Risk assessment in the context of 21st century toxicology relies on the elucidation and understanding of mechanisms of toxicity. For that purpose, datasets generated by high-throughput technologies (e.g., high throughput/content screening) combined with various omics data types are now generated in vitro to test diverse set of chemicals (e.g. ToxCast). The development of relevant computational approaches for the analysis and integration of these big data remains challenging.The current scope of sbv IMPROVER (Industrial Methodology for Process Verification in Research; www.sbvimprover.com) is the verification of methods and concepts in systems biology research via challenges opened to the scientific community. Previous challenges brought new insights on methods and their associated results that address questions about diagnostic signatures, the translatability of biological responses/processes across species, and the relevance of biological causal network models. A new sbv IMPROVER challenge will be introduced aiming at evaluating methodologies for the identification of specific biomarkers of exposure when organisms are exposed to individual chemical molecules or mixtures. Participants will be provided with high quality data sets to develop predictive models/classifiers. For this challenge, the integration of a priori biological knowledge in the development of computational approaches may be required to enable biological interpretability/understanding of the predictions. The results and post-challenge analyses will be shared with the scientific community, and will open new avenues in the field of systems toxicology.