For definition of Groups, see Preamble Evaluation.
VOL.: 79 (2001) (p. 127)
Chem. Abstr. Name: 2,3-Dihydro-2-thioxo-4(1H)-pyrimidinone
5.1 Exposure data
Thiouracil was used briefly in the 1940s as the first thionamide anti-thyroid drug.
5.2 Human carcinogenicity studies
No epidemiological data on use of thiouracil and cancer were found. However, two analyses were published of one cohort study conducted in the United Kingdom and the USA of the cancer risk of patients, mainly women, with hyperthyroidism who had been treated with anti-thyroid drugs. The earlier analysis showed more malignant thyroid neoplasms in patients receiving these drugs than in those treated with surgery or 131I, but the excess may have been due to closer surveillance of the patients given drugs owing to more frequent use of thyroidectomy. In the later analysis, patients with hyperthyroidism treated only with anti-thyroid drugs had a modest increase in the risk for death from cancer, due chiefly to oral cancer and cancer of the brain. Neither report provided information on the type, quantity or dates of anti-thyroid drug use.
Two case–control studies of cancer of the thyroid showed no significant association with treatment with anti-thyroid medications.
5.3 Animal carcinogenicity data
Several early studies in mice showed that oral administration of thiouracil induced nodular thyroid follicular-cell hyperplasia, including some pulmonary metastases suggestive of thyroid neoplasia by current histopathological criteria. In one study in one strain of mice, thiouracil produced hepatocellular tumours. In one adequate study in rats, thiouracil produced thyroid follicular-cell adenomas and carcinomas. In one study in gerbils, thiouracil inhibited the progression of N-nitrosodiethylamine-induced cholangiomas into cholangiocarcinomas.
5.4 Other relevant data
Little is known about the disposition of thiouracil in humans. In rats and fetal rats, thiouracil accumulated in the thyroid. Thiouracil acts by inhibiting thyroid peroxidase, thus decreasing thyroid hormone production, and it increases proliferation by increasing the secretion of thyroid-stimulating hormone. This is the probable basis of its tumorigenic activity in the thyroid of experimental animals.
No data were available on the developmental or reproductive effects of thiouracil in humans. The only studies in experimental animals indicated altered adrenal function in young rats made hypothyroidal from birth.
In the only study in which thiouracil was tested for genotoxicity, it did not induce DNA strand breaks in cultured mammalian cells. It has not been tested for mutagenicity or clastogenicity.
There is inadequate evidence in humans for the carcinogenicity of thiouracil.
There is sufficient evidence in experimental animals for the carcinogenicity of thiouracil.
Thiouracil is possibly carcinogenic to humans (Group 2B).For definition of the italicized terms, see Preamble Evaluation.
Previous evaluations: Vol. 7 (1974) (p. 85); Suppl. 7 (1987) (p. 72)
See Also: Toxicological Abbreviations Thiouracil (IARC Summary & Evaluation, Volume 7, 1974)