Contact allergenic potency: Correlation of human and local lymph node assay data

G. Frank Gerberick, Michael K. Robinson, Cindy A. Ryan, Rebecca J. Dearman, Ian Kimber, David A. Basketter, Zoe Wright, James G. Marks

Research output: Contribution to journalArticle

150 Scopus citations

Abstract

Background: Effective toxicologic evaluation of skin sensitization requires that potential contact allergens are identified and that the likely risks of sensitization among exposed populations are assessed. By definition, chemicals that are classified as contact sensitizers have the capacity to cause allergic contact dermatitis (ACD) in humans. However, this hazard is not an all-or-nothing phenomenon; clear dose-response relationships can be discerned and thresholds identified for both the induction of sensitization and the elicitation of ACD. Commonly, these parameters are grouped under the heading of potency, the determination of which is vital for risk assessment. Preclinical testing for sensitization potential is critically important for hazard assessment before human exposure. The murine local lymph node assay (LLNA) is the most recently accepted test method for sensitization hazard assessment. Objective: The aim was to compare potency estimations derived from LLNA data with clinical determinations of relative potency based on human data. Methods: No-effect levels (NOELs) for a range of 21 chemicals were determined from nondiagnostic human repeat patch test studies as reported in the literature. These levels were compared with LLNA EC3 values, the estimated concentration required to produce a 3-fold increase (positive response) in draining lymph node cell (LNC) proliferative activity. Results: Using available human repeat patch test data, together with expert judgment, the compounds were classified as strong, moderate, weak, extremely weak, or nonsensitizing. Additionally, the potency of each chemical was classified independently based on its LLNA EC3 value. The results show clearly that LLNA EC3 values are very comparable with the NOELs calculated from the literature. Moreover, the potency rankings based upon LLNA EC3 data support their human classification. Conclusion: The present investigations show that the LLNA can be used to provide quantitative estimates of relative skin sensitizing potency EC3 values that correlate closely with NOELs established from human repeat patch testing and from our clinical experience.

Original languageEnglish (US)
Pages (from-to)156-161
Number of pages6
JournalUnknown Journal
Volume12
Issue number3
DOIs
StatePublished - Jan 1 2001

All Science Journal Classification (ASJC) codes

  • Dermatology

Fingerprint Dive into the research topics of 'Contact allergenic potency: Correlation of human and local lymph node assay data'. Together they form a unique fingerprint.

  • Cite this

    Gerberick, G. F., Robinson, M. K., Ryan, C. A., Dearman, R. J., Kimber, I., Basketter, D. A., Wright, Z., & Marks, J. G. (2001). Contact allergenic potency: Correlation of human and local lymph node assay data. Unknown Journal, 12(3), 156-161. https://doi.org/10.1053/ajcd.2001.23926