Mutagenicity tests of mofezolac (N-22).
1. The reverse mutation test was carried out on mofezolac (N-22) at dose range of 50-5000 micrograms/plate using Salmonella typhimurium strains, TA100, TA98, TA1535 and TA1537, and Escherichia coli strain WP2uvrA. In all tester strains no significant increases were observed in the number of revertant colonies as compared with solvent control in the absence or presence of mammalian metabolic activation system. 2. The chromosomal aberration test on N-22 was carried out using cultured Chinese hamster lung cells (CHL). The cells were treated with N-22 at the doses of 37.5, 75.0, 150 and 300 micrograms/ml without S9 Mix and at the doses of 150, 300, 450 and 600 micrograms/ml with S9 Mix. No significant differences were found in the incidence of structural-and numeral-aberrations of chromosomes as compared with the solvent control in the system without S9 Mix. However, in the system with S9 Mix, structural aberration (11.5%) and numeral aberration (14.2%) of chromosomes were observed in the groups of dosing 600 micrograms/ml with dose dependency. 3. These results indicate that N-22 has clastogenic activity by the metabolic activation.
Ohuchida
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Drug Safety Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Furukawa
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000633:toxicity*; D001711:Biotransformation; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007555:Isoxazoles / Q000493:pharmacokinetics / Q000633:toxicity*; D008168:Lung / Q000166:cytology; D016296:Mutagenesis / Q000187:drug effects*; D009152:Mutagenicity Tests / Q000379:methods; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007555:Isoxazoles; C054999:mofezolac