Sensitization potential of medical devices detected by in vitro and in vivo methods

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Lada Svobodová
Marian Rucki
Alena Vlkova
Kristina Kejlova
Dagmar Jírová
Marketa Dvorakova
Hana Kolarova
Helena Kandárová
Peter Pôbiš
Tuula Heinonen
Marek Maly

Abstract

Medical devices have to be tested before marketing in accordance with ISO EN 10993-10 in order to avoid skin sensitization. This standard predominantly refers to the in vivo test; however, it doesn't exclude the use of in vitro methods, which have been sufficiently technically and scientifically validated for the purpose of medical devices testing. It is foreseen that due to the complexity of the sensitization endpoint, combination of several methods will be needed to address all key events occurring in the sensitization process. The objective of this pilot study was to evaluate sensitization potential of selected medical devices using a combination of in vitro (LuSens, OECD TG 442D), in chemico (DPRA, OECD TG 442C) and in vivo (LLNA DA, OECD TG 442A) methods and to suggest a possible testing strategy for the safety assessment of medical devices extracts. Overall, one of the 42 tested samples exhibited positive results in all employed test methods, while 33 samples were predicted as samples with non-sensitizing potential in all three performed methods. This study demonstrated good agreement between in vitro and in vivo results regarding the absence of skin sensitization potential; however, discrepancies in positive classification have been recorded.  The mismatch between in vitro and in vivo results might be caused by specific response of the immune system of the living organism. The in vitro methods require optimization of procedure, in particular the choice of appropriate extraction vehicle and applied volumes.

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How to Cite
Svobodová, L., Rucki, M., Vlkova, A., Kejlova, K., Jírová, D., Dvorakova, M., Kolarova, H., Kandárová, H., Pôbiš, P., Heinonen, T. and Maly, M. (2021) “Sensitization potential of medical devices detected by in vitro and in vivo methods”, ALTEX - Alternatives to animal experimentation. doi: 10.14573/altex.2008142.
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References

Adler, S., Basketter, D., Creton, S. et al. (2011). Alternative (non-animal) methods for cosmetics testing: current status and future prospects-2010. Archives of Toxicology 85, 367-485. doi:10.1007/s00204-011-0693-2.

Ahlfors, S. R., Sterner, O., Hansson, C. (2003). Reactivity of contact allergenic haptens to amino acid residues in model carrier peptide, and characterisation of formed peptide-hapten adducts. Skin Pharmacology and Applied Skin Physiology 16(1), 59-68. doi:10.1159/000068288.

Andres, E., Sá-Rocha, V. M., Barrichello, C. et al. (2013). The sensitivity of KeratinoSensTM assay to evaluate plant extracts: A pilot study. Toxicology in Vitro 27(4), 1220-1225. doi:10.1016/j.tiv.2013.02.008.

Bauch, C., Kolle, S.N., Ramirez, T. et al. (2012). Putting the parts together: combining in vitro methods to test for skin sensitizing potentials. Regulatory Toxicology and Pharmacology, 63(3), 489-504. doi:10.1016/j.yrtph.2012.05.013.

Basketter, D.A., Andersen, K.E., Liden, C. et al. (2005). Evaluation of the skin sensitizing potency of chemicals by using the existing methods and conciderations of relevance for elicitation. Contact Dermatitis 52(1), 39-43. doi:10.1111/j.0105-1873.2005.00490.x.

Basketter, D.A., Jírova, D., Kandárová, H. (2012). Review of skin irritation/corrosion hazards on the basis of human data: a regulatory perspective. Interdiscip Toxicol 5, 98–104. doi:10.2478/v10102-012-0017-2.

Bergal, M., Puginier, M., Gerbeix, C. et al. (2020). In vitro testing strategy for assessing the skin sensitizing potential of "difficult to test" cosmetic ingredients. Toxicol in vitro 65, 104781. doi:10.1016/j.tiv.2020.104781

Bleasel, N., Tate, B., Rademaker, M. (2002). Allergic contact dermatitis following exposure to essential oils. Australasian Journal of Dermatology 43(3), 211-213. doi:10.1046/j.1440-0960.2002.00598.x.

Coleman, K.P., McNamara, L.R., Grailer, T.P. et al. (2015). Evaluation of an in vitro human dermal sensitization test for use with medical device extracts. Applied In vitro Toxicology 1(2), 118–130. doi:10.1089/aivt.2015.0007.

