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    1967 EVALUATIONS OF SOME PESTICIDE RESIDUES IN FOOD

    THE MONOGRAPHS

    The content of this document is the result of the deliberations of the
    Joint Meeting of the FAO Working Party of Experts and the WHO Expert
    Committee on Pesticide Residues, which met in Rome, 4 - 11 December,
    1967. (FAO/WHO, 1968)

    FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS
    WORLD HEALTH ORGANIZATION
    Rome, 1968

    ZIRAM

    This pesticide was evaluated toxicologically by the 1965 Joint Meeting
    of the FAO Committee on Pesticides in Agriculture and the WHO Expert
    Committee on Pesticide Residues (FAO/WHO, 1965). Additional
    toxicological information, together with information for evaluation
    for tolerances, is summarized and discussed in the following monograph
    addendum.

    EVALUATION FOR ACCEPTABLE DAILY INTAKES

    Short-term studies

    Rat. In a reproduction study, rats were given ziram in doses of 10
    and 50 mg/kg/day and zineb in doses of 50 and 100 mg/kg/day orally for
    2-6 months. Sterility, resorption of fetuses and anomalous tails in
    new born rats were observed at the high levels. The lower doses did
    not cause any significant changes, compared with a control group
    (Ryazanova, 1967).

    Long-term studies

    Rat. Weanling rats in groups of 25 males and 25 females were fed
    diets containing 25, 250 and 2500 ppm of ziram for 2 years. Growth was
    reduced at the highest concentration only; life-span was normal in all
    groups. Neurological changes were observed in the animals receiving
    2500 ppm but not at the lower levels. In some of the males the testes
    were atrophied and there was a slight indication of thyroid
    hyperplasia, notably in the 2500 ppm group. There was no increase in
    tumour incidence in the treated animals (Hodge et al., 1956).

    Comments on experimental studies reported

    Although ziram was only found in trace amounts in tissues of rats and
    dogs fed the compound, storage of metabolites should be investigated
    as part of the metabolic studies needed on the dithiocarbamates.

    In long-term studies in the rat a level of 250 ppm was without
    toxicological effect.

    From the one-year study in the dog the daily dose of 5 mg/kg body-
    weight was without toxicological effect.

    The chemical nature of the residues of ziram in or on the plant has
    not been ascertained. Studies are needed on the metabolism of the
    dithiocarbamates. While these data are being obtained a temporary ADI,
    based on the long-term studies in the rat, is proposed.

    TOXICOLOGICAL EVALUATION

    Level causing no toxicological effect

    Rat. 250 ppm in the diet, equivalent to 12.5 mg/kg body-weight per
    day.

    Dog. 5 mg/kg body-weight per day.

    Estimate of temporary acceptable daily intake for man

    0 - 0.025 mg/kg body-weight (alone or in combination with other
    dimethyl-dithiocarbamates).

    This value is based on experiments carried out with ziram and does not
    take account of chemical alterations after application.

    Further work required

    Studies of the compound in plants to determine the chemical nature of
    the residues, followed by appropriate toxicological studies.

    Results of the above work should be made available not later than 30
    June 1971 after which a re-evaluation of this compound will be made.
    The re-evaluation may be made at an earlier meeting should relevant
    information become available.

    EVALUATION FOR TOLERANCES

    USE PATTERN

    Pre-harvest treatments

    Ziram is used primarily as a pre-harvest spray to protect a number of
    agricultural products from plant pathogens.

    RESIDUES RESULTING FROM SUPERVISED TRIALS

    Twelve applications of equal parts ziram and ferbam at 2 lb/acre to
    celery and allowing 7 days for weathering resulted in a residue of 10
    ppm (trimmed) and 4.1 ppm (trimmed and washed). Spraying snap beans
    with one application at 1 1/2 lb/gal/acre and a 6 day time interval
    before sampling resulted in a residue of 3.2 ppm.

    RESIDUES IN FOOD AT TIME OF CONSUMPTION

    A recent survey of five composite basic 2-week diets for males 14-19
    years old showed the presence of 6 dithiocarbamates with values
    ranging from 0.4 to 0.8 ppm (Duggan, Barry and Johnson, 1966). No
    residues were found in a more recent survey based upon the analyses of
    prepared foods (Duggan and Weatherwax, 1967), possibly because the
    residues decomposed rapidly as the foods were being prepared.


