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

    ZINEB

    Chemical name

           Zinc ethylene-1,2-bisdithiocarbamate

    Empirical formula

           C4H6N2S4Zn

    Structural formula

    

    BIOLOGICAL DATA

    Biochemical aspects

           The capacity of the human gut to absorb zineb is not known,
    though in the rat 11-17% is taken up after ingestion. It is believed
    that thiocarbamates may act as inhibitors of certain -SH enzymes in
    the body.

           A person suffering from hypocatalasaemia developed
    sulfhaemoglobinaemia, haemolytic anaemia and Heinz body formation
    after contact with zineb (Pinkhas et al., 1963).

    Acute toxicity

    Animal    Route   LD50 mg/kg    References
                      body-weight
                                                                

    Rat       Oral       >5200      Blackwell-Smith et al., 1953
                                                                

    Short-term studies

           Rat. Groups of 40 weanling rats, 20 females and 20 males, were
    given diets containing 500, 1000, 2500, 5000 and 10 000 ppm of zineb
    for up to 30 days. Thyroid enlargement was seen at all dose levels,
    but, unequivocal histopathological changes were observed only at 10
    000 ppm (Blackwell-Smith et al., 1953; Kampmeier & Haag, 1954).

           Dog. Three groups each of 3 dogs were fed for one year diets
    containing 20, 2000 and 10 000 ppm of zineb. All the animals survived
    and no persistent change in growth rate was seen in any of the groups;
    there were no histopathological changes in the tissues, except in the
    thyroid gland, and haematological findings were normal. At 10 000 ppm
    thyroid hyperplasia was found (Blackwell-Smith et al., 1963; Kampmeier
    & Haag, 1954).

    Long-term studies

           Rat. Groups, each of 10 young male and 10 young female rats,
    were fed diets containing 500, 1000, 2500, 5000 and 10 000 ppm of
    zineb for 2 years. At the two highest dose levels there was an
    apparent increase in mortality rate among the females and at 10 000
    ppm there was a tendency towards diminished growth in both sexes.
    Haematological studies were all normal. A goitrogenic effect was seen
    at all dose levels. Kidney damage was seen in 6 animals at the 10 000
    ppm dose level, and in one animal in each of the groups receiving
    1000, 2500, and 5000 ppm, but not in any of those given 500 ppm. The
    tumour incidence was not significantly greater among any of the
    treated animals than it was in the controls (Blackwell-Smith et al.,
    1953; Kampmeier & Haag, 1954).

    Comments on the experimental studies reported

           For zineb, 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 the toxicity of the plant
    residues. Extension of the long-term studies, including reproduction
    studies, which should concern at least two species, with special
    attention to neurological changes, goitrogenicity and occurrence of
    anaemia.

    REFERENCES

    Blackwell-Smith, R., jr, Finnegan, J. K., Larson, P. S., Sahyoun,
    P. F., Dreyfuss, M. L. & Haag, H. B. (1953) J. Phamacol. exp.
    Ther., 109, 159

    Kampmeier, C. & Haag, H. B. (1954) Agricult. Chemicals, April, 49

    Pinkhas, J., Djaldetti, M., Joshua, H., Reswick, C. & de Vries, A.
    (1963) Blood, 21, 484
    

    See Also:
       Toxicological Abbreviations
       Zineb (ICSC)
       Zineb (FAO/PL:1967/M/11/1)
       Zineb (Pesticide residues in food: 1993 evaluations Part II Toxicology)
       Zineb (IARC Summary & Evaluation, Volume 12, 1976)