{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:51:10Z","timestamp":1760143870498,"version":"build-2065373602"},"reference-count":54,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T00:00:00Z","timestamp":1709164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Hearing loss (HL) is associated with poorer language development and school performance. Ototoxic substances such as metals and solvents, including benzene, are a risk factor associated with HL. This study examines potential associations between the benzene metabolite trans,trans-muconic acid (t,t-MA) and HL in youth of the National Health and Nutrition Examination Survey (NHANES). Logistic regression calculated adjusted odds ratio (aOR) associations between HL and urinary t,t-MA quartiles, natural-log transformed, and doubled urinary t,t-MA. Hearing threshold pure-tone average (PTA) at speech frequencies (SF) 0.5, 1, 2, and 4 kHz and high frequencies (HF) 3, 4, and 6 kHz were analyzed for slight HL (PTA &gt; 15 dB) and mild HL (PTA &gt; 20 dB). Urinary t,t-MA was statistically significantly associated with both slight SF and HF HL. For each doubling of t,t-MA there were increased odds of having slight SFHL (aOR = 1.42; 95% CI: 1.05, 1.92), slight HFHL (aOR = 1.31; 95% CI: 1.03, 1.66), mild SFHL (aOR = 1.60; 95% CI: 1.10, 2.32), and mild HFHL (aOR = 1.45; 95% CI: 1.03, 2.04). To our knowledge, this is the first population-based report of an association between SFHL, HFHL, and the benzene metabolite t,t-MA in youth 6 to 19 years old.<\/jats:p>","DOI":"10.3390\/toxics12030191","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T02:59:39Z","timestamp":1709175579000},"page":"191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hearing Loss and Urinary trans,trans-Muconic Acid (t,t-MA) in 6- to 19-Year-Old Participants of NHANES 2017\u2013March 2020"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5837-350X","authenticated-orcid":false,"given":"Rae T.","family":"Benedict","sequence":"first","affiliation":[{"name":"Office of Innovation and Analytics, Agency for Toxic Substances and Disease Registry (ATSDR), Atlanta, GA 30341, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Scinicariello","sequence":"additional","affiliation":[{"name":"Office of Innovation and Analytics, Agency for Toxic Substances and Disease Registry (ATSDR), Atlanta, GA 30341, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry G.","family":"Abadin","sequence":"additional","affiliation":[{"name":"Office of Innovation and Analytics, Agency for Toxic Substances and Disease Registry (ATSDR), Atlanta, GA 30341, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6897-3720","authenticated-orcid":false,"given":"Gregory M.","family":"Zarus","sequence":"additional","affiliation":[{"name":"Office of Innovation and Analytics, Agency for Toxic Substances and Disease Registry (ATSDR), Atlanta, GA 30341, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Attanasio","sequence":"additional","affiliation":[{"name":"Department of Biology, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,29]]},"reference":[{"key":"ref_1","unstructured":"Blackwell, D.L., Lucas, J.W., and Clarke, T.C. (2014). Summary Health Statistics for U.S. Adults: National Health Interview Survey, 2012, Vital Health Stat 10."},{"key":"ref_2","unstructured":"GBD 2019 Hearing Loss Collaborators (2021). Hearing loss prevalence and years lived with disability, 1990\u20132019: Findings from the Global Burden of Disease Study 2019. Lancet, 397, 996\u20131009."},{"key":"ref_3","unstructured":"WHO, World Health Organization (2024, February 27). World Report on Hearing, Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240020481."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1001\/jamaoto.2019.3585","article-title":"Association of slight to mild hearing loss with behavioral problems and school performance in children","volume":"146","author":"Labuschagne","year":"2020","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref_5","first-page":"107","article-title":"Unilateral hearing loss in children: Speech-language and school performance","volume":"21","author":"Lieu","year":"2013","journal-title":"B-ENT"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"76s","DOI":"10.1097\/AUD.0000000000000219","article-title":"Language outcomes in young children with mild to severe hearing loss","volume":"36","author":"Tomblin","year":"2015","journal-title":"Ear Hear."