In October 2007, ICCVAM forwarded recommendations on in vitro test methods to identify
corrosives or severe irritants to U.S. Federal agencies. These were the first recommendations made
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
considered before using animals for ocular testing and used when determined appropriate.
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
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.
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
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
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
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.
- 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