The adverse outcome pathway for skin sensitisation: Moving closer to replacing animal testing

Area of Science:

• Toxicology and Chemical Safety
• Regulatory Science
• In silico toxicology

Background:

• The Organisation for Economic Co-operation and Development (OECD) received the 2015 Lush Black Box Prize for its work on skin sensitization.
• The core of this work was the development of the 'Adverse Outcome Pathway for Skin Sensitisation Initiated by Covalent Binding to Proteins'.

Purpose of the Study:

• To present the OECD's award-winning work on the Adverse Outcome Pathway (AOP) for skin sensitization.
• To summarize recent advancements in integrated approaches to testing and assessment (IATA) based on this AOP.
• To discuss the AOP's influence on regulatory policy and the Three Rs (Replacement, Reduction, Refinement) in animal testing.

Main Methods:

• Development of the Adverse Outcome Pathway (AOP) for skin sensitization.
• Integration of mechanistic data for skin sensitization assessment.
• Application of the AOP within integrated approaches to testing and assessment (IATA).
• Overview of the next-generation skin sensitization AOP module in the OECD QSAR Toolbox.

Main Results:

• The established AOP provides a mechanistic framework for understanding and assessing skin sensitization.
• Recent developments enable enhanced integrated approaches to testing and assessment (IATA) for skin sensitization.
• The AOP has demonstrably impacted regulatory policy and the implementation of the Three Rs.

Conclusions:

• The OECD's Adverse Outcome Pathway for Skin Sensitisation is a significant advancement in toxicological science.
• This AOP facilitates data integration, supports regulatory decision-making, and promotes animal welfare.
• Ongoing development, including the OECD QSAR Toolbox module, promises further refinement of skin sensitization assessment.