FAO Meeting Report No. PL/1965/10/1
    WHO/Food Add./27.65

    EVALUATION OF THE TOXICITY OF PESTICIDE RESIDUES IN FOOD

    The content of this document is the result of the deliberations of the
    Joint Meeting of the FAO Committee on Pesticides in Agriculture and
    the WHO Expert Committee on Pesticide Residues, which met in Rome,
    15-22 March 19651

    Food and Agriculture Organization of the United Nations
    World Health Organization
    1965

                
    1 Report of the second joint meeting of the FAO Committee on
    Pesticides in Agriculture and the WHO Expert Committee on Pesticide
    Residues, FAO Meeting Report No. PL/1965/10; WHO/Food Add./26.65

    ZIRAM

    Chemical name

           Zinc dimethyldithiocarbamate

    Empirical formula

           C6H12N2S4Zn

    Structural formula

    

    BIOLOGICAL DATA

    Biochemical aspects

           The compound ziram does not appear to be stored in the tissues of
    rats and dogs, but in the rat the feeding of ziram increases the
    skeletal stores of zinc (Hodge et al., 1956).

    Acute toxicity

                                                                      
    Animal         Route        LD50 mg/kg    References
                                body-weight
                                                                      

    Mouse     Intraperitoneal    73 and 17    Hodge et al., 1952
                                              Kligman & Rosenweig, 1948

    Rat            Oral          1400, 500    Disks et al., 1947
                                              Hodge et al., 1952

    Rat       Intraperitoneal      23-33      Hodge et al., 1952

    Rabbit         Oral             400       Brieger & Hodes, 1951
                                                                      

    Short-term studies

           Rat. Groups each of 10 male and 10 female weanling rats were
    fed diets containing 100, 500, 2500 and 5000 ppm of ziram for one
    month. Growth retardation was marked in the 5000 ppm group and
    somewhat less, though still evident, in the 2500 ppm group. There was

    also a slight retardation in the 500 ppm group, but growth was normal
    in the animals receiving 100 ppm. Except for slight anaemia in the
    2500 and 5000 ppm groups haematological findings were normal and no
    significant histopathological changes were seen in any of the animals
    (Hodge et al., 1952).

           In a separate experiment, 10 male and 10 female rats were
    maintained for one month on a diet containing 2500 ppm of ziram. No
    thyroid abnormalities were revealed (Hodge et al., 1952).

           Dog. One dog was given ziram and ferbam together for one month,
    each at a dosage of 5 mg/kg body-weight per day, without adverse
    effects, except for slight anaemia. Another remained healthy - again
    except for slight anaemia - when given ziram alone at a dosage of 25
    mg/kg body-weight daily for one month and also on 50 mg/kg body-weight
    per day for one week, though an attempt to raise the dosage to 100
    mg/kg body-weight per day immediately provoked severe vomiting and
    malaise (Hodge et al., 1952).

           Groups, each of 2 adult dogs, were given daily doses of 0.5, 5
    and 25 mg of ziram per kg body-weight for one year. At the highest
    dose, convulsions occurred. Urine analyses, haematological
    examinations, organ weights and histological appearances (including
    that of the thyroid) were normal (Hodge et al., 1956).

    Long-term studies

           Rat. Weanling rats in groups each of 25 males and 25 females
    were fed for 2 years diets containing 25, 250 and 2500 ppm of ziram.
    The growth-rate and life-span were normal in all groups; neurological
    changes were observed in the animals receiving 2500 ppm, but no cystic
    lesions were discovered in the brain post mortem. Neurological changes
    were not observed 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

           For ziram, as for most of the dithiocarbamates, short- and
    long-term studies in animals have been reported, but for all of them
    biochemical data are inadequate.

    EVALUATION

           The chemical nature of the residues of the dithiocarbamates in 
    or on the plant has not been ascertained. The compounds themselves 
    have effects on the thyroid, nervous system and blood in animals. In 
    the absence of information about their mode of action an acceptable 
    intake for man cannot be estimated.

    Further work required

           Determination and evaluation of toxicity of the residues
    occurring in the plant. Extension of the long-term studies, including
    reproduction studies which should concern at least two species.
    Special attention should be given to neurological changes,
    goitrogenicity and occurrence of anaemia.

    REFERENCES

    Brieger, H. & Hodes, W. A. (1949) Proc. 9th Intern. Congr. Ind.
    Med., London, 1948, 598-602

    Dieke, S. H. et al. (1947) J. Pharmacol. exp. Ther., 90, 260

    Hodge, H. C., Maynard, E. A., Downs, W. L., Blanchet, H. J. & Jones,
    C. K. (1952) J. Amer. pharm. Ass. sci. Ed., 41, 662

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

    Kligman, A. M. & Rosenweig, W. (1948) J. invest. Derm., 10, 59
    

    See Also:
       Toxicological Abbreviations
       Ziram (ICSC)
       Ziram (FAO/PL:1967/M/11/1)
       Ziram (Pesticide residues in food: 1996 evaluations Part II Toxicological)
       Ziram (IARC Summary & Evaluation, Volume 53, 1991)