Drinking water must be disinfected prior to its distribution for human consumption. This water treatment process generates disinfection by-products (DBPs), formed by the interaction of the disinfectant with organic matter, anthropogenic contaminants and inorganic (bromide/iodide) matter naturally present in source water. Due to the potential genotoxic/carcinogenic risk of these DBPs, we have investigated the mutagenic potential of six of such compounds on the thymidine kinase (Tk) gene in the well-validated mouse lymphoma assay (MLA). The MLA quantifies a wide range of genetic alterations affecting the expression of this gene in L5178Y/Tk+/--3.7.2C cells. In this study we selected six emerging DBPs, corresponding to three different chemical classes: halonitromethanes (bromonitromethane and trichloronitromethane), halogenated acetaldehydes (tribromoacetaldehyde and chloral hydrate) and hydroxyfuranones (mucobromic and mucochloric acids), each class including one chlorinated and one brominated form. The results showed that after 4h of treatment, only mucobromic acid increased the frequency of mutant colonies, with a higher proportion of small colonies, which would indicate a clastogenic potential. This is the first study reporting mutagenicity data in mammalian cells for the six selected DBPs. © 2011 Elsevier B.V.