Toxicological studies of plafibride. Part 2: Subacute and subchronic toxicity in rats and chronic toxicity in dogs.

The toxicity of N-2-(p-chlorophenoxy)-isobutyryl-N'-morpholinomethylurea (plafibride, ITA 104) was studied by repeated administration in Wistar rat for one and three months and in beagle dog for six months. Clofibrate was used as the standard product. In subacute toxicity in rat hepatomegaly and increase in kidney weight were observed in the animals treated with plafibride. A smaller increase in body weight was also observed in the males. The rats treated with 500 mg/kg of plafibride showed slight anaemia. Clofibrate at the same dose (500 mg/kg) caused the same effects as plafibride. In subchronic toxicity in rat for a period of 3 months both plafibride and clofibrate produced hepatomegaly and an increase in kidney weight but did not affect hepatic and renal functions. In chronic toxicity in beagle dog (6-month period) plafibride was tolerated at the dose of 100 mg/kg, causing slight anaemia, hepatomegaly and an increase in kidney weight, although no functional alterations of these organs were noticed. Clofibrate was administered at the dose of 50 mg/kg but was not tolerated at higher doses.