In vitro and in vivo studies on the potential mutagenicity of alclofenac, dihydroxyalclofenac and alclofenac epoxide

Alclofenac (A) and two of its metabolites, dihydroxyalclofenac (DHA) and alclofenac epoxide (AE), were tested for their mutagenic potential. Alclofenac and DHA showed no mutagenic, transforming or clastogenic potential in any in vitro experiment. The addition of a supplementary metabolic activation system did not change the response of those two compounds in any test procedures in vitro. AE, an intermediary metabolite between A and DHA, was mutagenic by itself in the Ames test, but in the presence of a liver post‐mitochondrial fraction its activity of Salmonella typhimurium was greatly decreased. Dominant lethal mutations were not induced in male rats given alclofenac, and AE had no effect in the micronucleus test. In human volunteers given alclofenac at therapeutic dose levels, no mutagenic activity was found in the urine and no significant increase in the incidence of structural chromosome aberrations was observed in peripheral blood lymphocytes.