In Silico Approaches for Predicting Toxicity

Perspectives on the Development, Evaluation, and Application of in Silico Approaches for Predicting Toxicity Dr Patlewicz (US EPA) and Professor Cronin (Liverpool John Moores University) discuss the QSARs that can be used to meet regulatory testing requirements under REACH. The use of read-across is presented – emphasising both the availability of different frameworks for the development of read-across and frameworks for the assessment and evaluation of read-across justification – highlighting examples published in the literature as well as regulatory technical guidance (OECD, ECHA). Tools that can help facilitate the development of read-across, including the OECD QSAR Toolbox, are outlined. Attention is drawn to ongoing research that is evolving the way in which read-across approaches can be undertaken, including by exploiting the use of high-throughput screening data such as those generated under the US EPA’s ToxCast programme. The use of read-across and QSARs is framed in the context of integrated approaches to testing and assessment (IATA). Examples highlight how some IATA have evolved, particularly in the arena of skin sensitisation, where defined approaches have been developed. These formalise the use of certain non-animal test methods that characterise the key events within the associated adverse outcome pathway.