{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:32:25Z","timestamp":1788280345497,"version":"build-2803163510"},"reference-count":52,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"name":"National Research Service Award through the National Institutes of Health","award":["F32ES026005"],"award-info":[{"award-number":["F32ES026005"]}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology"],"published-print":{"date-parts":[[2017,8]]},"DOI":"10.1016\/j.tox.2016.11.007","type":"journal-article","created":{"date-parts":[[2016,11,13]],"date-time":"2016-11-13T11:32:32Z","timestamp":1479036752000},"page":"30-39","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"special_numbering":"C","title":["Inhalation dosimetry modeling provides insights into regional respiratory tract toxicity of inhaled diacetyl"],"prefix":"10.1016","volume":"388","author":[{"given":"Joseph A.","family":"Cichocki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B.","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.tox.2016.11.007_bib0005","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1183\/09031936.04.00013903","article-title":"Bronchiolitis obliterans syndrome in popcorn production plant workers","volume":"24","author":"Akpinar-Elci","year":"2004","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.tox.2016.11.007_bib0010","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1093\/toxsci\/kfq067","article-title":"Evaluation of dicarbonyls generated in a simulated indoor air environment using an in vitro exposure system","volume":"115","author":"Anderson","year":"2010","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.tox.2016.11.007_bib0015","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1177\/000348947007900315","article-title":"The uptake of inhaled gases by the nose","volume":"79","author":"Brain","year":"1970","journal-title":"Ann. Oto. Laryngol."},{"key":"10.1016\/j.tox.2016.11.007_bib0020","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/path.1700580315","article-title":"The absorption of war gases by the nose","volume":"58","author":"Cameron","year":"1946","journal-title":"J. Pathol."},{"key":"10.1016\/j.tox.2016.11.007_bib0025","doi-asserted-by":"crossref","first-page":"333","DOI":"10.3109\/08958378.2014.896059","article-title":"A hybrid CFD-PBPK model for naphthalene in rat and human with IVIVE for nasal tissue metabolism and cross-species dosimetry","volume":"26","author":"Campbell","year":"2014","journal-title":"Inhal. Toxicol."},{"key":"10.1016\/j.tox.2016.11.007_bib0030","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1093\/toxsci\/kfu165","article-title":"Tissue sensitivity of the rat upper and lower extrapulmonary airways to the inhaled electrophilic air pollutants diacetyl and acrolein","volume":"142","author":"Cichocki","year":"2014","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.tox.2016.11.007_bib0035","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1093\/toxsci\/kfs168","article-title":"Comparative computational modeling of airflows and vapor dosimetry in the respiratory tracts of rat monkey, and human","volume":"128","author":"Corley","year":"2012","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.tox.2016.11.007_bib0040","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1093\/toxsci\/kfv071","article-title":"Comparative risks of aldehyde constituents in cigarette smoke using transient computational fluid dynamics\/physiologically based pharmacokinetic models of the rat and human respiratory tracts","volume":"146","author":"Corley","year":"2015","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.tox.2016.11.007_bib0045","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1080\/009841098158430","article-title":"Short-term exposures of rats to airborne hydrogen fluoride","volume":"55","author":"Dalbey","year":"1998","journal-title":"J. Toxicol. Environ. Health A"},{"key":"10.1016\/j.tox.2016.11.007_bib0050","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1006\/taap.1998.8492","article-title":"Application of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry extrapolation of acidic vapors in the upper airways","volume":"152","author":"Frederick","year":"1998","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.tox.2016.11.007_bib0055","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1006\/taap.2002.9451","article-title":"Use of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry comparisons of ester vapors","volume":"183","author":"Frederick","year":"2002","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.tox.2016.11.007_bib0060","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/0041-008X(91)90175-E","article-title":"A model for the uptake of inhaled vapors in the nose of the dog during cyclic breathing","volume":"109","author":"Gerde","year":"1991","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.tox.2016.11.007_bib0065","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.rmed.2008.01.016","article-title":"An international collaborative pathologic study of surgical lung biopsies from mustard gas-exposed patients","volume":"102","author":"Ghanei","year":"2008","journal-title":"Respir. Med."