{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T22:37:37Z","timestamp":1777934257962,"version":"3.51.4"},"reference-count":40,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T00:00:00Z","timestamp":1721001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82360671"],"award-info":[{"award-number":["82360671"]}]},{"name":"National Natural Science Foundation of China","award":["82060580"],"award-info":[{"award-number":["82060580"]}]},{"name":"National Natural Science Foundation of China","award":["GJHZ202308"],"award-info":[{"award-number":["GJHZ202308"]}]},{"name":"Shihezi University International Science and Technology Cooperation Promotion Program Project","award":["82360671"],"award-info":[{"award-number":["82360671"]}]},{"name":"Shihezi University International Science and Technology Cooperation Promotion Program Project","award":["82060580"],"award-info":[{"award-number":["82060580"]}]},{"name":"Shihezi University International Science and Technology Cooperation Promotion Program Project","award":["GJHZ202308"],"award-info":[{"award-number":["GJHZ202308"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Brominated flame retardants (BFRs), commonly found in consumer products, have been identified as potential hazards to liver function. While the individual effects of specific BFRs are somewhat understood, there is limited evidence on how mixtures of these chemicals, especially when influenced by demographic factors, interact to affect liver function. This study utilized data from 10,828 participants aged 12 and above from the National Health and Nutrition Examination Survey (2005\u20132016) to investigate the associations between BFRs (both individually and in combinations) and biomarkers of liver injury. The study focused on how age, gender, and body mass index (BMI) modify modulate these effects. Multivariate linear regression, restricted cubic spline function, weighted quantile sum (WQS) regression, and quantile g-computation (qgcomp) models were used to analyze the linear, non-linear, and joint associations between BFR levels and liver function parameters. We found positive associations between the mixed BFRs index and AST, ALT, GGT, ALP, and TBIL levels and a negative association with ALB levels. PBDE28, PBDE47, and PBB153 consistently contributed to the top weight in both the WQS and qgcomp models. Most critically, the study demonstrated that the relationship between co-exposure to BFRs and liver function parameters was modified by age, gender, and BMI. Therefore, our study highlights the importance of considering demographic diversity in assessing the risk of BFR-induced liver damage and supports the implementation of tailored preventive and intervention strategies.<\/jats:p>","DOI":"10.3390\/toxics12070509","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T14:15:49Z","timestamp":1721052949000},"page":"509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Age, Gender, and BMI Modulate the Hepatotoxic Effects of Brominated Flame Retardant Exposure in US Adolescents and Adults: A Comprehensive Analysis of Liver Injury Biomarkers"],"prefix":"10.3390","volume":"12","author":[{"given":"Tingting","family":"Li","sequence":"first","affiliation":[{"name":"Department of Preventive Medicine, School of Medicine, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, School of Medicine, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), School of Medicine, Shihezi University, Shihezi 832000, China"},{"name":"NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panpan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, School of Medicine, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), School of Medicine, Shihezi University, Shihezi 832000, China"},{"name":"NHC Key Laboratory of 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levels, knowledge and information gaps in the African continent","volume":"8","author":"Katima","year":"2017","journal-title":"Atmos. Pollut. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"115240","DOI":"10.1016\/j.envpol.2020.115240","article-title":"Inevitable human exposure to emissions of polybrominated diphenyl ethers: A perspective on potential health risks","volume":"266","author":"Maddela","year":"2020","journal-title":"Environ. Pollut."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.scitotenv.2018.02.199","article-title":"Traditional and novel halogenated flame retardants in urban ambient air: Gas-particle partitioning, size distribution and health implications","volume":"630","author":"Barbas","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"106041","DOI":"10.1016\/j.envint.2020.106041","article-title":"Phasing-out of legacy brominated flame retardants: The UNEP Stockholm Convention and other legislative action worldwide","volume":"144","author":"Sharkey","year":"2020","journal-title":"Environ. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"117475","DOI":"10.1016\/j.envpol.2021.117475","article-title":"Health toxicity effects of brominated flame retardants: From environmental to human exposure","volume":"285","author":"Feiteiro","year":"2021","journal-title":"Environ. Pollut."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"115998","DOI":"10.1016\/j.jenvman.2022.115998","article-title":"An updated review on environmental occurrence, scientific assessment and removal of brominated flame retardants by engineered nanomaterials","volume":"321","author":"Rani","year":"2022","journal-title":"J. Environ. Manag."