Overview

Federal agencies require safety testing to determine whether consumer products or other substances may cause temporary or permanent damage to the eye. In October 2003, the U.S. Environmental Protection Agency (EPA) nominated four in vitro ocular toxicity test methods for evaluation as potential screening methods for eye corrosion or severe irritation. The four nominated test methods were:

• The Isolated Rabbit Eye (IRE) Test Method
• The Isolated Chicken Eye (ICE) Test Method
• The Bovine Corneal Opacity and Permeability (BCOP) Test Method
• The Hen's Egg Test - Chorioallantoic Membrane (HET-CAM) Test Method

NICEATM compiled data and information on each test method and released four comprehensive draft Background Review Documents (BRDs) for public comment in November 2004. ICCVAM, in collaboration with NICEATM, convened an independent Expert Panel in January 2005 to determine the validation status of these methods. The Expert Panel Report: Evaluation of the Current Validation Status of In Vitro Test Methods for Identifying Ocular Corrosives and Severe Irritants, was made available in March 2005. Submission of additional data after the Expert Panel Meeting led to release of addenda to the BRDs. The Expert Panel was subsequently reconvened in September 2005 to reconsider their evaluation. The Expert Panel Report of the Current Validation Status of In Vitro Test Methods for Identifying Ocular Corrosives and Severe Irritants: Addendum was made available in November 2005. Final BRDs were published in 2006. ICCVAM and its Ocular Toxicity Working Group considered the Expert Panel report and Addendum, the revised accuracy and reliability analyses, all public comments, and the comments of the Scientific Advisory Committee on Alternative Toxicological Methods in preparing the final Test Method Evaluation Report, published in November 2006.

ICCVAM recommended that the BCOP Test Method and the ICE Test Method can be used in a tiered testing strategy to determine ocular hazards, with specific limitations for certain chemical classes and/or physical properties. Substances that test positive in these assays can be classified as ocular corrosives or severe irritants without further testing in animals. The report also recommends that these in vitro test methods should be considered before using animals for ocular testing and used when determined appropriate. These recommendations, once accepted by Federal agencies, will result in a reduction of the number of animals used for safety testing to determine permanent or temporary damage to the eye.

ICCVAM evaluated two other in vitro test methods, the Isolated Rabbit Eye (IRE) Test Method and the Hen's Egg Test - Chorioallantoic Membrane (HET-CAM) Test Method. Before these two methods can be recommended for use as screening tests for the identification of ocular corrosives and severe irritants, the protocol and decision criteria for the identification of ocular corrosives and severe irritants need to be optimized and undergo further validation.

In October 2007, the ICCVAM Test Method Evaluation Report, as well as the supporting final BRDs, were forwarded to Federal agencies for their consideration of regulatory acceptance as required by the ICCVAM Authorization Act of 2000 (42 U.S.C. 285l-3). These are the first alternative non-animal test methods for ocular safety testing reviewed by ICCVAM and transmitted to agencies. Agencies' response to the test method recommendations, which are due in April 2008, will be posted as they are received.

Federal Register Notice (Vol. 72, No. 226, page 65964-65965, November 26, 2007):
Availability of the ICCVAM Test Method Evaluation Report on In Vitro Ocular Toxicity Test Methods for Identifying Severe Irritants and Corrosives and Final In Vitro Ocular Test Method Background Review Documents; Notice of Transmittal of ICCVAM Test Method Recommendations to Federal Agencies