title: Respiratory toxicologic pathology of inhaled diacetyl in sprague-dawley rats.
abstract: Inhalation of butter flavoring vapors by food manufacturing workers causes an emerging lung disease clinically resembling bronchiolitis obliterans. Diacetyl, an alpha-diketone, is a major component of these vapors. In rats, we investigated the toxicity of inhaled diacetyl at concentrations of up to 365 ppm (time weighted average), either as six-hour continuous exposures or as four brief, intense exposures over six hours. A separate group inhaled a single pulse of ~1800 ppm diacetyl (92.9 ppm six-hour average). Rats were necropsied 18 to 20 hours after exposure. Diacetyl inhalation caused epithelial necrosis and suppurative to fibrinosuppurative inflammation in the nose, larynx, trachea, and bronchi. Bronchi were affected at diacetyl concentrations of 294.6 ppm or greater; the trachea and larynx were affected at diacetyl concentrations of 224 ppm or greater. Both pulsed and continuous exposure patterns caused epithelial injury. The nose had the greatest sensitivity to diacetyl. Ultrastructural changes in the tracheal epithelium included whorling and dilation of the rough endoplasmic reticulum, chromatin clumping beneath the nuclear membrane, vacuolation, increased inter-cellular space and foci of denuded basement membrane. Edema and hemorrhage extended into the lamina propria. These findings are consistent with the conclusion that inhaled diacetyl is a respiratory hazard.
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia 26505, USA. ahubbs@cdc.gov
authors.forename: Ann F
authors.initials: AF
authors.lastname: Hubbs
authors.forename: William T
authors.initials: WT
authors.lastname: Goldsmith
authors.forename: Michael L
authors.initials: ML
authors.lastname: Kashon
authors.forename: David
authors.initials: D
authors.lastname: Frazer
authors.forename: Robert R
authors.initials: RR
authors.lastname: Mercer
authors.forename: Lori A
authors.initials: LA
authors.lastname: Battelli
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Kullman
authors.forename: Diane
authors.initials: D
authors.lastname: Schwegler-Berry
authors.forename: Sherri
authors.initials: S
authors.lastname: Friend
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
mesh_terms: D000280:Administration, Inhalation; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001485:Basement Membrane / Q000187:drug effects / Q000648:ultrastructure; D001980:Bronchi / Q000187:drug effects / Q000648:ultrastructure; D003931:Diacetyl / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009336:Necrosis; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000473:pathology; D012140:Respiratory Tract Diseases / Q000139:chemically induced* / Q000473:pathology; D014132:Trachea / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D000395:Air Pollutants, Occupational; D003931:Diacetyl