Chronic toxicity/carcinogenicity studies of sulphamethazine in Fischer 344/N rats: Two-generation exposure

Fischer 344 rats were given 10, 40, 600, 1200 or 2400 ppm sulphamethazine (SMZ) in the diet to determine the toxicity and potential carcinogenicity of SMZ. There were 225 rats of each sex in the control groups and 135 of each sex in each dose group. Animals were killed after 3, 12, 18 or 24 months of continuous dosing. Body weights, feed consumption, clinical observations, organ weights and histopathology data were collected. A slight decrease in body-weight gain was observed in the high-dose groups compared with the controls. No difference in feed consumption was found between the control and dosed rats. Mortality was inversely related to SMZ dose, especially in females, that is mortality was highest in the controls and decreased as the dose of SMZ increased. A statistically significant dose-related increase in the incidence of follicular cell adenocarcinomas of the thyroid gland was observed in the animals killed after 24 months. The incidences of non-neoplastic lesions of the thyroid gland in treated animals were significantly higher among treated animals than among controls; these lesions included follicular cell hyperplasia, follicular cell focal cellular change and multilocular cysts. The incidences of retinal atrophy, atrophy of the acinar pancreas (males), and dilatation of the uterine lumen also increased with increasing SMZ dose.