},{"key":"10.1016\/j.tox.2016.11.007_bib0070","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1093\/toxsci\/kfr165","article-title":"A validated hybrid computational fluid dynamics-phsiologiclly based pharmacokinetic model for respiratory tract vapor absorption in the human and rat and its application to inhalation dosimetry of diaetyl","volume":"123","author":"Gloede","year":"2011","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.tox.2016.11.007_bib0075","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S0021-9258(18)85261-9","article-title":"The absorption, distribution and elimination of ethyl ether. V. The importance of the volume of breathing during the induction and termination of ether anesthesia","volume":"59","author":"Haggard","year":"1924","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.tox.2016.11.007_bib0080","series-title":"In Noxious Gases and the Principles of Respiration Influencing Their Action","author":"Henderson","year":"1943"},{"key":"10.1016\/j.tox.2016.11.007_bib0085","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1093\/toxsci\/kfi091","article-title":"Validation of human physiologically based pharmacokinetic model for vinyl acetate against human nasal dosimetry data","volume":"85","author":"Hinderliter","year":"2005","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.tox.2016.11.007_bib0090","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1177\/0192623307312694","article-title":"Respiratory toxicologic pathology of inhaled diacetyl in sprague-dawley rats","volume":"36","author":"Hubbs","year":"2008","journal-title":"Toxicol. Pathol."},{"key":"10.1016\/j.tox.2016.11.007_bib0095","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.ajpath.2012.05.021","article-title":"Respiratory and olfactory cytotoxicity of inhaled 2,3-pentanedione in Sprague-Dawley rats. Respiratory and olfactory cytotoxicity of inhaled 2,3-pentanedione in Sprague-Dawley rats","volume":"181","author":"Hubbs","year":"2012","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.tox.2016.11.007_bib0100","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1001\/jama.1913.04350130001001","article-title":"Ozone: its bacteridical, physiologic and deodorizing action","volume":"61","author":"Jordan","year":"1913","journal-title":"J. Amer. Med. Assoc."},{"key":"10.1016\/j.tox.2016.11.007_bib0105","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1177\/003335491112600405","article-title":"Occupational lung disease risk and exposure to butter-flavoring chemicals after implementation of controls at a microwave popcorn plant","volume":"126","author":"Kanwal","year":"2011","journal-title":"Public Health Rep."},{"key":"10.1016\/j.tox.2016.11.007_bib0110","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1165\/rcmb.2013-0339OC","article-title":"Diacetyl induces amphiregulin shedding in pulmonary epithelial cells and in experimental bronchiolitis obliterans","volume":"51","author":"Kelly","year":"2014","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"10.1016\/j.tox.2016.11.007_bib0115","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0031-6997(25)07246-1","article-title":"The theory and applications of the exchange of inert gas at the lungs and tissues","volume":"3","author":"Kety","year":"1951","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.tox.2016.11.007_bib0120","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1006\/taap.1993.1152","article-title":"Application of computational fluid dynamics to regional dosimetry of inhaled chemicals in the upper respiratory tract of the rat","volume":"121","author":"Kimbell","year":"1993","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.tox.2016.11.007_bib0125","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0027-5107(97)00132-2","article-title":"Correlation of regional formaldehyde flux predictions with the distribution of formaldehyde-induced squamous metaplasia in F344 rat nasal passages","volume":"380","author":"Kimbell","year":"1997","journal-title":"Mutat. Res."