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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    WORLD HEALTH ORGANIZATION



    TOXICOLOGICAL EVALUATION OF CERTAIN
    VETERINARY DRUG RESIDUES IN FOOD



    WHO FOOD ADDITIVES SERIES 31





    Prepared by:
      The fortieth meeting of the Joint FAO/WHO Expert
      Committee on Food Additives (JECFA)



    World Health Organization, Geneva 1993


         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 laboratory, and risk-
    assessment methods that could produce 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.


    CONTENTS

    Preface

    Monograph Format

    Anthelminthic agents

           Flubendazole
           Ivermectin
           Tiabendazole (Thiabendazole)
           Triclabendazole

    Antimicrobial agents

           Furazolidone
           Nitrofural (Nitrofurazone)

    Production aids

           Bovine somatotropins
           Ractopamine

    Trypanocide

           Isometamidium

    Annexes

           Annex 1       Reports and other documents
                         resulting from previous meetings
                         of the Joint FAO/WHO Expert
                         Committee on Food Additives

           Annex 2       Abbreviations used in the
                         Monographs

           Annex 3       Joint FAO/WHO Expert Committee
                         on Food Additives, Geneva,
                         9-18 June 1992

           Annex 4       Recommendations on compounds
                         on the agenda
    
    PREFACE

           The monographs contained in this volume were prepared by the
    fortieth Joint FAO/WHO Expert Committee on Food Additives (JECFA),
    which met in Geneva, Switzerland, 9-18 June 1992. These monographs
    summarize the safety data on selected veterinary drug residues
    reviewed by the Committee. The data reviewed in these monographs
    form the basis for acceptable daily intakes (ADIs) established by
    the Committee.

           The fortieth report of JECFA will be published by the World
    Health Organization as WHO Technical Report Series No. 832. The
    participants in the meeting are listed in Annex 3 of the present
    publication and a summary of the conclusions of the Committee is
    included as Annex 4.

           Residue monographs on the veterinary drugs that were evaluated
    at the fortieth meeting of JECFA will be issued separately by FAO as
    FAO Food and Nutrition Paper No. 41/5. These toxicological
    monographs should be read in conjunction with the residues
    monographs and the report.

           Reports and other documents resulting from previous meetings of
    the Joint FAO/WHO Expert Committee on Food Additives are listed in
    Annex 1.

           JECFA serves as a scientific advisory body to FAO, WHO, their
    Member States, and the Codex Alimentarius Commission, primarily
    through the Codex Committee on Food Additives and Contaminants and
    the Codex Committee on Residues of Veterinary Drugs in Foods,
    regarding the safety of food additives, residues of veterinary
    drugs, naturally occurring toxicants, and contaminants in food.
    Committees accomplish this task by preparing reports of their
    meetings and publishing specifications or residues monographs and
    toxicological monographs, such as those contained in this volume, on
    substances that they have considered.

           The toxicological monographs contained in this volume are based
    upon working papers that were prepared by Temporary Advisers. A
    special acknowledgement is given at the beginning of each monograph
    to those who prepared these working papers.

           Many proprietary unpublished reports are referenced. These were
    voluntarily submitted to the Committee by various producers of the
    veterinary drugs under review and in many cases these reports
    represent the only safety data available on these substances. The
    Temporary Advisers based the working papers they developed on all
    the data that were submitted, and all these studies were available
    to the Committee when it made its evaluations.

           From 1972 to 1975 the toxicology monographs prepared by JECFA
    were published in the WHO Food Additives Series; after 1975 this
    series was available in the form of unpublished WHO documents
    provided upon request to the Organization. WHO Food Additives Series
    No. 20 which was prepared by the twenty-ninth Committee in 1985,
    through WHO Food Additives Series No. 24, which was prepared by the
    thirty-third Committee in 1988, were published by the Cambridge
    University Press. Beginning with WHO Food Additives Series No. 25,
    which was prepared by the thirty-fourth Committee, WHO is producing
    these volumes as priced documents.

           The preparation and editing of the monographs included in this
    volume have been made possible through the technical and financial
    contributions of the Participating Institutions of the International
    Programme on Chemical Safety (IPCS), which support the activities of
    JECFA. IPCS is a joint venture of the United Nations Environment
    Programme, the International Labour Organisation, and the World
    Health Organization, which is the executing agency. 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.

           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 organizations participating in 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 those organizations 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 Expert
    Committee on Food Additives, International Programme on Chemical
    Safety, World Health Organization, Avenue Appia, 1211 Geneva 27,
    Switzerland.

    MONOGRAPH FORMAT

    Note:         Each monograph in this document follows the general format
    presented below. All monographs may not, however, require the use of
    each heading.

    1.     EXPLANATION

    2.     BIOLOGICAL DATA

           2.1    Biochemical aspects
                  2.1.1                Absorption, distribution and excretion.
                  2.1.2                Biotransformation
                  2.1.3                Effects on enzymes and other biochemical 
                                       parameters

           2.2    Toxicological studies
                  2.2.1                Acute toxicity studies
                  2.2.2                Short-term toxicity studies
                  2.2.2.1-2.2.2.X  Species tested
                  2.2.3                Long-term/carcinogenicity studies
                  2.2.4                Reproduction studies
                  2.2.5-2.2.X  Special studies

                  2.3    Observations in humans

    3.     COMMENTS

    4.     EVALUATION

    5.     REFERENCES




























    See Also:
       Toxicological Abbreviations