Furuhashi T, Uehara M, Kodama R, Yoshida R, Maruden A, Shimamura K
NRI Life Science, Kanagawa, Japan.
J Toxicol Sci. 1992 Dec;17 Suppl 4:201-19. doi: 10.2131/jts.17.supplementiv_201.
FUT-187 was given orally at 20, 120 and 720 mg/kg during the pre-pairing period (63 days prior to pairing in males and 14 days prior to pairing in females) and the pairing period to male and female rats and in the early stage of pregnancy (days 0 through 7 of gestation) to female rats, and the effects of the test compound on male and female reproductive performance and fetal development were evaluated. One male of the 720 mg/kg group died due to treatment. Temporary salivation was observed in males and females in the 20 mg/kg or more groups. In males, increases in the weight of the pancreas in the 120 mg/kg or more groups and the adrenals in the 720 mg/kg group, a depression of body weight gain and decreases in food intake and weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. In females, an increase in the weight of the pancreas in the 120 mg/kg or more groups, a slight depression of body weight gain during the early stage of pregnancy and a decrease in the food intake, and a decrease in the weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. No dose-related changes were found in the estrus, copulation, insemination and fertility indices. In fetuses, decreased numbers of corpora lutea, implantation and live fetuses were observed in the 720 mg/kg group. There were no treatment-related abnormalities in fetal mortality, sex ratio, weights of fetuses and placenta, and external and visceral examinations. Based on these results, it is concluded that the no-effect-dose levels of FUT-187 are less than 20 mg/kg for the parents, 720 mg/kg for reproductive performance and 120 mg/kg for fetal development.
在配对前期（雄性配对前63天，雌性配对前14天）以及配对期，给雄性和雌性大鼠口服FUT - 187，剂量分别为20、120和720 mg/kg；在妊娠早期（妊娠第0天至第7天）给雌性大鼠口服该药物，评估受试化合物对雄性和雌性生殖性能以及胎儿发育的影响。720 mg/kg组有1只雄性大鼠因治疗死亡。20 mg/kg及以上剂量组的雄性和雌性大鼠均出现暂时性流涎。在雄性大鼠中，120 mg/kg及以上剂量组胰腺重量增加，720 mg/kg组肾上腺重量增加，720 mg/kg组体重增加受抑制、食物摄入量和胴体重量减少，与对照组相比差异有统计学意义。在雌性大鼠中，120 mg/kg及以上剂量组胰腺重量增加，妊娠早期体重增加略有受抑制、食物摄入量减少，720 mg/kg组胴体重量减少，与对照组相比差异有统计学意义。在发情、交配、受精和生育指数方面未发现与剂量相关的变化。在胎儿方面，720 mg/kg组黄体、着床和活胎数量减少。在胎儿死亡率、性别比、胎儿和胎盘重量以及外观和内脏检查方面未发现与治疗相关的异常。基于这些结果，得出结论：FUT - 187对亲代的无作用剂量水平低于20 mg/kg，对生殖性能的无作用剂量水平为720 mg/kg，对胎儿发育的无作用剂量水平为120 mg/kg。
