Skip to main content
SpringerLink
Log in
Book cover

Alternatives for Dermal Toxicity Testing pp 463–476Cite as

Overview on the Current Status of Available Test Methods and Additional Promising Methods for Assessing UV-Induced Effects

  • Chapter
  • First Online:

Abstract

Photo-induced effects are based on the photosensitization processes by which a photosensitizer, i.e., a molecule absorbing nontoxic dose of ultraviolet (UV) or visible (VIS) radiation (chromophores), interacts with other molecules leading eventually to an adverse effect. The assessment of photo-induced toxicity is required when chemical preparations are intended to be used on sunlight-exposed skin, i.e., products topically applied to the skin or systemic drugs. It includes evaluation of phototoxic effects and of photoallergy, which will be discussed hereafter. Moreover, the recommended tiered phototoxic strategy, including nonbiological and biological assays, will be reported together with the ICH (International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use) recommendations. In this photosafety strategy, UV/VIS spectral analysis should be employed as the first screening to indicate a potential phototoxic risk by measuring the molar extinction coefficient (MEC), followed by the ROS (reactive oxygen species) assay. The biological assays are then carried out to evaluate the phototoxic potential of those materials presenting potential phototoxic risk and include the 3T3 neutral red uptake phototoxicity test (3T3 NRU-PT) followed, if a positive result is obtained, by the human 3D reconstructed skin model phototoxicity test (H3D-PT). The last step is the confirmatory photopatch test to be applied to a group of volunteers and to be performed using the first non-phototoxic concentration determined in the H3D-PT using a margin of safety factor of 10. Finally, some epidemiological data regarding photoallergy will be presented.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. ICH. Photosafety evaluation of pharmaceuticals S10. 2013. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Safety/S10/S10_Step_4.pdf. Accessed 8 Jul 2016.

  2. Wilm A, Berneburg M. Photoallergy. J Dtsch Dermatol Ges. 2015;13(1):7–12.

    PubMed  Google Scholar 

  3. Spielmann H, Muller L, Averbeck D, Balls M, Brendler-Schwaab S, Castell JV, Curren R, de Silva O, Gibbs NK, Liebsch M, Lovell WW, Merk HF, Nash JF, Neumann NJ, Pape WJW, Ulrich P, Vohr HW. The second ECVAM workshop on phototoxicity testing. ATLA. 2000;28:777–814.

    Google Scholar 

  4. Gould JW, Mercurio MG, Elmets CA. Cutaneous photosensitivity diseases induced by exogenous agents. J Am Acad Dermatol. 1995;33(4):551–73.

    Article  CAS  PubMed  Google Scholar 

  5. JaCVAM. Reactive oxygen species (ROS) assay to examine photoreactivity of chemicals. 2013. http://www.jacvam.jp/files/doc/02_03/02_03_E2.pdf. Accessed 8 Jul 2016.

  6. Onoue S, Hosoi K, Wakuri S, Iwase Y, Yamamoto T, Matsuoka N, Nakamura K, Toda T, Takagi H, Osaki N, Matsumoto Y, Kawakami S, Seto Y, Kato M, Yamada S, Ohno Y, Kojima H. Establishment and intra−/inter-laboratory validation of a standard protocol of reactive oxygen species assay for chemical photosafety evaluation. J Appl Toxicol. 2013;33:1241–50.

    Google Scholar 

  7. Henry B, Foti C, Alsante K. Can light absorption and photostability data be used to assess the photosafety risks in patients for a new drug molecule? J Photochem Photobiol B. 2009;96:57–62.

    Article  CAS  PubMed  Google Scholar 

  8. EMA. Questions and answers on the “Note for guidance of photosafety testing”. 2011. http://www.ema.europa.eu/ema/. Accessed 8 Jul 2016.

  9. Ceridono M, Tellner P, Bauer D, Barroso J, Alépée N, Corvi R, De Smedt A, Fellows MD, Gibbs NK, Heisler E, Jacobs A, Jirova D, Jones D, Kandárová H, Kasper P, Akunda JK, Krul C, Learn D, Liebsch M, Lynch AM, Muster W, Nakamura K, Nash JF, Pfannerbecker U, Phillips G, Robles C, Rogiers V, Van de Water F, Liminga UW, Vohr HW, Wattrelos O, Woods J, Zuang V, Kreysa J, Wilcox P. The 3T3 neutral red uptake phototoxicity test: practical experience and implications for phototoxicity testing- the report of an ECVAM-EFPIA workshop. Regul Toxicol Pharmacol. 2012;63(3):480–8.

