes. Con dosis altas
    únicas de naftaleno se indujo en ratones, ratas y hámsteres necrosis
    bronquiolar.

    En estudios de corta duración se pusieron de manifiesto efectos
    hematológicos adversos en forma de mielotoxicidad con el
    benzo[a]-pireno, cambios hemolinfáticos con el dibenz[a,h]antraceno y
    anemia con el naftaleno; sin embargo, en un estudio de siete días en
    el que se administró a ratones naftaleno por vía oral e
    intraperitoneal se observó tolerancia al efecto de este producto.

    Sólo raramente se han descrito efectos sistémicos provocados por un
    tratamiento prolongado con HAP, porque el efecto final de la mayor
    parte de los estudios ha sido la carcinogenicidad. Se manifiestan
    efectos tóxicos importantes a dosis en las cuales se desencadenan
    también respuestas carcinogénicas

    En estudios de los efectos adversos en la piel tras la aplicación
    cutánea, los productos con carcinogenicidad nula o débil, como el
    perileno, el benzo[e]pireno, el fenantreno, el pireno, el antraceno,
    el acenaftaleno, el fluoreno y el fluoranteno, fueron inactivos,
    mientras que los compuestos carcinógenos; como el benz[a]antraceno, el
    dibenz[a,h]antraceno y el banzo[a]pireno provocaron hiperqueratosis.
    Los vapores de antraceno y de naftaleno provocaron irritación ocular
    leve. El benzo[a]pireno indujo hipersensibilidad por contacto en
    cobayas y ratones.

    El benz[a]antraceno, el benzo[a]pireno, el dibenz[a,h]antraceno y el
    naftaleno fueron embriotóxicos para ratones y ratas. El benzo[a]-
    pireno mostró asimismo teratogenicidad y efectos en la reproducción.
    Se han realizado grandes esfuerzos para aclarar la base genética de
    los efectos embriotóxicos del benzo[a]pireno. Sólo se observan
    mortalidad fetal y malformaciones si es inducible el sistema citocromo
    P-450 monooxigenasa, bien en la madre (con permigración placentaria) o
    bien en el embrión. No todos los efectos observados se pueden explicar
    por la predisposición genética, pero en ratones y conejos el
    benzo[a]pireno mostró actividad carcinogénica transplacentaria,
    produciendo adenomas pulmonares y papilomas cutáneos en la
    descendencia. Se observó asimismo reducción de la fecundidad y
    destrucción de oocitos.

    Se han estudiado también ampliamente los HAP en valoraciones de la
    genotoxicidad y de la transformación celular; la mayor parte de los 33
    HAP comprendidos en la presente monografía son genotóxicos o
    probablemente genotóxicos. Los únicos compuestos para los cuales se
    obtuvieron resultados negativos en todas las valoraciones fueron el
    antraceno, el fluoreno y el naftaleno. Habida cuenta de la falta de
    uniformidad de los resultados, el fenantreno y el pireno no podrían
    clasificarse de manera fidedigna como genotóxicos.

    En un trabajo amplio sobre la carcinogenicidad de los HAP se ha puesto
    de manifiesto que 26 de los 33 productos estudiados son, o se sospecha
    que son, carcinogénicos (Cuadro 2). El compuesto mejor caracterizado
    es el benzo[a]pireno, que se ha estudiado aplicando todos los métodos
    actuales en siete especies. Los HAP que han sido objeto de 12 estudios
    o más son el antantreno, el antraceno, el benz[a]-antraceno, el
    criseno, el dibenz[a,h]antraceno, el dibenzo[a,i]pireno, el 5-
    metilcriseno, el fenantreno y el pireno. Los estudios especiales de
    fototoxicidad, inmunotoxicidad y hepatotoxicidad de los HAP se
    complementan con informes sobre la toxicidad ocular del naftaleno.

