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目的探讨SD大鼠胚胎-胎仔发育毒性试验中,皮下给予不同剂量的环磷酰胺进行其剂量相关性的比较研究,建立阳性模型,积累实验室背景数据。方法取健康受孕SD大鼠100只,按体质量随机分为溶媒对照组(Veh:7.5 mg·kg-1氯化钠注射液)、环磷酰胺低(L:7 mg·kg-1)、中(M:10 mg·kg-1)、高(H:15 mg·kg-1)剂量组,每孕鼠组不少于20只,按程序皮下注射给药,观察临床表现,统计各剂量组孕鼠的体质量、摄食量、窝质量、黄体数、着床数、活胎数、死胎数和吸收胎数等指标,以及胎鼠的性别、体质量、身长、外观畸形、内脏畸形和骨骼畸形等指标。结果环磷酰胺低、中、高各剂量组对大鼠胚胎-胎仔发育均有毒性作用且具有明显的量效关系。结论皮下给予不同剂量的环磷酰胺对大鼠胚胎-胎仔发育毒性均产生影响且具有明显的量效关系,三种给药剂量均可建立胚胎-胎仔发育毒性试验阳性模型。
OBJECTIVE: To investigate the dose-dependent comparative study of different dose of cyclophosphamide in SD rat embryo-fetal developmental toxicity test, establish a positive model and accumulate laboratory background data. Methods 100 healthy pregnant SD rats were randomly divided into vehicle control group (Veh: 7.5 mg · kg-1 sodium chloride injection), low cyclophosphamide (L: 7 mg · kg-1) (M: 10 mg · kg-1) and high dose (H: 15 mg · kg-1), no less than 20 in each group were administered subcutaneously according to the procedure. The clinical manifestations were observed. The body weight, food intake, litter quality, luteal number, implantation number, number of live births, number of stillbirths and number of absorbed fetuses of pregnant rats in the test group were compared with those of the pregnant rats, such as gender, body weight, body length, appearance deformity, Skeletal deformities and other indicators. Results Cyclophosphamide low dose, middle dose and high dose groups had toxic effects on embryo-fetal development of rats and had a significant dose-response relationship. Conclusion Cyclophosphamide administered subcutaneously at different dosages has an effect on the developmental toxicity of embryo-fetus in rats and has a significant dose-effect relationship. The positive rates of embryo-fetal developmental toxicity test can be established in all three doses.