title: In vitro toxicological characterization of two arsenosugars and their metabolites.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Graduate School of Chemistry, University of Münster, Münster, Germany.
authors.forename: Larissa
authors.initials: L
authors.lastname: Leffers
authors.forename: Franziska
authors.initials: F
authors.lastname: Ebert
authors.forename: Mojtaba S
authors.initials: MS
authors.lastname: Taleshi
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Francesconi
authors.forename: Tanja
authors.initials: T
authors.lastname: Schwerdtle
mesh_terms: D001149:Arsenates / Q000493:pharmacokinetics / Q000633:toxicity*; D018053:Arsenites / Q000493:pharmacokinetics / Q000633:toxicity*; D001682:Biological Availability; D018938:Caco-2 Cells; D002101:Cacodylic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage / Q000187:drug effects; D005506:Food Contamination / Q000032:analysis*; D006801:Humans; D009005:Monosaccharides / Q000493:pharmacokinetics / Q000633:toxicity*; D018570:Risk Assessment; D018675:Toxicity Tests
chemical_list: D001149:Arsenates; D018053:Arsenites; D009005:Monosaccharides; C449161:arsenosugar; C523062:thio-dimethylarsinate; D002101:Cacodylic Acid
keywords: Arsenosugars; Cellular and intestinal bioavailability; Cellular toxicity; Genotoxicity; Marine food
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