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"58828","DOI":"10.1007\/s11356-022-19850-3","article-title":"A nationwide survey of 20 legacy brominated flame retardants in indoor dust from China: Continuing occurrence, national distribution, and implication for human exposure","volume":"29","author":"Li","year":"2022","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"139455","DOI":"10.1016\/j.chemosphere.2023.139455","article-title":"Independent and combined associations of urinary metals exposure with markers of liver injury: Results from the NHANES 2013\u20132016","volume":"338","author":"Tang","year":"2023","journal-title":"Chemosphere"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"126816","DOI":"10.1016\/j.chemosphere.2020.126816","article-title":"Novel brominated flame retardants\u2014A review of their occurrence in indoor air, dust, consumer goods and food","volume":"255","author":"Zuiderveen","year":"2020","journal-title":"Chemosphere"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"R1147","DOI":"10.1016\/j.cub.2017.09.019","article-title":"The liver","volume":"27","author":"Trefts","year":"2017","journal-title":"Curr. Biol. CB"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nrendo.2017.42","article-title":"Endocrine-disrupting chemicals and fatty liver disease","volume":"13","author":"Foulds","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"139049","DOI":"10.1016\/j.scitotenv.2020.139049","article-title":"Polybrominated diphenyl ethers and decabromodiphenyl ethane in paired hair\/serum and nail\/serum from corresponding chemical manufacturing workers and their correlations to thyroid hormones, liver and kidney injury markers","volume":"729","author":"Zhao","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"111467","DOI":"10.1016\/j.ecoenv.2020.111467","article-title":"Serum levels of novel brominated flame retardants (NBFRs) in residents of a major BFR-producing region: Occurrence, impact factors and the relationship to thyroid and liver function","volume":"208","author":"Zhao","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1210\/js.2016-1011","article-title":"Developmental Exposure to 2,2\u2032,4,4\u2032-Tetrabromodiphenyl Ether Induces Long-Lasting Changes in Liver Metabolism in Male Mice","volume":"1","author":"Khalil","year":"2017","journal-title":"J. Endocr. Soc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"120766","DOI":"10.1016\/j.jhazmat.2019.120766","article-title":"Chronic exposure to tetrabromodiphenyl ether (BDE-47) aggravates hepatic steatosis and liver fibrosis in diet-induced obese mice","volume":"378","author":"Yang","year":"2019","journal-title":"J. Hazard. Mater."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106206","DOI":"10.1016\/j.envint.2020.106206","article-title":"Ten years of research on synergisms and antagonisms in chemical mixtures: A systematic review and quantitative reappraisal of mixture studies","volume":"146","author":"Martin","year":"2021","journal-title":"Environ. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"128658","DOI":"10.1016\/j.jhazmat.2022.128658","article-title":"Chemical and biological assessments of environmental mixtures: A review of current trends, advances, and future perspectives","volume":"432","author":"Luo","year":"2022","journal-title":"J. Hazard. Mater."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"116046","DOI":"10.1016\/j.envpol.2020.116046","article-title":"Polybrominated diphenyl ethers in serum from residents living in a brominated flame retardant production area: Occurrence, influencing factors, and relationships with thyroid and liver function","volume":"270","author":"Zhao","year":"2021","journal-title":"Environ. Pollut."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1021\/envhealth.3c00202","article-title":"Environmental Obesogens and Their Perturbations in Lipid Metabolism","volume":"2","author":"Wang","year":"2024","journal-title":"Environ. Health"},{"key":"ref_20","unstructured":"Centers for Disease Control and Prevention (2023, March 01). National Health and Nutrition Examination Survey: 1999\u20132022 Survey Content Brochur, Available online: https:\/\/www.cdc.gov\/nchs\/nhanes\/participant\/participant-selected.htm."},{"key":"ref_21","unstructured":"Centers for Disease Control and Prevention (2023, March 01). National Health and Nutrition Examination Survey: What to Expect and Infomation Collected, Available online: https:\/\/www.cdc.gov\/nchs\/nhanes\/participant\/information-collected.htm."},{"key":"ref_22","unstructured":"Centers for Disease Control and Prevention (2023, March 01). National Health and Nutrition Examination Survey 2005\u20132006 Data Documentation, Codebook, and Frequencies. Demographic Variables & Sample Weights (DEMO_D), Available online: https:\/\/wwwn.cdc.gov\/Nchs\/Nhanes\/2005-2006\/DEMO_D.htm."},{"key":"ref_23","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, Vital and Health Statistics, Series 2, Data Evaluation and Methods Research."