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Info from various viewpoints

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With the public health community sharply divided over the potential benefit and harm of the popular device-and with conclusive scientific evidence in short supply-the World Health Organization (WHO) released a report in August 2014 that raised serious questions about the health impact of e-cigarettes and called for a ban on indoor use and sales to minors. The report expressed "grave concern" over the growing role of multinational tobacco companies, warning that they could turn e-cigarettes into a gateway for a new generation of smokers at a time when a decades-long public health campaign has successfully reduced smoking rates in the US and other developed countries.

"In theory-and how they're marketed- e-cigarettes are a safer product because they don't have tobacco, which has known carcinogens," Spira says. "The question is: does safer mean safe?"

Also in August 2014, the Centers for Disease Control (CDC) reported that more than a quarter million youth who had never smoked a cigarette used e-cigarettes in 2013, three times the number of users since 2011. The Food and Drug Administration (FDA) proposed bringing e-cigarettes under its control alongside tobacco in the spring of 2014, but that proposal is enmeshed in debate and lawsuits. Dozens of states and cities across the country, including Boston, have already banned the use of e-cigarettes indoors.

At Boston University, Avrum Spira (ENG'02), a pulmonary care physician and School of Medicine professor of medicine and pathology and bioinformatics who studies genomics and lung cancer, was one of the first scientists to receive funding from the FDA to investigate the health effects of e-cigarettes. "In theory-and how they're marketed-e-cigarettes are a safer product because they don't have tobacco, which has known carcinogens," Spira says. "The question is: does safer mean safe?"

Across BU's Medical Campus from Spira, Michael Siegel, a physician and professor of community health sciences at the School of Public Health, has emerged as perhaps the country's most high-profile public health advocate for e-cigarettes. Siegel, who is not currently researching e-cigarettes, says he believes that the device could potentially help large numbers of smokers quit, or drastically decrease, a habit that is the leading cause of preventable deaths in the US. He points out that despite all the existing smoking cessation products on the market, only a small fraction of cigarette smokers manage to quit. Only 4 to 7 percent break the habit without some nicotine replacement or medication, according to the American Cancer Society. At the same time, Siegel says, more research is needed on the health effects of e-cigarettes as well as their effectiveness in helping people quit smoking.

Josh Jason, a 21-year-old junior at BU's College of Communication, is just the sort of consumer (young and hooked on smoking) who the e-cigarette industry is targeting and researchers want to better understand. Thinking it might be time to try to quit smoking, he bought his first e-cigarette a year ago. Jason says "vaping," as the e-cigarette habit is known, helped him cut way back-until the battery on his device died and, in need of a quick nicotine fix, he bummed a cigarette from a friend. Now, he is a dual user, trading off between vaping and smoking, depending on which form of nicotine delivery he has on hand. He buys his vaping supplies online (online sales are brisk) or at stores specializing in the product, and prefers e-cigarettes made by independent companies rather than Big Tobacco.

"I hate Big Tobacco," Jason says. "They know about the risks of cigarettes. They're pussyfooting around the fact that these things will probably kill you."

As much as he enjoys e-cigarettes, Jason is not unmindful of the risks. "There's no way e-cigarettes are totally safe," he says. "The only things our lungs were meant to take in is oxygen." On the other hand, he notes, vaping doesn't make him a social outcast the way smoking does. It doesn't smell bad or make his breath reek. "Hopefully, I'll move toward vaping rather than smoking," he says.

Siegel is among those experts critical of the WHO report who worry that overregulation could spell the end of what he and others believe could be the most disruptive public health tool to have come along in some time in the war on smoking. "Electronic cigarettes represent one of the greatest threats to cigarette smoking in many years," says Siegel, who has been battling Big Tobacco, cigarette smoking, and the harmful effects of secondhand smoke for well over two decades. "The WHO is trying to protect cigarettes from the threat posed by these fake cigarettes."

With research still in the early stages, here are things consumers currently don't know about e-cigarettes, according to the FDA:

The potential risks when used as intended. How much nicotine or other potentially harmful chemicals are being inhaled during use.

Whether there are any benefits of using them.

Recharchable Battery

Usually a lithium-ion battery powers the atomizer.

When a user inhales, the atomizer makes contact with the battery, activating the heating element. The liquid from the cartridge is then heated and vaporized.

Cartridge / Inhaler

The liquid cartridge can contain propylene glycol and/or vegetable glycerin, water, flavoring, nicotine, and other chemicals.

E-cigarettes are battery-powered-many can be recharged through USB ports-and while there are a dizzying array of varieties, they come in three main categories: cigalikes, which look like conventional cigarettes; eGos, which are larger than cigalikes and usually come with a removable tank that can be refilled with a liquid containing varying amounts of nicotine and a syrupy synthetic liquid called propylene glycol, a chemical that has been shown to be generally safe to consumers except at very high levels; and modular e-cigarettes (mods), which are usually larger than eGos and can be endlessly customized.

E-cigarette users inhale a vapor made by heating the nicotine-containing liquid and flavoring. Nicotine is a highly addictive substance, but e-cigarette users get their fix without the deadly carcinogenic tar that comes with combustible cigarettes. And yet, Spira says, there are crucial unanswered questions about just what e-cigarette users are inhaling into their lungs along with nicotine. "This is not a tobacco product," he says, "but when you burn a liquid, it changes the composition, and when you inhale that liquid, you get nicotine plus other chemicals. The question is, are those other chemicals harmful or not?"

Spira's preliminary research, using genomics to test the effects of the nicotine vapor on human bronchial cells, suggests that e-cigarettes may not be benign.

"It's cause for concern," Spira says. "We need to learn a lot more."

Avrum Spira says e-cigarettes may be safer than regular cigarettes, but that doesn't mean they're safe.

Avrum Spira is a Boston University School of Medicine professor of medicine and pathology and bioinformatics, the Alexander Graham Bell Professor of Healthcare Entrepreneurship, and chief of the Division of Computational Biomedicine. He is a pulmonologist at Boston Medical Center. With funding from the National Institutes of Health and, more recently, the Department of Defense, he has been working to develop molecular tests for early detection of lung cancer. Spira talked with BU Research about his research into the health effects of e-cigarettes, which is being funded by the FDA.

BU Research: You're a pulmonary researcher who has done groundbreaking work on early-stage lung cancer detection. You're also a pulmonary care physician and you've spent years treating patients with advanced lung cancer who had been heavy smokers. What are your concerns about e-cigarettes?

It took decades after cigarettes were introduced to sort out the health effects, which were devastating. Many people got addicted and they couldn't quit once the health effects became clear. The devastation is truly hard to imagine; according to the 2014 Surgeon General's report, more than 20 million deaths have been attributed to smoking in the US since the 1960s. The tobacco companies have recognized for many years that their product is hurting their customers, which also impacts their sales. So they have recently started to develop "safer" products. There is a lot of controversy around this. How do we know a "safer" product is really safer?

But before the big tobacco companies got involved, weren't e-cigarettes introduced and produced by independent companies as a way to get a nicotine hit without the tobacco and carcinogenic tar-as a safe alternative to cigarettes?

Yes, we could say that e-cigarette products have exploded in the marketplace, specifically in terms of brands, delivery devices, flavors, nicotine concentrations, as well as the delivery liquids. It's a complicated, fascinating, and rapidly moving space. There are currently a myriad of ingredients that can be combined in different ways to produce the vapor. This does present a challenge for researchers looking to identify the agents that are harmful, as each e-cigarette product is potentially different than the next. The FDA is trying to get a handle on standardization and potential risks of e-cigarette products by funding groups like ours to develop systems to rapidly assess these factors. But the research community is still scrambling to keep up with the rapid and unanticipated changes in this field.

Can you explain how e-cigarettes work?

