{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T13:01:18Z","timestamp":1754398878058,"version":"3.41.2"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T00:00:00Z","timestamp":1649289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Chem."],"abstract":"<jats:p>Chemicals of unknown inhalational toxicity are present in electronic cigarette and vaping products. E-cigarettes typically contain nicotine and other relatively hydrophilic chemicals while vaping products typically contain cannabinoids and other hydrophobic chemicals. For example, vaping products can include hydrophobic terpenes such as squalane (SQA) and squalene (SQE). However, little is known about the SQA and SQE transmission from liquid to aerosol. SQA and SQE are used in commercial products that are applied dermally and ingested orally, but limited information is available on their inhalational exposure and toxicity. We developed and validated a quantitative method to measure SQE and SQA in bronchoalveolar lavage fluid to assess if these chemicals accumulate in lung epithelial lining fluid after inhalation. Calibration curves spanned a range of 0.50\u201330.0\u00a0\u00b5g analyte per mL bronchoalveolar lavage fluid. Recoveries were found to be 97\u2013105% for SQE and 81\u2013106% for SQA. Limits of detection were 0.50\u00a0\u03bcg\/ml for both SQE and SQA. The method was applied to bronchoalveolar lavage fluid samples of patients from the 2019 outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) and a comparison group. Neither SQA nor SQE was detected above the method LOD for any samples analyzed; conversely, SQA or SQE were reproducibly measured in spiked quality control BAL fluids (relative standards deviations &amp;lt;15% for both analytes). Further applications of this method may help to evaluate the potential toxicity of SQA and SQE chronically inhaled from EVPs.<\/jats:p>","DOI":"10.3389\/fchem.2022.874373","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T05:08:30Z","timestamp":1649308110000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["The Quantitation of Squalene and Squalane in Bronchoalveolar Lavage Fluid Using Gas Chromatography Mass Spectrometry"],"prefix":"10.3389","volume":"10","author":[{"given":"Elizabeth A.","family":"Cowan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Tran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clifford H.","family":"Watson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin C.","family":"Blount","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liza","family":"Valent\u00edn-Blasini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e2019176","DOI":"10.1001\/jamanetworkopen.2020.19176","article-title":"Clinical, Bronchoscopic, and Imaging Findings of E-Cigarette, or Vaping, Product Use-Associated Lung Injury Among Patients Treated at an Academic Medical Center","volume":"3","author":"Aberegg","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1080\/10942912.2020.1833033","article-title":"Measurement of Squalene in Olive Oil by Fractional Crystallization or Headspace Solid Phase Microextraction Coupled with Gas Chromatography","volume":"23","author":"Aresta","year":"2020","journal-title":"Int. J. Food Properties"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1056\/NEJMc2000231","article-title":"An Animal Model of Inhaled Vitamin E Acetate and EVALI-like Lung Injury","volume":"382","author":"Bhat","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1056\/NEJMoa1916433","article-title":"Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI","volume":"382","author":"Blount","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.envint.2014.05.021","article-title":"Development and Application of an Inhalation Bioaccessibility Method (IBM) for lead in the PM10 Size Fraction of Soil","volume":"70","author":"Boisa","year":"2014","journal-title":"Environ. Int."},{"key":"B6","doi-asserted-by":"publisher","first-page":"106345","DOI":"10.1016\/j.addbeh.2020.106345","article-title":"How Are Adolescents Getting Their Vaping Products? Findings from the International Tobacco Control (ITC) Youth Tobacco and Vaping Survey","volume":"105","author":"Braak","year":"2020","journal-title":"Addict. Behaviors"},{"key":"B7","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1021\/acsomega.1c04815","article-title":"Rapid Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method to Measure Cannabinoids in Bronchoalveolar-Lavage Fluid of Patients with E-Cigarette, or Vaping, Product Use-Associated Lung Injury","volume":"7","author":"Brosius","year":"2022","journal-title":"ACS Omega"},{"key":"B8","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.mex.2018.12.001","article-title":"Determination of Squalene in Edible Oils by Transmethylation and GC Analysis","volume":"6","author":"Budge","year":"2019","journal-title":"MethodsX"},{"key":"B9","doi-asserted-by":"publisher","first-page":"4094","DOI":"10.1002\/sim.3222","article-title":"Multi-rule Quality Control for the Age-Related Eye Disease Study","volume":"27","author":"Caudill","year":"2008","journal-title":"Statist. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1111\/crj.13015","article-title":"Clinical and Radiological Manifestations of Lipoid Pneumonia According to Etiology: Squalene, omega\u20103\u2010acid Ethyl Esters, and Idiopathic","volume":"13","author":"Cha","year":"2019","journal-title":"Clin. Respir. J."