Abstract: Objective To observe the embryo-fetal developmental toxicity of intravenous cyclophosphamide on pregnant rabbits, and provide basis for using cyclophosphamide as a positive control in embryo-fetal developmental toxicity test. Method Pregnant New Zealand rabbits were randomly divided into control group (0.9% Sodium chloride injection, GD11, i.v), and cyclophosphamide group(cyclophosphamide 30 mg/kg, GD11, i.v). At termination (GD28), the uterine content was removed by caesarean section. Live fetuses were examined for external, visceral and skeletal malformations and variations. Result There were no noticeable changes in the reproductive function and embryogenesis of rabbits by cyclophosphamide. But cyclophosphamide could cause the teratogenic in external, visceral and skeletal malformations. The rate of cleft palate was 32.95%, the rate of visceral variation was 10.23%, and the rate of skeletal malformation was 23.37%. Conclusion Inject cyclophosphamide (30 mg/kg) into the New Zealand rabbits can cause fetal malformation. Type and ratio of fetal malformations are proportional. Cyclophosphamide can be used as a positive control for embryo-fetal developmental toxicity test in rabbits.

Key words: Cyclophosphamide, reproductive toxicity, pregnant rabbits, positive control

摘要： 目的 孕兔静脉给予环磷酰胺，以观察其对孕兔胚胎及胎仔的毒性作用及表现，为选择环磷酰胺作为阳性对照提供使用参考。方法 将孕兔随机分为对照组[0.9%氯化钠注射液，GD11(GD,妊娠日)，i.v]和环磷酰胺组(环磷酰胺30 mg/kg体质量，GD11，i.v)。GD28对孕兔实施安乐死，剖宫取胎仔，检查胎仔外观、内脏和骨骼。结果 环磷酰胺组对兔生殖功能及胚胎形成无明显影响，可引起外观、内脏和骨骼畸变。胎仔外观腭裂畸形率为32.95%；内脏变异率为10.23%；骨骼畸形率为23.37%。结论 新西兰兔GD11静脉给予环磷酰胺30 mg·kg-1可引起胎仔畸形，畸形种类和比例适当，可用于生殖试验阳性对照。

关键词: 环磷酰胺, 生殖毒性, 孕兔, 阳性对照