E-cigarettes are a device that delivers nicotine-which is one of the addictive substances in cigarettes-without any actual tobacco, or tar. Tar has hundreds of known carcinogens. E-cigarettes have a battery-powered cartridge that heats a liquid containing nicotine and potentially a flavoring, which creates an aerosol that is inhaled. The e-cigarette community refers to this as "vaping," where traditionally we'd call it "smoking." Now, when you heat a liquid, it changes the chemical composition of that liquid and additional chemicals can form (e.g., formaldehyde, acetaldehyde, and acrolein), which are then inhaled by the user. The question is: are those other chemicals harmful or not?

Avrum Spira (MED) on the dangers of regulation without research

What do you think about the public health argument Professor Michael Siegel (of the School of Public Health) and others make, that e-cigarettes are an important tool for helping cigarette smokers quit who might not otherwise be able to?

I understand his perspective and don't entirely disagree. If there's a smoker who can't quit but who can use this product instead, that has a health benefit. This is almost certainly better than smoking traditional tobacco cigarettes. If this is a vehicle for quitting or a better alternative to traditional cigarettes, it could have a huge public health benefit. There are 45 million current smokers, adults in the US, who are unable or unwilling to quit. It's still a major public health problem. The other side of the debate is that this normalizes smoking behavior, that it's an entry point for younger people. A 15-year-old, an 18-year-old, says, "Okay, this is safe product," and gets addicted and it becomes a gateway to other products, including traditional cigarettes.

Our group was one of the first, in collaboration with Dr. Steve Dubinett (a pulmonologist at UCLA) to get funding from the FDA to study the health consequences of vaping. Our approach to evaluating e-cigarettes is based on what we've done with tobacco cigarettes, where we've developed genomic signals of exposure and, to take that a step further, signals of disease risk (e.g., lung cancer and chronic obstructive pulmonary disease, or COPD).

The question is: Does exposure to e-cigarettes create the same genomic changes in the airway as tobacco cigarettes do? Our prior work, over the past decade, has characterized a large number of genomic changes that traditional cigarette smoke causes in epithelial cells that line the upper airway (e.g., the windpipe) and has identified a smaller subset of changes that are associated with development of lung cancer and/or COPD among smokers. We are currently evaluating whether e-cigarettes produce similar gene expression changes as traditional cigarettes. In addition, we can correlate these genomic signatures to signatures of disease risk and begin to assess the chronic potential harmful impact of these products.

We decided to do our research in two phases. We started off with cells in culture. We took human bronchial epithelial cells that contained some mutations found in smokers at risk of lung cancer and cultured them with media that contains everything that comes out of an e-cigarette. The idea is that you're "smoking" the cells.

We found that the electronic cigarette was able to cause cells to become more cancer-like-they grew more quickly than a cell should be able to. That is one of the things that cancer cells do. That is the only thing we found-that it did change their growth rate significantly, more than smoking nothing and similar to smoking regular tobacco. That raised concerns on our end. Then we looked at the cells' genome and found that many of the same genes turned off and on by tobacco cigarette smoke are being turned on and off by e-cigarettes.

And you're now in Phase Two of your study? Can you tell us about that?

Our ultimate objective in Phase Two is to take people who smoke tobacco cigarettes, have them switch to e-cigarettes for at least two months, and sample the cells in their windpipe and their nose both before and after they switch. We would then perform genomic profiling on these samples. This entails measuring the activity of all 20,000 genes in your cells, which we can do in 24 to 48 hours. This produces a large amount data, so this is where computation comes in.

We are able to compile all of the data for all of the people we profiled and ask general questions, such as: when individuals switch to e-cigarettes, do their gene expression patterns or profiles resemble that of a former smoker? This would suggest that the product is potentially safer. Alternatively, does your genetic profile continue to look abnormal? And in that case, we would argue that e-cigarettes aren't necessarily safer.

With regard to disease, some smokers' genes turn on differently and that puts them at risk for cancer. So we can also look and see whether electronic cigarette exposure produces similar genomic changes that are associated with lung cancer.

Should e-cigarette users be concerned? Should they stop vaping?

We're not saying that e-cigarettes cause cancer. We can't say that based on this data. What we're saying is that we have evidence from cells in culture that e-cigarettes could have effects that are similar to tobacco smoking and that many more studies are needed before we can say this is a much safer product. That's where this fits into the whole public health debate. The FDA wants the academic community to come to the table with new approaches. That is what we responded to. The FDA has made a significant investment in our group and many other groups across the country to help study this in far greater depth. While it will likely take years via longitudinal studies to be absolutely certain of the safety of this new product, we're in the process of getting more data in the short term that will give us some more insight into the potential risks of e-cigarettes, so that potential users have that information.

John Caroll (COM) on the genius of Big Tobacco's ad machine

What about the public health history in terms of cigarette smoking and the lessons learned there?

We don't want to go down the road we did with cigarette smoking. It took 20, 30 years until the epidemiologic data came out convincingly that cigarettes cause cancer and other diseases. For many people, it was too late, as they were unable to quit and/or had already developed disease.

The genomic technology we have today-these approaches weren't available back then. It took long-term epidemiologic data before risks of exposure became clear.

We are in a new era of science and technology and medicine where we can do new types of translational studies. This type of science can potentially be done very quickly. We're not there yet and we won't be in a few months. Maybe in a couple years...but it need not be decades. We don't have to repeat the past. More science needs to be done as quickly as possible. We need to take a very careful look at this product and come to some preliminary conclusions. It's going to be very difficult to put the genie back in the bottle-the longer people use it, the more difficult it becomes to stop.

Why do you care so much about this research?

My passion is to care for patients with diseases. An ounce of prevention is worth a pound of cure. Most people start smoking when they're young. I take care of them many years later when they become a patient. I wish I could go back and stop them from starting smoking. I feel like this is my opportunity with a different product to perhaps prevent young folks from engaging in a behavior that could be harmful-so at least they're armed with information. E-cigarettes are, in theory, a safer product. They don't have a lot of the components found in tobacco. It's just-they may be safer, but they may not be safe. We need to clarify and I think it's important the public have that information. Even if e-cigarettes are not as bad as tobacco, it's important that we know what their health impacts are.

When I became a lung doctor, I was seeing a huge population of smokers who were getting diagnosed with lung cancer at this institution at an advanced stage where I couldn't offer them any effective treatment. We need to detect this disease earlier and prevent it. Once you're diagnosed with lung cancer, your survival rate is very poor.

What do you think about people who smoke cigarettes?

I'm okay with someone eating wrong, not exercising, smoking-as long as they know about the consequences of that behavior. I take care of a lot of people who smoke. A lot of them started when they didn't know it was bad to smoke. Smoking was a cultural phenomenon. People didn't know the health effects-and it's addictive. Later you can say, "Now we know," but if you're doing an addictive behavior for 20, 30 years, it's really hard to stop.

I don't judge smoking at all. I take care of patients unable to quit. That's why I see Siegel's argument. I know how hard it is to quit. Even some patients with lung cancer still can't quit.

Public Health professor Michael Siegel says concerns are premature and overblown

Michael Siegel, a Boston University School of Public Health professor of community health sciences, is a nationally known expert on the health risks, marketing, and regulatory policies concerning cigarettes. He argues that the controversy over e-cigarettes is misguided, and that it clouds the important benefits of the devices to help people quit smoking. Because only about 6 percent of cigarette smokers who try to quit are successful, and because the tobacco industry will continue to sell cigarettes despite tobacco's known health risks, Siegel is concerned that the government's focus on the potential harms of e-cigarettes will detract from their potential benefits to those who want to stop smoking.

BU Research discussed the controversy with Siegel.

BU Research: CDC director Tom Frieden has said the findings of increased teen use are "deeply troubling," deeming e-cigarettes a gateway drug to a lifelong addiction to nicotine and regular cigarettes. Do you disagree?