},{"key":"B11","doi-asserted-by":"publisher","first-page":"122985","DOI":"10.1016\/j.talanta.2021.122985","article-title":"A Gas Chromatography-Mass Spectrometry Method for Quantifying Squalane and Squalene in Aerosol Emissions of Electronic Cigarette, or Vaping, Products","volume":"238","author":"Cowan","year":"2022","journal-title":"Talanta"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.15585\/mmwr.mm6745a5","article-title":"Notes From the Field: Use of Electronic Cigarettes and Any Tobacco Product Among Middle and High School Students - United States, 2011-2018","volume":"67","author":"Cullen","year":"2018","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1001\/jama.2019.18387","article-title":"E-Cigarette Use Among Youth in the United States, 2019","volume":"322","author":"Cullen","year":"2019","journal-title":"Jama"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e8898","DOI":"10.1002\/rcm.8898","article-title":"Novel Methods for the Analysis of Toxicants in Bronchoalveolar Lavage Fluid Samples from E-Cigarette, or Vaping, Product Use-Associated Lung Injury Cases: Selected Petroleum Distillates","volume":"34","author":"De Jes\u00fas","year":"","journal-title":"Rapid Commun. Mass. Spectrom."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.8879","article-title":"Novel Methods for the Analysis of Toxicants in Bronchoalveolar Lavage Fluid Samples from E\u2010cigarette, or Vaping, Product Use Associated Lung Injury (EVALI) Cases: Terpenes","volume":"34","author":"De Jes\u00fas","year":"","journal-title":"Rapid Commun. Mass. Spectrom."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1093\/ntr\/nty192","article-title":"Formation of Flavorant-Propylene Glycol Adducts with Novel Toxicological Properties in Chemically Unstable E-Cigarette Liquids","volume":"21","author":"Erythropel","year":"2019","journal-title":"Nicotine Tob. Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/7151834","article-title":"Vaping-Induced Lung Injury: A Case of Lipoid Pneumonia Associated with E-Cigarettes Containing Cannabis","volume":"2020","author":"Gay","year":"2020","journal-title":"Case Rep. Pulmonology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"695940","DOI":"10.3389\/fchem.2021.695940","article-title":"A Novel UHPLC-MS\/MS Method for Measuring 8-Iso-Prostaglandin F2\u03b1 in Bronchoalveolar Lavage Fluid","volume":"9","author":"Holder","year":"2021","journal-title":"Front. Chem."},{"key":"B19","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1097\/maj.0b013e31811ec1a0","article-title":"Positron Emission Tomography-Positive Squalene-Induced Lipoid Pneumonia Confirmed by Gas Chromatography-Mass Spectrometry of Bronchoalveolar Lavage Fluid","volume":"335","author":"Kanaji","year":"2008","journal-title":"Am. J. Med. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1111\/j.1442-200X.2009.02902.x","article-title":"Squalene-induced Exogenous Lipoid Pneumonia in an Infant","volume":"51","author":"Kim","year":"2009","journal-title":"Pediatr. Int."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1001\/jama.2018.10488","article-title":"Electronic Cigarette Sales in the United States, 2013-2017","volume":"320","author":"King","year":"2018","journal-title":"Jama"},{"key":"B22","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1056\/NEJMp1916171","article-title":"The EVALI and Youth Vaping Epidemics - Implications for Public Health","volume":"382","author":"King","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.jadohealth.2018.07.012","article-title":"Emerging Trends in Cannabis Administration Among Adolescent Cannabis Users","volume":"64","author":"Knapp","year":"2019","journal-title":"J. Adolesc. Health"},{"key":"B24","doi-asserted-by":"publisher","first-page":"10","DOI":"10.18001\/TRS.3.1.2","article-title":"Sources of Electronic Cigarette Acquisition Among Adolescents in Connecticut","volume":"3","author":"Kong","year":"2017","journal-title":"Tobacco Reg. Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1093\/ntr\/ntu078","article-title":"Carbonyl Compounds in Electronic Cigarette Vapors: Effects of Nicotine Solvent and Battery Output Voltage","volume":"16","author":"Kosmider","year":"2014","journal-title":"Nicotine Tob. Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.drugalcdep.2015.12.020","article-title":"Online Survey Characterizing Vaporizer Use Among Cannabis Users","volume":"159","author":"Lee","year":"2016","journal-title":"Drug and Alcohol Dependence"},{"key":"B27","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1007\/s003300050669","article-title":"Exogenous Lipoid Pneumonia: High-Resolution CT Findings","volume":"9","author":"Lee","year":"1999","journal-title":"Eur. Radiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/s0022-2275(20)37014-0","article-title":"Measurement of Squalene in Human Tissues and Plasma: Validation and Application","volume":"17","author":"Liu","year":"1976","journal-title":"J. Lipid Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1542\/peds.2019-0338","article-title":"Cannabis Concentrate Use in Adolescents","volume":"144","author":"Meier","year":"2019","journal-title":"Pediatrics"},{"key":"B30","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1001\/jamapediatrics.2020.5667","article-title":"Trends in Use and Perceptions of Nicotine Vaping Among US Youth from 2017 to 2020","volume":"175","author":"Miech","year":"2021","journal-title":"JAMA Pediatr."