{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T08:17:23Z","timestamp":1787991443351,"version":"build-2784847793"},"reference-count":18,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K14355"],"award-info":[{"award-number":["22K14355"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"abstract":"ABSTRACT<\/jats:title>\n \n 6PPD\u2010quinone (6PPD\u2010Q), a transformation product of the tire antioxidant 6PPD, causes acute mortality in several salmonid species, but its toxicity varies markedly among fish species. Disruption of vascular\u2010barrier integrity and inflammatory signaling has been proposed as a key mechanism of 6PPD\u2010Q toxicity. However, it remains unclear whether related transcriptional responses are specific to lethal effects. In this study, juvenile Japanese medaka (\n \n Oryzias latipes<\/jats:italic>\n <\/jats:styled-content>\n ) aged 30\u201335\u2009days post\u2010hatch, an insensitive species, were exposed to 6PPD\u2010Q at 31\u2013500\u2009\u03bcg\/L to examine acute lethality and the expression of selected genes related to tight\u2010junction function, inflammation, antioxidant defense, and neurotoxicity. No mortality or abnormal behavior was observed after 48\u2009h of exposure at nominal concentrations up to 500\u2009\u03bcg\/L. After 24\u2009h of exposure, the tight\u2010junction\u2010related genes\n cldn7<\/jats:italic>\n ,\n cldn15<\/jats:italic>\n , and\n zo1<\/jats:italic>\n generally showed concentration\u2010dependent increases at concentrations ranging from 62.5 to 500\u2009\u03bcg\/L. In contrast, the inflammation\u2010related gene\n il1b<\/jats:italic>\n was downregulated, whereas\n il8<\/jats:italic>\n was unaffected. Antioxidant\u2010 and neurotoxicity\u2010related genes showed modest or nonmonotonic responses, including decreases in\n cat<\/jats:italic>\n ,\n gpx1<\/jats:italic>\n , and\n ache<\/jats:italic>\n . These results demonstrate that 6PPD\u2010Q can alter tight\u2010junction\u2010 and epithelial\u2010barrier\u2010related genes and other stress\u2010response genes in medaka without causing overt acute toxicity. Thus, transcriptional changes in these genes alone are not sufficient predictors of acute lethality, although functional vascular\u2010barrier disruption may remain a critical key event in sensitive salmonids.\n <\/jats:p>","DOI":"10.1002\/jat.70420","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T08:05:11Z","timestamp":1787990711000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Short\u2010Term 6PPD\u2010Q Exposure alters Tight\u2010Junction\u2010Related Gene Expression Without Acute Lethality in Japanese Medaka\n \n Oryzias latipes<\/i>\n <\/scp>"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7898-9486","authenticated-orcid":false,"given":"Kyoshiro","family":"Hiki","sequence":"first","affiliation":[{"name":"Department of Urban Engineering, Graduate School of Engineering The University of Tokyo Tokyo Japan"},{"name":"Health and Environmental Risk Division National Institute for Environmental Studies Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpc.2023.109697"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.5c01559"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.estlett.2c00050"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.3c01040"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2026.107899"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.estlett.1c00453"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.estlett.2c00683"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/edn3.532"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2022.119082"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bimj.200810425"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3EM00047H"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2023.12.045"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.1c04533"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2026.107707"},{"key":"e_1_2_10_16_1","volume-title":"OECD Guidelines for the Testing of Chemicals, Section\u00a02","author":"OECD","year":"2019"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2023.165240"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.5c03697"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd6951"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.70420","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jat.70420","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.70420","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T08:05:12Z","timestamp":1787990712000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.70420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,29]]},"references-count":18,"alternative-id":["10.1002\/jat.70420"],"URL":"https:\/\/doi.org\/10.1002\/jat.70420","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,29]]},"assertion":[{"value":"2026-07-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"jat.70420"}}