VOL.: 79 (2001) (p. 659)
Chem. Abstr. Name: 2-Imidazolidinethione
5.1 Exposure data
Ethylenethiourea is used as a vulcanization accelerator in the rubber industry. It is a degradation product of and an impurity in ethylenebisdithiocarbamate fungicides, and field workers may be exposed to ethylenethiourea while applying these fungicides. The general population may be exposed to low concentrations of residues of ethylenethiourea in foods.
5.2 Human carcinogenicity data
The available data were inadequate to evaluate the carcinogenicity of ethylenethiourea to humans.
5.3 Animal carcinogenicity data
Ethylenethiourea was tested for carcinogenicity by oral administration in two studies in three strains of mice, with perinatal exposure in one study. It was also tested in five studies in rats by oral administration, with perinatal exposure in one study. In mice, it produced thyroid follicular-cell tumours and tumours of the liver and anterior pituitary gland. In rats, it consistently produced thyroid follicular-cell adenomas and carcinomas. Ethylenethiourea did not cause neoplasms in one strain of hamsters.
5.4 Other relevant data
Ethylenethiourea caused thyroid gland enlargement (goitre) in rats and mice as a result of diffuse hypertrophy and hyperplasia of thyroid follicular cells. Administration of ethylenethiourea under bioassay conditions that caused predominantly benign follicular-cell tumours resulted in alteration of thyroid hormone homeostasis, including increased secretion of thyroid-stimulating hormone. The underlying mechanism of the changes induced by ethylenethiourea is interference with the functioning of thyroid peroxidase activity. This is considered to be the basis for its tumorigenic activity in experimental animals.
One retrospective study of pregnancy outcomes in women employed in the manufacture of rubber containing ethylenethiourea showed no exposure-related effects. Ethylenethiourea was teratogenic in rats, but not in mice, hamsters or guinea-pigs. The central nervous system was particularly vulnerable in rats. The available data suggest that both toxicokinetics and embryo sensitivity are components of the species-specificity of the teratogenicity of ethylenethiourea. Furthermore, effects on thyroid function do not appear to be involved.
Ethylenethiourea was not genotoxic in appropriate tests in bacteria and cultured mammalian cells or in rodents in vivo. Ethylenethiourea induced chromosomal recombination and aneuploidy in yeast and cell transformation in mammalian cells.
There is inadequate evidence in humans for the carcinogenicity of ethylenethiourea.
There is sufficient evidence in experimental animals for the carcinogenicity of ethylenethiourea.
Ethylenethiourea is not classifiable as to its carcinogenicity to humans (Group 3).
In making its evaluation, the Working Group concluded that ethylenethiourea produces thyroid tumours in mice and rats by a non-genotoxic mechanism, which involves interference with the functioning of thyroid peroxidase resulting in a reduction in circulating thyroid hormone concentrations and increased secretion of thyroid-stimulating hormone. Consequently, ethylenethiourea would not be expected to produce thyroid cancer in humans exposed to concentrations that do not alter thyroid hormone homeostasis.
An additional consideration of the Working Group, based on the lack of genotoxicity of ethylenethiourea, was that the liver tumours and benign pituitary tumours in mice were also produced by a non-genotoxic mechanism.
Evidence from epidemiological studies and from toxicological studies in experimental animals provide compelling evidence that rodents are substantially more sensitive than humans to the development of thyroid tumours in response to thyroid hormone imbalance.
Previous evaluations: Vol. 7 (1974); Suppl. 7 (1987)For definition of the italicized terms, see Preamble Evaluation.
See Also: Toxicological Abbreviations Ethylenethiourea (Pesticide residues in food: 1988 evaluations Part II Toxicology) Ethylenethiourea (IARC Summary & Evaluation, Volume 7, 1974)