{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:02:58Z","timestamp":1790600578027,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"am","delay-in-days":385,"URL":"http:\/\/rsc.li\/journals-terms-of-use"}],"content-domain":{"domain":["rsc.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The in chemico Direct Peptide Reactivity Assay (DPRA) was developed as a non-animal, relatively high throughput, screening tool for skin sensitization potential. Although the Adverse Outcome Pathway (AOP) for respiratory sensitization remains to be fully elucidated, it is recognized that the molecular initiation event for both skin and respiratory sensitization to low molecular weight chemicals involves haptenation with proteins. The DPRA examines the reactivity of a test compound to two model peptides (containing either cysteine or lysine) and consequently is able to screen for both skin and respiratory sensitization potential. The DPRA was primarily developed for and validated with organic compounds and assessment of the applicability of the assay to metal compounds has received only limited attention. This paper reports the successful application of the DPRA to a series of platinum compounds, including hexachloroplatinate and tetrachloroplatinate salts, which are some of the most potent chemical respiratory sensitizers known. Eleven platinum compounds were evaluated using the DPRA protocol as detailed by Lalko et al., with only minor modification. Two palladium compounds with structures similar to that of the platinum species studied and cobalt chloride were additionally tested for comparison. The hexachloroplatinate and tetrachloroplatinate salts showed exceptionally high reactivity with the cysteine peptide (EC15 values of 1.4 and 14 \u03bcM, respectively). However, for platinum compounds (e.g. hydrogen hexahydroxyplatinate and tetraammineplatinum) where clinical and epidemiological evidence indicates limited sensitization potential, the cysteine DPRA showed only minor or no reactivity (EC15 values of 24\u2009600 and &amp;gt;30\u2009000 \u03bcM, respectively). The outcomes of the lysine peptide assays were less robust and where EC15 was measurable, values were substantially higher than the corresponding results from the cysteine assay. This work supports the value of in chemico peptide reactivity as a metric for assessment of platinum sensitization potential and therefore in screening of new platinum compounds for low or absent sensitization potential. Additional studies are required to determine whether the DPRA may be successfully applied to other metals. We provide details on method modifications and precautions important to the success of the DPRA in the assessment of metal reactivity.<\/jats:p>","DOI":"10.1039\/c9tx00242a","type":"journal-article","created":{"date-parts":[[2019,11,20]],"date-time":"2019-11-20T09:19:31Z","timestamp":1574241571000},"page":"802-814","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Application of the direct peptide reactivity assay (DPRA) to inorganic compounds: a case study of platinum species"],"prefix":"10.1093","volume":"8","author":[{"given":"Jocelyn D. C.","family":"Hemming","sequence":"first","affiliation":[{"name":"Wisconsin State Laboratory of Hygiene, School of Medicine & Public Health, University of Wisconsin-Madison, 2601 Agricultural Drive, Madison, WI 53718, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Hosford","sequence":"additional","affiliation":[{"name":"International Platinum Group Metals Association, Schiess-Staett-Strasse 30, 80339 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0810-298X","authenticated-orcid":false,"given":"Martin M.","family":"Shafer","sequence":"additional","affiliation":[{"name":"Wisconsin State Laboratory of Hygiene, School of Medicine & Public Health, University of Wisconsin-Madison, 2601 Agricultural Drive, Madison, WI 53718, USA"},{"name":"Environmental Chemistry and Technology Program, University of Wisconsin-Madison, 660 N. Park St., Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,20]]},"reference":[{"key":"2020012303462337400_cit1","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.yrtph.2017.03.002","article-title":"Behaviour of Chemical Respiratory Allergens in Novel Predictive Methods for Skin Sensitisation","volume":"86","author":"Basketter","year":"2017","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"2","key":"2020012303462337400_cit2","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.tiv.2012.10.016","article-title":"Reactivity of Chemical Respiratory Allergens in the Peroxidase Peptide Reactivity Assay","volume":"27","author":"Lalko","year":"2013","journal-title":"Toxicol. 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Shafer (ORCID)","URL":"http:\/\/orcid.org\/0000-0002-0810-298X","name":"identifier","group":{"name":"author_identifiers","label":"IDENTIFIERS"}},{"value":"Single-blind","order":2,"name":"peer_review_method","group":{"name":"peer_review_method","label":"PEER REVIEW METHOD"}},{"value":"Received 4 September 2019; Accepted 4 November 2019;  Advance Article published 20 November 2019;  Version of Record published 9 December 2019","order":1,"name":"history","group":{"name":"publication_history","label":"PUBLICATION HISTORY"}}]}}