title: Alternative methods for the replacement of eye irritation testing.
abstract: In the last decades significant regulatory attempts were made to replace, refine and reduce animal testing to assess the risk of consumer products for the human eye. As the original in vivo Draize eye test has been criticized for limited predictivity, costs and ethical issues, several animal-free test methods have been developed to categorize substances according to the global harmonized system (GHS) for eye irritation.This review summarizes the progress of alternative test methods for the assessment of eye irritation. Based on the corneal anatomy and the current knowledge of the mechanisms causing eye irritation, different ex vivo and in vitro methods will be presented and discussed in regard of possible limitations and their status of regulatory acceptance. In addition to established in vitro models, this review will also highlight emerging, full thickness cornea models that might be applicable to predict all GHS categories.
authors.affiliation: Department Tissue Engineering & Regenerative Medicine (TERM), University Hospital Würzburg, Würzburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Lotz
authors.affiliation: Translational Center Würzburg 'Regenerative therapies in oncology and musculoskeletal diseases' Würzburg branch of the Fraunhofer Institute for Interfacial Engineering and Biotechnology, Würzburg, Germany.
authors.forename: Freia F
authors.initials: FF
authors.lastname: Schmid
authors.affiliation: Department Tissue Engineering & Regenerative Medicine (TERM), University Hospital Würzburg, Würzburg, Germany.|Translational Center Würzburg 'Regenerative therapies in oncology and musculoskeletal diseases' Würzburg branch of the Fraunhofer Institute for Interfacial Engineering and Biotechnology, Würzburg, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Department Tissue Engineering & Regenerative Medicine (TERM), University Hospital Würzburg, Würzburg, Germany.
authors.forename: Szymon
authors.initials: S
authors.lastname: Kurdyn
authors.affiliation: Department of Ophthalmology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kampik
authors.affiliation: ATERA S.A., Esch-sur-Alzette, Luxembourg.
authors.forename: Bart
authors.initials: B
authors.lastname: De Wever
authors.affiliation: Department Tissue Engineering & Regenerative Medicine (TERM), University Hospital Würzburg, Würzburg, Germany.|Translational Center Würzburg 'Regenerative therapies in oncology and musculoskeletal diseases' Würzburg branch of the Fraunhofer Institute for Interfacial Engineering and Biotechnology, Würzburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Walles
authors.affiliation: Translational Center Würzburg 'Regenerative therapies in oncology and musculoskeletal diseases' Würzburg branch of the Fraunhofer Institute for Interfacial Engineering and Biotechnology, Würzburg, Germany.
authors.forename: Florian K
authors.initials: FK
authors.lastname: Groeber
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D003228:Conjunctiva / Q000187:drug effects*; D003315:Cornea / Q000187:drug effects*; D005128:Eye Diseases / Q000517:prevention & control; D006801:Humans; D066298:In Vitro Techniques; D007509:Irritants / Q000145:classification / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D007509:Irritants
keywords: Draize eye test; OECD guideline; corneal equivalent; eye irritation