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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 41





        Prepared by:
          The 50th meeting of the Joint FAO/WHO Expert
          Committee on Food Additives (JECFA)



        World Health Organization, Geneva 1998




    Antimicrobial Agents

         The Committee examined the results of studies of antimocrobial
    activity in vitro in which relevant gut microflora were used to
    calculate ADIs for some of the antimocrobial agents that were
    reviewed.  The equation used for deriving the ADIs is based on that
    described in the report of the forty-seventh meeting of the Committee
    (Annex 1, reference 125).

         The upper limit of the ADI was derived as follows:

         Upper limit     MIC50 (µg/g) × MCC(g)
           of ADI    =                        
         (µg/kg bw)       FA × SF × BW(kg

    where:

    MIC50 =   The minimum concentration of an antimicrobial drug that
              completely inhibits the growth of 50% of cultures of a given
              microorganism, as judged by the naked eye, after a given
              period of incubation.  For the purposes of the evaluation,
              the MIC50 value is the mean MIC50 value(s) for the
              strain(s) of the relevant species tested.  Alternatively,
              the lowest MIC50 value for the most sensitive species can be
              used.

    MCC =     Mass of colonic content; a value of 220 g is used.

    FA =      Fraction of an oral dose available to act upon
              microorganisms in the colon

    SF =      The safety factor used to account for uncertainty about the
              amount and relevance of data for MIC values available for
              review; may range from 1 to 10, a value of 1 being used when
              extensive, relevant microbiological data are available.

    BW =      Body weight; a value of 60 kg is used.
    


    See Also:
       Toxicological Abbreviations
       Antimicrobial agents (WHO Food Additives Series 39)