CRUFOMATE                                  JMPR 1972


    This insecticide was previously evaluated in 1968 (FAO/WHO, 1969) at
    which time an acceptable daily intake and temporary tolerances were
    recommended. Four requirements for further work or information were
    set forth. Since the previous evaluation, additional data and
    information have become available.

    At the Sixth Session of the Codex Committee on Pesticide Residues, it
    was requested that the Joint Meeting clarify the question of the
    distribution of the pesticide between the fat and aqueous phase of


    Fulfillment of requirements

    In the following paragraphs, the numbers refer to the corresponding
    requirement set forth by the 1968 Joint Meeting.

    1.   Data from countries other than the United States of America and
         the United Kingdom on use pattern and residues

         No data were available from countries other than U.S.A. and U.K.
         However, the manufacturer gave written assurance that the main
         uses were only in these two countries (Dow Chemical Co., 1972).
         New data were supplied which gave more details on use patterns
         and withdrawal periods recommended, which are summarized in the
         following sections.

    2.   Further data on use pattern and residues in milk

         No gas chromatographic data were available; however, the results
         shown In Table 1 were obtained using the indicated methods.

    3.   Data on residues in the non-fatty portion of meat and meat

         Data were available from supervised trials which indicated the
         distribution of crufomate in body tissues of cattle and sheep
         after various applications. These are summarized in Table 2.

        TABLE 1  Residues in milk following application of crufomate to dairy cattle


    No. of       Application1         Post-
    animals   type         rate       treatment     Residues in      Sensitivity (ppm)
                           (mg/kg)    interval      milk (ppm)       and method2
    1         Topical-     50         12 h          0.18             0.02
              pour-on                 2 days        0.09             (Flyhead CLE
                                      2 days        0.03             inhibition)
                                      3-8 days      <0.02

    1         pour-on      37         12 h          0.24             "
                                      1 day         0.08
                                      2-4 days      <0.02

    1                      52.4       6 h           0.100            0.025
                                      22 h          0.042            (P determination)
                                      28 h          0.028
                                      46 h          0.024

    1                      49.2       6 h           0.170            "
                                      12 h          0.024
                                      28 h          0.026
                                      46 h          0.014

    1         pour-on      65.9       6 h           0.195            0.025
                                      22 h          0.053            (P determination)
                                      28 h          0.066
                                      46 h          0.057

    3         "            55.6       12 h          0.100-0.195      0.02
                                      1 day         0.020-0.042      (P determination)
                                      2 days        0.014-0.057

    1         Oral         37.5       1 day         0.14             0.02
              (drench)                2 days        <0.02            (Flyhead ChE
                                      3 days        <0.02            inhibition)

    1         Intra -      10         12 h          0.08             0.02
              peritoneal              1 day         0.05             (Flyhead ChE
                                      2-4 days      0.02             inhibition)

    1    The recommended use pattern included all formulations of
         crufomate applied to dry dairy cattleg not to be used on
         lactating cattle nor applied within 3 days of freshening.

    2    Data obtained by coloximetric analysis are omitted because the
         sensitivity of the method (0.2 ppm) is not adequate for the
         recommended tolerance of 0.05 ppm.

    TABLE 2  Residues in animal tissues following application of crufomate


    No. of           Application                      treatment1     Residues in cattle tissues (ppm)2
    animals      type           rate (mg/kg)          interval       Fat              Muscle         Liver        Brain

    3            topical-       52-78                 7              (R) 0.2-0.7      0.05-0.3
                 spray                                               (S) 0.3-1.3

    3            "              105-156               7              (R) 0.5-0.8      0.2-0.9        0.06-0.2     0.2-0.3
                                                                     (S) 0.6-1.6

    3            "              52-78                 7              (R) 0.5-1.6      0.2-0.4

                                (3 treatments at                     (S) 0.8-1.4
                                7 day intervals)

    3            topical-       52-78                 7              (R) 0.06-0.2     0.05-0.2
                 spray                                               (S) 0.07-0.2

    3            spray          104-156               7              (R)<0.05-0.7     0.1-0.2
                                                                     (S) 0.1 -2.4
    3            "              52-78                 7              (R)<0.05-0.08    0.05-0.2
                                (3 treatments at                     (S) 0.1-0.2
                                7 day intervals)

    3            spray          37.5                  7              0.07-0.09        0.03-0.08      <0.02-0.07

    10           topical-       52                    7              (O)<0.02

    TABLE 2  (Cont'd.)


