IPCS INCHEM Home


    Pesticide residues in food -- 1998





    Toxicological and environmental 
    evaluations




    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 Core Assessment Group

    Rome, 21-30 September 1998



    The summaries and evaluations contained in this book are, in most
    cases, based on unpublished proprietary data submitted for the purpose
    of the JMPR assessment.  A registration authority should not grant a
    registration on the basis of an evaluation unless it has first
    received authorization for such use from the owner who submitted the
    data for JMPR review or has received the data on which the summaries
    are based, either from the owner of the data or from a second party
    that has obtained permission from the owner of the data for this
    purpose.

    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.

    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) within the framework of the
    Inter-Organization Programme for the Sound Management of Chemicals.

    The International Programme on Chemical Safety (IPCS), established in
    1980, is a joint venture of the United Nations Environment Programme
    (UNEP), the International Labour Organisation (ILO), and the World
    Health Organization (WHO). The overall objectives of the IPCS are to
    establish the scientific basis for assessing the risk to human health
    and the environment from exposure to chemicals, through international
    peer-review processes as a prerequisite for the promotion of chemical
    safety, and to provide technical assistance in strengthening national
    capacities for the sound management of chemicals.

    The Inter-Organization Programme for the Sound Management of Chemicals
    (IOMC) was established in 1995 by UNEP, ILO, the Food and Agriculture
    Organization of the United Nations, WHO, the United Nations Industrial
    Development Organization, and the Organisation for Economic Co-
    operation and Development (Participating Organizations), following
    recommendations made by the 1992 United Nations Conference on the
    Environment and Development to strengthen cooperation and increase
    coordination in the field of chemical safety. The purpose of the IOMC
    is to promote coordination of the policies and activities pursued by
    the Participating Organizations, jointly or separately, to achieve the
    sound management of chemicals in relation to human health and the
    environment.


    IPCS gratefully acknowledges the assistance of Mrs E. Heseltine, St
    Léon-sur-Vézère, France, for editing these monographs.

    Health & Environment International Ltd, by agreement with WHO,
    performed independent literature searches on some of the substances on
    which data are summarized in this document in order to ensure that all
    relevant toxicological and related information was reviewed.


    ISBN 92 4 1665 149

    (c)  World Health Organization 1999


    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 expression of any opinion whatsoever on
    the part of the Secretariat of the World Health Organization
    concerning the legal status of any country, territory, city or area or
    of its authorities, nor 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 participants
    Abbreviations

    Introduction 

    Toxicological evaluations
         Amitraz
         Bentazone (addendum)
         Bitertanol
         Dicloran 
         Dinocap 
         Diphenylamine (addendum) 
         Endosulfan
         Ethoxyquin
         Kresoxim-methyl* 
         Methiocarb 
         Phosmet (addendum)
         Thiophanate-methyl (addendum)


    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
    

    1998 Joint Meeting of the FAO Panel of Experts on Pesticide Residues
    in Food and the Environment and the WHO Core Assessment Group

    Rome, 21-30 September 1998

    PARTICIPANTS

     Toxicological Core Assessment Group

    Professor J.F. Borzelleca, Pharmacology, Toxicology, Medical College
    of Virginia, Richmond, Virginia, United States  (Vice-Chairman)

    Dr P. Fenner-Crisp, Senior Science Advisor to the Director, Office of
    Pesticide Programs, US Environmental Protection Agency, Washington DC
    United States

    Dr D. L. Grant, Director, Health Evaluation Division, Pest Management
    Regulatory Agency, Ottawa, Ontario, Canada  (Rapporteur)

    Dr A. Moretto, Laboratorio di Tossicologia Industriale, Istituto di
    Medicina del Lavoro, Università di Padova, Padova, Italy

    Dr B.G. Priestly, Scientific Director, Chemicals & Non-Prescription
    Drug Branch, Therapeutic Goods Administration, Commonwealth Department
    of Health and Family Services, Woden, ACT, Australia

    Professor A. Rico, Biochemistry-Toxicology, Physiopathology and
    Experimental Toxicology Laboratory, Ecole Nationale Vétérinaire,
    Toulouse, France

