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Peer Review Panel Report now available [PDF] Federal Register Notice announcing availability of Peer Review Panel Report; request for comments View the FR Notice [PDF] Go to comment page for Ocular FR Notice View a summary of the May 2009 Ocular Review Panel meeting [PDF] An international independent scientific peer review panel met on May 19-21, 2009 to evaluate alternative test methods and approaches that may further reduce and refine the use of animals for ocular safety testing. Dr. Wallace Hayes of the Harvard School of Public Health chaired the public meeting of the Panel, composed of 22 scientists from the U.S., Japan, Canada, the Netherlands, Belgium, and Spain. The Panel represented a wide range of expertise, including human and veterinary ophthalmology, in vitro toxicology, biostatistics, anesthesiology, pathology, and regulatory toxicology. The Panel reviewed several proposed test methods and testing approaches nominated by the U.S. Environmental Protection Agency, including: Non-animal testing strategies using three in vitro test methods to assess the eye irritation potential of antimicrobial cleaning products for EPA ocular hazard classification and labeling purposes. The in vitro methods included the bovine corneal opacity and permeability (BCOP) assay, the Cytosensor Microphysiometer® (CM) assay, and the EpiOcular™ (EO) assays. Six individual in vitro test methods for identifying ocular irritants, including BCOP, CM, EO, isolated chicken eye, isolated rabbit eye, and the hen’s egg test – chorioallantoic membrane (HET-CAM) assays. The in vivo low volume eye test (LVET), proposed as an alternative to the current in vivo eye test. A proposal for the routine use of topical anesthetics, systemic analgesics, and humane endpoints to avoid and minimize pain and distress during required in vivo ocular irritation testing The Panel evaluated the validation status of each of the above proposed alternative test methods and approaches according to established Federal and international criteria. The Panel also commented on draft ICCVAM recommendations regarding the usefulness and limitations of each proposed test method and approach. The Panel's conclusions and recommendations will be published in the Panel's report, which will be available on this page in July.

View Meeting Agenda [PDF]

Announcement of an Independent Scientific Peer Review Panel on Alternative Ocular Safety Testing Methods; Availability of Draft Background Review Documents (BRD); Request for Comments

Documents to be Reviewed by the Ocular Peer Review Panel

Draft Proposed ICCVAM Test Method Recommendations: Evaluation of the Validation Status of Alternative Ocular Safety Testing Methods and Approaches [PDF]

View list of key general references

Draft Background Review Documents

Draft Background Review Document: Use of Topical Anesthetics, Systemic Analgesics, and Earlier Humane Endpoints to Minimize Pain and Distress in Ocular Toxicity Testing

Background Review Document with all appendices (87 pages) [PDF]

References for Use of Anaesthesia and Analgesia in In Vivo Ocular Hazard Testing

Draft Summary Review Document (SRD): The In Vivo Low Volume Eye Test (LVET)

• Main Body (32 pages) [PDF]
  Erratum (May 15): A typographical error in the Executive Summary of the draft ICCVAM LVET SRD incorrectly states that there is “no information on the performance of known human corrosives in the LVET”. Section 5.0 of the SRD recognizes that there are limited data on such substances. Therefore, the Executive Summary should instead indicate that there is “limited information on the performance of known human corrosives in the LVET”. We apologize for any confusion this oversight has created.


• Appendix A: Low Volume Eye Test (LVET) A.I.S.E. Submission To ECVAM - Technical Dossier, February 2007
  This document was originally submitted to the European Centre for the Validation of Alternative Methods (ECVAM). Because this document forms part of the basis for one or more draft ICCVAM test method recommendations, NICEATM has requested authorization from ECVAM to make this document publicly available. However, ECVAM has not been able to obtain agreement for release of this document from companies that produced unpublished data that are included in the document. Therefore, this document is not included here.

References for the Low Volume Eye Test

Draft Summary Review Document: Strategy for U.S. Environmental Protection Agency Ocular Hazard Classification and Labeling of Antimicrobial Cleaning Products Using In Vitro Alternative Test Methods

• Main Body (78 pages) [PDF]
• Appendix A: Background Review Document (BRD) of an In Vitro Approach for EPA Toxicity Labeling of Anti-Microbial Cleaning Products
  View webpage with appendix contents
• Appendix B: ECVAM BRD Submission - The Low Volume Eye Test
• Appendix C: ECVAM BRD Submission - Cytosensor Microphysiometer
• Appendix D: ECVAM BRD Submission - EO OCL-200 Model for Assessing Eye Irritation of Surfactants and Surfactant-Based Formulations
  The documents for Appendices B, C, and D were prepared by ECVAM, and ECVAM has agreed to make them publicly available for review and comment. However, ECVAM has not been able to obtain agreement for release of these documents from companies that produced unpublished data that are included in the documents. Therefore, these documents are not included here.
• Appendix E: ICCVAM Background Review Document - Current Status of In Vitro Test Methods for Identifying Ocular Corrosives and Severe Irritants: Bovine Corneal Opacity and Permeability Test Method (206 pages) [PDF]
• Appendix F: Physicochemical Properties of Substances Evaluated in the AMCP BRD (4 pages) [PDF]
• Appendix G: Data Used for the Performance Analysis of the AMCP BRD (2 pages) [PDF]

References for the Classification of Antimicrobial Cleaning Products Using In Vitro Alternative Test Methods

Draft Background Review Documents: Current Status of In Vitro Test Methods for Identifying Mild/Moderate Ocular Irritants

