{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T09:24:27Z","timestamp":1767864267479,"version":"3.49.0"},"reference-count":18,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The amino acid derivative reactivity assay (ADRA) is an alternative method for evaluating key event 1 (KE\u20101) in the skin sensitization mechanism included in OECD TG442C (OECD, 2021). Recently, we found that ADRA with a 4\u2010mM test chemical solution had a higher accuracy than the original ADRA (1\u00a0mM). However, ADRA (4\u00a0mM) has yet to be evaluated using integrated approaches to testing and assessment (IATA), a combination of alternative methods for evaluating KE. In this study, the sensitization potency of three defined approaches (DAs) using ADRA (4\u00a0mM) as KE\u20101 was predicted and compared with those of two additional ADRAs or direct peptide reactivity assay (DPRA): (i) \u201c2 out of 3\u201d approach, (ii) \u201c3 out of 3\u201d approach, and (iii) integrated testing strategy (ITS). In the hazard identification of chemical sensitizers, the accuracy of human data and local lymph node assay (LLNA) remained almost unchanged among the three approaches evaluated. Potency classifications for sensitization were predicted with the LLNA and human data sets using ITS. The potency classifications for the sensitization potency prediction accuracy of LLNA data using any alternative method were almost unchanged, at approximately 70%, and those with ITS were not significantly different. When ITS was performed using DPRA, the prediction accuracy was approximately 73% for human data, which was similar to that of the LLNA data; however, the accuracy tended to increase for all ADRA methods. In particular, when ITS was performed using ADRA (4\u00a0mM), the prediction accuracy was approximately 78%, which proved to be a practical level.<\/jats:p>","DOI":"10.1002\/jat.4283","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T20:23:15Z","timestamp":1641500595000},"page":"1159-1167","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Applicability of amino acid derivative reactivity assay (4\u00a0mM) for the prediction of skin sensitization by combining multiple alternative methods to evaluate key events"],"prefix":"10.1002","volume":"42","author":[{"given":"Mika","family":"Imamura","sequence":"first","affiliation":[{"name":"Safety Evaluation Center Fujifilm Corporation  Minamiashigara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2014-9457","authenticated-orcid":false,"given":"Yusuke","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Safety Evaluation Center Fujifilm Corporation  Minamiashigara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4345-1154","authenticated-orcid":false,"given":"Masaharu","family":"Fujita","sequence":"additional","affiliation":[{"name":"Safety Evaluation Center Fujifilm Corporation  Minamiashigara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayaka","family":"Wanibuchi","sequence":"additional","affiliation":[{"name":"Safety Evaluation Center Fujifilm Corporation  Minamiashigara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natsumi","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Safety Evaluation Center Fujifilm Corporation  Minamiashigara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hajime","family":"Kojima","sequence":"additional","affiliation":[{"name":"Biological Safety Research Center, Division of Risk Assessment National Institute of Health Sciences  Kawasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Ono","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences Okayama University  Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7115-8452","authenticated-orcid":false,"given":"Toshihiko","family":"Kasahara","sequence":"additional","affiliation":[{"name":"Safety Evaluation Center Fujifilm Corporation  Minamiashigara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2014.06.001"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2019.04.014"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2019.02.004"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3707"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3834"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.4082"},{"key":"e_1_2_7_8_1","unstructured":"Ministry of Health Labor and WelfareSyokuseiyakushinhatsu. 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Guideline on defined approaches for skin sensitization. Organisation for Economic Cooperation and Development Paris. Available at:https:\/\/www.oecd\u2010ilibrary.org\/docserver\/b92879a4\u2010en.pdf?expires=1630407219&id=id&accname=guest&checksum=7BBB120042C0DF01F25ED80C280DF222 DOI:https:\/\/doi.org\/10.1787\/b92879a4-en","DOI":"10.1787\/b92879a4-en"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3127"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2014.12.008"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.2131\/jts.44.821"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2019.01.001"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.2131\/jts.44.585"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3139"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4283","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jat.4283","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4283","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T14:35:35Z","timestamp":1760538935000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.4283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,20]]},"references-count":18,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1002\/jat.4283"],"URL":"https:\/\/doi.org\/10.1002\/jat.4283","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,20]]},"assertion":[{"value":"2021-10-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}