    Article  CAS  PubMed  Google Scholar 

  10. OECD. OECD guidelines for the testing of chemicals, test no. 432: in vitro 3T3 NRU phototoxicity test. 2004. http://www.oecd.org/. Accessed 8 Jul 2016.

  11. Kejlová K, Jírová D, Bendová H, Kandárová H, Weidenhoffer Z, Kolárová H, Liebsch M. Phototoxicity of bergamot oil assessed by in vitro techniques in combination with human patch tests. Toxicol In Vitro. 2007;21(7):1298–303.

    Article  CAS  PubMed  Google Scholar 

  12. SCCS. SCCS/1564/15: the SCCS notes of guidance for the testing of cosmetic ingredients and their safety evaluation 9th revision, adopted by SCCS during the 11th plenary meeting of 29 September 2015 (revised version of 25 Apr 2016). 2016.

    Google Scholar 

  13. Liebsch M, Spielmann H. INVITTOX protocol No. 78: 3T3 NRU phototoxicity assay. European Commission DB-ALM, ECVAM. 2002. https://eurl-ecvam.jrc.ec.europa.eu. Accessed 8 Jul 2016.

  14. Liebsch M. INVITTOX protocol No. 121: EpiDerm™ Phototoxicity assay. European Commission DB-ALM, ECVAM. 1999. https://eurl-ecvam.jrc.ec.europa.eu. Accessed 8 Jul 2016.

  15. Liebsch M, Spielmann H, Pape W, Krul C, Deguercy A, Eskes C. UV-induced effects. Altern Lab Anim. 2005;33:131–46.

    PubMed  CAS  Google Scholar 

  16. Gaspar LR, Tharmann J, Maia Campos PM, Liebsch M. Skin phototoxicity of cosmetic formulations containing photounstable and photostable UV-filters and vitamin a palmitate. Toxicol In Vitro. 2013;27(1):418–25.

    Article  CAS  PubMed  Google Scholar 

  17. Kandárová H. Evaluation and validation of reconstructed human skin models as alternatives to animal tests in regulatory toxicology. Dissertation, Freie Universit ät Berlin, 2006.

    Google Scholar 

  18. Freitas JV, Praça FSG, Bentley MVLB, Gaspar LR. Trans-resveratrol and beta-carotene from sunscreens penetrate viable skin layers and reduce cutaneous penetration of UV-filters. Int J Pharm. 2015;484(1–2):131–7.

    Article  CAS  PubMed  Google Scholar 

  19. Liebsch M, Traue D, Barrabas C, Spielmann H, Gerberick GF, Cruse L, Diembeck W, Pfannenbecker U, Spieker J, Hottzhutter H, Brantom P, Aspin P, Southee J. Prevalidation of the Epiderm™ phototoxicity test. In: Clark DG, Lisansky SG, Macmillan R, editors. Alternatives to animal testing II. Brussels: COLIPA; 1999. p. 160–7.

    Google Scholar 

  20. Bruynzeel DP, Ferguson J, Andersen K, Gonçalo M, English J, Goossens A, Holzle E, Ibbotson SH, Lecha M, Lehmann P, Leonard F, Moseley H, Pigatto P, Tanew A. Photopatch testing: a consensus methodology for Europe. J Eur Acad Dermatol Venereol. 2004;18(6):679–82.

    Article  CAS  PubMed  Google Scholar 

  21. Dean JH, Luster MI, Munson AE, Kimber I, editors. lmmunotoxicology and immunopharmacology. New York: Raven Press; 1994.

    Google Scholar 

  22. Oeda S, Hirota M, Nishida H, Ashikaga T, Sasa H, Aiba S, Tokura Y, Kouzuki H. Development of an in vitro photosensitization test based on changes of cell-surface thiols and amines as biomarkers: the photo-SH/NH2 test. J Toxicol Sci. 2016;41(1):129–42.

    Article  PubMed  Google Scholar 

  23. OECD. OECD guideline for the testing of chemicals No. 442E: in vitro skin sensitisation: human cell line activation test (h-CLAT). Paris, France: Organisation for Economic Cooperation and Development. 2016. Available at http://www.oecd.org/env/testguidelines.

  24. Hino R, Orimo H, Kabashima K, Atarashi K, Nakanishi M, Kuma H, Tokura Y. Evaluation of photoallergic potential of chemicals using THP-1 cells. J Dermatol Sci. 2008;52(2):140–3.

    Article  CAS  PubMed  Google Scholar 

  25. Hoya M, Hirota M, Suzuki M, Hagino S, Itagaki H, Aiba S. Development of an in vitro photosensitization assay using human monocyte-derived cells. Toxicol In Vitro. 2009;23(5):911–8.