Cornish, K., Williams, J. L., Kirk, M. et al. (2010). Evaluation & control of potential sensitizing & irritating chemical components in natural rubber latex extracted from the industrial crop guayule. Industrial Biotechnology 5(4), 245-252. doi:10.1089/ind.2009.5.245.

Cottrez, F., Boitel, E., Berrada-Gomez, M.P. et al. (2020). In Vitro Measurement of Skin Sensitization Hazard of Mixtures and Finished Products: Results Obtained With the SENS-IS Assays. Toxicology in Vitro 62, pp. 10. doi:10.1016/j.tiv.2019.104644.

De Ávila, R.I., Teixeira, G.C., Veloso, D.F.M.C. et al. (2017). In vitro assessment of skin sensitization and photosensitization and phototoxicity potential of commercial glyphosate-containing formulations. Toxicology in Vitro 45(3), 386-392. doi:10.1016/j.tiv.2017.04.001.

De Ávila, R.I., Velosa, D.F.M. C., Teixeira, G.C. et al. (2019). Evaluation of in vitro testing strategies for hazard assessment of the skin sensitization potential of real-life mixtures: The case of henna-based hair-colouring products containing p-phenylenediamine. Contact Dermatitis 81(3), 194-209. doi:10.1111/cod.13294.

De Jong W.H., Hoffmann S., Lee M. et al. (2018). Round robin study to evaluate the reconstructed human epidermis (RhE) model as an in vitro skin irritation test for detection of irritant activity in medical device extracts. Toxicology in Vitro, 50, 439-449. doi:10.1016/j.tiv.2018.01.001

EPA (2018). Interim Science Policy: Use of Alternative Approaches for Skin Sensitisation as a Replacement for Laboratory Animal Testing. https://www.regulations.gov/document?D=EPA-HQ-OPP-2016-0093-0090 (accessed 26 June, 2020).

Gan, D., Norman, K., Barnes, N. et al. (2013). Application of the KeratinoSensTM Assay for Prediction of Dermal Sensitization Hazard for Botanical Cosmetic Ingredients. http://iivs.org/wp-content/uploads/2016/09/iivs_poster_application-of-the-keratinosens-assay-for-prediction-of-dermal-sensitization-hazard-for-botanical-cosmetic-ingredients.pdf (accessed 12 June 2020).

Gerberick, G.F., Vassallo, J.D., Bailey, R.E. et al. (2004). Development of a peptide reactivity assay for screening contact allergens. Toxicol Sci 81, 332-343. doi:10.1093/toxsci/kfh213.

Goud, N.S. (2017). Biocompatibility Evaluation of Medical Devices. In A.S. Fagi (ed.), A Comprehensive Guide to Toxicology in Nonclinical Drug Development (825-840). Academic Press, 2nd edition.

Grundrtröm, G. and Borrebaeck, C.A.K. (2019). Skin Sensitization Testing-What´s Next? Int J Mol Sci 20(3), pp. 6. doi:10.3390/ijms20030666.

Hemming, J.D.C., Hosford, M., Shafer, M.M. (2019). Application of the direct peptide reactivity assay (DPRA) to inorganic compounds: a case study of platinum species. Toxicology Research 8(6), 802-814. doi:10.1039/c9tx00242a.

Hoffmann, S. (2015). LLNA variability: An essential ingredient for a comprehensive assessment of non-animal skin sensitisation test methods and strategies. ALTEX 32, 379-383. doi:10.14573/altex.1505051.

ICCVAM (2010). ICCVAM Test Method Evaluation Report. Nonradioactive local lymph node assay: modified by Daicel Chemical Industries, Ltd., based on ATP content test method protocol (LLNA: DA). NIH Publication No. 10-7551. Research Triangle Park, NC 27709: National Institute of Environmental Health Sciences. https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-da/tmer.pdf.

ICCVAM (2011). ICCVAM Test Method Evaluation Report: Usefulness and Limitations of the Murine Local Lymph Node Assay for Potency Categorization of Chemicals Causing Allergic Contact Dermatitis in Humans. NIH Publication No. 11-7709. Research Triangle Park, NC: National Institute of Environmental Health Sciences. https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-pot/tmer.pdf

ISO (2009). ISO 10993-1:2009- Biological evaluation of medical devices—part 1: evaluation and testing within a risk management process. https://www.iso.org/standard/44908.html.

ISO (2010). ISO 10993-10:2010- Biological evaluation of medical devices—part 10: tests for irritation and skin sensitization. https://www.iso.org/standard/40884.html.

