Human-relevant Approaches to Assess Eye Corrosion/irritation Potential

Although multiple internationally harmonized test guidelines describe in vitro and ex vivo eye irritation and corrosion test methods for regulatory use, these methods have not been widely adopted for testing agrochemical formulations due to a lack of concordance with parallel results from the rabbit eye test. The inherent variability of the rabbit test, differences in the anatomy of the rabbit and human eyes, and differences in modeling exposures in rabbit eyes relative to human eyes contribute to this lack of concordance. Because the regulatory purpose for these tests is protection of human health, there is a need for a testing approach based on human biology. A paper coauthored by EPA and NICEATM (Clippinger et al. 2021) reviews the available in vivo, in vitro, and ex vivo test methods with respect to their relevance to human ocular anatomy, anticipated exposure scenarios, and the mechanisms of eye irritation/corrosion in humans. Consideration of the mechanisms of eye irritation and the strengths and limitations of the in vivo, in vitro, and ex vivo test methods show that the in vitro and ex vivo methods are as or more reflective of human biology and less variable than the currently used rabbit approach. The paper suggests approaches to further optimize the most promising methods to distinguish between severe (corrosive), moderate, mild, and non-irritants and provide information about the reversibility of effects. It also considers the utility of including additional information such as physicochemical properties in a hazard assessment, consistent with accepted guidance (OECD 2019) on integrated approaches to testing and assessment for potential eye irritation.