    Dr P. Yao, Professor of Toxicology, Institute of Occupational
    Medicine, Ministry of Health, Beijing, China


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

    Dr A. Ambrus, Food and Environmental Protection Section, Joint
    FAO/IAEA Division of Nuclear Techniques in Food and Agriculture,
    International Atomic Energy Agency, Vienna, Austria

    Dr U. Banasiak, Federal Biological Research Centre for Agriculture and
    Forestry, Kleinmachnow, Germany

    Mr S. Crossley, Pesticide Safety Directorate, Ministry of Agriculture,
    Fisheries and Food,  Kings Pool, York, United Kingdom  (Rapporteur)

    Dr E. Dutra Caldas, Instituto de Saúde do DF/Gerência de Bromatologia
    e Químicam and Department of Pharmaceutical Sciences, University of
    Brasilia, Brasília, Brazil

    Dr S. Funk, Health Effects Division, US Environmental Protection
    Agency, Washington DC, United States

    Mr D.J. Hamilton, Principal Scientific Officer, Animal & Plant Health
    Service, Department of Primary Industries, Brisbane, Australia
     (Chairman)

    Ms E. Masoller, Dirección General Servicios Agrícolas, División
    Analisis y Diagnósticos, Ministerio de Ganadería, Agricultura y Pesca,
    Montevideo, Uruguay

    Mr T. Sakamoto, Head of Technical Research Section, Agricultural
    Chemicals Inspection Station, Ministry of Agriculture, Forestry and
    Fisheries, Tokyo, Japan


     Secretariat

    Dr R. Bhula, National Registration Authority, Chemistry and Residue
    Evaluation Section, Kingston, ACT, Australia  (FAO Consultant)

    Dr K. Fujimori, Division of Xenobiotics, Metabolism and Disposition,
    National Institute of Health Sciences,  Tokyo, Japan  (WHO Temporary 
     Adviser)

    Dr W.H. van Eck, Chairman, Codex Committee on Pesticide Residues,
    Division of Public Health, Ministry of Health Welfare and Sport, The
    Hague, Netherlands

    Professor J. Hajslová, Institute of Chemical Technology, Department of
    Food Chemistry and Analysis, Prague, Czech Republic  (WHO Temporary 
     Adviser)

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

    Mrs E. Heseltine, Communication in Science, Lajarthe ,
    Saint-Léon-sur-Vézère, France

    Mrs J. Jempson, London, United Kingdom  (FAO Consultant)

    Dr J.-J. Larsen, Head, Department of General Toxicology, Institute of
    Food Safety and Toxicology, Danish Veterinary and Food Administration,
    Sœborg, Denmark  (WHO Temporary Adviser)

    Mr A.F. Machin, London, United Kingdom  (FAO Consultant)

    Dr T. C. Marrs, Joint Food Standards and Safety Group, London, United
    Kingdom  (WHO Temporary Adviser)

    Dr D. McGregor, Unit of Carcinogen Identification and Evaluation,
    International Agency for Research on Cancer, Lyon, France  (WHO 
     Temporary Adviser)

    Dr C. Moase, Health Evaluation Division, Pest Management Regulatory
    Agency, Health Canada, Ottawa, Ontario, Canada  (WHO Temporary 
     Adviser)

    Dr G. Moy, Food Safety Unit, Programme of Food Safety and Food Aid,
    World Health Organization, Geneva, Switzerland

    Mr N. Nakashima, International Programme on Chemical Safety, World
    Health Organization, Geneva, Switzerland

    Dr A. Protzel, Health Effects Division, US Environmental Protection
    Agency, Washington DC, United States  (WHO Temporary Adviser)

    Dr R. Solecki, Bundesinstitut für gesundheitlichen Verbraucherschutz
    und Veterinärmedizin, Berlin, Germany  (WHO Temporary Adviser)

    Dr G. Vaagt, Senior Officer, Pesticide Management Group, Food and
    Agriculture Organization of the United Nations, Rome, Italy  (FAO 
     Joint Secretary)

