Mutagenic evaluation of ronidazole.
Ronidazole was evaluated for mutagenic potential using in vitro microbial tests and in vivo studies in mice. The microbial test used the histidine requiring mutants of Salmonella typhimurium with and without a rat liver microsomal activation system (Ames test). The studies in mice included the dominant lethal test, micronucleus test and cytogenetic assays. Ronidazole was given orally in doses of 50, 100 and 200 mg/kg/day in the in vivo studies. In the dominant lethal test, groups of male mice were treated for five consecutive days before being mated with untreated females. In the micronucleus test, the mice were administered the compound for 2 or 5 consecutive days; they were killed 6 h after the last dose and bone marrow was examined for the presence of micronuclei in developing erythrocytes. In the cytogenetic assays, bone marrow cells in metaphase were examined for chromosome aberrations, 6, 24 and 48 h after mice were treated acutely with the test compound. In addition, similar examinations of chromosomes were made on mice given five consecutive dosages of ronidazole and killed 6 h after the last dose. The results of the various in vivo studies did not suggest that ronidazole would be mutagenic for the mammal. Ronidazole at concentrations of 10 and 50 mug/plate was found to increase the number of back mutations of missense mutants in the in vitro bacterial test. This finding confirms the results of Voogd et al. [19]. Incorporation of the microsomal activation system had no effect on the mutagenic capability of the test compound. In conclusion, although ronidazole was shown to be mutagenic in in vitro bacterial systems, the in vivo systems did not suggest that the compound would be mutagenic for the mammal.
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D005799:Genes, Dominant; D005804:Genes, Lethal; D006639:Histidine / Q000378:metabolism; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens; D009154:Mutation / Q000187:drug effects; D009593:Nitroimidazoles / Q000494:pharmacology*; D012385:Ronidazole / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects
D009153:Mutagens; D009593:Nitroimidazoles; D006639:Histidine; D012385:Ronidazole