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Use of the Murine Local Lymph Node Assay for Potency Categorization
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Overview and Recommendations Test Method Evaluation Report

Test Method Evaluation Report

ICCVAM Test Method Evaluation Report
Usefulness and Limitations of the Murine Local Lymph Node Assay for Potency Categorization of Chemicals Causing Allergic Contact Dermatitis in Humans

NIH Publication No. 11-7709
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 Cover of the ICCVAM LLNA Potency Test Method Evaluation Report

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Front Matter and Main Body [PDF]
Includes Table of Contents, Lists of Tables and Figures, List of Abbreviations and Acronyms, Acknowledgements, Preface, Executive Summary

Main Body sections:

  • Section 1: Introduction
  • Section 2: ICCVAM Recommendations: Usefulness and Limitations of the LLNA for Potency Categorization of Chemicals Causing Allergic Contact Dermatitis in Humans, Test Method Protocol, and Future Studies
  • Section 3: Validation Status for Use of the LLNA to Determine Skin Sensitization Potency Categories
  • Section 4: ICCVAM Consideration of Independent Peer Review Panel Report and Other Comments

Appendix A: Timeline for ICCVAM Evaluation on Usefulness and Limitations of the Murine Local Lymph Node Assay for Potency Categorization of Chemicals Causing Allergic Contact Dermatitis in Humans [PDF]

Appendix B: Updated ICCVAM-Recommended Protocol: The Murine Local Lymph Node Assay: A Test Method for Assessing the Allergic Contact Dermatitis Potential of Chemicals and Products [PDF]

  • Main Body
  • Annex I: An Approach to Dissection and Identification of the Draining (“Auricular”) Lymph Nodes
  • Annex II: An Example of How to Reduce the Number of Animals in the Concurrent Positive Control Group of the Local Lymph Node Assay
  • Annex III: Evaluating Local Irritation and Systemic Toxicity in the Local Lymph Node Assay
  • Annex IV: Procedures for Calculating the Estimated Concentration of a Substance Expected to Produce a Stimulation Index of 3 (EC3) in the Murine Local Lymph Node Assay

Appendix C: Final Background Review Document: Use of the Murine Local Lymph Node Assay for Potency Categorization of Chemicals Causing Allergic Contact Dermatitis in Humans
  • Main body [PDF]
    • Front matter: Includes Table of Contents, Acknowledgements, Preface, and Executive Summary
    • Section 1: Introduction and Rationale for the Proposed Use of the Murine Local Lymph Node Assay for Potency Assessment
    • Section 2: LLNA Test Method Protocol Components
    • Section 3: Substances Used for Validation of the LLNA for Potency Determinations
    • Section 4: Comparative In Vivo Reference Data
    • Section 5: LLNA Data and Results
    • Section 6: Test Method Accuracy
    • Section 7: Test Method Reliability
    • Section 8: LLNA Data Quality
    • Section 9: Other Scientific Reports and Reviews
    • Section 10: Animal Welfare Considerations
    • Section 11: Practical Considerations
    • Section 12: References
    • Section 13: Glossary

  • Annex I: LLNA/EC3 Validation – Submission from David Basketter, Frank Gerberick, and Ian Kimber [PDF]

  • Annex II: Comparative LLNA, Guinea Pig, and Human Data Used in the Performance Evaluation
    • II-1: LLNA Data for 196 Substances Used for the Evaluation of Skin Sensitization Potency (Alphabetical Order) [PDF]
    • II-2: Human Data for LLNA Potency Evaluation [PDF]
    • II-3: Guinea Pig Data for LLNA Potency Evaluation [PDF]
    • II-4: Summary LLNA, Human, and Guinea Pig Data Used in the Regression and Classification Rate Analyses [PDF]

  • Annex III: Physicochemical Properties of Substances Evaluated [PDF]

  • Annex IV: Analyses to Determine Representative EC3 Values [PDF]

