Evaluation of the mutagenicity of simple substituted quinoxalines in Salmonella typhimurium

Limited information is available on the genotoxicity of simple quinoxalines, distinct from the food related carcinogenic derivatives bearing an aromatic amino group. Isolated positive results, with no apparent structure–activity relationships, were reported in earlier studies on alkyl substituted quinoxalines, raising a safety concern in some regulatory authorities in view of the potential human exposure related to their use as food flavors. In order to elucidate the genotoxic hazard posed by simple quinoxalines, in this work a random set of mono- and bi-substituted methyl, chloro- and hydroxyl- quinoxalines have been tested in an OECD-compliant bacterial reversion test (TG 471). The results obtained do not highlight any genotoxic potential in the set of quinoxalines examined, and suggest that this may be a common trait for other simple substituted quinoxalines. Earlier published positive findings were not confirmed in this work, which call for a cautious approach in the use of literature data for regulatory purpose.