Questions for the SAP Panel - December 2001
November 26, 2001
FIFRA SCIENTIFIC ADVISORY PANEL (SAP)
December 11, 2001
OPP Docket Telephone: (703) 305-5805
1. The LLNA is generally applicable to testing a wide range of chemicals except for metallic compounds and substances which do not sufficiently adhere to the ear, such as aqueous materials. Compared to currently accepted guinea pig methods, the LLNA:
- provides quantitative as well as qualitative data and an assessment of dose-response;
- is suitable for testing colored substances since an erythematous response is not produced; and,
- provides various advantages for animal welfare (e.g. less animal discomfort, shorter test duration, and potentially fewer animals).
Question: Does the Panel agree with the Agency's proposal that, when appropriate, the LLNA should be the preferred dermal sensitization test?
2. ICCVAM recommended and EPA agrees that a concurrent positive control should be included as part of each LLNA to assess proper assay conduct and to use as a standard for comparison of results between studies and laboratories.
Question: Does the Panel agree that a concurrent positive control should be included with each chemical assessed by the LLNA? If not, what does the panel suggest?
3. EPA proposes that both stimulation index and statistical evaluations of dosed versus control animals be developed to aid in the evaluation of the test outcome.
Question: Has enough guidance been provided in the revised guidelines as to what constitutes a positive hypersensitivity response in the LLNA? If not, what guidance does the Panel suggest?
4. LLNA, guinea pig and human patch test outcomes are available for some 200 chemicals. Results in the LLNA compared favorably with those from the guinea pig. The LLNA was at least as good as the guinea pig test in predicting human responsiveness.
Question: Does the Panel agree that the LLNA guideline can be used for chemicals regulated in both the pesticides and toxic substances programs?
5. The OPPTS guideline builds upon the recommendations made by ICCVAM and it is harmonized with the guideline recently approved in principle by OECD.
Local Lymph Node Assay (LLNA): Questions for the SAP
Question: Is the draft LLNA test method complete and clearly presented in the revised OPPTS guideline for skin sensitization? If not, please supply guidance for improving the presentation.