{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:05:30Z","timestamp":1789607130683,"version":"build-2803163510"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100002822","name":"Central South University","doi-asserted-by":"publisher","award":["2026zzts639"],"award-info":[{"award-number":["2026zzts639"]}],"id":[{"id":"10.13039\/501100002822","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Food and Chemical Toxicology"],"published-print":{"date-parts":[[2026,11]]},"DOI":"10.1016\/j.fct.2026.116345","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T15:14:11Z","timestamp":1787411651000},"page":"116345","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Intestinal toxicity mechanisms of 6PPD and 6PPD-Q and their potential relevance to inflammatory bowel disease: network toxicology and experimental evidence"],"prefix":"10.1016","volume":"217","author":[{"given":"Yixuan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyang","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"Suppl. 2","key":"10.1016\/j.fct.2026.116345_bib1","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1093\/ibd\/izae085","article-title":"Challenges in IBD Research 2024: environmental Triggers","volume":"30","author":"Ananthakrishnan","year":"2024","journal-title":"Inflamm. Bowel Dis."},{"issue":"12","key":"10.1016\/j.fct.2026.116345_bib2","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1097\/MIB.0000000000000235","article-title":"Transcriptional analysis of left-sided colitis, pancolitis, and ulcerative colitis-associated dysplasia","volume":"20","author":"Bjerrum","year":"2014","journal-title":"Inflamm. Bowel Dis."},{"issue":"3","key":"10.1016\/j.fct.2026.116345_bib3","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.pop.2023.03.009","article-title":"Inflammatory bowel disease","volume":"50","author":"Bruner","year":"2023","journal-title":"Prim Care"},{"issue":"17","key":"10.1016\/j.fct.2026.116345_bib4","doi-asserted-by":"crossref","DOI":"10.3390\/cancers16173079","article-title":"Orally ingested Micro- and Nano-Plastics: a hidden driver of inflammatory bowel disease and colorectal cancer","volume":"16","author":"Bruno","year":"2024","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.fct.2026.116345_bib5","first-page":"15.25.1","article-title":"Dextran sulfate sodium (DSS)-induced colitis in mice","volume":"104","author":"Chassaing","year":"2014","journal-title":"Curr. Protoc. Im."},{"key":"10.1016\/j.fct.2026.116345_bib7","doi-asserted-by":"crossref","DOI":"10.1016\/j.envpol.2025.126489","article-title":"Enantioselectivity in human urinary excretion of N-(1,3-dimethylbutyl)-N'-phenyl-1,4-benzenediamine (6PPD) and 6PPD-quinone","volume":"378","author":"Chen","year":"2025","journal-title":"Environ. Pollut."},{"key":"10.1016\/j.fct.2026.116345_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhazmat.2023.131245","article-title":"Analysis, environmental occurrence, fate and potential toxicity of tire wear compounds 6PPD and 6PPD-quinone","volume":"452","author":"Chen","year":"2023","journal-title":"J. Hazard Mater."},{"issue":"W1","key":"10.1016\/j.fct.2026.116345_bib8","doi-asserted-by":"crossref","first-page":"W357","DOI":"10.1093\/nar\/gkz382","article-title":"SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules","volume":"47","author":"Daina","year":"2019","journal-title":"Nucleic Acids Res."},{"issue":"12","key":"10.1016\/j.fct.2026.116345_bib9","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1021\/acs.estlett.2c00821","article-title":"First report on the occurrence of N-(1,3-Dimethylbutyl)-N\u2032-phenyl-p-phenylenediamine (6PPD) and 6PPD-Quinone as pervasive pollutants in human urine from South China","volume":"9","author":"Du","year":"2022","journal-title":"Environ. Sci. Technol. Lett."