{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T17:04:45Z","timestamp":1771261485325,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Hangzhou Medical and Health Science and Technology Project","award":["A20231030"],"award-info":[{"award-number":["A20231030"]}]},{"name":"Scientific Research Fund of Anhui Medical University","award":["2023xkj043"],"award-info":[{"award-number":["2023xkj043"]}]},{"name":"hospital of Anhui medical university north area scientific research cultivation fund project","award":["2023YKJ11, 2023YKJ06, 2023YKJ14"],"award-info":[{"award-number":["2023YKJ11, 2023YKJ06, 2023YKJ14"]}]},{"name":"Health Research Project of Anhui Province","award":["AHWJ2023A20294, AHWJ2024Aa20424"],"award-info":[{"award-number":["AHWJ2023A20294, AHWJ2024Aa20424"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073566"],"award-info":[{"award-number":["82073566"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Diethylhexyl phthalate (DEHP) as a common environmental pollutant has toxic effects on a variety of biological systems, including liver toxicity and immunotoxicity. Previously we had demonstrated that DEHP cause cholestatic liver injury, but whether macrophages play a role in this is unclear, and few studies have focused on the direct effects of DEHP on macrophages. Therefore, this study investigated whether DEHP affects macrophages in vivo and the mechanism by which DEHP regulates macrophages in vitro. The results showed that DEHP induced cholestatic liver injury by up-regulating TBA levels of serum and liver. Simultaneously, DEHP increased the number of F4\/80 positive macrophages and promoted the transcriptional level of IL-1\u03b2 and IL-6 in liver tissue. Further in vitro, We found that DEHP decreased M2 macrophage marker Arg1 level and increased the levels of M1 macrophage marker iNOS, accompanied by up-regulation of the transcriptional levels of IL-1\u03b2, TNF-\u03b1 and CCl2. Moreover, DEHP increased glycolytic flux, which was confirmed by the increased Glut1, HK2 and pfkfb3 expression. Mechanistically, we found DEHP inhibited NRF2 activation, and down-regulated the expression of downstream target NOQ1. While, CDDO (an NRF2 activator) could abrogate the promotion of DEHP on M1 macrophage polarization and glycolysis. These findings indicated that promotion effect of DEHP on M1 macrophage polarization is associated with regulating energy metabolism of macrophages through NRF2\/NQO1 pathway.<\/jats:p>","DOI":"10.1093\/toxres\/tfaf151","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T12:10:03Z","timestamp":1760703003000},"source":"Crossref","is-referenced-by-count":1,"title":["Di (2-ethylhexyl) phthalate induces cholestasis liver injury in mice associated with promoting macrophage polarization through NRF2 signaling pathway"],"prefix":"10.1093","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7770-6138","authenticated-orcid":false,"given":"Yun","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University , No. 100, Huaihai Avenue, Xinzhan District, Hefei 230012 ,","place":["China"]},{"name":"Department of Pharmacy, Anhui Public Health Clinical Center , No. 100, Huaihai Avenue, Xinzheng District, Hefei 230012 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University , No. 100, Huaihai Avenue, Xinzhan District, Hefei 230012 ,","place":["China"]},{"name":"Department of Pharmacy, Anhui Public Health Clinical Center , No. 100, Huaihai Avenue, Xinzheng District, Hefei 230012 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hangzhou Hospital of Traditional Chinese Medicine (Dingqiao District) , No. 1630, Huanding Road, Shangcheng District, Hangzhou 310000 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University , No. 100, Huaihai Avenue, Xinzhan District, Hefei 230012 ,","place":["China"]},{"name":"Department of Pharmacy, Anhui Public Health Clinical Center , No. 100, Huaihai Avenue, Xinzheng District, Hefei 230012 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianqian","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University , No. 100, Huaihai Avenue, Xinzhan District, Hefei 230012 ,","place":["China"]},{"name":"Department of Pharmacy, Anhui Public Health Clinical Center , No. 100, Huaihai