INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
ENVIRONMENTAL HEALTH CRITERIA 1
MERCURY
This report contains the collective views of an international
group of experts and does not necessarily represent the
decisions or the stated policy of either the World Health
Organization or the United Nations Environment Programme
Published under the joint sponsorship of
the United Nations Environment Programme
and the World Health Organization
World Health Organization Geneva, 1976
ISBN 92 4 154061 3
(c) World Health Organization 1976
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proprietary products are distinguished by initial capital letters.
CONTENTS
BACKGROUND AND PURPOSE OF THE WHO ENVIRONMENTAL HEALTH
CRITERIA PROGRAMME
ENVIRONMENTAL HEALTH CRITERIA FOR MERCURY
1. SUMMARY AND RECOMMENDATIONS FOR FURTHER RESEARCH
1.1. Some definitions
1.2. Summary
1.2.1. Analytical methods
1.2.2. Sources of environmental pollution
1.2.3. Environmental distribution and transport
1.2.4. Environmental exposure levels
1.2.5. Metabolism of mercury
1.2.6. Experimental studies on the effects of mercury
1.2.7. Epidemiological and clinical studies
1.2.8. Evaluation of health risks to man and guidelines
for health protection
1.3. Recommendations for further research
1.3.1. Environmental sources and pathways of mercury
intake
1.3.2. Metabolic models in man
1.3.3. Epidemiological studies
1.3.4. Interaction of mercury with other environmental
factors
1.3.5. Biochemical and physiological mechanisms of
toxicity
2. PROPERTIES AND ANALYTICAL METHODS
2.1. Chemical and physical properties
2.2. Purity of compounds
2.3. Sampling and analysis
2.3.1. Sample collection
2.3.2. Analytical methods
2.3.3. Analysis of alkyl mercury compounds in the presence
of inorganic mercury
3. SOURCES OF ENVIRONMENTAL POLLUTION
3.1. Natural occurrence
3.2. Industrial production
3.3. Uses of mercury
3.4. Contamination by fossil fuels, waste disposal, and
miscellaneous industries.
4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION
4.1. Distribution between media -- the global mercury cycle
4.2. Environmental transformation -- the local mercury cycle
4.3. Interaction with physical or chemical factors
4.4. Bioconcentration
5. ENVIRONMENTAL LEVELS AND EXPOSURES
5.1. Levels in air, water, and food
5.2. Occupational exposures
5.3. Estimate of effective human exposure
6. METABOLISM OF MERCURY
6.1. Uptake
6.1.1. Uptake by inhalation
6.1.2. Uptake by ingestion
6.1.3. Absorption through skin
6.2. Distribution in organisms
6.3. Elimination in urine and faeces
6.4. Transplacental transfer and secretion in milk
6.5. Metabolic transformation and rate of elimination
6.6. Accumulation of mercury and biological half-time (metabolic
model)
6.7. Individual variations -- strain and species comparisons
7. EXPERIMENTAL STUDIES ON THE EFFECTS OF MERCURY
7.1. Experimental animal studies
7.1.1. Acute studies
7.1.2. Subacute and chronic studies
7.1.2.1 Reversible damage
7.1.2.2 Irreversible damage
7.1.2.3 Interactions with physical and chemical
factors
7.1.3. Biochemical and physiological mechanisms of
toxicity
8. EFFECTS OF MERCURY ON MAN -- EPIDEMIOLOGICAL AND CLINICAL STUDIES
8.1. Epidemiological studies
8.1.1. Occupational exposure to mercury vapour,
alkylmercury vapour and other exposures
8.1.2. General population
8.1.3. Children and infants with in utero exposure
8.2. Clinical studies of effects of mercury binding compounds
8.3. Pathological findings and progression of disease
8.3.1. Psychiatric and neurological disturbances
8.3.2. Eye and visual effects
8.3.3. Kidney damage
8.3.4. Skin and mucous membrane changes
9. EVALUATION OF HEALTH RISKS TO MAN FROM EXPOSURE TO MERCURY
AND ITS COMPOUNDS
9.1. General considerations
9.1.1. Elemental mercury vapour
9.1.2. Methylmercury compounds
9.1.3. Ethylmercury compounds and other short-chain
alkylmercurials
9.1.4. Inorganic mercury, aryl- and alkoxyalkylmercurials
9.2. Summary and guidelines
REFERENCES
BACKGROUND AND PURPOSE OF THE WHO ENVIRONMENTAL HEALTH
CRITERIA PROGRAMMEa
ORIGIN AND OBJECTIVES OF THE PROGRAMME
During the last two decades, evaluation of the health hazards from
chemical and other environmental agents has received considerable
attention in several WHO programmes. High priority was given to
drinking water quality (1), food additives (2), and pesticide residues
(3), to occupational exposure (4), air quality in urban areas (5),
and, more recently, to the carcinogenic risk of chemicals to man (6).
In most instances, man's total exposure to a given agent, from
different media or conditions (air, water, food, work, home), was not
considered. The inadequacy of this approach is obvious for pollutants
that may reach man by several pathways, as is the case with lead,
cadmium, and some other metals, and certain persistent organic
compounds. In response to a number of World Health Assembly
resolutions (WHA23.60, WHA24.47, WHA25.58, WHA26.68) and taking into
consideration the relevant recommendations of the United Nations
Conference on the Human Environment (7) held at Stockholm in 1972, and
of the Governing Council of the United Nations Environment Programme
(UNEP) (8), an integrated and expanded programme on the assessment of
health effects of environmental conditions was initiated in 1973 under
the title of: WHO Environmental Health Criteria Programme, with the
following objectives:
(i) to assess existing information on the relationship between
exposure to environmental pollutants (or other physical and
chemical factors) and man's health, and to provide guidelines
for setting exposure limits consistent with health protection,
i.e., to compile environmental health criteria documents;
(ii) to identify new or potential pollutants by preparing
preliminary reviews on the health effects of agents likely to
be increasingly used in industry, agriculture, in the home or
elsewhere.
(iii) to identify gaps in knowledge concerning the health effects of
recognized or potential pollutants or other environmental
factors, to stimulate and promote research in areas where
information is inadequate, and
(iv) to promote the harmonization of toxicological and
epidemiological methods in order to obtain research results
that are internationally comparable.
a Prepared by the WHO Secretariat. References are listed on page 14.
The general framework of the Environmental Health Criteria
Programme was formulated by a WHO meeting held in November 1972 (9),
and further elaborated by a WHO Scientific Group that met in April
1973 (10).
DEFINITIONS, TERMINOLOGY, AND UNITS
Terminology
In the framework of the WHO Environmental Health Criteria
Programme, it is understood that the term "criteria" designates the
relationship between exposure to a pollutant or other factor and the
risk or magnitude of undesirable effects under specified circumstances
defined by environmental and target variables (9). This corresponds to
the definition proposed by the Preparatory Committee for the United
Nations Conference on the Human Environment (11). Other Preparatory
Committee definitions of immediate interest to the criteria programme
are:
-- " exposure: the amount of a particular physical or chemical agent
that reaches the target";
-- " target (or receptor): the organism, population, or resource to
be protected from specific risks";
-- " risk: the expected frequency of undesirable effects arising
from a given exposure to a pollutant".
The WHO Scientific Group on Environmental Health Criteria (10)
accepted these definitions for the purposes of its discussions, but
felt that they were not altogether satisfactory, and recommended that
WHO, in collaboration with other international organizations, should
reconsider them, along with other necessary definitions, at an
appropriate international meeting. In accordance with this
recommendation, the WHO Secretariat is preparing a list of basic terms
to be used in the Environmental Health Criteria Programme that will be
submitted to the national institutions and other international
organizations for discussion.
The Scientific Group (10) found the definition of "exposure"
particularly inadequate and considered that it should be expanded to
include the concepts of concentration and length of exposure in
addition to the amount of the agent.
The WHO Secretariat considers it useful to attach specific
meanings to the terms "effect", "response" and "dose" as was done by
the Subcommittee on the Toxicology of Metals of the Permanent
Commission and International Association on Occupational Health at the
Tokyo meeting (12). These terms will be used in the following sense
unless indicated differently in specific criteria documents:
-- " effect: a biological change caused by (or associated with)a an
exposure";
-- " response: the proportion of a population that demonstrates a
specific effect";
-- " dose: the amount or concentration of a given chemical at the
site of the effect".
The concept of "response" as defined above is generally accepted
but the terminology used to describe this concept varies widely. Many
toxicologists use the terms "effect" and "response" interchangeably to
denote a specific biological change associated with exposure, whereas
different terms are used to indicate the proportion of a population
affected (e.g., incidence, cumulative response frequency, response
rate, etc.).
There is no general agreement as to the use of the term "dose" for
chemical agents. Its common usage is to express the amount of
substance administered, for instance, to an experimental animal (e.g.,
oral dose, injected dose, etc.). In most cases, the amount or
concentration of a given agent at the site where its presence induces
a given effect cannot be determined by direct measurement and has to
be estimated from experimental, occupational, or general environmental
exposure, or from measurements in biological indicator media such as
blood, urine, faeces, sweat, or hair (12). To avoid misunderstanding,
it is, therefore, necessary in each case to make as clear as possible
the way in which the "dose" is measured or estimated, including the
units used.
Because of the existing differences in the use of terms, no
attempt has been made at this stage to impose a uniform terminology in
all criteria documents. Until an internationally agreed terminology
becomes available, the task groups on specific criteria documents are
given freedom to choose their terminology, provided the terms are
defined and used consistently throughout the document under
consideration.
a Added by the WHO Secretariat.
Units
An attempt has been made to express all numerical values in a
uniform fashion, for instance, the concentrations are always expressed
as mass concentrations in units acceptable to the SI system (e.g.
mg/litre or mg/kg) (13). Some departures from this are made where the
introduction of new units would cause confusion, e.g., lead in blood
is expressed in µg/100 ml and not in µg/litre.
Priorities
Considering the large number of environmental agents and factors
that may adversely influence human health, a practical programme for
the preparation of criteria documents must be based on clearly defined
priorities. The list of priorities has been established by a WHO
Scientific Group (10), and is based on the following considerations:
-- " Severity and frequency of observed or suspected adverse effects
on human health. Of importance are irreversible or chronic
effects, such as genetic, neurotoxic, carcinogenic, and
embryotoxic effects including teratogenicity. Continuous or
repeated exposures generally merit a higher priority than isolated
or accidental exposures.
-- Ubiquity and abundance of the agent in man's environment. Of
special concern are inadvertently produced agents, the levels of
which may be expected to increase rapidly, and agents that add to
a natural hazard.
-- Persistence in the environment. Pollutants that resist
environmental degradation and accumulate, in man, in the
environment, or in food chains, deserve attention.
-- Environmental transformations or metabolic alterations. Since
these alterations may lead to the production of chemicals that
have greater toxic potential, it may be more important to
ascertain the distribution of the derivatives than that of the
original pollutant.
-- Population exposed. Attention should be paid to exposures
involving a large portion of the general population, or
occupational groups, and to selective exposures of highly
vulnerable groups represented by pregnant women, the newborn,
children, the infirm or the aged."
The full list contains some 70 chemicals and physical hazards, and
it will be periodically reviewed. In preparing this list, it was
realized that each country must assess environmental health problems
in the light of its own national situation and establish its own
priorities, which may not have been covered by this list.
