Furuhashi T, Uehara M, Takei A, Kurihara H, Yoshida R, Maruden A, Shimamura K
NRI Life Science, Kanagawa, Japan.
J Toxicol Sci. 1992 Dec;17 Suppl 4:263-86. doi: 10.2131/jts.17.supplementiv_263.
FUT-187 was given orally at 20, 120 and 720 mg/kg to female rats during the perinatal and postnatal periods and the effect on dams and offspring were evaluated. One dam during the terminal period of gestation and 3 dams after delivery in the 720 mg/kg group died due to FUT-187. In dams, an increased pancreas weight in the 20 mg/kg or more groups, temporary salivation after dosing in the 120 mg/kg or more groups, and a depression of body weight gain and decreased food intake and weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. In offspring, postnatal death rate in the 720 mg/kg group tended to increased. Decreased body weight gain and delayed appearance of abdominal hair and descent of testis in the 720 mg/kg group were statistically significant in comparison with controls. There were no treatment-related abnormalities in visceral examination, organ weight, skeletal examination, sensory function, behavioral function, learning ability or reproductive function. Based on these results, it is concluded that the no-effect-dose levels of FUT-187 are less than 20 mg/kg for dams, and 120 mg/kg for reproductive performance of dams and offspring development.
在围产期和产后期间，对雌性大鼠口服给予FUT - 187，剂量分别为20、120和720 mg/kg，并评估其对母鼠和子代的影响。在720 mg/kg组中，有1只母鼠在妊娠末期死亡，3只母鼠在分娩后死亡，死因均为FUT - 187。与对照组相比，在母鼠中，20 mg/kg及以上剂量组胰腺重量增加，120 mg/kg及以上剂量组给药后出现暂时性流涎，720 mg/kg组体重增加受抑制、食物摄入量减少且胴体重量下降，这些差异具有统计学意义。在子代中，720 mg/kg组产后死亡率有上升趋势。与对照组相比，720 mg/kg组体重增加减少、腹部毛发出现延迟以及睾丸下降延迟，这些差异具有统计学意义。在内脏检查、器官重量、骨骼检查、感觉功能、行为功能、学习能力或生殖功能方面，未发现与治疗相关的异常。基于这些结果，得出结论：FUT - 187对母鼠的无作用剂量水平低于20 mg/kg，对母鼠生殖性能和子代发育的无作用剂量水平为120 mg/kg。
