FAO/PL:1967/M/11/1
    WHO/Food Add./68.30

    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

    THIRAM

    This pesticide was evaluated by the 1965 Joint Meeting of the FAO
    Committee on Pesticides in Agriculture and the WHO Expert Committee on
    Pesticide Residues (FAO/WHO, 1965). A re-evaluation of the
    toxicological data and an evaluation for tolerances is given in the
    following monograph addendum.

    EVALUATION FOR ACCEPTABLE DAILY INTAKES

    Comments

    In long-term studies in rats toxic effects were seen at a level of 300
    ppm in the diet with questionable effects at 100 ppm. In a study that
    extended over three generations, a dietary level of 48 ppm was without
    toxicological affect. Chicks appear to be especially susceptible to
    thiram brut confirmation and extension of these experiments are
    needed.

    The biochemical investigations on the homologue, tetra ethyl thiuram
    disulfide, are considered relevant to the evaluation of thiram.

    It is known that tetra methyl thiuram disulfide in a dose of 0.5 to
    1.5 per day can be taken by man for many weeks without ill-effect
    unless alcohol is consumed.

    While additional data are being obtained, a temporary ADI, based on
    the long-term studies in rat, is proposed.

    TOXICOLOGICAL EVALUATION

    Level causing no toxicological effect

    Rat. 48 ppm in the diet, approximately equivalent to 2.5 mg/kg
    body-weight per day.

    Dog. 5 mg/kg body-weight/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 thiram 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

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

    RESIDUES IN FOOD AT TIME OF CONSUMPTION

    A recent survey of five composite basic 2-week diets for males 14-19
    years showed the presence of six 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.

    METHODS OF RESIDUE ANALYSIS

    Residues have been determined by releasing either the dimethylamine
    (Barr, Clark 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).

    NATIONAL TOLERANCES

    Thiram is registered for use in Canada on apples, celery, peaches,
    strawberries and tomatoes at a residue level of 7 ppm (FDD/Canada,
    1967). The United States use at the same level also includes bananas
    (1 ppm in pulp), while no tolerance has been set for a number of
    agricultural pesticide chemical uses (USDA, 1967). The West German
    tolerance has been set at 3 ppm for leafy vegetables, and fruits.

    RECOMMENDATIONS FOR TOLERANCES

    Although some progress has been reported, neither the chemical nature
    nor the mode of action of the residues of thiram 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 by 30 June 1971

    Further work is required on the metabolism of thiram in or on the
    plant to include the identification and mode of action of any critical
    intermediates.

    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 de pesticides. Mededel. Landbouwhogeschool
    Opzoekingstat. Staat Gent 31: 447-473.

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

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

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

    See Also:
       Toxicological Abbreviations
       Thiram (ICSC)
       Thiram (FAO Meeting Report PL/1965/10/1)
       Thiram (Pesticide residues in food: 1984 evaluations)
       Thiram (Pesticide residues in food: 1992 evaluations Part II Toxicology)
       Thiram (IARC Summary & Evaluation, Volume 53, 1991)