| Sign In to gain access to subscriptions and/or personal tools. |
Subchronic Toxicity of Thalidomide in Rodents After 13 Weeks of Oral AdministrationCelgene Corporation, Warren, New Jersey, USA
Battelle Pulmonary Therapeutics, Columbus, Ohio, USA
Battelle Pulmonary Therapeutics, Columbus, Ohio, USA
Therlmmune Research Corporation, Maryland, USA
Celgene Corporation, Warren, New Jersey, USA The subchronic toxicology of thalidomide was determined in CD-1 mice and F344 rats. Animals (10/sex/dose) were orally dosed at 30,300, and 3000 mg/kg/day over 13 weeks. Control animals were given 1% carboxymethylcellulose. No thalidomide-related mortality occurred throughout the study. Some species and sex differences were seen. In mice, thalidomide had no effect on body weight, food consumption, ophthalmic function or clinical chemistry/hematology, but a dose-dependent orange-pink urine was observed in both sexes. The discoloration was probably due to chromogenic breakdown products of thalidomide. The only significant finding in the mouse study was dose-related hepatic centrilobular hypertrophy in the males. This appeared only at the highest dose in the females. The hypertrophy was correlated with increased liver weight for the high dose of both sexes suggesting enzyme induction. In rats, thalidomide produced lower body weights in both sexes compared to control with a dose-response more evident in males. Male rats dosed at 30, 300, and 3000 mg/kg had body weights that were 8, 11, and 19% below control weight just before necropsy. Corresponding female rats were only 6–7% below control weights at all dose levels. Lower food consumption was observed in male rats and varied between 6–13% below control with no dose-response. Decreased forelimb strength was noted in males and could be due to the lower body weights. Functional observational battery tests and histopathology of the sural nerve and lumbar spinal cord sections suggested that the rat did not develop thalidomide-induced peripheral neuropathy. Mild anemia and leukopenia were seen only in some treated males. A decrease in total and free T4 was more consistent in females. Both sexes had lower thymus weights with no histological correlate compared to control. The no-observed-adverse-effect level for mice and female rats were 3000 mg/kg and 30 mg/kg for male rats.
Key Words: Oral • Rodents • Subchronic Toxicology • Thalidomide
International Journal of Toxicology, Vol. 18, No. 5,
337-352 (1999) This article has been cited by other articles:
|
||||||||||||||||||||||||||||||||||||||||
 |
|
|
 |
|
Sign In to gain access to subscriptions and/or personal tools.