Siegel: Well, first, it's important to point out that this alarming conclusion is premature. There is no evidence that electronic cigarettes are serving as a gateway to a lifelong addiction to nicotine and conventional cigarettes.

There is something that Dr. Frieden didn't mention. The overwhelming majority of the youths who reported experimenting with e-cigarettes were already smokers. So the fact that these smokers are experimenting with e-cigarettes is not really a problem. The concern would be if nonsmokers were using electronic cigarettes, and then moving on to regular cigarettes. But the prevalence of nonsmokers experimenting with e-cigarettes in the CDC study was only 0.5 percent. Moreover, the study did not document any examples of youth starting to smoke as a result of first trying electronic cigarettes.

While there is every reason to be concerned about the potential for electronic cigarettes to become popular among youth, there is no reason to be alarmed at this point. It is essential that we continue to carefully monitor this. It is also important that the FDA promulgate regulations that will help prevent the use of electronic cigarettes by youth.

What do we know about the rising number of people who are using e-cigarettes as devices to quit smoking?

We do know that the predominant reason so many people are using e-cigarettes is that they want to quit smoking in order to improve their health. While we don't have a lot of quantitative studies about the effectiveness of e-cigarettes in smoking cessation, a clinical trial published recently found that e-cigarettes are just as effective as the nicotine patch for smoking cessation. Unfortunately, the e-cigarettes tested were a first-generation product that did not deliver nicotine very well. It is possible that more advanced products could actually surpass the nicotine patch in their effectiveness.

Josh Jason, the BU junior you talked with on our video, said he started vaping with the idea that it might help him quit smoking and is now vaping and smoking. Is he the "dual user" people are talking about?

Yes, he is an example of the classic "dual user." I can't predict what will happen for an individual, but we do know on a population basis that many dual users do go on to quit smoking completely. So it is simply not the case that someone who becomes a dual user will always be a dual user. For many smokers, dual use is a step along the progression to quitting smoking completely.

Do you think the intense government focus on e-cigarettes' potential negative effects is misplaced?

It is certainly reasonable to carefully scrutinize any consumer product like this. However, what I have a problem with is the fact that the FDA has given its seal of approval to the irredeemably toxic regular tobacco cigarettes-while they are doing everything they can to discourage people from switching to the much safer fake ones. That makes no sense from a public health perspective.

Leonard Glantz (CAS'70, LAW'73) on the wisdom of risk reduction

What about the WHO report that came out in August calling for some of the toughest regulations yet proposed on e-cigs, raising serious concerns about their health effects and expressing "grave concern" about the growing market encroachment of Big Tobacco? What do you think about the WHO's tough stance on e-cigarettes and do you share its concern about the tobacco companies' growing industry role?

There is no question that the WHO is overreacting to the supposed "threat" posed by electronic cigarettes. In fact, not only is the WHO overreacting, but it is taking exactly the wrong approach with respect to these products. Electronic cigarettes represent one of the greatest threats to cigarette smoking in many years. These products have already helped hundreds of thousands of people to quit smoking or to substantially cut down on the amount that they smoke. The WHO is actually taking the side of trying to protect cigarettes from the threat posed by these fake cigarettes. The WHO has consistently discouraged smokers from quitting by using e-cigarettes. This invariably has discouraged many smokers who might have quit successfully from trying to quit at all. In addition, the WHO has drawn shoddy scientific conclusions that are not backed up by the actual science. I'm afraid that the WHO has done a lot of public health harm on this issue.

But is there conclusive scientific evidence that e-cigarettes help smokers quit?

No, there isn't. We need more research. There needs to be a randomized trial. I want to do that study. The way to do it is to take a group of smokers and get them to switch to e-cigarettes and follow them over time. A randomized trial is the gold standard, but it would cost about $4 million. It's very difficult to get funding for that kind of study.

Are you concerned that big US tobacco companies, such as Altria and Reynolds, have entered the e-cigarette business, given the type of marketing they might do?

There are actually some benefits to having the major tobacco companies become players in the e-cigarette field. For one thing, they have better access to large retail outlets, and it is possible that their entrance into the market may greatly expand the access smokers have to these products.

In terms of marketing practices, it is essential that the FDA allow companies to tell the truth about the intended use of these products-that they are intended to be used for smoking cessation. That would avoid the need for companies to resort to some sort of glamorized marketing campaign that glorifies smoking behavior.

You've long opposed Big Tobacco and cigarettes, but now, ironically, are you on the same side as Big Tobacco when it comes to e-cigarettes?

I don't think it's fair to say that I'm on the same side as Big Tobacco regarding electronic cigarettes. It's a very complex issue. I think that the tobacco companies see a prospective niche market-there are many smokers who want to quit and e-cigarettes are a potentially lucrative business. So it makes economic sense for tobacco companies to try to derive some of their income from noncombustible nicotine products. In fact, I think the industry can see long term that the field is changing and that the combustible market will eventually shrink. They want to expand their offerings so that they can derive income from noncombustible sources.

Are you worried that e-cigarette advertising and photos of celebrities vaping will make cigarette smoking-a behavior you've spent your career trying to decrease drastically-glamorous again?

I don't think that e-cigarette advertising glamorizes smoking. I think it glamorizes vaping. However, I do think that the more advertising is focused on marketing these products as ways to quit smoking, the more public health benefit will come from these products. Right now, if an e-cigarette company marketed its product for smoking cessation, it would run the risk of being deemed as having made a therapeutic claim and having the FDA pull it off the market. My opinion is that the FDA should explicitly allow companies to tell the truth about the intent of the product without having it considered a therapeutic claim.

Most scientists believe nicotine, while highly addictive, is not what causes cancer in smokers or people exposed to secondhand smoke. Has there been any scientific research into the negative health effects of e-cigarettes?

It is very true that nicotine is not the main component of the tobacco smoke that is responsible for most of the adverse health effects. Because electronic cigarettes deliver nicotine without most of the tens of thousands of other chemicals-and without the more than 60 known carcinogens-it is clear that electronic cigarettes are much safer than tobacco cigarettes.

The scientific research conducted so far suggests that electronic cigarettes are much safer than regular cigarettes, and that in particular, they carry a greatly reduced risk of lung cancer, other cancers, and chronic obstructive lung disease. Evidence presented just recently suggests that they also likely present a lower risk of heart disease. We need more research to understand whether there may be long-term adverse effects. But what we can say for sure is that they are much safer than the real cigarettes.

Do you think science will settle the debate over e-cigarettes that has divided the public health community?

I don't think science will settle this because many opponents of e-cigarettes are so biased in their views that I don't think they will objectively look at the science. In fact, this is already happening. A large group of researchers has already concluded that e-cigs are a gateway to smoking, but the science doesn't support such a conclusion.

How did you get interested in e-cigarettes?

I have been following the issue of electronic cigarettes since they entered the US market several years ago. My interest was piqued by the response that these products received from public health and antismoking groups.

Rather than embracing these products as a potential way to get thousands of smokers to quit smoking, antismoking groups have attacked these products and discouraged smokers from quitting by using them. This is so contrary to the principles of public health that it caught my attention-and I continue to be puzzled by this inane public health response.

The only hypothesis I have come up with is that the ideology in the antismoking movement is so strong that the very thought of condoning a behavior that looks like cigarette smoking is just something that these groups are not capable of doing-even though it is likely saving the lives of thousands of ex-smokers.

Mike Seigel (SPH) on the balancing act of public health

What is the most effective smoking cessation tool we have?

Unfortunately, we don't have an effective cessation tool. The best available treatments, such as Chantix and nicotine replacement therapy, only work long-term for about 8 percent or so of the population. We need to do better than that.

Why do you feel so passionately about e-cigarettes?

Because I've seen them save the lives of thousands of individual smokers who would not have quit smoking without them.

