Comparative toxicity of oral all-trans-retinoic acid and the aromatic retinoids Ro 10-9359 and Ro 12-7554 in rats: Hematologic and biochemical studies

Reduced bodyweight gains and bone fractures are the most obvious effects in rats after repeated ingestion of high doses of vitamin A derivatives. These effects are dose dependent and well reproducible. Doses of different retinoids causing similar reductions of bodyweight gain and comparable frequencies of bone fractures can be called equitoxic in this respect. The following study was performed with approximately equitoxic doses of all-trans-retinoic acid (15 mg/kg/d) and the aromatic retinoids Ro 10-9359, etretinate (7.5 mg/kg/d), and Ro 12-7554 (2 mg/kg/d) administered as dietary admix to 18 rats/sex/group for 4 weeks. An additional group of 18 rats/sex remained untreated and served as controls. The aim of this experiment was to investigate and compare the toxic effect of these retinoids on additional parameters such as red blood counts, hemoglobin, alkaline phosphatase, cholesterol, and serum proteins known to be altered in rats exposed to this class of compounds. Under the conditions of this study, using doses which were approximately equitoxic as regards weight gain and bone fractures, the most pronounced changes on the additional parameters mentioned above were caused by retinoic acid. Less influence was shown by etretinate. The degree of compound-related effects was lowest in the rats treated with the newly developed aromatic retinoid Ro 12-7554.