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Respiratory toxicologic pathology of inhaled diacetyl in Sprague-Dawley rats.

Authors
Hubbs-AF; Goldsmith-WT; Kashon-ML; Frazer-D; Mercer-RR; Battelli-LA; Kullman-GJ; Schwegler-Berry-D; Friend-S; Castranova-V
Source
Toxicol Pathol 2008 Feb; 36(2):330-344
NIOSHTIC No.
20034064
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 intercellular 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.
Keywords
Volatiles; Organic-compounds; Sensitization; Hypersensitivity; Vapors; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Inhalation-studies; Pulmonary-disorders; Pulmonary-system-disorders; Work-environment; Worker-health; Workplace-studies; Toxic-vapors; Risk-analysis; Risk-factors; Chemical-hypersensitivity; Author Keywords: diacetyl; bronchiolitis obliterans; flavorings; airways obstruction; food processing workers; ketones; 2,3-butanedione
Contact
Ann Hubbs DVM, PhD, DACVP, Experimental Pathology Laboratory, Pathology and Physiology Research Branch, Health Effects Laboratory Division, NIOSH, Centers for Disease Control and Prevention, 1095 Willowdale Rd., Morgantown, WV 26505
CODEN
TOPADD
CAS No.
431-03-8
Publication Date
20080201
Document Type
Journal Article
Email Address
ahubbs@cdc.gov
Fiscal Year
2008
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
0192-6233
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Toxicologic Pathology
State
WV
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