Butter flavourings causing lung disease

Artificial butter flavouring 2,3-pentanedione is an ‘inhalation hazard’ that could possibly cause severe lung disease in food industry workers.

The ingredient has been used by many manufacturers of microwave popcorn after it emerged that another butter flavouring – called diacetyl – was connected to a life-threatening lung disease known as bronchiolitis obliterans in factory workers who inhaled the substance.

However, researchers from the US National Institute for Occupational Safety and Health – part of the US Centres for Disease Control and Prevention (CDC) – have said that being exposed to 2,3-pentanedione (PD) could mean comparable risks to diacetyl in terms of respiratory toxicity.

Ann Hubbs of the CDC, said: “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”.

Hubbs said 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 connection 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”.

Hubbs added: “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”.

Often referred to as popcorn workers lung, Bronchiolitis obliterans is a rare lung disease that causes scar tissue to gradually block the small airways of the lungs.

Despite there being several causes of bronchiolitis obliterans, research of many years before 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. Thus, there is increasing pressure to control the use of the ingredient in products where it could cause health risks.

Hubbs explained: “By recognising 2,3-pentanedione as a inhalation hazard, it is hoped that exposures to workers will be controlled so that workers stay healthy”.

In the recent study, Hubbs and her co-workers initially exposed groups of rats to different concentrations of PD, a comparable concentration of diacetyl, or filtered air for six hours.

They discovered that both diacetyl and 2,3-pentanedione concluded 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 discovered respiratory epithelial injury in the upper nose, compared 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 apotosis) 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.

Hubbs said: “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 concluded”.

She explained that the data also supports established recommendations that “flavourings should be substituted only when there is evidence that the substitute is less toxic than the agent it replaces”.


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