  • Annex V: Performance Characteristics for Use of LLNA EC3 Values to Predict Human Skin Sensitization Potency Categories [PDF]

Appendix D: Independent Scientific Peer Review Panel Assessment
  • Appendix D1: Summary Minutes from Peer Review Panel Meeting on March 4-6, 2008 [PDF]
  • Appendix D2: Independent Scientific Peer Review Panel Report: Validation Status of New Versions and Applications of the Murine Local Lymph Node Assay: A Test Method for Assessing the Allergic Contact Dermatitis Potential of Chemicals and Products [PDF]
Appendix E: GHS Materials on Skin Sensitization Potency
  • Appendix E1: Meetings of the Sub-Committee of Experts on the Globally Harmonized System of Classification and Labelling of Chemicals Relevant to Subcategorization of Skin Sensitizers [PDF]
  • Appendix E2: ST/SG/AC.10/C.4.2006/16, Strong versus Weak Sensitizers [PDF]
  • Appendix E3: UN/SCEGHS/12/INF.16 (OECD), Progress Report on OECD Work Since the Last Sub-Committee Meeting [PDF]
  • Appendix E4: UN/SCEGHS/15/INF.14 (OECD), Proposal for Revising Chapter 3.4 with Respect to Strong versus Weak Sensitizers: Explanatory Notes and Revised Chapter with Visible Changes [PDF]
  • Appendix E5: ST/SG/AC.10/C.4/2008/18 (Secretariat), Revision of Chapter 3.4 with Respect to Strong versus Weak Sensitizers [PDF]
  • Appendix E6: ST/SG/AC.10/C.4/2008/18/Add.1 (Secretariat), Revision of Chapter 3.4 with Respect to Strong versus Weak Sensitizers, Addendum [PDF]
  • Appendix E7: UN/SCEGHS/16/INF.3 (Secretariat), Section 3.4.2 of Chapter 3.4 [PDF]
Appendix F: Federal Register Notices and Public Comments
  • Appendix F1: Federal Register Notices
    • 72 FR 27815 (May 17, 2007): The Murine Local Lymph Node Assay: Request for Comments, Nominations of Scientific Experts, and Submission of Data [PDF]
    • 72 FR 52130 (September 12, 2007): Draft Performance Standards for the Murine Local Lymph Node Assay: Request for Comments [PDF]
    • 73 FR 1360 (January 8, 2008): Announcement of an Independent Scientific Peer Review Panel Meeting on the Murine Local Lymph Node Assay; Availability of Draft Background Review Documents; Request for Comments [PDF]
    • 73 FR 25754 (May 7, 2008): Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) [PDF]
    • 73 FR 29136 (May 20, 2008): Peer Review Panel Report on the Validation Status of New Versions and Applications of the Murine Local Lymph Node Assay (LLNA): A Test Method for Assessing the Allergic Contact Dermatitis Potential of Chemicals and Products: Notice of Availability and Request for Public Comments [PDF]

  • Appendix F2: Public Comments Received in Response to Federal Register Notices

  • Appendix F3: SACATM Comments: SACATM Meeting on June 18-19, 2008
    Download minutes of the SACATM meeting from the NTP website [PDF]

Appendix G: Relevant Skin Sensitization Regulations and Testing Guidelines

  • Appendix G1: Table of Relevant Skin Sensitization Test Regulations [PDF]
  • Appendix G2: Health Effects Test Guidelines OPPTS 870.2600: Skin Sensitization [PDF]
  • Appendix G3: ISO 10993-10: Biological Evaluation of Medical Devices Part 10: Tests for Irritation and Delayed-type Hypersensitivity
    Available for purchase on the ISO website
  • Appendix G4: OECD Guideline 429: Skin Sensitisation – Local Lymph Node Assay [PDF]
  • Appendix G5: OECD Guideline 406: Skin Sensitisation [PDF]
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