SCOPE AND CONTENT OF ENVIRONMENTAL HEALTH CRITERIA DOCUMENTS
Scope
As stated on page 5, the purpose of the criteria documents is to
compile, review, and evaluate available information on the biological
effects of pollutants and other environmental factors that may
influence man's health, and to provide a scientific basis for
decisions aimed at protecting man from the adverse consequences of
exposure to such environmental factors, both in the occupational and
general environment. Although attainment of this objective entails
consideration of a wide range of data, no attempt is made to include
in the documents an exhaustive review of all published information on
the environmental and health aspects of specific agents. In the
process of collecting the required information, the available
literature has been carefully evaluated and selected as to its
validity and its relevance to the assessment of human exposure, to the
understanding of the mechanism of biological effects, and to the
establishment of dose-effect and dose-response relationships.
Environmental considerations are limited to information that can help
in understanding the pathways leading from the natural and man-made
sources of pollutants to man. Non-human targets (e.g., plants,
animals) are not considered unless the effects of their contamination
are judged to be of direct relevance to human health. For similar
reasons much of the published information on the effects of chemicals
on experimental animals has been omitted.
Content
The criteria documents consist of three parts:
(i) A summary, which highlights the major issues, followed by
recommendations for research to fill existing gaps in
knowledge;
(ii) The bulk of the report, which contains the findings on which
the evaluation of the health risks is based. This part has a
similar structure in all the criteria documents on chemical
agents and contains the following chapters: chemical and
physical properties and analytical methods; sources of
environmental pollution; environmental transport, distribution
and transformation; metabolism; experimental studies of
effects; and epidemiological and clinical studies of the
effects. The subdivision of these chapters differs from
document to document.
(iii) Evaluation of health risks to man from exposure to the
specific agent. This part of the criteria document states the
considered opinion of the task group, which examined the
findings contained in the second part (see (ii) above), and
typically contains the following sections: relative
contributions to the total dose from air, food, water, and
other exposures; dose-effect relationships; dose-response
relationships and, whenever possible, guidelines on exposure
or dose limits.
Chemical and physical data
The chemical and physical data included in the criteria documents
are limited to the properties that are considered relevant to the
assessment of exposure and to the understanding of the effects. Where
applicable, the impurities that may occur in commercial products are
examined. Analytical techniques are discussed only to the extent
needed to understand and evaluate data on levels in the environment
and biological samples. The methods described should not be considered
as recommended procedures. Where feasible, information is included on
the applicability of a given method for the analysis of different
types of sample, on detection limits, precision, and accuracy. The
detection limit represents the smallest total amount the method is
able to determine. In most cases, the amount of sample is limited so
that it is useful in practice to express the smallest concentration
that can be determined by that method. Precision of a method is
defined in terms of the standard deviation or the coefficient of
variation of a number of analyses made on the sample. Accuracy denotes
systematic deviation of the measured values from the true value. It is
impossible to ascertain the accuracy with absolute certainty; the
evidence for the accuracy of a method is often circumstantial and is
based either on inter-laboratory data-quality control studies or on
the agreement of results obtained with procedures using different
approaches. The results of one "accurate" procedure should agree with
those of another "accurate" procedure for a given set of samples.
Production, use, and environmental levels
Data on the production, use, and levels in the environment of
pollutants are reported only to illustrate the magnitude and extent of
the problem and are not meant to represent an exhaustive and critical
review. It is hoped that, in the future, better data will be available
and that closer collaboration will be established with other
governmental and non-governmental organizations qualified to supply
such information.
Biological data
Although every effort is made to review the whole literature, it
is possible that some publications have been overlooked. Some studies
have purposely been omitted because the information contained therein
was not considered valid or relevant to the scope of the criteria
documents, or because they only confirmed findings already described.
In general, the information is summarized as given by the author;
however, certain shortcomings of reporting or of experimental design
are also pointed out. The data on carcinogenicity have been examined
and evaluated in consultation with the International Agency for
Research on Cancer.
Whenever possible, the dose-effect and the dose-response
relationships reported in the criteria documents are based on
epidemiological and other human studies, and animal data are used, in
general, as supporting evidence.
ARRANGEMENTS FOR THE PREPARATION OF CRITERIA DOCUMENTS
In order to obtain balanced and unbiased information, the
collection and evaluation of information is done in close
collaboration with national scientific and health institutions. About
20 Member States of WHO have designated national focal points for
collaboration in the WHO Environmental Health Criteria Programme.
Without this collaboration no progress could have been made in its
implementation.
In addition, a number of WHO collaborating centres on
environmental health effects have been designated to extend and
complement the expertise available in the WHO Secretariat.
Two procedures have been used in preparing the criteria documents.
One is based on the consolidation of national contributions and the
other on a draft criteria document prepared by consultants or the
collaborating centres in association with the Secretariat.
Procedure based on national contributions
Criteria documents are prepared in four stages: (1) the
preparation of national contributions by focal points in the Member
States reviewing all relevant research results obtained in these
countries; (2) consolidation of the national contributions into a
draft document, which is done on a contractual basis with individual
experts or WHO collaborating centres; (3) the draft criteria documents
are circulated to the national focal points for comments and
additions, based on which a second draft is prepared, and (4) the
second draft document is reviewed and the information assessed at a
meeting of internationally recognized experts (the task group
meetings).
National contributions to the criteria documents consist of a
review of data on health effects of environmental agents, as revealed
by experimental, clinical, and epidemiological studies, and of other
relevant information on research carried out in each country and
published in scientific journals or official publications. In order to
facilitate the integration of national contributions into draft
criteria documents, detailed outlines are prepared for each
environmental agent considered, and the national focal points are
requested to follow these outlines as closely as possible and to
attach all publications referred to in the review in the form of
reprints or microfiches.
Procedure for drafts prepared by the Secretariat
With the exception of steps 1 and 2 (which are replaced by the
preparation of a draft criteria document by individual experts or WHO
collaborating centres), the procedure is the same as described above.
This procedure is applied in cases where much preparatory work has
been done in Member States and where criteria-like documents (WHO or
national) already exist.
Task group meetings
The task group meetings that are convened to complete the criteria
documents have the following terms of reference:
(i) to verify, as far as possible, that all available data have
been collected and examined;
(ii) to select those data relevant to the criteria documents;
(iii) to determine whether the data, as summarized in the draft
criteria document, will enable the reader to make his own
judgement concerning the adequacy of an experimental,
epidemiological, or clinical study;
(iv) to judge the health significance of the information contained
in the draft criteria document, and
(v) to make an evaluation of the dose-effect, dose-response
relationships and of the health risks from exposure to the
environmental agents under examination.
Members of task groups serve in a personal capacity, as experts
and not as representatives of their governments or of any organization
with which they are affiliated. In addition to the first and second
draft criteria documents, the members of the task group are requested
to refer to the original publications whenever they deem that
necessary, and to review national and other comments on the first
draft criteria document to make sure that no significant information
is omitted and that the final document properly reflects the work done
in different countries.
Collaboration with the United Nations Environment Programme (UNEP) and
other international organizations
The WHO Environmental Health Criteria Programme has received
substantial financial assistance from UNEP which is acknowledged with
appreciation. In addition, the programme has been planned from the
outset in consultation with the UNEP Secretariat. The UNEP Secretariat
receives all the drafts of criteria documents and their comments are
carefully considered in the preparation of the final documents. UNEP
is regularly invited to be represented at the task group meetings.
The United Nations, their subsidiary bodies and specialized
agencies, and the IAEA are as a rule invited to provide comments on
the draft criteria documents and to participate in the task group
meetings. The same applies to selected nongovernmental organizations
in official relationship with WHO.
Note to readers of the criteria documents
While every effort has been made to present information in the
criteria documents as accurately as possible without unduly delaying
their publication, mistakes might have occurred and are likely to
occur in the future. In the interest of all users of the environmental
health criteria documents, readers are kindly requested to communicate
any errors found to the Division of Environmental Health, World Health
Organization, Geneva, Switzerland, in order that they may be included
in corrigenda which will appear in subsequent volumes.
In addition, experts in any particular field dealt with in the
criteria documents are kindly requested to make available to the WHO
Secretariat any important published information that may have
inadvertently been omitted and which may change the evaluation of
health risks from exposure to the environmental agent under
examination, so that the information may be considered in the event of
updating and re-evaluation of the conclusions contained in the
criteria documents.
REFERENCES
1. International Standards for Drinking Water, third edition,
Geneva, World Health Organization, 1971.
2. WHO Technical Report Series, Nos: 129 (1957), 228 (1962), 281
(1964), 309 (1965), 339 (1966), 373 (1967), 383 (1968), 430
(1969), 445 (1970), 462 (1971), 488 (1972), 505 (1972), 539
(1974).
3. WHO Technical Report Series, Nos: 370 (1967), 391 (1968), 417
(1969), 458 (1970), 474 (1971), 502 (1972), 525 (1973), 545
(1974), 574 (1975), 592 (1976).
4. WHO Technical Report Series, No.: 415 (1969).
5. WHO Technical Report Series, No.: 506 (1972).
6. INTERNATIONAL AGENCY FOR RESEARCH ON CANCER. IARC Monographs on
the Evaluation of Carcinogenic Risk of Chemicals to Man,
Vol. 1-11 (1972-76).
7. UNITED NATIONS GENERAL ASSEMBLY. Report of the United Nations
Conference on the Human Environment held at Stockholm, 5-16
June 1972 A/CONF.48/14, 3 July 1972.
8. UNITED NATIONS ENVIRONMENT PROGRAMME. Report of the Governing
Council of the United Nations Environment Programme (First
session) UNEP/GC/10, 3 July 1973.
9. The WHO Environmental Health Criteria Programme (unpublished
WHO document EP/73.1).
10. Environmental Health Criteria. Report of a WHO Scientific Group
(unpublished WHO document EP/73.2).
11. UNITED NATIONS GENERAL ASSEMBLY. Report of the Preparatory
Committee for the United Nations Conference on the Human
Environment on its Third Session. United Nations document
A/CONF.48/PC/13, 30 September 1971.
12. NORDBERG, G. F., ed. Effects and dose-response relationships of
toxic metals, Proceedings from an international meeting
organized by the Sub-committee on the Toxicology of Metals
of the Permanent Commission and International Associations
on Occupational Health, Tokyo, 18-23 November 1974.
Amsterdam, Oxford, New York, Elsevier Scientific Publishing
Company, 1976.
13. LOWE, D. A. A guide to international recommendations on names and
symbols for quantities and on units of measurement. Geneva,
World Health Organization, 1975, 314pp. (Progress in
Standardization No. 2.)
WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR MERCURY
Geneva 4-10 February 1975
Participants:
Members
Professor T. Beritic, Institute for Medical Research and
Occupational Medicine, Zagreb, Yugoslavia
Dr H. Blumenthal, Division of Toxicology, Bureau of Foods, Food
and Drug Administration, Department of Health, Education and
Welfare, Washington, DC, USA (Rapporteur)
Dr J. Bouquiaux, Department of the Environment, Institute of
Hygiene and Epidemiology, Brussels, Belgium
Dr G. J. van Esch, Laboratory for Toxicology, National Institute
of Public Health, Bilthoven, Netherlands
Professor L. Friberg, Department of Environmental Hygiene,
Karolinska Institute, Stockholm, Sweden (Chairman)
Professor G. L. Gatti, Istituto Superio di Sanità, Rome, Italy
Dr L. Magos, Toxicology Research Unit, Medical Research Council
Laboratories, Carshalton, Surrey, England
Dr J. Parizek, Institute of Physiology, Czechoslovak Academy of
Sciences, Prague, Czechoslovakia
Dr J. K. Piotrowski, Department of Biochemistry, Institute of
Environmental Research, Medical Academy in Lodz, Lodz, Poland
(Vice-Chairman)
Dr E. Samuel, Health Protection Branch, Department of National
Health and Welfare, Ottawa, Ontario, Canada
Dr S. Skerfving, Department of Internal Medicine, University
Hospital, Lund, Sweden
Dr T. Tsubaki, Brain Research Insitiute, Niigata University,
Niigata, Japan
Professor H. Valentin, Institute for Occupational and Social
Medicine, Erlangen, Federal Republic of Germany
Representatives from other organizations
Dr A. Berlin, Health Protection Directorate, Commission of the
European Communities, Luxembourg
Dr D. Djordjevic, Occupational Health and Safety Branch, ILO,
Geneva, Switzerland
Dr W. J. Hunter, Commission of the European Communities,
Luxembourg
G. D. Kapsiotis, Senior Officer, Food Policy and Nutrition
Division, FAO, Rome, Italy
Dr E. Mastromatteo, Chief, Occupational Health and Safety Branch,
ILO, Geneva, Switzerland
Secretariat
Dr T. Clarkson, University Center in Environmental Health
Sciences, The University of Rochester, School of Medicine and
Dentistry, Rochester NY, USA (Temporary Adviser)
Dr F. C. Lu, Chief, Food Additives, WHO, Geneva, Switzerland
(Secretary)
Dr B. Marschall, Medical Officer, Occupational Health, WHO,
Geneva, Switzerland
ENVIRONMENTAL HEALTH CRITERIA FOR MERCURY
A WHO Task Group on Environmental Health Criteria for Mercury met
in Geneva from 4-10 February 1975. Dr B. H. Dietrich, Director,
Division of Environmental Health, opened the meeting on behalf of the
Director-General. The Task Group reviewed and amended the second draft
criteria document and made an evaluation of health risks from exposure
to mercury and its compounds. The revised draft was sent for comments
to all members of the Task Group.
A group of WHO temporary advisers (Dr T. Clarkson, Dr L. Friberg,
Dr A. Jernelöv,a Dr L. Magos, and Dr G. Nordbergb) assisted the
Secretariat in the final scientific editing of the document. They met
in Geneva on 13 and 14 November 1975.
The first and second draft criteria documents were prepared by
Dr T. Clarkson, Environmental Health Sciences Centre, the University
of Rochester School of Medicine and Dentistry, Rochester, New York,
USA. The comments on which the second draft was based were received
from the national focal points for the WHO Environmental Health
Criteria Programme in Bulgaria, Czechoslovakia, the Federal Republic
of Germany, Italy, Japan, the Netherlands, New Zealand, Poland,
Sweden, the USA, and the USSR; and from the United Nations
Industrial Development Organization (UNIDO), Vienna, and the United
Nations Scientific, Educational and Cultural Organization (UNESCO),
Paris. Comments from the International Labour Organisation, Geneva,
the United Nations Food and Agriculture Organization, Rome, and the
Commission of the European Communities Health Protection Directorate,
Luxembourg, were submitted at the task group meeting.
Comments were also received, at the request of the Secretariat,
from Dr L. Amin-Zaki, Iraq, Dr G. J. van Esch, Netherlands, Dr K.
Kojima, Japan, and Dr S. I. Shibko, USA.
The collaboration of these national institutions, international
organizations, WHO collaborating centres and individual experts is
gratefully acknowledged. Without their assistance the document could
not have been completed. The Secretariat wishes to thank in particular
Dr T. Clarkson for his help in all phases of the preparation of the
document.
a Institute for Water and Air Pollution Research, Stockholm, Sweden.
b Department of Environmental Hygiene, Karolinska Institute,
Stockholm, Sweden.
This document is based primarily on original publications listed
in the reference section. However, several recent publications broadly
reviewing health aspects of mercury and its compounds have also been
used. These include reviews by the Swedish Expert Group (1971).,
Hartung & Dinman (1972), IAEA (1972), and Wallace et al. (1971).
Reviews devoted primarily to the biological effects of mercury have
been published by Clarkson (1972a, 1972b) and Miller & Clarkson
(1973). Furthermore, several recent symposia have provided extensive
reviews of the environmental aspects of mercury (Bouquiaux, 1974;
D'Itri, 1972; Krenkel, 1975). A systematic review of various
environmental health aspects of mercury, including a broad review of
the accessible literature up to 1971, has been presented by Friberg &
Vostal (1972).
1. SUMMARY AND RECOMMENDATIONS FOR FURTHER RESEARCH
1.1 Some definitions
In order to clarify the meaning of certain terms used in the
document, some definitions are given below. However, it should be
noted that these definitions have not been formally adopted by WHO.
The terms critical effects, critical organ, and critical organ
concentration have recently been defined by the Sub-Committee on
Toxicology of Metals of the Permanent Commission and International
Association of Occupational Health (Nordberg, 1976). The term
"critical" as defined by the Committee differs from its usual meaning
in clinical medicine, where it refers to a situation in which the
patient's condition may deteriorate suddenly and dramatically. It also
differs in meaning from that used in the field of radiation
protection, where the "critical" organ is defined as the organ of the
body whose damage by radiation results in the greatest injury to the
individual. In this document, the term "critical" does not refer to a
life-threatening situation, but to a key decision point for taking
preventive action. For example, at some point in the dose-effect
relationship, a critical effect can be identified. The appearance of
an effect in an individual signals the point at which measures should
be taken to reduce or prevent further exposure.
1.2 Summary
1.2.1 Analytical methods
The method of choice for determining total mercury in
environmental and biological samples is flameless atomic absorption.
The technique is rapid and sensitive and the procedure is technically
simple. Neutron activation is now principally used as a reference
method against which the accuracy of atomic absorption procedures may
be checked. Gas-liquid chromatography combined with an
electron-capture detector is the most widely used method for
identifying methylmercury in the presence of other compounds of
mercury.
The methods of sampling require careful consideration of the type
of exposure to be monitored and the material to be analysed. Errors
arising in collection, storage, and transportation of samples may be
as important as instrument errors in contributing to the total error
in the measurement of mercury in the sample. These include
contamination of the sample, and the loss of mercury by adsorption on
the walls of the container, and by volatilization. In estimating human
exposure, special care should be taken to see that the sample is truly
representative, e.g. the mercury vapour concentration in the breathing
zone and the concentration of methylmercury in the daily diet.
1.2.2 Sources of environmental pollution
The major source of mercury is the natural degassing of the
earth's crust and amounts to between 25 000 and 125 000 tonnes per
year. Anthropogenic sources are probably less than natural sources.
World production of mercury by mining and smelting was estimated at
10 000 tonnes per year in 1973 and has been increasing by an annual
rate of about 2%. The chloralkali, electrical equipment, and paint
industries are the largest consumers of mercury, accounting for about
55% of the total consumption. Mercury has a wide variety of other uses
in industry, agriculture, military applications, medicine, and
dentistry.
Several of man's activities not directly related to mercury
account for substantial releases into the environment. These include
the burning of fossil fuel, the production of steel, cement, and
phosphate, and the smelting of metals from their sulfide ores. It was
extimated that the total anthropogenic release of mercury would amount
to 20 000 tonnes per year in 1975.
1.2.3 Environmental distribution and transport
Two cycles are believed to be involved in the environmental
transport and distribution of mercury. One is global in scope and
involves the atmospheric circulation of elemental mercury vapour from
sources on land to the oceans. However, the mercury content of the
oceans is so large, at least seventy million tonnes, that the yearly
increases in concentration due to deposition from the global cycle are
not detectable.
The other cycle is local in scope and depends upon the methylation
of inorganic mercury mainly from anthropogenic sources. Many steps in
this cycle are still poorly understood but it is believed to involve
the atmospheric circulation of dimethylmercury formed by bacterial
action.
The methylation of inorganic mercury in the sediment of lakes,
rivers, and other waterways and in the oceans is a key step in the
transport of mercury in aquatic food chains leading eventually to
human consumption. Methylmercury accumulates in aquatic organisms
according to the trophic level, the highest concentrations being found
in the large carnivorous fish.
Alkylmercury fungicides used as seed dressings are important
original sources of mercury in terrestrial food chains. Mercury is
passed first to seed eating rodents and birds and subsequently to
carnivorous birds.
Accumulation of methylmercury in aquatic and terrestrial food
chains represents a potential hazard to man by consumption of certain
species of oceanic fish, of fish or shellfish from contaminated
waters, and of game birds in areas where methylmercury fungicides are
used.
1.2.4 Environmental exposure levels
The concentration of mercury in the atmosphere is usually below
50 ng/m3 and averages approximately 20 ng/m3. A concentration of
50 ng/m3 would lead to a daily intake of about 1 µg. "Hot spots" near
mines, smelting works, and refineries require further investigation
but could lead to daily intakes as high as 30 µg. Daily intakes would
be higher for occupational exposures to mercury vapour. An average
mercury concentration in air of 0.05 mg/m3 would lead to an average
daily intake via inhalation of about 480 µg. The highest occupational
exposures usually occur in mining operations but over 50 specific
occupations or trades involve frequent exposure to mercury vapour.
Mercury in drinking water would contribute less than 0.4 µg to the
total daily intake. Bodies of fresh water for which there is no
independent evidence of contamination contain mercury at less than
200 ng/litre. Oceanic mercury is usually less than 300 ng/litre.
Food is the main source of mercury in nonoccupationally exposed
populations, and fish and fish products account for most of the
methyl-mercury in food. Mercury in food other than fish is usually
present at concentrations below 60 µg/kg. Mercury is present in
freshwater fish from uncontaminated waters at concentrations of
between 100 and 200 µg/kg wet weight. In contaminated areas of
freshwater, mercury levels between 500 and 700 µ/kg wet weight are
often described and in some cases, concentrations are even higher.
Most species of oceanic fish have mercury levels of about 150 µg/kg.
However, the large carnivorous species (e.g. swordfish and tuna)
usually fall in the range of 200-1500 µg/kg. With few exceptions
methylmercury accounts for virtually all the mercury in both
freshwater and marine fish.
Intake of mercury from food is difficult to estimate with
precision. Daily intake from food other than fish is estimated as 5 µg
but the chemical form of mercury is not known. Most of the
methylmercury in diet probably comes from fish and fish products. The
median daily intake of methylmercury in Sweden has been estimated as
5 µg. In most countries the daily intake is less than 20 µg but in
subgroups in certain countries where there is an unusually high fish
intake (dieters) the daily intake may rise to 75 µg and may even be as
high as 200-300 µg (in coastal villages dependent on large oceanic
fish as the main source of protein). In areas of high local pollution,
daily intakes could be well in excess of 300 µg and these levels have
led to two recorded outbreaks of methylmercury poisoning.
1.2.5 Metabolism of mercury
Approximately 80% of inhaled mercury vapour is retained.
Information on pulmonary retention of other forms of mercury in man is
lacking. Absorption of inorganic mercury compounds from foods is about
7% of the ingested dose. In contrast, gastrointestinal absorption of
methylmercury is practically complete. Little information is available
on skin absorption although it is suspected that most forms of mercury
can penetrate the skin to some extent. In the case of methylmercury,
poisoning has resulted from skin application.
Animal data indicate that the kidneys accumulate the highest
tissue concentrations no matter what form of mercury is administered.
The distribution of mercury between red cells and plasma depends upon
the form of mercury. The red cell to plasma ratio is highest for
methylmercury (approximately 10) and lowest for inorganic mercury
(approximately 1) in man.
