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    PESTICIDE RESIDUES IN FOOD - 1997


    Sponsored jointly by FAO and WHO
    with the support of the International Programme
    on Chemical Safety (IPCS)




    TOXICOLOGICAL AND ENVIRONMENTAL
    EVALUATIONS 1994




    Joint meeting of the
    FAO Panel of Experts on Pesticide Residues
    in Food and the Environment
    and the
    WHO Core Assessment Group 

    Lyon 22 September - 1 October 1997



    The summaries and evaluations contained in this book are, in most
    cases, based on unpublished proprietary data submitted for the purpose
    of the JMPR assessment. A registration authority should not grant a
    registration on the basis of an evaluation unless it has first
    received authorization for such use from the owner who submitted the
    data for JMPR review or has received the data on which the summaries
    are based, either from the owner of the data or from a second party
    that has obtained permission from the owner of the data for this
    purpose.


    This report contains the collective views of two international
    groups of experts and does not necessarily represent the decisions
    or the stated policy of the Food and Agriculture Organization of
    the United Nations or the World Health Organization.


    The preparatory work for the toxicological evaluations of pesticide
    residues carried out by the WHO Expert Group on Pesticide Residues
    for consideration by the FAO/WHO Joint Meeting on Pesticide Residues
    in Food and the Environment is actively supported by the International
    Programme on Chemical Safety (IPCS) within the framework of the Inter-
    Organization Programme for the Sound Management of Chemicals.

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

    The Inter-Organization Programme for the Sound Management of Chemicals
    (IOMC) was established in 1995 by UNEP, ILO, the Food and Agriculture
    Organization of the United Nations, WHO, the United Nationals
    Industrial Development Organization, and the Organisation for Economic
    Co-operation and Development (Participating Organizations), following
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    coordination of the policies and activities pursued by the
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    sound management of chemicals in relation to human health and the
    environment.

    IPCS gratefully acknowledges the assistance of Mrs. E. Heseltine, St
    Léon-sur-Vézère, France, for editing these monographs.

    Health & Environment International Ltd, by agreement with WHO,
    performed independent literature searches on some of the substances on
    which data are summarized in this document in order to ensure that all
    relevant toxicological and related information was reviewed.

    ISBN 92 4 1665 13 0

    (c) World Health Organization 1998

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    publication do not imply the expression of any opinion whatsoever on
    the part of the Secretariat of the World Health Organization
    concerning the legal status of any country, territory, city or area or
    of its authorities, or concerning the delimitation of its frontiers or
    boundaries.

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    products does not imply that they are endorsed or recommended by the
    World Health Organization in preference to others of a similar nature
    that are not mentioned.  Errors and omissions excepted, the names of
    proprietary products are distinguished by initial capital letters.

    TABLE OF CONTENTS

    List of participants
    Abbreviations

    Introduction

    Toxicological evaluations
         Abamectin (addendum)
         Amitrole (addendum)
         Aminomethylphosphonic acid (AMPA)
         Chlormequat (addendum)
         Fenamiphos
         Fenbuconazole*
         Fenthion (addendum)
         Fipronil*
         Guazatine
         Lindane (addendum)
         Malathion
         Methidathion (addendum)
         Phosalone (addendum)
         Triforine

    Environmental evaluations
         2,4-Dichlorophenoxyacetic acid (2,4-D), salts and esters
         Mevinphos

    Annex 1.  Reports and other documents resulting from previous Joint
              Meetings of the FAO Panel of Experts on Pesticide Residues
              in Food and the Environment and WHO Expert Groups on
              Pesticide Residues

    Annex 2.  Corrigenda to previous editions of JMPR toxicological and
              environmental evaluations


    ____________
    * First full evaluation
    

    1997 Joint Meeting of the FAO Panel of Experts on Pesticide Residues
    in Food and the Environment and the WHO Core Assessment Group

    Lyon, 22 September-1 October 1997

    PARTICIPANTS

     Toxicological Core Assessment Group1

    Dr P. Fenner-Crisp, Acting Director, Office of Science Coordination
    and Policy, US Environmental Protection Agency, Washington DC, United
    States  (Chairman) 

    Dr D.L. Grant, Director, Health Evaluation Division, Health Canada,
    Tunney's Pasture, Ottawa, Ontario, Canada  (Rapporteur)

    Dr A. Moretto, Istituto di Medicina del Lavoro, Universita di Padova,
    Padova, Italy 

    Professor O. Pelkonen, Department of Pharmacology and Toxicology,
    University of Oulu, Oulu, Finland

    Dr B.G. Priestly, Scientific Director, Chemicals and Non-prescription
    Drug Branch, Therapeutic Goods Administration, Commonwealth Department
    of Health and Family Services, Woden, ACT, Australia

    Dr P. Yao, Professor of Toxicology, Institute of Occupational
    Medicine, Ministry of Health, Beijing, China

     FAO Panel of Experts on Pesticide Residues in Food and the 
     Environment

    Dr A. Ambrus, Budapest Plant Health and Soil Conservation Station,
    Budapest, Hungary