Avenue, Xinzheng District, Hefei 230012 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"2025112822562169900_ref1","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1289\/ehp.1306681","article-title":"Temporal trends in phthalate exposures: findings from the National Health and nutrition examination survey, 2001\u20132010","volume":"122","author":"Zota","year":"2014","journal-title":"Environ Health Perspect"},{"key":"2025112822562169900_ref2","doi-asserted-by":"publisher","first-page":"17(12)","DOI":"10.2903\/j.efsa.2019.5838","article-title":"Update of the risk assessment of di-butylphthalate (DBP), butyl-benzyl-phthalate (BBP), bis(2-ethylhexyl)phthalate (DEHP), di-isononylphthalate (DINP) and di-isodecylphthalate (DIDP) for use in food contact materials","volume":"17","author":"Silano","year":"2019","journal-title":"EFSA J"},{"key":"2025112822562169900_ref3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/1750368","article-title":"Toxic effects of Di-2-ethylhexyl phthalate: an overview","volume":"2018","author":"Rowdhwal","year":"2018","journal-title":"Biomed Res Int"},{"key":"2025112822562169900_ref4","doi-asserted-by":"publisher","first-page":"120173","DOI":"10.1016\/j.envpol.2022.120173","article-title":"Health risks of phthalates: a review of immunotoxicity","volume":"313","author":"Zhang","year":"2022","journal-title":"Environ Pollut"},{"key":"2025112822562169900_ref5","doi-asserted-by":"publisher","first-page":"654","DOI":"10.3389\/fendo.2018.00654","article-title":"Lipid metabolism alteration by endocrine disruptors in animal models: an overview","volume":"9","author":"Maradonna","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2025112822562169900_ref6","doi-asserted-by":"publisher","first-page":"314","DOI":"10.31083\/j.fbl2711314","article-title":"Heavy metals, halogenated hydrocarbons, phthalates, glyphosate, cordycepin, alcohol, drugs, and herbs, assessed for liver injury and mechanistic steps","volume":"27","author":"Teschke","year":"2022","journal-title":"Front Biosci (Landmark Ed)"},{"key":"2025112822562169900_ref7","doi-asserted-by":"publisher","first-page":"152653","DOI":"10.1016\/j.tox.2020.152653","article-title":"Metabolic, reproductive and thyroid effects of bis(2-ethylhexyl) phthalate (DEHP) orally administered to male and female juvenile rats at dose levels derived from children biomonitoring study","volume":"449","author":"Tassinari","year":"2021","journal-title":"Toxicology"},{"key":"2025112822562169900_ref8","doi-asserted-by":"publisher","first-page":"110956","DOI":"10.1007\/s11356-023-30149-9","article-title":"Obeticholic acid alleviates intrauterine growth restriction induced by di-ethyl-hexyl phthalate in pregnant female mice by improving bile acid disorder","volume":"30","author":"Zhao","year":"2023","journal-title":"Environ Sci Pollut Res Int"},{"key":"2025112822562169900_ref9","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.taap.2015.01.015","article-title":"Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis","volume":"283","author":"Woolbright","year":"2015","journal-title":"Toxicol Appl Pharmacol"},{"key":"2025112822562169900_ref10","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41420-023-01326-z","article-title":"Hepatic TNFRSF12A promotes bile acid-induced hepatocyte pyroptosis through NFkappaB\/Caspase-1\/GSDMD signaling in cholestasis","volume":"9","author":"Liao","year":"2023","journal-title":"Cell Death Discov"},{"key":"2025112822562169900_ref11","doi-asserted-by":"publisher","first-page":"215","DOI":"10.3727\/105221619X15614873062730","article-title":"Inflammation and cell death during cholestasis: the evolving role of bile acids","volume":"19","author":"Woolbright","year":"2019","journal-title":"Gene Expr"},{"key":"2025112822562169900_ref12","doi-asserted-by":"publisher","first-page":"102328","DOI":"10.1016\/j.jaut.2019.102328","article-title":"The challenges of primary biliary cholangitis: what is new and what needs to be done","volume":"105","author":"Terziroli Beretta-Piccoli","year":"2019","journal-title":"J Autoimmun"},{"key":"2025112822562169900_ref13","doi-asserted-by":"publisher","first-page":"1127743","DOI":"10.3389\/fimmu.2023.1127743","article-title":"Gut microbiota derived