Kai S, Kohmura H, Ishikawa K, Takeuchi Y, Ohta S, Kuroyanagi K, Kadota T, Kawano S, Chikazawa H, Kondo H
Drug Safety Research Department, Bristol-Myers Research Institute, Ltd., Aichi, Japan.
J Toxicol Sci. 1988 Jul;13 Suppl 2:23-34. doi: 10.2131/jts.13.supplementii_23.
Carboplatin, an oncostatic drug, was administered intravenously to male Crj: CD (Sprague-Dawley) rats for 63 days and to female rats of the same strain for 14 days prior to mating at dose levels of 1, 2 and 4 mg/kg/day. These animals were then mated under the consecutive administration of this drug and the females confirmed to be copulated were further dosed from day 0 through 7 of gestation. The summarized results obtained are as follows: 1. Carboplatin 2 mg/kg and higher suppressed body weight gains accompanied by the decreases in food and water consumption in male rats. Further, body weight gains were suppressed in female rats followed by the decreases in food consumption at the same dose levels. 2. Though there were no differences between dosed animals and controls regarding the organ weights, the incidence of necrosis of the tails around the injection site was increased in male rats at 4 mg/kg. 3. Carboplatin failed to affect the reproductive ability of both sexes. 4. As for fetuses, the mortality was elevated at 2 mg/kg and higher and the number of live fetuses reduced at 4 mg/kg, but the influences on prenatal development were not apparently observed for live fetuses even at the highest dose level. Based on these results, the no-effect dose level of carboplatin under the present experimental condition was estimated to be 1 mg/kg/day against parent rats of both sexes and their offspring.
卡铂是一种抗癌药物,以1、2和4毫克/千克/天的剂量水平分别对雄性Crj:CD(斯普拉格-道利)大鼠静脉给药63天,对同一品系的雌性大鼠在交配前14天给药。然后在连续给药该药物的情况下使这些动物交配,并对确认已交配的雌性大鼠从妊娠第0天至第7天进一步给药。得到的汇总结果如下:1. 卡铂剂量为2毫克/千克及以上时,雄性大鼠体重增加受到抑制,同时食物和水的摄入量减少。此外,相同剂量水平下雌性大鼠体重增加也受到抑制,随后食物摄入量减少。2. 给药动物与对照动物的器官重量虽无差异,但4毫克/千克组雄性大鼠注射部位周围尾巴坏死的发生率增加。3. 卡铂未影响两性的生殖能力。4. 对于胎儿,2毫克/千克及以上剂量时死亡率升高,4毫克/千克时活胎数量减少,但即使在最高剂量水平,对活胎的产前发育也未观察到明显影响。基于这些结果,在本实验条件下,卡铂对雌雄亲代大鼠及其后代的无作用剂量水平估计为1毫克/千克/天。