Listen to Michael Siegel discussing e-cigarettes during an interview with WBUR's On Point here.

Discuss this story on BU Today.
The FDA has proposed regulations that would bring the device under its control as a tobacco product. What do you think?

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With the public health community sharply divided over the potential benefit and harm of the popular device-and with conclusive scientific evidence in short supply-the World Health Organization (WHO) released a report in August 2014 that raised serious questions about the health impact of e-cigarettes and called for a ban on indoor use and sales to minors.

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"You go to the bathroom, there's a zero percent chance that anyone's smoking a cigarette and there's a 50-50 chance that there's five guys Juuling." Credit Credit Photo Illustration by Caroline Tompkins for The New York Times

Kids will keep Juuling until we make vaping as uncool as smoking. Is the Juul craze almost over? Probably not!

"You go to the bathroom, there's a zero percent chance that anyone's smoking a cigarette and there's a 50-50 chance that there's five guys Juuling." Credit Credit Photo Illustration by Caroline Tompkins for The New York Times

When Brennan McDermott was an underclassman at Simsbury High in Connecticut, he found himself in a timeless situation, familiar to watchers of horny 1980s comedies and after-school specials alike. "A couple of my buddies were like, 'Hey, let's go to the bathroom,'" said Mr. McDermott, now Simsbury's senior class president. "I was like, 'Whoa, what's going on here?!' I got kind of uncomfortable with it. They were all passing it around. I didn't take it."

In a modern twist from coming-of-age canon, though, "it" wasn't a cigarette - it was a small, rectangular vape product known as the Juul.

In the public imagination, vaping - with its oversize, multipart manipulatable products - has become associated with a techier, dweebier slice of the population. But as early as 2015, e-cigarette use by high-school and middle-school students had eclipsed cigarette use.

And by late 2017, an informal consensus had burbled up from students, teachers, parents and the internet: All across the country teenagers who in generations past would have become cigarette smokers - or, perhaps, would have never taken up smoking - were falling in love with the Juul.

"Cigarettes, they're not even a factor anymore," Mr. McDermott said. " Nobody smokes cigarettes. You go to the bathroom, there's a zero percent chance that anyone's smoking a cigarette and there's a 50-50 chance that there's five guys Juuling. And it's like, how Band-Aid has become synonymous with 'bandage'? Juul has become synonymous with 'vape.'"

Created by two former Stanford University design students, the Juul attempts to mimic the nicotine hit of a real cigarette, and sells for $49.99. Over Christmas, Nielsen reported Juul had achieved a 46.8 percent market share - exceeding the top market share achieved by Marlboro cigarettes at the peak of that product's measured success. Then, last month, Nielsen said Juul had 54 percent of the market.

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Credit Caroline Tompkins for The New York Times

I, an adult, first noticed the Juul on the various Instagram feeds of the unapologetically dumb Barstool Sports. In recent months, they've been flooded with college kids finding creative ways to display their prowess with, or devotion to, their Juuls: kids hitting their Juuls at their parents' dining room table over fall break; kids hitting their Juuls in the hospital after a bloody drunken escapade. It was all a bit bewildering.

It took oodles of efficient pop-culture manipulation for America to accept cigarettes as the ultimate symbol of rebellious cool. But now, all of a sudden, a vape is cool?

Sebastian and Gio, students at a continuation high school in Northern California, both Juul. "I'm on probation so I can't smoke marijuana," Gio said, by way of explanation. (The students asked that their last names not be used, for fear of disciplinary infractions.) "And I don't want to smoke cigarettes. Cigarettes taste nasty."

Sebastian said: "I like the feeling of it. The lightheadedness. It makes me feel sober and high at the same time. Plus it looks sleek - you smoke it, you look kind of bougie." Both are also fans of Juul's flavored tobacco pods. In particular, Gio said: "Mango! That Mango go hard." (Other flavor options include Cool Mint, Fruit Medley and Creme Brulee.)

As for discretion, Gio said, "It looks like a USB drive. It doesn't look suspicious."

Chidum Okeke, 18, of Louisville, Ky., said, "In my opinion it looks like the coolest thing ever. Almost futuristic."

Mr. Okeke doesn't Juul, but he has gone a bit viral tweeting about it.

He traces the inflection point to early 2017. That is when the "Juul wave," as some have called it, started to go from the popular-kid set in his grade to entire neighboring schools. "It's so small, so easy to hide in the palm of your hand," he said. "And they're rechargeable! I've lost track of the number of people I have found charging their Juuls in class through their laptops. It's almost comical."

Mr. Okeke said he also knows kids who have named their Juuls; names he has heard include "Juulia" and "Richard."

In February, Greta Frontero, an 18-year-old senior at Westfield High in New Jersey, wrote an article for her school paper about the Juul. It is a true gem of reportage: "A senior male was caught Juuling during class when his chemistry teacher's back was turned. 'I took a hit of it and blew it in my sweatshirt, but the smoke came out the back of my jacket,' he said. 'When my teacher asked why there was smoke coming out of my jacket and I opened my mouth to respond, more smoke came out of my mouth.'"

"It's almost like a game," Ms. Frontero said. "Like if the teachers would catch you doing it or not." But it's not just school, she said: At house parties, Juuls are so rampant that theft has become an issue.

"It's so small, so easy to hide in the palm of your hand." Credit Photo Illustration by Caroline Tompkins for The New York Times

That's where customization has come in. "I've seen nail-paint polish, initials carved in, smiley-face stickers," Ms. Frontero said. "It's really just to make sure that if someone steals yours you know it's yours. And they're everywhere. You're in someone's basement and the host doesn't even know you're doing it 'cause they don't smell."

For the record: At least in Westfield, kids use a different product, wax pen vaporizers, for smoking weed. The Juul is strictly for tobacco.

After her article came out, Ms. Frontero said, "the teachers had to catch up." Now kids at Westfield are getting handed three-day suspensions for Juuling. Gio, from Northern California, agreed that "teachers are starting to see what they really are."

So have kids started carrying actual USB drives, just to throw teachers off the scent? Gio laughed. "Not yet!"

And getting a Juul is as easy as ever. "My friend has a middle school brother and they walk into Krauszer's" - a local New Jersey grocery store - "and buy it without any question," Ms. Frontero said. "It's ironic. This product was made to wean addicts off cigarettes, and in reality it's attracting teenagers who would never smoke."

The glamorization of the cigarette took place over decades and throughout countless Hollywood movies and glossy ads. The Juul iconicity was birthed much faster: through social media. That includes personal accounts, kids eager to fuel the Juul wave with winkingly knowing tweets about the hype cycle.

With more cynicism, Barstool Sports and other youth-targeting brands have jumped on the bandwagon, too. Arya Toufanian is the 25-year-old proprietor of I'm Shmacked, a Girls Gone Wild-style roving party and video series. "We started to post Juul stuff maybe six months ago, and we started getting submissions right away," Mr. Toufanian said. "You can tell immediately when a product is viral."

I'm Shmacked then paired the Juul with another recent teenager obsession. "We made fidget spinners out of Juuls," Mr. Toufanian said with pride. "We thought, you know, people are holding Juuls all the time anyway! A university student built a render and we 3-D-printed it. It was kind of a grass-roots project in a way."

"One of the things I'm super-interested in is meme culture," said Mr. McDermott, the Simsbury High class president. "What resonates with our generation is the memes. I haven't seen the Juul on TV. But you'll see a bunch of memes about Juuling. It's just, like, making it more socially acceptable - it's perpetuating the thing that vaping is cool."

Ashley Gould, the chief administrative officer of Juul Labs, is careful to walk a line between pride and responsibility. "We're the No. 1 e-cigarette in the United States," Ms. Gould said. "And we're not a big tobacco company. We're an independent company."

