For definition of Groups, see Preamble Evaluation.
Vol.: 79 (2001) (p. 341)
Chem. Abstr. Name: 4-Amino-N-(4,6-dimethyl-2-pyrimidinyl)benzenesulfonamide
Chem. Abstr. Name: 4-Amino-N-(4,6-dimethyl-2-pyrimidinyl)benzenesulfonamide, monosodium salt
5.1 Exposure data
Sulfamethazine is a sulfonamide drug that has been used to treat bacterial diseases in human and veterinary medicine and to promote growth in cattle, sheep, pigs and poultry.
5.2 Human carcinogenicity data
No data were available to the Working Group.
5.3 Animal carcinogenicity data
Sulfamethazine was tested by oral administration in one study in mice and in one study in rats that included exposure in utero. It produced thyroid follicular-cell adenomas in mice and follicular-cell adenomas and carcinomas in rats. No statistically significant increase was seen in the incidence of tumours at other sites in mice or rats.
5.4 Other relevant data
Sulfamethazine shows a trimodal pattern of polymorphic acetylation in humans. It caused thyroid gland enlargement (goitre) in rats and diffuse hypertrophy and hyperplasia in rats and mice. Administration of sulfamethazine to rats under bioassay conditions that caused tumours resulted in alteration of thyroid hormone homeostasis, including increased secretion of thyroid-stimulating hormone and morphological changes in the thyroid consistent with this increase. The underlying mechanism for these changes is reversible inhibition of thyroid peroxidase activity. A study in which cynomolgus monkeys were given sulfamethazine did not result in alterations in thyroid gland function.
In a continuous breeding study in mice, sulfamethazine reduced fertility in both males and females but did not change sperm parameters.
No data were available on the genetic and related effects of sulfamethazine in humans. The compound did not induce chromosomal aberrations in bone-marrow cells of rats treated in vivo or in Chinese hamster cells. It did induce sister chromatid exchange in Chinese hamster cells in the absence but not in the presence of an exogenous metabolic system in one experiment. It did not induce DNA damage or mutations in mammalian cells in vitro or in bacteria. Sulfamethazine is considered not to be genotoxic in vitro or in vivo.
There is inadequate evidence in humans for the carcinogenicity of sulfamethazine.
There is sufficient evidence in experimental animals for the carcinogenicity of sulfamethazine.
Sulfamethazine is not classifiable as to its carcinogenicity to humans (Group 3).
Sulfamethazine produces thyroid tumours in mice and rats by a non-genotoxic mechanism, which involves inhibition of thyroid peroxidase resulting in alterations in thyroid hormone concentrations and increased secretion of thyroid-stimulating hormone. Consequently, sulfamethazine would be expected not to be carcinogenic to humans exposed to doses that do not alter thyroid hormone homeostasis.
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.For definition of the italicized terms, see Preamble Evaluation.
See Also: Toxicological Abbreviations