{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T02:41:34Z","timestamp":1787625694851,"version":"build-2736575974"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:00:00Z","timestamp":1710374400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:00:00Z","timestamp":1710374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"United States National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health","award":["HHSN273201500010C"],"award-info":[{"award-number":["HHSN273201500010C"]}]},{"name":"Bundesinstitut f\u00fcr Risikobewertung (BfR)"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Toxicol"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Since the 1940s, patch tests in healthy volunteers (Human Predictive Patch Tests, HPPTs) have been used to identify chemicals that cause skin sensitization in humans. Recently, we reported the results of a major curation effort to support the development of OECD Guideline 497 on Defined Approaches (DAs) for skin sensitization (OECD in Guideline No. 497: Defined Approaches on Skin Sensitisation, 2021a. <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1787\/b92879a4-en\">https:\/\/doi.org\/10.1787\/b92879a4-en<\/jats:ext-link>). In the course of this work, we compiled and published a database of 2277 HPPT results for 1366 unique test substances (Strickland et al. in Arch Toxicol 97:2825\u20132837, 2023. <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1007\/s00204-023-03530-3\">https:\/\/doi.org\/10.1007\/s00204-023-03530-3<\/jats:ext-link>). Here we report a detailed analysis of the value of HPPT data for classification of chemicals as skin sensitizers under the United Nations\u2019 Globally Harmonized System of Classification and Labelling of Chemicals (GHS). As a result, we propose the dose per skin area (DSA) used for classification by the GHS to be replaced by or complemented with a dose descriptor that may better reflect sensitization incidence [e.g., the DSA causing induction of sensitization in one individual (DSA1+) or the DSA leading to an incidence of induction in 5% of the tested individuals (DSA05)]. We also propose standardized concepts and workflows for assessing individual HPPT results, for integrating multiple HPPT results and for using them in concert with Local Lymph Node Assay (LLNA) data in a weight of evidence (WoE) assessment. Overall, our findings show that HPPT results are often not sufficient for deriving unambiguous classifications on their own. However, where they are, the resulting classifications are reliable and reproducible and can be integrated well with those from other skin sensitization data, such as the LLNA.<\/jats:p>","DOI":"10.1007\/s00204-023-03656-4","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T10:03:48Z","timestamp":1710410628000},"page":"1253-1269","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Use of human predictive patch test (HPPT) data for the classification of skin sensitization hazard and potency"],"prefix":"10.1007","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5636-8152","authenticated-orcid":false,"given":"Matthias","family":"Herzler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8021-0977","authenticated-orcid":false,"given":"Jaleh","family":"Abedini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8575-9547","authenticated-orcid":false,"given":"David G.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4072-1956","authenticated-orcid":false,"given":"Dori","family":"Germolec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9781-9842","authenticated-orcid":false,"given":"John","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9915-7275","authenticated-orcid":false,"given":"Hon-Sum","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9912-0322","authenticated-orcid":false,"given":"Joanna","family":"Matheson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0995-7792","authenticated-orcid":false,"given":"Emily","family":"Reinke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4112-7484","authenticated-orcid":false,"given":"Judy","family":"Strickland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9655-681X","authenticated-orcid":false,"given":"Hermann-Josef","family":"Thierse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7973-4602","authenticated-orcid":false,"given":"Kim","family":"To","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3550-5602","authenticated-orcid":false,"given":"James","family":"Truax","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8900-8209","authenticated-orcid":false,"given":"Jens T.","family":"Vanselow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7914-3682","authenticated-orcid":false,"given":"Nicole","family":"Kleinstreuer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,14]]},"reference":[{"issue":"12","key":"3656_CR1","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1289\/ehp.1409385","volume":"123","author":"WA Chiu","year":"2015","unstructured":"Chiu WA, Slob W (2015) A unified probabilistic framework for dose\u2013response assessment of human health effects. 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This article may include the work product of employees of the NTP, NIEHS, other governmental agencies or other organizations; however, the statements, opinions, or conclusions contained therein were not approved by, and do not necessarily represent, statements, opinions, or conclusions of the United States or German government, or of any of the organizations to which the authors of this publication are affiliated. Inotiv staff provide technical support for NICEATM, but do not represent NIEHS, NTP, or any U.S. or German agency.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}