Popcorn worker's lung: In vitro exposure to diacetyl, an ingredient in microwave popcorn butter flavoring, increases reactivity to methacholine

Workers who inhale microwave popcorn butter flavorings experience decrements in lung function and can develop clinical bronchiolitis obliterans, i.e., “popcorn worker's lung” (Kreiss, K., Gomaa, A., Kullman, G., Fedan, K., Simoes, E.J., Enright, P.L., 2002. Clinical bronchiolitis obliterans in...

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Published in:	Toxicology and applied pharmacology Vol. 215; no. 1; pp. 17 - 22
Main Authors:	Fedan, J.S., Dowdy, J.A., Fedan, K.B., Hubbs, A.F.
Format:	Journal Article
Language:	English
Published:	San Diego, CA Elsevier Inc 15-08-2006 Elsevier
Subjects:	60 APPLIED LIFE SCIENCES Airway reactivity Animals BERRIES Bioelectric properties Biological and medical sciences BUTTER Diacetyl Diacetyl - toxicity Dose-Response Relationship, Drug EPITHELIUM Flavoring Agents - toxicity Food Industry Guinea pig GUINEA PIGS IN VITRO In Vitro Techniques INHALATION KETONES Lung - drug effects LUNGS Medical sciences Methacholine Methacholine Chloride - pharmacology MICROWAVE RADIATION NECROSIS Occupational Exposure Perfused trachea Popcorn worker's lung POTASSIUM CHLORIDES RATS REACTIVITY RELAXATION REYNOLDS NUMBER SENSITIVITY Terbutaline Toxicology TRACHEA Trachea - drug effects VAPORS Terbutaline Guinea pig Bioelectric properties Methacholine Airway reactivity Epithelium Perfused trachea Trachea Diacetyl Popcorn worker's lung Agonist Lung Microwave β2-Adrenergic receptor β-Adrenergic receptor agonist Occupational exposure Respiratory system Respiratory tract Worker Human Bronchodilator Rodentia Butter Increase In vitro Vertebrata Mammalia Reactivity Animal Occupational medicine
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Summary:	Workers who inhale microwave popcorn butter flavorings experience decrements in lung function and can develop clinical bronchiolitis obliterans, i.e., “popcorn worker's lung” (Kreiss, K., Gomaa, A., Kullman, G., Fedan, K., Simoes, E.J., Enright, P.L., 2002. Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant. N. Engl. J. Med. 347, 330–338.). In a rat inhalation model, vapors of an artificial butter flavoring damaged the epithelium of the upper and lower airways (Hubbs, A.F., Battelli, L.A., Goldsmith, W.T., Porter, D.W., Frazer, D., Friend, S., Schwegler-Berry, D., Mercer, R.R., Reynolds, J.S., Grote, A., Castranova, V., Kullman, G., Fedan, J.S., Dowdy, J., Jones, W.G., 2002. Necrosis of nasal and airway epithelium in rats inhaling vapors of artificial butter flavoring. Toxicol. Appl. Pharmacol. 185, 128–135.). Diacetyl, a butter flavoring component, is a major volatile ketone in the popcorn-processing workplace. We investigated the effects of diacetyl on epithelium of guinea pig isolated airway preparations and the effects of diacetyl in vitro on reactivity to bronchoactive agents. In the isolated, perfused trachea preparation, diacetyl added to the intraluminal (mucosal) bath elicited responses that began with contraction (threshold ca. 3 mM) and ended with relaxation. After a 4-h incubation with intraluminal diacetyl (3 mM), contractions to extraluminal (serosal) methacholine (MCh) were slightly increased; however, sensitivity to intraluminally (mucosally) applied MCh was increased by 10-fold. Relaxation responses of MCh (3 × 10 −7 M)-contracted tracheas to extraluminally applied terbutaline and intraluminally applied 120 mM KCl, to evoke epithelium-derived relaxing factor release, were unaffected by diacetyl. Exposure of the tracheal epithelium in Ussing chambers to diacetyl decreased transepithelial potential difference and resistance. These findings suggest that diacetyl exposure compromised epithelial barrier function, leading to hyperreactivity to mucosally applied MCh. The respiratory epithelium appears to serve as an initial target for the toxic effects of diacetyl in the airways.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0041-008X 1096-0333
DOI:	10.1016/j.taap.2006.02.001