{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:08:59Z","timestamp":1792804139761,"version":"4.5.0"},"reference-count":121,"publisher":"Oxford University Press (OUP)","issue":"1","funder":[{"name":"The U.S. Environmental Protection Agency through its Office of Research and Development","id":[{"id":"https:\/\/ror.org\/011qyt180","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Inhalation is the most relevant route of volatile organic chemical (VOC) exposure; however, due to unique challenges posed by their chemical properties and poor solubility in aqueous solutions, in vitro chemical safety testing is predominantly performed using direct application dosing\/submerged exposures. To address the difficulties in screening toxic effects of VOCs, our cell culture exposure system permits cells to be exposed to multiple concentrations at air-liquid interface (ALI) in a 24-well format. ALI exposure methods permit direct chemical-to-cell interaction with the test article at physiological conditions. In the present study, BEAS-2B and primary normal human bronchial epithelial cells (pHBEC) are used to assess gene expression, cytotoxicity, and cell viability responses to a variety of volatile chemicals including acrolein, formaldehyde, 1,3-butadiene, acetaldehyde, 1-bromopropane, carbon tetrachloride, dichloromethane, and trichloroethylene. BEAS-2B cells were exposed to all the test agents, whereas pHBECs were only exposed to the latter 4 listed above. The VOC concentrations tested elicited only slight cell viability changes in both cell types. Gene expression changes were analyzed using benchmark dose (BMD) modeling. The BMD for the most sensitive gene set was within one order of magnitude of the threshold-limit value reported by the American Conference of Governmental Industrial Hygienists, and the most sensitive gene sets impacted by exposure correlate to known adverse health effects recorded in epidemiologic and in vivo exposure studies. Overall, our study outlines a novel in vitro approach for evaluating molecular-based points-of-departure in human airway epithelial cell exposure to volatile chemicals.<\/jats:p>","DOI":"10.1093\/toxsci\/kfac040","type":"journal-article","created":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T07:18:37Z","timestamp":1649920717000},"page":"88-107","source":"Crossref","is-referenced-by-count":15,"title":["Benchmark Dose Modeling Approaches for Volatile Organic Chemicals Using a Novel Air-Liquid Interface\n                    <i>In Vitro<\/i>\n                    Exposure System"],"prefix":"10.1093","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3153-8378","authenticated-orcid":false,"given":"Adam M","family":"Speen","sequence":"first","affiliation":[{"name":"Oak Ridge Institute for Science and Education (ORISE) , Oak Ridge, Tennessee 37830, USA"},{"name":"CPHEA, U.S. Environmental Protection Agency, Research Triangle Park , North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica R","family":"Murray","sequence":"additional","affiliation":[{"name":"CPHEA, U.S. Environmental Protection Agency, Research Triangle Park , North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin Todd","family":"Krantz","sequence":"additional","affiliation":[{"name":"CPHEA, U.S. Environmental Protection Agency, Research Triangle Park , North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Davies","sequence":"additional","affiliation":[{"name":"CPHEA, U.S. Environmental Protection Agency, Research Triangle Park , North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Evansky","sequence":"additional","affiliation":[{"name":"CPHEA, U.S. Environmental Protection Agency, Research Triangle Park , North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4317-6391","authenticated-orcid":false,"given":"Joshua A","family":"Harrill","sequence":"additional","affiliation":[{"name":"CCTE, U.S. Environmental Protection Agency, Research Triangle Park , North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9713-6099","authenticated-orcid":false,"given":"Logan J","family":"Everett","sequence":"additional","affiliation":[{"name":"CCTE, U.S. Environmental Protection Agency, Research Triangle Park , North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L","family":"Bundy","sequence":"additional","affiliation":[{"name":"CCTE, U.S. Environmental Protection Agency, Research Triangle Park , North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A","family":"Dailey","sequence":"additional","affiliation":[{"name":"CPHEA, U.S. Environmental Protection Agency, Research Triangle Park , North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jazzlyn","family":"Hill","sequence":"additional","affiliation":[{"name":"CPHEA, U.S. Environmental