ISO (2012). ISO 10993-12:2012. Biological evaluation of medical devices—sample preparation and reference materials https://www.iso.org/standard/53468.html.

ISO (2020). ISO 10993-23: Biological evaluation of medical devices – Part 23: Test for irritation. https://www.iso.org/obp/ui/#iso:std:iso:10993:-23:dis:ed-1:v1:en.

Jowsey, I.R., Basketter, D.A., Westmoreland, C. and Kimber, I. (2006). A future approach to measuring relative skin sensitising potency: a proposal. J Appl Toxicol 26, 341–350. doi:10.1002/jat.1146.

Kimber, I., Basketter, D.A., Gerberick, G.F. and Dearman, R.J. (2002). Allergic contact dermatitis. International Immunopharmacology 2, 201–211. doi:10.1016/S1567-5769(01)00173-4.

Kimber, I., Basketter, D.A., Gerberick, G.F. et al. (2011). Chemical allergy: Translating Biology into Hazard Characterisation. Toxicological Sciences 120(1), 238–268. doi:10.1093/toxsci/kfq346.

Kirk, R.G.W. (2018). Recovering The Principles of Humane Experimental Technique: The 3Rs and the Human Essence of Animal Research. Sci Technol Human Values 43(4), 622–648. doi:10.1177/0162243917726579.

Lalko, J. and Api, A. M. (2006). Investigation of dermal sensitization potential of various essential oils in the local lymph node assay. Food and Chemical Toxicology 44(5), 739-746. doi:10.1016/j.fct.2005.10.006.

MacKay, C. (2013). From pathways to people: applying the adverse outcome pathway (AOP) for skin sensitization to risk assessment. ALTEX 30, 473–486. doi:10.14573/altex.2013.4.473.

McHugh, M.L. (2012). “Interrater reliability: the kappa statistic.” Biochemia medica 22(3), 276-282. https://hrcak.srce.hr/89395.

McNemar, Q. (1947). Note on the sampling error of the difference between correlated proportions or percentages. Psychometrika 12, 153–157. doi:10.1007/BF02295996.

Mertl, E., Riegel, E., Glück, N. et al. (2019). A dual luciferase assay for evaluation of skin sensitizing potential of medical devices. Molecular Biology Reports 46, 5089–5102. doi:10.1007/s11033-019-04964-8.

Moreira, L. C., de Ávila, R.I., Veloso, D.F.M.C. et al. (2017). In vitro safety and efficacy evaluations of a complex botanical mixtures of Eugenia dysenterica DC. (Myrtaceae): Prospects for developing a new dermocosmetic product. Toxicology in Vitro 45(3), 397-408. doi:10.1016/j.tiv.2017.04.002.

Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods 65(1-2), 55-63. doi:10.1016/0022-1759(83)90303-4

Myers, D., Goldberg, A., Poth, A. et al. (2017). “From in vivo to in vitro: The medical device testing paradigm shift”, ALTEX 34(4), 479-500. doi:10.14573/altex.1608081.

Natsch, A. (2010). The Nrf2-Keap1-ARE toxicity pathway as a cellular sensor for skin sensitizers – functional relevance and a hypothesis on innate reactions to skin sensitizers. Toxicological Sciences 113(2), 284-292. doi:10.1093/toxsci/kfp228.

Natsch, A., Bauch, C., Foertsch, L. et al. (2011). The intra-and inter-laboratory reproducibility and predictivity of the KeratinoSensTM assay to predict skin sensitizers in vitro: Results of a ring-study in five laboratories. Toxicology In vitro 25(3), 733-744. doi:10.1016/j.tiv.2016.01.004.

Nishijo, T., Miyazawa, M., Saito, K. et al. (2019). Sensitivity of KeratinoSensTM and h-CLAT for detecting minute amounts of sensitizers to evaluate botanical extracts. Journal of Toxicological Sciences 44(1), 13-21. doi:10.2131/jts.44.13.

OECD (1992). Test No. 406: Skin sensitisation. 406:9. doi:10.1787/9789264070660-en.OECD (2010). Test No. 442A: Skin sensitisation: Local Lymph Node Assay: DA, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, doi:10.1787/9789264090972-en.

OECD (2010), Test No. 442A: Skin Sensitization: Local Lymph Node Assay: DA, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, doi:10.1787/9789264090972-en.

OECD (2012). The Adverse Outcome Pathway for Skin Sensitisation Initiated by Covalent Binding to Proteins. Part 1: Scientific Evidence Series on Testing and Assessment No.168 JT03321047. Organisation for Economic Co-operation and Development (OECD). Paris, France. doi:10.1787/9789264221444-en.