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.scitotenv.2017.12.091","article-title":"Hearing loss in children with e-waste lead and cadmium exposure","volume":"624","author":"Liu","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1001\/archoto.2011.202","article-title":"Heavy metals exposure and hearing loss in US adolescents","volume":"137","author":"Shargorodsky","year":"2011","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"118772","DOI":"10.1016\/j.envpol.2021.118772","article-title":"Association of polycyclic aromatic hydrocarbons exposure, systemic inflammation with hearing loss among adults and adolescents","volume":"296","author":"Li","year":"2022","journal-title":"Environ. Pollut."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1001\/archoto.2011.109","article-title":"Secondhand smoke and sensorineural hearing loss in adolescents","volume":"137","author":"Lalwani","year":"2011","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1038\/s41598-018-37739-5","article-title":"Association of obesity with hearing impairment in adolescents","volume":"9","author":"Scinicariello","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s00420-019-01419-2","article-title":"Association of organic solvents and occupational noise on hearing loss and tinnitus among adults in the U.S., 1999\u20132004","volume":"92","author":"Staudt","year":"2019","journal-title":"Int. Arch. Occup. Environ. Health"},{"key":"ref_13","unstructured":"Johnson, A.C., and Morata, T.C. (2010). 142. Occupational Exposure to Chemical and Hearing Impairment. The Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals, University of Gothenburg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3109\/01050399709074987","article-title":"Hearing loss from combined exposures among petroleum refinery workers","volume":"26","author":"Morata","year":"1997","journal-title":"Scand. Audiol."},{"key":"ref_15","unstructured":"ATSDR, Agency for Toxic Substances and Disease Registry (2024, January 26). Toxicological Profile for Benzene, Available online: https:\/\/www.epa.gov\/foia\/toxicological-profile-benzene."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9653","DOI":"10.1021\/acs.est.2c09289","article-title":"Gas and propane combustion from stoves emits benzene and Increases indoor air pollution","volume":"57","author":"Kashtan","year":"2023","journal-title":"Environ. Sci. Technol."},{"key":"ref_17","unstructured":"FDA, US Food and Drug Administration (2024, January 26). FDA Search Benzene and Cosmetics, Available online: https:\/\/www.fda.gov\/search?s=benzene+and+cosmetics&sort_bef_combine=rel_DESC."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ijheh.2016.10.002","article-title":"Exposure to environmental chemicals among Korean adults-updates from the second Korean National Environmental Health Survey (2012\u20132014)","volume":"220","author":"Choi","year":"2017","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_19","first-page":"122","article-title":"Urinary t,t-muconic acid as an indicator of exposure to benzene","volume":"46","author":"Inoue","year":"1989","journal-title":"Br. J. Ind. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ijheh.2016.11.006","article-title":"Three cycles of human biomonitoring in Flanders\u2014Time trends observed in the Flemish Environment and Health Study","volume":"220","author":"Schoeters","year":"2017","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Akinbami, L.J., Chen, T.C., Davy, O., Ogden, C.L., Fink, S., Clark, J., Riddles, M.K., and Mohadjer, L.K. (2022). National health and Nutrition Examination Survey, 2017\u2013March 2020 Prepandemic File: Sample Design, Estimation, and Analytic Guidelines, Vital Health Stat 1.","DOI":"10.15620\/cdc:115434"},{"key":"ref_22","unstructured":"CDC, Centers for Disease Control and Prevention (2024, January 26). NHANES-NCHS Research Ethics Review Board Approval (cdc.gov), Available online: https:\/\/www.cdc.gov\/nchs\/nhanes\/irba98.htm."},{"key":"ref_23","unstructured":"CDC, Centers for Disease Control and Prevention (2024, January 26). NHANES Audoiometry Manual, Available online: https:\/\/wwwn.cdc.gov\/nchs\/data\/nhanes\/2017-2018\/manuals\/2018-Audiometry-Procedures-Manual-508.pdf."