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

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From: Toxicology in Vitro(Vol. 50)
Publisher: Elsevier B.V.
Document Type: Report
Length: 667 words

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Keywords Medical devices; Irritation; Alternative testing; In vitro; Reconstructed human epidermis Highlights * Alternative in vitro testing of medical device extracts for irritation is possible. * Reconstructed human epidermis (RhE) model detects presence of irritant in extracts. * High predictivity RhE model for presence of strong irritants in material extracts. * Predictivity in saline or sesame oil extract depends on hydrophilicity of irritant. * Four positive polymer test materials containing a known irritant were evaluated. Abstract Assessment of skin irritation is an essential component of the safety evaluation of medical devices. OECD Test Guideline 439 describes the use of reconstructed human epidermis (RhE) as an in vitro test system for classification of skin irritation by neat chemicals. An international round robin study was conducted to evaluate the RhE method for determination of skin irritant potential of medical device extracts. Four irritant polymers and three non-irritant controls were obtained or developed that had demonstrated their suitability to act as positive or negative test samples. The RhE tissues (EpiDerm[TM] and SkinEthic[TM] RHE) were dosed with 100 [mu]L aliquots of either saline or sesame oil extract. Incubation times were 18 h (EpiDerm[TM]) and 24 h (SkinEthic[TM] RHE). Cell viability reduction 50% was indicative of skin irritation. Both the EpiDerm[TM] and SkinEthic[TM] RHE tissues were able to correctly identify virtually all of the irritant polymer samples either in the saline, sesame oil or both solvent extracts. Our results indicate that RhE tissue models can detect the presence of strong skin irritants at low levels in dilute medical device polymer extracts. Therefore, these models may be suitable replacements for the rabbit skin irritation test to support the biological evaluation of medical devices. Abbreviations DPBS, Dulbecco's phosphate buffered saline; ET-50, Exposure time that induces 50% cell viability; I, Irritant; MTT, 3-[4, 5-dimethyl-thiazol-2-yl]-2,5-diphenyltetrazolium bromide; MDS, methods documentation sheet; NC, negative control; VC, vehicle control; NI, non-irritant; OD, optical density; PC, positive control; RhE, reconstructed human epidermis; SDS, Sodium dodecyl sulfate; PVC, Polyvinyl chloride Author Affiliation: (a) National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands (b) Seh consulting + services, Paderborn, Germany (c) Nelson Laboratories, Inc., Salt Lake City, UT, USA (d) MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia (e) EPISKIN, Lyon, France (f) National Institute of Health Sciences (NIHS), Division of Medical Devices, Tokyo, Japan (g) Arthrex, Inc., Naples, FL, USA 1 1 Currently Quality Tech Services, Inc., Bloomington, MN, USA. (h) NAMSA, Northwood, OH, USA (i) Cyprotex US LCC, Kalamazoo, MI, USA 2 2 Currently IonTox, LCC, Kalamazoo, MI, USA. (j) MatTek Corporation, Ashland, MA, USA (k) American Preclinical Services LLC, Minneapolis, MN, USA (l) US Food and Drug Administration, Center for Devices and Radiological Health, Silver Spring, MD, USA (m) WuXi AppTec, St Paul, MN, USA (n) Becton Dickinson, Research Triangle Park, NC, USA (o) Eurofins Biolab Srl, Vimodrone, Milan, Italy (p) SP Technical Research Institute of Sweden, Boras, Sweden (q) Yonsei University, College of Dentistry, Seoul, South Korea (r) Eurofins Biopharma, Planegg, Munich, Germany (s) VitroScreen, Milan, Italy (t) Envigo CRS GmbH, Rossdorf, Germany (u) NAMSA, Chasse sur Rhone, France (v) Arthrex, Inc., Naples, FL, USA (w) Medtronic, plc, Minneapolis, MN, USA * Corresponding author. Article History: Received 23 October 2017; Revised 29 December 2017; Accepted 3 January 2018 (footnote)1 Currently Quality Tech Services, Inc., Bloomington, MN, USA. (footnote)2 Currently IonTox, LCC, Kalamazoo, MI, USA. Byline: Wim H. De Jong [Wim.de.jong@rivm.nl] (a,*), Sebastian Hoffmann (b), Michelle Lee (c), Helena Kandarova (d), Christian Pellevoisin (e), Yuji Haishima (f), Beau Rollins (g), Austin Zdawczyk (h), Jamin Willoughby (i), Michael Bachelor (j), Timothy Schatz (k), Shelby Skoog (l), Sherry Parker (m), Anita Sawyer (n), Paolo Pescio (o), Kristina Fant (p), Kwang-Mahn Kim (q), Jae Sung Kwon (q), Helge Gehrke (r), Hana Hofman-Huther (r), Marisa Meloni (s), Conrad Julius (t), Damien Briotet (u), Silvia Letasiova (d), Reiko Kato (f), Atsuko Miyajima (f), Liset J.J. De La Fonteyne (a), Christelle Videau (e), Carine Tornier (e), Audrey P. Turley (c), Nicholas Christiano (v), Thor S. Rollins (c), Kelly P. Coleman (w)

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Gale Document Number: GALE|A541609434