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    ANNEX 4

    Acceptable Daily Intakes, other toxicological information, and
    information on specifications

    Adrenoceptor agonists

                                                                        

    Clenbuterol

    Acceptable daily intake (ADI): 0-0.004 µg per kg of body weight

    Recommended maximum residue limits (MRLs)1

                Muscle    Liver     Kidney    Fat       Eggs      Milk
                (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)   (µg/l)
                                                                        

    Cattle      0.2       0.6       0.6       0.2                 0.05
    Horses      0.2       0.6       0.6       0.2
                                                                        

    1    MRLs are expressed as the parent drug.

                                                                        

    Xylazine

    The Committee was unable to establish an ADI for xylazine because it
    concluded that a metabolite, 2,6-xylidine, is genotoxic and
    carcinogenic.

    The Committee was unable to establish MRLs for xylazine because of the
    lack of information on metabolism and residue depletion in edible
    tissues.

    The following information would be required for further review:

    *    Data on xylazine metabolism in target species sufficient to
         identify a suitable marker residue and target tissues.

    *    Additional data on residue depletion of xylazine and its
         metabolites in target species. These data should include evidence
         to show, in particular, whether 2,6-xylidine is present at the
         recommended withdrawal times.

    *    A suitable analytical method for determining the marker residue
         in target tissues.

    Anthelminthic agents

                                                                        

    Abamectin

    ADI: 0-1 µg per kg of body weight1

    Recommended maximum residue limits (MRLs)2

                 Muscle    Liver     Kidney    Fat       Eggs     Milk
                 (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)  (µg/l)
                                                                        

    Cattle       100       50        100
                                                                        

    1    This ADI, which applies to the parent drug abamectin, was
         established by the 1995 Joint FAO/WHO Meeting on Pesticide
         Residues (JMPR; FAO Plant Production and Protection
         Paper 133, 1996).
    2    MRLs are expressed as avermectin B1a.

                                                                        

    Moxidectin

    ADI: 0-2 µg per kg of body weight1

    Recommended maximum residue limits (MRLs)2

                Muscle    Liver     Kidney    Fat       Eggs      Milk
                (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)   (µg/l)
                                                                        

    Cattle      20        100       50        500
    Sheep       503       100       50        500
    Deer4       20        100       50        500
                                                                        

    1    This ADI was established at the forty-fifth meeting of the
         Committee.
    2    MRLs are expressed as the parent drug.
    3    This MRL was established at the present meeting. All other MRLs
         were established at the forty-fifth meeting of the Committee. At
         that meeting the Committee noted the high concentration of
         residues at the injection site over a 35-day period after
         subcutaneous or intramuscular administration of the drug at the
         recommended dose.
    4    Temporary MRLs (see the report of the forty-fifth meeting of the
         Committee).

    Antimicrobial agents

    Chlortetracycline, oxytetracycline and tetracycline

    ADI: 0-3 µg per kg of body weight1

    Recommended maximum residue limits (MRLs)2

                Muscle    Liver     Kidney    Fat       Eggs     Milk
                (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)  (µg/l)
                                                                        

    Cattle      100       300       600                          100
    Pigs        100       300       600
    Sheep       100       300       600                          100
    Poultry     100       300       600                 200
    Giant
     prawn      1003
    (Penaeus
    monodon)
                                                                        

    1    This ADI was established at the forty-fifth meeting of the
         Committee.
    2    MRLs are expressed as the parent drug.
    3    This MRL applies only to oxytetracycline.

                                                                        

    Neomycin

    ADI: 0-60 µg per kg of body weight

    Recommended maximum residue limits (MRLs)1

                Muscle    Liver     Kidney    Fat       Eggs     Milk
                (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)  (µg/l)
                                                                        

    Cattle      500       500       10 000    500                500
    Pigs        500       500       10 000    500
    Sheep       500       500       10 000    500
    Goats       500       500       10 000    500
    Chickens    500       500       10 000    500       500
    Ducks       500       500       10 000    500
    Turkeys     500       500       10 000    500
                                                                        