Pointing out she is not a smoker, Ms. Gould ticked off some of the properties of the Juul that the company believes have made it big: the way the "formation of the e-liquid mimics the way the nicotine is delivered in a cigarette"; the fact that Juul was the first to "design an e-cigarette that was not cylindrical." But, she added, "what we've seen happening with youth we did not want to be happening."

"We're taking it extremely seriously," Ms. Gould said. "We do not want underage kids using our products. Our marketing is directed toward adults, tested with adults. And I do think it's worth noting: All of the things you see on social media, we have absolutely nothing to do with. We actively try to take these things down. But unless there's an infringement of our intellectual property it's quite difficult."

So the teen love caught the Juul team off guard?"Yeah," Ms. Gould said. "I think that's a fair statement. We're actively trying to understand it so that we can combat it - but I can't tell you that we currently understand it today."

Recently, memes and health fears have collided: now kids are going viral by warning each other to stop Juuling. In February the Twitter user @MateaCannavino collected screen grabs of messages purportedly from friends of friends diagnosed with Juul-related diseases. (Her commentary: "the Juul wave is ~over~.")

"A few weeks ago there was a whole thing going around that it caused lung cancer. And for probably, like, a day people were like, 'I'm going to stop doing it!'" Ms. Frontero said, and laughed. "And then that quickly faded. I don't think anyone's all that concerned."

So can anything stop this youthful fandom? Perhaps the only hope to end the teenagers' winking love of the Juul is to expand the demographic out of its hipness. To that end, I'm doing my part. On a recent winter evening, a buddy and I walked out of a show and into a surprisingly pleasant Thursday evening in Manhattan. We'd just seen Yung Lean and Thaiboy Digital, two delightfully strange international musicians, and we were buzzing.

It was one of those latish, drunkish weekday nights that had the potential to become a properly late, properly drunk weekday night. In fact, in a few minutes, we'd find an Irish bar and drink more, fast. But first my buddy wanted to smoke. In the past, in times like these, I might bum a cigarette or two or seven. Instead, he took out a small, square vape. Here we were. A couple of grown men. Hitting the Juul.

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Kids will keep Juuling until we make vaping as uncool as smoking. Is the Juul craze almost over? Probably not! "You go to the bathroom, there's a zero percent chance that anyone's smoking a cigarette and there's a 50-50 chance that there's five guys Juuling."

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That smoking causes cancer is a well known and scientifically proven fact. Everyone knows that nicotine is present in cigarettes, and causes addiction to smoking; however, what's a little less well known is the range of chemicals contained within cigarette smoke that can lead to carcinogenic (cancer causing) effects, and what other effects they can have on the body. The effects of some of these chemicals also explain why it's advised that women shouldn't smoke during pregnancy.

Cigarette smoke contains a huge number and range of organic compounds. Estimates in the past few years state that there are almost 7360 different compounds present, and it is likely that this number could still increase. Of this massive number of compounds, 70 have confirmed carcinogenic activity in humans, and many more are suspected carcinogens.

Let's start with an obvious chemical first, however: the non-carcinogenic nicotine. Nicotine is a member of the alkaloid family of compounds, a family of which caffeine is also a member. Cigarettes contain, on average, around 10mg of nicotine; when it is inhaled in cigarette smoke, it is absorbed into the bloodstream, and when it reaches the brain it stimulates the production of a number of neurotransmitters. Nicotine impersonates the neurotransmitter acetylcholine (ACh), and by binding to receptors ACh would usually bind to, stimulates the production of dopamine, which is involved in your body's 'reward' pathways. This leads to the addictiveness of smoking. Nicotine is actually toxic to humans in high doses - much higher than those obtained from smoking cigarettes.

Let's take a look at some of the other organic compounds in cigarette smoke with more harmful effects:
N-Nitrosamines
These are a large class of nitrogen-containing organic compounds. The majority of nitrosamines that have been studied have been shown to cause DNA mutations, and several are known human carcinogens, including some that are specific to tobacco. Of these, NNK (nicotine-derived nitrosamine ketone) and NNN (nitrosonornicotine) are considered to have the highest risk for carcinogenic action. Research has shown that the amounts of tobacco specific nitrosamines varies widely, and that low tar brands tend to exhibit lower levels of these compounds - though they remain present.
Benzene
Benzene is an organic chemical that is actually formed naturally, as a result of occurrences such as forest fires or volcanic eruptions. However, an important source of human exposure to this compound comes from cigarettes, which are estimated to account for up to 50% of exposure in the USA. Benzene is a proven carcinogen, based on evidence from both animal and human studies. It's also been shown to cause changes to chromosomes in bone marrow under laboratory conditions. Bone marrow is where new blood cells are made, so damage to this can lead to anaemia, and low levels of other blood constituents.

Industrially, benzene is useful to make ethylbenzene, a precursor to styrene. Styrene can be polymerised to form polystyrene.
Aromatic Amines
Aromatic amines are another family of compounds, often used in the synthesis of pesticides, plastics, and pharmaceuticals. They're also found in cigarette smoke, with their levels tending to be higher in sidestream smoke (that produced at the lit end of the cigarette). Several of these compounds are confirmed human carcinogens, with increasing evidence that they contribute to bladder cancer in smokers in particular.
Formaldehyde & Acetaldehyde
These two compounds are both members of the aldehyde family of compounds. Formaldehyde is known to be a human carcinogen, whilst acetaldehyde is classified as a confirmed carcinogen in animals and a probable carcinogen in humans. Acetaldehyde is in fact the most abundant carcinogen in tobacco smoke, and dissolves into saliva when smoking. Both acetaldehyde and formaldehyde cause irritation of the skin, eyes, throat, mucus membranes, and respiratory tract.
1,3-Butadiene
1,3-butadiene is a simple hydrocarbon molecule, containing 2 double bonds. In a 2003 study (Fowles & Dybing), the risk factor of various compounds in cigarette smoke for cancer and heart disease was considered, and 1,3-butadiene presented the highest cancer risk by some margin. It's also a suspected human teratogen (causes deformation of embryos). Studies on animals have shown that breathing butadiene during pregnancy can increase the number of birth defects.
Acrolein
Acrolein is an unsaturated aldehyde (an aldehyde also containing a carbon-carbon double bond). It's a toxic compound, and an irritant to the eyes, skin, and respiratory tract. Links have been made between acrolein in cigarette smoke and the development of lung cancers, though no there is no current scientific evidence that it is a carcinogen in humans. However, it is a known DNA mutagen, and this in turn could lead to carcinogenic effects. Acrolein has also been been linked with heart disease as a contributor, and is one of the most abundant chemicals in cigarette smoke.
Polyaromatic Hydrocarbons
Polyaromatic hydrocarbons are a group of over 100 different organic chemicals formed by incomplete combustion of organic compounds. Several have been identified are carcinogenic, mutagenic, or teratogenic. Benzo-a-pyrene is one of the most potent, and notably was the first chemical carcinogen to be isolated. High exposure to polyaromatic hydrocarbons in the womb has been associated with lower IQ and childhood asthma, as well as adverse post-birth effects including heart malformations and DNA damage.

The graphic in this article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. See the site's content usage guidelines.
References & Further Reading

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The Chemicals in Cigarette Smoke & Their Effects

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That smoking causes cancer is a well known and scientifically proven fact. Everyone knows that nicotine is present in cigarettes, and causes addiction to smoking; however, what's a little less well known is the range of chemicals contained within cigarette smoke that can lead to carcinogenic (cancer causing) effects, and what other effects they can have on the body.

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THEY ARE EVERYWHERE, FROM GAS STATIONS TO DRUG STORES TO BODEGAS TO VAPE SHOPS, and they come in a wide range of flavors: menthol, scotch, vanilla, and even cappuccino. Also, unlike regular cigarettes, people under the age of 18 are legally allowed to purchase e-cigarettes in many states.

