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Related Experiment Videos

The local lymph node assay being too sensitive?

Vohr Hans-Werner1, Ahr Hans Jürgen

  • 1Toxicology, Bayer HealthCare AG, Aprather Weg, 42096 Wuppertal, Germany. Hans-werner.vohr@bayerhealthcare.com

Archives of Toxicology
|July 19, 2005
PubMed
Summary

The Local Lymph Node Assay (LLNA) can produce false positives due to skin irritation. Accounting for irritation reveals the LLNA may not be more sensitive than guinea pig tests for skin sensitization.

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Area of Science:

  • Toxicology
  • Dermatology
  • Immunology

Background:

  • The Local Lymph Node Assay (LLNA) is recognized by the OECD for detecting skin sensitization potential.
  • Concerns exist regarding false positive LLNA results due to non-specific cell activation from skin irritation.
  • Inflammatory skin processes can mimic sensitization responses by activating dendritic cells and promoting lymph node cell proliferation.

Purpose of the Study:

  • To compare cell proliferation alone versus cell proliferation combined with inflammatory processes in LLNA.
  • To identify and exclude false positive results in LLNA assessments.
  • To re-evaluate the sensitivity of the LLNA compared to traditional guinea pig assays.

Main Methods:

  • Comparison of two endpoints: cell proliferation and cell proliferation with inflammatory (irritating) processes.
  • Analysis of test items to determine if results were false positives due to irritation.
  • Sensitivity assessment of the LLNA against established guinea pig assays.

Main Results:

  • A significant number of LLNA tests yielded false positive results when irritation was not considered.
  • Excluding these false positives indicated that the LLNA's sensitivity may be comparable to guinea pig assays.
  • The study highlights the critical need to account for irritant properties in skin sensitization testing.

Conclusions:

  • The LLNA, without accounting for irritation, can overestimate skin-sensitizing potential.
  • Differentiating between true sensitization and irritation-induced responses is crucial for accurate assessment.
  • The LLNA's diagnostic value for skin sensitization is improved by considering irritant effects, potentially matching guinea pig assay performance.

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