The hair is a useful indicator medium for people exposed to
methylmercury. The concentration of mercury in hair is proportional to
the concentration in the blood at the time of formation of the hair.
The relationship between hair and blood concentrations is not known
for other forms of mercury.
Most forms of mercury are predominantly eliminated with urine and
faeces. In workers exposed over a long period to mercury vapour,
urinary excretion slightly exceeds faecal elimination. On a group
basis, mercury excretion in urine is proportional to the time-weighted
average air concentration. Large individual fluctuations are common in
daily mercury excretion in urine in people under the same exposure
conditions.
Faecal elimination accounted for approximately 90% of total
mercury elimination in volunteers given a single dose of
methylmercury. Urinary concentrations of total mercury do not
correlate with blood levels after exposure to methylmercury.
Animal data indicate that elemental mercury vapour rapidly crosses
the placenta. The transplacental transfer of methylmercury compounds
is well documented in man. The mercury concentrations in plasma in the
mother and the newborn infant are similar but the concentration in the
fetal red blood cells is approximately 30% higher than in those of the
mother.
Details on transmission into breast milk are available only for
methylmercury. The concentration of mercury in breast milk is
approximately 5% of the simultaneous mercury level in blood in the
mother, and infants can accumulate dangerously high blood
concentrations by suckling if their mothers are heavily exposed.
Tracer studies in volunteers and in exposed populations have
established the main features of the metabolic model for methylmercury
in man. Clearance half-times from the whole body and from blood are
about 70 days. Daily intakes of methylmercury will lead to a
steady-state balance in about one year, when the body burden will be
approximately one hundred times the daily intake. In steady-state, the
numerical value of the concentration of mercury in whole blood in
µg/litre is virtually equal to the numerical value of the daily intake
in µg/day/70 kg body weight. Considerable individual variation around
these average values has been noted, which must be taken into account
in the estimation of risk in exposed populations.
The metabolic models for other forms of mercury are less well
developed.
1.2.6 Experimental studies on the effects of mercury
Reversible and irreversible toxic effects may be caused by mercury
and its compounds, depending upon the dose and duration of exposure.
Reversible behavioural changes may be produced in animals by exposure
to mercury vapour.
Methylmercury compounds produce irreversible neurological damage
in animals. Many of the neurological signs seen in man have been
reproduced in animals. Methylmercury is equally toxic to animals
whether it is given in the pure chemical state or in fish where it has
accumulated naturally. A latent period lasting weeks or months is
observed between cessation of exposure and onset of poisoning.
Morphological changes have been seen in the brain before onset of
signs. This phenomenon has been referred to as "silent damage". Animal
data support epidemiological evidence from Japan, that the fetus is
more sensitive than the adult.
Little is known about the physical and chemical factors affecting
the toxicity of mercury. Selenium is believed to be protective against
inorganic and methylmercury compounds.
1.2.7 Epidemiological and clinical studies
The classic symptoms of poisoning by mercury vapour are erethism
(irritability, excitability, loss of memory, insomnia), intentional
tremor, and gingivitis. Most effects of mercury vapour are reversible
on cessation of exposure, although complete recovery from the
psychological effects is difficult to determine. Recovery may be
accelerated by treatment with penicillamine and unithiol
(2,3,dimercaptopropansulfonate).
Studies of occupational exposure to mercury vapour reveal that the
classic symptoms of mercurialism do not occur below a time-weighted
average mercury concentration in air of 0.1 mg/m3. Symptoms such as
loss of appetite and psychological disturbance have been reported to
occur at mercury levels below 0.1 mg/m3.
The most common signs and symptoms of methylmercury poisoning are
paraesthesia, constriction of the visual fields, impairment of
hearing, and ataxia. The effects are usually irreversible but some
improvement in motor coordination may occur. Complexing and chelating
agents may be useful in prevention if given early enough after
exposure but BAL is contraindicated in cases of methylmercury
poisoning as it leads to increased brain levels of mercury.
Epidemiological investigations have been made on populations in
whom the intensity and duration of exposure to methylmercury through
diet differs, for example, a population in Iraq having-high daily
mercury intakes (as high as 200 µg/kg/day) for a brief period (about 2
months), populations in Japan having lower daily intakes with exposure
for several months or years, and several fish-eating populations
having daily intakes of mercury usually below 5 µg/kg but with
exposure lasting for the lifetime of the individual. The results of
these studies indicate that the effects of methylmercury in adults
become detectable in the most sensitive individuals at blood levels of
mercury of 20-50 µg/100 ml, hair levels from 50-120 mg/kg, and body
burdens between about 0.5 and 0.8 mg/kg body weight.
Observations on the Minamata outbreak in Japan indicate that the
fetus is more sensitive to methylmercury than the adult but the
difference in degree of sensitivity has not yet been established.
1.2.8 Evaluation of health risks to man from exposure to mercury
and its compounds
Adverse health effects have not yet been identified in workers
occupationally exposed to a time-weighted average air concentration of
mercuryof 0.05mg/m3. This air concentration is equivalent to an
average mercury concentration in blood of 3.5 µ/100 ml and an average
mercury concentration in urine of 150 µg/litre on a group basis. The
corresponding ambient air concentration of mercury for exposure of the
general population would be 0.015 mg/m3.
It is estimated that the first effects associated with long-term
daily intake of methylmercury should occur at intake levels between 3
and 7 µg/kg/day. The probability of an effect (paraesthesia) at this
intake level is about 5% or less in the general population. These
figures apply only to adults. Prenatal life may be the most sensitive
stage of the life cycle to methylmercury. Furthermore experiments on
animals indicate a potential for genetic damage by methylmercury.
1.3 Recommendations for Further Research
1.3.1 Environmental sources and pathways of mercury intake
More information is needed on the physical and chemical forms of
mercury in air, food, and water. With the exception of fish tissue,
little is known of the proportion of total mercury in the diet that is
in the form of methylmercury.
The concentration of mercury in the air in "hot spots" near points
of industrial release is not yet adequately documented. The few
reports reviewed in this criteria document indicate that people living
near points of emission may receive substantial exposure to airborne
mercury. Levels of mercury in the oceans are still inadequately
documented. The pathways of methylation of mercury in the ocean and
its uptake by fish of different trophic levels are poorly understood.
Studies are needed to estimate quantitatively the dietary intake
of methylmercury in populations dependent on fish for their main
source of protein. Average dietary intakes for the populations of
several industrialized countries have been reported. However, of much
greater importance are the identification of those subgroups of the
population having unusually high dietary intakes of methylmercury and
the careful quantitative estimation of average daily intake in these
groups.
1.3.2 Metabolic models in man
The kinetic parameters of uptake, distribution, and excretion of
methylmercury in man are documented in much more detail than for other
forms of mercury. However, questions still remain on the linearity of
this metabolic model at high toxic doses of methylmercury.
Specifically, the applicability of the metabolic model derived from
human tracer-dose studies should be verified at higher dose levels.
Information on this point would greatly facilitate the interpretation
of results of epidemiological studies on heavily exposed populations.
Recent findings of large individual variations in clearance
half-times of methylmercury from blood are of considerable importance
in the estimation of risks from long-term dietary intake. Further
studies are needed to establish the statistical parameters of the
distribution of individual clearance half-times, and on the biological
mechanisms underlying these differences.
A more complete metabolic model for inhaled mercury vapour in man
is urgently needed. Despite the continuous occupational exposure of
thousands of workers annually and the long history of man's exposure
to this form of mercury, we still do not have sufficient information
to relate mercury concentrations in air to accumulated body burdens
and to identify the most appropriate indicator media for levels of
mercury vapour in the target organ (the brain). Animal experiments
have indicated the ability of the inhaled vapour to cross the
placenta; no information is available on human subjects concerning
this important question.
1.3.3 Epidemiological studies
Several types of epidemiological study are needed. Long-term
studies on adults should concentrate on those areas of the
dose-response relationship where the effects of methylmercury become
just detectable. There are still uncertainties concerning the
concentrations of total mercury in indicator media and the equivalent
long-term daily intake of mercury as methylmercury associated with the
earliest effects in the most sensitive group in the adult population.
So far, dose-response relationships in human populations have been
based on outbreaks of poisoning in which daily exposure was high and
limited to months or a few years at the most. To extrapolate these
relationships to the general population, more information is needed on
the potential influence of long-term exposure.
In addition to continuing studies on mature adults, groups of the
population specially sensitive to methylmercury should be identified.
Special studies should be made on the relationship between the dose
received by the expectant mother and the effect on her infant
including the development and growth of the child.
Further epidemiological studies are needed on groups
occupationally exposed to mercury vapour. Whenever possible,
collaborative studies should be carried out in which cohorts should be
followed in time and different groups related to each other.
1.3.4 Interaction of mercury with other environmental factors
The extrapolation to the general population of epidemiological
data from outbreaks of methylmercury poisoning that have occurred in
certain parts of the world is fraught with uncertainties, unless the
possible interaction of local environmental factors can be taken into
account. For example, the conditions under which selenium exerts
antagonistic and synergistic effects and its mode of action should be
studied. Alcohol influences the metabolism of mercury and may affect
the toxicity of inhaled vapour in man. Genetic factors should also be
considered. Acatalasaemic individuals may metabolize inhaled mercury
vapour differently from normal individuals.
Mercury, along with other heavy metals, has the potential to alter
the activity of drug metabolizing enzymes. Studies should be made on
these potential effects with special emphasis on those individuals
carrying high body burdens of mercury.
1.3.5 Biochemical and physiological mechanisms of toxicity
Long-term investigations of the mode of toxic action of mercury
and its compounds are needed to give an insight into the causes of
individual differences in sensitivity to mercury and into differences
in metabolism such as clearance half-times. Methylmercury is known to
produce "silent damage" in that morphological changes can be seen in
the brains of experimental animals before functional disturbances are
detectable. Biochemical disturbances such as inhibition of protein
synthesis precede overt signs of damage. There is a great need to
develop sensitive biochemical and physiological tests, especially in
the case of methylmercury poisoning.
A deeper understanding of the toxic action of mercury should lead
to the development of more effective means of treatment. Present
methods depend mainly on prevention, using complexing and chelating
agents to remove the metal from the body before serious damage has
occurred.
2. PROPERTIES AND ANALYTICAL METHODS
2.1 Chemical and Physical Properties
Mercury can exist in a wide variety of physical and chemical
states. This property presents special problems to those interested in
assessing the possible risk to public health. The different chemical
and physical forms of this element all have their intrinsic toxic
properties and different applications in industry, agriculture, and
medicine, and require a separate assessment of risk.
The chemistry of mercury and its compounds has been outlined in
several standard chemistry texts (Rochow et al., 1957; Gould, 1962;
Cotton & Wilkinson, 1972). Mercury, along with cadmium and zinc, falls
into Group IIb of the Periodic Table. In addition to its elemental
state, mercury exists in the + 1 (mercury(I)) and +2 (mercury(II))
states in which the mercury atom has lost one and two electrons,
respectively. The chemical compounds of mercury(II) are much more
numerous than those of mercury(I).
