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    PESTICIDE RESIDUES IN FOOD - 1990


    JOINT FAO/WHO MEETING ON PESTICIDE RESIDUES






    EVALUATIONS 1990

    TOXICOLOGY



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

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

    Rome, 17-26 September 1990




 

    This report contains the collective views of two international
    groups of experts and does not necessarily represent the decisions
    nor the stated policy of the Food and Agriculture Organization of
    the United Nations or the World Health Organization.



    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    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).

    The International Programme on Chemical Safety (IPCS) is a joint
    venture of the United Nations Environment Programme, the International
    Labour Organisation, and the World Health Organization.  One of the
    main objectives of the IPCS is to carry out and disseminate
    evaluations of the effects of chemicals on human health and the
    quality of the environment.

    IPCS gratefully acknowledges the assistance of Dr. G. Burin, U.S.
    Environmental Protection Agency, for editing these monographs.

    ISBN 92 4 166506 8

    (c) World Health Organization 1991

          Publications of the World Health Organization enjoy copyright
    protection in accordance with the provisions of Protocol 2 of the
    Universal Copyright Convention.  For rights of reproduction or
    translation of WHO publications, in part or  in toto, application
    should be made to the Office of Publications, World Health
    Organization, Geneva, Switzerland.  The World Health Organization
    welcomes such applications.

          The designations employed and the presentation of the material in
    this publication do not imply the impression of any opinion whatsoever
    on the part of the Secretariat of the World Health Organization
    concerning the legal status of every country, territory, city, or area
    or of its authorities, or 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
    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 those attending the meeting
         Abbreviations
         Introduction

    The Monographs

         Acephate
         Captan
         Chlorothalonil
         Coumaphos
     *   Cyromazine
         Ethion
         Folpet
     *   Hexaconazole
         Methacrifos
         Methamidophos
         2-Phenylphenol
     *   Profenofos
     *   Terbufos

    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

             

    * First full evaluation

    1990 JOINT MEETING OF THE FAO PANEL OF EXPERTS ON PESTICIDE RESIDUES
    IN FOOD AND THE ENVIRONMENT AND THE WHO EXPERT GROUP ON PESTICIDE
    RESIDUES

    Rome, 17 - 26 September 1990

    PARTICIPANTS

    WHO Expert Group on Pesticide Residues

    Professor U.G. Ahlborg, Head, Unit of Toxicology, Karolinska
         Institute, Institute of Environmental Medicine, Stockholm, Sweden

    Dr A.L. Black, Medical Services Adviser in Toxicology, Department of
         Community Services and Health, Canberra, A.C.T., Australia

    Dr J.F. Borzelleca, Professor Pharmacology, Toxicology, Medical
         College of Virginia, Virginia Commonwealth University, Richmond,
         Virginia, USA  (Vice-Chairman)

    Mr D.J. Clegg, Head, Agricultural Chemicals Section, Toxicological 
         Evaluation Division, Health Protection Branch, Health and Welfare
         Canada, Ottawa, Ontario, Canada  (Rapporteur)

    Professor A. Rico, Head, Biochemical and Metabolic Toxicology
         Laboratory (INRA) Ecole Nationale Vétérinaire, Toulouse, France

    Dr G. Ungvary, Head, Section of Toxicology, National Institute of
         Occupational Health, Budapest, Hungary

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

    Mr J.A.R. Bates, Formerly Head, Pesticide Registration and
         Surveillance Department Ministry of Agriculture Fisheries and
         Food, Westoning, Beds, England

    Professor Dr A.F.H. Besemer, Formerly Chair of Phytopharmacy,
         Agricultural University, Wageningen, Netherlands

    Dr R. Greenhalgh, Plant Research Centre, Agriculture Canada, Ottawa,
         Ontario, Canada  (Rapporteur)

    Mr D.J. Hamilton, Assistant Director, Agricultural Chemistry Branch,
    Department of Primary Industries, Queensland Government, Brisbane,
    Queensland, Australia  (Chairman)

    Mr N.F. Ives, Health Effects Division, Office of Pesticide Programs,
         US Environmental Protection Agency, Washington, DC, USA

    Mr K. Voldum-Clausen, National Food Agency of Denmark, Soborg, Denmark

    Mr Wuji Zhuang, Associate Professor, Head of the Department of
         Research Chemical China Import and Export Commodity Inspection
         Institute, Beijing, China

    Secretariat

    Mrs E. Arnold, Toxicological Evaluation Division, Health Protection
         Branch  Health and Welfare Canada, Ottawa, Ontario, Canada  (WHO
          Temporary Adviser)

    Professor C.L. Berry, Department of Morbid Anatomy, The London
         Hospital Medical College, The Royal London Hospital, London,
         England  (WHO Temporary Adviser)

    Dr G. Burin Health Effects Division, Office of Pesticide Programs, US
         Environmental Protection Agency, Washington, DC, USA  (WHO
          Temporary Adviser)

    Dr S. Caroldi University of Padua, Padua Italy  (WHO Temporary
          Adviser)

    Dr E. Casadei, Joint FAO/WHO Food Standards Programme, Food and
         Agriculture Organization, Rome Italy

    Dr H. Galal-Gorchev, International Programme on Chemical Safety, WHO,
         Geneva, Switzerland

    Dr J.L. Herrman, International Programme on Chemical Safety, WHO,
         Geneva, Switzerland  (WHO Joint Secretary)

    Dr J. van der Kolk, Foodstuffs Division, Ministry of Welfare, Health
         and Cultural Affairs, Rijswijk, Netherlands

