Still Searching for Better Butter Flavoring

After diacetyl (2,3-butanedione) was shown to cause bronchiolitis obliterans in workers who inhaled high levels of this volatile butter flavoring at microwave popcorn processing plants, 1,2,3 some manufacturers switched to a substitute assumed to be safer. Recent rodent studies, however, suggest that the substitute, 2,3-pentanedione, may be as damaging to the respiratory tract as the diacetyl it replaced. Bronchiolitis obliterans, or " popcorn lung, " is a rare, irreversible, debilitating lung disease in which inflammation and scarring obstruct the smallest airways, the bronchioles. There is no good treatment for the disease short of a lung transplant. 6 Ironically, lung transplant itself can trigger bronchiolitis obliterans through organ rejection mechanisms, limiting the survival of many transplant patients. 7 After the disease was identified in popcorn workers, researchers at the National Institute for Occupational Safety and Health (NIOSH) reported bronchial epithelial damage in rats inhaling vapors of butter flavoring. 8 This type of injury causes fibrosis (thickening and scarring) of the bronchioles, which is the underlying cause of bronchiolitis obliterans. In 2008 some of the same NIOSH researchers narrowed their studies to diacetyl, a major component of butter flavoring vapors, and reported similar acute damage in rats. The same year, Daniel Morgan, head of the Respiratory Toxicology Group at the National Institute of Environmental Health Sciences, and colleagues reported that mice develop bronchial epithelial damage after inhaling diacetyl vapors at concentrations equivalent to worker exposures. 6 Rats proved even more susceptible than mice and developed full-blown bronchiolitis obliterans after repeated exposure to diacetyl. Because diacetyl and 2,3-pentanedione, both diketones, are chemically very similar, Morgan suspected that inhaled 2,3-pentanedione may be toxic to the respiratory tract as well. He exposed rats to up to 200 ppm of 2,3-pentanedione for either 10 or 12 days, using the same doses and exposure times as the earlier diacetyl rat experiments. Like diacetyl, 2,3-pentanedione caused fibrosis of the small airways. Morgan's team also reported an increase in growth factors and cytokines in the lungs, including C-reactive protein and fibroblast growth factor 9. 4 In recent unpublished studies , they observed that the gene for transforming growth factor β was highly upregulated in fibrotic airways of rats exposed to 2,3-pentanedione. This potent fibrogenic agent initiates the fibrosis pathway, causing thickening of bronchial walls and airway obstruction. 11 Morgan's findings provide strong evidence that inhaled diketone vapors can produce airway fibrotic disease and support a causal relationship between workplace …