Teratogenicity and embryolethality of acrolein and structurally related compounds in rats.
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 micrograms/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 micrograms/fetus caused a significant increase in the incidence of fetal malformations. Of the other compounds tested, only glycidol at a dose of 1,000 micrograms/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.
D000433:1-Propanol / Q000009:adverse effects; D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000171:Acrolein / Q000009:adverse effects*; D000179:Acrylates / Q000009:adverse effects; D000447:Aldehydes / Q000009:adverse effects*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000009:adverse effects; D005260:Female; D005313:Fetal Death / Q000139:chemically induced*; D005327:Fetal Resorption / Q000139:chemically induced; D005985:Glyceraldehyde / Q000009:adverse effects; D011247:Pregnancy; D020005:Propanols; D051381:Rats / Q000196:embryology*; D011919:Rats, Inbred Strains
D000179:Acrylates; D000447:Aldehydes; D004852:Epoxy Compounds; D020005:Propanols; D005985:Glyceraldehyde; C006463:allyl alcohol; D000171:Acrolein; D000433:1-Propanol; C005556:propionaldehyde; C036658:acrylic acid; C004312:glycidol