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Prediction of microvesicular liver steatosis: Read-across case study with VPA analogues

pdf fileGrapel R; Tluczkiewicz I; Abdelaziz A; van de Burg B; van de Water B; Fisher C; Aguayo A; Bischoff L; Hengstler J; Escher S; Maclennan R; Exner T; Norinder U; Taboureau O; Drewe WC; Long A; Hatley O; Pawar G; Ecker G; Bois F; Jennings P; Stober R; Goldmann D; Gautier F; Limonciel A; Lindberg J; Braunbeck T; Tebby C; Moritz W; Kelm J; Brotzmann K;

This case study aims to develop non-animal approaches which can be used to reduce the uncertainty of read across predictions. Valproic acid (VPA), a short-branched carboxylic acid, was selected as the lead compound for this case study. VPA is used in the treatment of epilepsy in humans and induces microvesicular hepatic steatosis in the liver of some patients. In this read-across case study, it is investigated whether the EU-ToxRisk in silico and in vitro models predict the in vivo potential of VPA analogues to induce microvesicular steatosis, qualitatively and quantitatively.


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