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    PESTICIDE RESIDUES IN FOOD - 1989


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




    EVALUATIONS 1994

    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, 18-27 September 1989


 

    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 102941-5

    All rights reserved.  No part of this publication may be reproduced,
    stored in a retrieval system, or transmitted in any form or by any
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    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 1990

    TABLE OF CONTENTS

    List of those attending the meeting
    Abbreviations
    Introduction

    The Monographs

         * Anilazine
           Azocyclotin
           Cyhexatin
           Daminozide
           Demeton-S-Methyl and Related Compounds
           Dinocap
           Endosulfan
         * Flusilazole
           Lindane
           Methomyl
           Procymidone
           Propoxur
         * Triadimenol
         * Triazolyl alanine


    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 1989 Meeting


                 
    * First full evaluation
    

    1989 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, 18 - 27 September 1989

    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

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

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

    Dr D.J. Hamilton, Assistant Director, Agricultural Chemistry Branch,
    Department of Primary Industries, Brisbane, Australia (Vice-
    Chairman)

    Mr N.F. Ives, US Environmental Protection Agency, Office of Pesticide
    Programs, Washington, D.C., USA

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

    WHO Expert Group on Pesticide Residues

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

    Dr J. Borzelleca, President, Medical College of Virginia, Virginia
    Commonwealth University, Richmond, USA (Rapporteur)

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

    Prof. M. Lotti, Professor of Industrial Toxicology, Universitŕ di
    Padova, Istituto di Medicina del Lavoro, Padua, Italy

    Dr  F.R. Puga, Secao de Toxicologia e Higiene Comparada, Instituto
    Biolňgico, Sao Paulo, Brazil

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

    Secretariat

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

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

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

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

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

    Dr J. van der Kolk, Foodstuffs Division, Ministry of Welfare, Health
    and Cultural Affairs, Rijswijk, The Netherlands (Chairman of Codex
    Committee on Pesticide Residues)

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

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

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

    Prof. R. Nilsson, Chief of Section, The National Swedish Chemicals
    Inspectorate, Department for Scientific Documentation and Research,
    Solna, Sweden  (WHO Temporary Adviser)

    Dr O.E. Paynter, Chief Scientist, Health Effects Division, Office of
    Pesticide Programs, US Environmental Protection Agency, Washington,
    D.C., USA (WHO Temporary Adviser)

    Dr J. Quest, Toxicologist, Toxicology Branch, Health Effects Division,
    US Environmental Protection Agency, Washington, D.C., (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, The Netherlands  (WHO Temporary Adviser)

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

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

    Mr J. Wilbourn, Unit of Carcinogen Identification and Evaluation,
    International Agency for Research on Cancer, Lyon, France (WHO
    Temporary Adviser)*

                 
    *  Invited but unable to attend.

    ABBREVIATIONS USED IN THESE MONOGRAPHS

    AChE        acetylcholinesterase
    ALAT        alanine aminotransferase 
    BUN         blood urea nitrogen

    ChE         cholinesterase
    CMC         carboxymethylcellulose
    CNS         central nervous system

    DMSO        dimethylsulfoxide
    DNA         deoxyribonucleic acid

    EC          emulsifiable concentrate

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

    GGT         gamma-glutamyltransferase
    G.I.        gastrointestinal
    GOT         glutamate-oxoloacetate transaminase
    GPT         glutamate-pyruvate transaminase

    Hb          haemoglobin
    HCG         human chorionic gonadotropin
    HGRPT       hypoxanthine-guanine phosphoribosyl transferase

    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

    NOAEL       no-observed-adverse-effect level

    PCV         hematocrit (packed corpuscular volume)

    RBC         red blood cell

    SAP         serum alkaline phosphatase

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

    UDMH        unsymmetrical dimethylhydrazine
    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, 18 September to 27 September 1989.  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.  Thererfore,
    monographs on them have been published previously and 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. 99.  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 will be
    published as a companion volume to this one: Evaluations 1989, 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 1989 Joint Meeting.  A special
    acknowledgement is given to those who prepared these working papers,
    Drs G. Burin and J. Quest, US Environmental Protection Agency,
    Washington, D.C., USA; Professor R. Nilsson, National Swedish
    Chemicals Inspectorate, Solna, Sweden; Dr A. Moretto, University of
    Padua, Padua, Italy; Dr E. Arnold, Health and Welfare Canada, Ottawa,
    Canada; and Dr E.M. den Tonkelaar, National Institute of Public Health
    and Environmental Protection, 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