The EyeIRR-IS assay: Development and evaluation of an in vitro assay to measure the eye irritation sub-categorization of liquid chemicals. (March 2021)

• Record Type: Journal Article
• Authors: Cottrez, Françoise; Leblanc, Virginie; Boitel, Elodie; Groux, Hervé; Alépée, Nathalie
• Is Part Of: Toxicology in vitro. Volume 71(2021)
• Publication Date: 2021-03
• Subjects: EyeIRR-IS assay on liquids -- SkinEthic™ HCE model -- Serious eye damage and irritation -- UN GHS classification and labelling of chemicals -- Reconstructed human corneal tissue -- Toxicogenomic; BCOP Bovine Corneal Opacity and Permeability -- C Classified -- CAS RN Chemical Abstracts Service Registry Number -- Cat. 1 UN GHS classification for chemicals causing irreversible effects on the eye/serious damage to the eye -- Cat. 2 UN GHS classification for chemicals causing reversible effects on the eye/eye irritation, sub-categorised in 2A (irritant to eyes, eye effects are not fully reversible within 7 days of observation) and 2B (mildly irritant to eyes, eye effects fully reversible within 7 days of observation) -- CO Corneal Opacity -- Conj Conjunctival effects -- D Day -- HCE SkinEthic™ Human Corneal Epithelium -- ICE Isolated Chicken Eye -- IR Iritis -- LII liquid Irritation Index -- No-Cat. Chemicals not classified for serious eye damage/eye irritation under UN GHS/EU CLP -- NC Not Classified -- NgC Negative control -- PC Positive control -- Pers Persistence -- PBS Phosphate Buffered Saline -- PCP Physico-Chemical Properties -- RhCE Reconstructed human Cornea-like Epithelium -- UN GHS United Nations Globally Harmonized System of Classification and Labelling of Chemicals; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2020.105072
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Several alternative methods have been developed and regulatory adopted by OECD as in vitro alternatives to the Draize eye irritation assay either to detect chemicals not requiring classification (No Category) or inducing serious damage to the eye (Category 1) but none are sensitive enough to identify chemicals inducing reversible eye effects (category 2) which are categorised by default. Therefore, the discriminatory power of a genomic approach applied to the SkinEthic™ Human Corneal Epithelium (HCE) model was investigated to allow subcategorization capacity according to UN GHS classification. An algorithm based on gene expression modulation on a training (62) and a test (31 liquids) chemical set, tested neat and at 30%was evaluated in an assay called EyeIRR-IS. Its accuracy prediction to distinguish Cat1/Cat2 from No Cat was 95% with a specificity of 89% and a sensitivity of 98%. For subcategorization into the 3 GHS classes the accuracy reached 84% with 94% Cat1, 67% Cat2 and 89% No Cat correctly predicted. No Cat.1 chemicals were underestimated as negative with a majority of misclassified Cat2 over predicted as Cat 1. In conclusion, the performance of the assay suggests its added value in a defined approach for liquids to replace the Draize assay. Highlights: Toxicogenomic approach is applied to SkinEthic™ HCE model to develop an assay for eye irritation subcategorization. Evaluation of the EyeIRR-IS assay performed on 100 liquids Accuracy was 84% with 94% Cat1, 67% Cat2 and 89% No Cat correctly predicted. EyeIRR-IS assay is able to distinguish Cat 2 from Cat 1 liquid chemicals.