Comparative carcinogenicity of ethylene thiourea with or without perinatal exposure in rats and mice

Abstract

Chronic toxicity and carcinogenicity studies of ethylene thiourea (ETU), 97% pure, were conducted in F344 N rats and B6C3F1 mice of each sex. The major objective of the study was to determine if incorporation of perinatal exposure, in addition to the conventional exposure of young adult animals for 2 years, enhances the sensitivity of the bioassay in identification of the carcinogenic potential of chemicals when compared to the conventional exposure of animals to a chemical for 2 years, usually beginning at the age of 6–8 weeks. The studies were designed to determine (1) the toxic and carcinogenic effects of dietary ETU in rats and mice receiving perinatal exposure up to 8 weeks of age followed by control diet for 2 years, (2) the effects of ETU in rats and mice receiving exposure for 2 years beginning at the age of 8 weeks, and (3) the effects of combined perinatal/adult exposure to ETU (perinatal exposure to 8 weeks of age followed by the adult exposure for 2 years). During the perinatal period, rats were exposed to dietary ETU concentrations ranging from 9 to 90 ppm and adult exposure concentrations ranged from 25 to 250 ppm. In the mice, the perinatal exposure concentrations of ETU in the diet ranged from 33 to 330 ppm, and in the adults the concentrations were 100 to 1000 ppm. A total of eight exposure groups (including controls) were used with 60 animals in each group. Ten animals from each group were killed at Month 9 of the study for interim evaluation. The thyroid gland in rats and mice and the liver in mice were identified as target organs of ETU toxicity at the 9-month interim evaluation. The perinatal only exposure to ETU was not carcinogenic in rats or mice, while adult or perinatal/adult combination exposures to ETU were carcinogenic both in rats and in mice. The thyroid gland was the major site of ETU carcinogenicity both in rats and in mice. The liver and pituitary glands were other major sites of ETU carcinogenicity in mice. The carcinogenic effects of ETU were generally similar by adult and perinatal/adult combination protocols except that the incidences of thyroid tumors were slightly higher in the rats receiving the perinatal/adult combination of ETU exposure in the diet.