In addition to simple salts, such as chloride, nitrate, and
sulfate, mercury(II) forms an important class of organometallic
compounds. These are characterized by the attachment of mercury to
either one or two carbon atoms to form compounds of the type RHgX and
RHgR' where R and R' represent the organic moiety. The most numerous
are those of the type RHgX. X may be one of a variety of anions. The
carbon-mercury bond is chemically stable. It is not split in water nor
by weak acids or bases. The stability is not due to the high strength
of the carbon-mercury bond (only 15-20 cal/mol and actually weaker
than zinc and cadmium bonds) but to the very low affinity of mercury
for oxygen. The organic moiety, R, takes a variety of forms, some of
the most common being the alkyl, the phenyl, and the methoxyethyl
radicals. If the anion X is nitrate or sulfate, the compound tends to
be "salt like" having appreciable solubility in water; however, the
chlorides are covalent non-polar compounds that are more soluble in
organic solvents than in water. From the toxicological standpoint, the
most important of these organometallic compounds is the subclass of
short-chain alkylmercurials in which mercury is attached to the carbon
atom of a methyl, ethyl, or propyl group.
An expert committee, considering occupational hazards of mercury
compounds, distinguished two major classes of mercury compounds --
"organic" and "inorganic" (MAC Committee, 1969). Inorganic mercury
compounds included the metallic form, the salts of mercury(I) and
mercury(II) ions, and those complexes in which mercury(II) was
reversibly bound to such tissue ligands as thiol groups and protein.
Compounds in which mercury was directly linked to a carbon atom by a
covalent bond were classified as organic mercury compounds. This
distinction is of limited value because the toxic properties of
elemental mercury vapour differ from those of the inorganic salts and,
furthermore, the short-chain alkylmercurials differ dramatically from
other mercurials that fall within the definition of organic mercury.
From the standpoint of risk to human health, the most important forms
of mercury are elemental mercury vapour and the short-chain
alkylmercurials.
Mercury in its metallic form is a liquid at room temperature. Its
vapour pressure is sufficiently high to yield hazardous concentrations
of vapour at temperatures normally encountered both indoors and
outdoors under most climatic conditions. For example, at 24°C, a
saturated atmosphere of mercury vapour would contain approximately
18 mg/m3 -- a level of mercury 360 times greater than the average
permissible concentration of 0.05 mg/m3 recommended for occupational
exposure by the National Institutes of Safety and Health, USA (NIOSH,
1973). Apart from the noble gases, mercury is the only element having
a vapour which is monatomic at room temperature. However, little is
known about the chemical and physical states of mercury found in the
ambient air and in the air where occupational exposure occurs.
Elemental mercury vapour is generally regarded as insoluble.
Nevertheless, small amounts dissolved in water and other solvents are
important from the toxicological point of view. At room temperatures,
in air-free water, its solubility is approximately 20 µg/litre. In the
presence of oxygen, metallic mercury is rapidly oxidized to the ionic
form -- mercury(II) -- and may attain concentrations in water as high
as 40 µg/litre.
Calomel or mercury(I) chloride (Hg2Cl2) is the best known
mercury(I) salt. Widely used in the first half of this century in
teething powders and in anthelmintic preparations, the low toxicity of
this compound is due principally to its very low solubility in water.
Mercury(I) forms few complexes with biological molecules. However, in
the presence of protein and other molecules containing SH groups, it
gives one atom of metallic mercury and one mercury(II) ion. In
general, an equilibrium is established between Hg0, Hg2++ and Hg++
in aqueous solution. The distribution of mercury between the three
oxidation states is determined by the redox (oxidation-reduction)
potential of the solution and the concentration of halide, thiol, and
other groups that form complexes with Hg++. The dissociation of
mercury(I) chloride by thiol groups should be understood in this
context. Extra halide and thiol compounds, added to solution, form
complexes with mercury(II) ions and the mercury(I) chloride splits to
restore the equilibrium between Hg0, Hg2++ and Hg++. The split
results in the formation of one atom of mercury for every mercury(I)
chloride molecule dissociated.
The mercury(II) ion, Hg++, is able to form many stable complexes
with biologically important molecules. Mercury(II) chloride (corrosive
sublimate), a highly reactive compound, readily denatures proteins and
was extensively used in the past century as a disinfectant. It is
soluble in water and, in solution, forms four different complexes with
chloride, HgCI+, HgCl2, HgCl3- and HgCl4=. It has been
suggested that the negatively charged chlorine complexes are present
in sea water (see section 5).
Phenylmercury compounds have a low volatility. However, the halide
salts of methyl-, ethyl-, and methoxyethylmercury can give rise, at
20°C, to saturated mercury vapour concentrations of the order of 90,
8, and 26 mg/m3, respectively (Swensson & Ulfvarsson, 1968). In the
case of methylmercury this saturated vapour concentration is several
orders of magnitude greater than the maximum allowable concentration
in the working atmosphere. This hazardous property of the halide salts
of the short-chain alkylmercurials is not always fully appreciated in
industrial and agricultural use and even in research laboratories
(Klein & Hermen, 1971). In contrast, methylmercury dicyandiamide,
previously widely used as a fungicide, has a much lower vapour
pressure, being 340 times less volatile than the chloride salt.
Although the carbon-mercury bond is chemically stable, in the
living animal, the bond is subject to cleavage (for review, see
Clarkson, 1972a). The nature of the R radical is all important. If R
is a phenyl or methoxyalkyl group, rapid breakdown occurs in animal
tissues so that most of the organic compound has disappeared within a
few days. Enzymes that break the carbon mercury bond have been
discovered and isolated (Tonomura et al., 1968a, 1968b, 1968c). The
short-chain alkylmercurials undergo the slowest breakdown in vivo
with methylmercury being the most stable. Differences in the stability
of the carbon-mercury bond play an important role in determining the
toxicity and mode of action in man. The rapid breakdown of phenyl- and
methoxymercury results in toxic effects similar to those of inorganic
mercury salts. The relative stability of the alkylmercurials is one
important factor in their unique position with regard to toxicity and
risks to human health.
The organic and inorganic cations of mercury, in common with other
heavy metal cations, will react reversibly with a variety of organic
ligandsa found in biologically important molecules. The chemical
affinity of mercury(II) and of its monovalent alkylmercury cations for
a variety of biologically occurring ligands is so great that free
mercury would be present in vivo at concentrations so low as to be
undetectable by present methods.
2.2 Purity of Compounds
Impurities in mercury and its compounds are not important in
assessing the hazards to man. Those compounds of mercury used in
industry and agriculture have impurities of less than 10%. Bakir et
al. (1973) reported that a methylmercury fungicide responsible for an
epidemic of poisoning in Iraq contained 10% or less of ethylmercury as
an impurity. Inorganic mercury usually amounts to no more than 1% of
the total mercury in organomercurial preparations and rarely exceeds
5%.
Impurities are of importance in the preparation of standard
solutions for analytical procedures and in experimental research in
animals where impurities in radioactive mercury may give misleading
results. Preparations of methylmercury labelled with the isotope 203Hg
are subject to radiolytic breakdown to inorganic compounds depending
on the pH. This instability must be taken into account in the
interpretation of some original reports in which the purity of the
radioisotope was not checked properly.
2.3 Sampling and Analysis
Before reviewing various aspects of sample collection and analysis
it may be worth taking an overview of the various sources of error in
the determination of mercury content. Not only are there errors in the
instrumental determination of mercury and in the laboratory
procedures, but significant and often major errors occur during the
collection, transportation, and storage of the samples. The accuracy
of the determination of mercury in environmental samples should be
assessed from this broad point of view. The error will be the sum of
a Ligands are chemical groups within a molecule that are capable of
donating electrons to a metal cation to form a chemical bond.
Examples of biologically important ligands are the carboxyl, and
especially with regard to heavy metals, the sulfhydryl (SH)
groups.
the errors in collection, storage, transportation and, in the
instrumental determination. It is of the greatest importance to
determine the greatest source of error in each particular case. This,
in itself, may lead to considerable improvement in the overall
accuracy of the determination. For example, the introduction of a new
and more sensitive instrumental technique may allow the collection of
smaller samples and thus facilitate storage and transport. On the
other hand, there is little value in proceeding further with
improvements in instrumental measurements if major errors remain at
the collection, storage, or transport stages.
2.3.1 Sample collection
Methods of sample collection for the determination of mercury in
air have recently been reviewed (NIOSH, 1973). A recommended method
for the determination of total mercury in air is presented.
Essentially the method consists of using two bubblers in series,
containing sulfuric acid and potassium permanganate. The mercury in
these traps is subsequently determined by atomic absorption
procedures. Problems of the determination of mercury in air are
critically evaluated. Included in these problems is the fact that
numerous chemical and physical forms of mercury may exist in air and
that these are subject to interconversion. The volatility of mercury
and its compounds is a special problem in the determination of mercury
bound to particles. The separation of particulates from air, such as
by filtration, may result in the loss of mercury by volatilization
from the particulate. Published methods of sample collection consist
of removal of mercury from the air by passing it through scrubbing
devices, or direct collection of the air sample, for example in a
plastic bag or syringe. The scrubbing device may take the form of
bubblers, filters, absorbants, or amalgam collectors. Unfortunately
many of the published procedures do not report collection efficiency.
Attention is drawn to the importance of the use of standard dust
chambers to check the efficiency of absorption.
The procedure recommended by NIOSH (1973) has a collection
efficiency for total mercury of more than 90%, when mercury is in the
form of elemental vapour or inorganic salts. Organomercurials in air
are collected with an efficiency of more than 80%, except in the case
of the short-chain alkylmercurials. Bramen (1974) has described a
procedure for separating and measuring different physical and chemical
forms of mercury in air. Previous reports distinguishing between
mercury vapour and particle-bound mercury have not reported the
efficiency of collection.
An early method (Polesajev, 1936) for the determination of mercury
in air involved absorption in iodine and subsequent determination of
the coloured complex in the sediment. This method is still widely used
in the Soviet Union and some countries of eastern Europe.
Commercially available portable monitoring devices are used to
determine mercury directly in air. The air is pumped through an
optical cell that measures the absorption of light emitted from a
mercury vapour lamp. These units, although convenient, measure only
elemental mercury vapour and are subject to a wide variety of
interferences and interfering substances many of which are likely to
be present in the working environment. These units should be
calibrated each time before use. The commercial units also suffer from
the deficiency that they sample only small volumes of air that may not
give a representative picture of the working environment. Research
should be directed towards the development of personal monitoring
devices. These devices should be small and portable so that they can
be carried by workmen throughout the working day and thereby give a
cumulative picture of the exposure of each individual. In most cases
it would be necessary only to devise systems for collecting total
mercury.
The method of Wolf et al. (1974) allows the direct detection of
mercury using reactive tubes (Draeger tubes) providing a simple
screening method for determining mercury in working places at sporadic
intervals.
The collection of samples for the determination of mercury in
water must take into account the following factors; (a) the low
concentration of mercury in water, normally of the order of
10 ng/litre; (b) the tendency of mercury to adsorb on to the surface
of the collection vessel at these low concentrations; (c) the
possibility, if not likelihood, of volatilization of mercury from the
sample (Toribara et al., 1970) and (d) the type of collection vessel.
Greenwood & Clarkson (1970) have reported on the rates of loss of
mercury from containers made from ten different materials and
suggested that Pyrex, polycarbonate, and Teflon are the best materials
for storing and handling mercury. Further studies of possible losses
of organomercurials through the walls of some plastic containers
should, however, be studied. Losses due to volatilization may be
reituced by the addition of oxidizing substances such as potassium
permanganate (Toribara et al., 1970). Lamm & Ruzika (1972) have
recommended that radioactive-tracer mercury be added to the sample to
check the losses discussed above. They note that this procedure has
rarely been adopted to date.
For the collection and storage of food samples, acceptable
procedures are usually followed. The most important food items for
determination of mercury are those containing fish and fish products.
