Genotoxicity studies on ebrotidine

Arzneimittelforschung. 1997 Apr;47(4A):511-4.

Abstract

Five genotoxicity studies on ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio] ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542), including at least four of the battery of tests recommended by toxicological regulatory guidelines for new drugs, were conducted. These tests were the Ames test for determination of bacterial gene mutations, sex-linked recessive lethal mutation test in Drosophila for gene mutations in eukaryotic systems, in vitro chromosome aberration test and micronucleus test for evaluation of structural and numerical aberrations, and sister chromatid exchange frequency test for assessment of non-specific damage to chromatin. 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 dose range toxicity study was also performed to determine the dosage levels or concentrations to be tested for the assessment of genotoxic effects. 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 clastogenic effects in any of the experimental systems tested.

MeSH terms

  • Animals
  • Benzenesulfonates / toxicity*
  • Chromosome Aberrations
  • Drosophila melanogaster / genetics
  • Erythrocytes / drug effects
  • Genes / drug effects*
  • Genes, Bacterial / drug effects
  • Histamine H2 Antagonists / toxicity*
  • Humans
  • Lymphocytes / drug effects
  • Mice
  • Micronucleus Tests
  • Mutagenicity Tests
  • Salmonella typhimurium / genetics
  • Sister Chromatid Exchange
  • Thiazoles / toxicity*

Substances

  • Benzenesulfonates
  • Histamine H2 Antagonists
  • Thiazoles
  • ebrotidine