National Toxicology Program

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Test Method Evaluation Report

Cover of the In Vitro Methods TMERICCVAM Test Method Evaluation Report: Current Validation Status of In Vitro Test Methods Proposed for Identifying Eye Injury Hazard Potential of Chemicals and Products

NIH Publication No. 10-7553
Download complete report:
Volume 1 (Main Body and Appendices A-D - 654 pages, 47 MB)
Volume 2 (Appendices E-J - 670 pages, 12 MB)

Large files may take some time to download: times will vary based on the speed of the online connection. The complete report files may not be accessible to all readers; files of individual sections of the report linked below may provide improved accessibility. If you would like assistance in accessing this document, please send an email to the ICCVAM Webmaster [Send Email] or call NICEATM at 919-316-4729.


Correction to the test method evaluation report (October 2011)

The correction affects the BCOP false negative substances for the EPA classification system, specifically the contents of Table 2-1 of the main body of the report (page 5 of Volume 1) and Table 6-10 of the Background Review Document (Appendix C; page C-58 of Volume 1) and the associated text. If you have a hard copy of this document (NIH Publication No. 10-7553) you may wish to print out the PDF document above and keep it with the hard copy. In addition, please note that the electronic versions of the main body and BRD linked below do not include these updates.


View Test Method Evaluation Report by Section

Front Matter
Includes Table of Contents, Lists of Tables and Figures, List of Abbreviations and Acronyms, Acknowledgements, Preface, and Executive Summary

Main Body

  • Section 1: Introduction
  • Section 2: The Bovine Corneal Opacity and Permeability Test Method
  • Section 3: The Cytosensor Microphysiometer Test Method
  • Section 4: The Hen’s Egg Test–Chorioallantoic Membrane Test Method
  • Section 5: The Isolated Chicken Eye Test Method
  • Section 6: The Isolated Rabbit Eye Test Method
  • Section 7: ICCVAM Consideration of Public, SACATM, and ICATM Comments
  • Section 8: References

Appendix A: ICCVAM Evaluation Timeline

Appendix B: ICCVAM-recommended Test Method Protocols

  • Appendix B1: ICCVAM-Recommended Protocol for Future Studies Using the Bovine Corneal Opacity And Permeability (BCOP) Test Method
  • Appendix B2: ICCVAM-Recommended Protocol for Future Studies Using the Cytosensor Microphysiometer (CM) Test Method
  • Appendix B3: ICCVAM-Recommended Protocol for Future Studies Using the Hen's Egg Test–Chorioallantoic Membrane (HET-CAM) Test Method
  • Appendix B4: ICCVAM-Recommended Protocol for Future Studies Using the Isolated Chicken Eye (ICE) Test Method
  • Appendix B5: ICCVAM-Recommended Protocol for Future Studies Using the Isolated Rabbit Eye (IRE) Test Method

Appendix C: Background Review Document – Current Status of In Vitro Test Methods for Identifying Mild/Moderate Ocular Irritants: Bovine Corneal Opacity and Permeability Test Method

Appendix D: Background Review Document of Existing Methods for Eye Irritation Testing: Silicone Microphysiometer and Cytosensor Microphysiometer
Provided to ICCVAM by the European Centre for the Validation of Alternative Methods: Available on request from NICEATM

Appendix E: Background Review Document – Current Status of In Vitro Test Methods for Identifying Mild/Moderate Ocular Irritants: The Hen's Egg Test–Chorioallantoic Membrane (HET-CAM) Test Method

Appendix F: Background Review Document – Current Status of In Vitro Test Methods for Identifying Mild/Moderate Ocular Irritants: The Isolated Chicken Eye (ICE) Test Method

Appendix G: Independent Scientific Peer Review Panel Assessment

  • Appendix G1: Summary Minutes from the Peer Review Panel Meeting on May 19-21, 2009
  • Appendix G2: Independent Scientific Peer Review Panel Report: Evaluation of the Validation Status of Alternative Ocular Safety Testing Methods and Approaches

Appendix H: Federal Register Notices and Public Comments

Appendix I: Relevant U.S. Federal and International Ocular Toxicity Regulations, Labeling, and Test Guidelines

  • Appendix I1: Table of Relevant U.S. Federal and International Ocular Testing Regulations for Hazard Classification and Labeling
  • Appendix I2: U.S. Environmental Protection Agency Health Effects Test Guidelines: OPPTS 870.2400 - Acute Eye Irritation
  • Appendix I3: U.S. Environmental Protection Agency Office of Pesticide Programs Label Review Manual
    View on U.S. Environmental Protection Agency website
  • Appendix I4: Organisation for Economic Co-operation and Development Test Guideline 405: Acute Eye Irritation/Corrosion

Appendix J: NICEATM Analysis: Reduced Eye Hazard Labeling Resulting from Using Globally Harmonized System (GHS) Instead of Current U.S. Regulatory Classification Criteria

  • Main Body
    • Front Matter: Includes Table of Contents, List of Tables, and Summary
    • Section 1: Background
    • Section 2: Overview of NICEATM and ICCVAM Analyses
    • Section 3: Analysis of the ECETOC Eye Irritation Database
    • Section 4: Analysis of the 1999 OECD Detailed Review Document on Classification Systems for Eye Irritation/Corrosion in OECD Member Countries
    • Section 5: Summary of Analyses
    • Section 6: Possible Options for GHS Hazard Categories for Classification and Labeling of Reversible Eye Irritation
    • Section 7: References
    • Section 8: Isolated Chicken Eye Test Method Data Quality
    • Section 9: Other Scientific Reports and Reviews
    • Section 10: Animal Welfare Considerations (Reduction, Refinement, and Replacement)
    • Section 11: Practical Considerations
    • Section 12: References
    • Section 13: Glossary
  • Annex I: OECD Series on Testing and Assessment - Number 14: Detailed Review Document on Classification Systems for Eye Irritation/Corrosion in OECD Member Countries (ENV/JM/MONO(99)4)
  • Annex II: Grades for Ocular Lesions
  • Annex III: Consideration of the Minimum Number of Animals with Positive Eye Injury Responses Required for Classification of a Chemical as an Eye Irritation Hazard
  • Annex IV: Nature, Duration, and Severity of Ocular Lesions for 31 ECETOC Substances that are EPA Irritants (Category I, II, or III) or FHSA Irritants but Not Classified as Ocular Hazards by GHS Classification Criteria
  • Annex V: OECD Database: Comparison of Percent Irritant Classification Using EPA, FHSA, and GHS Classification Systems
  • Annex VI: Nature, Duration, and Severity of Ocular Lesions for 33 OECD DRD Substances that are EPA Irritants (Category I, II, or III) or FHSA Irritants but Not Classified as Ocular Hazards by GHS Classification Criteria
  • Annex VII: Representative Rabbit Eye Test Data Used in the NICEATM Evaluation of the GHS Classification System

Appendix K: ECVAM Scientific Advisory Committee Statement oon the Scientific Validity of Cytotoxicity/Cell-Function Based In Vitro Assays for Eye Irritation Testing

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