Protection Agency, Research Triangle Park , North Carolina 27709, USA"},{"name":"Oak Ridge Associated Universities (ORAU), Oak Ridge , Tennessee 37830, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wyatt","family":"Zander","sequence":"additional","affiliation":[{"name":"CPHEA, U.S. Environmental Protection Agency, Research Triangle Park , North Carolina 27709, USA"},{"name":"Oak Ridge Associated Universities (ORAU), Oak Ridge , Tennessee 37830, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Carlsten","sequence":"additional","affiliation":[{"name":"CPHEA, U.S. Environmental Protection Agency, Research Triangle Park , North Carolina 27709, USA"},{"name":"Oak Ridge Associated Universities (ORAU) , Oak Ridge, Tennessee 37830, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Monsees","sequence":"additional","affiliation":[{"name":"CPHEA, U.S. Environmental Protection Agency, Research Triangle Park , North Carolina 27709, USA"},{"name":"Oak Ridge Associated Universities (ORAU) , Oak Ridge, Tennessee 37830, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8286-6577","authenticated-orcid":false,"given":"Jose","family":"Zavala","sequence":"additional","affiliation":[{"name":"MedTec BioLab Inc. , Hillsborough, North Carolina 27278, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6202-2369","authenticated-orcid":false,"given":"Mark A","family":"Higuchi","sequence":"additional","affiliation":[{"name":"CPHEA, U.S. Environmental Protection Agency, Research Triangle Park , North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,4,15]]},"reference":[{"key":"2022062811300054100_kfac040-B1","year":"2018"},{"key":"2022062811300054100_kfac040-B2","first-page":"50","article-title":"Vapor toxicity of carbon tetrachloride determined by experiments on laboratory animals","volume":"6","author":"Adams","year":"1952","journal-title":"AMA Arch. Ind. Hyg. Occup. Med"},{"key":"2022062811300054100_kfac040-B3","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1109\/TAC.1974.1100705","article-title":"New look at statistical-model identification","volume":"AC19","author":"Akaike","year":"1974","journal-title":"IEEE Trans. Automat. Control"},{"key":"2022062811300054100_kfac040-B4","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1080\/10962247.2019.1629355","article-title":"Inhalation exposure to volatile organic compounds in the printing industry","volume":"69","author":"Alabdulhadi","year":"2019","journal-title":"J. Air Waste Manag. Assoc"},{"key":"2022062811300054100_kfac040-B5","first-page":"597","article-title":"Gaseous formaldehyde and hydrogen chloride induction of nasal cancer in the rat","volume":"68","author":"Albert","year":"1982","journal-title":"J. Natl. Cancer Inst"},{"key":"2022062811300054100_kfac040-B6","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/0300-483X(82)90068-3","article-title":"Inhalation toxicity of acetaldehyde in rats. I. Acute and subacute studies","volume":"23","author":"Appelman","year":"1982","journal-title":"Toxicology"},{"key":"2022062811300054100_kfac040-B7","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/jat.2550060506","article-title":"Effect of variable versus fixed exposure levels on the toxicity of acetaldehyde in rats","volume":"6","author":"Appelman","year":"1986","journal-title":"J. Appl. Toxicol"},{"key":"2022062811300054100_kfac040-B8","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/jat.2550080204","article-title":"One-year inhalation toxicity study of formaldehyde in male rats with a damaged or undamaged nasal mucosa","volume":"8","author":"Appelman","year":"1988","journal-title":"J. Appl. Toxicol"},{"key":"2022062811300054100_kfac040-B9","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/0272-0590(86)90184-3","article-title":"The effects of inhalation of organic chemical air contaminants on murine lung host defenses","volume":"6","author":"Aranyi","year":"1986","journal-title":"Fundam. Appl. Toxicol"},{"key":"2022062811300054100_kfac040-B10","year":"2012"},{"key":"2022062811300054100_kfac040-B11","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3109\/08958378.2014.987361","article-title":"Cellular RNA is chemically modified by exposure to air pollution mixtures","volume":"27","author":"Baldridge","year":"2015","journal-title":"Inhal. Toxicol"},{"key":"2022062811300054100_kfac040-B12","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1023\/A:1016244310970","article-title":"Direct calculation of likelihood-based benchmark dose levels for quantitative responses","volume":"9","author":"Banga","year":"2002","journal-title":"Environm. Ecol. Stat"},{"key":"2022062811300054100_kfac040-B13","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1152\/japplphysiol.00706.2002","article-title":"Measuring