    Cuadro 2. Resumen de los resultados de las pruebas de genotoxicidad
    y carcinogenicidad de los 33 hidrocarburos aromáticos policiclicos
    estudiados

                                                                       

    Compuesto                    Genotoxicidad      Carcinogenicidad
                                                                       

    Acenafteno                   (?)                (?)
    Acenaftileno                 (?)                No hay estudios
    Antraceno                    -                  -
    Benz[a]antraceno             +                  +
    Benzo[a]fluoreno             (?)                (?)
    Benzo[a]pireno               +                  +
    Benzo[b]fluoranteno          +                  +
    Benzo[b]fluoreno             (?)                (?)
    Benzo[c]fenantreno           (+)                +
    Benzo[e]pireno               +                  ?
    Benzo[ghi]fluoranteno        (+)                (-)
    Benzo[ghi]perileno           +                  -
    Benzo[j]fluoranteno          +                  +
    Benzo[k]fluoranteno          +                  +
    Criseno                      +                  +
    Coroneno                     (+)                (?)
    Ciclopenta[cd]pireno         +                  +
    Dibenzo[a,e]pireno           +                  +
    Dibenz[a,h]antraceno         +                  +
    Dibenzo[a,h]pireno           (+)                +
    Dibenzo[a,i]pireno           +                  +
    Dibenzo[a,l]pireno           (+)                +
    Fluoranteno                  +                  (+)
    Fluoreno                     -                  -
    Indeno[1,2.3-cd]pireno       +                  +
    1-Metilfenantreno            +                  -
    5-Metilcriseno               +                  +
    Naftaleno                                       ?
    Perileno                     +                  -
    Fenantreno                   (?)                (?)
    Pireno                       (?)                -
    Trifenileno                  +                  -
                                                                       

    +, positivo; -, negativo; ?, dudoso
    Paréntesis, resultado derivado de un número de datos pequeño

    El antraceno, el benzo[a]pireno y algunos otros HAP mostraron
    fototoxicidad en la piel de mamíferos y en cultivos de células in
    vitro cuando se aplicaron con radiación ultravioleta. Se ha notificado
    que en general estos compuestos tienen efectos inmunosupresores. Tras
    la administración intraperitoneal de benzo[a]pireno a ratones, se
    manifestó una fuerte supresión de los parámetros inmunitarios en la
    descendencia durante un período de hasta 18 meses. Se observó asimismo
    una mayor regeneración hepática y un aumento del peso del hígado. El
    efecto del naftaleno en la aparición de cataratas en un roedor se ha
    atribuido a su capacidad de inducción del sistema del citocromo P-450
    en estudios realizados con estirpes de ratones genéticamente
    diferentes.

    Los modelos teóricos para pronosticar la actividad carcinogénica de
    los HAP a partir de sus estructuras, basados en una gran cantidad de
    trabajos experimentales, se presentaron ya en los años treinta. El
    primer modelo se basaba en la elevada reactividad química de
    determinados dobles enlaces (teoría de la región K). Más tarde se
    aplicó un método más sistemático, basado en la síntesis química de
    posibles metabolitos y en su actividad mutagénica. Según esta teoría
    de la región "bay", los epóxidos adyacentes a una región "bay" dan
    lugar a iones carbonio muy estables. Otros métodos teóricos son la
    "teoría de la región di" y la "teoría del potencial del radical
    catiónico".

    Muchos de los distintos HAP son carcinógenos para los animales y
    pueden serio para el ser humano y se ha observado que la exposición a
    varias mezclas con HAP aumenta la incidencia de cáncer en poblaciones
    humanas. Existe la preocupación de que los HAP cuya carcinogenicidad
    se ha demostrado en animales de experimentación puedan serio también
    para el ser humano. Los HAP producen rumores, tanto en el lugar del
    contacto como en otros lejanos. Su actividad carcinogénica puede
    variar en función de la vía de exposición. Se han propuesto diversos
    métodos para evaluar el riesgo asociado a la exposición a estos
    productos aislados y en mezclas. En la presente monografía no se
    respalda ningún método; sin embargo, se describen las necesidades de
    datos, las hipótesis, la aplicabilidad y otras características de tres
    procesos de evaluación cuantitativa del riesgo que han sido validados
    en cierta medida.

