Pulsed and continuous patterns of diacetyl (2,3butanedione) inhalation cause rhinitis, laryngitis, tracheitis, and bronchitis in rats.
Diacetyl is an alpha-diketone imparting the flavor of butter to food. During microwave popcorn and flavoring production, some workers inhaling diacetyl-containing vapor mixtures develop fixed airways obstruction. Workplace studies demonstrate large diacetyl air concentration fluctuations. To assess the airway toxicity of diacetyl and the use of time-weighted averages (TWAs) as the exposure metric, rats inhaled diacetyl at comparable TWAs over 6 hours, delivered either continuously or as four 15 minute pulses. The target concentrations for the four 15 minute pulses were 600, 1200, and 1800 ppm. The resulting 6 hour TWAs were 122 (low), 225 (medium), or 365 (high) ppm. Rats in the continuous groups inhaled diacetyl continuously over 6 hours, producing TWAs of 120 (low), 224 (medium) or 356 (high) ppm. An additional group, the single pulse group, inhaled one high (approximately 1800 ppm) diacetyl pulse (92.9 ppm 6 hour TW A). Diacetyl caused concentration-dependent epithelial necrosis and neutrophilic inflammation in the nose, larynx, trachea and bronchus. Significant bronchial epithelial damage was observed only in the high exposure groups. In the first nasal section, the continuous pattern of low exposure caused greater damage than the pulsed low exposure. In remaining sections and concentrations, the pathology score was unaffected by exposure pattern. The single high pulse diacetyl exposure also caused significant necrosis and/or inflammation in the first nasal section. These findings suggest that at concentrations exceeding 100 ppm, TWAs are a reasonable measure for diacetyl exposures. However, a single, pulse, high diacetyl exposure can cause respiratory epithelial injury.