Review of the genotoxicity of 4-chloro-2-methylphenoxyacetic acid

4-Chloro-2-methylphenoxyacetic acid (MCPA) has been examined for genotoxicity in a range of in vitro and in vivo assays, including assays for gene mutation and clastogenicity. MCPA is non-mutagenic in bacterial and mammalian cell gene mutation assays. Increases in percentage aberrant cells were found on analysis of metaphases of human peripheral lymphocytes treated in vitro in the presence of auxiliary metabolic activation (S9), but only at doses approaching 10 mM and causing significant cytotoxicity. These increases may therefore be non-specific. No evidence for clastogenicity in vivo was found in the mouse bone marrow micronucleus assay or the Chinese hamster bone marrow metaphase assay. No evidence for either increases in sister chromatid exchange (SCE) frequency or DNA binding was found in the rat. Very small (less than 1.5 times controls) increases in SCE were observed in vivo in the hamster at toxic or maximum tolerated dose levels. MCPA is not alerting for likely genotoxic activity using established structure-activity relationship principles and it is concluded that, on the weight of evidence from the available data, MCPA is not genotoxic in vivo. This is consistent with its lack of carcinogenicity in rats and mice.