The embryotoxicity of the cyclophosphamide metabolite acrolein in rabbits, tested in vivo by i.v. injection and by the yolk-sac method.

On the 9th day of gestation the embryotoxic effects of acrolein were tested in vivo by i.v. injection in rabbits (3, 4.5 and 6 mg/kg) and by injection into the yolk sac of rabbits embryos (10, 20 and 40 microliter/blastoderm of an 0.84% acrolein solution: yolk-sac method). After i.v. injection acrolein caused mainly embryolethal effects in a dose-dependent manner. After direct injection into the rabbit embryos acrolein led to an increase of resorption and malformation rate in a dose-dependent manner. The highest dose in both investigations showed that by i.v. injection acrolein acts as an embryotoxic agent in a 50-60 times lower concentration. As acrolein plays an important role in the metabolism of cyclophosphamide the results are discussed in relation to the embryotoxicity of cyclophosphamide.