{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T03:46:01Z","timestamp":1774928761717,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973034"],"award-info":[{"award-number":["81973034"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["YJSCX2023-30HYD"],"award-info":[{"award-number":["YJSCX2023-30HYD"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Postgraduate Research &amp; Practice Innovation Program of Harbin Medical University","award":["81973034"],"award-info":[{"award-number":["81973034"]}]},{"name":"Postgraduate Research &amp; Practice Innovation Program of Harbin Medical University","award":["YJSCX2023-30HYD"],"award-info":[{"award-number":["YJSCX2023-30HYD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Background: Co-exposure to multiple volatile organic compounds (VOCs) is common in daily life. However, few studies have evaluated the associations between the patterns of simultaneous exposure to multiple VOCs and the risk of hyperuricemia. Methods: This study included 7490 adults from the National Health and Nutrition Examination Survey conducted between 2003 and 2012. The K-means clustering method was applied to cluster eight kinds of VOCs in the blood into various co-exposure patterns, including benzene, bromodichloromethane, chloroform, dibromochloromethane, 1,4-dichlorobenzene, ethylbenzene, methyl tertiary-butyl ether (MTBE), and o-xylene. Binary logistic regression analysis was utilized to assess the association between single VOCs, the co-exposure patterns of multiple VOCs, and the hyperuricemia risk. Restricted cubic spline functions were utilized to investigate the non-linear relationships. Results: Based on eight VOCs, four characteristic co-exposure patterns were generated. Compared with the low-level exposure group, the levels of volatile organic compound (VOC) co-exposure in cluster 2, characterized by relatively high levels of MTBE and moderate levels of bromodichloromethane, chloroform, and dibromochloromethane, were associated with increased hyperuricemia risk, with an odds ratio of 1.32 (1.02, 1.71). Increasing levels of bromodichloromethane and chloroform were significantly associated with an increased risk of hyperuricemia. A strong J-shaped relationship was found between MTBE and hyperuricemia. Conclusions: This study indicated that blood bromodichloromethane and chloroform were positively associated with hyperuricemia risk. Blood MTBE had a J-shaped association with hyperuricemia. In addition, the significant association of the co-exposure patterns of multiple VOCs in the blood with hyperuricemia risk was observed. Changing VOC co-exposure patterns may play a crucial role in the occurrence of hyperuricemia.<\/jats:p>","DOI":"10.3390\/toxics12110772","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T04:11:38Z","timestamp":1729743098000},"page":"772","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Assessing the Co-Exposure Patterns of Volatile Organic Compounds and the Risk of Hyperuricemia: An Analysis of the National Health and Nutrition Examination Survey 2003\u20132012"],"prefix":"10.3390","volume":"12","author":[{"given":"Xue","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene, College of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, College of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, College of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuli","family":"An","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, College of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuangshuang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, College of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongqi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, College of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linwei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, College of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinjie","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, College of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, College of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1097\/BOR.0000000000000028","article-title":"Definition of hyperuricemia and gouty conditions","volume":"26","author":"Bardin","year":"2014","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1053\/j.ajkd.2017.12.009","article-title":"Hyperuricemia, Acute and Chronic Kidney Disease, Hypertension, and Cardiovascular Disease: Report of a Scientific Workshop Organized by the National Kidney Foundation","volume":"71","author":"Johnson","year":"2018","journal-title":"Am. J. Kidney Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.ijcard.2017.11.035","article-title":"Unraveling the relationship between serum uric acid levels and cardiovascular risk","volume":"253","author":"Carluccio","year":"2018","journal-title":"Int. J. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1136\/annrheumdis-2012-201916","article-title":"Serum urate association with hypertension in young adults: Analysis from the Coronary Artery Risk Development in Young Adults cohort","volume":"72","author":"Gaffo","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"110903","DOI":"10.1016\/j.envres.2021.110903","article-title":"Exposure to volatile organic compounds\u2014Acrolein, 1,3-butadiene, and crotonaldehyde\u2014Is associated with vascular dysfunction","volume":"196","author":"McGraw","year":"2021","journal-title":"Environ. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.scitotenv.2011.12.055","article-title":"Blood\/air distribution of volatile organic compounds (VOCs) in a nationally representative sample","volume":"419","author":"Jia","year":"2012","journal-title":"Sci. Total. Environ."