Takahashi N, Kai S, Kohmura H, Ishikawa K, Kuroyanagi K, Hamajima Y, Ohta S, Kadota T, Kawano S, Ohta K
J Toxicol Sci. 1986 Apr;11 Suppl 1:281-300. doi: 10.2131/jts.11.supplementi_281.
VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered intravenously to female Crj: CD (Sprague-Dawley) rats from day 17 of gestation through postpartum day 20 at dose levels of 0.05, 0.2 and 0.8 mg/kg/day. The summarized results obtained are as follows: VP 0.2 and 0.8 mg/kg suppressed the body weight increase and brought thymic atrophy in dams. VP failed to affect the states of birth of newborns (F1). In F1 offspring, VP 0.8 mg/kg increased the days required for testicular descending and vaginal opening, and suppressed the body weight increase, but failed to affect the growth of genital organs, reproductive ability, learning ability, motility, motor activity or emotional development. F2 newborns derived from F1 rats whose dams had ever received VP during the prenatal and lactation periods showed no changes in observation items at birth. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 0.05 mg/kg/day against dams and 0.2 mg/kg/day against their offspring.
依托泊苷(VP 16 - 213,简称VP)是一种抗癌药物,在妊娠第17天至产后第20天,以0.05、0.2和0.8毫克/千克/天的剂量水平对雌性Crj:CD(斯普拉格 - 道利)大鼠进行静脉注射。获得的汇总结果如下:0.2和0.8毫克/千克的VP抑制了母鼠的体重增加并导致胸腺萎缩。VP对新生仔鼠(F1)的出生状态没有影响。在F1代仔鼠中,0.8毫克/千克的VP延长了睾丸下降和阴道开口所需的天数,并抑制了体重增加,但对生殖器官的生长、生殖能力、学习能力、运动能力、活动能力或情感发育没有影响。来自产前和哺乳期母鼠曾接受过VP的F1代大鼠的F2代新生仔鼠,出生时观察项目没有变化。基于这些结果,在当前实验条件下,VP对母鼠的无作用剂量水平估计为0.05毫克/千克/天,对其后代为0.2毫克/千克/天。