The first reporting period of EU-ToxRisk established the scientific and technical groundwork and involved the development of CSs to test the strength of NAMs for a number of endpoints. The second project period ensured the full maturation of the scientific toolbox for chemical safety assessment and its extensive deployment in testing batteries for the first set of project CSs. Moreover, a direct link was created between the project’s scientific innovations and regulatory practice through the establishment of a regulatory advisory board. In the third reporting period, several CSs were fully finalised, reported on, and reviewed. Novel mechanism-based human-relevant test systems were deployed, including new fluorescent stress-responsive reporter assays in human induced-pluripotent stem cells, toxicity screening in diseased 3D spheroid models of the liver, four-organ microfluidics chip test systems, and high-throughput transcriptomics. Advanced in-silico prediction tools and PBPK models were made fully fit for purpose. New CSs deploying these technologies were initiated in close collaboration with international experts, and practical testing was started. Importantly, regulatory readiness of the testing toolbox for read-across approaches was now demonstrated, and the project’s commercialisation platform aiming to exploit the toolbox was inaugurated. The final reporting period brought all project expertise together to maximise scientific and regulatory impact of the project. All project CSs were experimentally finalised. They provided new tools and information on NAM-based read-across, with several CSs also addressing uncharted areas, like how to test chemicals with little or no-observed adverse effects, or with multi-target organ toxicity, or the involvement of metabolism, or chemicals without any prior knowledge of their in-vivo effects and without known structurally similar molecules. The output was assessed by regulatory experts and learnings were condensed in the EU-ToxRisk Advisory Document on NAM-based read-across to assist regulatory toxicologists in all sectors. Several EU-ToxRisk CSs have now also been published at the OECD. All project CSs comprise biokinetics information and high-throughput transcriptomics data on all CS chemicals. Also, the fully sponsored industry CS, based on the project’s NAMs and read-across strategy, further proved its value. The commercialisation efforts were expanded and further consolidated in the joint Commercialization Platform. Training of the next generation of toxicology scientists came to its effective conclusion, yielding a workforce of young researchers with not only proven scientific excellence in non-animal toxicology approaches, but also trained in awareness of the regulatory context, much adding to their value beyond the walls of academia. Lastly, EU-ToxRisk partners made their findings sustainable and useful for others by establishing new long-term international initiatives, such as the ASPIS research cluster (including the RISK-HUNT3R project) and the PARC partnership. This will ensure that EU-ToxRisk results (data, knowledge, and methodology) will be taken up by the community.
