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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

    ZINEB

    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.

    IDENTITY

    Other relevant chemical properties

    There are various proprietary formulations of zineb, including
    Parzate, Dithane Z-78, Siaprit and Polyram (also known as Metiram, a
    zinc-activated polyethylene thiuramdisulfide).

    Parzate and Dithane Z-78 contain 65 per cent of active ingredient and
    are formulated for use as dusts or water suspensions. Siaprit, on the
    other hand, contains 45 per cent zineb plus 5 per cent ethylene
    thiuram monosulfide (ETM), together with the usual inert diluents,
    dispersants, stickers, etc. Polyram (Metiram) is formulated as an 80
    per cent wettable powder, a 53.5 per cent seed protectant for cereals
    and flax and a 7 per cent duct for foliar dusting and potato seed
    treatment.

    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).

    Comments on experimental studies reported

    The lowest level used in the long-term study in the rat, 500 ppm,
    produced a goitrogenic effect. This was the only effect seen at this
    level.

    In the one-year study in the dog a level of 2000 ppm (50 mg/kg) was
    associated with normal thyroid, and no toxicological effects were
    observed at this level.

    Apart from the goitrogenic effect in the rat, zineb is less toxic than
    ziram in both rat and dog. A temporary ADI may be estimated using the
    no-effect level in the rat for ziram (250 ppm), until data containing
    a level that is non-goitrogenic in rats are provided.

    TOXICOLOGICAL EVALUATION

    Estimate of temporary acceptable daily intake for man

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

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

    Further work required

    Studies in the rat, using levels below 500 ppm, to establish a level
    that is non-goitrogenic.

    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

    Zineb is primarily used as a pre-harvest spray or dust to protect
    agricultural crops, both fruit and plants, from invasion by fungal
    plant pathogens. Since the material is insoluble and non-systemic,
    spraying involves the whole plant.

    RESIDUES IN FOOD AT TIME OF CONSUMPTION

    A recent survey of five composite basic 2-week diets for males, 14 to
    19 years, showed the presence of six dithiocarbamates, ferbam, maneb,
    metiram, thiram, zineb and ziram with values ranging from 0.4 to 0.8
    ppm (Duggan, Barry and Johnson, 1966).

    FATE OF RESIDUES

    General considerations

    Residues are reduced by a variety of factors such as weathering,
    metabolism, physical removal by washing and trimming or brushing the
    food product. During weathering, moisture, air and the plant may
    participate in the production of a number of products such as
    ethylenethiuram monosulfide, ethylene thiourea and ethylene
    thiuramdisulfide.


        
    RESIDUES RESULTING FROM SUPERVISED TRIALS
                                                                                                          
                       Rate of         Number       Pre-harvest
                     application         of           interval
    Crop              (lb/acre)      applications      (days)      Residue (ppm)     Reference
                                                                                                          

    apples                                                           3.1             Rohm + Haas (1956)

    apples               2                6              49          0.15            du Pont (1957)

    celery               1               12               7         11 (unwashed)    Rohm + Haas (1956)
                                                                     3.4 (washed)         "

    cherries             2                4              30          3.6                  "

    cranberries          2                2              82          0.3                  "

    cucumbers            2                6               3          0.1             du Pont (1957)

    lettuce                               1               7          3.6             Rohm + Haas (1956)

    oats                                  2               2          nil                  "

    peppers              2                7              15          0.27            du Pont (1957)

    potatoes            13                9              25          nil                  "

    snapbeans            1.5              1               0          5.6                  "
                                                          3          7.6                  "
                                                          6          6.2                  "

    squash               2                7              30          0.05                 "

    tomatoes             1.5              1               0          1.7                  "
                                                                                                          
    

    Although the zinc salt is relatively inert and insoluble, degradation
    slowly occurs when exposed to the atmosphere. Ethylene thiuram
    disulfide (ETD) and ETM were identified (Morehart and Crossan, 1965)
    as well as ethylene thiourea (ETU) and an unknown (Fishbein and
    Fawkes, 1965) by chromatography. The former authors suggested, from
    their metabolism studies with fungal spores, that toxicity is due
    mainly to ETD. However others (Kovacs and Caumo, 1966) showed that a
    formulation (Siaprit) gradually releases ETM which is immediately
    effective in the control of the fungal pathogen. Zineb is insoluble
    while ETM, although water solubility is only 200 ppm, exhibits
    systemic activity (Kovacs and Caumo, 1966).

