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SEURAT-1 is a European public-private research consortium that is working towards animal-free testing of chemical compounds and the highest level of consumer protection. A research strategy was formulated around harnessing knowledge about toxicological modes-of-action and an organisational model was developed that combines crowd-sourcing with individual excellence. The proof of the initiative will be in demonstrating the applicability of the concepts on which SEURAT-1 is built. This is done on three levels: (i) Theoretical prototypes for adverse outcome pathways are formulated based on knowledge already available in the scientific literature on investigating the toxicological mode-of-actions leading to adverse outcomes; (ii) adverse outcome pathway descriptions are used as a guide for the formulation of case studies to further elucidate the theoretical model and to develop integrated testing strategies for the prediction of certain toxicological effects; (iii) further case studies target the application of knowledge gained within SEURAT-1 in the context of safety assessment. The ultimate goal would be to perform ab initio predictions based on a complete understanding of toxicological mechanisms. In the near-term it is more realistic that data from innovative testing methods will support read-across arguments. Both scenarios, the ab initio prediction and the read-across approach, are addressed with respective case studies for improved safety assessment. A conceptual framework for a rational integrated assessment strategy emerged from the efforts of designing the case studies and is discussed in the context of international developments focussing on alternative approaches for evaluating chemicals using the new 21st century tools for toxicity testing. JRC.I.5-Systems Toxicology