TRETINOIN - A REVIEW OF PRECLINICAL TOXICOLOGICAL STUDIES

Tretinoin (all-trans-retinoic acid) has shown efficacy in the treatment of acute promyelocytic leukemia. The preclinical toxicological profile of tretinoin was similar to that of other retinoids. The compound had a relatively low acute toxicity; repeated doses resulted in a substantial increase in toxicity that was a function of dose and duration of exposure. Bone fractures, elevated alkaline phosphatase, and testicular degeneration were produced by repeated doses of tretinoin. Teratogenicity was demonstrated in several species. Tretinoin was inactive in the Ames test but appeared to induce sister-chromatid exchanges in human diploid fibroblasts. Insufficient data are available to evaluate the carcinogenic potential of tretinoin. (C) 1993 Wiley-Liss, Inc.