Next-generation risk assessment of chemicals – Rolling out a human-centric testing strategy to drive 3R implementation: The RISK-HUNT3R project perspective

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Giorgia Pallocca
Martijn J. Moné
Hennicke Kamp
Mirjam Luijten
Bob van de Water
Marcel Leist


In many industrial sectors, there is a need for reliable ways to evaluate the safety of chemicals with methods anchored to human biology and pathology. For this purpose, many animal-free new approach methods (NAMs) have been developed and implemented in various stages of risk assessment. Now it is time to assemble individual NAMs into a comprehensive next-generation risk assessment (NGRA) strategy. The European Horizon 2020 RISK-HUNT3R project (“Risk assessment of chemicals integrating human-centric next-generation testing strategies promoting the 3Rs”) has been designed to promote a combination of computational toxicology, in vitro toxicology, and systems biology. It is assumed that this approach will lead to faster and more accurate risk assessment procedures. The RISK-HUNT3R NGRA strategy will be developed to address the implementation of a comprehensive NAM toolbox into the regulatory framework. Critical conceptual approaches of the project include i) the integration of human-relevant data on biotransformation and elimination, ii) the translation of high-content mode-of-action datasets into predictions of adverse outcomes, iii) development of quantitative adverse outcome pathways (qAOPs), and iv) quantification of uncertainties associated with the predictions based on NGRA strategies. Many of the project steps will be used iteratively to generate datasets with sufficient quality and certainty for NGRA. Scientists and regulators will work together on case studies to evaluate NAMs’ practical applicability and the strategies to combine information therefrom. Here we delineate how the strategy will be deployed to establish an overall NGRA framework for chemicals, pesticides, food additives, and drugs.

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Pallocca, G., Moné, M. J., Kamp, H., Luijten, M., van de Water, B. and Leist, M. (2022) “Next-generation risk assessment of chemicals – Rolling out a human-centric testing strategy to drive 3R implementation: The RISK-HUNT3R project perspective”, ALTEX - Alternatives to animal experimentation. doi: 10.14573/altex.2204051.

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