Toxicological studies of plafibride. Part 3: Study of teratogenic activity in rats and rabbits

Teratological studies of N-2-(p-chlorophenoxy)-isobutyryl-N'-morpholinomethylurea (plafibride, ITA 104) were carried out in rats and rabbits. The rats were given doses of 125, 250 and 500 mg/kg/d p.o. and the rabbits 25, 50 and 100 mg/kg/d p.o. during the whole period of organogenesis. As a positive control, vitamin A was administered to the rats at the dose of 60,000 IU/rat p.o. for 3 days and thalidomide was given to the rabbits at the dose of 150 mg/kg/d p.o. A group was added treated with clofibrate at the dose of 500 mg/kg/d p.o. in rat and 100 mg/kg/d in rabbit. Plafibride caused malformations in both species. In rat a considerable number of fetuses appeared with hydrocephalus, correlated to the dose. In rabbit, malformations were observed at the lower doses whereas at 100 mg/kg the toxic action on the embryos avoided the appearance of malformed fetuses. Both vitamin A and thalidomide were teratogenic in the experiments in rat and rabbit, respectively. The number of malformations and postimplantations losses were significant in relation to the control group in both cases. The standard product, clofibrate, reduced the viability of the fetuses which showed weight loss in rat and lower survival rate in rabbit. Plafibride is advised against in pregnant women.