{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T18:16:05Z","timestamp":1778436965150,"version":"3.51.4"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T00:00:00Z","timestamp":1571616000000},"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":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Thioxanthone and its analogues, 2\u2010 or 4\u2010isopropylthioxanthone, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.tcichemicals.com\/eshop\/ja\/jp\/commodity\/C0292\/\">2\u2010chlorothioxanthone<\/jats:ext-link>, 2,4\u2010diethylthioxanthone (DETX) and xanthone, are used as photoinitiators of ultraviolet (UV) light\u2010initiated curable inks. As these photoinitiators were found in numerous food\/beverage products packaged in cartons printed with UV\u2010cured inks, the cytotoxic effects and mechanisms of these compounds were studied in freshly isolated rat hepatocytes. The toxicity of DETX was greater than that of other compounds. DETX elicited not only concentration (0\u20132.0 m<jats:sc>m<\/jats:sc>)\u2010 and time (0\u20133 hours)\u2010dependent cell death accompanied by the depletion of cellular adenosine triphosphate (ATP), and reduced glutathione (GSH) and protein thiol levels, but also the accumulation of GSH disulfide and malondialdehyde. Pretreatment of hepatocytes with either fructose at a concentration of 10 m<jats:sc>m<\/jats:sc> or <jats:italic>N<\/jats:italic>\u2010acetyl\u2010<jats:sc>l<\/jats:sc>\u2010cysteine (NAC) at a concentration of 5.0 m<jats:sc>m<\/jats:sc> ameliorated DETX (1 m<jats:sc>m<\/jats:sc>)\u2010induced cytotoxicity. Further, the exposure of hepatocytes to DETX resulted in the induction of reactive oxygen species (ROS) and loss of mitochondrial membrane potential, both of which were partially prevented by the addition of NAC. These results indicate that: (1) DETX\u2010induced cytotoxicity is linked to mitochondrial failure and depletion of cellular GSH; (2) insufficient cellular ATP levels derived from mitochondrial dysfunction were, at least in part, ameliorated by the addition of fructose; and (3) GSH loss and\/or ROS formation was prevented by NAC. Taken collectively, these results suggest that the onset of toxic effects caused by DETX may be partially attributable to cellular energy stress as well as oxidative stress.<\/jats:p>","DOI":"10.1002\/jat.3899","type":"journal-article","created":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T10:43:23Z","timestamp":1571654603000},"page":"234-244","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Cytotoxic effects of thioxanthone derivatives as photoinitiators on isolated rat hepatocytes"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3156-467X","authenticated-orcid":false,"given":"Yoshio","family":"Nakagawa","sequence":"first","affiliation":[{"name":"Division of Toxicology Tokyo Metropolitan Institute of Public Health  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko","family":"Inomata","sequence":"additional","affiliation":[{"name":"Division of Toxicology Tokyo Metropolitan Institute of Public Health  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takako","family":"Moriyasu","sequence":"additional","affiliation":[{"name":"Division of Toxicology Tokyo Metropolitan Institute of Public Health  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshinari","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Toxicology Tokyo Metropolitan Institute of Public Health  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,10,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/S0026-895X(25)14164-3","article-title":"Mechanisms of N\u2010acetyl\u2010p\u2010benzoquinone imine cytotoxicity","volume":"28","author":"Albano E.","year":"1985","journal-title":"Molecular Pharmacology"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2010.532887"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-015-1478-9"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/10715769009053373"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/19393210.2012.725774"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7121"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/19440040903367153"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(91)90087-U"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2013.07.008"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1996.0623w.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-3589(08)60985-0"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2010.01.022"},{"key":"e_1_2_7_14_1","first-page":"1","article-title":"Opinion of the scientific panel of food additives, flavourings, processing aids and materials in contact with food on a request from the commission related to 2\u2010isopropyl thioxanthone (ITX) and 2\u2010ethylhexyl\u20104\u2010dimehtylaminobenzoate (EHDAB) in food contact materials","volume":"293","author":"EFSA","year":"2005","journal-title":"EFSA Journal"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2007.1064"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01977355"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986711803414368"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx400383p"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-2288-8_2"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(00)80293-5"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/19440041003596543"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1992.tb08910.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(90)90238-P"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx100237w"},{"key":"e_1_2_7_25_1","first-page":"779","article-title":"Photoinitiators: a food safety review","volume":"32","author":"Lago M. A.","year":"2015","journal-title":"Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-461205-1.50040-0"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.8b02457"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470372531.ch3"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600840120"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(94)34119-2"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(78)52006-5"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2006.12.002"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(92)90139-A"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3523"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-013-1096-3"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2009.02.003"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2006.08.024"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.32.040192.002313"},{"key":"e_1_2_7_40_1","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1016\/S0021-9258(19)39990-9","article-title":"Toxic injury from mercuric chloride in rat hepatocytes","volume":"265","author":"Nieminen A.\u2010L.","year":"1990","journal-title":"Journal Biological Chemistry"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2008.05.032"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(59)90414-X"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867311320190004"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2010.06.004"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1039\/B610213C"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.30.040190.003131"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(80)90118-9"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfs332"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1080\/02652030601182664"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf0615956"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(86)90392-8"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(96)00019-6"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2006.07.001"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1006\/faat.1997.2320"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(99)00107-0"},{"key":"e_1_2_7_56_1","first-page":"11904","article-title":"Metabolic susceptibility of 2\u2010chlorothioxanthone and its toxic effects on mRNA and protein expression and activities of human CYP1A2 and CYP3A4 enzymes","volume":"52","author":"Zhan T.","year":"2018","journal-title":"Environmental Science & Technology"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjat.3899","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.3899","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jat.3899","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.3899","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T15:33:48Z","timestamp":1760542428000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.3899"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,21]]},"references-count":55,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["10.1002\/jat.3899"],"URL":"https:\/\/doi.org\/10.1002\/jat.3899","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,21]]},"assertion":[{"value":"2019-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}