Kai S, Kohmura H, Hiraiwa E, Koizumi S, Ishikawa K, Kawano S, Kuroyanagi K, Hattori N, Chikazawa H, Kondoh H
Preclinical Research Laboratories, Bristol-Myers Squibb K.K., Aichi, Japan.
J Toxicol Sci. 1994 Aug;19 Suppl 1:69-91. doi: 10.2131/jts.19.supplementi_69.
Paclitaxel, an antineoplastic agent, was administered intravenously to pregnant Crj: CD (SD) rats daily at dose levels of 0 (saline and vehicle), 0.15, 0.3 and 0.6 mg/kg from day 7 to day 17 of gestation. Results were as follows: 1. The ossification of hyoid bodies was retarded in F1 fetuses by the vehicle. However, the vehicle-treated group had no effect in the other parameters that were measured in this study when compared to the saline-treated group. 2. Body weight gains and food consumption in F0 dams were not affected by paclitaxel during the gestation and lactation periods. 3. Paclitaxel failed to affect the organ weights in F0 dams. 4. Paclitaxel did not alter the prenatal development in F1 fetuses. 5. External, internal and skeletal malformations were not induced by paclitaxel. Further, paclitaxel did not affect the skeletal variations and ossification processes. 6. Paclitaxel did not alter the delivery status of F0 dams or viability and weaning indices in F1 pups. 7. The day required for presence of hair was significantly delayed in 0.6 mg/kg F1 pups at paclitaxel. However, the days required for pinnae detachment, incisor eruption, eye opening, testicular descent and vaginal opening were not affected by paclitaxel. 8. No effects on body weight gains or food consumption were observed in both male and female F1 rats. 9. Paclitaxel did not alter the developmental behavior, learning ability and memory, spontaneous motor activity or emotionality in F1 rats. 10. The reproductive performance in both male and female F1 rats were not affected by paclitaxel. 11. Paclitaxel did not alter the organ weights in both male and female F1 rats. 12. No influence on prenatal development was observed for F2 fetuses even at the highest dose level of paclitaxel. Based on the reproductive and developmental indices, the no toxic-effect dose level of paclitaxel is 0.6 mg/kg/day and 0.3 mg/kg/day for dams (F0) and their offspring (F1), respectively.
抗肿瘤药物紫杉醇在妊娠第7天至第17天，以0（生理盐水和赋形剂）、0.15、0.3和0.6mg/kg的剂量水平每日静脉注射给妊娠的Crj:CD(SD)大鼠。结果如下：1.赋形剂使F1代胎儿舌骨骨化延迟。然而，与生理盐水处理组相比，赋形剂处理组在本研究中测量的其他参数上没有影响。2.紫杉醇在妊娠和哺乳期对F0代母鼠的体重增加和食物消耗没有影响。3.紫杉醇未能影响F0代母鼠的器官重量。4.紫杉醇没有改变F1代胎儿的产前发育。5.紫杉醇没有诱导外部、内部和骨骼畸形。此外，紫杉醇没有影响骨骼变异和骨化过程。6.紫杉醇没有改变F0代母鼠的分娩状态或F1代幼崽的活力和断奶指数。7.紫杉醇处理的0.6mg/kg F1代幼崽出现毛发的天数显著延迟。然而，耳廓分离、门齿萌出、睁眼、睾丸下降和阴道口开放所需的天数不受紫杉醇影响。8.在雄性和雌性F1代大鼠中均未观察到对体重增加或食物消耗的影响。9.紫杉醇没有改变F1代大鼠的发育行为、学习能力和记忆力、自发运动活动或情绪。10.紫杉醇对雄性和雌性F1代大鼠的生殖性能没有影响。11.紫杉醇没有改变雄性和雌性F1代大鼠的器官重量。12.即使在紫杉醇的最高剂量水平下，也未观察到对F2代胎儿产前发育的影响。根据生殖和发育指标，紫杉醇对母鼠（F0）及其后代（F1）的无毒性作用剂量水平分别为0.6mg/kg/天和0.3mg/kg/天。
