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    PESTICIDE RESIDUES IN FOOD - 1985


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    with the support of the International Programme
    on Chemical Safety (IPCS)




    EVALUATIONS 1985

    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, 23 September - 2 October 1985

    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 92-5-102485-5

    All rights reserved.  No part of this publication may be reproduced,
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    prior permission of the copyright owner.  Applications for such
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    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 1986


    CONTENTS

    PART II: TOXICOLOGY

    List of those attending the meeting
    Abbreviations
    Introduction

    Toxicology monographs and monograph addenda

         Binapacryl

         Carbendazim
         Chlordimeform
         Chlorothalonil

         Diflubenzuron
         Dimethipin*

         Fenamiphos
         Flucythrinate*

         Imazalil

         Methamidophos

         Omethoate
         Oxamyl

         2-Phenylphenol and its sodium salt
         Phorate
         Propineb

         Thiodicarb*
         Triadimefon

         Vamidothion

    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 (ADIs), Maximum residue limits
              (MRLs), and Guideline levels proposed at the 1985 Meeting

              

    *    Full monograph
    

    1985 JOINT MEETING OF THE FAO PANEL OF EXPERTS ON PESTICIDE RESIDUES
    IN FOOD AND THE ENVIRONMENT AND A WHO EXPERT GROUP ON PESTICIDE
    RESIDUES

    Geneva, 23 September - 2 October 1985

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

    Dr D.C Abbott, Ashtead, United Kingdom.

    Mr J.A.R. Bates, Head, Pesticide Registration Department, Ministry of
         Agriculture, Fisheries and Food, Harpenden, United Kingdom
         (Chairman).

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

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

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

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

    Observers invited by FAO

    Dr W. Bosse, GTZ Pesticide Residue Laboratory, Darmstadt, West
         Germany.

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

    WHO Expert Group on Pesticide Residues

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

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

    Dr A.H. El-Sebae, Chairman, Pesticides Division, Faculty of
         Agriculture, Alexandria University, Alexandria, Egypt.

    Professor M. Lotti, Assistant Professor of Occupational Medicine,
         Istituto di Medicina del Lavoro, Padua, Italy.

    Dr O.E. Paynter, Chief Scientist, Hazard Evaluation Division, US
         Environmental Protection Agency, Washington, D.C., USA.

    Professor T.J. Pekkanen, Department of Food Hygiene, College of
         Veterinary Medicine, Helsinki, Finland.

    Dr R. Plestina, Director, Institute for Medical Research and
         Occupational Health, Zagreb, Yugoslavia.

    Professor Dr F.G. Reyes, Departamento Ciencias de Alimentos, Faculdade
         de Engenharia de Alimentos e Agrícola, Universidade Estadual de
         Campinas, Campinas SP, Brazil.

    Secretariat

    Dr A.L. Black, Medical Services Adviser, Commonwealth Department of
         Health Woden, Australia (WHO Temporary Adviser).

    Dr E. Budd, Supervisory Toxicologist, Hazard Evaluation Division, US
         Environmental Protection Agency, Washington, D.C., USA (WHO
         Temporary Adviser).

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

    Dr A. Di Muccio, Research Officer, Laboratorio Tossicologia Applicata,
         Istituto Superiore di Sanitŕ, Rome, Italy (WHO Temporary
         Adviser).

    Dr M. Gilbert, Scientific Affairs Officer, IRPTC/UNEP, Geneva,
         Switzerland (WHO Temporary Adviser).

    Dr H. Galal Gorchev, Food Safety, Division of Environmental Health,
         WHO, Geneva, Switzerland.

    Dr J.L. Herman, Center for Food Safety and Applied Nutrition, Food and
         Drug Administration, Washington, D.C., USA (WHO Consultant).

    Mr G. van den Hurk, Technical Officer, International Programme on
         Chemical Safety, Division of Environmental Health, WHO, Geneva,
         Switzerland.

    Dr R.B. Jaeger, Section Head, Toxicology Branch, Hazard Evaluation
         Division, US Environmental Protection Agency, Washington, D.C.,
         USA (WHO Temporary Adviser).

    Dr F.K. Kaeferstein, Manager, Food Safety, Division of Environmental
         Health, WHO, Geneva, Switzerland.

    Dr F-W. Kopisch-Obuch, Pesticide Residues 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.

    Dr M. Mercier, Manager, International Programme on Chemical Safety,
         Division of Environmental Health, WHO, Geneva, Switzerland.

    Dr A. Pelfrčne, Pesticides Development and Safe Use, Division of
         Vector Biology and Control, WHO, Geneva, Switzerland.

