REPRODUCTIVE AND DEVELOPMENTAL TOXICITY STUDIES OF TALTIRELIN HYDRATE (2) TERATOGENICITY STUDY IN RATS BY ORAL ADMINISTRATION

Teratogenicity study of taltirelin hydrate, a thyrotropin releasing hormone analogue, was carried out in Wistar rats. Female rats were orally given taltirelin hydrate at a dose of 0 (control), 0.15, 1.5, or 15 mg/kg from day 7 to day 17 of gestation. Twenty-seven female rats in each group were sacrificed on day 21 of gestation and their fetuses were examined. The remaining 13 female rats in each group were allowed to deliver spontaneously and their newborns were examined. In the 15 mg/kg group, the dams (P) showed wet dog shaking behavior and hyperlocomotion. No adverse effect of taltirelin hydrate on the body weight gain, food consumption, water intake, and reproductive performance was observed in this group. In the 0.15 and 1.5mg/kg groups, taltirelin hydrate did not show any adverse effects. In F1 generation groups, taltirelin hydrate had no teratogenic, lethal, or growth retardation effects in any groups. There were also no adverse effects of taltirelin hydrate on postnatal development, emotionality, coordinated activity, sensitivity, learning ability, and reproductive performance of F1 offspring, and development of F2 fetuses. These results show that the no-toxic dose levels of taltirelin hydrate are 1.5 mg/kg for general toxicity in dams, and 15 mg/kg for reproductive function of dams (P) and for development of F1 generation.