    Mr S. Warren, Pesticides Safety Directorate, Ministry of Agriculture,
    Fisheries and Food, King's Pool, York, United Kingdom  (WHO 
     Temporary Adviser)

    Mr G. Wyrwal, Pesticide Group, Plant Protection Service, Food and
    Agriculture Organization of the United Nations, Rome, Italy

    Abbreviations used

    ADI         acceptable daily intake
    ALAT        alanine aminotransferase
    AP          alkaline phosphatase
    ASAT        aspartate aminotransferase
    BrdU        5-bromo-2'-deoxyuridine
    bw          body weight
    CCPR        Codex Committee on Pesticide Residues
    CMC         carboxymethyl cellulose
    CYP         cytochrome P450
    DMSO        dimethyl sulfoxide
    DNHCP       methyl heptyl isomer of dinocap
    F           female
    F0          parental generation
    F1          first filial generation
    F2          second filial generation
    GABA        gamma-aminobutyric acid
    GGT         gamma-glutamyl transferase
    GLP         good laboratory practice
    GST-P       placental form of glutathione  S-transferase
    gamma-GT    gamma-glutamyl transpeptidase
    H&E         haematoxylin and eosin
    HID         highest ineffective dose
    HPLC        high-performance liquid chromatography
     hprt        hypoxanthine-guanine phosphoribosyl transferase gene
    Ig          immunoglobulin
    ip          intraperitoneally
    IPCS        International Programme on Chemical Safety
    JMPR        Joint FAO/WHO Meeting on Pesticide Residues
    LED         lowest effective dose
    LC50        median lethal concentration
    LD50        median lethal dose
    LOAEL       lowest-observed-adverse-effect level
    M           male
    MRL         maximum residue limit
    NOAEL       no-observed-adverse-effect level
    NOEC        no-observed-effect concentration
    NR          not reported
    po          orally
    ppm         parts per million
    S9          9000 ×  g supernatant fraction of rodent liver
    SPF         specific pathogen-free
    w/w         weight per weight

    Introduction

         The toxicological monographs and monograph addenda  contained in
    this volume were prepared by a WHO Core Assessment Group 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, on 21-30 September 1998.

         One of the substances evaluated by the Core Assessment Group at
    this Meeting, kresoxim-methyl, was evaluated for the first time. The
    other substances had been evaluated at earlier meetings. For five of
    these, bentazone, dinocap, diphenylamine, phosmet, and thiophanate-
    methyl, only information received since the previous evaluations is
    summarized, in 'monograph addenda'. The appropriate earlier documents
    should be consulted in order to obtain full toxicological profiles of
    these chemicals. Toxicological monographs were prepared on amitraz,
    bitertanol, dicloran, endosulfan, ethoxyquin, kresoxim-methyl, and
    methiocarb, summarizing new data and, where relevant, incorporating
    information from previous monographs and addenda. Reports and other
    documents resulting from previous Joint Meetings on Pesticide Residues
    are listed in Annex 1.

         The report of the Joint Meeting has been published by the FAO as
     FAO Plant Production and Protection Paper 148. That  report contains
    brief comments on the compounds considered, acceptable daily intakes
    established by the WHO Core Assessment Group, and maximum residue
    limits or guideline levels established by the FAO Panel of Experts.
    Monographs on residues prepared by the FAO Panel of Experts are
    published as a companion volume, as  Evaluations 1998, Part I, 
     Residues, in the FAO Plant Production and Protection Paper series.

         The toxicological monographs and addenda contained in this volume
    are based on working papers that were prepared by temporary advisers
    before the 1998 Joint Meeting. A special acknowledgement is made to
    those advisers. The monographs were edited by Mrs E. Heseltine, St
    Léon-sur-Vézère, France.

         The preparation and editing of this volume were made possible by
    the technical and financial contributions of the lead institutions of
    the International Programme on Chemical Safety (IPCS), which supports
    the activities of the 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 of its authorities, nor 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 biology or toxicology of
    the compounds included in this volume 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