Mechanism based in silico evaluation of hepatotoxicity
Milen Todorov · 2014
Efforts to develop new predictive methods to assess the likelihood of a xenobiotics being a hepatotoxicants have been challenging due to the increasing concerns of safety chemical assessments. A huge variety of chemicals exist in the environment without information for their ability to exert hepatotoxic effect. Based on the assumption that damages on DNA may lead to hepatotoxic outcome it is assumed that available models for identification of mutagens can be used for prediction of the effect. In the current study this assumption is investigated by in silico application of DNA reactivity profilers over dataset of chemicals with known hepatotoxic effect. The results suggest that the approach can be used for identification of hepatotoxins with special concern about the influence of their metabolism. The overall predictions show high statistical performance - 86% correct predictions for hepatotoxins. Regarding non hepatotoxins it was found that the role of metabolic detoxification should be taken into account for explanation the effect of in vitro mutagenic chemicals.