Developmental toxicology of retinylidene methyl nitrone in the golden hamster

A single oral dose in pregnant hamsters of 50, 75 or 100 mg/kg of all-trans-retinylidene methyl nitrone, a retinoid with potential cancer chemo-preventive properties, resulted in a significant increase in the number of litters containing abnormal offspring. An elevated mean litter frequency of malformed offspring was also observed following doses of 50 mg/kg or greater of the retinoid. Doses of 12.5 mg/kg or greater were associated with a significant increase in embryonic death. Intubation of the retinoid failed to induce signs of illness in any of the pregnant hamsters and the maternal weight gain of the treated animals was not significantly different from that of dams given an equivalent volume of the vehicle. The dysmorphic syndrome induced by treatment with all-trans-retinylidene methyl nitrone during the early primitive streak stage of gestation was identical to that induced by treatment with all-trans-retinoic acid. The teratogenic effects of all-trans-retinylidene methyl nitrone may be associated with biotransformation of the parent nitrone in the acidic environment of the stomach to all-trans-retinoic acid.