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    DINOCAP       JMPR 1974

    Explanation

         Dinocap was evaluated at the Joint Meeting in 1969 (FAO/WHO,
    1970) at which time neither an acceptable daily intake nor tolerances
    could be established because the data were insufficient. Further
    information was required on the compounds included in dinocap, on the
    nature of terminal residues and on residues in countries other than
    the USA. Assurance of a standardized technical product was also
    required.

         Since the 1969 meeting, some additional experimental work has
    been reported.

    IDENTITY

    Composition of Technical Product

         Data on the composition of two dinocap products, Karathane
    Technical and Karathane WD, from the same manufacturer have been
    reported (Kurtz et al., 1970). Data were presented on the GLC analysis
    of Karathane Technical samples over the period December 1963 to May
    1969. Karathane Technical contained approximately 74% (range 72.0
    - 76.7%) of 2,4- and 2,6-dinitro-octylphenyl crotonates and
    approximately 6% of mixed nitro-octylphenyls, 0.54 - 0.86%
    mononitro-octylphenols and 4.0 - 6.9% dinitro-octylphenols.
    Non-volatile material accounted for 6 - 13%. Infra-red and biological
    examination of the non-volatile fraction indicated that the material
    was a complex polymeric mixture, inactive against mildews and fungi
    and not phytotoxic.

         GLC analysis of the technical dinitro-octylphenols showed that
    ortho-octyl isomers (2,4-dinitro-6-octylphenols) and the para-octyl
    isomers (2,6-dinitro-4-octylphenols) made up 65.6 - 69.3 and
    30.7 - 34.4% respectively of the dinitro-octylphenols in the
    formulation.

         Analysis of four Karathane WD samples showed 16.8 - 17.7%
    2,4- and 2,6-dinitro-octylphenyl crotonates, 2.4 - 3.1%
    dinitro- octylphenols and 0.19 - 0.21% mononitro-octylphenols giving
    a total active ingredient content of 19.4 - 20.7%, which is in good
    agreement with the declared content.

         The foregoing data demonstrated that the composition of Karathane
    Technical was relatively constant over the period 1963-1969. The
    limited data on Karathane WD showed good agreement between the total
    active ingredient found and the value to be expected from the assay of
    Karathane Technical.

         Data were not available to the Meeting to evaluate the
    composition of other manufacturers' products.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

         This compound was reconsidered by the 1974 Joint Meeting on the
    basis of two new metabolism studies (Rohm and Haas, 1970; Graham and
    Bornak, 1972). These studies, however, did not meet Joint Meeting data
    requirements (FAO/WHO, 1970) for an ADI. The Meeting emphasized that
    additional studies with a larger number of ducks at various dose
    levels were needed to establish the exact dosage of dinocap which does
    not produce cataracts.

         Significant data were not available to allocate an ADI for man.

    RESIDUES RESULTING FROM SUPERVISED TRIALS

         Studies with 14C-dinocap fed to rats and cows are described in
    detail in the following section. Rats fed 10 mg per day for seven days
    followed by a four-day withdrawal period showed low levels of
    radioactivity in the tissues, the highest being in the liver and
    kidney and corresponding to about 3.5 mg/kg, calculated as dinocap.
    Lactating cows fed up to 1 ppm in the diet had no detectable residues
    in milk or tissues. Although the feeding levels were low, they
    reflected those likely to be encountered in practice.

    FATE OF RESIDUES

    In Animals

         One adult female and one adult male albino rat were each dosed
    for 7 consecutive days with 14C-dinocap, labelled uniformly in the
    aromatic ring (Rohm and Haas, 1970). The dosing period was followed by
    a four-day withdrawal period prior to slaughter. The daily dose was
    10 mg/animal or 500 ppm in the daily diet. The results of this study,
    summarized in Table 1, showed that virtually all of the dinocap and/or
    its metabolites was quickly excreted in the faeces and urine, about
    equally by each route. Only approximately 0.3% of the administered
    dinocap and/or metabolites remained in the tissues or organs. The
    tissue and organ residue data, Table 2, show that there was no
    tendency for residues to concentrate in any particular tissue or
    organ. The highest levels of radioactivity were in the kidney and
    liver, where they were equivalent to about 3.5 mg/kg calculated as
    dinocap.

