We synthesised and toxicologically characterised the arsenic metabolite thiodimethylarsinic acid (thio-DMAV). Successful synthesis of highly pure thio-DMAV was confirmed by state-of-the-art analytical techniques including 1H-NMR, HPLC-FTMS, and HPLC-ICPMS. Toxicological characterization was carried out in comparison to arsenite and its well-known trivalent and pentavalent methylated metabolites. It comprised cellular bioavailability as well as different cytotoxicity and genotoxicity end points in cultured human A549 lung cells. Of all arsenicals investigated, thio-DMAV exerted the strongest cytotoxicity. Moreover, thio-DMAV did not induce DNA strand breaks and an increased induction of both micronuclei and multinucleated cells occurred only at beginning cytotoxic concentrations, indicating that thio-DMAV does not act via a genotoxic mode of action. Finally, to assess potential implications of thio-DMAV for human health, further mechanistic studies are urgently necessary to identify the toxic mode of action of this highly toxic, unusual pentavalent organic arsenical.
