There are more than 7,000 different flavors of electronic cigarettes now on the market — many of them with candy-like flavors of caramel, apple, and cherry that appeal to young people — but little is known about the safety of the chemical compounds behind those flavors when they are inhaled.
A new study by researchers at Harvard University's T.H. Chan School of Public Health found that most of the flavored e-cigarette liquids they tested contained diacetyl, a chemical linked to severe respiratory disease when inhaled. The study was released on Tuesday in the journal Environmental Health Perspectives.
Diacetyl is most widely known for being associated with the lung disease bronchiolitis obliterans in workers whose job consisted of mixing and handling the artificial butter flavoring that was added to microwave popcorn, earning the disease the moniker "popcorn lung." The Occupational Safety and Health Administration put in place strict guidelines regarding workers' exposure to diacetyl after an outbreak of the disease in 2000, but there are currently no regulations for exposure through e-cigarettes, according to the study's authors.
Joseph G. Allen, a Harvard professor of exposure assessment science who led the research, became curious about e-cigarettes and diacetyl after seeing a report about the explosive growth of the flavored e-cigarette market.
"Right away, I searched to see if the connection had been made between the likely flavor chemicals in these cigarettes and our experience in public health with workers who had developed this lung disease," he said.
Finding no evidence that the public was aware of the potential link, Allen began testing e-cigarettes in his lab and found that at least one of the three most harmful flavor chemicals were present in 92 percent of the samples they tested. An overwhelming 76 percent of them contained diacetyl.
'We don't know how much of the chemicals are in any brand or given batch of a brand.'
"Due to the associations between diacetyl, bronchiolitis obliterans and other severe respiratory diseases observed in workers," the study concluded, "urgent action is recommended to further evaluate this potentially widespread exposure via flavored e-cigarettes."
"Our goal was to raise awareness about this issue, enter it into this discussion about the e-cigarettes, and add to our knowledge about serious health concerns," Allen said.
In a blog post published after the study's release, Dr. Konstantinos Farsalinos, a cardiologist who researches e-cigarettes and who released a study last year that highlighted the potential risk of compounds like diacetyl that are used in e-liquids, raised what he said were shortcomings in the Harvard study.
"We emphasized the fact that none should deliberately add these compounds in e-liquids and tests should be conducted to detect potential sources of contamination. All these are, in my opinion, responsible measures to avoid this unnecessary exposure," he wrote of his previous study. "However, we also presented literature data that tobacco cigarette smoke contains high levels of diacetyl and acetyl propionyl, on average 100 and 10 times higher compared to our samples respectively."
Farsalinos argued that the Harvard study suggested that this chemical hazard was new, when in fact exposure through traditional smoking is much greater.
"The article is creating false impressions and exaggerates the potential risk from diacetyl and acetyl propionyl exposure through e-cigarettes," he said. "They failed to mention that these chemicals are present in tobacco cigarette smoke and violated a classical toxicological principle that the amount determines the toxicity and the risk."
In response, Allen said that Farsalinos had "misused occupational health limits and applied them to flavored e-cigarettes," and that Allen's own research had focused solely on the levels of diacetyl in e-cigarettes, so he could not speak to the levels found in tobacco cigarettes.
Last year, the e-liquid manufacturer Mt. Baker Vapor referred in a blog post to a study on diacetyl that found that levels of the chemical found in tobacco were higher than the levels found in factories where workers developed popcorn lung.
"Diacetyl exposures from cigarette smoking far exceeded occupational exposures for most food/flavoring workers," it quoted from the study. "This suggests that previous claims of a significant exposure-response relationship between diacetyl inhalation and respiratory disease in food/flavoring workers were confounded. Further, smoking has not been shown to be a risk factor for bronchiolitis (popcorn lung)."
Flavor chemicals are well regulated under the Food and Drug Administration's Generally Regarded as Safe (GRAS) designation. Many of them are banned for sale to e-cigarette companies by the Flavor and Extract Manufacturers Association (FEMA), according to Tracy Cesario, director of corporate communications and public affairs at FONA International, one of the major flavor manufactures in the US. They adhere to FEMA's standards that the GRAS chemicals are approved for ingestion, not inhalation.
"Therefore they do not stand behind use of flavors in e-cigarettes, and most companies like mine will not sell to any e-cigarette company since [FEMA's guidelines] came out. There are probably companies selling to them anyway — there must be if these flavors are getting in there — but we have a policy not to," Cesario said. "The challenge for a company like ours is that if an e-cigarette company asks for a sample and we say no, they can call back and say they're calling from Tracy's Fudge Company, and it's hard for us to tell."
Cesario said that most companies she was aware of did not want to get in the way of public health policy by selling the flavors to e-cigarette companies. FEMA did not immediately return calls from VICE News for comment.
Allen said that beyond the chemical flavor industry's efforts to try to regulate the inclusion of such chemicals in e-cigarettes, the FDA needs to regulate e-cigarettes more broadly. There is currently a proposal to include them under regulations for tobacco products, he said, but it has not yet gone through.
Michael Weaver, a professor at the University of Texas Center for Neurobehavioral Research on Addiction, said that because e-cigarettes contain many other liquid ingredients besides nicotine — few of which have been carefully studied — determining what each brand contains has been difficult. This is partly why they are not currently regulated by the FDA, but the problem cuts both ways, he said.
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"Because there's not regulation, we don't know how much of the chemicals are in any brand or given batch of a brand," Weaver remarked. "There's no standardization or incentive for appropriate labeling, because there's no regulation of that sort."
Some states have tried to pass regulations governing e-cigarettes, but consumers can often buy other products over state lines or on the internet. What's needed, he and Allen agreed, are federal regulations.
"We're very early in our understanding of potential adverse health effects of e-cigarettes, in particular around flavoring," Weaver said. "Not much is known at this point. But we know workers are required to receive warnings about these flavors, the flavor association recommends giving warnings, there are occupational health limits for workers, and we don't see same warnings begin given to consumers."
The danger of exposure is particularly worrisome for young users of e-cigarettes, according to Allen and Weaver. Because the flavors are generally marketed toward younger users, there is the potential for exposure starting at a young age and lasting longer than exposure in food plant workers. More than 1.8 million kids have tried flavored e-cigarettes as of 2012, Allen said.
"We know now that there are flavors being marketed toward children, and that the flavors have chemicals that have adverse effects," he stated. "I think it would prudent and protective of public health to take action now."
The FDA held three public workshops this year to gather safety information on e-cigarettes, but has not yet announced any proposed regulations.