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        PESTICIDE RESIDUES IN FOOD - 1996


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




        EVALUATIONS - 1996

        PART II - TOXICOLOGY



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

        Rome 15-25 September, 1996


    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 and environmental
    evaluations of pesticides carried out by the WHO Core Assessment Group
    for consideration by the Joint FAO/WHO 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.

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

    The summaries and evaluations contained in this books are, in most
    cases, based on unpublished data submitted for the purpose of the
    JMPR assessment.  A registration authority should not grant a
    registration on the basis on 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.

    ISBN 92 4 1665 12 2

    (c) World Health Organization 1997

    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
       Carbaryl
       Carbofuran
       2,4-Dichlorophenoxyacetic acid (2,4-D)
       Dimethoate
       Ferbam
       Flumethrin*
       Maleic hydrazide
       Mevinphos
       Phorate (addendum)
       Tebufenozide*
       Ziram

    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
    

    1996 Joint Meeting of the FAO Panel of Experts on Pesticide Residues
    in Food and the Environment and the WHO Core Assessment Group

    Rome, 16-25 September 1996

    PARTICIPANTS

     Toxicological Core Assessment Group

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

    Dr P. Fenner-Crisp, Deputy Director, Office of Pesticide Programs, US
       Environmental Protection Agency, Washington DC, United States
        (Vice-Chairman)

    Dr M. Joffe, Department of Epidemiology and Public Health, Imperial
       College of Medicine at St Mary's, London, United Kingdom

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

    Professor O. Pelkonen, Department of Pharmacology and Toxicology,
       University of Oulu, Oulu, Finland  (Rapporteur)

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

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

    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

    Mr D.J. Hamilton, Department of Natural Resources, Resource Sciences
       Centre, Indooroopilly, Brisbane, Queensland, Australia
        (Rapporteur)

    Mr N.F. Ives, Health Effects Division, US Environmental Protection
       Agency, Washington DC, United States  (Chairman)

    Mrs E. Masoller, Servicios de Laboratorios, Ministerio de Ganadería,
       Agricultura y Pesca, Montevideo, Uruguay

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

     Secretariat

    Dr A. Ambrus, Pesticide Group, Plant Protection Service, Food and
       Agricultural Organization, Rome, Italy  (FAO Joint Secretary)

    Dr E. Bosshard, Wettswil, Switzerland  (WHO Temporary Adviser)

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

    Dr K. Fujimori, Division of Pharmacology, Biological Safety Research
       Center, National Institute of Health Sciences, Ministry of Health
       and Welfare, Tokyo, Japan  (WHO Temporary Adviser)

    Dr D.L. Grant, Health Evaluation Division, Health Canada, Tunney's
       Pasture, Ottawa, Ontario, Canada  (WHO Temporary Adviser)

    Dr R.J. Hance, Pesticides Section, Joint FAO/IAEA Division, Vienna,
       Austria

    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, St Léon-sur-Vézère, France
        (WHO Consultant)

    Mrs P.H. van Hoeven-Arentzen, National Institute of Public Health and
       Environment, Bilthoven, Netherlands  (WHO Temporary Adviser)

    Dr F.-W. Kopisch-Obuch, Pesticide Group, Plant Protection Service,
       Food and Agricultural Organization, Rome, Italy

    Dr J.-J. Larsen, Department of General Toxicology, Institute of
       Toxicology, National Food Agency of Denmark, Soborg, Denmark  (WHO
        Temporary Adviser)

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

    Dr T.C. Marrs, Medical Toxicology and Environmental Health, Department
       of Health, 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 G. Moy, Food Safety Unit, Division of Food and Nutrition, World
       Health Organization, Geneva, Switzerland

    Dr J.C. Rowland, Toxicology Branch II, Health Effects Division, US
       Environmental Protection Agency, Washington DC, USA  (WHO
        Temporary Adviser)

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

    Mr M. Walsh, Commission of the European Communities, Législation des
       produits végétaux et de nutrition animale, VI/B/II.1, Brussels,
       Belgium

    Mr M. Watson, Risk Evaluation Branch, Pesticides Safety Directorate,
       Ministry of Agriculture, Fisheries and Food, Kings Pool, York,
       United Kingdom  (WHO Temporary Adviser)

    Dr Y. Yamada, Joint FAO/WHO Food Standards Programme, Food and
       Nutrition Division, Food and Agriculture Organization of the United
       Nations, Rome, Italy

    Abbreviations used

    ADI            acceptable daily intake
    ADP            adenosine diphosphate
    AMP            adenosine monophosphate
    ATP            adenosine triphosphate
    AUC            area under the curve
    bw             body weight
    CCPR           Codex Committee on Pesticide Residues
    CI             confidence interval
    DMSO           dimethyl sulfoxide
    EEG            electroencephalogram
    EMG            electromyogram
    F0             parental generation
    F1             first filial generation
    F2             second filial generation
    GC-MS          gas chromatography-mass spectrometry
    HPLC           high-performance liquid chromatography
    hprt           hypoxanthine-guanine phosphoribosyl transferase gene
    IC50           median inhibitory dose
    IPCS           International Programme on Chemical Safety
    JECFA          Joint FAO/WHO Expert Committee on Food Additives
    JMPR           Joint FAO/WHO Meeting on Pesticide Residues
    LC50           median lethal concentration
    LD50           median lethal dose
    LOAEL          lowest-observed-adverse-effect level
    NAD            nicotinamide adenine dinucleotide
    NADH+          reduced nicotinamide adenine dinucleotide
    NADP           nicotinamide adenine dinucleotide phosphate
    NADPH+         reduced nicotinamide adenine dinucleotide phosphate
    NOAEL          no-observed-adverse-effect level
    NR             not reported
    OECD           Organisation for Economic Co-operation and Development
    OR             odds ratio
    P450           cytochrome P450
    ppm            parts per million
    RR             relative risk
    S9             9000 × g supernatant fraction
    SD             standard deviation
    TLC            thin-layer chromatography
    TOCP           tri-ortho-cresyl phosphate
    v/v            volume per volume
    w/v            weight per volume
    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 16-25 September 1996.

         Nine of the compounds considered by the WHO Core Assessment
    Group at this Meeting had been evaluated at earlier meetings. For
    one of these, phorate, only information received since the previous
    evaluation is summarized, in a 'monograph addendum'. The appropriate
    earlier documents should be consulted in order to obtain a full
    toxicological profile of this chemical. Toxicological monographs
    were prepared on carbaryl, carbofuran, 2,4-D, dimethoate, ferbam,
    flumethrin, maleic hydrazide, mevinphos, tebufenozide, and ziram,
    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 will be published by the FAO
    in the  FAO Plant Production and Protection Paper series. The 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 1996, Part I,
     Residues, in the FAO Plant Production and Protection Paper series.

         The toxicological monographs and addendum contained in this
    volume are based on working papers that were prepared by temporary
    advisers before the 1996 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