Imahie H, Kobayashi T, Imado N, Inui T, Ariyuki F, Asano Y
Safety Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
J Toxicol Sci. 1997 Nov;22 Suppl 2:371-9. doi: 10.2131/jts.22.supplementii_371.
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.
对促甲状腺激素释放激素类似物水合他替瑞林进行了生育力研究，实验对象为Wistar大鼠。水合他替瑞林的口服给药剂量分别为0（对照组）、0.15、1.5或15mg/kg。雄性大鼠在交配前63天至解剖前一天给药（共121天），雌性大鼠在交配前14天至妊娠第7天给药。在妊娠第21天处死雌性大鼠，并确定妊娠结局。在15mg/kg组中，雄性和雌性大鼠均出现湿狗摇晃行为和活动增多，雄性大鼠的食物消耗量略有下降。水合他替瑞林引起的这些变化在0.15和1.5mg/kg组中未出现。在任何组中均未检测到水合他替瑞林对生殖功能的不良影响。在胎儿检查中，水合他替瑞林在任何组中均未产生致畸、致死或生长迟缓作用。这些结果表明，水合他替瑞林对成年动物一般毒性的无毒剂量水平为1.5mg/kg，对成年动物生殖功能及其胎儿发育的无毒剂量水平为15mg/kg。