lung function in mice: The phenotyping uncertainty principle","volume":"94","author":"Bates","year":"2003","journal-title":"J. Appl. Physiol"},{"key":"2022062811300054100_kfac040-B14","year":"1981"},{"key":"2022062811300054100_kfac040-B15","author":"Benson","year":"1999"},{"key":"2022062811300054100_kfac040-B16","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1080\/15287399109531516","article-title":"Effects of acute exposure to formaldehyde on surface morphology of nasal epithelia in rats","volume":"33","author":"Bhalla","year":"1991","journal-title":"J. Toxicol. Environ. Health"},{"key":"2022062811300054100_kfac040-B17","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/0041-008X(84)90295-3","article-title":"Respiratory tract lesions induced by sensory irritants at the RD50 concentration","volume":"74","author":"Buckley","year":"1984","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"2022062811300054100_kfac040-B18","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1093\/toxsci\/4.1.30","article-title":"Methylene chloride: A two-year inhalation toxicity and oncogenicity study in rats and hamsters1","volume":"4","author":"Burek","year":"1984","journal-title":"Toxicol. Sci"},{"key":"2022062811300054100_kfac040-B19","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1006\/faat.1996.0024","article-title":"Changes in the nasal epithelium of rats exposed by inhalation to mixtures of formaldehyde, acetaldehyde, and acrolein","volume":"29","author":"Cassee","year":"1996","journal-title":"Fundam. Appl. Toxicol"},{"key":"2022062811300054100_kfac040-B20","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0041-008X(83)90001-7","article-title":"Nasal cavity deposition, histopathology, and cell proliferation after single or repeated formaldehyde exposures in B6C3F1 mice and F-344 rats","volume":"68","author":"Chang","year":"1983","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"2022062811300054100_kfac040-B21","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1093\/annweh\/wxy099","article-title":"Pilot studies of voc exposure profiles during surgical operations","volume":"63","author":"Cheng","year":"2019","journal-title":"Ann. Work Expo Health"},{"key":"2022062811300054100_kfac040-B22","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1080\/10934529.2010.500932","article-title":"Inhalation risk assessment of exposure to the selected volatile organic compounds (VOCs) emitted from the facilities of a steel plant","volume":"45","author":"Chiang","year":"2010","journal-title":"J. Environ. Sci. Health A Tox. Hazard Subst. Environ. Eng"},{"key":"2022062811300054100_kfac040-B23","year":"1982"},{"key":"2022062811300054100_kfac040-B24","year":"1997"},{"key":"2022062811300054100_kfac040-B25","first-page":"286","article-title":"Altered lung function and structure in the rat after subchronic exposure to acrolein","volume":"133","author":"Costa","year":"1986","journal-title":"Am. Rev. Respir. Dis"},{"key":"2022062811300054100_kfac040-B26","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1080\/15298667991430316","article-title":"Inhalation toxicity studies with 1,3-butadiene \u2013 2. 3 month toxicity study in rats","volume":"40","author":"Crouch","year":"1979","journal-title":"Am. Ind. Hyg. Assoc. J"},{"key":"2022062811300054100_kfac040-B27","author":"Dailey","year":"2021"},{"key":"2022062811300054100_kfac040-B28","author":"Dailey","year":"2021"},{"key":"2022062811300054100_kfac040-B29","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/S0013-9351(89)80021-0","article-title":"The influence of inhaled formaldehyde on rat lung cytochrome p450","volume":"49","author":"Dallas","year":"1989","journal-title":"Environ. Res"},{"key":"2022062811300054100_kfac040-B30","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1128\/MCB.00756-09","article-title":"Cell-specific interaction of retinoic acid receptors with target genes in mouse embryonic fibroblasts and embryonic stem cells","volume":"30","author":"Delacroix","year":"2010","journal-title":"Mol. Cell Biol"},{"key":"2022062811300054100_kfac040-B31","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/0300-483X(96)03443-9","article-title":"A follow-up study of synthetic rubber workers","volume":"113","author":"Delzell","year":"1996","journal-title":"Toxicology"},{"key":"2022062811300054100_kfac040-B32","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1289\/ehp.7022","article-title":"Effects of 1,3-butadiene, isoprene, and their photochemical degradation products on human lung cells","volume":"112","author":"Doyle","year":"2004","journal-title":"Environ. Health