ArticleToxicology in vitro : an international journal published in association with BIBRA2019
An in vitro depth of injury prediction model for a histopathologic classification of EPA and GHS eye irritants.
Article in Toxicology in vitro : an international journal published in association with BIBRA, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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The trial behind it
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Who cites it
7 citing papers in PubMed.
- Effect of Periplaneta americana Extract on Corneal Fibrosis and Epithelial Healing After Rabbit Lamellar Keratectomy.Translational vision science & technology · 2025Article
- Washing with buffered vitamin C after corrosive chemical (sodium hypochlorite) exposure reduces ocular depth of injury.Toxicology in vitro : an international journal published in association with BIBRA · 2025Article
- Further optimisation of a macromolecular ocular irritation test (OptiSafeCutaneous and ocular toxicology · 2023Article
- Modeling the antioxidant properties of the eye reduces the false-positive rate of a nonanimal eye irritation test (OptiSafe).Toxicology in vitro : an international journal published in association with BIBRA · 2021Article
- Same-chemical comparison of nonanimal eye irritation test methods: Bovine corneal opacity and permeability, EpiOcular™, isolated chicken eye, ocular Irritection®, OptiSafe™, and short time exposure.Toxicology in vitro : an international journal published in association with BIBRA · 2021Review
- In vitro reconstructed 3D corneal tissue models for ocular toxicology and ophthalmic drug development.In vitro cellular & developmental biology. Animal · 2021Review
- Enhanced Transepithelial Riboflavin Delivery Using Femtosecond Laser-Machined Epithelial Microchannels.Translational vision science & technology · 2020Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The purpose of this study was to develop Globally Harmonized System (GHS) and U.S. Environmental Protection Agency (EPA) prediction models for classifying irritant materials based on histopathologic in vitro depth of injury (DoI) measurements. Sixteen different materials were selected, representing all classes of toxicity, according to the GHS and EPA classification systems. Food-source rabbit eyes, similar to eyes used for the widely accepted Bovine Corneal Opacity and Permeability and Isolated Chicken Eye ocular irritation tests, were used. Tissues were exposed to test material for 1 min, and corneas were collected at 3- and 24-hours post-exposure. Tissues were then fixed and processed for live/dead biomarker fluorescent staining using phalloidin. DoI was then measured, and the percent DoI values for the epithelium and stroma were compared to the EPA and GHS classifications. Excluding surfactants, EPA nonclassified (category IV) materials showed no stromal and very slight epithelial damage (≤10%) to the cornea, whereas EPA corrosive (category I) materials showed significantly greater damage (P < 0.001), ranging from 39% to 100% of the stromal depth. Importantly, EPA reversible (categories II and III) materials showed significant damage to the epithelium (>10%, P < 0.005) but significantly less severe damage to the corneal stroma (P < 0.001), ranging from 1% to 38% of the stromal depth. GHS nonclassified (category NC) irritants caused damage to the epithelium but not to the stroma. All GHS class 2 materials showed damage to the stroma (1-11%), whereas GHS corrosives caused significantly greater damage to the stroma (38-100%; P < 0.001). Additionally, one corrosive material, which produced a stromal DoI of 99% at 24 h, produced no apparent damage at 3-hours post-exposure. Based on these findings, histopathologic EPA and GHS prediction models are proposed that appear to separate and identify reversible irritants from other irritant classes. Furthermore, GHS classification appears to require stromal damage, whereas NC materials may or may not damage the corneal epithelium.
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