},{"key":"10.1016\/j.fct.2026.116345_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.tox.2025.154285","article-title":"Oral exposure to tire rubber-derived contaminant 6PPD and 6PPD-quinone induces intestinal toxicity in mice","volume":"518","author":"Fang","year":"2025","journal-title":"Toxicology"},{"issue":"6","key":"10.1016\/j.fct.2026.116345_bib11","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.suc.2019.08.001","article-title":"Inflammatory bowel disease presentation and diagnosis","volume":"99","author":"Flynn","year":"2019","journal-title":"Surg Clin North Am"},{"key":"10.1016\/j.fct.2026.116345_bib12","article-title":"Tire-wear particles and tire-related emerging contaminants: characteristics, occurrence, and toxicity in the environment","volume":"48","author":"Ghanadi","year":"2025","journal-title":"Curr. Opin. Environ. Sci. Health"},{"issue":"1","key":"10.1016\/j.fct.2026.116345_bib13","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1038\/s41598-022-05208-9","article-title":"High oncostatin M predicts lack of clinical remission for patients with inflammatory bowel disease on tumor necrosis factor \u03b1 antagonists","volume":"12","author":"Guo","year":"2022","journal-title":"Sci. Rep."},{"key":"10.1016\/j.fct.2026.116345_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2023.164842","article-title":"Four-week repeated exposure to tire-derived 6-PPD quinone causes multiple organ injury in male BALB\/c mice","volume":"894","author":"He","year":"2023","journal-title":"Sci. Total Environ."},{"key":"10.1016\/j.fct.2026.116345_bib15","article-title":"Hypoxia, hypoxia-inducible factors and inflammatory bowel diseases","volume":"12","author":"Hou","year":"2024","journal-title":"Gastroenterol Rep (Oxf)"},{"issue":"8067","key":"10.1016\/j.fct.2026.116345_bib16","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/s41586-025-08940-0","article-title":"Global evolution of inflammatory bowel disease across epidemiologic stages","volume":"642","author":"Hracs","year":"2025","journal-title":"Nature"},{"issue":"2","key":"10.1016\/j.fct.2026.116345_bib17","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.cell.2018.08.067","article-title":"Structural remodeling of the human colonic mesenchyme in inflammatory bowel disease","volume":"175","author":"Kinchen","year":"2018","journal-title":"Cell"},{"issue":"10","key":"10.1016\/j.fct.2026.116345_bib18","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph14101265","article-title":"Wear and tear of tyres: a stealthy source of microplastics in the environment","volume":"14","author":"Kole","year":"2017","journal-title":"Int. J. Environ. Res. Publ. Health"},{"issue":"10","key":"10.1016\/j.fct.2026.116345_bib19","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1084\/jem.20132496","article-title":"The Src family kinases Hck, Fgr, and Lyn are critical for the generation of the in vivo inflammatory environment without a direct role in leukocyte recruitment","volume":"211","author":"Kov\u00e1cs","year":"2014","journal-title":"J. Exp. Med."},{"issue":"Database issue","key":"10.1016\/j.fct.2026.116345_bib20","doi-asserted-by":"crossref","first-page":"D401","DOI":"10.1093\/nar\/gkt1207","article-title":"STITCH 4: integration of protein-chemical interactions with user data","volume":"42","author":"Kuhn","year":"2014","journal-title":"Nucleic Acids Res."},{"issue":"7","key":"10.1016\/j.fct.2026.116345_bib21","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/j.bbamcr.2017.03.007","article-title":"Disruption of the epithelial barrier during intestinal inflammation: quest for new molecules and mechanisms","volume":"1864","author":"Lechuga","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"issue":"3","key":"10.1016\/j.fct.2026.116345_bib22","doi-asserted-by":"crossref","first-page":"370","DOI":"10.5009\/gnl230179","article-title":"Environmental and microbial factors in inflammatory bowel disease model establishment: a review partly through Mendelian randomization","volume":"18","author":"Lin","year":"2024","journal-title":"Gut Liver"},{"key":"10.1016\/j.fct.2026.116345_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2025.108962","article-title":"Oxidative stress and antioxidant therapeutic mechanisms","volume":"278","author":"Liu","year":"2026","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.fct.2026.116345_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.envpol.2025.126114","article-title":"Associations of human exposure to 6PPD and 6PPDQ with colorectal cancer: a mixture analysis","volume":"373","author":"Lv","year":"2025","journal-title":"Environ. Pollut."},{"key":"10.1016\/j.fct.2026.116345_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2024.171153","article-title":"Where the rubber meets the road: emerging environmental impacts of tire wear particles and their chemical cocktails","volume":"927","author":"Mayer","year":"2024","journal-title":"Sci. Total Environ."