Perspect"},{"key":"2022062811300054100_kfac040-B33","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1165\/rcmb.2009-0453OC","article-title":"Do airway epithelium air-liquid cultures represent the in vivo airway epithelium transcriptome?","volume":"44","author":"Dvorak","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol"},{"key":"2022062811300054100_kfac040-B34","first-page":"5065","article-title":"Gaseous vocs rapidly modify particulate matter and its biological effects\u2014part 1: Simple vocs and model pm","volume":"12","author":"Ebersviller","year":"2012","journal-title":"Atmos. Chem. Phys. Discuss"},{"key":"2022062811300054100_kfac040-B35","author":"Elf Atochem","year":"1997"},{"key":"2022062811300054100_kfac040-B36","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0304-3835(88)90045-6","article-title":"Nasal tumours in rats after short-term exposure to a cytotoxic concentration of formaldehyde","volume":"39","author":"Feron","year":"1988","journal-title":"Cancer Lett"},{"key":"2022062811300054100_kfac040-B37","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ccr.2009.11.020","article-title":"DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia","volume":"17","author":"Figueroa","year":"2010","journal-title":"Cancer Cell"},{"key":"2022062811300054100_kfac040-B38","first-page":"505","article-title":"The benchmark dose method\u2013review of available models, and recommendations for application in health risk assessment","volume":"33","author":"Filipsson","year":"2003","journal-title":"Crit. Rev. Toxicol"},{"key":"2022062811300054100_kfac040-B39","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1093\/toxsci\/18.3.376","article-title":"Methylene chloride\u2014An inhalation study to investigate pathological and biochemical events occurring in the lungs of mice over an exposure period of 90 days","volume":"18","author":"Foster","year":"1992","journal-title":"Toxicol. Sci"},{"key":"2022062811300054100_kfac040-B40","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1093\/toxsci\/kfaa081","article-title":"Evaluation of 5-day in vivo rat liver and kidney with high-throughput transcriptomics for estimating benchmark doses of apical outcomes","volume":"176","author":"Gwinn","year":"2020","journal-title":"Toxicol. Sci"},{"key":"2022062811300054100_kfac040-B41","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1177\/0192623391019004-102","article-title":"Comparative aspects of nasal airway anatomy: Relevance to inhalation toxicology","volume":"19","author":"Harkema","year":"1991","journal-title":"Toxicol. Pathol"},{"key":"2022062811300054100_kfac040-B42","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1080\/01926230600713475","article-title":"The nose revisited: A brief review of the comparative structure, function, and toxicologic pathology of the nasal epithelium","volume":"34","author":"Harkema","year":"2006","journal-title":"Toxicol Pathol"},{"key":"2022062811300054100_kfac040-B43","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.cotox.2019.05.004","article-title":"Considerations for strategic use of high-throughput transcriptomics chemical screening data in regulatory decisions","volume":"15","author":"Harrill","year":"2019","journal-title":"Curr. Opi. Toxicol"},{"key":"2022062811300054100_kfac040-B44","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1093\/toxsci\/kfab009","article-title":"High-throughput transcriptomics platform for screening environmental chemicals","volume":"181","author":"Harrill","year":"2021","journal-title":"Toxicol. Sci"},{"key":"2022062811300054100_kfac040-B45","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1038\/sj.onc.1208383","article-title":"Microarray analyses reveal strong influence of DNA copy number alterations on the transcriptional patterns in pancreatic cancer: Implications for the interpretation of genomic amplifications","volume":"24","author":"Heidenblad","year":"2005","journal-title":"Oncogene"},{"key":"2022062811300054100_kfac040-B46","doi-asserted-by":"crossref","first-page":"274","DOI":"10.3109\/00016488909125528","article-title":"Histological changes in the nasal mucosa in rats after long-term exposure to formaldehyde and wood dust","volume":"108","author":"Holmstr\u00f6m","year":"1989","journal-title":"Acta Otolaryngol"},{"key":"2022062811300054100_kfac040-B47","first-page":"31","article-title":"Experimental carcinogenesis of the lung. Inhalation of gaseous formaldehyde or an aerosol of coal tar by C3H mice","volume":"30","author":"Horton","year":"1963","journal-title":"J. Natl. Cancer Inst"},{"key":"2022062811300054100_kfac040-B48","doi-asserted-by":"crossref","first-page":"168","DOI":"10.3389\/fgene.2017.00168","article-title":"A pipeline for