Validation of the OptiSafe™ eye irritation test

Area of Science:

• Toxicology and Chemical Safety
• In Vitro Toxicology Methods
• Ocular Irritation Testing

Background:

• The OptiSafe test method utilizes macromolecular damage to identify potential eye irritants.
• A prescreen assessment within the OptiSafe protocol defines the test method's applicability domain.
• Evaluating OptiSafe's utility for a bottom-up testing strategy is crucial for regulatory toxicology.

Purpose of the Study:

• To assess the usefulness and limitations of the OptiSafe in chemico test method.
• To determine the suitability of OptiSafe for identifying chemicals not requiring ocular irritation classification.
• To validate OptiSafe as a tool for a tiered-testing strategy in ocular toxicity assessment.

Main Methods:

• A multilaboratory, three-phased validation study involving 95 unique coded chemicals.
• Comparison of OptiSafe classifications with retrospective in vivo data using EPA and GHS systems.
• Assessment of intra- and interlaboratory reproducibility and accuracy across three laboratories.

Main Results:

• High intra- and interlaboratory reproducibility (91-100%) was demonstrated across validation phases.
• Test method accuracy ranged from 78% to 89% depending on classification system and data aggregation.
• False negative rates were low (0-15%), with potential causes for false positives in specific chemical classes under investigation.

Conclusions:

• The OptiSafe test method is a valuable tool for identifying nonsurfactant substances not requiring ocular irritancy classification.
• OptiSafe supports a tiered-testing strategy by enabling initial screening for ocular toxicity.
• This in vitro method offers a new approach for assessing ocular toxicity, reducing reliance on in vivo testing.