    1.8  Efectos en el ser humano

    Habida cuenta de la complejidad del perfil de los HAP en el medio
    ambiente y en los lugares de trabajo, la exposición humana a productos
    puros por separado se ha limitado a experimentos científicos con
    voluntarios, salvo en el caso del naftaleno, que se utiliza como
    antipolilla para la ropa.

    Tras la aplicación cutánea, el antraceno, el fluoranteno y el
    fenantreno indujeron reacciones específicas en la piel, y el benzo[a]-
    pireno produjo la formación de verrugas regresivas reversibles que se
    clasificaron como proliferaciones neoplásicas. Los efectos sistémicos
    del naftaleno se conocen por los numerosos casos de ingesta

    accidental, particularmente de niños. La dosis letal por vía oral es
    de 5000-15 000 mg para los adultos y 2000 mg ingeridos durante dos
    días en los niños. El efecto normal tras la exposición por vía cutánea
    u oral es una anemia hemolítica aguda que, a través de la placenta,
    puede afectar también a los fetos.

    El humo del tabaco es el factor aislado más importante en la inducción
    de tumores de pulmón y también de un aumento de la incidencia de
    tumores de la vejiga urinaria, la pelvis renal, la boca, la faringe,
    la laringe y el esófago. No se considera que sea elevada la
    contribución de los HAP en los alimentos a la aparición de tumores
    humanos. En zonas fuertemente industrializadas se detectó también una
    mayor carga corporal de HAP debido a la contaminación del aire. Están
    expuestos asimismo a estos compuestos los enfermos de psoriasis
    tratados con alquitrán de hulla.

    La exposición profesional al hollín como causa de cáncer de escroto se
    observó por primera vez en 1775. Más tarde se informó que la
    exposición a los alquitranes y la parafina inducían cáncer cutáneo.
    Ahora el cáncer inducido por HAP afecta principalmente al pulmón,
    mientras que el cáncer cutáneo es más raro gracias a una mayor higiene
    personal.

    Se han realizado estudios epidemiológicos de trabajadores expuestos en
    hornos de coque durante la coquificación del carbón y su gasificación,
    en obras de asfaltado, fundiciones e instalaciones de aluminio y a los
    gases de escape de los motores diesel. Se ha detectado un índice de
    cáncer de pulmón más elevado debido a su exposición a los HAP en los
    trabajadores de hornos de coque, los que utilizan asfalto y los de las
    salas de crisoles de Söderberg de las instalaciones de reducción de
    aluminio. El riesgo más elevado se observó en los trabajadores de
    hornos de coque, con una razón de mortalidad normalizada de 195. En
    varios estudios se hallaron relaciones dosis-respuesta. En las
    instalaciones de aluminio no sólo se detectó cáncer de la vejiga
    urinaria, sino también síntomas semejantes al asma, anomalías
    funcionales de los pulmones y bronquitis crónica. En los trabajadores
    de hornos de coque se observó asimismo una disminución de la
    concentración de inmunoglobulina en el suero y una reducción de la
    función immunitaria. Se notificó que una exposición durante cinco años
    al naftaleno había provocado cataratas.

    Se han elaborado varios métodos para evaluar la exposición interna a
    los HAP. En la mayoría de los estudios, se midieron en orina
    metabolitos de los HAP como los tioéteres urinarios, el 1-naftol, la
    ß-naftilamina, los hidroxifenantrenos y el 1-hidroxipireno. Este
    último se ha utilizado con frecuencia como indice biológico de
    exposición.

    Se han determinado los efectos genotóxicos de los HAP mediante pruebas
    de mutagenicidad en orina y heces y de la presencia de m/cm-núcleos,
    aberraciones cromosómicas e intercambio de cromátidas hermanas en
    linfocitos de la sangre periférica. Además, se han medido aductos de

    benzo[a]pireno con ADN en linfocitos periféricos y en otros tejidos y
    con proteínas como la albúmina, así como anticuerpos de aductos de
    ADN.

