title: A proposed eye irritation testing strategy to reduce and replace in vivo studies using Bottom-Up and Top-Down approaches.
abstract: In spite of over 20 years of effort, no single in vitro assay has been developed and validated as a full regulatory replacement for the Draize Eye Irritation test. However, companies have been using in vitro methods to screen new formulations and in some cases as their primary assessment of eye irritation potential for many years. The present report shows the outcome of an Expert Meeting convened by the European Centre for the Validation of Alternative Methods in February 2005 to identify test strategies for eye irritation. In this workshop test developers/users were requested to nominate methods to be considered as a basis for the identification of such testing strategies. Assays were evaluated and categorized based on their proposed applicability domains (e.g., categories of irritation severity, modes of action, chemical class, physicochemical compatibility). The analyses were based on the data developed from current practice and published studies, the ability to predict depth of injury (within the applicable range of severity), modes of action that could be addressed and compatibility with different physiochemical forms. The difficulty in predicting the middle category of irritancy (e.g. R36, GHS Categories 2A and 2B) was recognized. The testing scheme proposes using a Bottom-Up (begin with using test methods that can accurately identify non-irritants) or Top-Down (begin with using test methods that can accurately identify severe irritants) progression of in vitro tests (based on expected irritancy). Irrespective of the starting point, the approach would identify non-irritants and severe irritants, leaving all others to the (mild/moderate) irritant GHS 2/R36 categories.
authors.affiliation: The Procter & Gamble Company, Brussels, Belgium.
authors.forename: Laurie
authors.initials: L
authors.lastname: Scott
authors.forename: Chantra
authors.initials: C
authors.lastname: Eskes
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Els
authors.initials: E
authors.lastname: Adriaens
authors.forename: Nathalie
authors.initials: N
authors.lastname: Alepée
authors.forename: Monica
authors.initials: M
authors.lastname: Bufo
authors.forename: Richard
authors.initials: R
authors.lastname: Clothier
authors.forename: Davide
authors.initials: D
authors.lastname: Facchini
authors.forename: Claudine
authors.initials: C
authors.lastname: Faller
authors.forename: Robert
authors.initials: R
authors.lastname: Guest
authors.forename: John
authors.initials: J
authors.lastname: Harbell
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.forename: Hennicke
authors.initials: H
authors.lastname: Kamp
authors.forename: Béatrice Le
authors.initials: BL
authors.lastname: Varlet
authors.forename: Marisa
authors.initials: M
authors.lastname: Meloni
authors.forename: Pauline
authors.initials: P
authors.lastname: McNamee
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Osborne
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Pape
authors.forename: Uwe
authors.initials: U
authors.lastname: Pfannenbecker
authors.forename: Menk
authors.initials: M
authors.lastname: Prinsen
authors.forename: Christopher
authors.initials: C
authors.lastname: Seaman
authors.forename: Horst
authors.initials: H
authors.lastname: Spielmann
authors.forename: William
authors.initials: W
authors.lastname: Stokes
authors.forename: Kevin
authors.initials: K
authors.lastname: Trouba
authors.forename: Christine Van den
authors.initials: CV
authors.lastname: Berghe
authors.forename: Freddy Van
authors.initials: FV
authors.lastname: Goethem
authors.forename: Marco
authors.initials: M
authors.lastname: Vassallo
authors.forename: Pilar
authors.initials: P
authors.lastname: Vinardell
authors.forename: Valérie
authors.initials: V
authors.lastname: Zuang
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D002417:Cattle; D002645:Chickens; D019573:Epithelium, Corneal / Q000473:pathology; D005062:European Union; D005123:Eye / Q000473:pathology; D005128:Eye Diseases / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D007509:Irritants / Q000633:toxicity*; D007880:Legislation, Drug; D011817:Rabbits; D015203:Reproducibility of Results; D013552:Swine; D014116:Toxicology / Q000379:methods*
chemical_list: D007509:Irritants