         Dinocap, uniformly 14C-labelled in the aromatic ring was
    administered to 3 lactating Holstein dairy cows at dosing levels of
    0.1, 0.3 and 1.0 ppm based on the total daily diet (Graham and Bornak,
    1974). The sensitivity of detection of radioactivity was 0.004 mg/kg
    in milk and urine, 0.05 mg/kg in fat and 0.04 mg/kg in other tissues.
    Dinocap and/or its metabolites were eliminated almost entirely in the
    faeces with only small quantities in the urine. No radioactive
    residues above control levels were found in either the milk or the
    tissues at any of the dosing levels. Recovery of all the administered
    dinocap in the excreta was satisfactory.

    TABLE 1.  14C-dinocap material balance in rate fed 14C-dinocap
              in the diet

                                                                             

                                        Percent Recovery of
                                      Total Administered Dose
    Sample                        Female Rat               Male Rat
                                                                             

    Urine                            38.4                     50.8

    Faeces                           63.5                     49.5

    Cage Wash                         2.4                      2.5

    CO2                               0.2                      0.2

    Tissues and Organs                0.3                      0.3
                                                                             

    TOTAL                           104.8                    103.3
                                                                             


    TABLE 2  Residue data and recovery of radioactive residues in tissues
             and organs of rats fed 14C-dinocap in the diet

                                                                             

                                      FEMALE                   MALE
                                 mg/kg     Recovery      mg/kg      Recovery
    Organ                        average   %1            average    %1
                                                                             

    Kidneys                       3.48       0.007       2.76      0.006

    Liver                         3.31       0.034       3.79      0.044

    Stomach and Intestine         2.21       0.044       1.12      0.025

    Skin and Hair                 2.14       0.080       2.66      0.110

    Blood                         1.34       0.003       0.83      0.004

    Fat                           0.98       0.002       0.58      0.001

    Carcass                       0.92       0.160       0.51      0.080

    Adrenals                      0.82       0.000       0.83      0.000

    TABLE 2  (Cont'd.)

                                                                             

                                      FEMALE                   MALE
                                 mg/kg     Recovery      mg/kg      Recovery
    Organ                        average   %1            average    %1
                                                                             

    Spleen                        0.73       0.001       0.67      0.001

    Lung                          0.73       0.001       0.63      0.001

    Heart, Aorta, and Thymus      0.68       0.001       0.49      0.001

    Trachea and Esophagus         0.68       0.000       0.52      0.000

    Gonads                        -          -           0.25      0.002

    Ovaries and Oviduct           0.65       0.000       -         -

    Submaxillary Lymph Nodes      0.49       0.001       0.44      0.000

    Skeletal (Bone, Muscle)       0.42       0.001       0.25      0.001

    Brain, Spinal Cord,
      Pituitary                   0.13       0.000       0.16      0.000
                                                                             

    1  Recovery is based on total administered dose of 1.44  107
       DPM  7 = 1.01  108 DPM.


    METHODS OF RESIDUE ANALYSIS

         Colorimetric methods of residue analysis described in the 1969
    monograph (FAO/WHO, 1970) determine the dinitrophenol moiety. These
    methods are nonspecific since they would include residues of
    dinitrophenols arising from other sources. Such methods are suitable
    to determine residues in samples from supervised trials but not for
    regulatory purposes. Similar concerns were discussed in the 1969
    monograph (FAO/WHO, 1970) on binapacryl where colorimetric methods
    suggested for binapacryl will also determine its metabolite,
    2-sec-butyl-4,6-dinitrophenol (dinoseb) which also has uses as a
    pesticide. Other pesticides such as dinoprop, dinosam, dinoterbon,
    DNOC, etc., would also interfere with or be determined by the
    colorimetric methods for dinocap. The development and evaluation of a
    specific residue method for dinocap suitable for regulatory purposes
    is required.

