Study Finds Diacetyl Exposure Harmful to Mice

A new study conducted by scientists at the National Institute of Environmental Health Sciences (NIEHS) in collaboration with Duke University researchers shows that exposure to the chemical diacetyl, a component of artificial butter flavoring, can be harmful to the nose and airways of mice.

NIEHS, which is part of the National Institutes of Health, conducted the study because diacetyl has been implicated in causing obliterative bronchiolitis, or “popcorn lung,” in humans. The diacetyl controversy has been a hot topic recently as some workers in microwave popcorn packaging plants and other food-related occupations have developed this debilitating but rare lung disease.

The study found that when laboratory mice inhaled diacetyl vapors for three months, they developed lymphocytic bronchiolitis, a potential precursor of popcorn lung. None of the mice, however, were diagnosed with obliterative bronchiolitis.

“This is one of the first studies to evaluate the respiratory toxicity of diacetyl at levels relevant to human health. Mice were exposed to diacetyl at concentrations and durations comparable to what may be inhaled at some microwave popcorn packaging plants,” said Daniel L. Morgan, Ph.D., head of the Respiratory Toxicology Group at the NIEHS and co-author of the paper that appears online in the journal Toxicological Sciences.

The authors conclude that these findings suggest that workplace exposure to diacetyl contributes to the development of popcorn lung in humans, but more research is needed.

Additional Studies Planned

Although inhalation exposure in laboratory animals closely parallels the way humans are exposed to airborne toxicants, the study points out that some anatomical differences between the mice and humans may account for why the nasal cavity of mice is more susceptible to reactive vapors than that of humans. The study also took into account that mice breathe exclusively through their noses.

The researchers speculate that the extensive reaction of diacetyl vapors in the nose and upper airways of mice may have prevented toxic concentrations from penetrating deeper in the lung to the bronchioles or tiny airways where obstruction occurs in humans.

When the mice were exposed to high concentrations of diacetyl using a method that bypasses the nose, the researchers found lesions partially obstructing the small airways. More studies are under way to determine if these lesions progress to obliterative bronchiolitis in mice.

The National Toxicology Program (NTP), headquartered at the NIEHS, plans to do a larger set of studies to provide inhalation toxicity data on artificial butter flavoring and the two major components, diacetyl and another compound called acetoin.

These studies will more definitively pinpoint the toxic components of artificial butter flavoring and potentially help identify biomarkers for early detection. The NTP data will then be shared with public health and regulatory agencies so they can set safe exposure levels for these compounds and develop guidance to protect the health of workers in occupations where these chemicals are used.

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