high-throughput concentration response modeling of gene expression for toxicogenomics","volume":"8","author":"House","year":"2017","journal-title":"Front. Genet"},{"key":"2022062811300054100_kfac040-B49","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1093\/toxsci\/55.1.116","article-title":"1-bromopropane, an alternative to ozone layer depleting solvents, is dose-dependently neurotoxic to rats in long-term inhalation exposure","volume":"55","author":"Ichihara","year":"2000","journal-title":"Toxicol. Sci"},{"key":"2022062811300054100_kfac040-B50","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.taap.2013.10.019","article-title":"Case study on the utility of hepatic global gene expression profiling in the risk assessment of the carcinogen furan","volume":"274","author":"Jackson","year":"2014","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"2022062811300054100_kfac040-B51","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1093\/toxsci\/kfaa062","article-title":"A rat liver transcriptomic point of departure predicts a prospective liver or non-liver apical point of departure","volume":"176","author":"Johnson","year":"2020","journal-title":"Toxicol. Sci"},{"key":"2022062811300054100_kfac040-B52","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1289\/ehp.0901392","article-title":"In vitro screening of environmental chemicals for targeted testing prioritization: The toxcast project","volume":"118","author":"Judson","year":"2010","journal-title":"Environ. Health Perspect"},{"key":"2022062811300054100_kfac040-B53","first-page":"33","article-title":"Acute inhalation toxicity study of formaldehyde in rats: Effect of vapor on pulmonary surfactant","volume":"51","author":"Kamata","year":"1996","journal-title":"Oyo Yakuri"},{"key":"2022062811300054100_kfac040-B54","first-page":"1","article-title":"Effects of formaldehyde vapor on teh nasal cavity and lungs of f-344 rats","volume":"15","author":"Kamata","year":"1996","journal-title":"J. Environ. Pathol. Toxicol. Oncol"},{"key":"2022062811300054100_kfac040-B55","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2131\/jts.22.3_239","article-title":"Results of a 28-month chronic inhalation toxicity study of formaldehyde in male fisher-344 rats","volume":"22","author":"Kamata","year":"1997","journal-title":"J. Toxicol. Sci"},{"key":"2022062811300054100_kfac040-B56","first-page":"4382","article-title":"Carcinogenicity of formaldehyde in rats and mice after long-term inhalation exposure","volume":"43","author":"Kerns","year":"1983","journal-title":"Cancer Res"},{"key":"2022062811300054100_kfac040-B57","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"Hisat: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"2022062811300054100_kfac040-B58","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with hisat2 and hisat-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol"},{"key":"2022062811300054100_kfac040-B59","first-page":"121","article-title":"Acute and repeated inhalation toxicity of 1-bromopropane in SD rats","author":"Kim","year":"1999"},{"key":"2022062811300054100_kfac040-B60","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1128\/MCB.00444-09","article-title":"Regulation of the histone demethylase jmjd1a by hypoxia-inducible factor 1 alpha enhances hypoxic gene expression and tumor growth","volume":"30","author":"Krieg","year":"2010","journal-title":"Mol. Cell Biol"},{"key":"2022062811300054100_kfac040-B61","author":"Kutzman","year":"1981"},{"key":"2022062811300054100_kfac040-B62","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0300-483X(85)90163-5","article-title":"Changes in rat lung structure and composition as a result of subchronic exposure to acrolein","volume":"34","author":"Kutzman","year":"1985","journal-title":"Toxicology"},{"key":"2022062811300054100_kfac040-B63","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The sequence alignment\/map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2022062811300054100_kfac040-B64","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/0300-483X(96)03444-0","article-title":"Leukemia and cumulative exposure to butadiene, styrene and benzene among workers in the synthetic rubber industry","volume":"113","author":"Macaluso","year":"1996","journal-title":"Toxicology"},{"key":"2022062811300054100_kfac040-B65","volume-title":"Experimental Research on Trichloroethylene Carcinogenesis","author":"Maltoni","year":"1986"},{"key":"2022062811300054100_kfac040-B66","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0300-483X(86)90180-0","article-title":"Toxicity of formaldehyde vapor in b6c3f1 mice exposed for 13 