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    PESTICIDE RESIDUES IN FOOD - 1991


    JOINT FAO/WHO MEETING ON PESTICIDE RESIDUES






    EVALUATIONS 1991

    PART II - 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

    Geneva, 16-25 September 1991




 

    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, and Mr.
    D. Schutz U.S. Environmental Protection Agency, for editing these
    monographs.

    ISBN 92 4 166507 6

    (c) World Health Organization 1992

          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

              Azinphos-methyl
         *    Bentazone
              Bioresmethrin
         *    Buprofezin
         *    Cadusafos
              Chlorpyrifos-methyl
              Cyhexatin
              Daminozide
              Disulfoton
              Fentin
         *    Glufosinate-ammonium
              Heptachlor
         *    Hexythiazox
              Imazalil
              Monocrotophos
              Triazophos

    ANNEX I    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

    1991 JOINT MEETING OF THE FAO PANEL OF EXPERTS ON
    PESTICIDE RESIDUES IN FOOD AND THE ENVIRONMENT AND
    THE WHO EXPERT GROUP ON PESTICIDE RESIDUES

    Geneva, 16-25 September 1991

    PARTICIPANTS

    WHO Expert Group on Pesticide Residues

    Prof. 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 Health, Housing and Community Services, Canberra, Australia
           (Rapporteur)

    Dr    J.F. Borzelleca, Professor, Pharmacology, Toxicology, Medical
          College of Virginia, Virginia Commonwealth University, Richmond,
          Virginia, USA

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

    Prof. M. Lotti, Universitŕ di Padova, Istituto di Medicina del Lavoro,
          Padua, Italy

    Dr    F.R. Puga, Head, Section of Toxicology, Instituto Biolňgico, Sao
          Paulo, Brazil

    Dr    P. Yao, Vice-Director, Professor of Toxicology, Institute of
          Occupational Medicine, CAPM, Ministry of Public Health, Beijing,
          China

    FAO Members

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

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

    Dr    D. Hamilton, Assistant Director, Agricultural Chemistry Branch,
          Agricultural Research Laboratories, Department of Primary
          Industries, Brisbane, Queensland, Australia  (Chairman)

    Mr    F. Ives, Health Effects Division, US Environmental Protection
          Agency, Washington, D.C., USA

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

    Dr    K. Voldum-Clausen, Ministry of Health, National Food Agency of
          Denmark, Soborg, Denmark

    Mr    W. Zhuang, Associate Professor, Head of the Department of
          Research Chemicals, China Import & Export, Commodity Inspection
          Institute, Beijing, China

    Secretariat

    Dr    E. Bosshard, Fed. Office of Public Health, Division of Food
          Science, c/o Institute of Toxicology, Zürich, Switzerland
           (WHO Temporary Adviser)

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

    Dr    S. Caroldi, Universitŕ di Padova, Istituto di Medicina del
          Lavoro, Padua, Italy   (WHO Temporary Adviser)

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

    Dr    W.H. van Eck, Food and Product Safety Division, Ministry of
          Welfare, Health and Cultural Affairs, Rijswijk, Netherlands
           (Chairman, Codex Committee on Pesticide Residues)

    Dr    P. Fenner-Crisp, Director, Health Effects Division, Office of
          Pesticide Programs, Environmental Protection Agency, Washington,
          D.C., USA   (WHO Temporary Adviser)

    Dr    H. Galal-Gorchev, International Programme on Chemical Safety,
          Division of Environmental Health, World Health Organization,
          Geneva, Switzerland

    Dr    J.L. Herrman, International Programme on Chemical Safety,
          Division of Environmental Health, World Health Organization,
          Geneva, Switzerland   (WHO Joint Secretary)

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

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

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

    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, Soborg, Denmark   (WHO Temporary
           Adviser)

    Mr    B. Murray, Bureau of Chemical Safety, Health Protection Branch,
          Health and Welfare Canada, Ottawa, Ontario, Canada
           (FAO Consultant)

