The next hit off your flavored electronic cigarette will likely come with a dose of a flavoring compound suspected of causing respiratory problems, according to new research published Tuesday in the journal Environmental Health Perspectives.

Scientists from the Harvard T.H. Chan School of Public Health, building on earlier research, decided to test for the presence of diacetyl and two related chemicals, acetoin and 2,3-pentanedione, in 51 brands of flavored e-cigarettes and refill liquids, finding that more than 90 percent contained one of the three when inhaled. These chemicals have long been used as flavor enhancers, particularly for products meant to taste buttery, like microwave popcorn. And while they’re believed to be perfectly safe to ingest, there’s mounting evidence that inhaling diacetyl — as factory employees working at popcorn manufacturing plants often do — can trigger an incurable and progressive disease called obliterative bronchiolitis (OB), also known as bronchiolitis obliterans or more simply, "Popcorn Lung."

"Recognition of the hazards associated with inhaling flavoring chemicals started with 'Popcorn Lung' over a decade ago," explained lead author and assistant professor of exposure assessment science.Joseph Allen in a statement. "However, diacetyl and other related flavoring chemicals are used in many other flavors beyond butter-flavored popcorn, including fruit flavors, alcohol flavors, and, we learned in our study, candy flavored e-cigarettes."

Popcorn Lung

In 2000, eight former employees of the Gilster-Mary Lee popcorn plant were found to have come down with OB over a period of several years by the Missouri Department of Health and Senior Services. After a joint investigation in conjunction with the National Institute for Occupational Safety and Health (NIOSH), it was determined that the plant’s current workers who had more exposure to flavoring vapors were more likely to report worse airway function. Subsequent research, primarily in animals, has since singled out diacetyl inhalation as a leading culprit of worsening lung function, though 2,3-pentanedione is also considered to be potentially harmful.

While the use of diacetyl and related chemicals in flavored e-cigarettes has largely been an open secret, it wasn’t until 2014 that researchers conducted their own examination in Nicotine & Tobacco Research. Then as now, the authors found that a majority (75 percent) of the 159 brands studied contained either diacetyl and 2,3-pentanedione. Citing exposure guidelines developed by the NIOSH, they concluded that close to half of the products exposed users to "higher than safety levels."

In this latest study, which used a device to stimulate inhalation, diacetyl was found in 39 of the 51 products, whereas Acetoin and 2,3-pentanedione were found in 46 and 23 brands, respectively. What makes these results particularly concerning is that several e-cigarette companies has recently pledged to remove diacetyl from their products. There was even pushback against the company Five Pawns earlier this year after they seemingly misled their consumers about the levels of diacetyl and 2,3-pentanedione in their products, which subsequently led to 5 of its products being taken off the Canadian market. As of now, though, it appears that the industry has collectively done little to address any potential issues.

"Since most of the health concerns about e-cigarettes have focused on nicotine, there is still much we do not know about e-cigarettes," said co-author David Christiani, Elkan Blout Professor of Environmental Genetics at Harvard. "In addition to containing varying levels of the addictive substance nicotine, they also contain other cancer-causing chemicals, such as formaldehyde, and as our study shows, flavoring chemicals that can cause lung damage."

An Unclear Connection

Alarming as Christani and others’ findings are, however, they do need to be placed in a clearer context. For one, determining whether an environmental agent is harmful or not is rarely simple. Even if diacetyl and its ilk are widely present in e-cigarettes, that doesn’t necessarily mean they’re in high enough doses to do lasting damage. E-cigarettes may very well provide a negligible dose, or they could be even riskier than working in a poorly maintained popcorn factory — we don’t know enough yet to decide one way or the other.

Similarly, the link between diacetyl and lung disease itself isn’t fully settled either.  A 2014 study in Toxicology examined the exposure levels of diacetyl and 2,3-pentanedione found in regular cigarette smoke and determined these far exceeded "occupational exposures for most food/flavoring workers who smoke."  According to the researchers, because previous studies of these workers didn’t take their extensive smoking history into account, it’s possible that their findings might be fundamentally flawed.

"Further, because smoking has not been shown to be a risk factor for bronchiolitis obliterans, our findings are inconsistent with claims that diacetyl and/or 2,3-pentanedione exposure are risk factors for this disease," they concluded.

It seems that only more research will definitively answer these lingering questions.

Source: Allen J, Christiani D, et al. Environmental Health Perspectives. 2015.