{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T01:55:05Z","timestamp":1785462905947,"version":"3.56.0"},"reference-count":76,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R01 ES030722"],"award-info":[{"award-number":["R01 ES030722"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["P30 ES020957"],"award-info":[{"award-number":["P30 ES020957"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Urban environments are plagued by complex mixtures of anthropogenic volatile organic compounds (VOCs), such as mixtures of benzene, toluene, ethylene, and xylene (BTEX). Sources of BTEX that drive human exposure include vehicle exhaust, industrial emissions, off-gassing of building material, as well as oil spillage and leakage. Among the BTEX mixture, benzene is the most volatile compound and has been linked to numerous adverse health outcomes. However, few studies have focused on the effects of low-level benzene on exposure during early development, which is a susceptible window when hematological, immune, metabolic, and detoxification systems are immature. In this study, we used zebrafish to conduct a VOC exposure model and evaluated phenotypic and transcriptomic responses following 0.1 and 1 ppm benzene exposure during the first five days of embryogenesis (n = 740 per treatment). The benzene body burden was 2 mg\/kg in 1 ppm-exposed larval zebrafish pools and under the detection limit in 0.1 ppm-exposed fish. No observable phenotypic changes were found in both larvae except for significant skeletal deformities in 0.1 ppm-exposed fish (p = 0.01) compared with unexposed fish. Based on transcriptomic responses, 1 ppm benzene dysregulated genes that were implicated with the development of hematological system, and the regulation of oxidative stress response, fatty acid metabolism, immune system, and inflammatory response, including apob, nfkbiaa, serpinf1, foxa1, cyp2k6, and cyp2n13 from the cytochrome P450 gene family. Key genes including pik3c2b, pltp, and chia.2 were differentially expressed in both 1 and 0.1 ppm exposures. However, fewer transcriptomic changes were induced by 0.1 ppm compared with 1 ppm. Future studies are needed to determine if these transcriptomic responses during embryogenesis have long-term consequences at levels equal to or lower than 1 ppm.<\/jats:p>","DOI":"10.3390\/toxics10070351","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:07:02Z","timestamp":1656374822000},"page":"351","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Evaluating Phenotypic and Transcriptomic Responses Induced by Low-Level VOCs in Zebrafish: Benzene as an Example"],"prefix":"10.3390","volume":"10","author":[{"given":"Chia-Chen","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Global and Environmental Health, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica R.","family":"Blount","sequence":"additional","affiliation":[{"name":"Institute of Environmental Health Sciences, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Haimbaugh","sequence":"additional","affiliation":[{"name":"Institute of Environmental Health Sciences, Wayne State University, Detroit, MI 48202, USA"},{"name":"Department of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8348-1975","authenticated-orcid":false,"given":"Samantha","family":"Heldman","sequence":"additional","affiliation":[{"name":"Institute of Environmental Health Sciences, Wayne State University, Detroit, MI 48202, USA"},{"name":"Department of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5767-4626","authenticated-orcid":false,"given":"Jeremiah N.","family":"Shields","sequence":"additional","affiliation":[{"name":"Institute of Environmental Health Sciences, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracie R.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Global and Environmental Health, University of Florida, Gainesville, FL 32610, USA"},{"name":"Institute of Environmental Health Sciences, Wayne State University, Detroit, MI 48202, USA"},{"name":"Department of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.scitotenv.2012.02.018","article-title":"Human Health Risk Assessment of Air Emissions from Development of Unconventional Natural Gas Resources","volume":"424","author":"McKenzie","year":"2012","journal-title":"Sci. Total Environ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.atmosenv.2012.07.041","article-title":"Multi-Season, Multi-Year Concentrations and Correlations amongst the BTEX Group of VOCs in an Urbanized Industrial City","volume":"61","author":"Miller","year":"2012","journal-title":"Atmos. Environ."