Evaluation of In Vitro Test Methods to Identify Ocular Corrosives and Severe Irritants
In 2007, ICCVAM forwarded recommendations to U.S. Federal agencies on in vitro test methods used to identify ocular corrosives or severe irritants, substances with the potential to cause severe or permanent eye injuries. These recommendations were the first made by ICCVAM on the use of alternative non-animal test methods for ocular toxicity testing.
ICCVAM recommended the use of two test methods, the bovine corneal opacity and permeability (BCOP) and the isolated chicken eye (ICE) test methods, in a tiered-testing strategy to determine eye injury hazards, with specific limitations for certain chemical classes and/or physical properties. Substances that test positive using these test methods can be classified as ocular corrosives or severe irritants without further testing in animals. ICCVAM also recommended that these in vitro test methods be considered, and used when appropriate, before using animals for ocular toxicity testing. Implementation of these methods will
- Reduce the use of live animals for ocular toxicity testing
- Eliminate the need for ocular toxicity testing in animals for most substances likely to cause severe pain and discomfort
NIH Press Release (June 23, 2008): Newly Approved Ocular Safety Methods Reduce Animal Testing
View press release on NIH Website
Test Method Evaluation Report (November 2006) including ICCVAM recommendations
Background and ICCVAM Evaluation
In 2003, the U.S. Environmental Protection Agency (EPA) nominated four in vitro ocular toxicity test methods for evaluation as potential screening methods to identify ocular corrosives or severe irritants. ICCVAM, in collaboration with NICEATM, convened an independent Expert Panel in January 2005 to determine the validation status of these methods; the panel reconvened later in 2005 to consider additional submitted data relevant to the method review. ICCVAM considered the Expert Panel evaluation, revised accuracy and reliability analyses, the comments of the Scientific Advisory Committee on Alternative Toxicological Methods, and all public comments in preparing the final Test Method Evaluation Report, published in November 2006.
Expert Panel Report: Evaluation of the Current Validation Status of In Vitro Test Methods for Identifying Ocular Corrosives and Severe Irritants (March 2005)
Addendum to the Expert Panel Report (November 2005)
Final background review documents (March 2006)
OECD Test Guidelines 437 and 438
The ICCVAM recommendations on the BCOP and ICE test methods were used as the basis for proposals for new test guidelines to the Organisation for Economic Co-operation and Development (OECD). Test Guideline 437 describing the BCOP and Test Guideline 438 describing the ICE were formally adopted by the OECD in September 2009, allowing use of the methods in the 34 OECD member countries, which include Japan, Canada and most countries in the European Union. Both guidelines were updated in 2013 to allow broader use of the methods.
Recommendations and Agency Responses
The ICCVAM recommendations were communicated to Federal agencies in letters from Dr. Samuel H. Wilson, Acting Director, NIEHS, to each agency head. Links to these letters, and to the responses received from the agency heads, can be found below.
- National Institute of Environmental Health Sciences (NIEHS)
- Agency for Toxic Substances and Disease Registry (ASTDR)
- Consumer Products Safety Commission (CPSC)
- Environmental Protection Agency (EPA)
- Food and Drug Administration (FDA)
- National Cancer Institute (NCI)
- National Institutes of Health (NIH)
- National Institute for Occupational Safety and Health (NIOSH)
- National Library of Medicine (NLM)
- Occupational Safety and Health Administration (OSHA)
- U.S. Department of Agriculture
- U.S. Department of Defense
- U.S. Department of Energy
- U.S. Department of the Interior
- U.S. Department of Transportation