    1    MRLs are expressed as the parent drug.

    Spiramycin

    ADI: 0-50 µg per kg of body weight1

    Recommended maximum residue limits (MRLs)

                  Muscle    Liver     Kidney    Fat       Eggs     Milk
                  (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)  (µg/kg)  (µg/l)
                                                                        

    Cattle2       200       600       300       300                 100
    Pigs3         200       600       300       300
    Chickens2     200       600       800       300
                                                                        

    1    The ADI was established at the forty-third meeting of the
         Committee.
    2    MRLs are expressed as the sum of spiramycin and neospiramycin.
    3    MRLs are expressed as spiramycin equivalents (antimicrobially
         active residues).

                                                                        

    Thiamphenicol

    ADI: 0-6 µg per kg of body weight1

    Recommended maximum residue limits (MRLs)2

                  Muscle    Liver     Kidney    Fat      Eggs     Milk
                  (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)  (µg/kg)  (µg/l)
                                                                        

    Cattle        40        40        40        40
    Chickens      40        40        40        40
                                                                        

    1    Temporary ADI.
    2    Temporary MRLs, expressed as the parent drug.

    The following information is required for evaluation in 1999:

    *    Detailed reports of the carcinogenicity study in rats on which
         the summary report was available at the present meeting and the
         range-finding study used to establish dose levels in that study.

    *    Residue depletion studies with radiolabelled and unlabelled
         thiamphenicol for identification of the marker residue and target
         tissues in non-ruminant cattle, chickens and pigs.

    Tilmicosin

    ADI: 0-40 µg per kg of body weight

    Recommended maximum residue limits (MRLs)1

                Muscle    Liver     Kidney    Fat       Eggs      Milk
                (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)   (µg/l)
                                                                        

    Cattle      100       1000      300       100
    Pigs        100       1500      1000      100
    Sheep       100       1000      300       100                 502
                                                                        

    1    MRLs are expressed as the parent drug.
    2    Temporary MRL. The results of a study in lactating sheep with
         radiolabelled drug for estimation of the relationship between
         total residues and parent compound in milk are required for
         evaluation in 1999.

                                                                        

    Insecticides

    Cypermethrin

    ADI: 0-50 µg per kg of body weight

    Recommended maximum residue limits (MRLs)1

                Muscle    Liver     Kidney    Fat       Eggs      Milk
                (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)   (µg/l)
                                                                        

    Cattle      200       200       200       1000                50
    Sheep       200       200       200       1000
    Chickens    200       200       200       1000      100
                                                                        

    1    Temporary MRLs, expressed as the parent drug.

    The following information is required for evaluation in 2000:

    *    The results of radiodepletion studies that extend beyond the
         recommended withdrawal times using the drug in its topical
         formulation. The study should determine the depletion of the
         total residues and the parent drug in target species.

    *    Evidence to verify that no interconversion of isomeric forms
         occurs during metabolism in the target species.

    *    Further information on the validation of analytical methods,
         particularly data on the derivation of the limits of
         determination and limits of quantification.

    alpha-Cypermethrin

    ADI: 0-20 µg per kg of body weight

    Recommended maximum residue limits (MRLs)1

                Muscle    Liver     Kidney    Fat       Eggs      Milk
                (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)   (µg/kg)   (µg/l)
                                                                        

    Cattle      100       100       100       500                 25
    Sheep       100       100       100       500
    Chickens    100       100       100       500       50
                                                                        

    1    Temporary MRLs, expressed as the parent drug.

    The following information is required for evaluation in 2000:

    *    The results of radiodepletion studies in sheep and chickens that
         extend beyond the recommended withdrawal times using the drug in
         its topical formulation. The study should determine the depletion
         of the total residues and the parent drug.

    *    The radiodepletion study submitted for cattle should he
         reassessed to determine the depletion of the total residues and
         the parent drug.

    *    Evidence to verify that no interconversion of the  cis-isomeric
         forms to the  trans-isomeric forms occurs during metabolism in the
         target species.

    *    Further information on the validation of analytical methods,
         particularly data on the derivation of the limits of
         determination and limits of quantification.
    




























    See Also:
       Toxicological Abbreviations