This article has been updated with comments by researchers from VA San Diego and UC Riverside .

Electronic cigarettes could be made safer by improving control over their operating temperature and reducing deposits on heating elements, according to a study led by Lawrence Berkeley National Laboratory scientists.

If the study's findings are confirmed, they could provide a way to get the potential benefits from being used as a smoking cessation device, while reducing the risk of exposing those who haven't smoked to significant new harm. This issue is being hotly debated by public health agencies and scientists.

The new study, led by Hugo Destaillats, was published in the journal Environmental Science & Technology. Mohamad Sleiman, also of Lawrence Berkeley, was the first author. The study can be found at j.mp/vapchems.

The U.S. Food and Drug Administration is about to impose tough restrictions on e-cigarettes, but vaping advocates say it could destroy the innovation which has made e-cigarettes attractive as an alternative to smoking. The e-cigarette juices contain flavorings and in most cases varying levels of nicotine.

Researchers examined the chemicals emitted from two kinds of e-cigarettes, produced on a puffing simulator. One was an entry-level device with one heating coil; the other a more expensive one with two heating coils. These were tested with three types of juices, operated at varying battery voltages.

E-cigarette vaping generally produces far lower levels of potentially harmful chemicals such as diacetyl, formaldehyde and acrolein, than do tobacco cigarettes. So researchers generally agree that e-cigarettes provide a net health benefit compared to smoking cigarettes. For those who haven't been able to quit smoking any other way, e-cigarettes may provide a way out.

But researchers differ on whether e-cigarettes have been proven to be helpful as a general tool for stopping smoking, and what level of risk e-cigarettes pose. Some studies -- hotly disputed by vapers -- say e-cigarette use actually makes it harder to quit smoking.

Moreover, the discussion on potential harm from e-cigarettes focuses on indirect evidence. Studies have been performed on e-cigarette emissions applied to laboratory cell cultures, providing indications of potential harm. However, these studies haven't been performed on actual people.

Researchers measured production of possibly dangerous chemicals under these circumstances, and suggested ways that production could be reduced. It found that higher voltages produced more dangerous chemicals, as did extended operation and use of e-cigarettes with residues from previous use.

Inhalation risks

Researchers and a vaping advocacy group had mixed opinions on the study. The American Vaping Association and e-cigarette advocate researcher Dr. Michael Siegel of Boston University criticized it by email for using unrealistic conditions and overestimating potential harm.

In particular, they said battery voltages were tested up to a level that would have produced an unpleasant taste called "dry puff" that vapers avoid.

"This is a faulty study performed by researchers with limited to no understanding of how vapor products actually work," said Gregory Conley, president of the American Vaping Association. "The conclusions of respected organizations like the Royal College of Physicians and Public Health England -- that vaping is at least 95 percent less hazardous than smoking -- remain in force."

Other researchers took a more positive view of the study. Among them was Dr. Laura Crotty Alexander of the VA San Diego Healthcare System and UC San Diego, two major centers of e-cigarette research.

"These research findings are consistent with prior studies, and provide more detailed information about why and how dangerous chemicals are formed during the heating and aerosolization process," Crotty Alexander said by email.

"This is exciting information, as it moves us one step closer towards helping e-cigarette users choose safer devices, and use them in way that will produce fewer toxins. And along those same lines, help e-cigarette companies design safer devices."

Prue Talbot, a professor of cell biology and director of the UC Riverside Stem Cell Center, also praised it as well-performed and providing useful information.

Lawrence Berkeley National Laboratory is "well-equipped and skilled at performing these types of analyses," Talbot said by email.

"This is an important area of electronic cigarette research and this paper makes new and interesting observations on chemicals that could be inhaled by e-cigarette users," Talbot said.

A more restrained evaluation was provided by email from David W. Bareham, a respiratory physiotherapist at Louth County Hospital in Louth, England.

Bareham said the study provided some useful guidance in reducing levels of problematic chemicals, but it has significant limitations, such as the failure to test on actual vapers.

In summary, Bareham said "neither understated nor overstated headlines about this new research will be useful, and could be detrimental, if misinforming."

The chemicals in e-cigarette liquids are considered to be fairly benign by themselves. These include propylene glycol and glycerin, that carry flavoring agents.

