National Toxicology Program

Peer Review Panel Documents

Peer Review Panel report now available - View PDF document

Supplemental Information Relevant to Multiple Review Activities

• Power Calculations for LLNA Protocols [PDF]
• Power Calculations for the Traditional LLNA Protocol [PDF]
• ICCVAM 1999. Peer Review Evaluation Report: The Murine Local Lymph Node Assay - A Test Method for Assessing the Allergic Contact Dermatitis Potential of Chemicals/Compounds (NIH 99-4494; located on NICEATM-ICCVAM public website)
• Comments received in response to the Federal Register notice announcing the Peer Panel meeting and BRD availability (NICEATM-ICCVAM public website)
• EPA OPPTS 870.2600 Health Effects Test Guideline, Skin Sensitization
• ICCVAM Protocol for the LLNA, January 2001
• OECD Test Guideline 406 for Skin Sensitisation
• OECD Test Guideline 429 for Skin Sensitisation: Local Lymph Node Assay

LLNA Applicability Domain Documents

• Draft Updated Assessment of the Validity of the LLNA for Mixtures, Metals, and Aqueous Solutions
  
  • Main Body Text [PDF]
  • Appendix A: The Murine Local Lymph Node Assay (LLNA): A Test Method for Assessing the Allergic Contact Dermatitis Potential of Chemicals/Compounds (NIH Pub. No. 99-4494) [PDF]
  • Appendix B: Available Data and Information for Mixtures Tested in the LLNA
    
    • Appendix B1 - Physicochemical Properties of Tested Substances [PDF]
    • Appendix B2 - Comparative Data: Human, LLNA, Guinea Pig [XLS]
  • Appendix C: Available Data and Information for Metals Tested in the LLNA
    
    • Appendix C1 - Physicochemical Properties of Tested Substances [PDF]
    • Appendix C2 - Comparative Data: Human, LLNA, Guinea Pig [XLS]
      • References for Appendix C2 [PDF]
  • Appendix D: Available Data and Information for Aqueous Solutions Tested in the LLNA
    
    • Appendix D1 - Physicochemical Properties of Tested Substances [PDF]
    • Appendix D2 - Comparative Data: Human, LLNA, Guinea Pig [XLS]
      • References for Appendix D2 [PDF]
  • Appendix E: Available Generic Compositions for Substances Tested in the LLNA [PDF]


• Draft ICCVAM Test Method Recommendations: Updated Assessment of the Validity of the LLNA for Mixtures, Metals, and Aqueous Solutions [PDF]

Supplemental Information for LLNA Applicability Domain

1. Data Sheets of Textile Dyes Tested in the LLNA: Submitted by Bundesanstalt fur Arbeitsschutz und Arbeitsmedizin [PDF]

Documents on the Use of the LLNA for Potency Determinations

• Draft BRD for Use of the Murine Local Lymph Node Assay to Assess Relative Skin Sensitization Potency
  • Main Body Text [PDF]
  • Appendix A: LLNA/EC3 Validation - Submission from: David Basketter, Frank Gerberick and Ian Kimber [PDF]
    
    • Table 2: Human experimental vs LLNA EC3 thresholds [PDF]
  • Appendix B: Comparative LLNA, Guinea Pig, and Human Data Used in the Performance Evaluation [XLS]
  • Appendix C: Physicochemical Properties for Substances Included in the Performance Evaluation [XLS]
  • Appendix D: Performance Characteristics for Use of LLNA EC3 Values to Predict Draft GHS Categories of Human and Guinea Pig Skin Sensitization Potency [PDF]


• Draft ICCVAM Test Method Recommendations Assessment of the Use of the LLNA to Address Relative Skin Sensitization Potency [PDF]

Supplemental Information for LLNA Potency Determination

1. Comment from Dr. David Basketter, DABMEB Consultancy Ltd. [PDF]
2. NICEATM Response to OECD Queries [PDF]

LLNA Performance Standards Documents

• Revised Draft ICCVAM LLNA Performance Standards [PDF]

Supplemental Information for LLNA Performance Standards

1. Response from Dr. Joe Haseman to questions regarding the probability of successfully meeting the proposed accuracy criteria in the draft ICCVAM LLNA performance standards. [PDF]
2. Email from Dr. Nancy Flournoy to Dr. David Allen discussing statistical methodology. [PDF]
   Reference attached to Dr. Flournoy's email: Berger RL and Hsu JC. 1996. Bioequivalence trials, intersection-union tests and equivalence confidence sets. Statistical Science 11:283-319.