},{"issue":"3","key":"10.1016\/j.fct.2026.116345_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.autrev.2021.103017","article-title":"The influence of cytokines on the complex pathology of ulcerative colitis","volume":"21","author":"Nakase","year":"2022","journal-title":"Autoimmun. Rev."},{"issue":"6","key":"10.1016\/j.fct.2026.116345_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.cgh.2013.07.022","article-title":"Histologic remission: the ultimate therapeutic goal in ulcerative colitis?","volume":"12","author":"Peyrin-Biroulet","year":"2014","journal-title":"Clin. Gastroenterol. Hepatol."},{"issue":"1","key":"10.1016\/j.fct.2026.116345_bib28","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.1600-065X.2008.00758.x","article-title":"Multiple roles of Lyn kinase in myeloid cell signaling and function","volume":"228","author":"Scapini","year":"2009","journal-title":"Immunol. Rev."},{"issue":"12","key":"10.1016\/j.fct.2026.116345_bib29","doi-asserted-by":"crossref","first-page":"3450","DOI":"10.1093\/ibd\/izaf225","article-title":"Intestinal barrier dysfunction in inflammatory bowel disease: pathophysiology to precision therapeutics","volume":"31","author":"Selvakumar","year":"2025","journal-title":"Inflamm. Bowel Dis."},{"key":"10.1016\/j.fct.2026.116345_bib30","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cancergen.2025.04.004","article-title":"Clinicopathological correlation of PTPN3 expression in breast cancer and in silico drug screening against PTPN3 for therapeutics","volume":"294\u2013295","author":"Thankachan","year":"2025","journal-title":"Cancer Genet."},{"issue":"6525","key":"10.1016\/j.fct.2026.116345_bib31","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1126\/science.abd6951","article-title":"A ubiquitous tire rubber-derived chemical induces acute mortality in coho salmon","volume":"371","author":"Tian","year":"2021","journal-title":"Science"},{"issue":"10","key":"10.1016\/j.fct.2026.116345_bib32","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1097\/MIB.0000000000001246","article-title":"Genetic and transcriptomic bases of intestinal epithelial barrier dysfunction in inflammatory bowel disease","volume":"23","author":"Vancamelbeke","year":"2017","journal-title":"Inflamm. Bowel Dis."},{"issue":"10","key":"10.1016\/j.fct.2026.116345_bib33","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1093\/ibd\/izab032","article-title":"Oncostatin M is a biomarker of diagnosis, worse disease prognosis, and therapeutic nonresponse in inflammatory bowel disease","volume":"27","author":"Verstockt","year":"2021","journal-title":"Inflamm. Bowel Dis."},{"key":"10.1016\/j.fct.2026.116345_bib34","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2024.175057","article-title":"Potential human health risk of the emerging environmental contaminant 6-PPD quinone","volume":"949","author":"Wan","year":"2024","journal-title":"Sci. Total Environ."},{"key":"10.1016\/j.fct.2026.116345_bib35","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2024.116782","article-title":"A review of tire wear particles: occurrence, adverse effects, and control strategies","volume":"283","author":"Wang","year":"2024","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"10.1016\/j.fct.2026.116345_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhazmat.2024.136176","article-title":"-phenylenediamines (PPDs) and PPD-quinones (PPD-Qs) in human urine and breast milk samples: urgent need for focus on PPD-Qs and the establishment of health threshold criteria","volume":"480","author":"Wu","year":"2024","journal-title":"J. Hazard Mater."},{"key":"10.1016\/j.fct.2026.116345_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.abb.2025.110516","article-title":"The role of COX-2 and its use as a therapeutic target in IBD and related colorectal cancer","volume":"771","author":"Yang","year":"2025","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.fct.2026.116345_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2026.119812","article-title":"From exposure models to multi-organ toxicity of 6PPD-quinone in mice: a mini-review","volume":"310","author":"Yang","year":"2026","journal-title":"Ecotoxicol. Environ. Saf."},{"issue":"1","key":"10.1016\/j.fct.2026.116345_bib40","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s43556-025-00395-z","article-title":"Inflammatory bowel diseases: pathological mechanisms and therapeutic perspectives","volume":"7","author":"Yang","year":"2026","journal-title":"Mol Biomed."