International Agency for Research on Cancer (IARC) - Summaries & Evaluations

(Group 2B)

For definition of Groups, see Preamble Evaluation.

VOL.: 79 (2001) (p. 75)

CAS No.: 56-04-2
Chem. Abstr. Name: 2,3-Dihydro-6-methyl-2-thioxo-4(1H)-pyrimidinone

5.  Summary of Data Reported and Evaluation

5.1 Exposure data

Methylthiouracil is a thionamide anti-thyroid drug, introduced in the 1940s, which has been used in the treatment of hyperthyroidism. Little is known about its current use.

5.2 Human carcinogenicity studies

No epidemiological data on use of methylthiouracil 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

Although no conventional bioassay of carcinogenicity in rodents has been reported, methylthiouracil has produced tumours in three species of laboratory rodents after oral administration. In two studies in mice, multiple studies in rats and one study in hamsters, methylthiouracil produced thyroid follicular-cell adenomas and/or carcinomas after oral administration. In initiation–promotion studies with the known carcinogens 2-acetylaminofluorene and N-methyl-N-nitrosourea, methylthiouracil increased the incidence of thyroid follicular-cell tumours.

5.4 Other relevant data

Little is known about the disposition of methylthiouracil in humans. In rats, methylthiouracil was found to accumulate in the thyroid. The compound crosses the placental barrier and is transferred rapidly across the placenta throughout gestation.

Human exposure to methylthiouracil is associated with a high frequency of agranulocytosis.

The available data on the mechanism of action of methylthiouracil in experimental animals is limited, but inhibition of thyroid peroxidase and increased secretion of thyroid-stimulating hormone may be the basis of its tumorigenic activity in the thyroid.

No data were available on reproductive or developmental effects of methylthiouracil.

Methylthiouracil was not mutagenic in single studies of reverse mutation in bacteria and bone-marrow micronucleus formation in rodents. It induced chromosomal recombination in somatic cells of insects. It gave an inconclusive response in a test for micronucleus formation in fetal mouse blood cells.

5.5 Evaluation

There is inadequate evidence in humans for the carcinogenicity of methylthiouracil.

There is sufficient evidence in experimental animals for the carcinogenicity of methylthiouracil.

Overall evaluation

Methylthiouracil is possibly carcinogenic to humans (Group 2B).

For definition of the italicized terms, see Preamble Evaluation.

Previous evaluations: Vol. 7 (1974) (p. 53); Suppl. 7 (1987) (p. 66)


Last updated: 25 September 2001


    See Also:
       Toxicological Abbreviations
       Methylthiouracil  (IARC Summary & Evaluation, Volume 7, 1974)