Gilani S H, Chatzinoff M
Environ Res. 1983 Aug;31(2):296-301. doi: 10.1016/0013-9351(83)90007-5.
Cyclosphosphamide, dissolved in saline, was injected into the air sac of white Leghorn chick eggs in dose levels of 0.005, 0.007, 0.010, 0.012, 0.015, and 0.017 mg per egg. Eggs received a single injection of cyclophosphamide on Days 0, 1, 2, or 3 of incubation. Control eggs were injected with an equivalent volume of saline (0.1 ml per egg). In all 904 chicken eggs were used for this study. Surviving embryos were sacrificed when they reached 11 days of incubation. The LD50 values for Days 1, 2, and 3 were 0.017, 0.007, and 0.012 mg per egg, respectively. The overall incidence of abnormal embryos for Days 0, 1, 2, and 3 were 7, 6.3, 12, and 22%, respectively. Abnormalities such as reduced body size, everted viscera, short and twisted limbs, eye defects, abnormal beak, and short and twisted neck were commonly seen in survivors no matter when exposed to cyclophosphamide. The teratogenicity of cyclophosphamide was noted to be the highest in the embryos treated on Day 3. The present study has demonstrated that cyclophosphamide is toxic and teratogenic during the period of early organogenesis in the chick embryos.
将环磷酰胺溶于生理盐水中，以每枚鸡蛋0.005、0.007、0.010、0.012、0.015和0.017毫克的剂量水平注入白来航鸡胚的气室。在孵化的第0、1、2或3天，鸡蛋接受单次环磷酰胺注射。对照鸡蛋注射等量的生理盐水（每枚鸡蛋0.1毫升）。本研究共使用了904枚鸡蛋。存活的胚胎在孵化11天时处死。第1、2和3天的半数致死剂量值分别为每枚鸡蛋0.017、0.007和0.012毫克。第0、1、2和3天异常胚胎的总体发生率分别为7%、6.3%、12%和22%。无论何时接触环磷酰胺，存活胚胎中常见的异常情况包括体型减小、内脏外翻、四肢短小扭曲、眼部缺陷、喙异常以及颈部短小扭曲。环磷酰胺对在第3天处理的胚胎的致畸性最高。本研究表明，环磷酰胺在鸡胚早期器官发生期具有毒性和致畸性。
