Adverse Outcome Pathways-Organizing Toxicological Information to Improve Decision Making.

Area of Science:

• Environmental toxicology
• Regulatory science
• Computational toxicology

Background:

• Current chemical toxicity testing capacity is insufficient for regulatory needs.
• High-throughput screening (HTT) offers a potential solution to increase testing capacity.
• The Adverse Outcome Pathway (AOP) concept provides a framework to link HTT results to population-level impacts.

Purpose of the Study:

• To outline the AOP framework for connecting toxicity testing data to regulatory decision-making.
• To describe how AOPs and integrated approaches to testing and assessment (IATA) can enhance chemical risk evaluation.
• To highlight the importance of chemical-agnostic AOPs for broader applicability.

Main Methods:

• Utilizing the Adverse Outcome Pathway (AOP) concept as a central framework.
• Integrating high-throughput toxicity testing (HTT) data with chemical-specific ADME data.
• Developing Integrated Approaches to Testing and Assessment (IATA) that incorporate diverse data types.

Main Results:

• AOPs are well-defined and increasingly adopted internationally.
• AOPs represent chemical-agnostic pathways, enhancing generalizability.
• IATA can be developed with limited AOP and ADME information, guiding further research.

Conclusions:

• AOPs and HTT are crucial for expanding toxicity testing capacity.
• IATA, informed by AOPs and ADME, enables efficient risk assessment.
• Further research into AOPs and ADME is needed for specific regulatory contexts.