    Dr J.R. Plimmer, Head, Agrochemicals and Residues Section, Joint
         FAO/IAEA Division, IAEA, Vienna, Austria.

    Professor A. Rico, Director, I.N.R.A., Ecole National Vétérinaire,
         Toulouse, France (WHO Temporary Adviser).

    Professor V. Silano, Director, Department of Comparative Toxicology
         and Ecotoxicology, Istituto Superiore di Sanitŕ, Rome, Italy (WHO
         Temporary Adviser).

    Dr A. Takanaka, Head, Division of Pharmacology, Biological Safety
         Research Center, National Institute of Hygienic Sciences, Tokyo,
         Japan (WHO Temporary Adviser).

    Professor K. Topsy, Member Pesticide Control Board, Ministry of
         Health, Beau Bassin, Mauritius (WHO Temporary Adviser).

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

    Dr D. Wu-Lau, Scientific Adviser, Toxicological Evaluation Division,
         Food Directorate, Health Protection Branch, Ottawa, Canada (WHO
         Temporary Adviser).

    Mr J.R. Wessel, Director, Contaminants Policy Staff, Office of
         Regulatory Affairs, Food and Drug Administration, Rockville,
         Maryland, USA.

    ABBREVIATIONS USED IN THE MONOGRAPHS

    AchE      acetylcholinesterase

    ADI       acceptable daily intake

    a.i.      active ingredient

    ALD       acute lethal dose

    ALP       alkaline phosphatase

    BBN       N-butyl-N-(4-hydroxybutyl) nitrosamine

    BSP       bromosulfophathalein

    BUN       blood urea nitrogen

    c-AMP     cyclic adenosine monophosphate

    c-GMP     cyclic guanosine monophosphate

    ChE       cholinesterase

    CHO       Chinese hampster ovary

    CNS       central nervous system

    DMBA      7, 12-dimethylbenz(a)anthracene

    DMCF      dimethylcyanoformamide

    DMSO      dimethylsulfoxide

    ETU       ethylene thiourea

    FAO       Food and Agriculture Organization of the United Nations

    G.I.      gastrointestinal

    GLDH      glutamate dehydrogenase

    GOT       glutamate-oxoloacetate transaminase

    GPT       glutamate-pyruvate transaminase

    GSH       glutathione

    Hb        haemoglobin

    hr.       hour

    I50       inhibition, median

    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)

    kg        kilogram

    LD50      lethal dose, median

    LDH       lactate dehydrogenase

    MFO       mixed function oxidase

    µg        microgram

    µl        microlitre

    µM        micromolar

    mg        milligram

    ml        millilitre

    mM        millimolar

    MTD       maximum tolerated dose

    NADPH     nicotinamide adenine dinucleotide phosphate

    NCI       National Cancer Institute (United States)

    NOEL      no-observed-effect-level

    NTE       neurotoxic esterase

    OP        organophosphate

    OPP       2-phenylphenol (o-phenylphenol)

    2-PAM     2-pyridine aldoxine melthiodide (pralidoxime)

    PBI       protein-bound iodine

    PEG       polyethylene glycol

    PN        papillary/nodulary hyperplasia

    ppm       parts per million

    PSP       phenosulfophthalein

    PTU       propylene thiourea

    RBC       red blood cell

    SCE       sister chromatid exchange

    SOPP      sodium 2-phenylphenate (sodium o-phenylphenol)

    T3        triiodothyronine

    T4        tetraiodothyronine

    TADI      temporary acceptable daily intake

    TOCP      tri-o-cresyl phosphate

    TOTP      tri-o-tolyl phosphate

    TPA       12-o-tetradecanoylphorbol-13-acetate

    UDS       unscheduled DNA synthesis

    USDA      United States Department of Agriculture

    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
    Geneva, Switzerland, 23 September to 2 October 1985. 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 the FAO
    Plant Production and Protection Paper No. 68. 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 1985, Part I
    - Residues, as the FAO Plant Production and Protection Paper No. 72/1

         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 1985 Joint Meeting. A special
    acknowledgement is given to those who prepared these working papers,
    Dr A.L. Black, Commonwealth Department of Health, Woden, Australia;
    Dr E. Budd, U.S. Environmental Protection Agency, Washington, DC, USA;
    Dr A. DiMuccio, Istituto Superiore di Sanitŕ, Rome, Italy; Dr R.B.
    Jaeger, U.S. Environmental Protection Agency, Washington, DC, USA; and
    Dr D. Wu-Lau, Food Directorate, Health Protection Branch, Ottawa,
    Ontario, Canada.

         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 maufacturers' 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