A Pragmatic Approach to Adverse Outcome Pathway Development and Evaluation

Area of Science:

• Toxicology
• Chemical Safety Assessment
• Regulatory Science

Background:

• The Adverse Outcome Pathway (AOP) framework aids chemical safety assessment by organizing mechanistic knowledge.
• A significant bottleneck in AOP application is the extensive work required for peer-reviewed AOP development.

Purpose of the Study:

• To propose a pragmatic approach for accelerating the development and population of the AOP knowledge base (AOP-KB).
• To enhance the utility of AOPs for regulatory toxicology and chemical safety assessors.

Main Methods:

• Recognizing Key Event Relationships (KERs) as core building blocks within the AOP-KB.
• Implementing systematic review approaches for KER development, with exceptions for canonical knowledge.

Main Results:

• A streamlined approach to AOP development focusing on KERs can expedite knowledge assembly.
• Distinguishing between canonical and non-canonical knowledge simplifies review requirements for KERs.

Conclusions:

• Focusing on KERs as modular units can significantly increase the pace of AOP-KB population.
• This pragmatic approach aims to deliver more AOPs with regulatory utility faster.