title: The Isolated Chicken Eye test to replace the Draize test in rabbits.
abstract: In 1944, Draize et al., published a paper entitled "Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes". The Organization for Economic Co-operation and Development published their first guideline on eye irritation in 1981, using rabbits. In the early eighties the development of alternative non-animal tests to replace the Draize eye test started. The first attempts to validate alternative tests for eye irritation were considered to be relatively simple by comparing in vitro and in vivo irritation index scores. In the early nineteen-eighties, we introduced the use of isolated eyes as an alternative test for the Draize eye irritation test. What was expected to be a process of several years, however, turned out to be a decades spanning process still not fully completed. For a large part, this can be attributed to the nature of the in vivo test in rabbits, which is more complicated and compromised than originally believed. This paper describes, most chronologically, the development, performance, validation and application of the Isolated Eye Test and, in broader perspective, the international validation and acceptance of this alternative test by regulatory authorities and agencies.
authors.affiliation: Triskelion B.V., P.O. Box 844, 3700 AJ Zeist, The Netherlands. Electronic address: menk.prinsen@triskelion.nl.
authors.forename: Menk K
authors.initials: MK
authors.lastname: Prinsen
authors.affiliation: Utrecht University/Institute for Translational Vaccinology, P.O. Box 450, 3720 AL Bilthoven, The Netherlands. Electronic address: coenraad.hendriksen@intravacc.nl.
authors.forename: Coenraad F M
authors.initials: CFM
authors.lastname: Hendriksen
authors.affiliation: University of Applied Sciences Utrecht, Institute for Life Sciences & Chemistry, P.O. Box 12011, 2501 AA Utrecht, The Netherlands; TNO Innovation for Life, P.O. Box 360, 3700 AJ Zeist, The Netherlands. Electronic address: cyrille.krul@tno.nl.
authors.forename: Cyrille A M
authors.initials: CAM
authors.lastname: Krul
authors.affiliation: TNO Innovation for Life, P.O. Box 360, 3700 AJ Zeist, The Netherlands; Wageningen University Research Centre, Department Toxicology, Wageningen, The Netherlands. Electronic address: ruud.woutersen@tno.nl.
authors.forename: Ruud A
authors.initials: RA
authors.lastname: Woutersen
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D002645:Chickens; D005123:Eye / Q000187:drug effects*; D066298:In Vitro Techniques; D007509:Irritants / Q000633:toxicity*; D011817:Rabbits; D018675:Toxicity Tests
chemical_list: D007509:Irritants
keywords: Alternative testing method; CEET; Chicken Enucleated Eye test; Draize test; Eye irritation in vitro; ICE; Isolated Chicken Eye test