    Dr    W. Phang, Senior Toxicologist, Health Effects Division, Office
          of Pesticide Programs, US Environmental Protection Agency,
          Washington, D.C., USA   (WHO Temporary Adviser)

    Dr    R. Plestina, International Programme on Chemical Safety,
          Division of Environmental Health, WHO, Geneva, Switzerland

    Mr    D. Schutz, Office of Toxic Substances, US Environmental
          Protection Agency, Washington, D.C. USA   (WHO Consultant)

    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, The Netherlands   (WHO Temporary Adviser)

    Mr    M. Walsh, Administrator EEC, Législation des produits végétaux
          et de nutrition animale, Brussels, Belgium

    Mr    M. Watson, Head, Risk Evaluation Branch, Pesticide Safety
          Division, Ministry of Agriculture Fisheries and Food,
          Rothamsted, Harpenden, Herts, UK   (WHO Temporary Adviser)

    ABBREVIATIONS USED IN THESE MONOGRAPHS

    ACH            acetylcholine
    AChE           acetylcholinesterase
    ADP            adenosine diphosphate
    A/G            albumin/globulin ratio
    a.i.           active ingredient
    ALAT           alanine aminotransferase
    ALD50          approximate median lethal dose, 50%
    ALP            alkaline phosphatase
    ASAT           aspartate aminotransferase
    ATP            adenosine triphosphate

    BSP            bromosulfophthalein
    BUN            blood urea nitrogen

    cf             confer, compare to
    ChE            cholinesterase
    CMC            carboxymethylcellulose
    CNS            central nervous system

    DMPT           dimethyl phosphorothioate
    DMSO           dimethylsulfoxide
    DNA            deoxyribonucleic acid
    DOTDC          dioctyltindichloride
    DTH            delayed-type hypersensitivity

    EC             emulsifiable concentrate
    EL             emulsifiable liquid

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

    GGT            alpha-glutamyltransferase
    G.I.           gastrointestinal
    GIT            gastrointestinal tract
    GOT            glutamate-oxoloacetate transaminase
    GPT            glutamate-pyruvate transaminase
    GSH            reduced glutathione
    GSSG           oxidized glutathione
    GST            glutathione-S-transferase
    GTP            alpha-glutamyltranspeptidase

    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.m.           intramuscular
    inh            inhalation
    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
    MCHC           mean corpuscular haemoglobin concentration
    MCV            mean corpuscular volume
    MFO            mixed function oxidase(s)
    ml             milliliter
    MTD            maximum tolerated dose
    n.d.r.         not dose-related
    NOAEL          no-observed-adverse-effect level
    NTE            neurotoxic target esterase

    2-PAM          2-pralidoxime
    PCV            haematocrit (packed corpuscular volume)
    p.o.           by mouth
    POSO           disulfoton oxygen analog sulfoxide
    POSO2          disulfoton oxygen analog sulfone
    PSP            phenolsulfophthalein
    PrT            prothrombin time
    PSSO2          disulfoton sulfone
    PT             thromboplastin time
    PTT            partial thromboplastin time
    PTU            propyl-thionracil

    RBC            red blood cell
    RNA            ribonucleic acid

    SAP            serum alkaline phosphatase
    SGOT           serum GOT
    SGPT           serum GPT
    SPF            specific pathogen free

    T3             tri-iodothyronine
    T4             thyroxine
    TLC            thin layer chromatography
    TMPO           trimethylphosphate
    TOCP           tri-ortho-cresyl phosphate
    TPTA           triphenyltinacetate
    TPTCl          triphenyltinchloride
    TPTH           triphenyltinhydroxide
    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
    Geneva, Switzerland, 16 September to 25 September 1991.  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. 111.  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 1991, Part I
    Residues, in the FAO Plant Production and Protection Paper series.

         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 1991 Joint Meeting.  A special
    acknowledgement is given to those who prepared these working papers. 
    The monographs were edited by Dr G. Burin of US Environmental
    Protection Agency, Washington D.C.

         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
    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 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