National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/40462

Test Method Evaluation Report: Applicability Domain for the LLNA


Cover of the ICCVAM Report on the LLNA Applicability Domain ICCVAM Test Method Evaluation Report on Using the Murine Local Lymph Node Assay for Testing Pesticide Formulations, Metals, Substances in Aqueous Solutions, and Other Products

NIH Publication No. 10-7512
Complete report (26.2 Mb - revised May 2012)

Please note:

  • Large files may take some time to download: times will vary based on the speed of the online connection.
  • The file containing the complete document may not be fully accessible to some readers. The individual sections below may provide greater accessiblity. If you have difficulty accessing this document, please send an email to the ICCVAM Webmaster [Send Email] or call NICEATM at 919-316-4729.

Appendix D Corrections: May 2012

The corrected annexes are included in the PDF sections below and in the complete report linked above.


Report Main Body

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: ICCVAM Recommendations for the Updated Assessment of the Validity of the LLNA for Testing Pesticide Formulations, Metals, Substances in Aqueous Solutions, and Other Products
  • Section 3: Evaluation of the LLNA Applicability Domain
  • Section 4: ICCVAM Consideration of Public and SACATM Comments

Appendix A: ICCVAM Evaluation Timeline

Appendix B: ICCVAM-Recommended Protocol: The Murine Local Lymph Node Assay

  • 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

Appendix C: Comparison of LLNA Responses for Substances Tested in CBA and BALB/C Mice

  • Annex I: Data for Substances Tested in the LLNA in CBA and BALB/c Mice

Appendix D: Final Assessment of the Validity of the LLNA for Pesticide Formulations, Metals, Substances in Aqueous Solutions, and Other Products

2010 Addendum to NIH Publication No. 99-4494: The Murine Local Lymph Node Assay (LLNA): A Test Method for Assessing the Allergic Contact Dermatitis Potential of Chemicals and Products

Appendix E: Independent Scientific Peer Review Panel Assessment

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
    • 72 FR 52130 (September 12, 2007): Draft Performance Standards for the Murine Local Lymph Node Assay: Request for Comments
    • 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
    • 73 FR 25754 (May 7, 2008): Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM)
    • 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
    • 74 FR 8974 (February 27, 2009): Announcement of a Second Meeting of the Independent Scientific Peer Review Panel on the Murine Local Lymph Node Assay; Availability of Draft Background Review Documents (BRD); Request for Comments
    • 74 FR 19562 (April 29, 2009): Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM)
    • 74 FR 26242 (June 1, 2009): Independent Scientific Peer Review Panel Report: Updated 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: Notice of Availability and Request for Public Comments

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

  • Appendix F3: SACATM Comments: SACATM Meeting on June 18-19, 2008
    Please contact NICEATM to obtain this document

  • Appendix F4: SACATM Comments: SACATM Meeting on June 25-26, 2009
    Download minutes of the SACATM meeting from the NTP website

Appendix G: Relevant Skin Sensitization Regulations and Testing Guidelines

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