COMPARATIVE SUB-CHRONIC TOXICITY OF ALL TRANS-RETINOIC AND 13-CIS-RETINOIC ACID IN SPRAGUE-DAWLEY RATS

These studies were carried out to provide additional information on the toxicity of isomeric retinoic acids that may be useful for chemoprevention of epithelial cancer. Young adult Sprague-Dawley rats 52 days old and weighing approximately 200 g were treated for 4, 8, or 12 weeks with a daily oral dose of 0.5, 2.0, or 5.0 mg/kg of all-trans-retinoic acid or 4.0, 15.0, or 40.0 mg/kg of 13-cis-retinoic acid. No differences were observed in the percentage of weight gained or in food consumption between treated and control rats. Dose-related decreases in plasma albumin concentration were observed in female rats treated with either compound and in male rats treated with 13-cis-retinoic acid. Increases in plasma alkaline phosphatase activity appeared in rats treated with either compound. Decreased hemoglobin concentrations were dose-related in rats treated with 13-cis-retinoic acid but not in those treated with the all-trans compound. Overt toxicity was not observed after administration of either compound, but 13-cis-retinoic acid may have a greater potential for clinical utility, since higher dosages were tolerated. © 1979.