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Vapors from some flavored e-liquids contain high levels of aldehydes - American Chemical Society

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American Chemical Society: Chemistry for Life.

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Are E-cigs Safer Than Cigarettes? - American Chemical Society

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People have turned to "vaping" with electronic cigarettes. But is that vapor you're inhaling any safer than taking a drag on a cigarette?

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" Emissions from Electronic Cigarettes: Assessing Vapers' Intake of Toxic Compounds, Secondhand Exposures, and the Associated Health Impacts"
Environmental Science & Technology

E-cigarettes are often perceived to be less harmful than their traditional counterparts, but they could still expose the people who "vape" and those around them to harmful compounds. Researchers now report in ACS' journal Environmental Science & Technology that heavy use and secondhand emissions could lead to inhaled levels of toxins that exceed set exposure limits. But under typical use, secondhand exposure would have a lower impact on health than second- and third-hand cigarette smoke.

While e-cigarettes don't produce tobacco smoke with its associated toxins, the vapors they generate contain other compounds that are potentially dangerous to human health. These include acrolein, a toxin and irritant to the eyes, skin and nasal passages; formaldehyde, which is recognized as a human carcinogen; and diacetyl, a substance that can cause respiratory problems. Hugo Destaillats and colleagues wanted to find out how much of these compounds users and others nearby might be inhaling.

Vapers' intake of toxic compounds was modeled for scenarios in which different e-liquids were used with various vaporizers, battery power settings and vaping regimes. The study predicted that heavy users inhaling at a high rate of 250 puffs per day with devices at 3.8 to 4.8 volts would potentially inhale levels of acrolein (up to 10 mg per day), formaldehyde (up to 49 mg per day) and diacetyl (up to 0.5 mg per day) that exceed U.S. occupational limits of 1.3 mg per day, 0.1 mg per day and 7 micograms per day, respectively. Also, a model of indoor exposure estimated that in bars where vaping is permitted, formaldehyde and acrolein levels would often exceed California reference exposure limits. In comparison to secondhand and thirdhand tobacco smoke, the researchers computed that "disability-adjusted life years" lost due to exposure to secondhand vapor would be one to two orders of magnitude lower under typical vaping use.

The authors acknowledge major funding from the University of California Tobacco-Related Disease Research Program (TRDRP). Additional funding came from Argentina's National Scientific and Technical Research Council (CONICET), the Agencia Nacional de Promoción Científica y Tecnológica (Argentina) and the U.S. National institute on Drug Abuse.

The American Chemical Society is a not-for-profit organization chartered by the U.S. Congress. ACS is the world's largest scientific society and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. ACS does not conduct research, but publishes and publicizes peer-reviewed scientific studies. Its main offices are in Washington, D.C., and Columbus, Ohio.

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Exposure to toxins in e-cig vapor varies depending on scenario - American Chemical Society

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" Emissions from Electronic Cigarettes: Assessing Vapers' Intake of Toxic Compounds, Secondhand Exposures, and the Associated Health Impacts" Environmental Science & Technology E-cigarettes are often perceived to be less harmful than their traditional counterparts, but they could still expose the people who "vape" and those around them to harmful compounds.

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Abstract

Knowledge of the mechanism of formation, levels and toxicological profiles of the chemical products in the aerosols (i.e., vapor plus particulate phases) of e-cigarettes is needed in order to better inform basic research as well as the general public, regulators, and industry. To date, studies of e-cigarette emissions have mainly focused on chromatographic techniques for quantifying and comparing the levels of selected e-cigarette aerosol components to those found in traditional cigarettes. E-cigarettes heat and aerosolize the solvents propylene glycol (PG) and glycerol (GLY), thereby affording unique product profiles as compared to traditional cigarettes. The chemical literature strongly suggests that there should be more compounds produced by PG and GLY than have been reported in e-cigarette aerosols to date. Herein we report an extensive investigation of the products derived from vaporizing PG and GLY under mild, single puff conditions. This has led to the discovery of several new compounds produced under vaping conditions. Prior reports on e-cigarette toxin production have emphasized temperature as the primary variable in solvent degradation. In the current study, the molecular pathways leading to enhanced PG/GLY reactivity are described, along with the most impactful chemical conditions promoting byproduct production.

E-cigarettes have emerged as a major public health issue, having been introduced in the U.S. in 2007. By 2014, U.S. sales totaled $2.5 billion. While enabling many to stop using traditional cigarettes, a meta-analysis has shown that e-cigarettes are associated with significantly less quitting among smokers than may be commonly believed. Moreover, in a recent longitudinal study, e-cigarettes were consumed by adolescents who would not have otherwise used tobacco products. According to the National Youth Tobacco Survey, in 2013 > 250,000 middle and high school students in the US had used e-cigarettes prior to a traditional cigarette. By 2014, there were >450 brands and >7,770 e-cigarette flavors marketed. In 2015, 16.0% of high school and 5.3% of middle school students reported current use, representing 10- and 5-fold increases since 2011, respectively.

To date, studies of e-cigarette health effects on humans have been limited. For example, studies of the viability of vapers to self-regulate toxin intake by taste alone have typically involved very few human subjects. Moreover, the long-term effects of vaping cannot be known for at least another decade. There is also a lack of established in vivo animal models of e-cigarette exposure.

Knowledge of the mechanisms of formation, levels, and toxicological profiles of the chemical products in the aerosols (i.e., vapor plus particulate phases) from e-cigarettes is needed in order to better inform basic research as well as the general public, regulators, and industry. However, there is currently significant inter-laboratory variation in the published data on the levels of chemical components of electronic cigarette aerosols. As noted by others, this is a reflection of the novelty of the field as well as several major inherent challenges. These include the ongoing emergence of new device configurations, variability in the puffing patterns between individuals, the lack of standardized analytical protocols, and variability between devices.

Studies of e-cigarette emissions have mainly focused on chromatographic techniques for comparing the levels of selected e-cigarette aerosol components. While many studies have reported that e-cigarettes generally have fewer as well as lower levels of the toxins produced from traditional cigarettes, comparing the relative safety of e-cigarettes to traditional cigarettes does not take into account several key factors. For example, e-cigarettes do not combust tobacco, but instead heat and aerosolize nicotine and/or flavorants in the solvents propylene glycol (PG) and glycerol (GLY). Nicotine-free soluble components of e-cigarettes have been linked to dose-dependent loss of lung endothelial barrier function. E-cigarettes therefore produce unique product profiles as compared to traditional cigarettes. Although their study to date in the context of traditional cigarettes is informative, it is also limiting and, moreover, irrelevant to the growing number of young people that are vaping without having ever smoked a cigarette.

The chemistry of PG and GLY has a rich history. The preparation of GLY in 1779 by Scheele, and his determination that it was susceptible to thermal decomposition during simple distillation, predated even Wöhler's urea synthesis by half a century. By the mid-19 th century, acrolein and acetic acid had been identified as products of GLY decomposition. Wurtz synthesized PG in 1859, and determined that it could be oxidized to lactic acid in air in the presence of catalysts. In 1904, Nef provided the foundation for the current understanding of GLY and PG chemistry. He reported that heating GLY afforded hydroxyacetone, acetaldehyde, formaldehyde, acrolein, 3-hydroxypropanal, and a series of acetals. He discovered that GLY formed glycidol upon gentle heating in the presence of acetic acid. Nef also discovered that the decomposition of PG gave propanal. The literature moreover strongly suggests that there should be more compounds produced by PG and GLY than have been investigated in the majority of e-cigarette aerosol studies to date. We propose that since NMR is a technique that can enable relatively broad profiling of compound classes with limited sample perturbation, it will allow the detection and study of overlooked e-cigarette aerosol products as compared to studies that to date have relied nearly exclusively on chromatographic-based methods.