LLNA Limit Dose Documents

• Draft Background Review Document (BRD) for LLNA Limit Dose Procedure
  
  • Main Body Text [PDF]
  • Appendix A: ECVAM Scientific Advisory Committee (ESAC) Statement on the rLLNA [PDF]
  • Appendix B: Physico-chemical Properties for Substances Evaluated in the LLNA Limit Dose Procedure [XLS]
  • Appendix C: LLNA Limit Dose Procedure Data [XLS]
  • Appendix D: Substances in the NICEATM LLNA Database for Which a Concentration of ≥10% Elicited a Negative Result, but an Increased Concentration Elicited a Positive Response [XLS]


• Draft ICCVAM Test Method Recommendations for LLNA Limit Dose Procedure [PDF]

Non-radioactive LLNA Protocol Documents

Flow Cytometry Test Method

• Draft BRD for Flow Cytometry Test Method Protocol [PDF]
  • Appendix A: Flow Cytometery – Local Lymph Node Assay Protocol [PDF]
  • Appendix B: Physico-Chemical Properties of Substances Tested Using the LLNA: BrdU-FC/eLLNA: BrdU-FC Protocol [PDF]
  • Appendix C: Comparative LLNA: BRDU-FC/LLNA: BRDU-ELISA, Traditional LLNA, Guinea Pig Skin Sensitization, and Human Data [PDF]
  • Appendix D: MB Research Laboratories LLNA: 25% Hexyl Cinnamic Aldehyde (HCA) Historical Data [PDF]
• Draft ICCVAM Test Method Recommendations for the Flow Cytometry Test Method Protocol [PDF]

BrdU-ELISA Test Method Protocol

• Draft BRD for BrdU-ELISA Test Method Protocol [PDF]
  • Appendix A: BrdU-ELISA Local Lymph Node Assay Protocol [PDF]
    Supplemental Information: BrdU-ELISA Local Lymph Node Assay Protocol – Updated By the JaCVAM Interlaboratory Validation Study Management Team (Feb. 27, 2008) [PDF]
  • Appendix B: Analysis of Alternative Decision Criteria for Determination of Sensitizers [PDF]
  • Appendix C: Physico-Chemical Properties of Substances Tested Using the BrdU-ELISA LLNA [PDF]
  • Appendix D: Comparative BrdU-Elisa Local Lymph Node Assay, Traditional Local Lymph Node Assay, Guinea Pig Skin Sensitization, and Human Skin Sensitization Data [PDF]
• Draft ICCVAM Test Method Recommendations for the BrdU-ELISA Test Method Protocol [PDF]

Supplemental Information for the BrdU-ELISA Test Method

1. Power Calculations by Dr. Joe Haseman [PDF]
2. Data Supporting the Performance Evaluation of the LLNA: BrdU-ELISA (see Table 6-6 of the draft ICCVAM BRD) [PDF]
3. List of Chemicals Tested in a Two-Phased Interlaboratory Validation Study [XLS]

LLNA: DA Test Method Protocol

• Draft BRD for LLNA: DA Test Method Protocol [PDF]
  • Appendix A: Description of the LLNA: DA Protocol [PDF]
  • Appendix B: Physico-Chemical Properties and Chemical Classes of Substances Tested in the LLNA: DA [PDF]
  • Appendix C: Comparative LLNA: DA, Traditional LLNA, Guinea Pig Skin Sensitization, and Human Skin Sensitization Data [PDF]
  • Appendix D: Oral Presentations Relating to the Characterization and Validation of the LLNA: DA [PDF]
    • Appendix D-1: Characterization and current status of the LLNA: DA method: a non-RI modified LLNA based on ATP content [PDF]
    • Appendix D-2: Two validation studies on a non-RI Modification of the murine LLNA using ATP measurement [PDF]
    • Appendix D-3: Two validation studies on a non-RI Modification of the murine LLNA using ATP measurement: method of LLNA: DA and results of intralaboratory studies [PDF]
  • Appendix E: Analysis of Alternative Decision Criteria for Predicting Skin Sensitizing Potential in the LLNA: DA [PDF]
• Draft ICCVAM Test Method Recommendations for LLNA: DA Test Method Protocol [PDF]

Supplemental Information for LLNA: DA Test Method

1. Test results for the LLNA: DA Test Method in 31 chemicals tested by Daicel Chemical Industries, Ltd. [PDF]
2. Description of Variance and Confidence Interval SI for the LLNA: DA Interlaboratory Validation Studies [PDF]