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Respiratory Toxicologic Pathology of Inhaled Diacetyl in Sprague-Dawley Rats

¹ 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, USA
² Field Studies Branch, Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, USA

Correspondence: Address correspondence to: Ann Hubbs DVM, PhD, DACVP, Experimental Pathology Laboratory, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Rd., Morgantown, WV 26505, USA; e-mail: ahubbs{at}cdc.gov.

Inhalation of butter flavoring vapors by food manufacturing workers causes an emerging lung disease clinically resembling bronchiolitis obliterans. Diacetyl, an -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.

Key Words: diacetyl • bronchiolitis obliterans • flavorings • airways obstruction • food processing workers • ketones • 2 • 3-butanedione

Abbreviations: FEV1, forced expiratory volume in one second • HEPA, filtered high-efficiency particulate air filtered • HRCT, high-resolution computer tomography • ppm, parts per million • T1, first nasal section • T2, second nasal section • T3, third nasal section • T4, fourth nasal section • TWA, time-weight average • VOC, volatile organic compounds meter

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