Recently, we reported the discovery of hemiformals 1a and 1b (major isomers observed are shown in ), products of the reaction of PG/GLY with HCHO that are formed during PG/GLY aerosol generation. Herein, we describe an extensive investigation of the products derived from vaporizing PG and GLY under relatively mild e-cigarette conditions, along with a detailed description of the molecular pathways leading to product formation. Products identified by NMR include glycidol ( 2), an International Agency for Research on Cancer (IARC) Group 2A probable human carcinogen. In addition, we report several products identified for the first time in e-cigarette aerosols such as reactive vinyl alcohol isomers ( 3a and 3b) and dihydroxyacetone ( 4), the main ingredient in spray tan products that has raised concerns as an inhalation hazard.

Results and Discussion

General Methods

Aerosol sample production and initial analysis

The e-cigarettes used in this study consisted of two main components, a variable voltage/variable wattage (VV/VW) battery, the Innokin ® iTaste VV4, fitted with a KangerTech ® Protank-II clearomizer. The clearomizer contained a replaceable bottom heating coil (coils with resistances from 1.8-2.5 Ohms were provided by the manufacturer) embedded in a wick that was covered with the PG/GLY e-liquid during usage. E-liquids were composed of 1:1 v/v PG:GLY solutions, except where indicated. Single puffs of aerosolized e-liquid (50 mL) were drawn via a syringe directly into a DMSO-d ₆ solution for analysis by NMR spectroscopy. Between 6-22 mg of aerosol were collected per puff. Such data from single puff samples was obtained because NMR is non-destructive, meaning that one can signal-average until sufficient signal-to-noise is obtained for the required analyses. Typical parameters included: a 30° observation pulse angle, a 6.2 sec repetition rate, and 64 k data point acquisitions for between 64 and 2048 acquisitions (between 0.12 and 2 hr). Line broadening of 0.3 Hz and a final data size of 64 k real data points were used for data processing. Structure assignments were confirmed by minute addition of authentic standards. This was accomplished by first determining the concentration of the component of interest versus an internal standard, the value of which was used as a benchmark for the added amount of pure standard.

Results

illustrates that more PG/GLY was consumed as a function of increasing device power. In addition to raising the power settings to directly elevate heating coil temperatures, elongating the puff duration likewise promoted PG/GLY consumption. It is well-known that e-cigarette operating temperatures modulate the extent of PG/GLY degradation. In the context of the investigation herein, the experiments illustrated in show that the ability of the device to produce aerosol mass and the intensities of novel aerosol product peaks in an NMR spectrum are proportional to the power delivered to the e-cigarette coil.

Avoidance of dry coils and burnt e-liquid

Conditions were chosen to avoid drying the heating coil and associated overheating of the e-liquid; it has been proposed that users can detect and self-regulate toxin intake (including HCHO) based on taste. However, it is known that in traditional cigarettes the harsh taste from formaldehyde and other aldehydes is overcome due to the nicotine drive and to cross-desensitization of transient receptor potential ankyrin subtype 1 (TRPA1) channels in sensory neurons. Moreover, it has not been shown to what degree the use of flavorants in e-cigarettes dulls or overcomes any harsh taste from toxins.

Nonetheless, several steps were taken to avoid overheating of PG/GLY. First puffs were sampled as single acquisitions, or with 5 min puff intervals or longer between any two puffs, and no primer puffs were used. Extra wicking and cooling of the coil were performed by pulling the syringe (cold puff) without activating the device, again 5 min before the sampling puff. These methods ensured that aerosols were never generated from dried coils, since e-liquid had cooled between puffs and had completely covered the coils prior to drawing any aerosol samples. Also, an average 3-5 s puff duration was used. In addition, the Innokin ® iTaste VV4 battery (1000 mAh) that was used herein possesses a variable output of 6.0-15 W and variable voltages of 3.0-6.0 V, and is compatible with a variety of clearomizers. This device is described by the manufacturer as accurate to within 0.1 W with "no fluctuation and unexpected dry hits or burned e-liquid", and has its highest 15 W setting precisely maintained between 0.8 to 2.5 ohms. Both the Innokin battery and KangerTech ® Protank-II clearomizer had received positive reviews from the online vaping community.

Identification of aerosol products

The compounds that have been identified in this study are shown in ; all of these compounds could be predicted based on the existing PG and GLY literature. Several are reported here for the first time in electronic cigarette aerosols ( 3, 4, 6-8). The determination of others (e.g., 2, 15) validates their recent discovery in e-cigarette aerosols, and moreover shows that they can form under milder conditions than those reported. Structure assignments for all compounds were validated via spiking with authentic samples when available ( Supporting Information).

Formaldehyde hemiacetals

Glycerol formal was described by Nef in 1904, and propylene glycol formal was described by Trillat and Cambier in 1894. The production of 1a and 1b in e-cigarette aerosols was thus not surprising, particularly since hemiformals are relatively stable compared to other acyclic hemicacetals. The toxicity of 1a and 1b has not been investigated. They reverted to HCHO and PG over a period of hours in aqueous solution. Since 1a and 1b have not been separable to date we validated the structure assignment using isotopically labeled CH ₃OCH ₂OH (methoxymethanol) as a model hemiformal. As depicted in , labeled CH ₃OCH ₂OH exhibited analogous peak position as well as the characteristic O-H proton splitting pattern corresponding to those reported for 1a and 1b. The ¹H- ¹³C decoupled spectrum B corresponded to that of the product formed by bubbling ¹²CH ₂O in CH ₃OH (spectrum C). Upon spiking with D ₂O (spectrum D) the hydroxyl resonance at 6.14 ppm diminished and the methylene protons at 4.53 ppm appeared as a singlet. The full ¹H spectrum (E) of CH ₃OCH ₂OH/CH ₃OH in DMSO-d ₆ is shown for completeness. The data are consistent with the predominant NMR peaks as arising from the isomers of 1a and 1b shown in .

Glycidol (2) and enols (3)

NMR spectra derived from aerosols produced at increasingly higher wattage settings revealed that, in addition to greater overall PG/GLY consumption and product formation at higher coil temperatures (), specific products arise at different settings. An expansion of the regions in the NMR containing the proton resonances of glycidol ( 2) as well as those of the cis and trans isomers of the propanal enols ( 3) is shown in . At 10 W, the peaks from 2 are present; however, the enol resonances are observable with adequate S/N only beginning at 12 W. This observation is in keeping with observations by Nef in 1904 when he described glycidol ( 2) as a "low temperature" product. More recently, Laino and co-workers reported that the dehydration of glycerol to form 2 is the rate limiting step of a GLY degradation pathway. Compound 2 has been shown to react with DNA It appears to be a relatively minor aerosol component based our studies to date ( vide infra). Enols 3a and 3b have been previously found to persist for up to two weeks in dilute acetone at room temperature. Their potential inhalation toxicology is not clear, though enol reactivity is well-known.

Aldehydes

An expansion of the aldehyde region of the ¹H NMR spectrum of an aerosol generated from PG/GLY at 15 W, along with corresponding structure assignments, is shown in . Acrolein, compound 5, has long been known as a decomposition product of GLY. In fact, it is the target molecule of the most common qualitative chemical test for the detection of GLY. Several routes have been proposed for its formation, including one from a recent study showing its formation via the GLY dehydration product 2. Acrolein is a well-known hazardous air pollutant. Importantly, the doublet at 9.56 ppm corresponding to the aldehyde proton of 5 is highly prominent relative to those of the other products. This is significant because DNPH trapping cartridges used in prior chromatographic studies of e-cigarette aldehydes have been reported as unreliable for the determination of acrolein levels, affording low recoveries. Prior reports of acrolein levels approaching those of other aldehydes have been characterized as having been attributed to overheating conditions. Of the remaining aldehydes 6-10, acetaldehyde ( 9) has garnered significant attention in e-cigarette aerosols because it is a possible human carcinogen (IARC Group 2B).

