{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T06:44:24Z","timestamp":1762325064783,"version":"3.32.0"},"reference-count":56,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,8,15]],"date-time":"2021-08-15T00:00:00Z","timestamp":1628985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003958","name":"Stichting voor de Technische Wetenschappen","doi-asserted-by":"publisher","award":["13382"],"award-info":[{"award-number":["13382"]}],"id":[{"id":"10.13039\/501100003958","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Contact Dermatitis"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Metal alloys containing contact sensitizers (nickel, palladium, titanium) are extensively used in medical devices, in particular dentistry and orthopaedic surgery. The skin patch test is used to test for metal allergy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine whether metal salts, when applied to freshly excised skin at patch test\u2013relevant concentrations and using a method which mimics skin patch testing, cause in changes in the epidermis and dermis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Tissue histology, apoptosis, metabolic activity, and inflammatory cytokine release were determined for two nickel salts, two palladium salts, and four titanium salts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patch test\u2013relevant concentrations of all metal salts caused localized cytotoxicity. This was observed as epidermis separation at the basement membrane zone, formation of vacuoles, apoptotic nuclei, decreased metabolic activity, and (pro)inflammatory cytokine release. Nickel(II) sulfate hexahydrate, nickel(II) chloride hexahydrate, titanium(IV) bis(ammonium lactato)dihydroxide, and calcium titanate were highly cytotoxic. Palladium(II) chloride, sodium tetrachloropalladate(II), titanium(IV) isopropoxide, and titanium(IV) dioxide showed mild cytotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The patch test in itself may be damaging to the skin of the patient being tested. These results need further verification with biopsies obtained during clinical patch testing. The future challenge is to remain above the elicitation threshold at noncytotoxic metal concentrations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cod.13940","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T03:35:25Z","timestamp":1626406525000},"page":"531-542","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Patch test\u2013relevant concentrations of metal salts cause localized cytotoxicity, including apoptosis, in skin ex vivo"],"prefix":"10.1111","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6820-3072","authenticated-orcid":false,"given":"Yan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Oral Cell Biology, Academic Centre for Dentistry (ACTA) University of Amsterdam and Vrije Universiteit Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam University Medical Centre Vrije Universiteit Amsterdam, Amsterdam Infection and Immunity Institute  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels P. 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