Advertisement

The SENS-IS Assay

  • Françoise Cottrez
  • Elodie Boitel
  • Claude Auriault
  • Hervé Groux
Chapter

Abstract

We have developed SENS-IS, a method based on the quantitative analysis of specific biomarkers expressed in 3D reconstructed epidermis. The use of a reconstructed 3D human epidermis as the test system allows the testing of chemicals/ingredients under conditions close to the human use. Using this approach, the SENS-IS assay can also be used for the measurement of chemical sensitizing potency. The end point analysis measures the quantitative overexpression of a carefully selected set of 65 biomarkers regrouped into three subsets to take into account the irritation potential and the diversity of chemical induction of skin sensitization. The performance of the SENS-IS assay was evaluated here with a subset of 41 chemicals. Its hazard and potency predictivity as compared to the corresponding LLNA data were, respectively, of 97.5% and 90.2%. The reproducibility and predictivity of the SENS-IS assay have been evaluated during a ring study organized with three laboratories. The SENS-IS assay was shown to be robust and transferable and delivered results that compared very well with corresponding human sensitization data.

References

  1. 1.
    Martin SF, Esser PR, Weber FC, Jakob T, Freudenberg MA, Schmidt M, Goebeler M. Mechanisms of chemical-induced innate immunity in allergic contact dermatitis. Allergy. 2011;66(9):1152–63. doi: 10.1111/j.1398-9995.2011.02652.x.CrossRefPubMedGoogle Scholar
  2. 2.
    Nosbaum A, Vocanson M, Rozieres A, Hennino A, Nicolas J-F. Allergic and irritant contact dermatitis. Eur J Dermatol. 2009;19(4):325–32. doi: 10.1684/ejd.2009.0686.CrossRefPubMedGoogle Scholar
  3. 3.
    Freudenberg MA, Esser PR, Jakob T, Galanos C, Martin SF. Innate and adaptive immune responses in contact dermatitis: analogy with infections. G Ital Dermatol Venereol. 2009;144(2):173–85.PubMedGoogle Scholar
  4. 4.
    Moreilhon C, Gras D, Hologne C, Bajolet O, Cottrez F, Magnone V, et al. Live Staphylococcus aureus and bacterial soluble factors induce different transcriptional responses in human airway cells. Physiol Genomics. 2005;20(3):244–55. doi: 10.1152/physiolgenomics.00135.2004.CrossRefPubMedGoogle Scholar
  5. 5.
    Ade N, Leon F, Pallardy M, Peiffer J-L, Kerdine-Romer S, Tissier M-H, et al. HMOX1 and NQO1 genes are upregulated in response to contact sensitizers in dendritic cells and THP-1 cell line: role of the Keap1/Nrf2 pathway. Toxicol Sci. 2009;107(2):451–60. doi: 10.1093/toxsci/kfn243. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Cotovio J, Grandidier M-H, Portes P, Roguet R, Rubinstenn G. The in vitro skin irritation of chemicals: optimisation of the EPISKIN prediction model within the framework of the ECVAM validation process. ATLA. 2005;33(4):329–49.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Cottrez F, Boitel E, Auriault C, Aeby P, Groux H. Genes specifically modulated in sensitized skins allow the detection of sensitizers in a reconstructed human skin model. Development of the SENS-IS assay. Toxicology in Vitro. 2015;29(4):787–802. ISSN 0887-2333.CrossRefPubMedGoogle Scholar
  8. 8.
    Loveless SE, Api A-M, Crevel RWR, Debruyne E, Gamer A, Jowsey IR, et al. Potency values from the local lymph node assay: application to classification, labelling and risk assessment. Regul Toxicol Pharmacol. 2010;56(1):54–66. doi: 10.1016/j.yrtph.2009.08.016.CrossRefPubMedGoogle Scholar
  9. 9.
    Cottrez F, Boitel E, Ourlin J-C, Peiffer J-L, Fabre I, Henaoui I-S, Mari B, Vallauri A, Paquet A, Barbry P, Auriault C, Aeby P, Groux H. SENS-IS, a 3D reconstituted epidermis based model for quantifying chemical sensitization potency: Reproducibility and predictivity results from an inter-laboratory study. Toxicology in Vitro. 2016;32:248–260. ISSN 0887-2333.CrossRefPubMedGoogle Scholar
  10. 10.
    Basketter DA, Alépée N, Ashikaga T, Barroso J, Gilmour N, Goebel C, et al. Categorization of chemicals according to their relative human skin sensitizing potency. Dermatitis. 2014;25(1):11–21. doi: 10.1097/DER.0000000000000003.CrossRefPubMedGoogle Scholar
  11. 11.
    Basketter DA, Lea LJ, Cooper K, Stocks J, Dickens A, Pate I, et al. Threshold for classification as a skin sensitizer in the local lymph node assay: a statistical evaluation. Food Chem Toxicol. 1999;37(12):1167–74.CrossRefPubMedGoogle Scholar
  12. 12.
    Andersen A. Final report on the safety assessment of benzaldehyde. Int J Toxicol. 2006;25(Suppl 1):11–27. doi: 10.1080/10915810600716612.CrossRefPubMedGoogle Scholar
  13. 13.
    OECD (2014), The Adverse Outcome Pathway for Skin Sensitisation Initiated by Covalent Binding to Proteins, OECD Publishing, Paris. http://dx.doi.org/10.1787/9789264221444-en.
  14. 14.
    Hewitt NJ, Edwards RJ, Fritsche E, Goebel C, Aeby P, Scheel J, et al. Use of human in vitro skin models for accurate and ethical risk assessment: metabolic considerations. Toxicol Sci. 2013;133(2):209–17. doi: 10.1093/toxsci/kft080. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Françoise Cottrez
    • 1
  • Elodie Boitel
    • 1
  • Claude Auriault
    • 1
  • Hervé Groux
    • 1
  1. 1.ImmunoSearchGrasseFrance

Personalised recommendations