CARCINOGENICITY STUDIES AN EBROTIDINE

The results from two carcinogenicity studies on ebrotidine (N-[2-(E)-[ [2-[[[2-[(diaminomethylene)amino] o]ethyl]amino]methylene[-4-bromo-ben zensulfonamide CAS 100981-43-9, FI-3542) conducted in mice and rats ar e reported. Oral doses of 50, 200 and 500 mg/kg were administered to m ice for Is months and 50, 200 (150), 300 and 500 mg/kg were administer ed to rats for 24 months. The study design was prepared according to E EC guidelines, and the recommendations by the International Agency for Research on Cancer were used for the statistical analysis of data. We ekly palpations were made along the course of studies and general para meters were monitored. The only effects attributed to ebrotidine admin istration were a slight decrease in the survival rate of female mice g iven the 500 mg/kg dose and a lower weight gain in rats of both sexes. The histopathological data revealed that lipoid pneumonia and kidney calculi are more frequent in rats treated with doses of 500 and 300 mg /kg. No increment in the spontaneous occurrence of tumours or signific ant presence of tumours in treated animals differing from that in cont rol animals was observed, and a decrease in the time required for thei r onset that could be related to ebrotidine was not observed either. T here were no differences in hyperplastic and/or dysplastic changes bet ween treated and control animals. Therefore, it is deduced that ebroti dine does not induce neoplastic or preneoplastic effects in rats or mi ce even at doses of 500 mg/kg, at which some general toxicity effects are seen.