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        PESTICIDE RESIDUES IN FOOD - 1987


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




        EVALUATIONS 1987

        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
        Geneva, 21-30 September 1987

        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 102701-3

        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 1988

    CONTENTS

    PART II: TOXICOLOGY

    List of those attending the Meeting
    Abbreviations
    Introduction

    Toxicology monographs and monograph addenda

         Acephate
         Benalaxyl*
         Bitertanol
         Chlordimeform
         Chinomethionat
         Chlorothalonil
         Cyfluthrin*
         Dimethoate
         Ethoprophos
         Fenamiphos
         Permethrin
         Propiconazole*

    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.  Acceptable daily intakes, residue limits, and guideline
              levels proposed at the 1987 Meeting

              

    *First full evaluation
    

    1987 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. 21-30 September 1987

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

    Dr D.C. Abbott, formerly Deputy Director (Government Analyst),
    Laboratory of the Government Chemist, London, UK (Vice-Chairman)

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

    Dr P.F. Dos Santos, Head, National Research Centre for Plant Protection
    (EMBRAPA) Jaguariuna-SP, Brazil

    Dr Roy Greenhalgh, Plant Research Centre, Agriculture Canada,
    Ottawa, Ontario, KIA 0C6 Canada

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

    Dr E.D. Magallona, Head, Pesticide Toxicology and Chemistry Laboratory,
    National Crop Protection Center, College of Agriculture, University of
    the Philippines at Los Baņos, College, Laguna, Philippines

    WHO Expert Group on Pesticide Residues

    Professor Mrs Nabila M.S. Bakry, Head Professor of Pesticide Chemistry
    and Toxicology, Department of Plant Protection, Faculty of Agriculture,
    University of Alexandria, E1-Shatby, Alexandria, Egypt

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

    Professor J.F. Borzelleca, Professor of Pharmacology and Toxicology,
    Medical College of Virginia, Richmond, VA, USA

    Mr D.J. Clegg, Head, Pesticide Section, Toxicological Evaluation
    Division, Food Directorate, health Protection Branch,
    Ottawa, Ontario, K1A OL2

    Professor M. Lotti, Istituto di Medicina del Lavoro, University of Padua
    Medical School, Padua, Italy (Chairman)

    Professor F.G. Reyes, Department of Food Science, School of Food
    Engineering/UNICAMP, Campinas, Brazil (Rapporteur)

    Secretariat

    Mr J.A.R. Bates, formerly Head, Pesticide Registration and Surveillance
    Department, Ministry of Agriculture, Fisheries and Food, Harpenden, UK
    (FAO Consultant)

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

    Dr A.L. Black, medical Advisor in Toxicology, Commonwealth Department of
    health Woden, A.C.T., Australia (WHO Temporary Adviser)

    Dr J.R.P. Cabral, Scientist, Unit of Mechanisms of Carcinogenesis,
    International Agency for Research on Cancer, Lyon, France
    (WHO Temporary Adviser)

    Dr J.L. Herrman, Food and Drug Administration, Washington D.C., USA
    (WHO Consultant)

    *Dr G. Hudson, Head of Division, Directorate-General for Agriculture,
    Commission of the European Communities, Brussels, Belgium
    (WHO Temporary Adviser)

    Dr F.-W. Kopisch-Obuch, Pesticide Residue Specialist, Plant Protection
    Service, FAO, Rome, Italy (Joint Secretary)

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

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

    Dr M. Manno, Istituto di Medicina del Lavoro, University of Padua
    Medical School, Padua, Italy (WHO Temporary Adviser)

    Mr A.J. Pieters, Ministry of Welfare, Health and Cultural Affairs,
    Rijswiik, The Netherlands (FAO Consultant)

    Dr D.S. Saunders, Hazard Evaluation Division, US Environmental
    Protection Agency, Washington D.C., 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)

              

    * invited but unable to attend

    Dr Mrs Engelina M. den Tonkelaar, Toxicology Advisory Center, National
    Institute of Public Health and Environmental Hygiene,
    Bilthoven, The Netherlands (WHO Temporary Adviser)

    Dr G. Vettorazzi, Senior Toxicologist, International Programme on
    Chemical Safety, Division of Environmental Health, WHO,
    Geneva, Switzerland (Joint Secretary)

