Imahie H, Nishida A, Imado N, Asano Y
Safety Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
J Toxicol Sci. 1997 Nov;22 Suppl 2:395-403. doi: 10.2131/jts.22.supplementii_395.
Teratogenicity study of taltirelin hydrate, a thyrotropin releasing hormone analogue, was carried out in Japanese white rabbits. Female rabbits were orally given taltirelin hydrate at a dose of 0 (control), 0.15, 1.5, or 15 mg/kg from day 6 to day 18 of gestation. Females were sacrificed on day 29 and their fetuses were examined. Neither death nor adverse effects on food consumption in dams were found in any dose groups. In the 15 mg/kg group, rapid breathing and decreased body weight gain in dams were temporally observed. No adverse effect of taltirelin hydrate on reproductive function was 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 dams, and 15 mg/kg for reproductive function of dams and for development of their offspring.
对促甲状腺激素释放激素类似物水合他替瑞林进行了致畸性研究，实验对象为日本白兔。在妊娠第6天至第18天，给雌性兔子口服水合他替瑞林，剂量分别为0（对照）、0.15、1.5或15mg/kg。在第29天处死雌性兔子并检查其胎儿。在任何剂量组中，均未发现母兔死亡或对其食物消耗有不良影响。在15mg/kg组中，曾一过性观察到母兔呼吸急促和体重增加减少。在任何组中均未检测到水合他替瑞林对生殖功能有不良影响。在胎儿检查中，水合他替瑞林对任何组的胎儿均无致畸、致死或生长迟缓作用。这些结果表明，水合他替瑞林对母兔一般毒性的无毒剂量水平为1.5mg/kg，对母兔生殖功能及其后代发育的无毒剂量水平为15mg/kg。
