NAM projects in the areas of AOP development and transcriptomics for risk assessment - LOT 2

The assessment of an increasing number of chemicals in a way that better protects human health, requires a paradigm shift in the safety assessment of chemicals. It should involve an interdisciplinary approach that integrates the different types of knowledge and data derived from human relevant NAMs in a mechanism-based framework (Beal et al.short foret alii (lat. "and others"), 2022; Krewski et al.short foret alii (lat. "and others"), 2020). A NAM-based mechanism-based testing strategy has been the central paradigm in toxicity testing for the 21st century and has received uptake by various agencies covering different domains and across the globe. It is also central in the EFSAshort forEuropean Food Safety Authority NAM roadmap that has recently been published and that was developed by key leaders in the field in close cooperation with EFSAshort forEuropean Food Safety Authority. Toxicogenomics represents the ideal platform to provide detailed insights into the mechanism of action of chemicals and therefore covers various adverse outcomes and the pathways leading to them (adverse outcome pathways) (Beal et al.short foret alii (lat. "and others"), 2022; Harrill, Viant, et al.short foret alii (lat. "and others"), 2021; Johnson et al.short foret alii (lat. "and others"), 2022; Krewski et al.short foret alii (lat. "and others"), 2020). Toxicogenomics allows the mapping of biological perturbations that are caused by chemical-biological interactions. It can discriminate between different cellular responses that are representative for specific biological perturbations such as DNA damage, mitochondrial injury, cellular stress response activation as well as specific activation of molecular initiation events, such as direct targeting of nuclear hormone receptors. TXG-MAP will deliver an easy to use, integrated toolbox for toxicogenomics data analysis and pathway-based interpretation for safety assessors. We will demonstrate the applicability of this toolbox for EFSAshort forEuropean Food Safety Authority remits through dedicated case studies on selected pesticides in close cooperation with EFSAshort forEuropean Food Safety Authority. The key impact of TXG-MAP will be obtaining confidence in the fit-for-purpose of human NAM in vitro test systems for application in toxicogenomics mechanism-based chemical safety assessment.