A modular approach for assembly of quantitative adverse outcome pathways

Area of Science:

• Toxicology
• Environmental Science
• Computational Biology

Background:

• The adverse outcome pathway (AOP) framework links molecular events to adverse outcomes.
• Quantitative AOPs are vital for screening contaminants but are costly to develop.
• A modular approach can accelerate AOP development using existing knowledge.

Purpose of the Study:

• To present a modular approach for rapid assembly of quantitative AOPs.
• To demonstrate the utility of this approach for contaminant screening and prioritization.
• To enable faster development of biological pathway models for toxicological assessment.

Main Methods:

• Assembling quantitative AOPs using a modular approach based on existing knowledge.
• Deriving quantitative key event relationships (KERs) as response-function or probability matrices.
• Applying the approach to two case studies: aromatase inhibition and excitotoxicity.

Main Results:

• Successfully demonstrated the assembly of quantitative AOPs using a modular strategy.
• Validated the approach with case studies involving fish fecundity and rodent memory impairment.
• The developed models effectively characterize toxicological pathways and effects.

Conclusions:

• A modular approach enables the rapid development of quantitative AOPs.
• This method facilitates efficient screening and prioritization of contaminants for testing.
• The approach has broad applicability for creating biological pathway models in toxicology.