Mercury levels in other foodstuffs usually do not amount to a
significant fraction of daily exposure unless the food has accidently
been contaminated, such as by the use of pesticides. In the collection
and storage of food samples prior to analysis, care should be taken to
avoid bacterial growth leading either to the breakdown of organic
mercury compounds or to the volatilization of mercury (Magos et al.,
1964).
Samples of blood, hair, and urine have been used to monitor the
exposure of human beings to mercury. The methods of collecting and
storing these samples are of great importance. With respect to blood
samples, care should be exercised to avoid any clot formation. If this
does occur, the sample should be homogenized thoroughly before
analysis. It is useful, in certain situations, to determine mercury in
the red cells and plasma and it is thus important to avoid any
haemolysis of the blood sample. The nature of the anticoagulants used
does not affect the mercury determinations, of either the total
mercury in whole blood or the distribution of mercury between plasma
and red blood cells. "Vacutainers"a are convenient for blood
collection and allow storage of the blood samples in Pyrex tubing
under aseptic conditions. Blood samples that have been contaminated by
microorganisms and stored in the refrigerator at 4°C for a month or
more may give misleading results due to the breakdown of methylmercury
and other organic mercury compounds (Clarkson, personal communication,
1974). The storage of blood samples in the frozen state or
freeze-dried is suitable providing that mercury is determined only for
whole blood. Significant losses of mercury do not occur during
freeze-drying procedures (Albanus et al., 1972).
Measurement of mercury in urine samples has been used as a measure
of exposure to mercury under industrial conditions. The popularity of
this approach in early studies was mainly due to the case of digestion
of the urine sample. However, there are serious problems in the
collection and storage of urine samples that may seriously influence
the results. The following factors have been recognized; (a) the
time of day of urine collection (Piotrowski et al., 1975),
(b) bacterial contamination, which might give rise to significant
losses of mercury by volatilization (Magos et al., 1964), (c) the
nature of the container (Greenwood & Clarkson, 1970),
(d) contamination from mercury in workers' clothing and from the
collection of urine samples under working conditions. It should be
noted that urine samples do not give a reliable indication of exposure
to methylmercury (Bakir et al., 1973).
Hair samples are becoming the samples of choice in determining
exposure to methylmercury through diet. Depending upon the length of
the hair sample, it is possible to recapitulate exposure to
methylmercury for several yearsb. The concentration of mercury in
hair when formed is directly proportional to the concentration of
a Trade name of heparinized test-tube manufactured by Becton &
Dickinson, USA, and used for collection of blood samples.
b The average rate of growth of hair is approximately 1 cm
per month (Giovanoli et al., 1974; Shahristani & Shihab,
1974).
mercury in the blood, the concentration in hair being about 250 times
the concentration in blood. The ratios are well established for
exposure to methylmercury but only limited information is available
for inorganic mercury. Attention has been drawn to the errors
introduced during the collection and transportation of hair samples
(Giovanoli & Berg, 1974). Usually 50-100 strands of hair are needed
for analysis. Differential rates of growth for each strand and lateral
displacement of the samples during cutting and transportation of the
hair will affect the longitudinal profiles of mercury in the hair
sample. Giovanoli & Berg (1974) have described a computerized
procedure for the correction of these artifacts.
2.3.2 Analytical methods
Methods of analysis are usually classified according to the type
of instrument used in the final measurement. This convenient
classification will be used here. However this approach tends to
belittle the role of the skill and experience of the analyst. In fact
a poor method in the hands of a highly skilled analyst is more likely
to yield accurate results than a good method in the hands of a poor
analyst. In recent years it has become a practice to test methods by a
"round robin" distribution of a standard sample. Comparison of results
from the participating laboratories is more likely to give information
on the competence of the analysts in the laboratory than it is to give
a critical evaluation of the method itself.
Measurement of the very low levels of mercury found in the
non-contaminated environment makes special demands both on the skills
of the analyst and the resources of the method employed. No matter how
frequently used, a method for the determination of mercury in nanogram
quantities cannot be regarded as a routine procedure. Continued
vigilance over the results is an absolute requirement. Furthermore,
where conditions allow, it is highly desirable that the results with
one method and from one laboratory be checked against those with a
different method from another laboratory. One useful combination of
different procedures is the analysis of total and inorganic mercury by
selective atomic absorption and the selective analysis of organic
mercury compounds (usually methylmercury and other short-chain
mercurials) by gas chromatography (Giovanoli et al., 1974).
The literature is full of papers concerning methods of determining
mercury. Several recent reviews have appeared (D'Itri, 1972; NIOSH,
1973; Burrows, 1975, Swedish Expert Group, 1971; Wallace et al., 1971;
CEC Working Group of Experts, 1974). The most frequently used methods
for measurements of total mercury are colorimetric (dithizone),
flameless atomic absorption, and neutron activation. The flameless
atomic absorption method has become the "work-horse" for measurement
of environmental samples. Difficulties might arise in the measurement
of mercury owing to the fact that it is strongly bound to the organic
materials in most samples. Many procedures require the destruction of
organic materials by wet oxidation or by high temperatures. Loss of
mercury by volatilization may occur. If the wet oxidation is too mild
the result will be inadequate recovery. A high reagent blank may be
introduced by the chemicals used for oxidation. In certain procedures
involving atomic absorption or neutron activation the digestion of the
sample or heating of the sample is not necessary. These procedures
have the advantage of having a low blank but problems of variable
recovery or interference may arise.
The determination of mercury by colorimetric measurement of a
mercury dithizonate complex has been the basis of most of the methods
in the 1950s and in the 1960s. Other related methods using dithizone
for measuring mercury in environmental samples have been described by
Kudsk (1964) and Smart et al. (1969). The above procedures all make
use of wet oxidation of the sample followed by extraction of mercury
in an organic solvent as a dithizonate complex and finally the
colorimetric determination of the complex itselfa. Selectivity for
mercury is obtained by adjusting the conditions of extraction. Copper
is the metal most likely to interfere with mercury measurement by
dithizone.
The dithizone procedure has an absolute sensitivity of about
0.5 µg of mercury. A sample size of 10 g is suitable for most
digestion procedures so that mercury can be determined at the
0.05 mg/kg level in most foodstuffs and tissues.
Kudsk (1964) has described a dithizone procedure for measuring
mercury in air that will measure as little as 0.05 µg of mercury. With
the usual sample size of 0.1 m3, the detection limit would be
0.5 µg/m3. This is more than adequate sensitivity for monitoring air
in the working environment with the MAC levels in force. The quoted
recovery rates from foodstuffs and tissues are in the range of 85-99%
and the reproducibility can yield a coefficient of variation of as low
as 2%. On account of its long history of use, the dithizone procedure
has been used to measure mercury in virtually all types of
environmental samples including air, water, food, tissues, and soils.
It suffers from the disadvantage that it is time consuming and its
sensitivity is not high when compared with atomic absorption
procedures.
a The organic material may also be destroyed by combustion in an
oxygen flask (Gutenmann & Lisk, 1960; White & Lisk, 1970; and
Fujita et al., 1968). This allows all biological materials to be
treated alike but has the disadvantage of requiring dried
material.
The latest developments in atomic absorption procedures have
recently been reviewed by Burrows (1975). The most commonly used
method in the USA is that of Hatch & Ott (1968) as modified by Uthe et
al. (1970). The procedure involves oxidative digestion ("wet ashing"),
followed by reduction, aeration, and measurement of mercury vapour
absorption at 253.7 nm. The detection limit is approximately 1-5 ng of
mercury. The wide popularity of cold vapour atomic absorption has
resulted in a large number of publications dealing with various
applications of this procedure to the measurement of mercury in
sediments, soils, and biological samples (including foodstuffs). Of
the 16 publications reviewed by Burrows (1975), 13 reported recoveries
of 90% or more. The relative standard deviation was 10% or less in
half of the published procedures, and was less than 20% in more than
90% of these procedures.
The measurement of very low levels of mercury in water samples
requires some preconcentration. This may be achieved by dithizone
extraction (Chau & Saiton, 1970; Thomson & McComas, 1973), by
electrodeposition (Doherty & Dorsett, 1971) and by an amalgamation on
silver wire (Hinkle & Learned, 1969; Fishman, 1970), in each case
permitting detection limits of 1 ng/litre-10 ng/litre. Winter &
Clements (1972) have described a procedure that will measure mercury
in water in the range of 200 ng/litre and does not require
preconcentration.
Magos (1971) has described a reduction technique that selectively
determines total and inorganic mercury in biological samples without
digestion of the material. This technique has been modified by Magos &
Clarkson (1972) to permit determination of mercury in blood samples at
the low levels found in unexposed populations (0.1-1.0 µg/100 ml). The
technique has a sensitivity of approximately 0.5 ng of mercury.
Recently it has been successfully applied to the measurement of total
and inorganic mercury in hair samples (Giovanoli et al., 1974). The
relative standard deviation was 2% and the recovery rates were quoted
as being close to 100%. The technique has the advantage of high speed
-- each determination taking less than 2 minutes -- high sensitivity,
and the apparatus involved is light, portable, and suitable for field
applications. Its widest application to date has been in the
measurement of mercury in biological samples in the large Iraq
outbreak (Bakir et al., 1973). Since the procedure does not require
digestion of the biological sample, internal standards are used in
each determination. The rates in this procedure must be checked for
each new biological matrix.
The atomic absorption techniques referred to above are subject to
interference. The most common interfering substances are benzene and
other aromatic hydrocarbons that absorb strongly in the 253.7 nm
region. Interference from a variety of organic solvents has been
reported by Kopp et al. (1972).
The combustion-amalgamation method has undergone a series of
developments to avoid difficulties due to interfering substances.
Reference may be made to the work of Lidmus & Ulfvarson (1968), Okuno
et al. (1972), and Willford (1973) who developed techniques for
oxidation of the biological sample, and the trapping of mercury vapour
on silver or gold followed by its release into an atomic absorption
measuring device. All these methods have sensitivities down to the
1 µg/litre level and avoid the risk of interference from other
substances. However, as pointed out by Burrows (1975), care must be
taken in the design and operation of the combustion tube to avoid
losses of volatile mercury derivatives.
In summary, a wide variety of applications of atomic absorption
procedures have now been published. The technique is rapid and
sensitive and the procedure is technically simple. Procedures are
available for avoiding difficulties due to interfering substances.
Most procedures have a detection limit in the range of 0.5-5 ng of
mercury and a relative standard deviation of about 10% or less.
Recovery rates are usually of the order of 95-100% depending on the
technique used in the preparation of the biological sample and the
rate of release of mercury from it.
Procedures for neutron activation analysis of total mercury have
recently been reviewed by Wallace et al. (1971), Swedish Expert Group
(1971), Westermark & Ljunggren (1972), and Burrows (1975). The method
is based on the principle that when natural mercury (a mixture of
stable isotopes) is exposed to a high flux of thermal (slow) neutrons,
it is converted to a mixture of radioactive isotopes, principally
197Hg and 203Hg, which have decay half-lives of 65 hours and 47 days,
respectively. The Sjostrand (1964) technique has been used most in the
measurement of environmental samples. After the sample has been
irradiated with neutrons, a precise weight of carrier mercury is added
and the sample subjected to digestion and organic destruction. On
completion of digestion, mercury is isolated by electrodeposition on a
gold foil and the radioactivity is determined with a gamma counter.