    Dr U. Banasiak, Federal Biological Research Centre for Agriculture and
    Forestry, Kleinmachnow, Germany

    Mr S. Crossley, Pesticides Safety Directorate, Ministry of
    Agriculture, Fisheries and Food, Kings Pool, York, United Kingdom

    Mr D.J. Hamilton, Principal Scientific Officer, Animal and Plant
    Health Service, Department of Primary Industries, Brisbane,
    Queensland, Australia  (Rapporteur)


              

    1  Invited but unable to attend: Professor J.F. Borzelleca,
    Pharmacology, Toxicology, Medical College of Virginia, Virginia
    Commonwealth University, Richmond, VA, United States

    Mr N.F. Ives, Health Effects Division, US Environmental Protection
    Agency, Washington DC, United States  (Vice-Chairman)

    Mrs E. Masoller, Servicios de Laboratorios, Ministerio de Ganader'a,
    Agricultura y Pesca, Montevideo, Uruguay

    Mr T. Sakamoto, Head of Technical Research Section, Agricultural
    Chemicals Inspection Station, Ministry of Agriculture, Forestry and
    Fisheries, Tokyo, Japan

     Secretariat

    Dr E. Dutra Caldas, Instituto de Saude do DF/Gerência de Bromatologia
    e Quimica, Brasilia, Brazil  (FAO Temporary Adviser)

    Dr P.J. Campbell, Pesticides Safety Directorate, Ministry of
    Agriculture, Fisheries and Food, Kings Pool, York, United Kingdom
     (WHO Temporary Adviser)

    Mr D.J. Clegg, Carp, Ontario, Canada  (WHO Temporary Adviser)

    Dr I.C. Dewhurst, Pesticides Safety Directorate, Ministry of
    Agriculture, Fisheries and Food, Kings Pool, York, United Kingdom
     (WHO Temporary Adviser)

    Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood, Abbots
    Ripton, Huntindon, Cambridgeshire, United Kingdom  (WHO Temorary 
     Adviser)

    Dr W.H. van Eck, Division of Public Health, Ministry of Health,
    Welfare and Sport, Rijswijk, Netherlands  (Chairman, Codex Committee 
     on Pesticide Residues)

    Dr K. Fujimori, Division of Pharmacology, Biological Safety Research
    Center, National Institute of Health Sciences, Tokyo, Japan  (WHO 
     Temporary Adviser)

    Dr S. Funk, Health Effects Division, US Environmental Protection
    Agency, Washington DC, USA  (FAO Consultant)

    Dr S. Geertsen, Insecticide Toxicological Evaluation Section, Health
    Evaluation Division, Pest Management Regulatory Agency, Ottawa,
    Ontario, Canada  (WHO Temporary Adviser)

    Professor J. Hajslova, Institute of Chemical Technology, Department of
    Food Chemistry and Analysis, Prague, Czech Republic  (FAO Temporary 
     Adviser)

    Dr K. Hamernik, Toxicology Branch II, Health Effects Division, Office
    of Pesticide Programs, US Environmental Protection Agency, Washington
    DC, USA  (WHO Temporary Adviser)

    Dr J.L. Herrman, Assessment of Risk and Methodologies, International
    Programme on Chemical Safety, World Health Organization, Geneva,
    Switzerland  (WHO Joint Secretary)

    Mrs E. Heseltine, Communication in Science, St Léon-sur-Vézère, France
     (WHO Editor)

    Mrs P.H. van Hoeven-Arentzen, Centre for Substances and Risk
    Assessment, National Institute of Public Health and the Environment,
    Bilthoven, Netherlands  (WHO Temporary Adviser)

    Dr F.-W. Kopisch-Obuch, Senior Officer, Pesticide Group, Plant
    Protection Service, Food and Agricultural Organization of the United
    Nations, Rome, Italy

    Dr J.-J. Larsen, Head, Department of General Toxicology, Institute of
    Toxicology, Danish Veterinary and Food Administration, Soborg, Denmark
     (WHO Temporary Adviser)

    Mr A.F. Machin, London, United Kingdom  (FAO Consultant)

    Dr T.C. Marrs, Medical Toxicology and Environmental Health, Department
    of Health, London, United Kingdom  (WHO Temporary Adviser)

    Dr D. McGregor, Unit of Carcinogen Identification and Evaluation,
    International Agency for Research on Cancer, Lyon, France  (WHO 
     Temporary Adviser)

    Dr G. Moy, Programme of Food Safety and Food Aid, Division of Food and
    Nutrition, World Health Organization, Geneva, Switzerland

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

    Dr G. Vettorazzi, International Toxicology Information Centre, San
    Sebastian, Spain  (WHO Temporary Adviser)

    Mr M. Watson, Ricerca Inc., Painesville, Ohio, USA  (WHO Temporary 
     Adviser)

    Dr Y. Yamada, Food Standards Officer, Joint FAO/WHO Food Standards
    Programme, Food and Nutrition Division, Food and Agriculture
    Organization of the United Nations, Rome, Italy

