Teratogenicity and embryolethality of acrolein and structurally related compounds in rats

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Abstract
Acrolein, a metabolite of the anticancer agent cyclophosphamide, is teratogenic to rats after intraamniotic administration. It is not known whether acrolein or a metabolite of acrolein is responsible for the teratogenicity of this compound. We assessed the teratogenicity and embryolethality of acrolein and five structurally related compounds: acrylic acid, allyl alcohol, glycidol, glyceraldehyde, and propionaldehyde by intraamniotic injections in Sprague-Dawley rats on day 13 of gestation. All compounds tested were significantly embryolethal with at least one concentration of the drug. Acrolein was the most embryolethal of the drugs, causing a significant increase in resorptions with as little as 0.1 μg/fetus; the other drugs were embryolethal at doses 100–10,000 times that of acrolein. Acrolein was also the most teratogenic of the drugs tested; a dose as low as 5 μg/fetus caused a significant increase in the incidence of fetal malformations. Of the other compounds tested, only glycidol at a dose of 1,000 μg/fetus induced a significant number of malformed fetuses compared to control. These results suggest that it is acrolein itself that is responsible for its teratogenicity.