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

11/2023-11/2027

Funding programme / funding institution: Europäische Behörde für Lebensmittelsicherheit (EFSA)

Grant number: GP/EFSA/ED/2022/01

Project description:

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., 2022; Krewski et al., 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 EFSA NAM roadmap that has recently been published and that was developed by key leaders in the field in close cooperation with EFSA. 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., 2022; Harrill, Viant, et al., 2021; Johnson et al., 2022; Krewski et al., 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 EFSA remits through dedicated case studies on selected pesticides in close cooperation with EFSA. 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.

Coordination:

Universität Leiden

Project partners:

• Universität Leiden, Netherlands

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