    En varios estudios se han investigado el 1-hidroxipireno en orina y
    los aductos de ADN en linfocitos como marcadores. El primero se puede
    medir más fácilmente que los segundos, presenta menos variación entre
    los individuos y es posible detectar niveles de exposición más bajos.
    Ambos marcadores se han Utilizado para evaluar la exposición humana en
    diversas condiciones. En varios puestos de trabajo de instalaciones de
    coque, de fabricación de aluminio, de instalaciones de impregnación de
    la madera, de fundiciones y de obras de asfaltado se observó un
    aumento de la excreción de 1-hidroxipireno o de aductos de ADN. Las
    exposiciones más elevadas se detectaron en los trabajadores de hornos
    de coque y en los de impregnación de la madera con creosota, que
    absorbían hasta el 95% del total de HAP a través de la piel, a
    diferencia de la población general, en la que predomina la absorción
    mediante los alimentos y el humo del tabaco.

    Las estimaciones del riesgo relacionado con la exposición a HAP y sus
    mezclas se basan en estimaciones de la exposición y en los resultados
    de estudios epidemiológicos. Los datos obtenidos de trabajadores de
    hornos de coque pusieron de manifiesto un riesgo relativo de cáncer de
    pulmón de 15,7. Teniendo esto en cuenta, se ha calculado que el riesgo
    de aparición de cáncer de pulmón en la población general durante toda
    la vida es de 104 a 10-s por ng de banzo[a]pireno por m3 de aire.
    Dicho de otra manera, como consecuencia de la exposición al
    benzo[a]pireno en el aire cabra esperar la aparición de cáncer de
    pulmón a lo largo de toda la vida en una persona de cada 10 000 a 100
    000.

    1.9  Efectos en otros organismos en el laboratorio y en el medio
    ambiente

    Los HAP tienen toxicidad aguda para los peces y para Daphnia magna en
    combinación con la absorción de radiación ultravioleta y luz visible.
    El metabolismo y la degradación alteran la toxicidad de los HAP. A
    concentraciones bajas, los HAP pueden estimular el crecimiento de
    microorganismos y algas. Los HAY más tóxicos para las algas son el
    benz[a]antraceno (cuatro anillos), con una CE50 (concentración a la
    cual determinados parámetros vitales se reducen a la mitad) de 1-29
    µg/litro, y el benzo[a]pireno (cinco anillos), con una CE50 de 545
    µg/litro. Los valores de la CL50 en las algas para la mayor parte de
    los HAP de tres anillos son de 240-940 µg/litro. El naftaleno (dos
    anillos) es el menos tóxico, con valores de la CE50 de 2800-34 000
    µg/litro.

    No se han observado diferencias claras de sensibilidad entre distintos
    grupos taxonómicos de invertebrados, como los crustáceos, los
    insectos, los moluscos, los poliquetos y los equinodermos. El
    naftaleno es el menos tóxico, con valores de la CL50 en 96 horas de
    100-2300 µg/litro. Los valores de la CL50 en 96 horas para los HAP
    de tres anillos oscilan entre <1 y 3000 µg/litro. El antraceno puede

    ser más tóxico que los otros HA/' de tres anillos, con CL50 en 96
    horas entre <1 y 260 µg/litro: Los valores de la CL50 en 96 horas
    para los HAP de cuatro, cinco y seis anillos son de 0,2-1200 µg/litro.
    Se observó toxicidad aguda (CL50) en peces a concentraciones de 110
    a >10 000 µg/litro de naftaleno, 30-4000 µg/litro de HAP de tres
    anillos (antraceno, 2,8-360 µg/litro) y 0,7-26 µg/litro para los de
    cuatro o cinco altillos.

    La contaminación de los sedimentos con HAP a concentraciones de 250
    mg/kg se asoció a tumores hepáticos en peces vivos libres. Se han
    inducido asimismo tumores en peces expuestos en el laboratorio. La
    exposición de los peces a determinados HAP puede producir también
    cambios fisiológicos y afectar a su crecimiento, reproducción,
    capacidad natatoria y respiración.
    



    See Also:
       Toxicological Abbreviations