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.chemosphere.2016.07.088","article-title":"Investigation of Outdoor BTEX: Concentration, Variations, Sources, Spatial Distribution, and Risk Assessment","volume":"163","author":"Miri","year":"2016","journal-title":"Chemosphere"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"86","DOI":"10.26502\/jesph.9612009","article-title":"Sources and Fates of BTEX in the General Environment and Its Distribution in Coastal Cities of China","volume":"1","author":"Duan","year":"2017","journal-title":"J. Environ. Sci. Public Health"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Miller, C.J., Runge-Morris, M., Cassidy-Bushrow, A.E., Straughen, J.K., Dittrich, T.M., Baker, T.R., Petriello, M.C., Mor, G., Ruden, D.M., and O\u2019leary, B.F. (2020). A Review of Volatile Organic Compound Contamination in Post-Industrial Urban Centers: Reproductive Health Implications Using a Detroit Lens. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17238755"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"103518","DOI":"10.1016\/j.etap.2020.103518","article-title":"Effects of Inhaled Combined Benzene, Toluene, Ethylbenzene, and Xylenes (BTEX): Toward an Environmental Exposure Model","volume":"81","author":"Davidson","year":"2021","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.taap.2014.02.012","article-title":"Current Understandings and Perspectives on Non-Cancer Health Effects of Benzene: A Global Concern","volume":"276","author":"Bahadar","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1289\/ehp.0800465","article-title":"Maternal Personal Exposure to Airborne Benzene and Intrauterine Growth","volume":"117","author":"Slama","year":"2009","journal-title":"Environ. Health Perspect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1136\/oem.57.10.661","article-title":"Exposure to Benzene, Occupational Stress, and Reduced Birth Weight","volume":"57","author":"Chen","year":"2000","journal-title":"Occup. Environ. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0048-9697(02)00228-0","article-title":"Hematological Changes of Children Exposed to Volatile Organic Compounds Containing Low Levels of Benzene","volume":"299","author":"Lee","year":"2002","journal-title":"Sci. Total Environ."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/08880018.2013.831511","article-title":"Health Effects of Benzene Exposure among Children Following a Flaring Incident at the British Petroleum Refinery in Texas City","volume":"31","author":"Reddy","year":"2014","journal-title":"Pediatr. Hematol. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1177\/0009922815594358","article-title":"Adverse Health Effects of Benzene Exposure among Children Following a Flaring Incident at the British Petroleum Refinery in Texas City","volume":"55","author":"Reddy","year":"2016","journal-title":"Clin. Pediatr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1289\/ehp.0800510","article-title":"Evidence That Humans Metabolize Benzene via Two Pathways","volume":"117","author":"Rappaport","year":"2009","journal-title":"Environ. Health Perspect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"673","DOI":"10.3109\/03602538409041076","article-title":"Correlation of Benzene Metabolism and Histological Lesions in Rainbow Trout (Salmo Gairdneri)","volume":"15","author":"Cooper","year":"1984","journal-title":"Drug Metab. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1177\/0960327107083974","article-title":"Benzene\u2019s Toxicity: A Consolidated Short Review of Human and Animal Studies by HA Khan","volume":"26","author":"Khan","year":"2007","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Spatari, G., Allegra, A., Carrieri, M., Pioggia, G., and Gangemi, S. (2021). Epigenetic Effects of Benzene in Hematologic Neoplasms: The Altered Gene Expression. Cancers, 13.","DOI":"10.3390\/cancers13102392"},{"key":"ref_17","first-page":"2333794X18789275","article-title":"Health Risks Associated with Benzene Exposure in Children: A Systematic Review","volume":"5","author":"Reddy","year":"2018","journal-title":"Glob. Pediatr. Health"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nature12111","article-title":"The Zebrafish Reference Genome Sequence and Its Relationship to the Human Genome","volume":"496","author":"Howe","year":"2013","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S1074-7613(04)00084-6","article-title":"The Use of Zebrafish to Understand Immunity","volume":"20","author":"Trede","year":"2004","journal-title":"Immunity"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.exphem.2014.06.001","article-title":"Developmental Hematopoiesis: Ontogeny, Genetic Programming and Conservation","volume":"42","author":"Monteiro","year":"2014","journal-title":"Exp. Hematol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4016","DOI":"10.1002\/1873-3468.12415","article-title":"Understanding the Regulation of Vertebrate Hematopoiesis and Blood Disorders\u2014Big Lessons from a Small Fish","volume":"590","author":"Robertson","year":"2016","journal-title":"FEBS Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5641","DOI":"10.4049\/jimmunol.0900082","article-title":"Transcriptome Profiling and Functional Analyses of the Zebrafish Embryonic Innate Immune Response to Salmonella Infection","volume":"182","author":"Stockhammer","year":"2009","journal-title":"J. Immunol."