However, these safety determinations were made for forms consumed with food, not inhaled into the lungs. And heating the liquid causes other chemicals to form that present dangers if taken in sufficient doses.

Some of the hazardous chemicals such as formaldehyde, are naturally present in the human body and in foods such as fruits. It's not clear whether e-cigarette use adds enough to the natural exposure to significantly harm health.

The study found that emission rates of aldehydes tripled when the voltage of single-coil devices was increased from 3.3 volts to 4.8 volts. Rates of acrolein, an irritant, increased by tenfold. It can cause COPD in low doses.

Safer, but not safe

Bareham said it remains clear that while e-cigarettes are safer than tobacco burning cigarettes, this doesn't mean e-cigarettes are safe.

"Obviously, lungs are not designed to routinely consume what constitutes heated food products, plus the chemical by-products subsequently produced through heating," Bareham said. "The specific effects of long-term inhalation of such a mixture of substances and by-products remains: unknown. Safe to digest is not the same as safe to inhale."

Bareham said the "dry puff" issue needs to be explored, to determine whether vapers actually do avoid the unpleasant taste or eventually become used to it.

He praised the study for offering actionable advice, such as reducing coil temperatures and proper maintenance such as more frequent coil replacements to prevent residue from accumulating.

One flavoring agent should simply be removed, because it is linked to disease and not needed, he said.

"The researcher’s finding of diacetyl – an additive utilized to produce a buttery taste – is relevant, due to a link to it causing Bronchiolitis Obliterans, an incurable lung disease," Bareham said.

The potential role of this chemical in e-cigarettes is unclear.

Diacetyl has caused the lung disease in microwave popcorn factory workers, who have been exposed to extremely high levels. Cigarette smoke hasn't been linked to the disease, although diacetyl is present in far higher concentrations than in e-cigarette vapor.

An anti-vaping campaign run by the state of California says that e-cigarette use is linked to popcorn lung disease, but doesn't cite any examples of the disease being actually being caused by vaping. Its Web page on the subject also doesn't discuss the far higher levels of diacetyl known to be present in tobacco cigarettes.

A state anti-vaping campaign claims that e-cigarettes are linked to popcorn lung disease, but doesn't cite any evidence. — Google screen capture

Bareham said there's no need to take on a potential risk from a chemical when it can be easily eliminated without impairing the vaping experience. And caution is needed, he said, because there's a lot more to learn about e-cigarettes.

"The new data may help us anticipate what long-term effects we may see in the distant future: it takes decades to see the full effects of inhaling tobacco smoke; the same will be true for e-cigarettes," he said.

Study flaws

Boston University's Michael Siegal said in his email that the study is "suspect" because the researchers didn't report the electrical resistance of the heating coils. This is needed to know how much power was actually delivered to the coils.

"However, based on investigating the resistance of the products used in the study, it appears that at least some of the testing was conducted under conditions that would never arise under real use because of the dry puff phenomenon," Siegel said. "The e-liquids were so overheated that no vaper would be able to tolerate it."

Siegel credited the study with providing useful information about how simple changes to technology could reduce risk even further.

"For example, it appears that most of these chemicals arise because of overheating of propylene glycol or glycerin. Therefore, by controlling the temperature, the presence of these chemicals can be avoided," Siegel said. "Similarly, the presence of propylene oxide is probably due to the use of non-pharmaceutical grade propylene glycol.

"The importance of these findings is that they demonstrate that technology is available to make vaping relatively safe by avoiding the production of virtually any hazardous chemicals at dangerous levels."

Siegel said the FDA could play a positive role by setting safety standards for e-cigarettes so they don't produce high levels of dangerous chemicals.

"Unfortunately, the FDA has chosen to go down a different path, which is to remove most of these products from the market," he said. "Moreover, the FDA regulations do nothing about e-cigarette devices that are problematic in terms of these chemicals.

Congress should stop the FDA, he said.

"Specifically, Congress must pass legislation that forces the FDA to regulate vaping products as their own category, not as cigarettes. The agency should be required to directly set safety standards for these products and not be allowed to require pre-approval of new products or product changes."

The research was funded by the Tobacco-Related Disease Research Program (TRDRP), managed by the University of California and funded by state cigarette taxes.

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