@article{WittEbertMeyeretal.2017,
  author    = {Witt, Barbara and Ebert, Franziska and Meyer, S{\"o}ren and Francesconi, Kevin A. and Schwerdtle, Tanja},
  title     = {Assessing neurodevelopmental effects of arsenolipids in pre-differentiated human neurons},
  series = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology},
  volume    = {61},
  journal   = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {1613-4125},
  doi       = {10.1002/mnfr.201700199},
  pages     = {10},
  year      = {2017},
  abstract  = {Scope: In the general population exposure to arsenic occurs mainly via diet. Highest arsenic concentrations are found in seafood, where arsenic is present predominantly in its organic forms including arsenolipids. Since recent studies have provided evidence that arsenolipids could reach the brain of an organism and exert toxicity in fully differentiated human neurons, this work aims to assess the neurodevelopmental toxicity of arsenolipids. Methods and results: Neurodevelopmental effects of three arsenic-containing hydrocarbons (AsHC), two arsenic-containing fatty acids (AsFA), arsenite and dimethylarsinic acid (DMA(V)) were characterized in pre-differentiated human neurons. AsHCs and arsenite caused substantial cytotoxicity in a similar, low concentration range, whereas AsFAs and DMA(V) were less toxic. AsHCs were highly accessible for cells and exerted pronounced neurodevelopmental effects, with neurite outgrowth and the mitochondrial membrane potential being sensitive endpoints; arsenite did not substantially decrease those two endpoints. In fully differentiated neurons, arsenite and AsHCs caused neurite toxicity. Conclusion: These results indicate for a neurodevelopmental potential of AsHCs. Taken into account the possibility that AsHCs might easily reach the developing brain when exposed during early life, neurotoxicity and neurodevelopmental toxicity cannot be excluded. Further studies are needed in order to progress the urgently needed risk assessment.},
  language  = {en}
}
@article{WittMeyerEbertetal.2017,
  author    = {Witt, Barbara and Meyer, S{\"o}ren and Ebert, Franziska and Francesconi, Kevin A. and Schwerdtle, Tanja},
  title     = {Toxicity of two classes of arsenolipids and their water-soluble metabolites in human differentiated neurons},
  series = {Archives of toxicology : official journal of EUROTOX},
  volume    = {91},
  journal   = {Archives of toxicology : official journal of EUROTOX},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {0340-5761},
  doi       = {10.1007/s00204-017-1933-x},
  pages     = {3121 -- 3134},
  year      = {2017},
  abstract  = {Arsenolipids are lipid-soluble organoarsenic compounds, mainly occurring in marine organisms, with arsenic-containing hydrocarbons (AsHCs) and arsenic-containing fatty acids (AsFAs) representing two major subgroups. Recently, toxicity studies of several arsenolipids showed a high cytotoxic potential of those arsenolipids in human liver and bladder cells. Furthermore, feeding studies with Drosophila melanogaster indicated an accumulation of arsenolipids in the fruit fly's brain. In this study, the neurotoxic potential of three AsHCs, two AsFAs and three metabolites (dimethylarsinic acid, thio/oxo-dimethylarsenopropanoic acid) was investigated in comparison to the toxic reference arsenite (iAsIII) in fully differentiated human brain cells (LUHMES cells). Thereby, in the case of AsHCs both the cell number and cell viability were reduced in a low micromolar concentration range comparable to iAsIII, while AsFAs and the applied metabolites were less toxic. Mechanistic studies revealed that AsHCs reduced the mitochondrial membrane potential, whereas neither iAsIII nor AsFAs had an impact. Furthermore, neurotoxic mechanisms were investigated by examining the neuronal network. Here, AsHCs massively disturbed the neuronal network and induced apoptotic effects, while iAsIII and AsFAs showed comparatively lesser effects. Taking into account the substantial in vitro neurotoxic potential of the AsHCs and the fact that they could transfer across the physiological barriers of the brain, a neurotoxic potential in vivo for the AsHCs cannot be excluded and needs to be urgently characterized.},
  language  = {en}
}