},{"key":"ref_24","unstructured":"CDC, Centers for Disease Control and Prevention (2024, January 26). NHANES Audiometry Procedures Manual, Available online: https:\/\/wwwn.cdc.gov\/nchs\/data\/nhanes\/2019-2020\/manuals\/2019-Audiometry-Procedures-Manual-508.pdf."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1001\/jamaoto.2016.3527","article-title":"Declining Prevalence of Hearing Loss in US Adults Aged 20 to 69 Years","volume":"143","author":"Hoffman","year":"2017","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1001\/jamaoto.2018.0651","article-title":"Association of iodine deficiency with hearing impairment in US adolescents aged 12 to 19 years: Analysis of NHANES 2007\u20132010 data","volume":"144","author":"Scinicariello","year":"2018","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.1542\/peds.2010-0926","article-title":"Prevalence of noise-induced hearing-threshold shifts and hearing loss among US youths","volume":"127","author":"Henderson","year":"2011","journal-title":"Pediatrics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1001\/jama.2020.17647","article-title":"Hearing loss in children: A review","volume":"324","author":"Lieu","year":"2020","journal-title":"JAMA"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bhandari, D., McCarthy, D., Biren, C., Movassaghi, C., Blount, B.C., and De Jes\u00fas, V.R. (2019). Development of a UPLC-ESI-MS\/MS method to measure urinary metabolites of selected VOCs: Benzene, cyanide, furfural, furfuryl alcohol, 5-hydroxymethylfurfural, and N-methyl-2-pyrrolidone. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 1126\u20131127.","DOI":"10.1016\/j.jchromb.2019.121746"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1289\/ehp.7337","article-title":"Urinary creatinine concentrations in the U.S. population: Implications for urinary biologic monitoring measurements","volume":"113","author":"Barr","year":"2005","journal-title":"Environ. Health Perspect."},{"key":"ref_31","unstructured":"Kuczmarski, R.J., Ogden, C.L., Grummer-Strawn, L.M., Flegal, K.M., Guo, S.S., Wei, R., Mei, Z., Curtin, L.R., Roche, A.F., and Johnson, C.L. (2000). CDC Growth Charts: United States, Advance Data."},{"key":"ref_32","unstructured":"CDC, Centers for Disease Control and Prevention (2024, January 26). National Report on Human Exposure to Environmental Chemicals (NHANES). Data Sources and Data Analysis, Available online: www.cdc.gov\/exposurereport\/data_sources_analysis.html."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3614","DOI":"10.1080\/03610926.2015.1066818","article-title":"Generalized definition of the geometric mean of a non negative random variable","volume":"46","author":"Feng","year":"2017","journal-title":"Commun. Stat. Theory Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1044\/2016_AJA-15-0060","article-title":"Minimal Hearing Loss: From a Failure-Based Approach to Evidence-Based Practice","volume":"25","author":"Winiger","year":"2016","journal-title":"Am. J. Audiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1097\/00003446-199810000-00001","article-title":"Children with minimal sensorineural hearing loss: Prevalence, educational performance, and functional status","volume":"19","author":"Bess","year":"1998","journal-title":"Ear Hear."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Theunissen, S.C., Rieffe, C., Netten, A.P., Briaire, J.J., Soede, W., Kouwenberg, M., and Frijns, J.H. (2014). Self-esteem in hearing-impaired children: The influence of communication, education, and audiological characteristics. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094521"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/j.ijporl.2011.07.023","article-title":"Depression in hearing-impaired children","volume":"75","author":"Theunissen","year":"2011","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"245","DOI":"10.5271\/sjweh.1477","article-title":"Effects of occupational exposure to organic solvents and noise on hearing","volume":"19","author":"Morata","year":"1993","journal-title":"Scand. J. Work Environ. Health"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"410","DOI":"10.4103\/1463-1741.144422","article-title":"A comparison of the effects of solvent and noise exposure on hearing, together and separately","volume":"16","author":"Unlu","year":"2014","journal-title":"Noise