Optimization of the EpiOcular™ eye irritation test for hazard identification and labelling of chemicals in response to the requirements of the EU Cosmetic Directive and REACH Legislation

Kaluzhny, Yulia; Kanďárová, Helena; d’Argembeau-Thornton, Laurence; Luca, Jane De; Hayden, Patrick; Hunter, Andrew; Truong, Thang; Klausner, Mitchell

doi:10.1016/j.toxlet.2013.05.325

Cited by 4 publications

(6 citation statements)

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“…In this case a functional check using freeze-killed tissue controls should be performed to evaluate whether the test material is binding to the tissue and leading to a false MTT reduction signal. If there is appreciable The EIT errs on the side of safety, as demonstrated by the low incidence of false negative classifications 14,15,18. Importantly, none of the GHS Category 1 chemicals, which are corrosive to the eye and which represent the most serious ocular hazard, were classified as non-irritating in this assay 14,15,18,19 . Finally, one of the major advantages of the RhCE in vitro test method is the possibility of testing neat liquid and solid materials (which is not possible with two-dimensional, submerged cell cultures).…”

Section: Discussionmentioning

confidence: 99%

“…Due to the high level of tissue-to-tissue reproducibility, n = 2 tissues instead of the usually recommended n = 3 are used. The ability to use n= 2 tissues is a critical aspect of the protocol, since it allows an experienced operator to process two tissues simultaneously, thereby minimizing the variability of the assay that can arise due to the different handling of individual tissues 14 . Also, by using n = 2 tissues per test article, the irritancy of 10 test substances of the same physical state (liquid or solid), along with the positive and negative controls, can be evaluated using one kit (24 tissues).…”

Section: Discussionmentioning

confidence: 99%

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Eye Irritation Test (EIT) for Hazard Identification of Eye Irritating Chemicals using Reconstructed Human Cornea-like Epithelial (RhCE) Tissue Model

Kaluzhny

Kanďárová

d’Argembeau-Thornton

et al. 2015

JoVE

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To comply with the Seventh Amendment to the EU Cosmetics Directive and EU REACH legislation, validated non-animal alternative methods for reliable and accurate assessment of ocular toxicity in man are needed. To address this need, we have developed an eye irritation test (EIT) which utilizes a three dimensional reconstructed human cornea-like epithelial (RhCE) tissue model that is based on normal human cells. The EIT is able to separate ocular irritants and corrosives (GHS Categories 1 and 2 combined) and those that do not require labeling (GHS No Category). The test utilizes two separate protocols, one designed for liquid chemicals and a second, similar protocol for solid test articles. The EIT prediction model uses a single exposure period (30 min for liquids, 6 hr for solids) and a single tissue viability cut-off (60.0% as determined by the MTT assay). Based on the results for 83 chemicals (44 liquids and 39 solids) EIT achieved 95.5/68.2/ and 81.8% sensitivity/specificity and accuracy (SS&A) for liquids, 100.0/68.4/ and 84.6% SS&A for solids, and 97.6/68.3/ and 83.1% for overall SS&A. The EIT will contribute significantly to classifying the ocular irritation potential of a wide range of liquid and solid chemicals without the use of animals to meet regulatory testing requirements. The EpiOcular EIT method was implemented in 2015 into the OECD Test Guidelines as TG 492.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Eye Irritation Test (EIT) for Hazard Identification of Eye Irritating Chemicals using Reconstructed Human Cornea-like Epithelial (RhCE) Tissue Model

Kaluzhny

Kanďárová

d’Argembeau-Thornton

et al. 2015

JoVE

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“…It is the first and also the main barrier to ocular penetration. Reconstructed human corneal epithelium (RCE) models could be used for eye irritation testing, assessment of the barrier function, drug transport, cell physiology, metabolism and the development of delivery systems (Pepic et al, 2014;Reichl et al, 2004;Kaluzhny et al, 2011).…”

Section: Two-dimensional Cell Based Assaysmentioning

confidence: 99%

“…A higher viability leads to a classification as non-irritant. The EpiOcular™ EIT differentiates those materials that are non-irritants from those that would require labeling as either GHS category 1 or category 2, but the assay is not able to distinguish between GHS category 1 and category 2 (Pfannenbecker et al, 2013;Kaluzhny et al, 2011).…”

Section: Three-dimensional Corneal Epithelial Modelsmentioning

confidence: 99%

Alternative methods for the replacement of eye irritation testing

Lotz¹

2016

ALTEX

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SummaryIn the last decades significant regulatory attempts were made to replace, refine and reduce animal testing to assess the risk of consumer products for the human eye. As the original in vivo Draize eye test is criticized for limited predictivity, costs and ethical issues, several animal-free test methods have been developed to categorize substances according to the global harmonized system (GHS) for eye irritation. This review summarizes the progress of alternative test methods for the assessment of eye irritation. Based on the corneal anatomy and current knowledge of the mechanisms causing eye irritation, different ex vivo and in vitro methods will be presented and discussed with regard to possible limitations and status of regulatory acceptance. In addition to established in vitro models, this review will also highlight emerging, full thickness cornea models that might be suited to predict all GHS categories.

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“…For toxicology applications, these models provide a number of important features (Kandárová et al, 2009;Kaluzhny et al, 2011).…”

Section: Automation-compatible Organotypic Microtissues For Drug and mentioning

confidence: 99%

Novel technologies and an overall strategy to allow hazard assessment and risk prediction of chemicals, cosmetics, and drugs with animal-free methods

Leist

Lidbury

Yang

et al. 2012

ALTEX

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Summary Several alternative methods to replace animal experiments have been accepted by legal bodies. An even larger number of tests are under development or already in use for non-regulatory applications or for the generation of information stored in proprietary knowledge bases. The next step for the use of the different in vitro methods is their combination into integrated testing strategies (ITS) to get closer to the overall goal of predictive "in vitro-based risk evaluation processes." We introduce here a conceptual framework as the basis for future ITS and their use for risk evaluation without animal experiments. The framework allows incorporation of both individual tests and already integrated approaches. Illustrative examples for elements to be incorporated are drawn from the session "

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Optimization of the EpiOcular™ eye irritation test for hazard identification and labelling of chemicals in response to the requirements of the EU Cosmetic Directive and REACH Legislation

Cited by 4 publications

References 0 publications

Eye Irritation Test (EIT) for Hazard Identification of Eye Irritating Chemicals using Reconstructed Human Cornea-like Epithelial (RhCE) Tissue Model

Eye Irritation Test (EIT) for Hazard Identification of Eye Irritating Chemicals using Reconstructed Human Cornea-like Epithelial (RhCE) Tissue Model

Alternative methods for the replacement of eye irritation testing

Novel technologies and an overall strategy to allow hazard assessment and risk prediction of chemicals, cosmetics, and drugs with animal-free methods

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