Subchronic toxicity of all-trans-retinoic acid and retinylidene dimedone in Sprague-Dawley rats |
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Authors: | P J Kurtz D C Emmerling D J Donofrio |
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Institution: | Biological Sciences Department, Battelle Memorial Institute, Columbus, Ohio 43201 U.S.A. |
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Abstract: | Sprague-Dawley rats received daily oral gavage doses of either 2-retinylidene-5,5-dimethyl-1,3-cyclohexanedione (retinylidene dimedone; 14, 50, 150, or 330 mg/kg) or all-trans-retinoic acid (1, 4, 14, or 50 mg/kg) for 13 weeks. Rats given 50 mg/kg of all-trans-retinoic acid developed numerous long-bone fractures and became moribund during the third week of the study. Those receiving lower dosages survived until scheduled termination, but the 14 mg/kg group showed clear signs of retinoid intoxication including growth depression, anemia, serum alkaline phosphatase elevation, bone fracture, and testicular degeneration. Exposure to retinylidene dimedone did not result in any treatment-related deaths, growth depression, or histopathologic lesions, even at the highest dose, 300 mg/kg. Animals given this dosage exhibited mild anemia, equivocal evidence of bone fracture, but no increase in alkaline phosphatase activity. Retinylidene dimedone appears to be considerably less toxic than all-trans-retinoic acid. |
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Keywords: | Retinoid Retinylidene dimedone Chemoprevention Vitamin A |
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