OECD (2014). The Adverse Outcome Pathway for Skin Sensitisation Initiated by Covalent Binding to Proteins; OECD Series on Testing and Assessment, No. 168; OECD Publishing: Paris, France. doi:10.1787/9789264221444-en.

OECD (2017). Guidance Document on the Reporting of Defined Approaches and Individual Information Sources to be Used within Integrated Approaches to Testing and Assessment (IATA) for Skin Sensitisation, OECD Series on Testing and Assessment, No. 256, OECD Publishing, Paris. doi:10.1787/9789264279285-en.

OECD (2018a). Test No. 442D: In vitro Skin sensitisation, ARENrf2 Luciferase Test Method. doi:10.1787/9789264229822-en.

OECD (2018b). Test No. 442E: In Vitro Skin Sensitisation: In Vitro Skin Sensitisation assays addressing the Key Event on activation of dendritic cells on the Adverse Outcome Pathway for Skin Sensitisation, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, doi:10.1787/9789264264359-en.

OECD (2019). Test No. 442C: In chemico Skin sensitisation: Assays addressing the Adverse Outcome Pathway key event on covalent binding to proteins, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris. doi:10.1787/9789264229709-en.

Otsubo, Y., Nishijo, T., Miyazawa, M. et al. (2017). Binary Test Battery With KeratinoSens™ and h-CLAT as Part of a Bottom-Up Approach for Skin Sensitization Hazard Prediction. Regulatory Toxicology and Pharmacology 88, 118-124. doi:10.1016/j.yrtph.2017.06.002.

Puka L. (2011). Kendall’s Tau. In M. Lovric (ed.) International Encyclopedia of Statistical Science. Springer, Berlin, Heidelberg. doi:10.1007/978-3-642-04898-2_324.

Ramirez, T., Mehling, A., Landsiedel, R. (2017). LuSens: Shedding Light on Skin Sensitisation. In C. Eskes, E. van Vliet, H. Maibach (eds.), Alternatives for Dermal Toxicity Testing (249-262). Springer doi:10.1007/978-3-319-50353-0.

Roberts, D.W. and Patlewicz, G. (2018). Non-animal Assessment of Skin Sensitization Hazard: Is an Integrated Testing Strategy Needed, and if So What Should Be Integrated? Journal of Applied Toxicology 38(1), 41-50. doi:10.1002/jat.3479.

Rovida, C., Alépée, N., Api, A. et al. (2015). “Integrated testing strategies (ITS) for safety assessment”, ALTEX 32(1), 25-40. doi:10.14573/altex.1411011.

Sakaguchi, H., Ashikaga, T., Miyazawa, M. et al. (2009). The relationship between CD86/CD54 expression and THP-1 cell viability in an in vitro skin sensitization test – human cell line activation test (h-CLAT). Cell Biology and Toxicology 25, 109–126. doi:10.1007/s10565-008-9059-9.

Scott, L., Eskes, Ch., Hoffmann, S. et al. (2010). A proposed eye irritation testing strategy to reduce and replace in vivo studies using Botto-Up and Top-Down approaches. Toxicology in Vitro 24(1), 1-9. doi:10.1016/j.tiv.2009.05.019.

Settivari, R.S., Gehen, S.C., Amado, R.A. et al. (2015). Application of the KeratinoSensTM assay for assessing the skin sensitization potential of agrochemical active ingredients and formulations. Regulatory Toxicology and Pharmacology 72(2), 350-360. doi:10.1016/j.yrtph.2015.05.006.

Strickland, J., Daniel, A.B., Allen, D. et al. (2019). Skin sensitisation testing needs and data uses by US regulatory and research agencies. Archives of Toxicology 93(2), 273-291. doi:10.1007/s00204-018-2341-6.

Urbisch, D., Mehling, A., Guth, K. et al. (2015). Assessing skin sensitization hazard in mice and men using non-animal test methods. Regulatory Toxicology and Pharmacology, 71(2), 337-51. doi:10.1016/j.yrtph.2014.12.008.

Valks, R., Conde-Salazar, L., Cuevas, M. (2004). Allergic contact urticaria from natural rubber latex in healthcare and non-healthcare workers. Contact Dermatitis 50(4), 222-224. doi:10.1111/j.0105-1873.2004.00327.x.

WHO (2020). Medical Device – Full Definition. https://www.who.int/medical_devices/full_deffinition/en/.

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