THIOPHANATE - METHYL         JMPR 1977

    Explanation

    Thiophante-methyl was previously evaluated in 1973 and 1975 (FAO/WHO,
    1974, 1976). An acceptable daily intake of 0-0.08 mg/kg was allocated.
    Further data on the degradation of thiophante-methyl in vivo and
    in vitro have been made available and are summarized in the
    following monograph addendum.

    EVALUATION FOR THE ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, distribution, biotransformation and excretion

    Male mice (8 weeks old, 20-25 g b.w.) and rams (ca 26 weeks old,
    ca 35 kg b.w.) received a single oral dose of 0.1 mg/kg
    thiophanate-methyl (as aqueous suspension) and excreta were collected
    for 72 h p.a. The excretion of metabolites in the sheep was similar to
    that in the mouse:

                                            urine     faeces
    carbendazim                             16-19%    9-11%
    5-hyclroxyoarbendazim                   4-11%     5-9%
    2-aminobenzimidazole                    3%        3%
    5-hydroxy-2-aminobenzimidazole          0.5-2%    1-2%

    The metabolites carbendazim and 2-aminobenzimidazole appeared as free
    compounds; the hydroxylated products were found both free and as
    glucuronide and sulphate conjugates (Douch, 1974).

    Data from quantitative and qualitative metabolism studies with enzyme
    preparations from mouse and sheep liver give the following scheme for
    the degradation of thiophanate methyl (Figure 1).


    



    In vitro also some other metabolites have been isolated and
    identified:

    2-bis(3-methoxycarbonyl-2-thioureido)aniline
    1- (3-methoxycarbonyl-2-ureido) -2- (3-methoxycarbonyl-2-thioureido)
    benzene
    1,2-bis(3-methoxycarbonyl-2-ureido)benzene
    2-(3-methoxycarbonyl-2-ureido)aniline
    1-thioureido-2-(3-methoxycarbonyl-2-thioureido)benzene
    1-(2-ureido)-2-(3-methoxycarbonyl-2-thioureido)benzene
    1-(2-ureido)-2-(3-methoxycarbonyl-2-ureido)benzene

    When incubated separately with liver enzymes, these intermediates gave
    rise to the formation of the same carbendazim and imidazole compounds
    as in vivo studies. Mouse kidney and brain enzymes produced the came
    compounds, while enzymes from mouse intestine and sheep rumen fluid
    did not produce the benzimidazole derivatives (Douch, 1974).

    COMMENTS

    New data on biochemical aspects were made available. The Meeting
    reconfirmed the previously established ADI for humane of
    0-0.08 mg/kg bw.

    REFERENCES

    Douch, P.G.C. (1974) The metabolism of some thicuraidobenzene
    fungicides in mice and sheep. Xenobiotica 4, 457-475.

    FAO/WHO (1974) 1971 evaluations of some pesticide residues in food.
    AGP:1973/M/9/1; WHO Pesticide Residue Series No. 3.

    FAO/WHO (1976) 1975 evaluations of some pesticide residues in food.
    AGP:1975/M/13; WHO Pesticide Residue Series No. 5.
    

    See Also:
       Toxicological Abbreviations
       Thiophanate-methyl (WHO Pesticide Residues Series 3)
       Thiophanate-methyl (WHO Pesticide Residues Series 5)
       Thiophanate-methyl (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)