},{"key":"B31","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1080\/10826084.2016.1268162","article-title":"Predictors of Adult E-Cigarette Users Vaporizing Cannabis Using E-Cigarettes and Vape-Pens","volume":"52","author":"Morean","year":"2017","journal-title":"Substance Use & Misuse"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jchromb.2021.122607","article-title":"Liquid Chromatography-Tandem Mass Spectrometry Method for Measuring Vitamin E Acetate in Bronchoalveolar Lavage Fluid","volume":"1171","author":"Morel Espinosa","year":"2021","journal-title":"J. Chromatogr. B"},{"key":"B33","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.foodcont.2019.03.005","article-title":"Simple and Rapid Method to Analyse Squalene in Olive Oils and Extra virgin Olive Oils","volume":"102","author":"Pacetti","year":"2019","journal-title":"Food Control"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1016\/S2213-2600(20)30321-0","article-title":"Pathological Findings in Suspected Cases of E-Cigarette, or Vaping, Product Use-Associated Lung Injury (EVALI): a Case Series","volume":"8","author":"Reagan-Steiner","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1016\/j.addr.2009.09.005","article-title":"Squalene: A Natural Triterpene for Use in Disease Management and Therapy","volume":"61","author":"Reddy","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B36","article-title":"E-cigarette Unit Sales, by Product and Flavor Type- United States, 2014-2020","volume-title":"Morbidity and Mortality Weekly Report, MMWR.","author":"Romeh","year":"2018"},{"key":"B37","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.jchromb.2017.07.031","article-title":"Development, Validation and Application of a GC-MS Method for the Simultaneous Detection and Quantification of Neutral Lipid Species in Trypanosoma Cruzi","author":"Santiva\u00f1ez-Veliz","year":"2017","journal-title":"J. Chromatogr. B"},{"key":"B38","article-title":"College Students & Adults Ages 19-60","volume-title":"Monitoring the Future National Survey Results on Drug Use 1975-2019: Volume II","author":"Schulenberg","year":"2019"},{"key":"B39","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.jradnu.2020.09.005","article-title":"E-cigarette or Vaping Product Use-Associated Lung Injury: A Case Study and Review of the Literature","volume":"39","author":"Shah","year":"2020","journal-title":"J. Radiol. Nurs."},{"key":"B40","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1158\/1055-9965.EPI-19-1245","article-title":"Biomarkers of Exposure and Effect in the Lungs of Smokers, Nonsmokers, and Electronic Cigarette Users","volume":"29","author":"Song","year":"2020","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"B41","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.copsyc.2019.04.002","article-title":"Changing Landscape of Cannabis: Novel Products, Formulations, and Methods of Administration","volume":"30","author":"Spindle","year":"2019","journal-title":"Curr. Opin. Psychol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1164\/rccm.201808-1467LE","article-title":"Electronic versus Combustible Cigarette Effects on Inflammasome Component Release into Human Lung","volume":"199","author":"Tsai","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B43","doi-asserted-by":"publisher","first-page":"106175","DOI":"10.1016\/j.ypmed.2020.106175","article-title":"Prevalence, Trends, and Distribution of Nicotine and Marijuana Use in E-Cigarettes Among US Adults: The Behavioral Risk Factor Surveillance System 2016-2018","volume":"139","author":"Uddin","year":"2020","journal-title":"Prev. Med."},{"key":"B44","doi-asserted-by":"crossref","DOI":"10.15585\/mmwr.mm6937e1","article-title":"E-cigarette Use Among Middle and High School Students - United States, 2020","volume-title":"Morbidity and Mortality Weekly Report, MMWR","author":"Wang","year":"2020"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1056\/NEJMoa1915314","article-title":"Hospitalizations and Deaths Associated with EVALI","volume":"382","author":"Werner","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1093\/clinchem\/27.3.493","article-title":"A Multi-Rule Shewhart Chart for Quality Control in Clinical Chemistry","volume":"27","author":"Westgard","year":"1981","journal-title":"Clin. Chem."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2357","DOI":"10.1007\/s00216-016-9335-0","article-title":"Gas Chromatography-Mass Spectrometry and Raman Imaging Measurement of Squalene Content and Distribution in Human Hair","volume":"408","author":"Wu","year":"2016","journal-title":"Anal. Bioanal. Chem."},{"key":"B48","doi-asserted-by":"publisher","first-page":"13962","DOI":"10.1021\/acsomega.0c05696","article-title":"Sensitive Quantification of Nicotine in Bronchoalveolar Lavage Fluid by Acetone Precipitation Combined with Isotope-Dilution Liquid Chromatography-Tandem Mass Spectrometry","volume":"6","author":"Xia","year":"2021","journal-title":"ACS Omega"}],"container-title":["Frontiers in Chemistry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fchem.2022.874373\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T05:08:39Z","timestamp":1649308119000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fchem.2022.874373\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,7]]},"references-count":48,"alternative-id":["10.3389\/fchem.2022.874373"],"URL":"https:\/\/doi.org\/10.3389\/fchem.2022.874373","relation":{},"ISSN":["2296-2646"],"issn-type":[{"type":"electronic","value":"2296-2646"}],"subject":[],"published":{"date-parts":[[2022,4,7]]},"article-number":"874373"}}