    Mr M. Walsh, Directorate General for Agriculture, Commission of the
    European Communities, Brussels, Belgium (FAO Consultant)

    ABBREVIATIONS WHICH MAY BE USED IN THESE MONOGRAPHS

    (N.B.: chemical elements and pesticides are not included in this list)

    AChE          acetylcholinesterase
    ADI           acceptable daily intake
    AG            ratio albumine/globulin ratio
    ai            active ingredient
    approx,       approximate
    at.wt.        atomic weight

    b.p.          boiling point
    bun           blood urea nitrogen

    c             centi - (× 10-2)
    °C            degree Celsius (centigrade)
    CCPR          Codex Committee on Pesticide Residues
    ChE           cholinesterase
    cm            centimetre
    CNS           central nervous system
    cu            cubic

    DL            racemic (optical configuration, a mixture of dextro- and
                  laevo-; preceding a chemical name)

    EC            emulsion concentrate
    ERL           extraneous residue limit
    F1            filial generation, first
    F2            filial generation, second
    f.p.          freezing point
    FAO           Food and Agriculture Organization of the United Nations

    g             gram
    ug            microgram
    GAP           good agricultural practice
    GC-MS         gas chromatography - mass spectrometry
    G.I.          gastro-intestinal
    GL            guideline level
    GLC           gas-liquid chromatography
    GPC           gel-permeation chromatography

    h             hour(s)
    ha            hectare
    Hb            haemoglobin
    Ht            haematocrit
    HPLC          high-performance liquid chromatography

    IARC          International Agency for Research on Cancer
    IBT           Industrial Bio-Test Laboratories
    i.m.          intramuscular
    i.p.          intraperitoneal
    IR            infrared
    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)

    k             kilo- (× 103)
    kg            kilogram

    l             litre
    LDH           lactate dehydrogenase
    LC50          lethal concentration, 50%
    LD50          lethal dose, median

    m             metre
    MCH           mean corpuscular haemoglobin
    MCV           mean corpuscular volume
    mg            milligram
    um            micrometre (micron)
    min           minute(s)
    ml            millilitre
    MLD           minimum lethal dose
    mm            millimetre
    M             molar
    mo            month(s)
    m.p.          melting point
    MRL           Maximum Residue Limit (This term replaces "tolerance")
    MTD           maximum tolerated resonance

    n             normal (defining isomeric configuration)
    NCI           National Cancer Institute (United States)
    NMR           nuclear magnetic resonance
    no.           number
    NOEL          no-observed-effect-level
    NOAEL         no-observed-adverse-effect-level
    NTE           neuropathy target esterase

    o             ortho (indicating position in a chemical name)
    OP            organophosphorus pesticide

    p             para (indicating position in a chemical name)
    2-PAM         2-pralidoxime
    PHI           pre-harvest interval
    ppm           parts per million (Used only reference to the
                  concentration of a pesticide in an experimental diet. In
                  all other contexts the terms mg/kg or mg/l are used).

    s.c.          subcutaneous
    SD            standard deviation
    SE            standard error
    sp./spp.      species (only after a generic name)
    sp gr         specific gravity
    sq            square

    t             tonne (metric ton)
    TADI          Temporary Acceptable Daily Intake
    tert          tertiary (in a chemical name)
    TLC           thin-layer chromatography
    TMRL          Temporary Maximum Residue Limit

    UV            ultraviolet

    v/v           volume ratio (volume per volume)

    WHO           World Health Organization

    wk            week
    WP            wettable powder
    wt            weight
    wt/volweight per volume
    w/w           weight per weight

    yr            year

    <            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 Geneva,
    Switzerland, 21 September to 30 September 1987. 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 intake.

         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 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. 84. 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 1987, Part I Residues, as
    FAO Plant Production and Protection Paper No. 86/1.

         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 1987 Joint Meeting. A special acknowledgement
    is given to those who prepared these working papers, Professor C.L.
    Berry, The London Hospital Medical College, London, UK, Dr A.L. Black,
    Commonwealth Department of Health, Woden, Australia; Dr M. Manno,
    University of Padua Medical School, Padua, Italy, Dr D.S. Saunders, U.S.
    Environmental Protection Agency, Washington, DC, USA, and Dr E.M. den
    Tonkelaar, National Institute of Public Health and Environmental
    Hygiene, Bilthoven, The Netherlands.

         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