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

(Group 3)

For definition of Groups, see Preamble Evaluation.

VOL.: 79 (2001) (p. 53)

CAS No.: 60-56-0
Chem. Abstr. Name: 1,3-Dihydro-1-methyl-2H-imidazole-2-thione

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Methimazole is an anti-thyroid drug, introduced in 1949, which is widely used in the treatment of hyperthyroidism. It has been used as a fattening agent in cattle, but this use has been banned.

5.2 Human carcinogenicity studies

No epidemiological data on use of methimazole 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

Methimazole was tested by oral administration in two limited studies in mice and in one study in rats. In one study in mice, it increased the incidence of thyroid follicular-cell adenomas but only in conjunction with a low-iodine diet. It produced thyroid follicular-cell adenomas and carcinomas in the study in rats.

5.4 Other relevant data

In humans and rodents, methimazole is readily absorbed and rapidly excreted. In rats, glucuronidation is the major metabolic pathway; less is known about its metabolism in humans.

The mode of action of methimazole in the thyroid in experimental animals involves inhibition of thyroid peroxidase, which decreases thyroid hormone production and increases proliferation by increasing the secretion of thyroid-stimulating hormone. This is the probable basis for the tumorigenic activity of methimazole for the thyroid in experimental animals.

While the overall incidence of malformations in the infants of women given methimazole during pregnancy does not appear to be elevated, there is equivocal evidence for an association with the occurrence of aplasia cutis, a skin defect. Most of the studies in experimental animals focused on the consequences of hypothyroidism subsequent to perinatal or early postnatal exposure of rats to methimazole; effects on adult neurobehavioural and testicular function were found. Neurobehavioural effects have also been reported in mice exposed perinatally to methimazole.

Methimazole has not been adequately tested for its ability to induce gene mutations. It induced chromosomal aberrations in mammalian cells in vitro, but the results of studies of its ability to induce chromosomal damage in vivo were mainly negative.

5.5 Evaluation

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

There is limited evidence in experimental animals for the carcinogenicity of methimazole.

Overall evaluation

Methimazole is not classifiable as to its carcinogenicity to humans (Group 3).

For definition of the italicized terms, see Preamble Evaluation.


Last updated: 25 September 2001


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