{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:40:02Z","timestamp":1770043202563,"version":"3.49.0"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"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":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>In recent years, nonanimal approaches for skin sensitization have been developed in response to political, regulatory, and ethical demands. The reconstructed human epidermis (RhE)\u2013based testing strategy (RTS)v1\u2013defined approach (DA) is used to categorize skin sensitization potency. However, the RTSv1 DA alone cannot be used to predict potency based on EC3 values [the estimated concentration that produces a stimulation index of 3 in the local lymph node assay (LLNA)], and underpredictions have been reported. Read\u2010across (RAx) can complement DA data and improve prediction confidence. Although case studies combining new approach methodology\/DA data with RAx have been reported, they focus on a single target chemical and lack a comprehensive and robust strategy with well\u2010examined reliability. This study developed a strategy incorporating the RTSv1 DA into RAx (RTSv1\u2010based RAx) to predict skin sensitization potency, applying it to 43 chemicals. The predictive performance of RTSv1\u2010based RAx was evaluated by comparing its predicted potency category and EC3 outcomes with those of RTSv1 DA and the LLNA. RTSv1\u2010based RAx accurately predicted the Globally Harmonized System of Classification (GHS) subcategorization for 38 chemicals and determined the predicted EC3 values for 17 sensitizers within a fourfold range of LLNA\u2010derived EC3 values. This study demonstrates that RTSv1\u2010based RAx offers robust predictivity for both GHS subcategorization and predicted EC3 values, making it useful for quantitative risk assessment.<\/jats:p>","DOI":"10.1002\/jat.4737","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T21:28:27Z","timestamp":1733174907000},"page":"620-635","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Skin Sensitization Potency Prediction Based on Read\u2010Across (RAx) Incorporating RhE\u2010Based Testing Strategy (RTSv1)\u2013Defined Approach: RTSv1\u2010Based RAx"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5514-0895","authenticated-orcid":false,"given":"Sho","family":"Suzuki","sequence":"first","affiliation":[{"name":"Safety Science Research Kao Corporation  Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8778-1951","authenticated-orcid":false,"given":"Hideyuki","family":"Mizumachi","sequence":"additional","affiliation":[{"name":"Safety Science Research Kao Corporation  Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaaki","family":"Miyazawa","sequence":"additional","affiliation":[{"name":"Safety Science Research Kao Corporation  Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2021.105019"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2020.104805"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2007.10.008"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100536.2007.00944.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3448"},{"key":"e_1_2_7_7_1","unstructured":"Casati S. K.Aschberger D.Asturiol et\u00a0al.2016. \u201cAbility of Non\u2010Animal Methods for Skin Sensitization to Detect Pre\u2010 and Pro\u2010Haptens. Report and Recommendations of an EURL ECVAM Expert Meeting.\u201dJoint Research Centre Technical Reports.https:\/\/doi.org\/10.2788\/01803."},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2020.104755"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2023.105458"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/01206501-200512000-00002"},{"key":"e_1_2_7_11_1","unstructured":"GHS. (2017).Globally Harmonized System (GHS) Classification Criteria for Skin Sensitization. Dated 2017\u201011\u201008.https:\/\/www.chemsafetypro.com\/Topics\/GHS\/GHS_classification_skin_sensitizer_LLNA_Guinea_pig_maximisation_test_Buehler.html(Accessed 8 May 2021)"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/rtph.2001.1498"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.14573\/altex.1505051"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408444.2018.1429385"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408444.2018.1429386"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2021.112705"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2017.12.026"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2021.104966"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3172"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2018.11.002"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.4551"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2023.105358"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfy135"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.14573\/altex.2201142"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2007.03.016"},{"key":"e_1_2_7_26_1","unstructured":"NICEATM LLNA Database(2013).https:\/\/ntp.niehs.nih.gov\/pubhealth\/evalatm\/resources\u2010for\u2010test\u2010method\u2010developers\/refchem\/index.html."},{"key":"e_1_2_7_27_1","unstructured":"OECD. (2010).Guideline for Testing of Chemicals No. 429: Skin Sensitization: Local Lymph Node Assay."},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1787\/9789264279285-en"},{"key":"e_1_2_7_29_1","unstructured":"OECD. (2022).Guideline for Testing of Chemicals No. 406: Skin Sensitization Guinea Pig Maximization Test and Buehler Test."},{"key":"e_1_2_7_30_1","unstructured":"OECD. (2023a).OECD Guidelines for the Testing of Chemicals No. 497: Defined Approaches on Skin Sensitization."},{"key":"e_1_2_7_31_1","unstructured":"OECD. (2023b).Guideline for Testing of Chemicals No. 442C: Assays Addressing the Adverse Outcome Pathway Key Event on Covalent Binding to Proteins."},{"key":"e_1_2_7_32_1","unstructured":"OECD. (2023c).Guideline for Testing of Chemicals No. 442E: In\u00a0Vitro Skin Sensitization Assays Addressing the Key Event on Activation of Dendritic Cells on the Adverse Outcome Pathway for Skin Sensitization."},{"key":"e_1_2_7_33_1","unstructured":"OECD.2024.Guideline for Testing of Chemicals No. 442D: Assays Addressing the Adverse Outcome Pathway Key Event on Keratinocyte activation."},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/1062936X.2014.900520"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx700169w"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.6b00055"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2014.12.008"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2021.104936"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.14573\/altex.1601252"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4737","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T10:04:42Z","timestamp":1760522682000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.4737"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,2]]},"references-count":38,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/jat.4737"],"URL":"https:\/\/doi.org\/10.1002\/jat.4737","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,2]]},"assertion":[{"value":"2024-09-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}