},{"key":"ref_23","unstructured":"National Research Council (2010). Guide for the Care and Use of Laboratory Animals, The National Academies Press. [8th ed.]."},{"key":"ref_24","unstructured":"(2006). U.S. Environmental Protection Agency. Method 8260C Volatile Organic Compounds by Gas Chromatography\/Mass Spectrometry (GC\/MS), U.S. Environmental Protection Agency."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/sj.embor.7400919","article-title":"Phosphoinositide-metabolizing Enzymes at the Interface between Membrane Traffic and Cell Signalling","volume":"8","author":"Haucke","year":"2007","journal-title":"EMBO Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/nature05185","article-title":"Phosphoinositides in Cell Regulation and Membrane Dynamics","volume":"443","year":"2006","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/mi.2009.3","article-title":"MEP1A Allele for Meprin A Metalloprotease Is a Susceptibility Gene for Inflammatory Bowel Disease","volume":"2","author":"Banerjee","year":"2009","journal-title":"Mucosal. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sch\u00fctte, A., Hedrich, J., St\u00f6cker, W., and Becker-Pauly, C. (2010). Let It Flow: Morpholino Knockdown in Zebrafish Embryos Reveals a pro-Angiogenic Effect of the Metalloprotease Meprin A2. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008835"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3544","DOI":"10.1096\/fj.09-152876","article-title":"Innate Immune Response Triggered by Triacyl Lipid a is Dependent on Phospholipid Transfer Protein (PLTP) Gene Expression","volume":"24","author":"Gautier","year":"2010","journal-title":"FASEB J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.gep.2014.01.001","article-title":"Spatial and Temporal Expression Patterns of Chitinase Genes in Developing Zebrafish Embryos","volume":"14","author":"Koch","year":"2014","journal-title":"Gene Expr. Patterns"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1002\/lary.20863","article-title":"Increased Expression of Acidic Mammalian Chitinase and Chitotriosidase in the Nasal Mucosa of Patients with Allergic Rhinitis","volume":"120","author":"Cho","year":"2010","journal-title":"Laryngoscope"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e03613","DOI":"10.7554\/eLife.03613","article-title":"TAF4, a Subunit of Transcription Factor II D, Directs Promoter Occupancy of Nuclear Receptor HNF4A during Post-Natal Hepatocyte Differentiation","volume":"3","author":"Alpern","year":"2014","journal-title":"Elife"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11063","DOI":"10.1038\/ncomms11063","article-title":"Essential Role of the TFIID Subunit TAF4 in Murine Embryogenesis and Embryonic Stem Cell Differentiation","volume":"7","author":"Langer","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4984","DOI":"10.1016\/j.febslet.2006.08.025","article-title":"Functions of the MAPK Family in Vertebrate-Development","volume":"580","author":"Krens","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Verbueken, E., Bars, C., Ball, J.S., Periz-Stanacev, J., Marei, W.F.A., Tochwin, A., Gabri\u00ebls, I.J., Michiels, E.D.G., Stinckens, E., and Vergauwen, L. (2018). From MRNA Expression of Drug Disposition Genes to in Vivo Assessment of CYP-Mediated Biotransformation during Zebrafish Embryonic and Larval Development. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123976"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Nawaji, T., Yamashita, N., Umeda, H., Zhang, S., Mizoguchi, N., Seki, M., Kitazawa, T., and Teraoka, H. (2020). Cytochrome P450 Expression and Chemical Metabolic Activity before Full Liver Development in Zebrafish. Pharmaceuticals, 13.","DOI":"10.3390\/ph13120456"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1073\/pnas.0712195105","article-title":"Anthrax Lethal Toxin Induces Cell Death-Independent Permeability in Zebrafish Vasculature","volume":"105","author":"Bolcome","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/nm.2759","article-title":"ApoB-Containing Lipoproteins Regulate Angiogenesis by Modulating Expression of VEGF Receptor 1","volume":"18","author":"Ely","year":"2012","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.dci.2014.01.010","article-title":"Complement System in Zebrafish","volume":"46","author":"Zhang","year":"2014","journal-title":"Dev. Comp. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"ra120","DOI":"10.1126\/scisignal.aaf1129","article-title":"Late-Phase Synthesis of I\u03baB\u03b1 Insulates the TLR4-Activated Canonical NF-\u039aB Pathway from Noncanonical NF-\u039aB Signaling in Macrophages","volume":"9","author":"Chatterjee","year":"2016","journal-title":"Sci. Signal."