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Contact Hypersensitivity as a Murine Model of Allergic Contact Dermatitis

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Correlation between experimental human and murine skin sensitization induction thresholds.

Anne Marie Api¹, David Basketter², Jon Lalko¹

¹a Research Institute for Fragrance Materials , Woodcliff Lake , NJ , USA and.

Cutaneous and Ocular Toxicology

|November 29, 2014

Summary

The local lymph node assay (LLNA) effectively predicts skin sensitization potency in humans. This study validated the LLNA EC3 value against human repeated insult patch tests (HRIPT) for fragrance chemicals.

Keywords:

Contact allergy induction EC3 value NESIL fragrance human repeated insult patch test local lymph node assay skin sensitization

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Area of Science:

Toxicology
Dermatology
Risk Assessment

Background:

Quantitative risk assessment for skin sensitization aims to prevent human contact allergy.
Predictive identification of relative skin sensitizing potency is crucial for this assessment.
The murine local lymph node assay (LLNA) measures the EC3 value, a key indicator of sensitization threshold.

Purpose of the Study:

To verify the accuracy of the LLNA EC3 value as a predictor of human skin sensitization.
To compare murine and human sensitization thresholds for a diverse set of fragrance chemicals.
To assess the correlation between LLNA predictions and human repeated insult patch test (HRIPT) results.

Main Methods:

Utilized the local lymph node assay (LLNA) to determine EC3 values for 57 fragrance chemicals.
Conducted human repeated insult patch tests (HRIPT) to establish human sensitization thresholds.
Compared LLNA-derived thresholds with HRIPT results across a wide range of chemical potencies.

Main Results:

A useful correlation was observed between LLNA EC3 values and human sensitization thresholds.
The LLNA EC3 value demonstrated particular efficacy in identifying stronger sensitizers.
Good correlation (within half an order of magnitude) was found for approximately 75% of the tested fragrance chemicals.
Identified specific chemical classes, such as salicylates and trans-2-hexenal, as potential outliers in predictive accuracy.

Conclusions:

The LLNA EC3 value serves as a valuable predictive tool for human skin sensitization.
LLNA data aids in identifying potent sensitizers and informs quantitative risk assessment strategies.
Further analysis of outlier chemistries can refine predictive models for skin sensitization.