The use of carrier mercury corrects for any losses of mercury during
the digestion, extraction, and isolation procedures. The limit of
detection is 0.1-0.3 ng of mercury. The sample size is 0.3 g giving a
concentration limit of 0.3-1 µg/kg in most biological samples. The
relative standard deviation in samples of kale, fish, minerals, oil,
blood, and water is less than 10%. Samuel (unpublished data)
decomposed biological material irradiated with neutrons using fuming
sulfuric acid and hydrogen peroxide and after the addition of hydrogen
bromide, distilled the mercury as bromide together with other trace
elements. This method, which is suitable for series analysis, is
characterized by high recovery (96%) and good reproducibility. Trace
mercury in biological and environmental materials can also be rapidly
and satisfactorily determined through isolation as mercury(II) oxide
or mercury(II) sulfide after digestion and clean-up procedures
following neutron activation (Pillay et al., 1971; Samuel, unpublished
data).
In general, the analyst is faced with three major options in the
use of neutron activation procedures; (a) destruction or
non-destruction of the sample, (destruction and isolation of the
mercury is usually required in samples containing less than 1 µg of
mercury); (b) the choice of isotope 197Hg (if the longer-lived
isotope, 203Hg, is used the sample may be allowed to stand to avoid
interference from short-lived elements activated along with the
mercury -- however, 203Hg requires a more intense neutron flux or a
longer irradiation time to achieve the same activity as the 197Hg);
(c) the choice of detector (the sodium iodide (thallium) detector
does not have as high a resolution as the germanium (lithium)
detector, although its sensitivity is significantly higher).
Interference may come from the following elements, produced at the
same time as the radioactive mercury isotopes, 24Na, 82Br, 32P, and
75Se. Interference from these isotopes may be avoided, as in the
Sjostrand (1964) procedure, by chemical isolation of the radioactive
isotope. However, 75Se may not be completely removed by the isolation
procedures and might interfere if the sodium iodide (thallium)
detector is used. The better resolution of the germanium (lithium)
detector allows correction for 75Se interference through use of other
lines in the 75Se spectrum. For samples containing more than 1 µg of
mercury, the required selectivity can be achieved without destruction
of the sample, i.e., by instrumental analysis only. One procedure is
to measure the 203Hg isotope, after allowing the sample to stand for
approximately one month to eliminate interference due to sodium,
phosphorous, and bromine. Another procedure is to make use of the
discriminating germanium (lithium) detector when the gamma irradiation
from the radioactive isotope may be determined to the exclusion of
most of the interfering radioactivity.
A recent non-destructive procedure for measuring mercury in coal
makes use of a low-energy photon detector to estimate levels at the
100 µg/kg level with a precision of 10% (Weaver, 1973).
Burrows (1975) has recently reviewed 11 publications describing
the application of neutron activation to a variety of environmental
samples. Non-destructive (instrumental) determination was used in only
two of these publications. In 9 of these publications the 197Hg
isotope was determined. Mercury levels were reported in lake water
(4 µg/litre, relative standard deviation 23%), in glacial ice
(0.2 µg/kg, relative standard deviation 90%), in coal (100 µg/kg,
relative standard deviation 10%), in whole blood (0.7 µg/100 ml,a
relative standard deviation 10%), in fish (1-3 mg/kg, relative
standard deviation less than 10%). Many environmental samples were
measured by neutron activation, especially in Sweden, before the
introduction of the atomic absorption technique (Westermark &
Ljunggren, 1972).
Compared with other methods reviewed here, the neutron activation
procedure has the following advantages; (1) high sensitivity
(approximately 0.5 µg/kg); (2) no reagent blank; (3) independence from
the chemical form of the element; and (4) non-destructive instrumental
methods applicable to samples containing 1 µg of mercury or more. It
has the disadvantages that it cannot be adapted to field use and, that
if there are large numbers of samples, special radiation facilities
and data processing are required. It is generally agreed that the
neutron activation procedure finds its most important use as a
reference method against which other procedures can be checked.
A variety of other instrumental techniques, such as X-ray
fluorescence, mass spectrometry, and atomic fluorescence, for the
measurement of total mercury have been reviewed by Lamm & Ruzicka
(1972) and by Burrows (1975). In general, some of these methods may
have a potentially higher sensitivity or selectivity for mercury. The
fact is that, at the time of writing, these procedures have not yet
found useful application in the measurement of mercury in
environmental samples.
To summarize the present methods for the determination of total
mercury in environmental samples, it would appear that the method of
choice is that of flameless atomic absorption. No single procedure is
appropriate, however, in all circumstances. The methods of sample
handling depend upon the particular biological matrix to be analysed.
Neutron activation is principally of use as a reference method against
which atomic absorption methods may be checked.
a In this document the concentration of mercury in blood is
expressed in µg/100 ml although in some original papers the values
are given in µg/100 g. For practical purposes the difference of
about 5% can be neglected.
2.3.3 Analysis of alkylmercury compounds in the presence of
inorganic mercury
Techniques for the identification and measurement of alkylmercury
compounds in the presence of other compounds of mercury have been
reviewed recently (Swedish Export Group, 1971; Tatton, 1972; Sumino,
1975; Westöö, 1973). In general, three methods are available for the
identification of alkylmercury compounds. These include (a) paper
chromatography (Kanazawa & Sato, 1959; Sera et al., 1962), (b) thin
layer chromatography (Johnson & Vickery, 1970; Westöö, 1966, 1967;
Tatton & Wagstaffe, 1969), (c) gas-liquid chromatography (Westöö,
1966, 1967; Sumino, 1968; Tatton & Wagstaff, 1969). The paper
chromatographic techniques have given way to thin-layer chromatography
(TLC) for qualitative identification of the organomercurial compounds.
Most quantitative work is now carried out using TLC techniques, and
also gas-liquid chromatography (Westöö, 1966, 1967; Sumino, 1968;
Tatton & Wagstaffe, 1969; Solomon & Uthe, 1971). However, the method
of Magos & Clarkson (1972) that selectively determines organic mercury
by cold vapour atomic absorption is frequently applicable to the
determination of methylmercury at levels occurring in fish and blood.
Methylmercury is the only organic form of mercury present in fish.
Blood samples from people exposed to methylmercury contain only
inorganic mercury and methylmercury compounds. Thus the determination
of organic mercury by this procedure is an accurate measure of
methylmercury in these situations.
The basic procedures for samples of food, soil, and biological
materials are first, homogenization of the sample, acidification by a
hydrogen halide acid followed by extraction with an organic solvent,
usually benzene, a clean-up step involving the conversion of the
organomercurial compound to a water soluble compound usually the
hydroxide or sulfate or a cysteine complex, and re-extraction with
benzene. The benzene layer is now ready for analysis by thin-layer
chromatography for qualitative purposes or by gas-liquid
chromatography if quantitative measurements are required. A recent
variant by Rivers et al. (1972) converts the organic into inorganic
mercury and then makes use of cold vapour atomic absorption for final
determination.
The gas-liquid chromatographic system is the one most commonly
used. Problems may be encountered both in the pre-treatment of the
sample and in the gas chromatographic determination itself. All these
techniques involve non-destructive extraction of mercury from the
sample. Thus recovery rates have to be checked for every different
type of sample matrix. The efficiency of extraction of mercury is
determined by both the nature of the sample matrix and the extraction
procedures themselves. Von Burg et al. (1974) introduced the idea of
adding a tracer amount of radioactively labelled methylmercury to the
homogenate and counting the final benzene extract to check variations
in the efficiency of extraction. This procedure is well worth
consideration for routine use as it is most difficult to check
extraction recovery rates.
Acidification of the homogenate is usually achieved by the
addition of a hydrogen halide acid (usually HCl). At this point
mercury(II) chloride may be added to either the homogenate or the
benzene to tie up excess sulfur compounds and prevent recombination of
methylmercury with sulfur. Westöö (1968) has shown that this approach
may give high recovery rates but cannot be used with liver as there is
a danger of methylation of the inorganic mercury. Clean-up of the
first benzene extract is usually achieved by using solutions of
cysteine. However, this complexing agent is subject to oxidation,
particularly by substances in muds. A more suitable system in the
presence of oxidizing agents is the ammonium hydroxide-sodium sulfate
solution described by Westöö. No problems are usually encountered in
the reextraction ofmethylmercury from cysteine to benzene using
3 mol/litre hydrochloric acid. However, in the extraction procedures,
volumetric errors may arise especially when the concentration of
hydrochloric acid is low (1 mol/litre) and when small amounts of
methyl-mercury are extracted from large volumes (Westöö, 1973).
In gas chromatography, the main object is to produce sharp peaks
and attain high sensitivity. Tatton (1972) has noted that most
commercial preparations ofalkylmercury salts are not pure enough to
use as standards. Sumino (1973) prepares pure methylmercury from the
combination of inorganic mercury with tetramethyl lead salts. The peak
is identified by electron-capture detectors using tritium or nickel as
the source of beta particles. These detectors are subject to
overloading and not more than 100 ng of mercury should be determined
at one time (Tatton, 1972). Absolute confirmation of the identity of
the peak should be made by mass fragmentation methods (Sumino, 1975).
The detection limit in the Westöö procedure is approximately
1-5 µg per kilogram of sample using a 10 g sample. The precision is 3%
at the 0.05 mg/kg level for fish samples. Recovery rates are generally
above 90% but do vary with the sample matrix. Solomon & Uthe (1971)
developed a semimicro-method for the rapid determination of
methylmercury in fish tissues. Samples of about 2 g were used. A
precision of 2% was reported with recovery rates of about 99%. Samples
such as blood, liver, and kidney are much more difficult to extract
than fish tissues.
Thin-layer chromatography usually requires, for optimum spot size,
2 µg of mercury for each type of compound.
3. SOURCES OF ENVIRONMENTAL POLLUTION
The sources of mercury leading to environmental pollution have
been the subject of several recent reviews (Wallace et al., 1971;
D'Itri et al., 1972; Joint FAO/WHO Expert Committee on Food Additives,
1972; Heindryckx et al., 1974; Korringa & Hagel, 1974). Estimates of
both natural and anthropogenic sources of mercury are subject to
considerable error. In the first place the levels of mercury in
environmental samples such as ice from Greenland are extremely low and
close to the limit of sensitivity of the analytical methods. These low
values are then converted by large multiplication factors (annual
total global rainfall, 5.2 x 105 km3) so as to obtain values for the
global sources and turnover of mercury. Enormous fluctuations may be
seen in samples such as coal and oil, which are believed to be an
important anthropogenic source of mercury. Values quoted by D'Itri
(1972) indicate ranges of concentrations of mercury in crude oil
varying by a factor of 1000 and ranges in coal even greater than this.
Estimates of industrial production and consumption of mercury are
subject to the vagaries of the economic market and in recent years to
government regulation because of concern over mercury pollution.
Nevertheless, despite all the assumptions and approximations in these
procedures, the general picture that emerges from a variety of
independent calculations is that the natural sources of mercury are at
least as great as, and may substantially outweigh, the anthropogenic
sources. However, man-made sources may be of considerable importance
in terms of local contamination of the environment. For example,
Korringa & Hagel (1974) have calculated that the man-made release of
mercury in the Netherlands is 100 times greater than the release of
mercury by natural degassing processes.