bile acid metabolites maintain the homeostasis of gut and systemic immunity","volume":"14","author":"Su","year":"2023","journal-title":"Front Immunol"},{"key":"2025112822562169900_ref14","doi-asserted-by":"publisher","first-page":"e90780","DOI":"10.1172\/jci.insight.90780","article-title":"Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response","volume":"2","author":"Cai","year":"2017","journal-title":"JCI Insight"},{"key":"2025112822562169900_ref15","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.intimp.2018.01.047","article-title":"Dexamethasone restores transforming growth factor-beta activated kinase 1 expression and phagocytosis activity of Kupffer cells in cholestatic liver injury","volume":"56","author":"Hsieh","year":"2018","journal-title":"Int Immunopharmacol"},{"key":"2025112822562169900_ref16","doi-asserted-by":"publisher","first-page":"322","DOI":"10.3389\/fimmu.2020.00322","article-title":"Hepatic macrophages in liver injury","volume":"11","author":"Shan","year":"2020","journal-title":"Front Immunol"},{"key":"2025112822562169900_ref17","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1111\/sji.12468","article-title":"Macrophage phenotype in liver injury and repair","volume":"85","author":"Sun","year":"2017","journal-title":"Scand J Immunol"},{"key":"2025112822562169900_ref18","doi-asserted-by":"publisher","first-page":"112439","DOI":"10.1016\/j.fct.2021.112439","article-title":"Di(2-ethylhexyl)phthalate exposure exacerbates metabolic disorders in diet-induced obese mice","volume":"156","author":"Hsu","year":"2021","journal-title":"Food Chem Toxicol"},{"key":"2025112822562169900_ref19","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s00011-011-0390-x","article-title":"Di-(2-ethylhexyl) phthalate induces production of inflammatory molecules in human macrophages","volume":"61","author":"Nishioka","year":"2012","journal-title":"Inflamm Res"},{"key":"2025112822562169900_ref20","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.3389\/fimmu.2019.01462","article-title":"The metabolic signature of macrophage responses","volume":"10","author":"Viola","year":"2019","journal-title":"Front Immunol"},{"key":"2025112822562169900_ref21","doi-asserted-by":"publisher","first-page":"109256","DOI":"10.1016\/j.neuropharm.2022.109256","article-title":"Methamphetamine and HIV-1 tat proteins synergistically induce microglial autophagy via activation of the Nrf2\/NQO1\/HO-1 signal pathway","volume":"220","author":"Yang","year":"2022","journal-title":"Neuropharmacology"},{"key":"2025112822562169900_ref22","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1007\/s10534-021-00324-x","article-title":"Effects of acute iron overload on Nrf2-related glutathione metabolism in rat brain","volume":"34","author":"Piloni","year":"2021","journal-title":"Biometals"},{"key":"2025112822562169900_ref23","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1093\/jmcb\/mjab033","article-title":"PSA controls hepatic lipid metabolism by regulating the NRF2 signaling pathway","volume":"13","author":"Huang","year":"2021","journal-title":"J Mol Cell Biol"},{"key":"2025112822562169900_ref24","doi-asserted-by":"publisher","first-page":"5232","DOI":"10.7150\/thno.53417","article-title":"c-MYC-directed NRF2 drives malignant progression of head and neck cancer via glucose-6-phosphate dehydrogenase and transketolase activation","volume":"11","author":"Tang","year":"2021","journal-title":"Theranostics"},{"key":"2025112822562169900_ref25","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.3892\/ijmm.2018.3371","article-title":"Genistein attenuates di-(2-ethylhexyl) phthalate-induced testicular injuries via activation of Nrf2\/HO-1 following prepubertal exposure","volume":"41","author":"Zhang","year":"2018","journal-title":"Int J Mol Med"},{"key":"2025112822562169900_ref26","doi-asserted-by":"publisher","first-page":"112696","DOI":"10.1016\/j.fct.2021.112696","article-title":"Effect of DEHP and DnOP on mitochondrial damage and related pathways of Nrf2 and SIRT1\/PGC-1alpha in HepG2 cells","volume":"158","author":"Liu","year":"2021","journal-title":"Food Chem Toxicol"},{"key":"2025112822562169900_ref27","doi-asserted-by":"publisher","first-page":"113119","DOI":"10.1016\/j.fct.2022.113119","article-title":"Di-2-ethylhexyl