Initial Submission: Combined Oncogenicity and Toxicity Study of N-(2,4-Difluorophenyl) -2-(3-(Trifluoromethyl)Phenoy) 3-Pyridine-Carboximide in Rats with Cover Letter dated 08/13/1992

摘要

This study was submitted under Section 8(e) because of increased severity of testicular degeneration and a significant increase in the incidence of skin fibromas for the high dose males. Test material was administered to F-344 rats (50/sex/group) via admixture into the diet at concentrations of 0, 500, 2500, or 12,500 ppm for approximately 104 weeks. A dose-related effect on body weights was observed throughout the study with high dose males showing approximately a 20 to 30% depression in body weight gain. Histopathological examination revealed a statistically significant increase in the incidence of a lack of sperm in the epididymides and extramedullary hemopoiesis and hemosiderosis in the spleen for high dose males. The findings in the epididymides was not clearly associated with histopathological changes in the testes related to treatment, but the labDratOry reported treated males sacrificed at study termination had an increased severity of testicular degeneration. A significant lucrease in the incidence of skin fibromas for the high dose males was also noted. However, this Increase is well within historical control ranges of 4 to 26% for this tumor. No treatment-related microscopic lesions were observed in females.