EU-ToxRisk aims to transform human safety evaluation of chemicals. Five distinct impacts were identified to reach this overall project objective. Firstly, EU-ToxRisk has established how to integrate more effective, faster, cheaper toxicological in silico and in vitro test systems to assess chemical safety and meet regulatory needs. The project learned how to optimise test strategies to effectively target regulatory questions and how to report on them for safety assessment. New CSs challenge the approaches further by focusing on test strategies to provide conclusions from NAM data on the human safety of substances that have no or low toxic concerns. Secondly, EU-ToxRisk has improved the toxicological knowledge to encourage and improve read-across procedures. Through extensive reviewing of the project’s panel of read-across CSs by international regulatory experts, including the OECD IATA Case Study Project, the project found consensus on read-across testing strategies that integrate mechanistic toxicological information. In particular, innovation involved the integration of high-throughput transcriptomics approaches for implementation for read-across. Thirdly, EU-ToxRisk established a commercialization platform to exploit the developed toxicological tests, products and services. This platform will offer NAMs in an integrated fashion from case design to risk assessment. Business development will be further enhanced, continuing engagement with industry and seeking new opportunities. Fourthly, the project has advanced the international co-operation in the field of toxicology and safety testing through continuous feedback on its CSs from international regulatory experts from ECHA, EFSA, EMA, and OECD. EU-ToxRisk is actively engaged with the US Tox21 consortium on high-throughput screening technologies. EU-ToxRisk also engaged with Health Canada and JaCVAM in the area of risk assessment in read-across CSs. Fifthly, the successful demonstration in EU-ToxRisk CSs of the application of NAM for safety assessment will support the reduced use of laboratory animals in safety testing. The improved read-across procedures and IATAs for RDT and DART started to lead to non-animal test studies for real industry cases. Ambitious new, ongoing CSs on prioritizing compounds of low or no toxicity should show how to steer away from performing animal testing of likely safe compounds.