phthalate (DEHP) induced lipid metabolism disorder in liver via activating the LXR\/SREBP-1c\/PPAR\u03b1\/\u03b3 and NF-\u03baB signaling pathway","volume":"165","author":"Huang","year":"2022","journal-title":"Food Chem Toxicol"},{"key":"2025112822562169900_ref28","doi-asserted-by":"publisher","first-page":"e70047","DOI":"10.1111\/bcpt.70047","article-title":"TCA cycle intermediate mitigates Di(2-ethylhexyl) phthalate-induced cholestatic liver injury through modulation of the Nrf2\/NQO1 signalling Axis","volume":"136","author":"Jiang","year":"2025","journal-title":"Basic & Clinical Pharmacology & Toxicology"},{"key":"2025112822562169900_ref29","doi-asserted-by":"publisher","first-page":"111024","DOI":"10.1016\/j.intimp.2023.111024","article-title":"Berberine ameliorates collagen-induced arthritis in mice by restoring macrophage polarization via AMPK\/mTORC1 pathway switching glycolytic reprogramming","volume":"124","author":"Cheng","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"2025112822562169900_ref30","doi-asserted-by":"publisher","first-page":"e0236038","DOI":"10.1371\/journal.pone.0236038","article-title":"Over-expression of miR-223 induces M2 macrophage through glycolysis alteration and attenuates LPS-induced sepsis mouse model, the cell-based therapy in sepsis","volume":"15","author":"Dang","year":"2020","journal-title":"PLoS One"},{"key":"2025112822562169900_ref31","doi-asserted-by":"publisher","DOI":"10.3390\/cells11233927","article-title":"Nrf2 deficiency exacerbated CLP-induced pulmonary injury and inflammation through autophagy- and NF-kappaB\/PPARgamma-mediated macrophage polarization","volume":"11","author":"Luo","year":"2022","journal-title":"Cells"},{"key":"2025112822562169900_ref32","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1515\/reveh-2022-0077","article-title":"Phthalate exposure and lung disease: the epidemiological evidences, plausible mechanism and advocacy of interventions","volume":"39","author":"Yu","year":"2024","journal-title":"Rev Environ Health"},{"key":"2025112822562169900_ref33","doi-asserted-by":"publisher","first-page":"156164","DOI":"10.1016\/j.phymed.2024.156164","article-title":"Chidan Tuihuang granule modulates gut microbiota to influence NOD1\/RIPK2 pathway in cholestatic liver injury recovery","volume":"135","author":"Chen","year":"2024","journal-title":"Phytomedicine"},{"key":"2025112822562169900_ref34","doi-asserted-by":"publisher","first-page":"e0020","DOI":"10.1097\/hc9.0000000000000020","article-title":"Thioredoxin reductase 1 regulates hepatic inflammation and macrophage activation during acute cholestatic liver injury","volume":"7","author":"Shearn","year":"2023","journal-title":"Hepatol Commun"},{"key":"2025112822562169900_ref35","doi-asserted-by":"publisher","first-page":"153650","DOI":"10.1016\/j.tox.2023.153650","article-title":"Subchronic exposure to di-(2-ethylhexyl) phthalate (DEHP) elicits blood\u2013brain barrier dysfunction and neuroinflammation in male C57BL\/6J mice","volume":"499","author":"Ren","year":"2023","journal-title":"Toxicology"},{"key":"2025112822562169900_ref36","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1097\/mog.0000000000000814","article-title":"Macrophages in cholangiopathies","volume":"38","author":"Bruneau","year":"2022","journal-title":"Curr Opin Gastroenterol"},{"key":"2025112822562169900_ref37","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.immuni.2014.06.008","article-title":"Macrophage activation and polarization: nomenclature and experimental guidelines","volume":"41","author":"Murray","year":"2014","journal-title":"Immunity"},{"key":"2025112822562169900_ref38","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1016\/j.jcmgh.2022.12.005","article-title":"Fibroblast activation protein activates macrophages and promotes parenchymal liver inflammation and fibrosis","volume":"15","author":"Yang","year":"2023","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"2025112822562169900_ref39","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.etap.2019.03.008","article-title":"Di(2-ethylhexyl) phthalate promotes hepatic fibrosis by regulation of oxidative stress and inflammation responses