The EpiDerm™ Phototoxicity Test (EpiDerm™ H3D-PT)
- 551 Downloads
Assessment of the phototoxicity hazard and phototoxic potency (i.e. phototoxic risk) of topically or systemically applied compounds and mixtures is a crucial step in the safety assessment of cosmetic, pesticide and pharmaceutical products absorbing UV and visible light. The validated and regulatory accepted in vitro assay, the 3T3 NRU PT (OED TG 432), provides high level of sensitivity and thus also protection for the end-users, however, it has been reported that it also generates high rate of false positive results due to the lack of barrier properties naturally appearing in the human skin or other targeted tissues.
In vitro reconstituted human skin models are increasingly being investigated for their usability in hazard identification and safety testing, because of their organotypic structure with a functional stratum corneum that allows for assessment of bioavailability of topically applied compounds and mixtures. An in vitro phototoxicity test using the human reconstructed epidermis model EpiDermTM (EpiDermTM H3D–PT) has been developed and pre-validated almost 20 years ago and can be used either as standalone method for the phototoxicity testing of topically applied materials, or in combination with the 3T3 NRU PT, to minimise the potentially false positive results from this assay.
This chapter describes in detail the EpiDermTM H3D–PT, which is an ECVAM pre-validated assay and accepted component of the pre-clinical testing strategy for topically applied pharmaceutical products as recommended within the ICH S10 Guideline. The chapter focuses on the technical details of the EpiDermTM H3D–PT and also provides information about the performance of this assay during the pre-validation study. Furthermore, it discusses the follow-up work conducted by independent research teams that confirmed findings from the pre-validation study regarding high sensitivity, specificity and relevance for topically tested compounds compared to human data.
- 1.OECD. OECD guidelines for the testing of chemicals no. 432: in vitro 3T3 NRU phototoxicity test. Paris: Organisation for Economic Co-operation and Development; 2004. p. 15.Google Scholar
- 2.EMEA. Note for Guidance on Photosafety Testing (CPMP/SWP/398/01). London, UK: European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products; 2002. p. 8. http://www.emea.eu.int.
- 3.SCCNFP. The Scientific Committee on Cosmetic Products and Non-Food Products Intended for Consumers: Notes of Guidance for Testing of Cosmetic Ingredients for their Safety Evaluation. 5th Revision, adopted by the SCCNFP during the plenary meeting of 20 October 2003 (SCCNFP/0690/03 Final). 102pp. Brussels, Belgium: DG SANCO/C/2, European Commission. 2003.Google Scholar
- 4.EC. Commission Regulation (EU) No. 1197/2013 of 25 November 2013 amending Annex III to Regulation (EC) No. 1223/2009 of the European Parliament and of the Council on cosmetic products; 2013. http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=celex:32013R1197.
- 7.Liebsch M, Traue D, Barrabas C, Spielmann H, Gerberick GF, Cruse L, Diembeck W, Pfannenbecker U, Spieker J, Holzhütter HG, Brantom P, Aspin P, Southee J. Prevalidation of the EpiDerm phototoxicity test. In: Clark D, Lisansky S, Macmillan R, editors. Alternatives to animal testing II: proceedings of the second international scientific conference organised by the European Cosmetic Industry, Brussels, Belgium. Newbury: CPL Press; 1999. p. 160–6.Google Scholar
- 8.ECVAM. ECVAM feasibility study. Can the pre-validated EpiDerm in vitro phototoxicity test be upgraded to quantify phototoxic potency of topical phototoxins? Contract no. 1986-2002-09 F1 EDISP DE. 2002.Google Scholar
- 9.Kandarova H. Evaluation and validation of reconstructed human skin models as alternatives to animal tests in regulatory toxicology. PhD thesis; 2006. http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000002248.
- 12.Jırova D, Kejlova K, Bendova H, Ditrichova D, Mezulanikova M. Phototoxicity of bituminous tars—correspondence between results of 3T3 NRU PT, 3D skin model and experimental human data. TIV. 2005;19:931–4.Google Scholar
- 13.Jones P, King A, Lovell W, Earl L. Phototoxicity testing using 3-D reconstructed human skin models. In: Clark D, Lisansky S, Macmillan R, editors. Alternatives to animal testing II: proceedings of the second international scientific conference organised by the European cosmetic Industry, Brussels, Belgium. Newbury, UK: CPL Press; 1999. p. 138–41.Google Scholar
- 15.Liskova A. Evaluation of the phototoxic potential of selected compounds using the 3D reconstructed human epidermis model – EpiDerm. Diploma Thesis. SCHK, Bratislava, Reg. number FCHPT-104538-42749; 2016. 93.p.Google Scholar
- 16.Pratt LF, Cerven DR, DeGeorge GL. Validation of 3D Skin Model for Cosmetic, Chemical and Medical Device Phototoxicity Testing (EPARS). MB Research Laboratories. IVTIP Conference. 2011.Google Scholar
- 17.Sohn S, Ju JH, Son KH, Lee JP, Kim J, Lim CH, Hong SK, Kwon TR, Chang M, Kim DS, Yoon HS, Park KL. Alternative methods for phototoxicity test using reconstructed human skin model. ALTEX. 2009;26(Spec. Issue):136.Google Scholar
- 18.ICH S10. ICH harmonised tripartite guideline photosafety evaluation of pharmaceuticals S10, 2013. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Safety/S10/S10_Step_4.pdf.
- 19.Api AM. In vitro assessment of phototoxicity. In Vitro Toxicol. 1997;10:339–50.Google Scholar
- 21.MatTek. Phototoxicity Protocol For EpiDerm™ Model (EPI-200) (Draft). Version April 21, 2015; 2015, p. 20.Google Scholar
- 23.ZEBET. Phototoxicity protocol for use with EpiDerm™ model (EPI-200). Version November 5; 1997. p. 22.Google Scholar
- 25.King A, Lovel W, Earl L. Phototoxicity tesing using 3D reconstructed human skin models. In: Clark D, Lisansky S, Macmillan R, editors. Alternatives to animal testing II: proceedings of the second international scientific conference organised by the European cosmetic Industry, Brussels, Belgium. Newbury, UK: CPL Press; 1999.Google Scholar