Reproductive Toxicity of γ-Ethyl-γ-phenyl-butyrolactone, a New Anticonvulsant and Hypnotic Drug, in Mice

The reproductive toxicity of γ-ethyl-γ-phenyl-butyrolactone (EPBL, CAS 53380-21-5), a new anticonvulsant and hypnotic drug, was investigated by performing fertility and peri- and post-natal studies in mice. In both studies, EPBL was administered by gavage at 0, 50, 10, or 200 mg/kg doses. The first study found parent toxicity as measured by reduced body weight at the higher dose. At the same dose, the number of live fetuses was decreased. However, neither male or female fertility nor the reproductive performance of mice were affected. The results of the second study showed that the only negative effects were a depression of maternal weight gain and a decrease in body weight of the litter at birth which was 200 mg/kg. A reduction in the survival rate was also seen. There was no evidence that treatment of F 0 females from day 15 of pregnancy to day 21 post-par-tum affected either the reproductive capacity of the F 1 offspring or the development of F 2 progenies. The non observed effects levels (NOEL) for both studies can be estimated at 100 mg/kg.