National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/40167

Evaluation of In Vitro Ocular Test Methods

In 2010, ICCVAM issued recommendations on the use of five in vitro test methods for identifying reversible and nonsevere eye injuries:
Related evaluation
An earlier evaluation of in vitro ocular test methods resulted in ICCVAM recommending the BCOP and ICE test methods for identifying ocular corrosives and severe irritants. Details of the earlier evaluation
  • The bovine corneal opacity and permeability (BCOP) test method
  • The Cytosensor® microphysiometer (CM) test method
  • The hen's egg test - chorioallantoic membrane (HET-CAM) test method
  • The isolated chicken eye (ICE) test method
  • The isolated rabbit eye (IRE) test method

These recommendations have been accepted by ICCVAM member agencies.

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. Substances that are appropriate for testing using the CM test method and yield positive results can be classified as having the potential to cause severe or permanent eye injuries without additional testing using animals. However, a substance that tests negative with the CM test method would need to be tested using another test method capable distinguishing between different hazard classifications of substances that can cause reversible and nonsevere eye injuries.

ICCVAM also recommended that the CM test method can be used, for a limited range of substances (water-soluble surfactants and surfactant-containing formulations such as cosmetics and personal care products), to determine that chemicals and products do not present sufficient potential to cause eye injuries to require eye hazard labeling. The CM test method is 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 must be improved before they can 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. The 2010 report on the ICCVAM evaluation of these test methods includes recommendations for future studies that could potentially improve these test methods. These test methods were previously evaluated by ICCVAM for their usefulness to identify substances that may cause permanent or severe eye injuries.

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

Transmittal letters, agency responses, and summary of all September 2010 ICCVAM recommendations on ocular test methods transmitted to Federal agencies

Background on the ICCVAM Evaluation of the In Vitro Test Methods

List of relevant references

In 2006, ICCVAM made recommendations on the use of the BCOP, HET-CAM, ICE, and IRE test methods to identify substances that may cause permanent or severe eye injuries. One of the ICCVAM recommendations resulting from that evaluation was to determine the ability of these test methods to identify substances that may cause reversible and nonsevere eye injuries. ICCVAM also reviewed the validation status of the CM test method, which was not part of the 2006 evaluation.

NICEATM and ICCVAM prepared draft background review documents (BRDs) that summarized the current validation status of the BCOP, HET-CAM, ICE, and IRE test methods. A BRD summarizing the available data on the CM test method was obtained from the European Centre for the Validation of Alternative Methods. Data in these documents were used as the basis for developing draft ICCVAM recommendations. The draft BRDs and draft ICCVAM recommendations were reviewed in May 2009 by an independent international peer review panel. ICCVAM considered the peer review panel's comments, as well as comments from the public and from the Scientific Advisory Committee on Alternative Toxicological Methods, before finalizing its recommendations for Federal agencies.

Peer Review Panel Report (July 2009)

Summary of the Peer Review Panel meeting

ICCVAM recommendations regarding the usefulness and limitations of the BCOP, CM, HET-CAM, ICE, and IRE test methods are contained in the ICCVAM Test Method Evaluation Report: Current Validation Status of In Vitro Test Methods Proposed for Identifying Eye Injury Hazard Potential of Chemicals and Products (2010). The report also includes ICCVAM-recommended test method protocols for future studies, as well as recommendations to further characterize and potentially improve the usefulness and applicability of the test methods.

The ICCVAM recommendations were transmitted to Federal agencies in September 2010. Agency responses indicated acceptance or endorsement of the ICCVAM recommendations.

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