IPCS INCHEM Home


    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    WORLD HEALTH ORGANIZATION



    TOXICOLOGICAL EVALUATION OF CERTAIN
    VETERINARY DRUG RESIDUES IN FOOD



    WHO FOOD ADDITIVES SERIES 34





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



    World Health Organization, Geneva 1995


         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.



    CONTENT

    Preface

    ß-Adrenoceptor-blocking agent
         Carazolol

    Antimicrobial agents
         Dihydrostreptomycin
         Streptomycin
         Enrofloxascin
         Gentamicin
         Neomycin
         Spiramycin

    Tranquillizing agent
         Azaperone

    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,
                   15-24 November 1994

         Annex 4   Recommendations on compounds
                   on the agenda

         Annex 5   Corrigenda

    PREFACE

         The monographs contained in this volume were prepared by the
    forty-third Joint FAO/WHO Expert Committee on Food Additives (JECFA),
    which met in Geneva, Switzerland, 15-24 November 1994.  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 forty-third report of JECFA will be published by the World
    Health Organization in the WHO Technical Report Series.  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 forty third meeting of JECFA will be issued separately by FAO as
    FAO Food and Nutrition Paper No. 41/7.  These toxicological monographs
    should be read in conjunction with the residue monographs and the
    report.

         Reports and other documents resulting from previous meetings of
    JECFA 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 residue 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 has been 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 supports 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.

    ANTIMICROBIAL AGENTS

         ADIs based on  in vitro experiments using relevant human gut
    microflora to identify MICs were derived for some of the antimicrobial
    agents that were reviewed. The equation used for deriving these ADIs
    is based on Annex 5 of the report of the thirty-eighth meeting of the
    Committee (Annex 1, reference 97), in which an equation was provided
    for the derivation of  temporary ADIs.  At the forty-second meeting
    (Annex 1, reference 110) the Committee concluded that this approach
    could also be used for the establishment of  final ADIs.

         The upper limit of the ADI is derived as follows:

    
                        Concentration without
                        effect on human gut           x    Daily faecal bolus (g)
    Upper limit of      flora (µg/ml)
    ADI (µg/bw) =                                                                
                        Fraction of 
                        oral dose      x   Safety     x    Weight of human (60 kg)
                        bioavailable       factor
    
         The  concentration without effect on human gut flora, the
     fraction of oral dose bioavailable, and  the safety factor may
    vary, depending upon the circumstances relating to the particular
    veterinary drug under consideration. The reasons for using particular
    factors are given in the individual evaluations.

         The average weight of the daily faecal bolus is known to vary
    widely among individuals between 150 to greater than 400 g per day;
    additionally, concentrations of substances in the rectum are greater
    than in the more proximal portions of the colon.  In the estimations
    of the ADIs in this report, a very conservative estimate of 150 g was
    selected for the weight of the daily faecal bolus.

         The body weight was taken to be 60 kg in the calculations in
    these evaluations.




























    See Also:
       Toxicological Abbreviations