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Alternatives for Dermal Toxicity Testing pp 273–287Cite as

Epidermal Equivalent (EE) Potency Assay

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Abstract

The epidermal equivalent (EE) potency assay is aimed at ranking sensitizing compounds according to their potency (extreme, strong, moderate and weak sensitizing potency) with the aid of a reconstructed human epidermal equivalent. The EE potency assay is based on our understanding from clinical observations that sensitizer potency is directly related to the irritant potency of the chemical. The primary readout is the chemical concentration, which reduces cell viability (as assessed by MTT assay) by 50% (EC50 value). Additional readouts are the chemical concentration which results in a twofold increase in IL-1alpha or IL-18 release. The lower the EC50 value, IL-1alpha (SI-2) or IL-18 (SI-2), the greater the sensitizer potency. Commercially available EE models can be used. The major advantage in using EE is that the chemical exposure mimics human exposure (topical application) and therefore overcomes drawbacks of traditional submerged culture, including chemical solubility and stability in culture medium. A pre-validation study with 4 laboratories and 13 coded chemicals succeeded in ranking sensitizers according to their potency and showed good correlation with human DSA05 and NOEL as well as animal LLNA data. Currently the EE potency assay is undergoing further technology transfer to naive partners in preparation for further validation in a ring study including America, Asia and Europe. Current results, limitations, critical steps in the protocol, correlation to human and animal data, challenges and opportunities are extensively described in this manuscript.

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Authors and Affiliations

  1. Department of Dermatology, VU University Medical Centre, Amsterdam, The Netherlands

    Susan Gibbs & Sander W. Spiekstra

  2. Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Amsterdam, The Netherlands

    Susan Gibbs

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  1. Susan Gibbs
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Correspondence to Susan Gibbs .

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Editors and Affiliations

  1. SeCAM, Magliaso, Switzerland

    Chantra Eskes

  2. Innovitox Consulting & Services, Houten, The Netherlands

    Erwin van Vliet

  3. Department of Dermatology, University of California School of Medicine, San Francisco, California, USA

    Howard I. Maibach

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Gibbs, S., Spiekstra, S.W. (2017). Epidermal Equivalent (EE) Potency Assay. In: Eskes, C., van Vliet, E., Maibach, H. (eds) Alternatives for Dermal Toxicity Testing. Springer, Cham. https://doi.org/10.1007/978-3-319-50353-0_20

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