},{"key":"10.1016\/j.fct.2026.116345_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2024.170679","article-title":"Environmentally realistic dose of tire-derived metabolite 6PPD-Q exposure causes intestinal jejunum and ileum damage in mice via cannabinoid receptor-activated inflammation","volume":"918","author":"Yang","year":"2024","journal-title":"Sci. Total Environ."},{"issue":"5","key":"10.1016\/j.fct.2026.116345_bib41","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s10822-016-9915-2","article-title":"TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models","volume":"30","author":"Yao","year":"2016","journal-title":"J. Comput. Aided Mol. Des."},{"key":"10.1016\/j.fct.2026.116345_bib42","doi-asserted-by":"crossref","DOI":"10.1016\/j.envpol.2025.126352","article-title":"Environmental fate, toxicity, and mitigation of 6PPD and 6PPD-Quinone: current understanding and future directions","volume":"375","author":"Yi","year":"2025","journal-title":"Environ. Pollut."},{"issue":"11","key":"10.1016\/j.fct.2026.116345_bib43","doi-asserted-by":"crossref","DOI":"10.3390\/toxics13110906","article-title":"Environmental occurrence, influencing factors, and toxic effects of 6PPD-Q","volume":"13","author":"Yin","year":"2025","journal-title":"Toxics"},{"issue":"D1","key":"10.1016\/j.fct.2026.116345_bib44","doi-asserted-by":"crossref","first-page":"D1180","DOI":"10.1093\/nar\/gkad1004","article-title":"The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods","volume":"52","author":"Zdrazil","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.fct.2026.116345_bib45","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.cancergen.2025.11.007","article-title":"WDR54 enhances NF-\u03baB signaling to promote progression of hepatocellular carcinoma","volume":"298\u2013299","author":"Zhai","year":"2025","journal-title":"Cancer Genet."},{"issue":"10","key":"10.1016\/j.fct.2026.116345_bib46","doi-asserted-by":"crossref","DOI":"10.3390\/toxics13100873","article-title":"Environmental and human health risks of 6PPD and 6PPDQ: assessment and implications","volume":"13","author":"Zhang","year":"2025","journal-title":"Toxics"},{"issue":"36","key":"10.1016\/j.fct.2026.116345_bib47","doi-asserted-by":"crossref","first-page":"13429","DOI":"10.1021\/acs.est.3c05026","article-title":"Urine excretion, organ distribution, and placental transfer of 6PPD and 6PPD-Quinone in mice and potential developmental toxicity through nuclear receptor pathways","volume":"57","author":"Zhao","year":"2023","journal-title":"Environ. Sci. Technol."},{"key":"10.1016\/j.fct.2026.116345_bib48","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2022.996057","article-title":"Molecular regulation after mucosal injury and regeneration in ulcerative colitis","volume":"9","author":"Zheng","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"10.1016\/j.fct.2026.116345_bib49","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhazmat.2025.138334","article-title":"6PPD-quinone exposure induces oxidative damage and physiological disruption in Eisenia fetida: an integrated analysis of phenotypes, multi-omics, and intestinal microbiota","volume":"493","author":"Zhou","year":"2025","journal-title":"J. Hazard Mater."}],"container-title":["Food and Chemical Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691526004205?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691526004205?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:54:32Z","timestamp":1789606472000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0278691526004205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,11]]},"references-count":49,"alternative-id":["S0278691526004205"],"URL":"https:\/\/doi.org\/10.1016\/j.fct.2026.116345","relation":{},"ISSN":["0278-6915"],"issn-type":[{"value":"0278-6915","type":"print"}],"subject":[],"published":{"date-parts":[[2026,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Intestinal toxicity mechanisms of 6PPD and 6PPD-Q and their potential relevance to inflammatory bowel disease: network toxicology and experimental evidence","name":"articletitle","label":"Article Title"},{"value":"Food and Chemical Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.fct.2026.116345","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"116345"}}