[Reproductive and developmental toxicity studies of taltirelin hydrate (4) perinatal and postnatal study in rats by...

Perinatal and postnatal study of taltirelin hydrate, a thyrotropin releasing hormone analogue, was carried out in Sprague-Dawley rats. Female rats were given taltirelin hydrate at a dose of 0 (control), 0.15, 1.5, or 15 mg/kg from day 17 of gestation to day 20 after delivery. All pregnant rats were allowed to deliver spontaneously and their offspring were examined. In the 15 mg/kg group, the dams showed the central nervous effects such as wet dog shaking during gestation periods. No adverse effect of taltirelin hydrate on the body weight gain, food consumption and reproductive performance was observed in this group. In the 0.15 and 1.5 mg/kg groups, the drug did not have any adverse effects. Taltirelin hydrate did not have any adverse effects on viability, growth, physical differentiation, functional and behavioral development (coordinated activity, auditory function, emotionality, learning ability, and spontaneous motor activity), 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 and for their offspring.