The Isolated Chicken Eye (ICE) Test Method

• Main Body (102 pages) [PDF]
• Appendix A: Chemical and Product Class Information for the Substances Tested in the ICE Test Method (10 pages) [PDF]
• Appendix B: In Vitro Data for Substances Tested in the ICE Test Method
  • B1 - ICE Data Sorted by Reference [XLS]
  • B2 - ICE Data Sorted by Substance Name [XLS]
• Appendix C: In Vivo and In Vitro Comparison of Ocular Irritancy Classification
  • C1 - ICE Data Sorted by Reference [XLS]
  • C2 - ICE Data Sorted by Substance Name [XLS]

Supplemental Information

1. False Negative Substances in the ICE Test Method (Revised May 10) [PDF]
2. Draft OECD Test Guideline 438: Isolated Chicken Eye (ICE) Test Method for Identifying Ocular Corrosives and Severe Irritants (December 2008 - available on OECD website) [PDF]

The Bovine Corneal Opacity and Permeability (BCOP) Test Method

• Main Body (131 pages) [PDF]
• Appendix A: Characterization of the Substances Tested in the BCOP Test Method
  • A1 - Chemical and Product Classes of Substances Tested in the BCOP Assay [XLS]
  • A2 - Components of Formulations Tested in Gettings et al. (1996) [XLS]
  • A3 - Components of Formulations Tested in Swanson et al. (1995) [XLS]
  • A4 - Components of Formulations Tested in Swanson and Harbell (2000) [XLS]
  • A5 - Components of AMCP Formulations Tested in Swanson [XLS]
• Appendix B: In Vitro Data for Substances Tested in the BCOP Test Method
  • B1 - BCOP Data Sorted by Reference [XLS]
  • B2 - BCOP Data Sorted by Substance Name [XLS]
• Appendix C: In Vivo and In Vitro Comparison of Ocular Irritancy Classification
  • C1 - BCOP Data Sorted by Reference [XLS]
  • C2 - BCOP Data Sorted by Substance Name [XLS]

Supplemental Information

1. False Negative Substances in the BCOP Test Method (Revised May 10) [PDF]
2. Draft OECD Test Guideline 437: Bovine Corneal Opacity and Permeability (BCOP) Test Method for Identifying Ocular Corrosives and Severe Irritants (December 2008 - available on OECD website) [PDF]

The Hen’s Egg Test – Chorioallantoic Membrane (HET-CAM) Test Method

• Main Body (119 pages) [PDF]
• Appendix A: Chemical and Product Class Information for the Substances Tested in the HET-CAM Test Method (46 pages) [PDF]
• Appendix B: In Vitro Data for Substances Tested in the HET-CAM Test Method
  • B1 - Test Method Protocols used to Generate In Vitro Data [XLS]
  • B2 - Data Sorted by Reference [XLS]
  • B3 - Data Sorted by Substance for IS(A) Analysis Method [XLS]
  • B4 - Data Sorted by Substance for IS(A)-10 Analysis Method [XLS]
  • B5 - Data Sorted by Substance for IS(A)-100 Analysis Method [XLS]
  • B6 - Data Sorted by Substance for IS(B) Analysis Method [XLS]
  • B7 - Data Sorted by Substance for IS(B)-10 Analysis Method [XLS]
  • B8 - Data Sorted by Substance for IS(B)-100 Analysis Method [XLS]
  • B9 - Data Sorted by Substance for Q-Score Analysis Method [XLS]
  • B10 - Data Sorted by Substance for S-Score Analysis Method [XLS]
• Appendix C: In Vivo and In Vitro Comparison of Ocular Irritancy Classification
  • C1 - Data Sorted by Reference [XLS]
  • C2 - Data Sorted by Substance for IS(A) Analysis Method [XLS]
  • C3 - Data Sorted by Substance for IS(A)-10 Analysis Method [XLS]
  • C4 - Data Sorted by Substance for IS(A)-100 Analysis Method [XLS]
  • C5 - Data Sorted by Substance for IS(B) Analysis Method [XLS]
  • C6 - Data Sorted by Substance for IS(B)-10 Analysis Method [XLS]
  • C7 - Data Sorted by Substance for IS(B)-100 Analysis Method [XLS]
  • C8 - Data Sorted by Substance for Q-Score Analysis Method [XLS]
  • C9 - Data Sorted by Substance for S-Score Analysis Method [XLS]
• Appendix D: Performance Analysis for All Protocols [XLS]

Supplemental Information

1. Revised HET-CAM Test Method Protocol Components (Section 2.0 of draft BRD - Revised May 11) [PDF]
2. Revised Draft Updated ICCVAM Recommended HET-CAM Test Method Protocol (Revised May 11) [PDF]
3. False Negative Substances in the HET-CAM Test Method [PDF]

Cell Function-Based Assays for Identifying Ocular Corrosives, Irritants, and Substances Not Labeled as Irritants

The Cytosensor Test Method

• Draft Proposed ICCVAM Recommendations for the Cytosensor Test Method: Uses and Limitations [PDF]

Supplemental Information

1. ECVAM Document: "Background Review Document of Existing Methods for Eye Irritation Testing: Silicone Microphysiometer and Cytosensor Microphysiometer"
   ECVAM has made a "cleansed" version of this document with proprietary information removed available for review at the Ocular Peer Review Panel meeting.
   • Main body [PDF]
   • Annexes A-L [PDF]
     (Please note the PDF of the annexes is a large document and may take several minutes to open.)