1. In vitro toxicological characterization of two arsenosugars and their metabolites.
- Author
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Leffers L, Ebert F, Taleshi MS, Francesconi KA, and Schwerdtle T
- Subjects
- Arsenates pharmacokinetics, Arsenites pharmacokinetics, Biological Availability, Caco-2 Cells, Cacodylic Acid analogs & derivatives, Cacodylic Acid pharmacokinetics, Cacodylic Acid toxicity, Chromatography, High Pressure Liquid, DNA Damage drug effects, Humans, Monosaccharides pharmacokinetics, Risk Assessment, Toxicity Tests, Arsenates toxicity, Arsenites toxicity, Food Contamination analysis, Monosaccharides toxicity
- Abstract
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., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2013
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