Carcinogenicity studies on ebrotidine.

The results from two carcinogenicity studies on ebrotidine (N-[2-(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl] methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) conducted in mice and rats are reported. Oral doses of 50, 200 and 500 mg/kg were administered to mice for 18 months and 50, 200 (150), 300 and 500 mg/kg were administered to rats for 24 months. The study design was prepared according to EEC guidelines, and the recommendations by the International Agency for Research on Cancer were used for the statistical analysis of data. Weekly palpations were made along the course of studies and general parameters were monitored. The only effects attributed to ebrotidine administration were a slight decrease in the survival rate of female mice given 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 significant presence of tumours in treated animals differing from that in control animals was observed, and a decrease in the time required for their onset that could be related to ebrotidine was not observed either. There were no differences in hyperplastic and/or dysplastic changes between treated and control animals. Therefore, it is deduced that ebrotidine does not induce neoplastic or preneoplastic effects in rats or mice even at doses of 500 mg/kg, at which some general toxicity effects are seen.