EU-ToxRisk is an Integrated European ‘Flagship’ Programme Driving Mechanism-based Toxicity Testing and Risk Assessment for the 21st century. The vision of this project is to drive the required paradigm shift in toxicological testing away from ‘black box’ animal testing towards a toxicological assessment based on human cell responses and a comprehensive mechanistic understanding of cause-consequence relationships of chemical adverse effects. EU-ToxRisk will integrate advancements in cell biology, omics technologies, systems biology and computational modelling to define the complex chains of events that link chemical exposure to toxic outcome. The consortium will provide proof of concept for such a mechanism-based chemical safety testing strategy. The focus of this project is on two areas: repeated dose systemic toxicity, using the lung, kidney, liver and nervous system as examples of potential target organs; and developmental and reproductive toxicity. It will also provide guidance for its universal application, allowing to push the entire field forward in an integrated manner. The ultimate goal is to deliver testing strategies to enable reliable, animal-free hazard and risk assessment of chemicals.