Advancing Genotoxicity Assessment by Building a Global AOP Network

Area of Science:

• Toxicology
• Genetics
• Regulatory Science

Background:

• Current genotoxicity testing faces challenges like misleading results and limited mechanistic insights.
• Existing testing batteries lack integration of advanced technologies and quantitative assessment.
• There's a need to reduce reliance on animal testing in genotoxicity assessment.

Purpose of the Study:

• To explore challenges in European regulatory frameworks for genotoxicity assessment.
• To discuss the development and implementation of Integrated Approaches for Testing and Assessment (IATAs) for genotoxicity.
• To present a global Adverse Outcome Pathway (AOP) network for DNA damage to guide IATA development.

Main Methods:

• Review of current genotoxicity testing strategies and regulatory frameworks.
• Exploration of New Approach Methodologies (NAMs) like 3D systems, ToxTracker, and transcriptomic biomarkers.
• Application of the Adverse Outcome Pathway (AOP) framework to integrate NAMs into IATAs.

Main Results:

• Identified key challenges and gaps in current genotoxicity assessment, particularly within European regulations.
• Highlighted the potential of NAMs and AOPs to create more accurate and efficient genotoxicity testing.
• Proposed a global AOP network for permanent DNA damage to support regulatory decision-making.

Conclusions:

• IATAs integrating NAMs, guided by AOPs, are essential for modernizing genotoxicity assessment.
• This approach can enhance accuracy, efficiency, and ethical standards while reducing animal testing.
• The proposed AOP network offers a framework for improved regulatory decision-making in chemical safety assessment.