Reproductive and developmental toxicity studies of taltirelin hydrate (1) fertility study in rats by oral administration

Fertility study of taltirelin hydrate, a thyrotropin releasing hormone analogue, was carried out in Wistar rats. Taltirelin hydrate was orally administrated at a dose of 0 (control), 0.15, 1.5, or 15 mg/kg. Male rats were given the drug from 63 days before mating to the day before autopsy (total of 121 days), and female rats were treated from 14 days before mating to day 7 of gestation. The females were sacrificed on day 21 of gestation and pregnancy outcome was determined. In the 15 mg/kg group, wet dog shaking behavior and hyperlocomotion were observed in males and females, and the food consumption was slightly decreased in male rats. These changes induced by taltirelin hydrate were not found in the 0.15 and 1.5 mg/kg groups. No adverse effects of taltirelin hydrate on reproductive function were detected in any groups. In the fetal examination, taltirelin hydrate had no teratogenic, lethal, or growth retardation effects in any groups. These results show that the no-toxic dose levels of taltirelin hydrate are 1.5 mg/kg for general toxicity in parent animals, and 15 mg/kg for reproductive function of parent animals and for development of their fetuses.