GENOTOXICITY STUDIES ON EBROTIDINE

Five genotoxicity studies on ebrotidine ethyl]amino]methylene]-4-bromo -benzenesulfonamide, CAS 100981-43-9, FI-3542), including at least fou r of the battery of tests recommended by toxicological regulatory guid elines for new drugs, were conducted. These tests were the Ames test f or determination of bacterial gene mutations, sex linked recessive let hal mutation test in Drosophila for gene mutations in eukaryotic syste ms, in vitro chromosome aberration lest and micronucleus test for eval uation of structural and numerical aberrations, and sister chromatid e xchange frequency test for assessment of non-specific damage to chroma tin. Negative and positive controls were used in all the experiments. The effects were investigated in the absence or presence of metabolic activation by S-9 microsomal fraction from rat liver homogenate. A dos e range toxicity study was also performed to determine the dosage leve ls or concentrations to be tested for the assessment of genotoxic effe cts. None of the tests showed a significant increase in the genotoxic parameters, both in vitro and in vivo in somatic or germ cells. It is, therefore, concluded that ebrotidine has not caused mutagenic or clas togenic effects in any of the experimental systems tested.