},{"key":"10.1016\/j.tox.2016.11.007_bib0130","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/toxsci\/64.1.111","article-title":"Dosimetry modeling of inhaled formaldehyde: binning nasal flux predictions for quantitative risk assessment","volume":"64","author":"Kimbell","year":"2001","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.tox.2016.11.007_bib0135","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1093\/toxsci\/64.1.100","article-title":"Dosimetry modeling of inhaled formaldehyde: comparisons of local flux predictions in the rat, monkey, and human nasal passages","volume":"64","author":"Kimbell","year":"2001","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.tox.2016.11.007_bib0140","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1056\/NEJMoa1101388","article-title":"Constrictive bronchiolitis in soldiers returning from Iraq and Afghanistan","volume":"365","author":"King","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.tox.2016.11.007_bib0145","article-title":"Recognizing occupational effects of diacetyl: what can we learn from this history?","author":"Kreiss","year":"2016","journal-title":"Toxicology"},{"key":"10.1016\/j.tox.2016.11.007_bib0150","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1080\/089583700402888","article-title":"A lung model describing uptake of organic solvents and roles of mucosal blood flow and metabolism in the bronchioles","volume":"12","author":"Kumagai","year":"2000","journal-title":"Inhal. Toxicol."},{"key":"10.1016\/j.tox.2016.11.007_bib0155","doi-asserted-by":"crossref","first-page":"12761","DOI":"10.1021\/jf103251w","article-title":"Reaction of the butter flavorant diacetyl (2,3-butanedione) with N-alpha-acetylarginine: a model for epitope formation with pulmonary proteins in the etiology of obliterative bronchiolitis","volume":"58","author":"Mathews","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.tox.2016.11.007_bib0160","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0300-483X(00)00448-0","article-title":"Sites and mechanisms for uptake of gases and vapors in the respiratory tract","volume":"160","author":"Medinsky","year":"2001","journal-title":"Toxicology"},{"key":"10.1016\/j.tox.2016.11.007_bib0165","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1093\/toxsci\/kfn016","article-title":"Respiratory toxicity of diacetyl in C57Bl\/6 mice","volume":"103","author":"Morgan","year":"2008","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.tox.2016.11.007_bib0170","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/0192623316638962","article-title":"Chemical reactivity and respiratory toxicity of the a-diketone flavoring agents: 2,3,-butanedione 2,3-pentanedione, and 2,3, hexanedione","volume":"44","author":"Morgan","year":"2016","journal-title":"Toxicol. Pathol."},{"key":"10.1016\/j.tox.2016.11.007_bib0175","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.pharmthera.2012.08.017","article-title":"Biologically-based modeling insights in inhaled vapor absorption and dosimetry","volume":"136","author":"Morris","year":"2012","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.tox.2016.11.007_bib0180","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1093\/toxsci\/kfn222","article-title":"Inhalation dosimetry of diacetyl and butyric acid: two components of butter flavoring vapors","volume":"108","author":"Morris","year":"2009","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.tox.2016.11.007_bib0185","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0041-008X(82)90104-1","article-title":"Regional deposition and absorption of inhaled hydrogen fluoride in the rat","volume":"62","author":"Morris","year":"1982","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.tox.2016.11.007_bib0190","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1006\/taap.1993.1228","article-title":"A physiologically based pharmacokinetic model for nasal uptake and metabolism of nonreactive vapors","volume":"123","author":"Morris","year":"1993","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.tox.2016.11.007_bib0195","series-title":"In Toxicology of the Nose and Upper Airway","first-page":"99","article-title":"Upper airway dosimetry of gases, vapors and particulate matter in rodents","author":"Morris","year":"2010"},{"key":"10.1016\/j.tox.2016.11.007_bib0200","volume":"vol. 3","author":"NRC","year":"2009"},{"key":"10.1016\/j.tox.2016.11.007_bib0205","doi-asserted-by":"crossref","first-page":"17883","DOI":"10.1074\/jbc.M110703200","article-title":"Molecular