The EpiDerm™ Skin Irritation Test (EpiDerm™ SIT)
Assessment of the skin irritation belongs to the basic battery of toxicology tests. Due to the enormous efforts from test methods developers, validation centers and regulators, several in vitro test methods have been developed, validated and regulatory adopted as potential replacements of the rabbit skin irritation test.
This chapter describes in details the skin irritation test (SIT) based on the use of the in vitro reconstructed human epidermis model EpiDerm™ (EpiDerm™ SIT). The EpiDerm™ SIT is a validated and regulatory adopted method under the OECD Test Guidelines 439 along with three other tissue models. The chapter focuses on the technical details of this assay and also provides information about the performance of this test method obtained during the validation study. Part of this chapter also describes other EpiDerm™ skin irritation protocols that can be used for the safety assessment of final cosmetic products and for testing extracts from Medical Devices in line with the ISO 10993.
- 1.United Nations (UN). Globally harmonized system of classification and labeling of chemicals (GHS), 2nd revised edn, UN New York and Geneva, 2007. Available: http://www.unece.org/trans/danger/publi/ghs/ghs_rev02/02files_e.html.
- 2.OECD. OECD guideline for testing of chemicals, No. 404: acute dermal irritation/corrosion. Organisation for economic cooperation and development, Paris; 2015.Google Scholar
- 3.Draize JH, Woodand G, Calvery HO. Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J Pharmacol Exp Ther. 1944;82:337–90.Google Scholar
- 8.Spielmann H, Hoffmann S, Liebsch M, Botham P, Fentem J, Eskes C, Roguet R, Cotovio J, Cole T, Worth A, Heylings J, Jones P, Robles C, Kandárová H, Gamer A, Remmele M, Curren R, Raabe H, Cockshott A, Gerner I, Zuang V. The ECVAM international validation study on in vitro tests for acute skin irritation: report on the validity of the EPISKIN and EpiDerm™ assays and on the skin integrity function test. ATLA. 2007;35:559–601.PubMedGoogle Scholar
- 9.ESAC. Statement on the scientific validity of in-vitro tests for skin irritation testing, April 2007. 2007. Downloadable from http://ecvam.jrc.it/.
- 11.Liebsch M, Gamer A, Curren R, Frank J, Genschow E, Tharmann J, Remmele M, Bauer B, Raabe H, Barnes N, Hilberer A, Wilt N, Lorngjad-Schäfer MR, Schäfer C, Spiller E, Hayden P, Kanďárová H. Follow-up validation of the modified EpiDerm™ skin irritation test (SIT): results of a multicentre study of twenty reference test substances. 15th congress on alternatives to animal experimentation, September 19-21 Linz, Austria. ALTEX. 2008;25(Suppl 1):43.Google Scholar
- 12.Liebsch M, Kandarova H. Submission of the follow-up validation study of the modified EpiDerm™ skin irritation test for hazard identification and labelling of chemicals according to EU classification system. 23 April 2008; 2008. p. 58, 10 Annexes.Google Scholar
- 13.OECD. Guidance document no. 34 on the validation and international acceptance of new or updated test methods for hazard assessment. Paris: OECD; 2005.Google Scholar
- 14.ECVAM. Performance standards for applying human skin models to in vitro skin irritation; 2007. Available under download study document, at http://ecvam.jrc.ec.europa.eu.
- 15.ESAC. Statement on the scientific validity of in-vitro tests for skin irritation testing, November 2008; 2008. Downloadable from http://ecvam.jrc.it/
- 16.EU. B.46 Guideline. In Vitro skin irritation: reconstructed human epidermis (RHE) model test; 2009.Google Scholar
- 20.OECD. Test no. 439: in vitro skin irritation reconstructed human epidermis test method. Organisation for economic cooperation and development, 23 July 2010. 2010.Google Scholar
- 21.ESAC. Esac statement on the performance standards (ps) for in vitro 2 skin irritation testing using reconstructed human epidermis; 2009. Downloadable from: https://eurl-ecvam.jrc.ec.europa.eu/validation-regulatory-acceptance/docs-skin-irritation-1/DOC9-ESAC_statement_updated-skin-irritation-PS_200909-22.pdf.
- 22.Kandárová H, Hayden P, Klausner M, Kubilus J, Sheasgreen J. An In Vitro skin irritation test (SIT) using the EpiDerm™ reconstructed human epidermal (RHE) model. JoVE. 2009;29 doi: 10.3791/1366.
- 23.MatTek SOP In Vitro EpiDerm™ Skin Irritation Test (EPI-200-SIT) For use with MatTek Corporation’s Reconstructed Human Epidermal Model EpiDerm™ (EPI-200-SIT). Doc. MK-24-007-0023, Version 07/11/2014; 2014. p. 35.Google Scholar
- 26.OECD GD No. 203. Guidance document on an integrated approach on testing and assessment (IATA) for skin corrosion and irritation. Series on testing and assessment; 2014. http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=env/jm/mono(2014)19&doclanguage=en.
- 28.Kandarova H, Willoughby JA, de Jong WH, Bachelor MA, Letasiova S, Milasova T, Breyfogle B, de la Fonteyne L, Coleman KP. Development, optimization, and standardization of an in vitro skin irritation test for medical devices using the reconstructed human tissue model EpiDerm. SOT 2015. The Toxicologist, 2015. p. 433. https://www.toxicology.org/pubs/docs/Tox/2015Tox.pdf.CrossRefGoogle Scholar