title: Development of an in vitro ocular test system for the prediction of all three GHS categories.
abstract: In the present study we considered a new approach that allows the individual quantification of damages induced in the epithelium and stroma of an in vitro hemi-cornea model after chemical treatment. We aimed at a stand-alone test system for classification according to the classification of the globally harmonized system of classification and labelling of chemicals (GHS). We have modified a previously developed 3D hemi-cornea model by the insertion of a collagen membrane between epithelium and stroma. This membrane allows the separation and independent assessment of these compartments after topical exposure to potential eye irritants. The cell viability quantified by MTT assay was used as the toxicological endpoint. The prediction model based on the results obtained from 30 test chemicals uses a single exposure period and the combination of cut-off values in tissue viability from both epithelium and stroma. The in vitro-in vivo concordance of the test system is 77%. All of the GHS category 1, 80% of the GHS category 2 and 50% of the GHS not categorized chemicals are predicted correctly. In conclusion, the test system predicts and discriminates GHS category 1 and GHS category 2 chemicals, but is over-predictive for GHS not categorized materials.
authors.affiliation: School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany. Electronic address: m.bartok@jacobs-university.de.
authors.forename: M
authors.initials: M
authors.lastname: Bartok
authors.affiliation: School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Gabel
authors.affiliation: Department of Dermatology and Venerology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Zorn-Kruppa
authors.affiliation: School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Engelke
mesh_terms: D060433:Administration, Ophthalmic; D002460:Cell Line; D002965:Classification; D003319:Corneal Stroma / Q000187:drug effects; D019573:Epithelium, Corneal / Q000187:drug effects; D005123:Eye / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D018675:Toxicity Tests / Q000379:methods; D014116:Toxicology / Q000379:methods*
keywords: Eye irritation; GHS classification; Human hemi-cornea model; Prediction model; Predictive capacity