    Abbreviations used

    ADI            acceptable daily intake
    AMPA           aminomethylphosphonic acid
    bw             body weight
    CCPR           Codex Committee on Pesticide Residues
    CoA            coenzyme A
    CoE            Council of Europe
    CYP            cytochrome P450
    D              decedents
    DMSO           dimethyl sulfoxide
    EBOB           1-[(4-ethyl)phenyl]-4- n-propyl-2,6,7-
                   trioxacicyclo[2.2.2]octane
    EPPO           European Plant Protection Organization
    F              female
    F0             parental generation
    F1             first filial generation
    F2             second filial generation
    GABA           gamma-aminobutyric acid
    HPLC           high-performance liquid chromatography
     hprt           hypoxanthine-guanine phosphoribosyl transferase gene
    IARC           International Agency for Research on Cancer
    IPCS           International Programme on Chemical Safety
    JMPR           Joint FAO/WHO Meeting on Pesticide Residues
    LC50           median lethal concentration
    LD50           median lethal dose
    lambdamax      maximum wavelength
    LOAEL          lowest-observed-adverse-effect level
    M              male
    MRL            maximum residue limit
    NOAEL          no-observed-adverse-effect level
    NOEC           no-observed-effect concentration
    NR             not reported
    PEC            predicted environmental concentration
    ppm            parts per million
    RFLP           restriction fragment length polymorphism
    S9             9000 ×  g supernatant fraction of rodent liver
    T              terminally killed animals
    T3             triodothyronine
    T4             thyroxine
    Tmax           time of maximum concentration
    TBPS            tert-butylbicyclophosphorothionate
    TER            toxicity:exposure ratio
    TSH            thyroid-stimulating hormone
    w/w            weight per weight

    Introduction

         The toxicological monographs and monograph addenda and the
    environmental monographs contained in this volume were prepared by a
    WHO Core Assessment Group that met with the FAO Panel of Experts on
    Pesticide Residues in Food and the Environment in a Joint Meeting on
    Pesticide Residues (JMPR) in Lyon, France, on 22 September-1 October
    1997.

         Two of the substances evaluated by the Core Assessment Group at
    this Meeting, fipronil and aminomethylphosphonic acid (AMPA), the
    primary degradation product of glyphosate in plants, soil, and water,
    were evaluated for the first time. Twelve of the substances had been
    evaluated at earlier meetings. For seven of these, abamectin,
    amitrole, chlormequat, fenthion, lindane, methidathion, and phosalone,
    only information received since the previous evaluations is
    summarized, in 'monograph addenda'. The appropriate earlier documents
    should be consulted in order to obtain full toxicological profiles of
    these chemicals. Toxicological monographs were prepared on AMPA,
    fenamiphos, fenbuconazole, fipronil, guazatine, malathion, and
    triforine, summarizing new data and, where relevant,  incorporating
    information from previous monographs and addenda. Reports and other
    documents resulting from previous Joint Meetings on Pesticide Residues
    are listed in Annex 1.

         Two environmental monographs are included, on
    2,4-dichlorophenoxyacetic acid (2,4-D) salts and esters and on
    mevinphos. These monographs were prepared by a Core Assessment Group
    that met in Leicester, United Kingdom, in March 1997.

         The report of the Joint Meeting has been published by the FAO as
     FAO Plant Production and Protection Paper 145. That  report contains
    brief comments on the compounds considered, acceptable daily intakes
    established by the WHO Core Assessment Group, and maximum residue
    limits or guideline levels established by the FAO Panel of Experts.
    Monographs on residues prepared by the FAO Panel of Experts are
    published as a companion volume, as  Evaluations 1997, Part I, 
     Residues, in the FAO Plant Production and Protection Paper series.

         The toxicological monographs and addenda and the environmental
    monographs contained in this volume are based on working papers that
    were prepared by temporary advisers before the 1997 Joint Meeting. A
    special acknowledgement is made to those advisers. The monographs were
    edited by Mrs E. Heseltine, St Léon-sur-Vézère, France.

         The preparation and editing of this volume were made possible by
    the technical and financial contributions of the lead institutions of
    the International Programme on Chemical Safety (IPCS), which supports
    the activities of the JMPR. The designations employed and the
    presentation of the material in this publication do not imply the
    expression of any opinion whatsoever on the part of the Central Unit
    of the IPCS concerning the legal status of any country, territory,
    city or area or of its authorities, nor concerning the delimitation of

    its frontiers or boundaries. The mention of specific companies or of
    certain manufacturers' products does not imply that they are endorsed
    or recommended by the IPCS in preference to others of a similar nature
    that are not mentioned. 

         Any comments or new information on the biology or toxicology of
    the compounds included in this volume should be addressed to: Joint
    WHO Secretary of the Joint FAO/WHO Meeting on Pesticide Residues,
    International Programme on Chemical Safety, World Health Organization,
    Avenue Appia, 1211 Geneva 27, Switzerland.





















    See Also:
       Toxicological Abbreviations