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    PESTICIDE RESIDUES IN FOOD - 1979


    Sponsored jointly by FAO and WHO






    EVALUATIONS 1979





    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, 3-12 December 1979



    CARBOPHENOTHION

    Explanation

    Carbophenothion was evaluated in 1972.  The temporary ADI allocated on
    that occasion was withdrawn in 1976 because required information on
    toxicological studies to substantiate marked species differences in
    sensitivity to plasma cholinesterase inhibition and an adequate
    reproduction study had not been provided.  In 1977, when some
    additional information had become available, the Meeting confirmed the
    previously listed need for further information and re-allocated the
    temporary ADI at a lower level.

    The 1977 Meeting recorded a desirability for the results from further
    studies on residues in crops.  The 11th Session of the CCPR, when
    considering the temporary MRLs for apples and pears suggested by the
    Meeting, asked for the figures to be reevaluated in the light of new
    information.

    These aspects are covered in this monograph addendum.

    Toxicological Comments

    The Meeting re-evaluated a previously reported study in man in which
    it was incorrectly stated that five people were administered
    carbophenothion at a dose of 0.8 mg/kg body weight/day for 30 days.
    This study, reviewed in 1972, gave rise to the questions relating to
    species sensitivity.  Upon reevaluation, this problem was resolved. 
    In the study no significant alteration in plasma or RBC cholinesterase
    activity was reported at the dose level of 0.8 mg/man/day.

    In light of the re-evaluation and in consideration of the previous
    evaluation, the Meeting allocated an acceptable daily intake, as
    follows.

    Level Causing No Toxicological Effect

    Rat: 3 ppm in the diet, equivalent to 0.15 mg/kg body weight
    Dog: 0.02 mg/kg body weight
    Man: 0.8 mg/man/day, corresponding to 0.01 mg/kg body weight

    Estimate of Acceptable Daily Intake for Man

    0-0.0005 mg/kg body weight

    RESIDUES IN FOOD AND THEIR EVALUATION

    Use Pattern

    Preharvest on apples and pears

              Country        Rate                Pre-harvest
                                                 Interval (days)
                                                                   

              USA            Up to 1.25 lb 30    30
                             a.i./A

    RESIDUES RESULTING FROM SUPERVISED TRIALS

    Considerable residue data for carbophenothion on apples and pears,
    representing several states, were received from the United States
    (Stauffer).  Determination was by cholinesterase inhibition.  Because
    of the late arrival at the Meeting, much of these data were not in a
    format for inclusion in the monograph in tabular form.  However, data
    which could not be readily tabulated in tabular form were presented in
    a residue decline curve form after adjusting to the U.S. dosage of 20
    oz/A.  A half-life of 30 days on apples was indicated by the
    analytical method used.

    For those data which could not be readily tabulated the estimated
    maximum residues from the decline curves at 30 days is summarized
    below:

    Estimated

              Formulation           Estimated
                                     Maximum
                                  Residue (mg/kg)
                                                   

                 4-F                  1.1
                 4-EV                 1.6
                 25W                  1.6

    Data which could be readily tabulated are summarized in Table 1. The
    above estimates together with the high value of 0.85 in Table 1 at 29
    days demonstrate that the proposed 0.5 mg/kg temporary MRL is too low.

    FATE OF RESIDUES

    In Plants

    A study on the metabolism of phenyl-14C carbophenothion in orange
    trees was received (McBain, et al, 1971) but did not arrive in time
    for evaluation at this Meeting.  This information will be evaluated at
    the next scheduled evaluation of this compound.