    EXAMPLES OF NATIONAL TOLERANCES REPORTED TO THE MEETING

                                                                             

                                                                   Tolerance
    Country        Commodity                                       (mg/kg)
                                                                             

    Australia      Apples, apricots, beets, carrots,
                   citrus, corn, cucumbers, grapes,
                   melons, onions, peaches, pears,
                   peppers, plums, potatoes,
                   tomatoes                                        7

    Belgium        Apples, apricots, beets, carrots,
                   citrus, corn, cucumbers, grapes,
                   melons, onions, peaches, pears,
                   peppers, plums, potatoes,
                   tomatoes                                        1

    Canada         Apples, cucumbers, grapes,
                   melons, peas, squash                            NR1

    Federal Rep.   Apples, apricots, beets, carrots,
    of Germany     citrus, corn, cucumbers, grapes,
                   melons, onions, peaches, pears,
                   peppers, plums, potatoes,
                   tomatoes                                        1

    Netherlands    Apples, apricots, beets, carrots,
                   citrus, corn, cucumbers, grapes,
                   melons, onions, peaches, pears,
                   peppers, plums, potatoes,
                   tomatoes                                        1

    Switzerland    Apples, apricots, citrus,
                   cucumbers, grapes, melons,
                   peaches, pears, plums                           0.1

    U.S.A.         Dried apple pomace                              0.32

                   Apples, apricots, cantaloupes,
                   cucumbers, grapes, honeydew
                   melons, muskmelons, nectarines,
                   peaches, pears, pumpkins,
                   squash (summer and winter),
                   watermelons                                     0.12
                                                                             

    1  Negligible residues (< 0.05 ppm).

    2  Including related nitro-octylphenols (principally dinitro, calculated
       as the ester).

    APPRAISAL

         Data presented to the Meeting concerning dinocap technical
    material (Karathane Technical from one manufacturer) indicated that
    this material was of relatively constant composition. This was
    confirmed by analyses of a formulation from the same manufacturer.
    Information was not available on technical materials or formulations
    from other manufacturers.

         Dinocap administered to animals is rapidly excreted. Residues
    were not detected in the milk or tissues of cows given 14C-dinocap in
    their diet at levels likely to be encountered in crop materials fed to
    cows. Colorimetric methods discussed in the 1969 Monograph (FAO/WHO,
    1970) would be adequate for the determination of residues of the
    parent compounds in samples from supervised trials but not suitable
    for regulatory purposes. Data are not available on the metabolism or
    degradation of dinocap.

         National tolerances are in effect in a number of countries.

    RECOMMENDATIONS

         The residue data from the 1969 monograph (FAO/WHO, 1970) were
    reviewed together with new information on technical material and
    animal studies. Since no ADI was established, no recommendations for
    tolerances could be made. However, provided good agricultural practice
    is observed, the following levels of dinocap and related
    nitro-octylphenols, expressed as dinocap, need not be exceeded.

    GUIDELINE LEVELS 1

    Crops                                                 mg/kg

    Apples, apricots, blackberries, boysenberries,
    cantaloupes, cucumbers, grapes, honeydew
    melons, muskmelons, peaches, pears, pumpkins,
    raspberries, squash, strawberries                    0.1 2

                
         1 Recommended guideline levels are based on following
         pre-harvest intervals: cantaloupes, cucumbers, honeydew melons,
         muskmelons, pumpkins, squash - 7 days; blackberries,
         boysenberries, raspberries - 14 days; apples, apricots, peaches,
         pears, strawberries - 21 days; grapes - 28 days.

         2 At or about the limit of determination.

    FURTHER WORK OR INFORMATION

    REQUIRED

    1.   Information on the nature of dinocap residues.

    2.   Residue data from countries other than the U.S.A. and Canada.

    3.   The development and evaluation of a specific residue method
         suitable for regulatory purposes.


    REFERENCES

    FAO/WHO.  (1970) 1969 Evaluations of some pesticide residues in food.
    FAO/PL/1969/M/17/1; WHO/Food Add./70.38.

    Graham, W.H. and Bornak, W.E. (1974) A study to determine residue
    levels in milk and tissues from cows fed C14-Karathane. Report No.
    23-49. Rohm and Haas Company, Philadelphia, USA. (Unpublished).

    Kurtz, C.P., Baum, H. and Swittenbank, C. (1970) Gas chromatographic
    determination of total active ingredient content of Karathane
    Technical and Karathane WD. I. Development of the method. J. Ass. off.
    analyt. Chem., 53:887-895.

    Rohm and Haas. (1970) A material balance study in rats using
    C14-Karathane uniformly labelled in the aromatic ring. Report No.
    23-27. Rohm and Haas Company, Philadelphia, USA. (Unpublished).
    


    See Also:
       Toxicological Abbreviations
       Dinocap (FAO/PL:1969/M/17/1)
       Dinocap (Pesticide residues in food: 1989 evaluations Part II Toxicology)
       Dinocap (JMPR Evaluations 1998 Part II Toxicological)