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Subcategorization of Eye Irritants Using the EpiOcular Time-to-Toxicity Test

Silvia Letasiova, Lenka Hudecova, Jan Markus, Yulia Kaluzhny, Els Adriaens, Mitch Klausner
Abstract

As per OECD TG 405 “Acute Eye Irritation/ Corrosion”, albino rabbits were traditionally used to assess the eye damage/eye irritation of test materials. However, in 2015, OECD TG 492 “Reconstructed human Cornea-like Epithelium (RhCE) test method for identifying chemicals not requiring classification and labelling for eye irritation or serious eye damage” was accepted and validated for the use of in vitro ocular tissue models. Initially, this TG allowed for distinguishing between substances and mixtures not requiring classification and those that must be labeled for eye irritation or serious eye damage. Differentiation between materials causing serious eye damage and less-severe eye irritation was not included in the TG. Recently, OECD TG 492B was accepted which allows for distinguishing between chemicals that: a) do not require labeling for serious eye damage or eye irritancy (No Category or No Cat), b) cause serious eye damage (Category 1 or Cat 1), and c) are eye irritants (Category 2 or Cat 2) according to the UN GHS ocular hazard categories.

Keywords

EpiOcular (OCL-200-EIT), OECD TG 492b, sub-categorization, prediction model, hazard assessment, 2-Hydroxy iso-butyric acid ethyl ester, Benzensulphonylchloride, bis-(3-Aminopropyl)-tetramethyldisiloxane, Cyclohexanol, Diethylethanolamine, Domiphen bromide (10%), Ethylhexyl acid phosphate ester, Lactic acid, Benzethonium chloride (10%), Cetyl pyridinium bromide (10%), Benzalkonium chloride (10%), (Ethylenediamine propyl)trimethoxysilane, 1-Chloroctan-8-ol, Benzyl alcohol, Cetyltrimethyl ammonium bromide (10%), Hexadecyltrimethylammonium chloride (25%), Hydroxyethyl acrylate, Stearyltrimethylammonium chloride (10%), Di(2-ethylhexyl)sodium sulphosuccinate (10%), Cetylpyridinium chloride (10%), Acetic acid (10%), (3-Aminopropyl)triethoxy silane, Methoxyethyl acrylate, Methyl thioglycolate, n-Octylamine, Tetrahydrofuran Tributyltin oxide, 2-Ethyl-1-hexanol, 2-Methyl-1-pentanol, 2-Propanl 1-phenoxy-3-Chloropropionitrile, Acetone, Butyl Dipropasol Solvent, Chlorhexidine gluconate (20%, aqueous), Cyclopentanol, iso-Butanal, Methyl acetate, Methyl ethyl ketone (Butanone CHROMASOLV®), n-Butanal, n-Hexanol, Propasol Solvent P, Cetyl pyridinium bromide (1%), Monoethanolamine (10%), Lauryl sulphobetaine (10%), Deoxycholic acid