    Dr F.-W. Kopisch-Obuch, Pesticide Residues Specialist, Plant
         Protection Service Food and Agriculture Organization, Rome Italy
          (FAO Joint Secretary)

    Dr J.-R. Lundehn, Federal Biological Research Centre for Agriculture
         and Forestry (BBA), Braunschweig, Germany

    Mr A.F. Machin, London, England  (FAO Consultant)

    Dr D. McGregor, Unit of Carcinogen Identification and Evaluation,
         International Agency for Research on Cancer, Lyon, France

    Dr O. Meyer, Ministry of Health, National Food Agency of Denmark,
         Institute of Toxicology, SØborg, Denmark  (WHO Temporary Adviser)

    Dr R. Plestina, International Programme on Chemical Safety, WHO,
         Geneva, Switzerland

    Dr J.A. Quest, Head, Science Support Section, Health Effects Division,
         Office of Pesticide Programs, US Environmental Protection Agency,
         Washington, DC, USA  (WHO Temporary Adviser)

    Dr A. Takanaka Head, Division of Pharmacology, Biological Safety
         Research Center, National Institute of Hygienic Sciences, Tokyo,
         Japan (WHO Temporary Adviser)

    Dr E.M. den Tonkelaar, Toxicologist, Toxicology Advisory Centre,
         National Institute of Public Health and Environmental Protection,
         Bilthoven, Netherlands (WHO Temporary Adviser)

    Mr M. Walsh Administrator EEC, Législation des produits végétaux et de
         nutrition animale, Brussels, Belgium  (WHO Temporary Adviser)

    ABBREVIATIONS USED IN THESE MONOGRAPHS

    ACH    acetylcholine
    AChE   acetylcholinesterase
    ADP    adenosine diphosphate
    a.i.   active ingredient
    ALAT   alanine aminotransferase
    ATP    adenosine triphosphate

    BUN    blood urea nitrogen

    ChE    cholinesterase
    CMC    carboxymethylcellulose
    CNS    central nervous system

    DMPT   dimethyl phosphorothioate
    DMSO   dimethylsulfoxide
    DNA    deoxyribonucleic acid

    EC     emulsifiable concentrate
    EL     emulsifiable liquid

    F0     parental generation
    F1     filial generation, first
    F2     filial generation, second

    GGT    (alpha)-glutamyltransferase
    G.I.   gastrointestinal
    GOT    glutamate-oxoloacetate transaminase

    GPT    glutamate-pyruvate transaminase
    GSH    glutathione

    GST    glutathione-S-transferase 

    Hb     haemoglobin
    HCG    human chorionic gonadotropin
    HGRPT  hypoxanthine-guanine phosphoribosyl transferase
    HPLC   high pressure liquid chromatography
    HT     haematocrit

    I50    inhibitory dose, 50%
    IBT      Industrial Bio-Test Laboratories, Inc.
    i.p.   intraperitoneal

    LC50   lethal concentration, median
    LD50   lethal dose, median
    LOAEL  lowest-observed-adverse-effect-level

    m      metre
    M      molar
    MCH    mean corpuscular haemoglobin
    MCV    mean corpuscular volume
    ml     milliliter

    NOAEL  no-observed-adverse-effect level
    NTE    neurotoxic target esterase

    2-PAM  2-pralidoxime
    PCV    haematocrit (packed corpuscular volume)

    RBC    red blood cell
    RNA    ribonucleic acid

    SAP    serum alkaline phosphatase
    SPF    specific pathogen free

    TLC    thin layer chromatography
    TMPO   trimethylphosphate
    TOCP   tri-o-cresyl phosphate
    TWA    time weighted average

    UDS    unscheduled DNA synthesis

    WBC    white blood cell
    WD     wettable dust

    INTRODUCTION

         The toxicology monographs and monograph addenda contained in this
    volume were prepared by a WHO Expert Group on Pesticide Residues 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
    Rome, Italy, 17 September to 26 September 1990. These monographs
    summarize the safety data on those pesticide residues for which
    sufficient information was provided to the WHO Expert Group for it to
    make decisions regarding acceptable daily intakes.

         Most of the compounds considered by the WHO Expert Group at this
    Meeting had been evaluated at previous meetings and only new
    information is summarized in the relevant "monograph addenda". In the
    case of coumaphos, a previously prepared monograph addendum which was
    not published has been included with new information.  In the case of
    terbufos, the monograph prepared for the 1989 meeting is published in
    its entirety.  Reference is made to 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 which are listed in Annex 1. The appropriate
    documents should be consulted to obtain a full toxicological profile
    of the chemicals under consideration.

         The report of the Joint Meeting has been published by the Food
    and Agriculture Organization (FAO) of the United Nations as FAO Plant
    Production and Protection Paper No. 102. The report contains brief
    comments on the compounds under consideration, acceptable daily
    intakes established by the WHO Expert Group, and maximum residue
    limits or guideline levels established by the FAO Panel of Experts.
    Residues monographs prepared by the FAO Panel of Experts have been
    published as a companion volume to this one: Evaluations 1990, Part I-
    Residues, in the FAO Plant Production and Protection Paper series
    103/1.

         The toxicology monographs and monograph addenda contained in this
    volume are based upon working papers that were prepared by temporary
    advisers in advance of the 1990 Joint Meeting. 

         The preparation and editing of the monographs included in this
    volume have been made possible through the technical and financial
    contributions of the lead institutions of the International Programme
    on Chemical Safety (IPCS), which support the activities of 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 its authorities, or con-
    cerning 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 biological or
    toxicological data on the compounds reported in this document 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