    Article  CAS  PubMed  Google Scholar 

  26. Karschuk N, Tepe Y, Gerlach S, Pape W, Wenck H, Schmucker R, Wittern K, Schepky A, Reuter H. A novel in vitro method for the detection and characterization of photosensitizers. PLoS One. 2010;23:e15221.

    Article  CAS  Google Scholar 

  27. Galbiati V, Bianchi S, Martínez V, Mitjans M, Corsini E. NCTC 2544 and IL-18 production: a tool for the in vitro identification of photoallergens. Toxicol In Vitro. 2014;28:13–7.

    Article  CAS  PubMed  Google Scholar 

  28. Kurita M, Shimauchi T, Kobayashi M, Atarashi K, Mori K, Tokura Y. Induction of keratinocyte apoptosis by photosensitizing chemicals plus UVA. J Dermatol Sci. 2007;45:105–12.

    Article  CAS  PubMed  Google Scholar 

  29. Lovell WW, Jones PA. Evaluation of mechanistic in vitro tests for the discrimination of photoallergic and photoirritant potential. Altern Lab Anim. 2000;28(5):707–24.

    Google Scholar 

  30. Bryden AM, Moseley H, Ibbotson SH, Chowdhury MM, Beck MH, Bourke J, English J, Farr P, Foulds IS, Gawkrodger DJ, George S, Orton DI, Shaw S, McFadden J, Norris P, Podmore P, Powell S, Rhodes LE, Sansom J, Wilkinson M, van Weelden H, Ferguson J. Photopatch testing of 1155 patients: results of the U.K. multicentre photopatch study group. Br J Dermatol. 2006;155(4):737–47.

    Article  CAS  PubMed  Google Scholar 

  31. Victor FC, Cohen DE, Soter NA. A 20-year analysis of previous and emerging allergens that elicit photoallergic contact dermatitis. J Am Acad Dermatol. 2010;62:605–10.

    Article  CAS  PubMed  Google Scholar 

  32. Benevenuto CG, Guerra LO, Gaspar LR. Combination of retinyl palmitate and UV-filters: phototoxic risk assessment based on photostability and in vitro and in vivo phototoxicity assays. Eur J Pharm Sci. 2015;68:127–36.

    Article  CAS  PubMed  Google Scholar 

  33. Erdmann F, Lortet-Tieulent J, Schüz J, Zeeb H, Greinert R, Breitbart EW, Bray F. International trends in the incidence of malignant melanoma 1953–2008 are recent generations at higher or lower risk? Int J Cancer. 2013;132(2):385–400.

    Article  CAS  PubMed  Google Scholar 

  34. Xiang F, Lucas R, Hales S, Neale R. Incidence of nonmelanoma skin cancer in relation to ambient UV radiation in white populations, 1978–2012: empirical relationships. JAMA Dermatol. 2014;150(10):1063–71.

    Article  PubMed  Google Scholar 

  35. Green A, Williams G, Neale R, Hart V, Leslie D, Parsons P, Marks GC, Gaffney P, Battistutta D, Frost C, Lang C, Russell A. Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial. Lancet. 1999;354(9180):723–9.

    Article  CAS  PubMed  Google Scholar 

  36. Green AC, Williams GM, Logan V, Strutton GM. Reduced melanoma after regular sunscreen use: randomized trial follow-up. J Clin Oncol. 2011;29(3):257–63.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Lorena Rigo Gaspar, Camila Martins Kawakami & Carolina Gomes Benevenuto

Authors
  1. Lorena Rigo Gaspar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Camila Martins Kawakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carolina Gomes Benevenuto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lorena Rigo Gaspar .

Editor information

Editors and Affiliations

  1. SeCAM, Magliaso, Switzerland

    Chantra Eskes

  2. Innovitox Consulting & Services, Houten, The Netherlands

    Erwin van Vliet

  3. Department of Dermatology, University of California School of Medicine, San Francisco, California, USA

    Howard I. Maibach

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Gaspar, L.R., Kawakami, C.M., Benevenuto, C.G. (2017). Overview on the Current Status of Available Test Methods and Additional Promising Methods for Assessing UV-Induced Effects. In: Eskes, C., van Vliet, E., Maibach, H. (eds) Alternatives for Dermal Toxicity Testing. Springer, Cham. https://doi.org/10.1007/978-3-319-50353-0_33

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-50353-0_33

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-50351-6

  • Online ISBN: 978-3-319-50353-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation