Findings of an Interlaboratory Trial of the Enucleated Eye Method as an Alternative Eye Irritation Test

Whittle, Edward; Basketter, David A.; York, Michael; Kelly, L.; Hall, Tyler Andrew; McCall, J.C.; Botham, Philip A.; Esdaile, David J.; Gardner, John R.

doi:10.3109/15376519209064803

Cited by 14 publications

(6 citation statements)

References 4 publications

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“…Exposure time and washing: Pre-warmed media is added to rabbit eyes prior to exposure to the substance. The eyes are exposed to the test substance for 10 s to identify a severe irritant (corrosive) and for 1 min (or longer) for less severely irritating substances [54,55]. They are washed until the test substance is removed, and assessments are made at several further time points.…”

Section: Mode Of Actionmentioning

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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Section: Mode Of Actionmentioning

confidence: 99%

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

Clippinger¹,

Raabe

Allen

et al. 2021

Cutaneous and Ocular Toxicology

View full text Add to dashboard Cite

show abstract

“…Ocular organotypic models use fresh isolated organs (eyeball, corneas) from bovine, porcine, chicken or rabbit from slaughterhouses or after euthanasia to avoid sacrificing animals only for the eye irritation test. In isolated rabbit eye test (IRE test) ( 16 ), a whole eyeball of rabbit extracted from the dead animal is loaded into a perfusion chamber and the irritation of the test substance is evaluated by measuring swelling and scoring of corneal opacity, the area of corneal involvement, and fluorescein penetration ( 17 , 18 ). IRE test addresses primarily the irritation or corrosion to the corneal surface as similar as the in vivo Draize rabbit eye irritation test.…”

Section: Alternatives To Draize Rabbit Eye Irritation Testmentioning

confidence: 99%

Alternatives toIn VivoDraize Rabbit Eye and Skin Irritation Tests with a Focus on 3D Reconstructed Human Cornea-Like Epithelium and Epidermis Models

2017

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Human eyes and skin are frequently exposed to chemicals accidentally or on purpose due to their external location. Therefore, chemicals are required to undergo the evaluation of the ocular and dermal irritancy for their safe handling and use before release into the market. Draize rabbit eye and skin irritation test developed in 1944, has been a gold standard test which was enlisted as OECD TG 404 and OECD TG 405 but it has been criticized with respect to animal welfare due to invasive and cruel procedure. To replace it, diverse alternatives have been developed: (i) For Draize eye irritation test, organotypic assay, in vitro cytotoxicity-based method, in chemico tests, in silico prediction model, and 3D reconstructed human cornea-like epithelium (RhCE); (ii) For Draize skin irritation test, in vitro cytotoxicity-based cell model, and 3D reconstructed human epidermis models (RhE). Of these, RhCE and RhE models are getting spotlight as a promising alternative with a wide applicability domain covering cosmetics and personal care products. In this review, we overviewed the current alternatives to Draize test with a focus on 3D human epithelium models to provide an insight into advancing and widening their utility.

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“…The eyeball is then either taken out of the chamber or left in situ (depending on the type of test material) and exposed to the test chemical. Exposure times are, for example, 10 seconds for the identification of severe irritants, and 1 minute (or longer) for the ranking of less severely-damaging materials or products (51,52). After removal of the chemical, the eye is repositioned in the chamber, and the cornea is examined for evidence of opacification and corneal thickness is measured.…”

Section: The Isolated Rabbit Eye (Ire) Testmentioning

confidence: 99%

“…Overall damage is assessed by means of a combination of the various parameters scored, depending on the nature of the effects observed, although inhouse classification systems may vary (51). Chemical substances causing the cornea to swell by more than 15% have been considered to have the potential to cause severe irritation of the eye in vivo (53), but a more complex classification model, in which opacity, corneal swelling and histological observations of the corneal epithelium are combined, has been published (47, 54).…”

Section: The Isolated Rabbit Eye (Ire) Testmentioning

confidence: 99%

“…1 Status of validation and/or standardisation. The IRE test initially underwent an interlaboratory trial between three laboratories, which used their own criteria to determine the overall in vitro rating of test materials (51). This trial concluded that the predictive ability of the test to separate moderatesevere eye irritants from lesser eye irritants and the consistency of results between laboratories were good.…”

Section: Developersmentioning

confidence: 99%

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3.3. Eye Irritation

et al. 2005

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Findings of an Interlaboratory Trial of the Enucleated Eye Method as an Alternative Eye Irritation Test

Cited by 14 publications

References 4 publications

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

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

Alternatives toIn VivoDraize Rabbit Eye and Skin Irritation Tests with a Focus on 3D Reconstructed Human Cornea-Like Epithelium and Epidermis Models

3.3. Eye Irritation

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