Teratogenic profile of retinylidene methyl nitrone and retinol in Swiss-Webster mice

A single oral dose of 75 mg/kg of all-trans-retinol or all-trans-retinylidene methyl nitrone, retinoids with potential cancer chemopreventive properties, on one of five successive days of embryogenesis resulted in a shift in the pattern of developmental anomalies in fetal mice. Treatment on days 7, 8, or 9 with retinal primarily induced malformations of the head whereas treatment on day 11 induced bilateral forelimb reduction defects. Treatment on day 8 with either retinoid produced the highest in utero death rate. Intubation of either retinoid on day 10 failed to induce a significant increase in the number of litters containing offspring with malformations, and the embryonic death rate declined to control values. The malformations induced by administration of either retinoid were similar, but retinol was always associated with a higher total percentage of malformed offspring. The similar teratogenic profile of these two retinoids may be related to their in vivo biotransformation to all-trans-retinoic acid.