Toxicological studies of plafibride. Part 1: Acute toxicity and its determination after several administrations of plafibride

Acute toxicity studies of N-2-(p-chlorophenoxy)-isobutyryl-N'-morpholinomethylurea (plafibride, ITA 104) were carried out in mouse, rat, guinea pig and hamster by different administration routes. The effect of pretreatment with plafibride on acute toxicity was also studied for several days. Plafibride had low toxicity. Its LD50 p.o. was about 4000 mg/kg in rat, mouse and hamster. The LD50 i.p. was between 760 (673-859) mg/kg in NMRI mouse and 1050 (830-1328) mg/Kg in hamster. The LD50 i.v. was similar for rat and mouse (about 100 mg/kg). Pretreatment with plafibride did not alter acute toxicity, which implies the absence of accumulation of the compound which would have led to an increase in toxicity. Nor was there any appearance of enzymatic induction, in which case a decrease would be observed in the toxicity of the product.