    The decomposition of radioactive labelled zineb when applied to plants
    has also been studied (Sato and Tomizawa, 1960). Chloroform extracts
    contained ETU and at least one other decomposition product.
    Accelerated decomposition by incubation with leaf washings was also
    shown (Kovacs and Cucchi, 1964).

    METHODS OF RESIDUE ANALYSIS

    To date the usual method of analysis is based on a colorimetric
    measurement of the carbon disulfide released on acid treatment of the
    residue with modifications for particular crops to get improved
    quantitative recovery (Gordon, Schuckert and Bornak, 1967).

    RECOMMENDATIONS FOR TOLERANCES

    Although some progress has been reported, neither the chemical nature
    nor the mode of action of the residues of zineb 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 before recommendations for tolerances can be
    made

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


        NATIONAL TOLERANCES
                                                                                              

    Country         Tolerance, ppm              Crop                         Reference
                                                                                              

    Canada                1           wheat                                  FDD, Canada (1967)

                          7           apples, apricots, beans, beets,
                                      blackberries, black-eyed peas,
                                      broccoli, Brussels sprouts,
                                      cabbage, carrots, cauliflower,
                                      celery, cherries, citrus fruits,
                                      collards, corn, cranberries,
                                      cucumbers, currants, eggplant,
                                      endive (escarole), gooseberries,
                                      grapes, guavas, kale, kohlrabi,
                                      lettuce, loganberries, melons,
                                      mushrooms, mustard greens,
                                      nectarines, onions, parsley,
                                      peaches, peanuts, pears, peas,
                                      peppers, plums (fresh prunes),
                                      pumpkins, quinces, radishes,
                                      raspberries, rutabagas, salsify,
                                      spinach, squash, strawberries,
                                      summer squash, Swiss chard,
                                      tomatoes, turnips.

    U.S.A.                1           wheat *                                USDA, 1967

                          7 **        apples, apricots, beans, beets,        USDA, 1967
                                      blackberries, broccoli, Brussels
                                      sprouts, cabbage, cantaloupes,
                                      carrots, cauliflower, celery,
                                      cherries, grapefruit, lemons, corn,
                                      cranberries, cucumbers, grapes,
                                      onions, peaches, peppers, radishes,
                                      strawberries, turnips.


                                                                                              

    Country         Tolerance, ppm              Crop                         Reference
                                                                                              
    U.S.A.               25           Swiss chard, ***   lettuce ****        USDA, 1967

    West Germany          3           leafy vegetables, fruits, pulses
                                                                                              

    *     3-4 week pre-harvest after application at 2.1 lb/acre
    **    various pre-harvest intervals following specific application rates
    ***   pre-harvest interval, 7 days
    ****  pre-harvest interval, head lettuce, 5 days.
    

    REFERENCES PERTINENT TO EVALUATION FOR ACCEPTABLE DAILY INTAKES

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

    REFERENCES PERTINENT TO EVALUATION FOR TOLERANCES

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

    du Pont. (1957) Submission to Food and Drug Directorate, Canada Dept.
    of Health and Welfare

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

    Fishbein, L., Fawkes, J. (1965) Thin layer chromatography of metallic
    derivatives of etheylenebis(dithiocarbamic acid) and their degradation
    products. J. Chromatog. 19 : 364-369.

    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.

    Kovacs, A., Cucchi, N.J.A. (1964) Influence of excreted substance from
    leaves on decomposition of zineb, a dithiocarbamate fungicide. Nature
    204 : 1090.

    Kovacs, A., Caumo, B. (1966) Systemicity of zinc
    ethylene-bisdithiocarbamate. Atti. Simp. Int. Agrochim. 6 : 263-269.

    Morehart, A.L., Crossan, D.F. (1965) Studies on the
    ethylenebisdithiocarbamate fungicides. Exp. Sta. Bull. 357, Agric.
    Exp. Stn. Univ. Delaware, Newark, Del. 26 p.

    Rohm and Haas. (1956) Submission to Food and Drug Directorate, Canada
    Dept. of Health and Welfare.

    Sato, T. and Tomizawa, C. (1960) Decomposition of zineb applied to
    plants. Bull. Natl. Inst. Agr. Sci., Ser. C, No. 12 : 181-187.

    USDA. (1967) Summary of registered agricultural chemical pesticide
    uses. 2nd ed. Suppl.III.
    


    See Also:
       Toxicological Abbreviations
       Zineb (ICSC)
       Zineb (FAO Meeting Report PL/1965/10/1)
       Zineb (Pesticide residues in food: 1993 evaluations Part II Toxicology)
       Zineb (IARC Summary & Evaluation, Volume 12, 1976)