|IDENTIFICATION AND USE: Diacetyl (DA) is a yellow liquid. It is used as synthetic flavoring substance and adjuvant. Diacetyl has been widely used as a chemical modifier of proteins, combining with arginine residues. |
HUMAN EXPOSURE AND TOXICITY: Diacetyl is a diketone flavoring agent that is commonly employed for buttery taste as well as other purposes. Industrial exposure to flavoring agents, particularly diacetyl, has recently been associated with bronchiolitis obliterans, a severe respiratory illness producing fibrosis and obstruction of the small airways. This has been most commonly reported in the microwave popcorn production industry, but it has occurred elsewhere. In addition to bronchiolitis obliterans, spirometry abnormalities (fixed airflow obstruction) and respiratory symptoms have been associated with exposure. A direct effect on the respiratory epithelium with the disorganized fibrotic repair appears most likely as the underlying mechanism. Current data suggest that diacetyl is the agent responsible, although it is possible that diacetyl is simply a marker for another causative agent. Workers at the microwave popcorn company experienced normal rates of all-cause mortality but higher rates of chronic obstructive pulmonary disease-associated mortality, especially workers employed before the company reduced diacetyl exposure. According to case reports, lung disease could also arise in the consumers of diacetyl-containing popcorn.
ANIMAL STUDIES: Male mice were exposed by inhalation to 200 or 400 ppm DA 6 hr/day for 5 days. 400 ppm caused deaths and acute necrotizing rhinitis, laryngitis and bronchitis (proximal large bronchi). Exposure to 200 ppm caused a few deaths and acute necrotizing rhinitis and erosive or necrotizing laryngitis in all mice. There were no lung or bronchiolar lesions in the DA exposed mice. Chronic bronchitis, laryngitis, and rhinitis were present after 2 and 4 weeks of exposure. In rats diacetyl inhalation increases substance P levels in sensory nerves of airway epithelium. Because substance P release in airways promotes inflammation and activation of sensory nerves mediates reflexes, neural changes may contribute to flavorings-related lung disease pathogenesis. When given i.p. to mice once weekly for 24 weeks, diacetyl (1.70 or 8.40 mg/kg [0.0197 or 0.0976 mmol/kg]) did not induce any lung tumors. Groups of hamsters, mice, and rats were given a solution containing 90% diacetyl by gavage on days 6-10 of gestation for hamsters and days 6-15 of gestation for mice and rats. The doses for all species were 16, 74, 345, or 1600 mg/kg bw per day. No effects were seen on maternal survival, weight, or reproductive parameters or on fetal survival or microscopic appearance of external, skeletal, or soft tissues. Diacetyl induced mitotic chromosome loss in Saccharomyces cerevisiae in the presence of propionitrile. In several bacterial assays, diacetyl generally showed mutagenic activity in Salmonella typhimurium strains TA100, 102, and 104 with and without metabolic activation but none against strain TA98. Conflicting results were obtained in Escherichia coli strain WP2 uvra, but nonmutagenicity was demonstrated in the SOS-chromotest using E. coli PQ37. Diacetyl was also negative in a micronucleus test using mouse bone marrow cells.