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.cmet.2005.07.002","article-title":"Foxa2 Integrates the Transcriptional Response of the Hepatocyte to Fasting","volume":"2","author":"Zhang","year":"2005","journal-title":"Cell Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1172\/JCI18698","article-title":"Role of Foxa-2 in Adipocyte Metabolism and Differentiation","volume":"112","author":"Wolfrum","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.ydbio.2010.12.018","article-title":"FoxA Transcription Factors Are Essential for the Development of Dorsal Axial Structures","volume":"350","author":"Thisse","year":"2011","journal-title":"Dev. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1042\/BCJ20160392","article-title":"Foxa2 and Hif1ab Regulate Maturation of Intestinal Goblet Cells by Modulating Agr2 Expression in Zebrafish Embryos","volume":"473","author":"Lai","year":"2016","journal-title":"Biochem. J."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Phua, W.W.T., Tan, W.R., Yip, Y.S., Hew, I.D., Wee, J.W.K., Cheng, H.S., Leow, M.K.S., Wahli, W., and Tan, N.S. (2020). PPAR\u03b2\/\u03b4 Agonism Upregulates Forkhead Box A2 to Reduce Inflammation in C2C12 Myoblasts and in Skeletal Muscle. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051747"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.2337\/db10-0845","article-title":"Pigment Epithelium-Derived Factor Regulates Lipid Metabolism via Adipose Triglyceride Lipase","volume":"60","author":"Borg","year":"2011","journal-title":"Diabetes"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11501","DOI":"10.1158\/0008-5472.CAN-05-2262","article-title":"Headpin: A Serpin with Endogenous and Exogenous Suppression of Angiogenesis","volume":"65","author":"Shellenberger","year":"2005","journal-title":"Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1053\/j.gastro.2015.08.034","article-title":"Zebrafish: An Important Tool for Liver Disease Research","volume":"149","author":"Goessling","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_49","first-page":"1","article-title":"Benzene Metabolism in Rodents at Doses Relevant to Human Exposure from Urban Air","volume":"113","author":"Turteltaub","year":"2003","journal-title":"Res. Rep. Health Eff. Inst."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"863","DOI":"10.3109\/08958378.2011.609918","article-title":"Assessing the Impact of the Duration and Intensity of Inhalation Exposure on the Magnitude of the Variability of Internal Dose Metrics in Children and Adults","volume":"23","author":"Valcke","year":"2011","journal-title":"Inhal. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1080\/15287397909529789","article-title":"Partial Hepatectomy Reduces Both Metabolism and Toxicity of Benzene","volume":"5","author":"Sammett","year":"1979","journal-title":"J. Toxicol. Environ. Health Part A Curr. Issues"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1080\/15287390490273488","article-title":"Kinetic Factors Involved in the Metabolism of Benzene in Mouse Lung and Liver","volume":"67","author":"Sheets","year":"2004","journal-title":"J. Toxicol. Environ. Health Part A"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1083\/jcb.150.6.1335","article-title":"Asymmetric P38 Activation in Zebrafish: Its Possible Role in Symmetric and Synchronous Cleavage","volume":"150","author":"Fujii","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_54","unstructured":"Wilbur, S.B., Keith, S., Faroon, O., and Wohlers, D. (2007). Toxicological Profile for Benzene, U.S. Department of Health & Human Services."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.scitotenv.2013.11.089","article-title":"Differential Gene Expression Profiling Analysis in Workers Occupationally Exposed to Benzene","volume":"472","author":"Gao","year":"2014","journal-title":"Sci. Total Environ."},{"key":"ref_56","first-page":"1211","article-title":"Cytochromes P450 in Benzene Metabolism and Involvement of Their Metabolites and Reactive Oxygen Species in Toxicity","volume":"104","author":"Gut","year":"1996","journal-title":"Environ. Health Perspect."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Thomas, R., Hubbard, A.E., McHale, C.M., Zhang, L., Rappaport, S.M., Lan, Q., Rothman, N., Vermeulen, R., Guyton, K.Z., and Jinot, J. (2014). Characterization of Changes in Gene Expression and Biochemical Pathways at Low Levels of Benzene Exposure. