Performance of the Bovine Corneal Opacity and Permeability (BCOP) test method in detecting ocular corrosives and severe irritants

RR Tice¹, DG Allen¹, BC Blackard¹, NY Choksi¹, CJ Inhof¹, JF Truax¹, WS Stokes²

1. Integrated Laboratory Systems, Inc./NICEATM, RTP, NC, USA
2. NICEATM/NIEHS, RTP, NC, USA

Ethical (animal welfare), economic (development of higher throughput testing), and scientific (development of mechanistic studies) concerns have led researchers to develop in vitro alternatives for the current in vivo rabbit eye test. NICEATM evaluated four in vitro test methods for their ability to identify substances that cause ocular corrosion or severe irritation. One of these test methods, BCOP, is an organotypic model that provides short-term maintenance of the cornea in an isolated system. The ability of BCOP to correctly and reproducibly identify ocular corrosives/severe irritants using available BCOP and corresponding in vivo eye irritation data was evaluated according to current hazard classification schemes for the U.S. Environmental Protection Agency, the European Union, and the UN Globally Harmonized System of Classification and Labeling of Chemicals. Based on an interim analysis, BCOP appears useful (with the exception of testing alcohols, ketones, and solids) in a weight-of-evidence tiered testing strategy. Accordingly, positive results could be used to classify and label a substance, while substances with negative results would undergo additional testing. This approach would reduce the number of animals used for eye irritation testing and the number of animals experiencing pain and distress. A proposed standardized test method protocol and a proposed list of reference substances have been developed for use in future validation and/or testing studies to further characterize the accuracy, the reliability, and the applicability domain of BCOP for the detection of ocular corrosives and severe irritants. ILS staff supported by NIEHS contract N01-ES 35504.

P157

Date: Tuesday, August 23, 2005, 13.00-14.00 h

5.5 Session: Advancements and Needs for Developing and Validating Alternatives for Ocular Irritancy and Corrosivity Testing.