weeks","volume":"41","author":"Maronpot","year":"1986","journal-title":"Toxicology"},{"key":"2022062811300054100_kfac040-B67","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1038\/sj.onc.1208447","article-title":"Gene expression profiling of plasma cell dyscrasias reveals molecular patterns associated with distinct IGH translocations in multiple myeloma","volume":"24","author":"Mattioli","year":"2005","journal-title":"Oncogene"},{"key":"2022062811300054100_kfac040-B68","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1165\/rcmb.2013-0515OC","article-title":"Ozone induces a proinflammatory response in primary human bronchial epithelial cells through mitogen-activated protein kinase activation without nuclear factor-\u03bab activation","volume":"51","author":"McCullough","year":"2014","journal-title":"Am. J. Respir. Cell Mol. Biol"},{"key":"2022062811300054100_kfac040-B69","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/j.1749-6632.1988.tb30121.x","article-title":"Inhalation toxicity and carcinogenesis studies of methylene chloride (dichloromethane) in F344\/N rats and B6C3F1 mice","volume":"534","author":"Mennear","year":"1988","journal-title":"Ann. N. Y. Acad. Sci"},{"key":"2022062811300054100_kfac040-B70","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1093\/toxsci\/kfu233","article-title":"Molecular mechanisms of acrolein toxicity: Relevance to human disease","volume":"143","author":"Moghe","year":"2015","journal-title":"Toxicol. Sci"},{"key":"2022062811300054100_kfac040-B71","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/0272-0590(86)90238-1","article-title":"Ultrastructural evaluation of acute nasal toxicity in the rat respiratory epithelium in response to formaldehyde gas","volume":"6","author":"Monteiro-Riviere","year":"1986","journal-title":"Fundam. Appl. Toxicol"},{"key":"2022062811300054100_kfac040-B72","first-page":"1012","article-title":"Correlation of regional and nonlinear formaldehyde-induced nasal cancer with proliferating populations of cells","volume":"56","author":"Monticello","year":"1996","journal-title":"Cancer Res"},{"key":"2022062811300054100_kfac040-B73","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/0041-008X(86)90201-2","article-title":"More precise localization of nasal tumors associated with chronic exposure of F-344 rats to formaldehyde gas","volume":"82","author":"Morgan","year":"1986","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"2022062811300054100_kfac040-B74","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1080\/08958370701628770","article-title":"Inhalation carcinogenicity and chronic toxicity of carbon tetrachloride in rats and mice","volume":"19","author":"Nagano","year":"2007","journal-title":"Inhal. Toxicol"},{"key":"2022062811300054100_kfac040-B75","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1539\/joh.49.249","article-title":"Thirteen-week inhalation toxicity of carbon tetrachloride in rats and mice","volume":"49","author":"Nagano","year":"2007","journal-title":"J. Occup. Health"},{"key":"2022062811300054100_kfac040-B76","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/0272-0590(88)90269-2","article-title":"Methylene chloride: A 2-year inhalation toxicity and oncogenicity study in rats","volume":"11","author":"Nitschke","year":"1988","journal-title":"Fundam. Appl. Toxicol"},{"key":"2022062811300054100_kfac040-B77","first-page":"1","year":"1984"},{"key":"2022062811300054100_kfac040-B78","first-page":"1","year":"1986"},{"key":"2022062811300054100_kfac040-B79","year":"1986"},{"key":"2022062811300054100_kfac040-B80","first-page":"1","year":"1993"},{"key":"2022062811300054100_kfac040-B81","first-page":"1","year":"2011"},{"key":"2022062811300054100_kfac040-B82","year":"2018"},{"key":"2022062811300054100_kfac040-B83","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/sj.onc.1209854","article-title":"Role of E2F3 expression in modulating cellular proliferation rate in human bladder and prostate cancer cells","volume":"26","author":"Olsson","year":"2007","journal-title":"Oncogene"},{"key":"2022062811300054100_kfac040-B84","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1289\/ehp.908619","article-title":"Inhalation toxicity and carcinogenicity of 1,3-butadiene in sprague-dawley rats","volume":"86","author":"Owen","year":"1990","journal-title":"Environ. Health Perspect"},{"key":"2022062811300054100_kfac040-B85","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1080\/15298668791384959","article-title":"Inhalation toxicity studies with 1,3-butadiene. 