3.1 Natural Occurrence
A recent review by the Joint FAO/WHO Expert Committee on Food
Additives (1972) quotes the major source of mercury as the natural
degassing of the earth's crust and quotes figures in the range of
25 000-150 000 tonnes of mercury per year. These figures originate
from a paper by Weiss et al. (1971) on concentrations of mercury in
Greenland ice that was deposited prior to 1900. The most recent
calculations on natural sources of mercury have been published by
Korringa & Hagel (1974). These authors also made use of the figures of
Weiss et al. (1971) to calculate the annual amount of mercury reaching
the earth's surface due to precipitation of rainfall and arrived at a
figure of approximately 30 000 tonnes. It was admitted that the
sources of this atmospheric mercury are not yet clearly established
but that volcanic gases and evaporation from the oceans are probably
significant sources. It was also calculated by these authors that the
run-off of mercury from rivers having a "natural mercury" content of
less than 200 ng/litre would account for approximately 5000 tonnes of
mercury per year. Measurements of the concentrations of mercury in air
attached to aerosols (Heindryckx et al., 1974) indicate that soil
dispersion to the atmosphere is not an important source of mercury.
Significant local contamination may result from natural sources of
mercury. For example, Wershaw (1970) has shown that water sources
located near mercury ore deposits may contain up to 80 µg/litre as
compared with the levels of 0.1 µg/litre in non-contaminated sources.
3.2 Industrial Production
According to a recent review by Korringa & Hagel (1974), world
production averaged about 4000 tonnes per year over the period
1900-1940. Production in 1968 was 8000 tonnes per year and, in 1973,
attained 10 000 tonnes per year. Although considerable yearly
fluctuations were noted, the average rate of increase since 1950 has
been about 2% per year. Recent concern over environmental problems
related to the use of mercury seems to have stabilized production
rates and to have led to a dramatic fall in the price of mercury. For
example, according to figures quoted by Korringa & Hagel (1974), the
1966 price was $452 per flask (a flask is 34.5 kg), the 1969 price had
risen to $510.00 but by 1972 it had fallen dramatically to $202 per
flask.
It is difficult to estimate the amount of mercury released into
the environment as a result of the mining and smelting of this metal.
High levels of mercury in lake and stream waters have been attributed
to the dumping of materials and tailings (for review, see Wallace et
al., 1971). It has been estimated that stack losses during smelting
operations should not exceed 2-3%. Thus, based on a production figure
for mercury of 10 000 tonnes in 1973, one might expect to find losses
to the atmosphere of the order of 300 tonnes per year.
3.3 Uses of Mercury
Wallace et al. (1971) have attempted to give a picture of the use
of mercury in the USA. They note that 26% of the mercury mined is not
reusable. They point out, however, that at least from the theoretical
point of view most of the remaining mercury (i.e. 74% of the mercury
mined) is reusable. To what extent these theoretical possibilities are
attained is debatable at the present moment.
Rauhut & Wild (1973) reported on the consumption and fate of
mercury in the Federal Republic of Germany in 1971. Flewelling (1975)
noted that the chloralkali industry, one of the largest users of
mercury, has been able to cut losses in water effluent by at least 99%
in the last two or three years; consequently losses from chloralkali
plants now occur predominantly by emission into the atmosphere. Losses
by volatilization into the atmosphere have been reduced (approximately
50%) by the introduction of cooling systems for effluent gases.
Korringa & Hagel (1974) take a more pessimistic point of view and
conclude that there is every reason to assume that by about 1975 all
the 10 000 to 11 000 tonnes of mercury produced per year due to mining
operations will finally find its way into the environment,
predominantly via the atmosphere.
Average consumption patterns for industrialized countries have
been summarized by Korringa & Hagel (1974) as follows: chloralkali
plants, 25%; electrical equipment, 20%; paints, 15%; measurements and
control systems, such as thermometers and blood pressure meters, 10%;
agriculture, 5%; dental, 3%; laboratory, 2%; and other uses including
military uses as detonators, 20%. This pattern of consumption in
industrialized countries is similar to that published by D'Itri (1972)
for the consumption in the USA in 1968. Included in "other uses" are
mercury compounds in catalysts, preservatives in paper pulp
industries, pharmaceutical and cosmetic preparations, and in
amalgamation processes. The use of mercury in the paper pulp
industries is dramatically declining and it was banned in Sweden in
1966 (Swedish Expert Group, 1971). Hasanen (1974) has reported that no
mercury compounds have been used in the paper pulp industry in Sweden
and Finland since 1968.
3.4 Contamination by Fossil Fuels, Waste Disposal, and
Miscellaneous Industries
Industrial activities not directly related to mercury can give
rise to substantial releases of this metal into the environment. The
most significant source is probably the burning of fossil fuels.
Heindryckx et al. (1974) calculated the following approximate figures
based on reports published in 1971 and 1972 (Joensuu, 1971; Cardozo,
1972): the combustion of coal and lignite, 3000 tonnes per year; the
refining and combustion of petroleum and natural gas, 400 tonnes per
year; the production of steel, cement, and phosphate, 500 tonnes per
year. Korringa & Hagel (1974) made similar calculations from published
material (Joensuu, 1971; Filby et al., 1970; Cardozo, 1972; Weiss et
al., 1971). They estimated for the year 1970, an annual release of
3000 tonnes of mercury from coal burning, 1250 tonnes from mineral
oil, and 250 tonnes from the consumption of natural gas. They expected
that, by 1975, a total of 5000 tonnes of mercury would be emitted from
burning fossil fuels.
Smelting of metals from their sulfate ores should contribute some
2000 tonnes annually and the making of cement and phosphate and other
processes involving heating should have contributed another 5000
tonnes per year by 1975.
D'Itri (1972) points out that the disposal of sewage might be an
important source of environmental mercury. Calculations from data in
the literature indicate that somewhere between 200 and 400 kg of
mercury per million population may be released from sewage disposal
units. This would amount to approximately 40-80 tonnes per year for
the entire poptilation of the USA. He further points out that sewage
sludge can retain high amounts of mercury according to published
studies from Sweden (6-20 mg/kg). This sludge is sometimes used as a
fertilizer resulting in widespread dispersal of mercury or is
sometimes heated in multiple hearth furnaces when most of the mercury
would probably be released into the atmosphere. If the United States
production is taken as being roughly 30% of world consumption, one
might extrapolate the sewage release figure for the United States to
indicate that something of the order of 1000 tonnes of mercury may be
released frow sewage systems on a global scale.
The anthropogenic release of mercury has been well summarized in a
recent article by Korringa & Hagel (1974) and will be briefly stated
here. The total global release of mercury is taken as the sum of the
global production (following their pessimistic view that all will be
released into the environment) plus the release from fossil fuels and
natural gas and release from non-mercury related industries.
It was calculated that by 1975 the total anthropogenic release of
mercury on a global scale would be about 20 000 tonnes per year. These
figures should be compared with a minimum estimated release of 25 000
to 30 000 tonnes per year from natural sources. The latter figure may,
in fact, be as high as 150 000 tonnes per year, given the
uncertainties in calculations on the natural global release of
mercury.
4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION
Jenson & Jernelov (1972) have suggested different types of cycle
for the distribution of mercury. One cycle is global in scope and
depends upon the atmospheric circulation of elemental mercury vapour.
The other cycle is local and is based on an assumed circulation of
volatile dimethylmercury compounds. In the global cycle most of the
mercury is derived from natural sources whereas the local cycle is
predominantly concerned with man-made release.
4.1 Distribution between Media -- the Global Mercury Cycle
Recent calculations on the global circulation of mercury have been
reported by Korringa & Hagel (1974). Their calculations are based
principally on data giving mercury levels in ice samples collected in
Greenland and in the Antarctic as reported by Weiss et al. (1971). The
circulation of mercury from natural sources was calculated using a
figure of 0.06 µg of mercury per kilogram of Greenland ice samples
collected prior to the year 1900. Using a reported figure for the
global precipitation of water as 5.2 x 105 km3 per year, they
estimated that minimum transport from the atmosphere to the earth
should have been about 30 000 tonnes annually, prior to 1900. The
contribution by dust particles was regarded as insignificant, an
assumption now supported by the findings of Heindryckx et al. (1974).
Based on a published figure of 4.1 x 105 km3 for annual
precipitation over the oceans, these authors estimated the annual
delivery of mercury to the oceans as 25 000 tonnes.
Korringa & Hagel (1974) also calculated the contribution of the
man-made release of mercury to the atmospheric transport cycle. They
assumed that 16 000 tonnes of mercury is now released per year to the
atmosphere from man-made sources and that the mercury is returned to
the continental land surfaces and would soon re-evaporate to the
atmosphere. The 16 000 tonnes per year would eventually find its way
into the oceans and thus the annual delivery to the oceans from both
natural and man-made sources would be 25 000 plus 16 000 tonnes which
on a proportional basis should increase the background level from the
0.06 µg/kg observed prior to the 1900s in Greenland ice to a predicted
level of 0.1 µg/kg. However, they point out that since most of the
man-made release is probably in the northern hemisphere, the present
level in Greenland ice should be somewhat higher than 0.1 µg/kg. They
note that this estimate agrees well with the observations of Weiss et
al. (1971) who found present levels in Greenland ice to range from
0.09 to 0.23 µg/kg with an average of 0.125 µg/kg. Thus, from these
rough estimates, it would appear that present day "background" levels
in rainwater, and presumably in the atmosphere, have a substantial
component related to man-made release (approximately one-third).
Observations on "background" mercury levels in the atmosphere tend
to confirm the quantitative features of this global picture
(Heindryckx et al., 1974). These authors assume that 50 000 tonnes are
released each year from the continental land masses, that the mercury
mixes up to a height of 1 km and that, in effect, the 50 000 tonnes
are located over the continental land masses that account for 30% of
the earth's surface.a The assumption of the location of this mercury
over the land masses is not in contradiction with the calculations of
Korringa & Hagel (1974). It assumes only that the atmosphere above the
land masses is in steady state, and receives 50 000 tonnes of mercury
a year as evaporation and loses 50 000 tonnes per year to the
atmosphere over the oceans. Their figure of 50 000 tonnes per year
comes from the publication of Bertini & Goldberg (1971) and agrees
well with the figure of 41 000 tonnes per year as indicated above.
With these assumptions, Heindryckx et al. (1974) concluded that the
background continental levels of mercury vapour plus aerosols should
be 10 ng/m3. The assumed mixing height of 1 km is probably the
maximum level and they suggest that the actual level of mercury in air
would lie between 1 and 10 ng/m3. These figures are in good agreement
with the published air levels as indicated in section 5.1.
Korringa & Hagel (1974) estimate the amount of mercury transported
by rivers to the oceans to be 5000 tonnes per year based on quoted
figures of 37 000 km3 of water flow via the rivers and a natural
mercury content of less than 0.2 µg/litre in river water. They note
that this figure does not change substantially if one takes into
account the fact that most of the mercury in river water is adsorbed
to suspended matter with a mercury content of 200-500 µg/kg and that
some 1010-1011 tonnes of sediment are carried each year to the
oceans. In fact river transport of mercury to the oceans may be less
than 5000 tonnes per year. Heindryckx et al. (1974) noted that the
concentrations of mercury in the North Sea and in the coastal areas
around the North Sea were far less than would be predicted if all the
mercury in the rivers entering this area were, in fact, delivered into
the oceans. Presumably a considerable amount of mercury observed in
river water is retained in sediments in the rivers and estuaries and
does not reach the ocean by normal flow of the river. Thus it would
appear that the major pathway of global transport of mercury is
metallic mercury transported in the atmosphere.
a Recent studies in Sweden cast some doubt on the validity of this
assumption.
An important conclusion from these calculations on the global
cycle of mercury is that the concentration of mercury in the oceans
should not change substantially in the foreseeable future, and that
the mercury concentration in the oceans has not changed significantly
since the beginning of the industrial era. The amount of mercury in
the oceans has been calculated as 70 million tonnes using a figure for
total ocean volume of 1.37 x 109 km3