Na salt (10%), Triton X-100 (5%), 2-Pseudoionone, Furfural, Glycolic acid (10%), iso-Propanol, iso-Propyl acetoacetate, Methyl cyanoacetate, 1-Hexadecanaminium, N,N,N-trimethyl-, chloride (2%), Dimethyl sulfoxide (DMSO), Ethyl acetoacetate, Methyl iso-butyl ketone, n-Butyl acetate, Cetyl pyridinium bromide (0.1%), Sodium lauryl sulphate (3%), 1,2,4-Trimethylbenzene, 1,2,6-Hexanetriol, 1,3-Di-iso-propyl benzene, 1,9-Decadiene, 1-Ethyl-3-methylimidazolium ethyl sulphate, 2,4-Pentanediol, 2-Ethylhexyl p-dimethylamino benzoate, 3-Methoxy-1,2-propanediol, Amyl acetate (neat) (= pentyl acetate), Bromo-2-butane, Dioctyl ether, Dodecane, Glycerol, Methyl cyclopentane, n-Hexane , n-Octyl bromide, 1-bromo octane, Petroleum ether, Propylene glycol, Tween 80, 2-Benzyl-4-chlorophenol, 2-Hydroxy iso-butyric acid, 4-(1,1,3,3-Tetramethylbutyl)phenol , 4,4'-(4,5,6,7-Tetrabromo-3H-2,1-benzoxathiol-3-ylidene)bis[2,6-dibromophenol] S,S-dioxide, alpha-Ketoglutaric acid, Dibenzoyl-L-tartaric acid, Distearyldimethylammonium chloride, Promethazine HCl, 1-Naphthalene acetic acid Na salt, Acid Red 92, Benzoic acid, Captan 90-concentrate, Lauric acid, m-Phenylene diamine, p-tert-Butylphenol, Sodium perborate tetrahydrate, Sodium salicylate, 1,2-Benzisothiazol-3(2H)-one, N-(2-Methylphenyl)-iminodicarbonimidic diamide (1-(o-Tolyl)biguanide), N-Acetyl-DL-methionine, Paraformaldehyde, Quinacrine, Triethanolamine orthovanadate, 1,2,4-Triazole sodium derivate, Chlorhexidine, 2-chloroaniline-5-sulfonic acid, 2-4-dihydrocybenzoic acid, 2,5-dimethyl-2,5-hexanediol, (2R,3R)-3-((R)-1-(Tert-butyldimethylsiloxy)ethyl)-4-oxoazetidin-2-yl acetate, 2,6-Dichloro-5-fluoro-beta-oxo-3-pyridinepropanoate, 3,3'-Dithiopropionic acid, 4-Amino-3-nitrophenol, 4-Carboxybenzaldehyde, Dibenzyl phosphate, 1,4-Dibutoxybenzene, 1,5-Naphthalenediol, 2-Amino-3-hydroxy pyridine, 2-Hydroxy-1,4-naphthoquinone, Ammonium nitrate, Camphene, m-Dinitrobenzene, p-Nitrobenzoic acid, Sodium benzoate, Sodium monochloroacetate, Betaine monohydrate, DL-Glutamic acid, Ethylenediaminetetraacetic acid di-potassium salt, Iminodibenzyl, Magnesium carbonate, Propyl-4-hydroxybenzoate, 1-(9H-Carbazol-4-yloxy)-3-[[2-(2-methoxyphenoxy)ethyl]amino]propan-2-ol, 1H-Indole-2,3-dione (Isatine), 2-Mercaptopyrimidine, 3,5-Dihydroxyacetophenone, Aluminium hydroxide, Anthracene, Gluconolactone, Methyl p-hydroxybenzoate, Phenothiazine, Potassium tetrafluoroborate, Silicic acid, Sodium tripolyphosphate, Tetrabromobisphenol A, Theobromine, Theophylline sodium acetate, Xanthinol nicotinate

