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U-SENS™: A U937 Cell Line Activation Test for Skin Sensitization

  • Nathalie Alépée
  • Cécile Piroird
  • Laurent Nardelli
Chapter

Abstract

The U-SENS™ assay is modelling the dendritic cell activation upon exposure to chemicals. Upon contact with sensitizers, U937 human histiocytic lymphoma cells are activated and increase the CD86 expression. The U-SENS™ assay addressing one biological mechanism of the skin sensitization pathway (formally described in an Adverse Outcome Pathway (AOP) for skin sensitization by the OECD) is foreseen to be combined with complementary information and evaluated in the context of Integrated Approaches to Testing and Assessment (IATA). In such context, the U-SENS™ assay is part of a decision strategy for skin sensitization hazard identification (contact skin sensitizer vs. non-sensitizer). It is also foreseen to be a part of integrated test batteries which will be able to fully replace the in vivo test methods (i.e. Local Lymph Node Assay-LLNA, Buehler and Magnusson & Kligman) to predict the sensitizing potential of the chemicals in humans (risk and safety assessment). The reproducibility and predictivity of the U-SENS™ assay were evaluated by two multicentric validation studies organized with four laboratories, and with a large set of 175 chemicals through a systematic in vitro and human and/or LLNA comparative evaluation for skin sensitization safety assessment. The U-SENS™ assay was shown to be robust, transferable and automatable, delivering results that matched well with corresponding human/LLNA sensitization data. On the basis of the data currently available, the U-SENS™ method was shown to be applicable to test chemicals (including cosmetics ingredients) covering a variety of organic functional groups, physicochemical properties and skin sensitization potencies (as determined in in vivo studies). The U-SENS™ assay is applicable to all mono-substances or mixtures (including pre- or pro-haptens) that are soluble in the aqueous testing conditions and compatible with flow cytometry analysis.

Keywords

Skin sensitization In vitro Dendritic cells activation CD86 induction U-SENS™ Reproducibility Predictivity OECD TG 442E 

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Nathalie Alépée
    • 1
  • Cécile Piroird
    • 1
  • Laurent Nardelli
    • 1
  1. 1.L’Oréal Research and InnovationAulnay-sous-Bois CedexFrance

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