},{"key":"ref_24","unstructured":"Centers for Disease Control and Prevention (2023, March 01). National Health and Nutrition Examination Survey 2005\u20132006 Data Documentation, Codebook, and Frequencies. Brominated Flame Retardants (BFRs)\u2014Pooled Samples (BFRPOL_D), Available online: https:\/\/wwwn.cdc.gov\/Nchs\/Nhanes\/2005-2006\/BFRPOL_D.htm."},{"key":"ref_25","unstructured":"Centers for Disease Control and Prevention (2023, March 01). National Health and Nutrition Examination Survey 2005\u20132006 Data Documentation, Codebook, and Frequencies. Standard Biochemistry Profile (BIOPRO_D), Available online: https:\/\/wwwn.cdc.gov\/Nchs\/Nhanes\/2005-2006\/BIOPRO_D.htm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"47004","DOI":"10.1289\/EHP5838","article-title":"A Quantile-Based g-Computation Approach to Addressing the Effects of Exposure Mixtures","volume":"128","author":"Keil","year":"2020","journal-title":"Environ. Health Perspect."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1136\/gutjnl-2017-314924","article-title":"Guidelines on the management of abnormal liver blood tests","volume":"67","author":"Newsome","year":"2018","journal-title":"Gut"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"106608","DOI":"10.1016\/j.envint.2021.106608","article-title":"Associations between urinary phthalate metabolite concentrations and markers of liver injury in the US adult population","volume":"155","author":"Yu","year":"2021","journal-title":"Environ. Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2220176","DOI":"10.1001\/jamanetworkopen.2022.20176","article-title":"Association of Prenatal Exposure to Endocrine-Disrupting Chemicals With Liver Injury in Children","volume":"5","author":"Midya","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_30","first-page":"2474","article-title":"The value of serum aspartate aminotransferase and gamma-glutamyl transpetidase as biomarkers in hepatotoxicity","volume":"35","author":"Navarro","year":"2015","journal-title":"Liver Int. Off. J. Int. Assoc. Study Liver"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1038\/ajg.2017.231","article-title":"Clinical Characteristics and Outcome of Hepatic Sarcoidosis: A Population-Based Study 1976-2013","volume":"112","author":"Ungprasert","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/bdrb.21180","article-title":"Gestational and Early Postnatal Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants: General Toxicity and Skeletal Variations","volume":"107","author":"Tung","year":"2016","journal-title":"Birth Defects Res. Part B Dev. Reprod. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6142","DOI":"10.1016\/j.scitotenv.2010.09.003","article-title":"Endocrine disrupting, haematological and biochemical effects of polybrominated diphenyl ethers in a terrestrial songbird, the European starling (Sturnus vulgaris)","volume":"408","author":"Eens","year":"2010","journal-title":"Sci. Total Environ."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1289\/ehp.11807","article-title":"Metabolism of polybrominated diphenyl ethers (PBDEs) by human hepatocytes in vitro","volume":"117","author":"Stapleton","year":"2009","journal-title":"Environ. Health Perspect."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Konstandi, M., and Johnson, E.O. (2023). Age-related modifications in CYP-dependent drug metabolism: Role of stress. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1143835"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"113061","DOI":"10.1016\/j.envpol.2019.113061","article-title":"Sex differences in the association between perfluoroalkyl acids and liver function in US adolescents: Analyses of NHANES 2013\u20132016","volume":"254","author":"Attanasio","year":"2019","journal-title":"Environ. Pollut."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.taap.2004.01.010","article-title":"The effects of gender, age, ethnicity, and liver cirrhosis on cytochrome P450 enzyme activity in human liver microsomes and inducibility in cultured human hepatocytes","volume":"199","author":"Parkinson","year":"2004","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1365-2125.2011.04076.x","article-title":"Metabolic capabilities of cytochrome P450 enzymes in Chinese liver microsomes compared with those in Caucasian liver microsomes","volume":"73","author":"Yang","year":"2012","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1021\/acs.est.6b04696","article-title":"Predictors of Serum Polybrominated Diphenyl Ether (PBDE) Concentrations among Children Aged 1\u20135 Years","volume":"51","author":"Darrow","year":"2017","journal-title":"Environ. Sci. Technol"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"122121","DOI":"10.1016\/j.envpol.2023.122121","article-title":"New brominated flame retardant decabromodiphenyl ethane (DBDPE) in water sediments: A review of contamination characteristics, exposure pathways, ecotoxicological effects and health risks","volume":"334","author":"Wang","year":"2023","journal-title":"Environ. Pollut."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/7\/509\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:17:06Z","timestamp":1760109426000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/7\/509"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,15]]},"references-count":40,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["toxics12070509"],"URL":"https:\/\/doi.org\/10.3390\/toxics12070509","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,15]]}}}