Materials Tested

EpiOcular (OCL-200-EIT), OECD TG 492b, sub-categorization, prediction model, hazard assessment, 2-Hydroxy iso-butyric acid ethyl ester, Benzensulphonylchloride, bis-(3-Aminopropyl)-tetramethyldisiloxane, Cyclohexanol, Diethylethanolamine, Domiphen bromide (10%), Ethylhexyl acid phosphate ester, Lactic acid, Benzethonium chloride (10%), Cetyl pyridinium bromide (10%), Benzalkonium chloride (10%), (Ethylenediamine propyl)trimethoxysilane, 1-Chloroctan-8-ol, Benzyl alcohol, Cetyltrimethyl ammonium bromide (10%), Hexadecyltrimethylammonium chloride (25%), Hydroxyethyl acrylate, Stearyltrimethylammonium chloride (10%), Di(2-ethylhexyl)sodium sulphosuccinate (10%), Cetylpyridinium chloride (10%), Acetic acid (10%), (3-Aminopropyl)triethoxy silane, Methoxyethyl acrylate, Methyl thioglycolate, n-Octylamine, Tetrahydrofuran Tributyltin oxide, 2-Ethyl-1-hexanol, 2-Methyl-1-pentanol, 2-Propanl 1-phenoxy-3-Chloropropionitrile, Acetone, Butyl Dipropasol Solvent, Chlorhexidine gluconate (20%, aqueous), Cyclopentanol, iso-Butanal, Methyl acetate, Methyl ethyl ketone (Butanone CHROMASOLV®), n-Butanal, n-Hexanol, Propasol Solvent P, Cetyl pyridinium bromide (1%), Monoethanolamine (10%), Lauryl sulphobetaine (10%), Deoxycholic acid Na salt (10%), Triton X-100 (5%), 2-Pseudoionone, Furfural, Glycolic acid (10%), iso-Propanol, iso-Propyl acetoacetate, Methyl cyanoacetate, 1-Hexadecanaminium, N,N,N-trimethyl-, chloride (2%), Dimethyl sulfoxide (DMSO), Ethyl acetoacetate, Methyl iso-butyl ketone, n-Butyl acetate, Cetyl pyridinium bromide (0.1%), Sodium lauryl sulphate (3%), 1,2,4-Trimethylbenzene, 1,2,6-Hexanetriol, 1,3-Di-iso-propyl benzene, 1,9-Decadiene, 1-Ethyl-3-methylimidazolium ethyl sulphate, 2,4-Pentanediol, 2-Ethylhexyl p-dimethylamino benzoate, 3-Methoxy-1,2-propanediol, Amyl acetate (neat) (= pentyl acetate), Bromo-2-butane, Dioctyl ether, Dodecane, Glycerol, Methyl cyclopentane, n-Hexane , n-Octyl bromide, 1-bromo octane, Petroleum ether, Propylene glycol, Tween 80, 2-Benzyl-4-chlorophenol, 2-Hydroxy iso-butyric acid, 4-(1,1,3,3-Tetramethylbutyl)phenol , 4,4'-(4,5,6,7-Tetrabromo-3H-2,1-benzoxathiol-3-ylidene)bis[2,6-dibromophenol] S,S-dioxide, alpha-Ketoglutaric acid, Dibenzoyl-L-tartaric acid, Distearyldimethylammonium chloride, Promethazine HCl, 1-Naphthalene acetic acid Na salt, Acid Red 92, Benzoic acid, Captan 90-concentrate, Lauric acid, m-Phenylene diamine, p-tert-Butylphenol, Sodium perborate tetrahydrate, Sodium salicylate, 1,2-Benzisothiazol-3(2H)-one, N-(2-Methylphenyl)-iminodicarbonimidic diamide (1-(o-Tolyl)biguanide), N-Acetyl-DL-methionine, Paraformaldehyde, Quinacrine, Triethanolamine orthovanadate, 1,2,4-Triazole sodium derivate, Chlorhexidine, 2-chloroaniline-5-sulfonic acid, 2-4-dihydrocybenzoic acid, 2,5-dimethyl-2,5-hexanediol, (2R,3R)-3-((R)-1-(Tert-butyldimethylsiloxy)ethyl)-4-oxoazetidin-2-yl acetate, 2,6-Dichloro-5-fluoro-beta-oxo-3-pyridinepropanoate, 3,3'-Dithiopropionic acid, 4-Amino-3-nitrophenol, 4-Carboxybenzaldehyde, Dibenzyl phosphate, 1,4-Dibutoxybenzene, 1,5-Naphthalenediol, 2-Amino-3-hydroxy pyridine, 2-Hydroxy-1,4-naphthoquinone, Ammonium nitrate, Camphene, m-Dinitrobenzene, p-Nitrobenzoic acid, Sodium benzoate, Sodium monochloroacetate, Betaine monohydrate, DL-Glutamic acid, Ethylenediaminetetraacetic acid di-potassium salt, Iminodibenzyl, Magnesium carbonate, Propyl-4-hydroxybenzoate, 1-(9H-Carbazol-4-yloxy)-3-[[2-(2-methoxyphenoxy)ethyl]amino]propan-2-ol, 1H-Indole-2,3-dione (Isatine), 2-Mercaptopyrimidine, 3,5-Dihydroxyacetophenone, Aluminium hydroxide, Anthracene, Gluconolactone, Methyl p-hydroxybenzoate, Phenothiazine, Potassium tetrafluoroborate, Silicic acid, Sodium tripolyphosphate, Tetrabromobisphenol A, Theobromine, Theophylline sodium acetate, Xanthinol nicotinate

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