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The KeratinoSens™ Assay for Skin Sensitization Screening

  • Andreas Natsh
Chapter

Abstract

The Keap1-Nrf2-ARE pathway is reported to be a major regulator of cytoprotective responses to electrophile and oxidative stress. It controls the expression of detoxification, antioxidant, and stress response enzymes and proteins. At the same time, the Nrf2 pathway is the pathway most commonly activated by skin sensitizers in studies on the transcriptome responses of different cell lines and ex vivo samples. The KeratinoSens™ assay is an in vitro test method which quantifies luciferase gene induction in an immortalized adherent reporter cell line as a measure of the activation of the Keap1-Nrf2-ARE pathway. The use of luciferase reporter technology makes this assay highly reproducible and allows for a rapid determination of dose-response curves. It has undergone full validation studies, and it was implemented in an OECD guideline (OECD test guideline 442d). It was recommended by ECVAM to be used as part of an integrated approach for testing and assessment (IATA). Recently, several proposals how KeratinoSens data can be implemented in a strategy to predict hazard and potency of skin sensitizers were put forward, based on the analysis of extended chemical datasets and combining the KeratinoSens data with other in vitro endpoints. These approaches are briefly summarized here along with the key scientific and technical information on the KeratinoSens™ assay.

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Givaudan Suisse SADuebendorfSwitzerland

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