3. Two year toxicity\/carcinogenicity study in rats","volume":"48","author":"Owen","year":"1987","journal-title":"Am. Ind. Hyg. Assoc. J"},{"key":"2022062811300054100_kfac040-B86","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/jtra.10026","article-title":"Changes of zinc, copper, and iron levels in the lung of male rats after subacute (4-week) and subchronic (13-week) exposure to formaldehyde","volume":"16","author":"\u00d6zen","year":"2003","journal-title":"J. Trace Elem. Exp. Med"},{"key":"2022062811300054100_kfac040-B87","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1093\/toxsci\/kfz201","article-title":"Utility of in vitro bioactivity as a lower bound estimate of in vivo adverse effect levels and in risk-based prioritization","volume":"173","author":"Paul Friedman","year":"2020","journal-title":"Toxicol. Sci"},{"key":"2022062811300054100_kfac040-B88","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.comtox.2020.100126","article-title":"Variability in in vivo studies: Defining the upper limit of performance for predictions of systemic effect levels","volume":"15","author":"Pham","year":"2020","journal-title":"Comput. Toxicol"},{"key":"2022062811300054100_kfac040-B89","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1093\/bioinformatics\/bty878","article-title":"Bmdexpress 2: Enhanced transcriptomic dose-response analysis workflow","volume":"35","author":"Phillips","year":"2019","journal-title":"Bioinformatics"},{"key":"2022062811300054100_kfac040-B90","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/0041-008X(67)90110-X","article-title":"Effects on experimental animals of long-term inhalation of trichloroethylene, carbon tetrachloride, 1,1,1-trichloroethane, dichlorodifluoromethane, and 1,1-dichloroethylene","volume":"10","author":"Prendergast","year":"1967","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"2022062811300054100_kfac040-B91","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1165\/rcmb.2006-0466OC","article-title":"Transcriptional profiling of mucociliary differentiation in human airway epithelial cells","volume":"37","author":"Ross","year":"2007","journal-title":"Am. J. Respir. Cell Mol. Biol"},{"key":"2022062811300054100_kfac040-B92","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1038\/sj.onc.1209177","article-title":"Identification of novel genomic markers related to progression to glioblastoma through genomic profiling of 25 primary glioma cell lines","volume":"25","author":"Roversi","year":"2006","journal-title":"Oncogene"},{"key":"2022062811300054100_kfac040-B93","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/0041-008X(83)90276-4","article-title":"A 26-week inhalation toxicity study with formaldehyde in the monkey, rat, and hamster","volume":"68","author":"Rusch","year":"1983","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"2022062811300054100_kfac040-B94","doi-asserted-by":"crossref","first-page":"350","DOI":"10.3109\/1547691X.2010.520139","article-title":"Suppression of pulmonary host defenses and enhanced susceptibility to respiratory bacterial infection in mice following inhalation exposure to trichloroethylene and chloroform","volume":"7","author":"Selgrade","year":"2010","journal-title":"J. Immunotoxicol"},{"key":"2022062811300054100_kfac040-B95","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/0041-008X(85)90411-9","article-title":"Carcinogenicity of formaldehyde and hydrogen chloride in rats","volume":"81","author":"Sellakumar","year":"1985","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"2022062811300054100_kfac040-B96","first-page":"277","article-title":"The chronic toxicity of carbon tetrachloride: Animal exposures and field studies","volume":"18","author":"Smyth","year":"1936","journal-title":"J. Ind. Hyg. Toxicol"},{"key":"2022062811300054100_kfac040-B97","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/leu.2016.267","article-title":"NUP98 is rearranged in 3.8% of pediatric aml forming a clinical and molecular homogenous group with a poor prognosis","volume":"31","author":"Struski","year":"2017","journal-title":"Leukemia"},{"key":"2022062811300054100_kfac040-B98","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/ng1490","article-title":"An oncogenic KRAS2 expression signature identified by cross-species gene-expression analysis","volume":"37","author":"Sweet-Cordero","year":"2005","journal-title":"Nat. Genet"},{"key":"2022062811300054100_kfac040-B99","first-page":"3398","article-title":"Induction of squamous cell carcinomas of the rat nasal cavity by inhalation exposure to formaldehyde vapor","volume":"40","author":"Swenberg","year":"1980","journal-title":"Cancer Res"},{"key":"2022062811300054100_kfac040-B100","doi-asserted-by":"crossref","first-page":"6628","DOI":"10.1158\/0008-5472.CAN-06-0458","article-title":"NUP98-HOXA9 induces long-term proliferation and blocks differentiation of primary human CD34+ hematopoietic cells","volume":"66","author":"Takeda","year":"2006","journal-title":"Cancer