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1126\/science.aaq0524","article-title":"Volatile chemical products emerging as largest petrochemical source of urban organic emissions","volume":"359","author":"McDonald","year":"2018","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"El Manouni El Hassani, S., Bosch, S., Lemmen, J.P., Brentar, M.B., Ayada, I., Wicaksono, A.N., Covington, J.A., Benninga, M.A., de Boer, N.K., and de Meij, T.G. (2019). Simultaneous Assessment of Urinary and Fecal Volatile Organic Compound Analysis in De Novo Pediatric IBD. Sensors, 19.","DOI":"10.3390\/s19204496"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1183\/09059180.00000714","article-title":"Volatile organic compounds and risk of asthma and allergy: A systematic review","volume":"24","author":"Nurmatov","year":"2015","journal-title":"Eur. Respir. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Huang, Y., Ho, S.S.H., Lu, Y., Niu, R., Xu, L., Cao, J., and Lee, S. (2016). Removal of Indoor Volatile Organic Compounds via Photocatalytic Oxidation: A Short Review and Prospect. Molecules, 21.","DOI":"10.3390\/molecules21010056"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.envpol.2007.06.012","article-title":"Human health effects of air pollution","volume":"151","author":"Kampa","year":"2007","journal-title":"Environ. Pollut."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1136\/oem.29.4.450","article-title":"Investigation of exposure of ships\u2019 painters to organic solvents","volume":"29","author":"Mikulski","year":"1972","journal-title":"Occup. Environ. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4029","DOI":"10.3168\/jds.2013-7416","article-title":"Effect of commercial or depurinized milk on rat liver growth-regulatory kinases, nuclear factor-kappa B, and endonuclease in experimental hyperuricemia: Comparison with allopurinol therapy","volume":"97","author":"Kocic","year":"2014","journal-title":"J. Dairy Sci."},{"key":"ref_14","first-page":"203","article-title":"Antioxidant potential in serum and liver of albino rats exposed to benzene","volume":"32","author":"Ahmad","year":"1994","journal-title":"Indian J. Exp. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1289\/ehp.7412","article-title":"Children\u2019s exposure to volatile organic compounds as determined by longitudinal measurements in blood","volume":"113","author":"Sexton","year":"2005","journal-title":"Environ. Health Perspect."},{"key":"ref_16","unstructured":"Johnson, C.L., Paulose-Ram, R., Ogden, C.L., Carroll, M.D., Kruszon-Moran, D., Dohrmann, S.M., and Curtin, L.R. (2013). National Health and Nutrition Examination Survey: Analytic Guidelines, 1999\u20132010, National Center for Health Statistics. Vital and Health Statistics."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/S0140-6736(16)32064-5","article-title":"Chronic Kidney Disease","volume":"389","author":"Webster","year":"2017","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/j.scitotenv.2018.04.391","article-title":"Regulated and emerging disinfection by-products in recycled waters","volume":"637\u2013638","author":"Alexandrou","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jes.2017.06.013","article-title":"Occurrence and formation of disinfection by-products in the swimming pool environment: A critical review","volume":"58","author":"Carter","year":"2017","journal-title":"J. Environ. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"115474","DOI":"10.1016\/j.envpol.2020.115474","article-title":"Disinfection by-products in drinking water: Occurrence, toxicity and abatement","volume":"267","author":"Srivastav","year":"2020","journal-title":"Environ. Pollut."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/10408444.2015.1052367","article-title":"Reassessment of MTBE cancer potency considering modes of action for MTBE and its metabolites","volume":"45","author":"Bogen","year":"2015","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5261","DOI":"10.1021\/es505316f","article-title":"New Look at BTEX: Are Ambient Levels a Problem?","volume":"49","author":"Bolden","year":"2015","journal-title":"Environ. Sci. Technol."},{"key":"ref_24","unstructured":"National Toxicology Program (2011). 1,4-Dichlorobenzene. Rep. Carcinog., 12, 139\u2013141."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/ina.12709","article-title":"Occupational exposure and health risks of volatile organic compounds of hotel housekeepers: Field measurements of exposure and health risks","volume":"31","author":"Lin","year":"2020","journal-title":"Indoor Air"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1093\/annweh\/wxaa067","article-title":"Occupational Exposure to Particulate Matter and Volatile Organic Compounds in Two Indoor Cannabis Production Facilities","volume":"64","author":"Silvey","year":"2020","journal-title":"Ann. Work. Expo. Health"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9043","DOI":"10.1021\/acs.est.1c00862","article-title":"Association of Blood Trihalomethane Concentrations with Risk of All-Cause and Cause-Specific Mortality in U.S. Adults: A Prospective Cohort Study","volume":"55","author":"Sun","year":"2021","journal-title":"Environ. Sci. Technol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.mrrev.2007.09.001","article-title":"Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: A review and roadmap for research","volume":"636","author":"Richardson","year":"2007","journal-title":"Mutat. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.envres.2012.02.002","article-title":"Concentrations and correlations of disinfection by-products in municipal drinking water from an exposure assessment perspective","volume":"114","author":"Villanueva","year":"2012","journal-title":"Environ. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.scitotenv.2015.03.050","article-title":"Trihalomethane exposure and biomonitoring for the liver injury indicator, alanine aminotransferase, in the United States population (NHANES 1999\u20132006)","volume":"521","author":"Burch","year":"2015","journal-title":"Sci. Total. Environ."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/toxsci\/kft104","article-title":"Environmental toxin\u2013Linked nonalcoholic steatohepatitis and hepatic metabolic reprogramming in obese mice","volume":"134","author":"Seth","year":"2013","journal-title":"Toxicol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1080\/15287390701551399","article-title":"Mechanisms of chloroform-induced hepatotoxicity: Oxidative stress and mitochondrial permeability transition in freshly isolated mouse hepatocytes","volume":"70","author":"Burke","year":"2007","journal-title":"J. Toxicol. Environ. Health Part A"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1093\/eurjhf\/hfp042","article-title":"Oxidative stress and hyperuricaemia: Pathophysiology, clinical relevance, and therapeutic implications in chronic heart failure","volume":"11","author":"Bergamini","year":"2009","journal-title":"Eur. J. Heart Fail."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7605","DOI":"10.1007\/s11356-022-22637-1","article-title":"Exposures to volatile organic compounds, serum vitamin D, and kidney function: Association and interaction assessment in the US adult population","volume":"30","author":"Liu","year":"2022","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1093\/toxsci\/64.2.269","article-title":"Nephrotoxicity and hepatotoxicity induced by inhaled bromodichloromethane in wild-type and p53-heterozygous mice","volume":"64","author":"Torti","year":"2001","journal-title":"Toxicol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1006\/rtph.1998.1273","article-title":"A comprehensive approach for integration of toxicity and cancer risk assessments","volume":"29","author":"Butterworth","year":"1999","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1177\/074823379501100202","article-title":"Methyl-tertiary-butyl ether (MTBE)\u2014A gasoline additive\u2014Causes testicular and lymphohaematopoietic cancers in rats","volume":"11","author":"Belpoggi","year":"1995","journal-title":"Toxicol. Ind. Health"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jes.2019.06.015","article-title":"Effect of methyl tert-butyl ether on adipogenesis and glucose metabolism in vitro and in vivo","volume":"85","author":"Tang","year":"2019","journal-title":"J. Environ. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.ijbiomac.2015.07.030","article-title":"Interaction of insulin with methyl tert-butyl ether promotes molten globule-like state and production of reactive oxygen species","volume":"80","author":"Valipour","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/jat.1178","article-title":"Methyl tert-butyl ether (MTBE)-induced cytotoxicity and oxidative stress in isolated rat spermatogenic cells","volume":"27","author":"Li","year":"2006","journal-title":"J. Appl. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1016\/j.fct.2008.03.024","article-title":"The effects of methyl tert-butyl ether (MTBE) on the male rat reproductive system","volume":"46","author":"Li","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8556","DOI":"10.1007\/s11356-016-6090-x","article-title":"Toxicity of methyl tertiary-butyl ether on human blood lymphocytes","volume":"23","author":"Salimi","year":"2016","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1039\/C7TX00016B","article-title":"SIRT1 attenuated oxidative stress induced by methyl tert-butyl ether in HT22 cells","volume":"6","author":"Ma","year":"2017","journal-title":"Toxicol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/jat.1674","article-title":"Toxicity of methyl tertiary-butyl ether (MTBE) following exposure of Wistar Rats for 13 weeks or one year via drinking water","volume":"32","author":"Bermudez","year":"2011","journal-title":"J. Appl. Toxicol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4091","DOI":"10.1016\/S0043-1354(03)00348-8","article-title":"Combined toxicity effects of MTBE and pesticides measured with Vibrio fischeri and Daphnia magna bioassays","volume":"37","author":"Hernando","year":"2003","journal-title":"Water Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1093\/toxsci\/kfi257","article-title":"DNA Hypomethylation induced by drinking water disinfection by-products in mouse and rat kidney","volume":"87","author":"Tao","year":"2005","journal-title":"Toxicol. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1177\/0960327107082224","article-title":"CYP2A6 activity in a healthy Spanish population: Effect of age, sex, smoking, and oral contraceptives","volume":"27","author":"Sinues","year":"2008","journal-title":"Hum. Exp. Toxicol."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/11\/772\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:19:20Z","timestamp":1760113160000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/11\/772"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,24]]},"references-count":47,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["toxics12110772"],"URL":"https:\/\/doi.org\/10.3390\/toxics12110772","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,24]]}}}