Embryopathic effects of cyclophosphamide.

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.