Malformations produced in mice and rats by oxidized linoleate

Abstract

Linoleate oxidation products were investigated for teratogenic activity in rats and mice. Linoleic acid was oxidized at ambient temperatures until about 30% conjugated diene was present. The mixture was characterized and fed to the experimental animals at a level of 10% in the diet on 3 days/wk before and during pregnancy. Each treated rat received during pregnancy, a total dose of 2·6–3·0 ml and each treated mouse a total dose of 1·2–1·6 ml. Malformations of the urogenital system occurred more frequently in the progeny of treated rats than in the offspring of control animals, but the linoleate oxidation products had no observable effect on the progeny of mice. An investigation was then made of the embryotoxicity in mice of purified linoleic acid, oxidized linoleic acid or purified linoleic acid hydroperoxide applied directly to the ovaries. After the treatment with linoleic acid hydroperoxide an increase in foetal malformations occurred in litters of the first generation, and second-generation litters showed an increase in embryonic resorptions. After treatment with oxidized linoleic acid no change was detected in litters of the first generation but an increase in embryonic resorptions occurred in the progeny of the second generation. The incidence of malformations after treatment with linoleic acid was similar to that occurring in a group of untreated controls.