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 must 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 but does not exclude the use of in vitro methods that have been sufficiently technically and scientifically validated for medical device testing. It is foreseen that, due to the complexity of the sensitization endpoint, a 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 the sensitization potential of selected medical devices using a combination of in chemico (DPRA, OECD TG 442C) and in vitro (LuSens, OECD TG 442D) methods in comparison with the in vivo (LLNA DA, OECD TG 442A) method and to suggest a possible testing strategy for the safety assessment of medical device extracts. Overall, one of the 42 tested samples exhibited positive results in all employed test methods, while 33 samples were predicted as non-sensitizing in all three performed methods. This study demonstrated good agreement between in vitro and in vivo results regarding non-sensitizing samples; however, some discrepancies in positive classification were recorded. A testing strategy is suggested in which negative results are accepted and any positive results in the in chemico or in vitro tests are followed up with a third in vitro test and evaluated in accordance with the “2 out of 3 approach”. This strategy may reduce and replace animal use for testing the sensitization potential of medical devices.

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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, 38(3), pp. 419-430. doi: 10.14573/altex.2008142.
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References

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

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

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, 39-43. doi:10.1111/j.0105-1873.2005.00490.x

Basketter, D. A., Jírova, D. and 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.

Bauch, C., Kolle, S. N., Ramirez, T. et al. (2012). Putting the parts together: Combining in vitro methods to test for skin sensitizing potentials. Regul Toxicol Pharmacol 63, 489-504. doi:10.1016/j.yrtph.2012.05.013

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. and Rademaker, M. (2002). Allergic contact dermatitis following exposure to essential oils. Australas J Dermatol 43, 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. Appl In Vitro Toxicol 1, 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. Ind Biotechnol 5, 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. Toxicol In Vitro 62, 104644. 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. Toxicol In Vitro 45, 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, 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. Toxicol 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 26.06.2020)

Gan, D., Norman, K., Barnes, N. et al. (2013). Application of the KeratinoSens™ Assay for Prediction of Dermal Sensitization Hazard for Botanical Cosmetic Ingredients. https://bit.ly/3cq5IHC (accessed 12.06.2020)

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). 2nd edition. Academic Press.

Grundrtröm, G. and Borrebaeck, C. A. K. (2019). Skin sensitization testing – What’s next? Int J Mol Sci 20, 666. doi:10.3390/ijms20030666

Hemming, J. D. C., Hosford, M. and Shafer, M. M. (2019). Application of the direct peptide reactivity assay (DPRA) to inorganic compounds: A case study of platinum species. Toxicol Res 8, 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 on the Murine Local Lymph Node Assay:DA. A Nonradioactive Alternative Test Method to Assess the Allergic Contact Dermatitis Potential of Chemicals and Products. NIH Publication No. 10-7551. Research Triangle Park, NC: 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 (2021). 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. et al. (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. et al. (2002). Allergic contact dermatitis. Int Immunopharmacol 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. Toxicol Sci 120, 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, 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 Chem Toxicol 44, 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. Biochem Med 22, 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. Mol Biol Rep 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. Toxicol In Vitro 45, 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. J Immunol Methods 65, 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, 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. Toxicol Sci 113, 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 KeratinoSens™ assay to predict skin sensitizers in vitro: Results of a ring-study in five laboratories. Toxicol In Vitro 25, 733-744. doi:10.1016/j.tiv.2016.01.004

Nishijo, T., Miyazawa, M., Saito, K. et al. (2019). Sensitivity of KeratinoSens™ and h-CLAT for detecting minute amounts of sensitizers to evaluate botanical extracts. J Toxicol Sci 44, 13-21. doi:10.2131/jts.44.13

OECD (1992). Test No. 406: Skin Sensitisation. OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris. doi:10.1787/9789264070660-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. OECD Series on Testing and Assessment, No.168. OECD Publishing, Paris. 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. 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, ARE-Nrf2 Luciferase Test Method. OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris. 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. Regul Toxicol Pharmacol 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. Berlin, Heidelberg: Springer. doi:10.1007/978-3-642-04898-2_324

Ramirez, T., Mehling, A. and Landsiedel, R. (2017). LuSens: Shedding light on skin sensitisation. In C. Eskes, E. van Vliet and 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? J Appl Toxicol 38, 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, 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 Biol Toxicol 25, 109-126. doi:10.1007/s10565-008-9059-9

Scott, L., Eskes, C., Hoffmann, S. et al. (2010). A proposed eye irritation testing strategy to reduce and replace in vivo studies using bottom-up and top-down approaches. Toxicol In Vitro 24, 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 KeratinoSens™ assay for assessing the skin sensitization potential of agrochemical active ingredients and formulations. Regul Toxicol Pharmacol 72, 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. Arch Toxicol 93, 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. Regul Toxicol Pharmacol 71, 337-351. doi:10.1016/j.yrtph.2014.12.008

Valks, R., Conde-Salazar, L. and Cuevas, M. (2004). Allergic contact urticaria from natural rubber latex in healthcare and non-healthcare workers. Contact Dermatitis 50, 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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