characterization of mammalian dicarbonyl\/l-xylulose reductase and its localization in kidney","volume":"277","author":"Nakagawa","year":"2002","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.tox.2016.11.007_bib0210","doi-asserted-by":"crossref","first-page":"e17644","DOI":"10.1371\/journal.pone.0017644","article-title":"Severe airway epithelial injury, aberrant repair and bronchiolitis obliterans develops after diacetyl instillation in rats","volume":"6","author":"Palmer","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.tox.2016.11.007_bib0215","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1080\/00028896309342961","article-title":"A toxicopathologic study in animals after brief single exposure to hydrogen fluoride","volume":"24","author":"Rosenholtz","year":"1963","journal-title":"Am. Ind. Hyg. Assoc. J."},{"key":"10.1016\/j.tox.2016.11.007_bib0220","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1080\/08958370290084647","article-title":"Physiologically based pharmacokinetic modeling of styrene and styrene oxide respiratory-tract dosimetry in rodents and humans","volume":"14","author":"Sarangapani","year":"2002","journal-title":"Inhal. Toxicol."},{"key":"10.1016\/j.tox.2016.11.007_bib0225","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1093\/toxsci\/kfl112","article-title":"Use of a pharmacokinetic-driven computational fluid dynamics model to predict nasal extraction of hydrogen sulfide in rats and humans","volume":"94","author":"Schroeter","year":"2006","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.tox.2016.11.007_bib0230","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/0272-0590(91)90152-T","article-title":"Relative acute toxicities of hydrogen fluoride, hydrogen chloride and hydrogen bromide in nose- and pseudo-mouth breathing rats","volume":"16","author":"Stavert","year":"1991","journal-title":"Fundam. Appl. Toxicol."},{"key":"10.1016\/j.tox.2016.11.007_bib0235","series-title":"Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry","author":"USEPA, United States Environmental Protection Agency","year":"1994"},{"key":"10.1016\/j.tox.2016.11.007_bib0240","series-title":"Advances in Inhalation Dosimetry of Gases and Vapors with Portal of Entry Effects in the Upper Respiratory Tract (Vol. EPA\/600\/R-09\/072)","author":"USEPA, United States Environmental Protection Agency","year":"2009"},{"key":"10.1016\/j.tox.2016.11.007_bib0245","series-title":"Advances in Inhalation Dosimetry for Gases with Lower Respiratory Tract and Systemic Effects (Vol. EPA\/600\/R-11\/068)","author":"USEPA, United States Environmental Protection Agency","year":"2011"},{"key":"10.1016\/j.tox.2016.11.007_bib0250","series-title":"Benchmark Dose Software (BMDS), Version 2.6.0.1","author":"USEPA, United States Environmental Protection Agency","year":"2016"},{"key":"10.1016\/j.tox.2016.11.007_bib0255","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3109\/15376510903483730","article-title":"Inhalation exposure systems for the development of rodent models of sulfur mustard-induced pulmonary injury","volume":"20","author":"Weber","year":"2010","journal-title":"Toxicol. Mech. Methods"},{"key":"10.1016\/j.tox.2016.11.007_bib0260","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.taap.2015.10.004","article-title":"Diacetyl and 2,3-pentanedione exposure of human cultured airway epithelial cells: ion transport effects and metabolism of butter flavoring agents","volume":"289","author":"Zaccone","year":"2015","journal-title":"Toxicol. Appl. Pharmacol."}],"container-title":["Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X16302669?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X16302669?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T23:35:39Z","timestamp":1759534539000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0300483X16302669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8]]},"references-count":52,"alternative-id":["S0300483X16302669"],"URL":"https:\/\/doi.org\/10.1016\/j.tox.2016.11.007","relation":{},"ISSN":["0300-483X"],"issn-type":[{"value":"0300-483X","type":"print"}],"subject":[],"published":{"date-parts":[[2017,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Inhalation dosimetry modeling provides insights into regional respiratory tract toxicity of inhaled diacetyl","name":"articletitle","label":"Article Title"},{"value":"Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tox.2016.11.007","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 Elsevier Ireland Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}