The ingredient has been used by many manufacturers of microwave popcorn after it was suggested that another butter flavouring – known as diacetyl – was linked to a life-threatening lung disease known as bronchiolitis obliterans in factory workers who inhaled the substance.
But now researchers from the US National Institute for Occupational Safety and Health – part of the US Centers for Disease Control and Prevention (CDC) – have suggested that exposure to 2,3-pentanedione (PD) could present comparable risks to diacetyl in terms of respiratory toxicity.
“Our study demonstrates that PD, like diacetyl, damages airway epithelium in laboratory studies. This finding is important because the damage is believed to be the underlying cause of bronchiolitis obliterans,” said Ann Hubbs of the CDC, who led the new investigation.
Hubbs told FoodNavigator that her research identifies the flavouring compound as a respiratory hazard that is capable of causing changes in RNA expression in the brains of animals.
In conjunction with human data on PD’s close structural analogue, diacetyl, the research “is part of the body of evidence supporting the importance of controlling 2,3-pentanedione exposures,” she said.
“Our study also suggests that shared features of the short-chain diketones may be related to their toxicity when inhaled. The direct effect of the reactive alpha-diketone group and the ability of the alpha-diketones to modify proteins and nucleic acids are features consistent with the direct cytotoxicity of diacetyl and PD,” said Hubbs.
Bronchiolitis obliterans – often referred to as popcorn workers lung – is a rare lung disease that causes scar tissue to gradually block the small airways of the lungs.
Though there are several other causes of bronchiolitis obliterans, research several years ago linked repeated inhalation of diacetyl which is used to flavour butter popcorn with the disease. As a result, in 2007 several of the largest popcorn producing firms stopped using the ingredient – replacing it with other flavouring substances, such as PD.
Since then, however, research studies have linked 2,3-pentanedione (a structural analogue of diacetyl) to similar health risks. As a result there is mounting pressure to control the use of the ingredient in products where it could cause health risks.
“By recognizing 2,3-pentanedione as a inhalation hazard, it is hoped that exposures to workers will be controlled so that workers stay healthy,” explained Hubbs.
In the new study, Hubbs and her colleagues initially exposed groups of rats to different concentrations of PD, a comparable concentration of diacetyl, or filtered air for six hours.
They found that both diacetyl and 2,3-pentanedione resulted in signs of toxicity. To further investigate this, the team then exposed additional rats to PD before examining their brains, lungs, and nasal tissues at 0-2 hours, 12-14 hours, and 18-20 hours after exposure.
The team found respiratory epithelial injury in the upper nose, comparable to that caused by diacetyl that progressed through 12 to 14 hours post-exposure.
They also revealed that PD exposure caused tissue damage and cell death (necrosis and apoptosis) in the olfactory neuroepithelium, in addition to activating caspase 3, a protein that plays a role in cell death, in axons of olfactory nerve bundles.
“Our study is a reminder that a chemical with a long history of being eaten without any evidence of toxicity can still be an agent with respiratory toxicity when appropriate studies are conducted,” Hubbs warned, explaining that the data also supports already established recommendations that “flavourings should be substituted only when there is evidence that the substitute is less toxic than the agent it replaces.”