EU-ToxRisk: status quo of the Horizon2020 flagship project on non-animal toxicology (#839)
1 University of Konstanz, CAAT-Europe, Konstanz, Germany
EU-ToxRisk is the Horizon2020 flagship research project for new approach method (NAM)-based toxicity testing in Europe. The ultimate aim of the project is to develop human-relevant toxicity testing strategies that can be applied in a regulatory or screening context using only NAMs. NAMs include different approaches such as cell-based models, omic technologies, in silico and toxicokinetic modelling. They can be used to investigate key and intermediate steps leading to apical endpoints of toxicity. The adverse outcome pathway (AOP) concept paves the way towards a use of mechanistic toxicological data for regulatory applications. Nonetheless, the integration of NAM data into a risk assessment strategy is challenging, in particular for complex endpoints such as repeated dose toxicity (RDT) or developmental/reproductive toxicity (DART). In this session, we will provide an overview of the use of NAMs developed by the EU-ToxRisk programme, which cover systemic RDT in different target organs and DART toxicity areas. A focus will be set on read-across approaches and their application for risk assessment, also from an industry perspective. We will discuss about practical applications of AOPs for safety assessment. Examples for the use of physiology-based pharmacokinetic modelling (PBPK) to extrapolate NAM data to in vivo doses will be given. Finally, we will report on recent results coming from the application of high-content technologies (e.g. RNA-seq).
Program of the session
Keywords: New approach methods (NAMs), adverse outcome pathway, repeated dose toxicity, developmental/reproductive toxicity, risk assessment