Adverse outcome pathway (AOP) development I: strategies and principles

Area of Science:

• Toxicology and Risk Assessment
• Mechanistic Toxicology
• Regulatory Science

Background:

• Adverse Outcome Pathways (AOPs) organize knowledge linking molecular disturbances to adverse outcomes.
• AOP frameworks can improve regulatory decision-making by integrating mechanistic data.
• Consistent AOP development is crucial for a robust toxicological knowledgebase.

Purpose of the Study:

• To propose five fundamental principles for consistent Adverse Outcome Pathway (AOP) development.
• To detail the rationale behind these core principles for AOP construction.
• To address uncertainties and foster consistency in the application of the AOP framework.

Main Methods:

• Synthesized experiences and scientific discourse among AOP practitioners.
• Formulated five core principles guiding AOP development.
• Detailed the strategic considerations and justifications for each principle.

Main Results:

• Five principles for AOP development were proposed: non-chemical specificity, modularity (key events/relationships), individual AOP as a unit, network utility, and evolving nature.
• These principles aim to standardize the creation and evaluation of AOPs.
• The proposed principles address current uncertainties in AOP framework application.

Conclusions:

• Adherence to these five principles will promote greater consistency in AOP development.
• Consistent AOPs will enhance their utility in human health and ecological risk assessment.
• AOPs are dynamic tools that require ongoing refinement as scientific knowledge advances.