In vitro toxicological characterization of two arsenosugars and their metabolites

SCOPE: In their recently published Scientific Opinion on Arsenic in Food, the European Food Safety Authority concluded that a risk assessment for arsenosugars is currently not possible, largely because of the lack of relevant toxicological data. To address this issue, we carried out a toxicological in vitro characterization of two arsenosugars and six arsenosugar metabolites. METHODS AND RESULTS: The highly pure synthesized arsenosugars, DMA(V)-sugar-glycerol and DMA(V)-sugar-sulfate, investigated in this study, as well as four metabolites, oxo-dimethylarsenoacetic acid (oxo-DMAA(V)), oxo-dimethylarsenoethanol (oxo-DMAE(V)), thio-DMAA(V) and thio-DMAE(V), exerted neither cytotoxicity nor genotoxicity up to 500 μM exposure in cultured human bladder cells. However, two arsenosugar metabolites, namely dimethyl-arsinic acid (DMA(V)) and thio-dimethylarsinic acid (thio-DMA(V)), were toxic to the cells; thio-DMA(V) was even slightly more cytotoxic than arsenite. Additionally, intestinal bioavailability of the arsenosugars was assessed applying the Caco-2 intestinal barrier model. The observed low, but significant transfer rates of the arsenosugars across the barrier model provide further evidence that arsenosugars are intestinally bioavailable. CONCLUSION: In a cellular system that metabolizes arsenosugars, cellular toxicity likely arises. Thus, in strong contrast to arsenobetaine, arsenosugars cannot be categorized as nontoxic for humans and a risk to human health cannot be excluded.