        NATIONAL TOLERANCES

                                                                                                             

    Country         Tolerance, ppm                        Crop                                Reference
                                                                                                             

    Canada               7            apples, apricots, beans, beets, blackberries,           FDD, Canada
                                      black-eyed peas, blueberries, broccoli,                 (1967)
                                      Brussels sprouts, cabbage, carrots, cauliflower,
                                      celery, cherries, collards, cranberries,
                                      cucumbers, eggplants, gooseberries, grapes, kale,
                                      kohlrabi, lettuce, loganberries, melons, mustard
                                      greens, nectarines, onions, peaches, peanuts,
                                      pears, peas, peppers, pumpkins, quinces, radishes,
                                      raspberries, rutabagas, spinach, squash,
                                      strawberries, summer squash, tomatoes turnips;

    U.S.                 7            apples, apricots, beans, blackberries, blueberries,
                                      broccoli, cabbage, cantaloupe, carrots, celery,
                                      cherries, citrus fruits, cranberries, cucumbers,
                                      gooseberries, grapes, lettuce, loganberries, peaches,
                                      pears, peppers, plums, potatoes, prunes, raspberries,
                                      squash, strawberries;

    West Germany         3            leafy vegetables, fruits and pulses;
                                                                                                             
    

    METHODS OF RESIDUE ANALYSIS

    Residues have been determined by releasing either the dimethylamine
    (Barr, Clerk and Jacks, 1957) or the carbon disulfide (Pease, 1957) on
    acid treatment of the sample and measuring the intensity of a coloured
    copper complex formed. Since the colour formation is critical an
    improved modification has been outlined (Cullen, 1964). Better
    recoveries from a variety of crops have resulted from changes in the
    order of the acid decomposition procedure (Gordon, Schuckert and
    Bornak, 1967). Methods using polarographic techniques have also been
    developed (Nangniot, 1966; Vogeler, 1967).

    RECOMMENDATIONS FOR TOLERANCES

    Although some progress has been reported, neither the chemical nature
    nor the mode of action of the residues of ziram, in or on the plant
    have been ascertained and there is no specific method of analysis
    available. Accordingly, no tolerance figures can be recommended.

    FURTHER WORK

    Further work required

    Further work is required on the metabolism of ziram in or on the plant
    to include the identification and mode of action of any critical
    intermediates. The data on this subject is required prior to 30 June
    1971.

    REFERENCES PERTINENT TO EVALUATION FOR ACCEPTABLE DAILY INTAKES

    Hodge, H.C., Maynard, E.A., Downs, W.L., Coye, R.D. & Steadman, L.T.
    (1956) J. Pharmacol. exp. Ther., 118, 174

    Ryazanova, R.A. (1967) Gigiena i sanitaria, 2, 26

    REFERENCES PERTINENT TO EVALUATION OF TOLERANCES

    Barr, H.E., Clark, P.J., Jacks, H. (1957) Determination of
    tetramethylthiuram disulfide and dimethyldithiocarbamate sprays on
    apples. New Zealand J. Sci. Tech. Sect. B, 38: 425-532.

    Cullen, T.E. (1964) Spectrophotometric determination of
    dithiocarbamate residues in food crops. Anal. Chem. 36: 221-224.

    Duggan, R.E., Barry, H.C., Johnson, L.Y. (1966) Pesticide residues in 
    total diet samples. Science 151: 101-104.

    Duggan, R.E., Weatherwax, J.R. (1967) Dietary intake of pesticide
    chemicals, Science 157: 1006-1010.

    FDD/Canada. (1967) Food and Drug Directorate, Canada. T. I. L. 290, 15
    September

    Gordon, C.F., Schuckert, R.J., Bornak, W.E. (1967) Improved method for
    the determination of ethylenebisdithiocarbamate residues in plants,
    fruits and vegetables. J. Assoc. Off. Anal. Chem. 50: 1102-1108.

    Nangniot, P. (1966) L'application des methodes electrochimiques a 
    l'etude des residus des pesticides. Medel. Landbouwhogeschool 
    Opzoekingstat. Staat Gent 31: 447-473

    Pease, H.L. (1957) Determination of dithiocarbamate fungicide
    residues. J. Assoc. Off. Agric. Chem. 40; 1113-1118.

    Vogeler, Von K. (1967) Kolorimetrische und polarographische
    bestimmungen von ruckstanden in und auf pflanzen nach anwedung von
    Antracol. Pflanzenschutz-Nachrichte Bayer.
    


    See Also:
       Toxicological Abbreviations
       Ziram (ICSC)
       Ziram (FAO Meeting Report PL/1965/10/1)
       Ziram (Pesticide residues in food: 1996 evaluations Part II Toxicological)
       Ziram (IARC Summary & Evaluation, Volume 53, 1991)