Integrating mechanisms and quantitative in vitro-in vivo extrapolation (QIVIVE) modelling for risk assessment based on in vitro testing (Risk-IT)
Risk-IT integrates expert knowledge gained from previous systems toxicology projects with innovative in vitro data generation technologies (High Content Screening, Metabolomics) and reverse physiologically-based pharmacokinetic modelling to address the unmet need for non-animal based approaches to predict repeat dose systemic toxicity. Focusing on kidney toxicity as an exemplary area and key target organ of chemical/drug induced toxicity, Risk-IT aims to provide a proof-of-concept for the successful integration of new mechanism-based in vitro methods and toxicokinetic modelling into a tiered testing strategy that is fit-for purposes of regulatory decision making. It is anticipated that the project will directly impact the 3Rs by developing a ready-to-use battery of in vitro assays predictive of nephrotoxicity for use in drug and chemical safety assessment. Moreover, by assessing the confidence in risk assessment based on in vitro data, the outcomes of Risk-IT are expected to boost similar activities in other areas of systemic toxicity.