Cellular viability and death biomarkers enables the evaluation of ocular irritation using the bovine corneal opacity and permeability assay

Xie, Zhang-Xian; Ye, K.; Chen, S.H.; Liu, L.; He, Lilin; Sang, Jing; Meng, Hong-Min; Kuang, Rongze

doi:10.1016/j.toxlet.2021.01.004

Cited by 2 publications

(1 citation statement)

References 16 publications

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“…In general, cell or tissue injury occurring progressively deeper into the cornea results in increasingly worse injuries. Whereas numerous attempts have been reported [45,46,74,[89][90][91][92] using various histopathology methods to determine the thresholds delineating the DOI between irritation categories in ex vivo/in vitro corneal systems, not surprisingly some overlap in the DOI between categories is observed. The following summarizes generalized findings on the depth of injuries, relative to chemical irritation potentials.…”

Section: Depth Of Injury Conceptmentioning

confidence: 99%

Human-relevant approaches to assess eye corrosion/irritation potential of agrochemical formulations

Clippinger¹,

Raabe

Allen

et al. 2021

Cutaneous and Ocular Toxicology

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There 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.

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