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A proposed eye irritation testing strategy to reduce and replace in vivo studies using Bottom–Up and Top–Down approaches

2009; Elsevier BV; Volume: 24; Issue: 1 Linguagem: Inglês

10.1016/j.tiv.2009.05.019

1879-3177

Laurie Scott, Chantra Eskes, Sebastian Hoffmann, Els Adriaens, Nathalie Alépée, Monica Bufo, Richard Clothier, Davide Facchini, Claudine Faller, Robert Guest, John W. Harbell, Thomas Härtung, Hennicke Kamp, Béatrice Le Varlet, Marisa Méloni, Pauline McNamee, Rosemarie Osborne, Wolfgang Pape, U. Pfannenbecker, M.K. Prinsen, Christopher Seaman, Horst Spielmann, William S. Stokes, Kevin J. Trouba, Christine Van den Berghe, Freddy Van Goethem, Marco Vassallo, M. Pilar Vinardell, Valérie Zuang,

Meta-analysis and systematic reviews

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.