    No. of           Application                      treatment1     Residues in cattle tissues (ppm)2
    animals      type           rate (mg/kg)          interval       Fat              Muscle         Liver        Brain

    3            topical        52                    28             (S)<0.05         <0.05          <0.05
    3            "              104                   28             (S) 0.05-0.22    <0.05          <0.05
    5            "              52                    8              (O) 0.02
    5            "              39                    7              (O) 0.05-0.15

    2            oral           75                    14             (R)<0.05         <0.03

    1            spray          473 ml. of            14             (O) 0.18         0.025-0.035    0.90         0.15
                                2% emulsion                             (analyses by 32P)

                                                                     Residues in sheep tissues (ppm)

    1            oral           89.8                  14             0.002            0.004          0.018
    3            oral           200                   7              <0.03            <0.05
    3            oral           200                   7              <0.03            <0.05
                 (3 doses at 2-week intervals)

    1    For all formulations, all treatments, and all animals, the
         recommended withdrawal period is 7 days minimum between last
         application and slaughter.

    2    (R) - renal fat; (S) - subcutaneous fat; (O) - omental fat.

    4.   Comparative evaluation of gas-liquid chromatographic methods
         for regulatory purposes

         A gas chromatographic method of analysis for crufomate residues
         in animal tissues has been developed (Rice and Dishburger, 1970).
         The method employs a phosphorus-sensitive detector and has a
         limit of determination of about 0.02 ppm. The extraction and
         clean-up procedures employed for various tissues allow for the
         nearly equal partitioning of crufomate into fat and aqueous
         phases. The method has many features in common with existing
         multi-residue methods of analysis for phosphorus containing
         pesticides (Abbott et al., 1970; and Storherr et al., 1971).
         On the basis of these similarities and taking into account the
         chemistry of the compound (methyphosphoramidate) it would appear
         reasonable that crufomate would be detected by these existing
         multi-residue methods. However, in the absence of collaborative
         testing data to verify these assumptions, the preferable
         multi-residue methods cannot be recommended at this time. The
         more specific method, with appropriate adaptations, is therefore

         The method of analysis for residues in milk using flame
         photometric gas chromatography, which was described in the 1968
         evaluation of crufomate (Bowman and Beroza, 1967), would be
         suitable for adaptation to regulatory use.


    The four items of further work or information required by the 1968
    Joint Meeting are considered to have been met. Although no data were
    available from countries other than U.S.A. and U.K. on the use pattern
    and resultant residues, the manufacturers gave assurance that the main
    uses are in these two countries. New information was available which
    better defined the use patterns and withdrawal periods. No information
    was available on residues in milk from treated animals using gas
    chromatographic methods of analysis. However, the intent of this
    requirement was satisfied by new comparative data on milk residues
    obtained by fly-head cholinesterase inhibition methods, colorimetric
    methods and phosphorus determination methods which supported the
    previously recommended tolerance for milk of 0.05 ppm. Data were
    received on residues in the non-fatty portion of meat (muscle, heart,
    liver, kidney and brain) which showed that residues were about equally
    distributed between these tissues and fat. Therefore, the previously
    recommended tolerance on meat should be amended by deleting the
    bracketed term "(on fat basis)". A method of analysis of residues in
    meat has been developed which, with appropriate adaptations, would be
    suitable for regulatory purposes. The method of analysis for residues
    in milk using flame photometric gas chromatography, which was
    described in the 1968 evaluation of crufomate (FAO/WHO, 1969), is
    suitable for adaptation to regulatory use.



    The temporary tolerances in effect until 1972 are replaced by
    tolerances, as amended below:


         Meat                               1

         Milk (whole)                       0.05


    REQUIRED (If tolerance is to be recommended)

    Data on residues in milk products and partition into milk fat.


    Further information on residues in milk from treated animals using
    modern gas chromatographic methods of analysis.


    Abbott, D.C., Crisp, S., Tarrant, K.R. and Tatton, J.O.G. (1970)
    Pesticide Residues in the total diet in England and Wales, 1966-1967.
    III. Organophosphorus pesticide residues in the total diet, Pest.
    Sci., 1: 10-13 (Jan.-Feb., 1970).

    Bowman, M.C. and Beroza, M. (1967) Temperature programmed gas
    chromatography of twenty phosphorus-containing insecticides on four
    different columns and the application to the analysis of milk and corn
    silage. J. Ass. off. analyt. Chem., 50: 1228-1236.

    Dow Chemical. (1972) Residue data and recommended use patterns for
    crufomate in meat and milk (unpublished).

    FAO/WHO. (1969) 1968 Evaluations of some pesticide residues in food.
    FAO/PL: 1968/M/9/1; WHO/FOOD ADD./69.35.

    Rice, J.R. and Dishberger, H.J. (1970) Gas chromatographic
    determination of residues of crufomate, 4-tert-butyl-2-chlorophenyl-
    methyl methylphosphoromidate, in bovine muscle, liver, fat and blood
    tissues. ACR 70.4, 16 February 1970.

    Storherr, R.W., Ott, P. and Watts, R.R. (1971) A general method for
    organophosphorus pesticide residues. J. Ass. off. analyt. Chem., 54:

    See Also:
       Toxicological Abbreviations
       Crufomate (ICSC)
       Crufomate (FAO/PL:1968/M/9/1)