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Inhalation toxicity of the flavoring agent, diacetyl (2,3-butanedione), in the upper respiratory tract of rats.

Hubbs AF; Battelli LA; Mercer RR; Kashon M; Friend S; Schwegler-Berry D; Goldsmith WT
Toxicologist 2004 Mar; 78(S-1):438-439
Diacetyl (2,3-butanedione) is a diketone found naturally in foods such as butter and "generally recognized as safe" for use in low concentrations as a food additive. Diacetyl imparts the odor and flavor of butter to foods and also has industrial applications. Recently, an increased prevalence of fixed airways obstruction was reported in workers at a microwave popcorn plant and the lung disease correlated with diacetyl exposure. In a previous study, inhalation of diacetyl-containing artificial butter flavoring caused necrosis of the nasal, bronchial, and bronchiolar epithelium in rats. We have now investigated the hypothesis that inhalation of diacetyl produces epithelial injury. Therefore, male Sprague-Dawley rats were exposed in a whole-body inhalation chamber for 6 hours to 0, 99.3 +/- 0.07, 198.4 +/- 0.10, or 294.6 +/- 0.20 ppm diacetyl and euthanized the next day. Four levels of nose, three levels of trachea, and two lung sections were examined by light microscopy. In addition, the nose was examined by transmission electron microscopy (TEM) and the trachea was examined by TEM and scanning electron microscopy (SEM). At 198.4 ppm or higher, diacetyl inhalation resulted in significant necrosis of nasal epithelium with associated neutrophilic inflammation. At 294.6 ppm, diacetyl inhalation also caused significant necrosis of tracheal epithelium with associated neutrophilic inflammation. By SEM, diacetyl-induced tracheal changes included multifocal denuding of basement membrane with cell swelling, loss of microvilli, and loss of ciliated cells in the remaining epithelium. By TEM, tracheal changes included epithelial necrosis, denuded basement membrane, and elongation of epithelial cells near foci of exposed basement membrane. Diacetyl did not produce significant changes in the lung under these exposure conditions. These findings suggest that acute exposure to diacetyl alone is sufficient to cause upper respiratory tract epithelial necrosis in rats at concentrations of 198.4 ppm or higher.
Respiratory-system-disorders; Laboratory-animals; Animals; Animal-studies; Food-additives; Airway-obstruction; Lung-disease; Exposure-levels; Pulmonary-system-disorders; Inhalation-studies; Microscopy
Publication Date
Document Type
Fiscal Year
NIOSH Division
Priority Area
Work Environment and Workforce: Mixed Exposures
Source Name
The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland
Page last reviewed: May 11, 2023
Content source: National Institute for Occupational Safety and Health Education and Information Division