Respiratory toxicologic pathology of inhaled diacetyl in sprague-dawley rats.
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.
Hubbs
Ann F
AF
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
Goldsmith
William T
WT
Kashon
Michael L
ML
Frazer
David
D
Mercer
Robert R
RR
Battelli
Lori A
LA
Kullman
Gregory J
GJ
Schwegler-Berry
Diane
D
Friend
Sherri
S
Castranova
Vincent
V
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
D000395:Air Pollutants, Occupational; D003931:Diacetyl