REPRODUCTION STUDY OF PROPIVERINE HYDROCHLORIDE (1) : Fertility Study in Rats by Oral Administration

A fertility study was performed in Sprague-Dawley rats by oral administration of propiverine hydrochloride (P-4) at dose levels of 0 (control), 2, 10 and 50 mg/kg/day. Male rats were treated for 9 weeks before mating and following 4 weeks including mating period. Female rats were administered the test substance from 2 weeks before mating to day 7 of pregnancy. The females were sacrificed on day 21 of pregnancy for examination of their fetuses. Toxic signs consisted of mydriasis, salivation and rale were observed in both male and female animals at the dose of 50 mg/kg group and in male animals at the dose of 10 mg/kg group. Body weight gain was supressed and food intake was decreased in the 50 mg/kg group throughout the administration period. Water intake of the 50 mg/kg group was decreased temporarily at the early stage of administration period, although increased thereafter. Autopsy revealed the enlargement of the liver with yellow-brownish coloration in one male rat at the 50 mg/kg group. Fertility and reproductive ability in both sexes were not affected by administration of P-4. There was no lethal effect and no growth-inhibiting or teratogenic effects on the embryos and the fetuses. The results suggest that the non-effective dose level of P-4 was 2 and 10 mg/kg/day for general toxicity in male and female parent animals respectively, 50 mg/kg/day for reproductive ability in parent animals and in embryos and fetuses.