Carcinogenicity and chronic toxicity of copovidone (Kollidon VA 64) in Wistar rats and Beagle dogs

Kollidon VA 64 (copovidone, CAS-No. 25086-89-9) was administered in the diet to male and female Wistar rats (0, 700, 1400, and 2800 mg/kg body weight) for 24 months, and to male and female beagle dogs (0, 500, 1500, and 2500 mg/kg body weight/day) for 52 weeks. Clinical signs, body weight, food consumption, hematology, and gross and histopathological evaluations were conducted on both rats and dogs, and dogs also underwent hearing tests, ophthalmoscopic examinations, electrocardiograms, blood pressure measurement, and clinical chemistry and urinalysis evaluations. No adverse in-life observations related to treatment were observed in either species. The rats exhibited dark discoloration of the feces that was attributed to the intake and excretion of large amounts of test substance and was not considered to be an adverse effect. No treatment-related hematological changes, or gross or histopathological lesions were observed in either species that could be considered clinically relevant. Vacuolated histiocytosis in the mesenteric lymph nodes of four dogs that was not accompanied by inflammation or degenerative changes reflected histiocytic removal and degradation of the test article rather than a toxic effect. The results of these studies demonstrate the absence of any significant toxicological findings of high dietary levels copovidone in rats and dogs, resulting in no-observed-adverse-effect levels of 2800 mg/kg body weight/day in rats and 2500 mg/kg body weight/day in dogs, the highest doses tested.