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