Health"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"500","DOI":"10.14639\/0392-100X-1574","article-title":"Acquired sensorineural hearing loss in children: Current research and therapeutic perspectives","volume":"37","author":"Ralli","year":"2017","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.heares.2013.01.021","article-title":"Current concepts in age-related hearing loss: Epidemiology and mechanistic pathways","volume":"303","author":"Yamasoba","year":"2013","journal-title":"Hear Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"34046","DOI":"10.1007\/s11356-018-3354-7","article-title":"Association of benzene exposure with insulin resistance, SOD, and MDA as markers of oxidative stress in children and adolescents","volume":"25","author":"Amin","year":"2018","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.scitotenv.2014.02.121","article-title":"Urinary benzene metabolite and insulin resistance in elderly adults","volume":"482\u2013483","author":"Choi","year":"2014","journal-title":"Sci. Total Environ."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.mrgentox.2013.04.008","article-title":"Genotoxicity and oxidative stress in gasoline station attendants","volume":"754","author":"Moro","year":"2013","journal-title":"Mutat. Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Chang, J., Ryou, N., Jun, H.J., Hwang, S.Y., Song, J.J., and Chae, S.W. (2016). Effect of Cigarette Smoking and Passive Smoking on Hearing Impairment: Data from a Population-Based Study. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146608"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1001\/jama.279.21.1715","article-title":"Cigarette smoking and hearing loss: The epidemiology of hearing loss study","volume":"279","author":"Cruickshanks","year":"1998","journal-title":"JAMA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.shaw.2016.09.004","article-title":"Urinary trans,trans-muconic acid is not a reliable biomarker for low-level environmental and occupational benzene exposures","volume":"8","author":"Jalai","year":"2017","journal-title":"Saf. Health Work"},{"key":"ref_48","first-page":"47","article-title":"Urinary trans,trans-muconic acid as an indicator of exposure to benzene in cigarette smokers","volume":"2","author":"Melikian","year":"1993","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0378-4347(98)00065-6","article-title":"Analysis and evaluation of trans,trans-muconic acid as a biomarker for benzene exposure","volume":"717","author":"Scherer","year":"1998","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.cbi.2010.01.022","article-title":"Defining the contribution of non-benzene sources of benzene metabolites in urine: Implications for biomonitoring and risk assessment","volume":"184","author":"Arnold","year":"2010","journal-title":"Chem. Biol. Interact."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1080\/00039890209602940","article-title":"Lack of sensitivity of urinary trans,trans-muconic acid in determining low-level (ppb) benzene exposure in children","volume":"57","author":"Barbieri","year":"2002","journal-title":"Arch. Environ. Health"},{"key":"ref_52","first-page":"749","article-title":"Lack of specificity of trans,trans-muconic acid as a benzene biomarker after ingestion of sorbic acid-preserved foods","volume":"9","author":"Weaver","year":"2000","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_53","first-page":"545640","article-title":"Benzene as a chemical hazard in processed foods","volume":"2015","year":"2015","journal-title":"Int. J. Food Sci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Walczak-Nowicka, \u0141.J., and Herbet, M. (2022). Sodium benzoate-harmfulness and potential use in therapies for disorders related to the nervous system: A review. Nutrients, 14.","DOI":"10.3390\/nu14071497"}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/3\/191\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:06:50Z","timestamp":1760105210000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/3\/191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,29]]},"references-count":54,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["toxics12030191"],"URL":"https:\/\/doi.org\/10.3390\/toxics12030191","relation":{},"ISSN":["2305-6304"],"issn-type":[{"type":"electronic","value":"2305-6304"}],"subject":[],"published":{"date-parts":[[2024,2,29]]}}}