Adverse outcome pathway development II: best practices.

Area of Science:

• Toxicology
• Computational Biology
• Risk Assessment

Background:

• Adverse Outcome Pathway (AOP) descriptions integrate toxicological knowledge.
• Mechanistic data from various approaches are increasingly used in risk-based decisions.
• AOP development is transitioning from an ad hoc process to a formalized one.

Purpose of the Study:

• To outline desired information content for formal AOP descriptions.
• To propose rules of thumb and best practices for AOP development.
• To facilitate the reuse and connectivity of AOP elements within a knowledgebase.

Main Methods:

• Defining Key Events (KEs) as independent measurements at specific biological organization levels.
• Utilizing the concept of "functional equivalence" for KE inclusion and specificity.
• Describing Key Event Relationships (KERs) by building upon existing AOP knowledgebase entries.

Main Results:

• Formalized guidance and principles are being developed for AOP construction.
• Best practices for KE and KER descriptions promote consistency and reduce redundancy.
• Proposed practices address challenges in AOP development, ensuring flexibility.

Conclusions:

• Standardized AOP descriptions enhance the application of mechanistic toxicology data.
• Formalized AOP development fosters a consistent, reliable, and flexible approach to risk assessment.
• Best practices facilitate the creation of interconnected AOP knowledgebases for improved toxicological understanding.