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

    FERBAM

    Chemical name

           Ferric dimethyldithiocarbamate.

    Synonym

           Fermate

    Empirical formula

           C9H18N3S6Fe

    Structural formula

    

    BIOLOGICAL DATA

    Biochemical aspects

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

    Acute toxicity

                                                                        
    Animal         Route            LD50 mg/kg        References
                                    body-weight
                                                                        

    Mouse          Oral                1 000          Zapp, 1950

    Mouse     Intraperitoneal    54 315 and 3 000*    Hodge et al., 1952
                                                      Kligman & Rosenweig,
                                                      1948

                                                      Zapp, 1950

    Rat            Oral         5 700-17 000(ALD)**   Hodge et al., 1952
                                                      Hodge et al., 1956
                                                      Zapp, 1950

    Rat       Intraperitoneal          2 700          Hodge et al., 1952
                                                                        

    *  Difference due to use of different vehicles.
    ** ALD = approximate lethal dose.

    Short-term studies

           Rat. Groups of 10 male and 10 female weanling rats were fed
    diets containing 100, 500, 2500 and 500 ppm of ferbam for one month.
    At 100 ppm no growth depression was found. At the 3 higher levels,
    growth depression was found, while in the 5000 ppm group the mortality
    rate was increased. No significant histopathological changes were seen
    in any of the animals (Hodge et al., 1952).

           Groups of 20 rats, 10 males and 10 females, were maintained for
    one month on a diet containing 2500 ppm ferbam. Post-mortem
    examination revealed no thyroid abnormalities (Hodge et al., 1952).

           Dog. One dog was given ferbam and ziram together for one month,
    each at a dosage of 5 mg/kg body-weight per day, without adverse
    effect, except slight anaemia. Another remained healthy - again except
    for slight anaemia - when given ferbam alone for one month at a dosage
    of 25 mg/kg body-weight per day and also on 50 mg/kg body-weight per
    day for one week, although 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 ferbam per kg body-weight for one year. Convulsions
    occurred at the highest dose level. Urine analysis, blood picture
    organ weights and histology (including the thyroid) were normal (Hodge
    et al., 1956).

    Long-term studies

           Rat. Weanling rats in groups of 25 males and 25 females were
    fed for 2 years diets containing 25, 250 and 2500 ppm of ferbam.
    Growth-rate was depressed and the life-span shortened only at the
    highest concentration. In this group, moreover, neurological changes
    appeared in the animals after 2 months; cystic brain lesions developed
    and in some of the males the testes atrophied. The thyroid glands were
    normal in all groups and there was no increase in tumour incidence
    (Hodge et al., 1956).

    Comments on experimental studies reported

           For ferbam, 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 2 species. Special
    attention should be given to neurological changes, goitrogenicity, and
    occurrence of anaemia.

    REFERENCES

    Hodge. H. C., Maynard. E. A., Downs, W., 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. Phamacol. exp. Ther., 118, 174

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

    Zapp, J. R. (1950) United States food and drug residue tolerance
    hearings, FDC, 57, 7757-7789
    

    See Also:
       Toxicological Abbreviations
       Ferbam (ICSC)
       Ferbam (FAO/PL:1967/M/11/1)
       Ferbam (Pesticide residues in food: 1996 evaluations Part II Toxicological)
       Ferbam (IARC Summary & Evaluation, Volume 12, 1976)