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091828"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.mce.2015.09.030","article-title":"Lxr Regulates Lipid Metabolic and Visual Perception Pathways during Zebrafish Development","volume":"419","author":"Pinto","year":"2016","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Sun, R., Cao, M., Zhang, J., Yang, W., Wei, H., Meng, X., Yin, L., and Pu, Y. (2016). Benzene Exposure Alters Expression of Enzymes Involved in Fatty Acid \u03b2-Oxidation in Male C3H\/He Mice. Int. J. Environ. Res. Public Health, 13.","DOI":"10.3390\/ijerph13111068"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"32506","DOI":"10.1007\/s11356-018-3160-2","article-title":"Plasma Metabonomics Investigation Reveals Involvement of Fatty Acid Oxidation in Hematotoxicity in Chinese Benzene-Exposed Workers with Low White Blood Cell Count","volume":"25","author":"Sun","year":"2018","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1038\/nm.2882","article-title":"A PML\u2013PPAR-\u03b4 Pathway for Fatty Acid Oxidation Regulates Hematopoietic Stem Cell Maintenance","volume":"18","author":"Ito","year":"2012","journal-title":"Nat. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nrm3772","article-title":"Metabolic Requirements for the Maintenance of Self-Renewing Stem Cells","volume":"15","author":"Ito","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_63","first-page":"1925","article-title":"Targeting the Leukemia Cell Metabolism by the CPT1a Inhibition: Functional Preclinical Effects in Leukemias","volume":"126","author":"Ricciardi","year":"2015","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1172\/JCI38942","article-title":"Pharmacologic Inhibition of Fatty Acid Oxidation Sensitizes Human Leukemia Cells to Apoptosis Induction","volume":"120","author":"Samudio","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"111562","DOI":"10.1016\/j.ecoenv.2020.111562","article-title":"Association between Benzene Exposure, Serum Levels of Cytokines and Hematological Measures in Chinese Workers: A Cross-Sectional Study","volume":"207","author":"Wang","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"103305","DOI":"10.1016\/j.jri.2021.103305","article-title":"Ambient BTEX Exposure and Mid-Pregnancy Inflammatory Biomarkers in Pregnant African American Women","volume":"145","author":"Burmeister","year":"2021","journal-title":"J. Reprod. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"937987","DOI":"10.1155\/2014\/937987","article-title":"Cytokine Network Involvement in Subjects Exposed to Benzene","volume":"2014","author":"Minciullo","year":"2014","journal-title":"J. Immunol. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3389\/fonc.2018.00160","article-title":"Phosphoinositide 3-Kinase\/Akt Signaling and Redox Metabolism in Cancer","volume":"8","author":"Koundouros","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1146\/annurev-immunol-032712-095946","article-title":"Signalling by the Phosphoinositide 3-Kinase Family in Immune Cells","volume":"31","author":"Okkenhaug","year":"2013","journal-title":"Annu. Rev. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1177\/09680519050110020501","article-title":"Apolipoproteins Modulate the Inflammatory Response to Lipopolysaccharide","volume":"11","author":"Havekes","year":"2005","journal-title":"J. Endotoxin Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"a001651","DOI":"10.1101\/cshperspect.a001651","article-title":"The Nuclear Factor NF-KappaB Pathway in Inflammation","volume":"1","author":"Lawrence","year":"2009","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.cbi.2010.01.007","article-title":"Low Level Occupational Benzene Exposure and Hematological Parameters","volume":"184","author":"Swaen","year":"2010","journal-title":"Chem. Biol. Interact."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1093\/jnci\/djs411","article-title":"Myelodysplastic Syndrome and Benzene Exposure among Petroleum Workers: An International Pooled Analysis","volume":"104","author":"Schnatter","year":"2012","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1126\/science.1102443","article-title":"Hematotoxicity in Workers Exposed to Low Levels of Benzene","volume":"306","author":"Lan","year":"2004","journal-title":"Science"},{"key":"ref_75","first-page":"3","article-title":"Personal Exposure to Mixtures of Volatile Organic Compounds: Modeling and Further Analysis of the RIOPA Data","volume":"181","author":"Batterman","year":"2014","journal-title":"Res. Rep. Health. Eff. Inst."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.fct.2017.03.012","article-title":"Human Exposure to Chemical Mixtures: Challenges for the Integration of Toxicology with Epidemiology Data in Risk Assessment","volume":"103","author":"Tsatsakis","year":"2017","journal-title":"Food Chem. Toxicol."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/10\/7\/351\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:39:02Z","timestamp":1760139542000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/10\/7\/351"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,27]]},"references-count":76,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["toxics10070351"],"URL":"https:\/\/doi.org\/10.3390\/toxics10070351","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,27]]}}}