National Toxicology Program

National Toxicology Program
http://ntp.niehs.nih.gov/go/40177

Evaluation of In Vitro Test Methods to Identify Ocular Corrosives and Severe Irritants

In October 2007, ICCVAM forwarded recommendations on in vitro test methods to identify ocular corrosives or severe irritants to U.S. Federal agencies. These were the first recommendations made by ICCVAM on the use of alternative non-animal test methods for ocular safety testing.

ICCVAM recommended that two test methods, the bovine corneal opacity and permeability and the isolated chicken eye test methods, 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 using these tests can be classified as ocular corrosives or severe irritants without further testing in animals. ICCVAM also recommended that these in vitro test methods should be considered before using animals for ocular testing and used when determined appropriate.

Test Method Evaluation Report (November 2006) including ICCVAM recommendations

Additional recommendations
A later evaluation of these in vitro ocular test methods resulted in additional ICCVAM recommendations on their use. View details of the later evaluation

The ICCVAM recommendations were accepted by Federal agencies, and the two in vitro test methods may now be used instead of conventional tests for certain regulatory testing purposes. The use of these two alternative test methods will likely reduce the use of live animals for eye safety testing and eliminate eye safety testing in animals of most substances likely to cause the most severe pain and discomfort.

NIH Press Release (June 23, 2008): Newly Approved Ocular Safety Methods Reduce Animal Testing
View press release on NIH Website

Background and ICCVAM Evaluation

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.

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 data submitted on the methods. ICCVAM and its Ocular Toxicity Working Group considered the Expert Panel evaluation, 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.

As stated above, ICCVAM recommended that the bovine corneal opacity and permeability and the isolated chicken eye test methods may be used for ocular hazard classification testing of some types of substances. The isolated rabbit eye and hen's egg test - chorioallantoic membrane test methods were not considered to currently have sufficient performance and/or sufficient data to substantiate they use for regulatory hazard classification purposes, but may have applicability for other uses.

View test method evaluation report

View final background review documents:

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. Formal adoption of these methods by OECD allow them to now be used in the 34 OECD member countries, which include Japan, Canada and most countries in the European Union.

View OECD Test Guideline 437

View OECD Test Guideline 438

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.

The NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.