        TABLE 1.  Residues of Carbophenothion on Apples and Pears (U.S.A. 1956/57)

                                                                                                                            

    CROP                  Application                   Residues in mg/kg, at intervals (days) after applicationsa
    Locality            rate       formulationd      0          1-3        5-7        12-13      14-15    21-25     27-31
                     oz. ai/A
                                                                                                                            

    APPLES

    Cal.             20            4-F              1.3                    0.64                  0.71     0.61      0.56
                     20            25-W             0.89                   0.59                  0.54     0.51      0.45
    N.Y.             24                             2.2                    0.70                           0.50      0.40
    Wash.            32            4-F                       2.9, 2.3                 1.8                 0.74
                     16            2-D              0.17     0.2, 0.13     0.09

    PEARS

    Wash.            32            4-F                       3.1, 1.8                 1.2
    Cal.             20            4-F              1.7                    1.76                           0.15
                                                    7.3                               1.6                           0.67b
                                                    2.4                    2.3                   1.5                0.85c
                     24            4-F              1.9                    1.3                   .64                0.50
                                                    1.1                    .89                   .37                0.28
                     Oz./100 gal
                     8             4-F                                                           1.6
                                                                                                 1.8
                                                                                                 0.95
                     4                                                                           1.2
                     4             4-EV                                                                   1.0
                     8                                                                                    1.8
                                                                                                          2.4
                                                                                                          2.5
                                                                                                                            

    a  Uncorrected for controls
    b  27 days (control 0.65 ppm apparent carbophenothion)
    c  29 days (control 0.02 ppm)
    d  4-F is an emulsion; 4-EV is an emulsifiable concentrate; 25-W is a wettable
    


    EVIDENCE OF RESIDUES IN FOOD IN COMMERCE OR AT CONSUMPTION

    No new data were available.

    NATIONAL MRLs REPORTED TO THE MEETING

    None reported.

    APPRAISAL

    Additional residue data from the use of carbophenothion on apples and
    pears were received from the U.S.A. as promised at the 11th Session of
    the CCPR.  Also received was a metabolism study for orange trees
    submitted in response to a request from the 1977 Meeting for further
    elucidation of the structure of terminal residues on crops.  The
    metabolism study arrived too late to permit evaluation at this Meeting
    and is reserved for the next scheduled review of this compound.

    The additional data for carbophenothion on apples and pears were
    determined by cholinesterase inhibition and indicate that the current
    0.5 ppm temporary MRL is too low.  Even the meagre data on which basis
    the current 0.5 ppm limit was made suggests that residues could be 0.7
    ppm at 30 days after application according to good agricultural
    practice (1972 Evaluations).

    The additional data indicate that residues could exceed even 1 ppm
    when determined by cholinesterase inhibition.  However, the high
    values and variability of controls on apples from the use of the
    cholinesterase method almost certainly result in apparent residues
    greater than actual, as could be elucidated by residue data from
    current analytical methods.

    RECOMMENDATIONS

    It is recommended that the previous recommendation on apples and pears
    be revised to the following:

              Commodity           MRL (mg/kg)*
                                                
              Apples, pears             1

    FURTHER WORK OR INFORMATION

    Desirable:

    1.  Studies on identity and relative toxicity of metabolites.

                   
    *Residues refer to the sum of carbophenothion, its sulphoxide and
    sulphone, together with their corresponding oxygen analogues.

    2.  Additional residue data for carbophenothion on apples and pears
    resulting from good agricultural practice in the USA and other
    countries and determined by current analytical methods.

    3.  Additional information listed as desirable by the 1977 meeting.

    REFERENCES

    McBain, J.B., Wren J.P. and Menn, J.J.  Metabolism of (Phenyl-14C)
    Carbophenothion by Orange Trees.  (1977) Unpublished data submitted by
    Stauffer - Chemical S.A., 25 rue des Carboubiers, 1227 Carouge,
    Geneva, Switzerland.

    Stauffer.  Section D, residue data on apples and pears from US
    Petition No.120 and as submitted with Dec. 23, 1957 labels to US
    regulatory agencies.  Made available by Stauffer Chemical Company,
    1200 S. 47th St. Richmond, CA, 94804.
    


    See Also:
       Toxicological Abbreviations
       Carbophenothion (ICSC)
       Carbophenothion (WHO Pesticide Residues Series 2)
       Carbophenothion (Pesticide residues in food: 1976 evaluations)
       Carbophenothion (Pesticide residues in food: 1977 evaluations)
       Carbophenothion (Pesticide residues in food: 1980 evaluations)
       Carbophenothion (Pesticide residues in food: 1983 evaluations)