in rats","volume":"68","author":"Zhao","year":"2019","journal-title":"Environ Toxicol Pharmacol"},{"key":"2025112822562169900_ref40","doi-asserted-by":"publisher","first-page":"82","DOI":"10.3109\/08830185.2014.969421","article-title":"Cellular metabolism and macrophage functional polarization","volume":"34","author":"Zhu","year":"2015","journal-title":"Int Rev Immunol"},{"key":"2025112822562169900_ref41","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s13045-023-01478-6","article-title":"Metabolism, metabolites, and macrophages in cancer","volume":"16","author":"Li","year":"2023","journal-title":"J Hematol Oncol"},{"key":"2025112822562169900_ref42","doi-asserted-by":"publisher","first-page":"175552","DOI":"10.1016\/j.ejphar.2023.175552","article-title":"Characterization of the effect of the GLUT-1 inhibitor BAY-876 on T cells and macrophages","volume":"945","author":"Chen","year":"2023","journal-title":"Eur J Pharmacol"},{"key":"2025112822562169900_ref43","doi-asserted-by":"publisher","first-page":"3447","DOI":"10.1038\/s41598-018-21800-4","article-title":"DEHP deregulates adipokine levels and impairs fatty acid storage in human SGBS-adipocytes","volume":"8","author":"Schaedlich","year":"2018","journal-title":"Sci Rep"},{"key":"2025112822562169900_ref44","doi-asserted-by":"publisher","first-page":"1259434","DOI":"10.3389\/fimmu.2023.1259434","article-title":"Myeloid PFKFB3-mediated glycolysis promotes kidney fibrosis","volume":"14","author":"Yang","year":"2023","journal-title":"Front Immunol"},{"key":"2025112822562169900_ref45","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1080\/07853890.2023.2191217","article-title":"Role of PFKFB3-driven glycolysis in sepsis","volume":"55","author":"Xiao","year":"2023","journal-title":"Ann Med"},{"key":"2025112822562169900_ref46","doi-asserted-by":"publisher","first-page":"e23854","DOI":"10.1096\/fj.202400283R","article-title":"Hypoxia activates macrophage-NLRP3 inflammasome promoting atherosclerosis via PFKFB3-driven glycolysis","volume":"38","author":"Wang","year":"2024","journal-title":"FASEB J"},{"key":"2025112822562169900_ref47","doi-asserted-by":"publisher","first-page":"154667","DOI":"10.1016\/j.phymed.2023.154667","article-title":"Astragalus polysaccharide ameliorates vascular endothelial dysfunction by stimulating macrophage M2 polarization via potentiating Nrf2\/HO-1 signaling pathway","volume":"112","author":"Sha","year":"2023","journal-title":"Phytomedicine"},{"key":"2025112822562169900_ref48","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.120596","article-title":"Myeloid HO-1 modulates macrophage polarization and protects against ischemia-reperfusion injury","volume":"3","author":"Zhang","year":"2018","journal-title":"JCI Insight"},{"key":"2025112822562169900_ref49","doi-asserted-by":"publisher","first-page":"175085","DOI":"10.1016\/j.ejphar.2022.175085","article-title":"Sodium salicylate induces browning of white adipocytes via M2 macrophage polarization by HO-1 upregulation","volume":"928","author":"Choi","year":"2022","journal-title":"Eur J Pharmacol"},{"key":"2025112822562169900_ref50","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1002\/jbmr.4099","article-title":"Macrophage GIT1 contributes to bone regeneration by regulating inflammatory responses in an ERK\/NRF2-dependent way","volume":"35","author":"Zhao","year":"2020","journal-title":"J Bone Miner Res"}],"container-title":["Toxicology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/toxres\/article-pdf\/14\/6\/tfaf151\/65614021\/tfaf151.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxres\/article-pdf\/14\/6\/tfaf151\/65614021\/tfaf151.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T03:56:27Z","timestamp":1764388587000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxres\/article\/doi\/10.1093\/toxres\/tfaf151\/8351072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,4]]},"references-count":50,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,11,4]]}},"URL":"https:\/\/doi.org\/10.1093\/toxres\/tfaf151","relation":{},"ISSN":["2045-4538"],"issn-type":[{"value":"2045-4538","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,12]]},"published":{"date-parts":[[2025,11,4]]},"article-number":"tfaf151"}}