Evaluation of the Genetic Toxicity of the Peroxisome Proliferator and Carcinogen Methyl Clofenapate, Including Assays Usin Muta TM Mouse and Big Blue™ Transgenic Mice

The rodent liver carcinogen and hepatic peroxisome proliferator methylclofenapate (MCP) has been evaluated for genetic toxicity in a range of in vitro and rodent genotoxicity assays. It gave a negative response in each of the following assays: mutagenicity to S.typhimurium and E.coli (± S9 mix, plate and pre-incubation assays), clastogenicity to cultured human lymphocytes and CHO cells (± S9 mix), a mouse bone marrow micronucleus assay (24h and 48h sampling), a rat liver assay for UDS in vivo (12h sampling), assays for lac I (Big Blue™) and lac Z (Muta™ Mouse) mutations in the liver of transgenic mice, and an assay of the ability of MCP to modify the mutagenicity to the liver of dimethylnitrosamine in both transgenic mutation assays. The micronucleus and UDS assays were conducted using a single administration of MCP at its maximum tolerated dose, while the transgenic assays were conducted using nine daily administrations of MCP at its cancer bioassay dose level. These nine daily administrations were shown...