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Quantitative relationship between the local lymph node assay and human skin sensitization assays
1Forschungs-und Beratungsinstitut Gefahrstoffe (FoBiG) GmbH, Werderring 16, D-79098 Freiburg, Germany. klaus.schneider@fobig.de
Regulatory Toxicology and Pharmacology : RTP
|May 12, 2004
Summary
The local lymph node assay (LLNA) in mice shows a strong correlation with human skin sensitization tests (HRIPTs and HMTs). This suggests the LLNA is a reliable method for assessing skin sensitizer potency and can inform regulatory decisions.
Area of Science:
- Toxicology
- Dermatology
- Regulatory Science
Background:
- The local lymph node assay (LLNA) is a mouse model for assessing skin sensitization.
- Human sensitization tests, such as human repeat insult patch tests (HRIPTs) and human maximization tests (HMTs), are used to evaluate skin sensitizers in humans.
- Quantitative correlation between LLNA and human test results is crucial for regulatory acceptance.
Purpose of the Study:
- To investigate the quantitative correlation between LLNA results and human sensitization tests (HRIPTs and HMTs).
- To evaluate the reliability of the LLNA for assessing the relative potency of skin sensitizers.
- To propose regulatory applications of the LLNA for classifying skin sensitizers.
Main Methods:
- Data from 57 substances were analyzed, comparing LLNA results with HRIPT and HMT data.
- Data were transformed to applied doses per skin area for comparability.
- Regression analysis was performed to determine the correlation between LLNA and human test results.
Main Results:
- A significant positive correlation was found between LLNA and human sensitization tests for 46 sensitizing substances.
- The correlation was stronger between LLNA and HRIPT (r=0.77) than between LLNA and HMT (r=0.65).
- LLNA predominantly yielded negative results for 11 substances that were non-sensitizing in human tests, further supporting its reliability.
Conclusions:
- The LLNA is a reliable method for the relative potency assessment of skin sensitizers.
- The LLNA can be used to establish four potency groups for characterizing skin sensitizing potential.
- Differentiated concentration limits for skin sensitizers in preparations can be derived from LLNA potency groups, improving upon current all-or-nothing classifications.