Performance of the Hen's Egg Test - Chorioallantoic Membrane (HET-CAM) test method in detecting ocular corrosives and severe irritants

NY Choksi¹, DG Allen¹, BC Blackard¹, CJ Inhof¹, RR Tice¹, 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 f test methods for their ability to identify substances that cause ocular corrosion or severe irritation. One of these test methods, HET-CAM, was developed to mimic the mucosal eye tissues. The ability of HET-CAM to correctly identify ocular corrosives and severe irritants using available HET-CAM and corresponding in vivo rabbit eye test 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. Results from an interim analysis suggest that HET-CAM has a high false positive rate. However, the assay may still be useful in a weight-of-evidence tiered testing strategy, where a positive substance could be either retested with a modified method to confirm the result or used to classify and label a substance. 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 HET-CAM for the detection of ocular corrosives and severe irritants. ILS staff supported by NIEHS contract N01-ES 35504.

P160

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.