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        PESTICIDE RESIDUES IN FOOD - 1986


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




        EVALUATIONS 1986

        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, 29 September - 8 October 1986

             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. The main objective of the IPCS is to carry out and
        disseminate evaluations of the effects of chemicals on human
        health and the quality of the environment. Supporting activities
        include the development of epidemiological, experimental
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        internationally comparable results, and the development of
        manpower in the field of toxicology. Other activities carried out
        by the IPCS include the development of know-how for coping with
        chemical accidents, coordination of laboratory testing and
        epidemiological studies, and promotion of research on the
        mechanisms of the biological action of chemicals.

        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.

        M-84
        ISBN 92-5 102598-3

        All rights reserved. No part of this publication may be
        reproduced, stored in a retrieval system, or transmitted in any
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        of the United Nations, Via delle Terme di Caracalla, 00100 Rome,
        Italy.

        (c) FAO 1987

    CONTENTS

    PART II - TOXICOLOGY

    List of those attending the Meeting
    Abbreviations
    Introduction

    Toxicology monographs and monograph addenda

         Carbosulfan
         Chlordane
         Clofentezine*

         Ethion

         Fenitrothion
         Folpet

         Glyphosate*

         Imazalil
         Isofenphos

         Mecarbam
         Methacrifos
         Methomyl*

         Paraquat*
         Phosphamidon
         Propamocarb

         Thiodicarb
         Triazophos

         Vinclozolin*

    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 1986 Meeting

              

    *Full monograph

    

    1986 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, 29 September - 8 October 1986

    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, United Kingdom.
       (Chairman)

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

    Dr E. Celma-Calamita, Ministerio de Agricultura, Pesca y Alimentacion,
       Madrid, Spain.

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

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

    Mr J.T. Snelson, Canberra, Australia, formerly Pesticides
       Co-Ordinator, Department of Primary Industry. (Rapporteur)

    Mr K. Voldum-Clausen, Division of Pesticides and Contaminants,
       National Food Agency, Soborg, Denmark.

    Observers invited by FAO

    Mr A.J. Pieters, Ministry of Welfare, Health and Cultural Affairs,
       Leidschendam, The Netherlands.

    Dr Sakdiprayoon Deema, Inspector General, Ministry of Agriculture and
       Cooperatives, Bangkok, Thailand. (Chairman of the CCPR ad hoc
       Working Group on Pesticide Residue Problems in Developing
       Countries)

    WHO Expert Group on Pesticide Residues

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

    Professor J.F. Borzelleca, Professor of Pharmacology & Toxicology,
       Medical College of Virginia, Richmond, VA., 23298 USA.

    Mr D.J. Clegg, Head, Pesticide Section, Toxicological Evaluation
       Division, Food Directorate, Health Protection Branch,
       Ottawa, Canada. (Vice-Chairman)

    Professor Mrs Julia Higa de Landoni, Professor of Toxicology, School
       of Medicine, University of Buenos Aires, Buenos Aires, Argentina.

    Professor M. Lotti, Professor of Industrial Toxicology, Istituto di
       Medicina del Lavoro, University of Padua Medical School,
       Padua, Italy.

    Professor R. Plestina, Head, Department of Toxicology, Institute for
       Medical Research and Occupational Health, Zagreb, Yugoslavia.

    Secretariat

    Mr H. Akagawa, Pharmaceutical Affairs Bureau, Ministry of Health and
       Welfare, Japanese Government, Tokyo, Japan.
       (WHO Temporary Adviser)

    Professor Mrs Nabila M.S. Bakry, Professor of Pesticide Chemistry and
       Toxicology, Faculty of Agriculture, University of Alexandria,
       Alexandria, Egypt. (WHO Temporary Adviser)

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

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

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

    Dr E. Johnson, Scientist, Unit of Analytical Epidemiology,
       International Agency for Research on Cancer, Lyon, France.
       (WHO Temporary Adviser)

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

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

    Dr D.S. Saunders, Toxicologist, Toxicology Branch, Hazard Evaluation
       Division (TS 769c), 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)

    Dr Mrs. E.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).

    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
    b.w.      body weight

    ChE       cholinesterase
    CHO       Chinese hampster 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

    GC        gas chromatography
    G.I.      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 dehydrogenase

    MCA       3-methylcholanthrene
    MCH       mean corpuscular haemoglobin
    MCHC      mean corpuscular haemoglobin concentration
    MCV       mean corpuscular volume
    MMS       methylmethane sulfonate
    MTD       maximum tolerated dose

    NADPH     nicotinamide adenine dinucleotide phosphate (reduced)
    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
    ppb       parts per billion (1000 ppb = 1 ppm)
    ppm       parts per million

    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
    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

    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, 29 September to 8 October 1986. 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 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. 77. 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 1986, Part I
    - Residues, as FAO Plant Production and Protection Paper No. 78.

         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 1986 Joint Meeting. A special
    acknowledgement is given to those who prepared these working papers,
    Professor N.S. Bakry, University of Alexandria, Alexandria, Egypt;
    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