03267nas a2200349   4500000000100000008004100001260001500042653000900057653000800066653001400074653001900088653000800107653001800115653001800133653001900151653001400170653002400184100002200208700001800230700001900248700002000267700002500287700002700312700001800339700001800357245010400375856005000479300001200529490000700541520235500548022001402903       2021                            d  c2021-04-0310aBCOP10aEPA10aEpiOcular10aEye irritation10aICE10aagrochemicals10aeye corrosion10ahuman-relevant10ain vitro10aneutral red release1 aAmy J. Clippinger1 aHans A. Raabe1 aDavid G. Allen1 aNeepa Y. Choksi1 aAnna J. van der Zalm1 aNicole C. Kleinstreuer1 aJoão Barroso1 aAnna B. Lowit00aHuman-relevant approaches to assess eye corrosion/irritation potential of agrochemical formulations  uhttps://doi.org/10.1080/15569527.2021.1910291  a145-1670 v403 aThere are multiple in vitro and ex vivo eye irritation and corrosion test methods that are available as internationally harmonized test guidelines for regulatory use. Despite their demonstrated usefulness to a broad range of substances through inter-laboratory validation studies, they have not been widely adopted for testing agrochemical formulations due to a lack of concordance with parallel results from the traditional regulatory test method for this endpoint, the rabbit eye test. The inherent variability of the rabbit test, differences in the anatomy of the rabbit and human eyes, and differences in modelling exposures in rabbit eyes relative to human eyes contribute to this lack of concordance. Ultimately, the regulatory purpose for these tests is protection of human health, and, thus, there is a need for a testing approach based on human biology. This paper 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. Each of the in vitro and ex vivo methods described is generally appropriate for identifying non-irritants. To discriminate among eye irritants, the human three-dimensional epithelial and full thickness corneal models provide the most detailed information about the severity of irritation. 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/ex vivo methods are as or more reflective of human biology and less variable than the currently used rabbit approach. Suggestions are made for further optimizing the most promising methods to distinguish between severe (corrosive), moderate, mild and non-irritants and provide information about the reversibility of effects. Also considered is the utility of including additional information (e.g. physical chemical properties), consistent with the Organization for Economic Cooperation and Development’s guidance document on an integrated approach to testing and assessment of potential eye irritation. Combining structural and functional information about a test substance with test results from human-relevant methods will ensure the best protection of humans following accidental eye exposure to agrochemicals.  a1556-9527