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von Kreybig首先报告在妊娠第10～14天给Wistar和Sprague-Dawley大鼠腹腔内注射不同剂量环磷酰胺(CP)的反应。第10天注射5 mg/kg CP对胚胎发育没有影响。但注射7.5和10 mg/kg时可使胚胎致死,阻碍胚胎发育。11天时注射5、10和20 mg/kgCP,最高剂量组动物产胎鼠甚少,但所有剂量组都有致畸作用。畸形的类型有脑膨出、露脑、小头、肢体不全(并趾和缺趾)、颜面发育不全和骨骼骨化障碍(CP综合征)。12～13天注射
von Kreybig first reported the response of intraperitoneal injection of different doses of cyclophosphamide (CP) to Wistar and Sprague-Dawley rats on days 10-14 of gestation. Injection of 5 mg / kg CP on day 10 had no effect on embryonic development. However, embryos were lethal at 7.5 and 10 mg / kg, hindering embryonic development. Injection of 5, 10, and 20 mg / kg CP at day 11 resulted in very few fetuses in the highest dose group but teratogenicity in all dose groups. Deformities of the brain are bulging, nocturnal, small head, incomplete body (toe and missing toe), facial hypoplasia and skeletal ossification disorders (CP syndrome). 12 to 13 days injection