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Evaluations of In Vitro Test Methods

ICCVAM evaluated and produced recommendations, published in 2006 and 2010, for in vitro test methods used to identify ocular irritants.

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

In its 2006 evaluation, ICCVAM recommended the use of 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. Substances that test positive using these test methods can be classified as ocular corrosives or severe irritants without testing in animals or additional in vitro eye irritation methods.

ICCVAM Report and Related Documents

Test Method Evaluation Report (November 2006) including ICCVAM recommendations

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 the basis for test guideline proposals submitted 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. Both test guidelines were revised in 2013 to allow classification of chemicals not requiring classification for eye irritation or serious eye damage; additional revisions to both test guidelines were made in 2017. 

View OECD Test Guideline 437 on the OECD iLibrary website

View OECD Test Guideline 438 on the OECD iLibrary website

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.

Further Evaluations of In Vitro Ocular Test Methods

In 2010, ICCVAM issued recommendations on the use of the BCOP, the ICE, and three other in vitro test methods for identifying reversible and nonsevere eye injuries:

  • The Cytosensor microphysiometer (CM) test method
  • The hen's egg test - chorioallantoic membrane (HET-CAM) test method
  • The isolated rabbit eye (IRE) test method

ICCVAM recommended that the CM test method can be used as a screening test to identify some types of water-soluble substances that may cause permanent or severe eye injuries. ICCVAM also recommended that the CM test method can be used, for a limited range of substances, to identify chemicals and products that do not present sufficient potential to cause eye injuries to require eye hazard labeling. The CM test method was the first in vitro test method available in the U.S. for this purpose.

ICCVAM concluded that the performance of the other four test methods required improvement before they could be used in regulatory safety testing to classify substances as having the potential to cause reversible, nonsevere eye injuries or as not requiring hazard labeling for eye irritation. As noted above, subsequent evaluations have validated the use of the BCOP and ICE methods to identify substances not requiring hazard labeling for eye irritation.

Test method evaluation report with details of ICCVAM recommendations and test method evaluation

Peer Review Panel Report (July 2009)

Recommendations and Agency Responses

The ICCVAM recommendatiossnicated to federal agencies in September 2010 letters from Dr. Linda Birnbaum, Director, NIEHS. These letters and responses received from federal agencies are available below.