The future trajectory of adverse outcome pathways: a commentary

Area of Science:

• Mechanistic Toxicology
• Environmental Health Sciences
• Regulatory Science

Background:

• Adverse Outcome Pathways (AOPs) provide a structured approach to understanding chemical toxicity mechanisms.
• AOPs facilitate the development of non-animal testing strategies, aligning with ethical and scientific advancements.
• The established value of AOPs is recognized, yet practical implementation faces hurdles.

Discussion:

• Challenges in AOP application include data integration and model validation.
• Opportunities lie in refining AOP knowledge bases and computational tools.
• Standardizing AOP reporting is crucial for consistent application.

Key Insights:

• AOPs enhance mechanistic toxicology by detailing molecular initiating events to adverse outcomes.
• The AOP framework supports the transition to New Approach Methodologies (NAMs) in chemical safety assessment.
• Addressing practical challenges is key to fully realizing AOP potential.

Outlook:

• Future AOP development should focus on broader applicability and predictive power.
• Integrating AOPs into regulatory frameworks will require further validation and standardization.
• Continued research into AOP network construction will improve understanding of complex toxicological interactions.