Res"},{"key":"2022062811300054100_kfac040-B101","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1093\/toxsci\/kfm092","article-title":"A method to integrate benchmark dose estimates with genomic data to assess the functional effects of chemical exposure","volume":"98","author":"Thomas","year":"2007","journal-title":"Toxicol. Sci"},{"key":"2022062811300054100_kfac040-B102","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1093\/toxsci\/kfq355","article-title":"Application of transcriptional benchmark dose values in quantitative cancer and noncancer risk assessment","volume":"120","author":"Thomas","year":"2011","journal-title":"Toxicol. Sci"},{"key":"2022062811300054100_kfac040-B103","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1093\/toxsci\/kft094","article-title":"Temporal concordance between apical and transcriptional points of departure for chemical risk assessment","volume":"134","author":"Thomas","year":"2013","journal-title":"Toxicol. Sci"},{"key":"2022062811300054100_kfac040-B104","first-page":"1","author":"Tobe","year":"1985"},{"key":"2022062811300054100_kfac040-B105","year":"1991"},{"key":"2022062811300054100_kfac040-B106","year":"2003"},{"key":"2022062811300054100_kfac040-B107","year":"2010"},{"key":"2022062811300054100_kfac040-B108","year":"2010"},{"key":"2022062811300054100_kfac040-B109","year":"2011"},{"key":"2022062811300054100_kfac040-B110","year":"2011"},{"key":"2022062811300054100_kfac040-B111","year":"2014"},{"key":"2022062811300054100_kfac040-B112","year":"2020"},{"key":"2022062811300054100_kfac040-B113","year":"2020"},{"key":"2022062811300054100_kfac040-B114","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1053\/j.gastro.2011.02.006","article-title":"Combining clinical, pathology, and gene expression data to predict recurrence of hepatocellular carcinoma","volume":"140","author":"Villanueva","year":"2011","journal-title":"Gastroenterology"},{"key":"2022062811300054100_kfac040-B115","year":"2001"},{"key":"2022062811300054100_kfac040-B116","author":"Woolhiser","year":"2006"},{"key":"2022062811300054100_kfac040-B117","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1186\/1471-2164-8-387","article-title":"Bmdexpress: A software tool for the benchmark dose analyses of genomic data","volume":"8","author":"Yang","year":"2007","journal-title":"BMC Gen"},{"key":"2022062811300054100_kfac040-B118","doi-asserted-by":"crossref","first-page":"e0178302","DOI":"10.1371\/journal.pone.0178302","article-title":"A trichostatin a expression signature identified by tempo-seq targeted whole transcriptome profiling","volume":"12","author":"Yeakley","year":"2017","journal-title":"PLoS One"},{"key":"2022062811300054100_kfac040-B119","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1039\/C7TX00109F","article-title":"Regulating temperature and relative humidity in air-liquid interface in vitro systems eliminates cytotoxicity resulting from control air exposures","volume":"6","author":"Zavala","year":"2017","journal-title":"Toxicol. Res"},{"key":"2022062811300054100_kfac040-B120","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1080\/08958378.2018.1483983","article-title":"A new cell culture exposure system for studying the toxicity of volatile chemicals at the air-liquid interface","volume":"30","author":"Zavala","year":"2018","journal-title":"Inhal. Toxicol"},{"key":"2022062811300054100_kfac040-B121","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0300-483X(88)90083-2","article-title":"Cytotoxic and adaptive effects in rat nasal epithelium after 3-day and 13-week exposure to low concentrations of formaldehyde vapour","volume":"51","author":"Zwart","year":"1988","journal-title":"Toxicology"}],"container-title":["Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/toxsci\/advance-article-pdf\/doi\/10.1093\/toxsci\/kfac040\/43518776\/kfac040.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxsci\/article-pdf\/188\/1\/88\/44272687\/kfac040.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxsci\/article-pdf\/188\/1\/88\/44272687\/kfac040.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T07:32:21Z","timestamp":1656401541000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxsci\/article\/188\/1\/88\/6569098"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,15]]},"references-count":121,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,4,15]]},"published-print":{"date-parts":[[2022,6,28]]}},"URL":"https:\/\/doi.org\/10.1093\/toxsci\/kfac040","relation":{},"ISSN":["1096-6080","1096-0929"],"issn-type":[{"value":"1096-6080","type":"print"},{"value":"1096-0929","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,7,1]]},"published":{"date-parts":[[2022,4,15]]}}}