AOP and IATA applied to ocular surface toxicity.

Area of Science:

• Toxicology
• Ocular toxicology
• Regulatory science

Background:

• The rabbit Draize test has been the standard for assessing ocular toxicity and irritation of pharmaceuticals.
• The Organisation for Economic Co-operation and Development (OECD) advocates for alternative methods to minimize animal testing.
• Current models are insufficient to capture the full biological response, necessitating integrated approaches.

Purpose of the Study:

• To describe OECD tools for developing alternative ocular toxicity testing methods.
• To propose novel adverse outcome pathways (AOP) for the ocular surface.
• To present an integrated approach to testing and assessment (IATA) for toxicity-induced dry eye (TIDE).

Main Methods:

• Review and description of existing OECD regulatory tools.
• Conceptualization of AOPs for ocular surface toxicity.
• Development of an IATA framework for TIDE.

Main Results:

• The commentary outlines OECD-endorsed tools for alternative testing strategies.
• Original AOP frameworks for ocular surface toxicity are proposed.
• A novel IATA for TIDE is presented, integrating multiple test methods.

Conclusions:

• Integrated Approaches to Testing and Assessment (IATA) and AOPs are crucial for robust ocular toxicity data.
• The proposed frameworks offer a path towards reducing and replacing animal testing in pharmaceutical safety evaluation.
• These approaches support the development of reliable alternatives for ocular toxicity assessment, specifically for TIDE.