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        PESTICIDE RESIDUES IN FOOD - 1988


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




        EVALUATIONS 1988

        PART II - TOXICOLOGY



        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, 19-28 September 1988


        The designations employed and the presentation of material in
        this publication do not imply the expression of any opinion
        whatsoever on the part of the Food and Agriculture Organization
        of the United Nations concerning the legal status of any country,
        city or area or of its authorities, or concerning the delimitation
        of its frontiers or boundaries.

        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.



        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.

        M-84
        ISBN 92-5 102815-X

        All rights reserved.  No part of this publication may be
        reproduced, stored in a retrieval system, or transmitted in any
        form or by any means, electronic, mechanical, photocopying or
        otherwise, without the prior permission of the copyright owner.
        Applications for such permission, with a statement of the purpose
        and extent of the reproduction, should be addressed to the
        Director, Publications Division, Food and Agriculture Organization
        of the United Nations, Via delle Terme di Caracalla,
        00100 Rome, Italy.

        (c) FAO 1989

    CONTENTS

    PART II - TOXICOLOGY

    List of those attending the Meeting

    Abbreviations

    Introduction

    Toxicology monographs and monograph addenda

         Acephate

         Bromide ion

         Dimethipin

         Ethylenethiourea (ETU)

         Fenitrothion

         Methacrifos

         *Paclobutrazol

         d-Phenothrin

         *Tolylfluanid

         Vamidothion

         Vinclozolin

    Corregenda to 1982 and 1986 Evaluations

    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

    Annex II.  Acceptable daily intakes, residue limits, and guideline
               levels proposed at the 1988 Meeting

              

    * First full evaluation
    

    1988 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, 19-28 September 1988

    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, Harpenden, UK.

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

    Dr R. Greenhalgh, Plant Research Centre, Agriculture Canada,
       Ottawa, Canada.

    Mr D.J. Hamilton, Assistant Director, Agricultural Chemistry Branch,
       Department of Primary Industries, Brisbane, Australia.

    Professor E.D. Magallona, Department of Entomology, College of
       Agriculture, University of the Philippines at Los Banos College,
       Laguna, Philippines.

    Mr K. Voldum-Clausen, Division of Chemical Contaminants in Food,
       National Food Agency, Soborg, Denmark.

    WHO Expert Group on Pesticide Residues

    Prof. N.M.S. Bakry, Head, Professor of Pesticide Chemistry and
       Toxicology, Faculty of Agriculture, University of Alexandria,
       El-Shatby, Alexandria, Egypt.

    Dr V. Benes, Chief, Department of Toxicology, Institute of Hygiene and
       Epidemiology, 10042 Prague 10, Czechoslovakia.

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

    Mr D.J. Clegg, Head, Agricultural Chemicals Section, Toxicological
       Evaluation Division, Food Directorate, Health Protection Branch,
       Tunneys Pasture, Ottawa, Ontario, KIA 0L2 Canada.

    Prof. M. Lotti, Università di Padova, Istituto di Medicina del Lavoro,
       Via Facciolati 71, 35127 Padova, Italy.

    Dr O.E. Paynter, Chief Scientist, Hazard Evaluation Division, US
       Environmental Protection Agency, Washington, D.C., USA.

    Secretariat

    Dr Mrs E.P. Arnold, Toxicologist, Agricultural Chemicals Section,
       Toxicological Evaluation Division, Health Protection Branch, Health
       & Welfare Canada, Ottawa, KIA 0L2 Canada.
       (WHO Temporary Adviser)

    Prof. C.L. Berry, Department of Morbid Anatomy, The London Hospital
       Medical College, Whitechapel, London E1 1.BB, UK.
       (WHO Temporary Adviser)

    Dr G. Burin, Office of Pesticide Programs, US Environmental Protection
       Agency, TS-769 Washington, D.C., 20460 USA.
       (WHO Consultant)

    Dr J.L. Herrman, International Programme on Chemical Safety, World
       Health Organization, 1211 Geneva 27, Switzerland.
       (WHO Joint Secretary)

    Dr R.B. Jaeger, Toxicologist, Section Head, Special Analyses and
       Coordination Branch, Health Effects Division, US Environmental
       Protection Agency, Washington, D.C., USA.
       (WHO Temporary Adviser)

    Dr J. van der Kolk, Foodstuffs Division, Ministry of Welfare, Health
       and Cultural Affairs, Rijswijk, Netherlands.
       (Chairman of the CCPR)

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

    Dr L.G. Ladomery, Food Standards Officer, Joint FAO/WHO Food Standards
       Programme, Food and Agriculture Organization, Rome, Italy.

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

    Dr A. Moretto, Università di Padova, Istituto di Medicina del Lavoro,
       Padova, Italy.
       (WHO Temporary Adviser)

    Dr R. Plestina, Division of Vector Biology and Control, World Health
       Organization, 1211 Geneva 27, Switzerland.

    Dr L. Shuker, Unit of Carcinogen Identification and Evaluation,
       International Agency for Research on Cancer, 150 Cours Albert
       Thomas, Lyon, Cedex 08 France.
       (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 Mrs. E.M. den Tonkelaar, Toxicology Advisory Center, National
       Institute of Public Health and Environmental Protection,
       Bilthoven, The Netherlands.
       (WHO Temporary Adviser)

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

    ABBREVIATIONS USED IN THESE MONOGRAPHS

    2-AAF     2-acetylaminofluorine
    AChE      acetylcholinesterase
    ADI       acceptable daily intake
    a.i.      active ingredient
    ALD       acute lethal dose
    ALP       alkaline phosphatase
    ALT       alanine aminotransferase
    AMP       aminomethylphosphonic acid
    AST       aspartate aminotransferase

    BUN       blood urea nitrogen
    bw        body weight

    CD        caesarian derived
    ChE       cholinesterase
    CHO       Chinese hamster ovary
    CMC       carboxymethylcellulose
    CNS       central nervous system

    EMS       ethylmethanesulfonate

    F1        filial generation, first
    F2        filial generation, second
    FAO       Food and Agriculture Organization of the United Nations
    FSH       follicle stimulating hormone

    GC        gas chromatography
    GH        growth hormone
    GI        gastrointestinal
    GLC       gas-liquid chromatography
    GMP       guanosine monophosphate
    GOT       glutamate-oxoloacetate transaminase
    GPT       glutamate-pyruvate transaminase
    GSSG      glutathione, oxidized

    Hb        haemoglobin
    HGPRT     hypoxanthine-guanine phosphoribosyl transferase
    HPLC      high pressure liquid chromatography

    IARC      International Agency for Research on Cancer
    IBT       Industrial Bio-Test Laboratories, Inc.
    i.m.      intramuscular
    i.p.      intraperitoneal
    IPCS      International Programme on Chemical Safety
    i.v.      intravenous

    JMPR      Joint FAO/WHO Meeting on Pesticide Residues (Joint Meeting
              of the FAO Panel of Experts on Pesticide Residues in Food
              and the Environment and a WHO Expert Group on Pesticide
              Residues)

    LC50      lethal concentration, median
    LD50      lethal dose, median
    LDH       lactate dehydrogensase

    MCA       3-methylcholanthrene
    MCH       mean corpuscular haemoglobin
    MCHC      mean corpuscular haemoglobin concentration
    MCV       mean corpuscular volume
    mmol/l    millimoles/liter
    MMS       methylmethane sulfonate
    MTD       maximum tolerated dose

    NADPH     nicotinamide adenine dinucleotide phosphate (reduced)
    ng        nanogram
    NOAEL     no-observed-adverse-effect level
    NOEL      no-observed-effect level
    NPMG      N-nitrosophosphonomethyl glycine
    NTE       neurotoxic esterase

    OECD      Organization for Economic Cooperation and Development
    op        organophosphate

    2-PAM     2-pyridine aldoxine methyl (pralidoxime)
    p.c.      post-coitum
    p.o.      per oral
    ppb       parts per billion (1000 ppb = 1 ppm)
    ppm       parts per million
    PRL       prolactin

    RBC       red blood cell
    RER       rough endoplasmic reticulum

    s.a.      specific activity
    SAP       serum alkaline phosphatase
    s.c.      subcutaneous
    SCE       sister chromatid exchange
    SER       smooth endoplasmic reticulum

    T3        triiodothyronine
    T4        thyroxin
    TADI      temporary acceptable daily intake
    TBG       thyroxine binding globulin
    TEM       triethylenemelamine
    TLC       thin layer chromatography
    TLV       threshold limit value
    TOCP      tri-o-cresyl phosphate
    TSH       thyrotropin

    UDS       unscheduled DNA synthesis

    WBC       white blood cell
    WHO       World Health Organization
    w/v       weight/volume

    <         less than
    <         less than or equal to

    >         greater than
    >         greater than or equal to

    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, 19-28 September 1988. 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 monographs on them
    have been published previously. In such cases, only new information is
    summarized in the relevant "monograph addenda". 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 I. 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. 92. 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 1988, Part I
    Residues (FAO Plant Production and Protection Paper No. 93/1).

         The toxicology monographs and monograph addenda contained in this
    volume are based on working papers that were prepared by temporary
    advisers in advance of the 1988 Joint Meeting. A special
    acknowledgement is given to those who prepared these working papers:
    Dr A. Moretto, University of Padua Medical School, Padua, Italy;
    Dr R.B. Jaeger, U.S. Environmental Protection Agency, Washington, DC,
    USA; Dr E.M. den Tonkelaar, National Institute of Public Health and
    Environmental Protection, Bilthoven, The Netherlands; and
    Dr E.P. Arnold, Health & Welfare Canada, Ottawa, Canada.

         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