An in vitro depth of injury prediction model for a histopathologic classification of EPA and GHS eye irritants.
Cornea
Depth of injury
EPA
GHS
In vitro eye irritation tests
Isolated rabbit eye
Ocular irritation
Journal
Toxicology in vitro : an international journal published in association with BIBRA
ISSN: 1879-3177
Titre abrégé: Toxicol In Vitro
Pays: England
ID NLM: 8712158
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
received:
05
06
2019
revised:
12
08
2019
accepted:
12
08
2019
pubmed:
17
8
2019
medline:
25
3
2020
entrez:
17
8
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31419508
pii: S0887-2333(19)30444-8
doi: 10.1016/j.tiv.2019.104628
pmc: PMC6922541
mid: NIHMS1058756
pii:
doi:
Substances chimiques
Irritants
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
104628Subventions
Organisme : NIEHS NIH HHS
ID : R44 ES025501
Pays : United States
Informations de copyright
Copyright © 2019. Published by Elsevier Ltd.
Références
Toxicol In Vitro. 1994 Jun;8(3):381-92
pubmed: 20692929
Cornea. 1990 Oct;9(4):294-8
pubmed: 2078958
J Am Vet Med Assoc. 1992 Mar 1;200(5):669-73
pubmed: 1568909
Toxicology. 2015 Jan 2;327:32-46
pubmed: 25445805
Altern Lab Anim. 2008 Feb;36(1):25-32
pubmed: 18333712
Arch Toxicol. 2017 Feb;91(2):521-547
pubmed: 26997338
ALTEX. 2000;17(3):127-33
pubmed: 11105194
Toxicol Appl Pharmacol. 1971 Jun;19(2):276-360
pubmed: 5570968
Fundam Appl Toxicol. 1984 Aug;4(4):508-16
pubmed: 6479495
Eye (Lond). 2011 Nov;25(11):1429-34
pubmed: 21836630
J Biomed Mater Res A. 2006 Apr;77(1):35-42
pubmed: 16345096
Exp Eye Res. 2016 Jan;142:110-8
pubmed: 26675407
Altern Lab Anim. 2015 Jul;43(3):163-79
pubmed: 26256395
Toxicol Pathol. 2001 May-Jun;29(3):308-19
pubmed: 11442017
Dev Ophthalmol. 2010;45:93-107
pubmed: 20502030
Toxicol Pathol. 2001 Mar-Apr;29(2):187-99
pubmed: 11421486
Br J Ophthalmol. 1994 May;78(5):401-8
pubmed: 8025077
Int J Mol Sci. 2017 Jun 12;18(6):null
pubmed: 28604651
Arch Toxicol. 2014 Mar;88(3):701-23
pubmed: 24374802
Ocul Surf. 2018 Jan;16(1):154-162
pubmed: 29129753