Reaction pathways

The reactions of PG and GLY under thermal conditions are predominantly dehydrations and oxidations ( and ). As mentioned previously, the conversion of PG to propanal ( 10) was reported in 1904 by Nef. The oxidation of PG has also been previously shown to afford acetone ( 11), acetaldehyde ( 9), HCHO, acetol ( 12) and its tautomer lactaldehdye ( 6) along with dehydration product ( 5).

At the lowest device power setting, 12 was the major detectable aerosol product in the ¹H NMR shown in . Compounds 12 and 6 can result from O-H proton abstraction via a higher temperature pathway owing to the relatively higher O-H bond dissociation energies. Cleavage of C-C bonds from the oxygen radicals would result in the formation of 13 and 14, which can also form as oxidation or retro-aldol products of 12. Compounds 13 and 14 were each observed herein at power settings between 10-15 W. A recent report on PG dehydration has shown that propylene oxide serves as an intermediate towards the formation of 10 and 11, or can alternatively form allyl alcohol ( 15)

GLY is oxidized to form dihydroxyacetone ( 4) and glyceraldehyde ( 8) by H atom abstraction, C-H bond cleavage and tautomerization. Compound 4 has been shown to possess genotoxic and mutagenic properties. Compound 12 is produced by the dehydration of GLY. Compound 12 can further degrade to HCHO and acetaldehyde ( 9). Compound 8 can furnish 7 via a retro-aldol reaction. An ensuing retro-aldol affords HCHO, the abundance of which increases while that of 7 diminishes at high temperatures. Dehydration of GLY affords 2 and subsequently 5.

Conclusion

In this investigation we used NMR for e-cigarette aerosol product identification with no aerosol sample processing, apart from dilution in DMSO-d ₆. As had been proposed, a main finding was that the e-cigarette solvents PG and GLY afford products that are fully consistent with prior studies of their pyrolysis and combustion. In addition, the results herein suggest NMR as a viable alternative to DNPH trapping cartridges for monitoring challenging, reactive toxins such as acrolein. Finally, (i) the sensitivity of PG and GLY to thermal oxidation, (ii) the catalysis of their dehydration reactions by acids and/or metals, and (iii) the variability in the heat transfer efficiencies of individual clearomizers and heating coils should be taken into account when considering strategies to minimize toxin production and inter-laboratory inconsistencies in evaluating these devices.

Additional Information

How to cite this article: Jensen, R. P. et al. Solvent Chemistry in the Electronic Cigarette Reaction Vessel. Sci. Rep. 7, 42549; doi: 10.1038/srep42549 (2017).

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Material
Supplementary Information:
Acknowledgments

We thank the NIH and FDA for support of this work via award R01ES025257. Research reported in this publication was supported by NIEHS and FDA Center for Tobacco Products (CTP). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration.

Footnotes

The authors declare no competing financial interests.

Author Contributions R.P.J. performed the experiments and wrote the initial draft of the manuscript. R.M.S. wrote the manuscript, especially focusing on mechanistic chemistry, and the background of degradation chemistry of P.G. and G.L.Y., as performed by other laboratories. D.H.P. directed the research. All authors reviewed the manuscript.

References

Grana R., Benowitz N. & Glantz S. A. Background paper on e-cigarettes (electronic nicotine delivery systems) (2013).

Barrington-Trimis J. L. et al. . E-cigarettes, Cigarettes, and the Prevalence of Adolescent Tobacco Use. Pediatrics e20153983 (2016). [PMC free article]

Bunnell R. E. et al. . Intentions to smoke cigarettes among never-smoking US middle and high school electronic cigarette users, National Youth Tobacco Survey, 2011-2013. Nicotine Tob. Res. ntu166 (2014). [PMC free article]

Scheele C. W. Kongl Vetensk. Acad. Nya Handl. 4, 324 (1783).

Behrens J. F. Dulcium Naturam Et Vires Expendens, University of Göttingen: Göttingen, Germany (1779).

Lawrie J. W. Glycerol and the Glycols: Production, Properties and Analyses (The Chemical Catalog Company, Inc. 1928).

INNOKIN ITASTE VV 4.0, http://www.smokeyjoes.biz/product/innokin-itaste-vv-4-0/.

Miner C. S. & Dalton N. N. Glycerol. (Reinhold Pub. Corp. 1953).

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Solvent Chemistry in the Electronic Cigarette Reaction Vessel

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Knowledge of the mechanism of formation, levels and toxicological profiles of the chemical products in the aerosols (i.e., vapor plus particulate phases) of e-cigarettes is needed in order to better inform basic research as well as the general public, ...

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Good intro article

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Is it safe to bogart that e-cig or even be in the same room with an e-cig bogarter?

OK, in this post we're going to clue you in on some of the potential issues with electronic cigarettes or e-cigs, as they're diminutively known. But before we do, we need to get one thing straight: Smoking cigarettes kills.

Per the Centers for Disease Control, smoking " is the leading cause of preventable death in the United States, accounting for more than 480,000 deaths, or one of every five deaths, each year."

Add to that the more than 16 million Americans who suffer from a smoking-related disease, and it's fairly clear anything that lowers the rate of cigarette smoking is going to improve our overall health.
Americans Are Smoking Less
The numbers are somewhat encouraging. While more than 40 percent of Americans smoked in 1965, only about 18 percent did in 2012. However, given that our population grew over that time, the net drop in American smokers -1965's 50 million smokers versus 2012's 42 million-is only 8 million.

That drop in the rate of smoking probably didn't just happen. The government and a host of nonprofits have waged a long and hard campaign against smoking: ever-increasing taxes, a ban on broadcast advertising, and anti-smoking ad campaigns that promote a healthy lifestyle and warn of the health risks of smoking. (California appears to be leading the pack in this fight.) And ever since 1966, Americans have not been able to purchase a pack of cigarettes free of a stern warning about the hazards of smoking.

Then there's the wide assortment of products to help smokers kick the habit - everything from patches and gum to prescription drugs, lozenges and lollipops.And more recently e-cigarettes.
The Newest and Coolest: 'Vaping'
Although they were patented back in the 1960s, electronic cigarettes didn't really come onto the scene until the past decade, appearing first in China in 2004 and spreading to other areas including Europe in 2006 and then the United States the following year. (See infographic on the history of e-cigarettes.)

These cigarette lookalikes basically consist of a cartridge, a battery and an LED light. When turned on, the e-cig heats up the liquid that is housed in the cartridge; thisproduces an aerosol mist or vapor, which the "smoker" inhales or "vapes," an alternate term that denotes the lack of combustion. The ingredients of the liquid vary, but generally include nicotine (though some are nicotine free), chemicals to vaporize the nicotine (like propylene glycol and vegetable glycerin), additives and flavoring.

Since they are tobacco free, e-cigs are currently unregulated in the United States but that may change. Already cities like Boston, Chicago, New York, and most recently Los Angeles have restricted their use. And Utah, New Jersey and North Dakota have banned their usewherever smoking is prohibited. Other states and localities including Minnesota and Oregon are considering restrictions as well.

It is my impression that there's some confusion in how e-cigs are being marketed. In some cases they are being touted as a nicotine replacement product that smokers can use to eventually quit smoking altogether or (more likely to me) a healthier way to get your nicotine.

And I guess if you "got to" smoke (whatever that means) I suppose e-cigs are probably a lot less unhealthy than good, old-fashioned cigarettes.

Given the long and sorry list of harmful and toxic chemicals in cigarettes,vaping is almost certainly less dangerous to your health.
The Potential Hazards of Vaping
But don't be fooled into thinking that e-cigs are without risks or that you should now be able to vape to your heart's content. Or that they're plain healthy.

First of all, nicotine is a drug and a powerfully habit-forming one at that, and a 2013 studysuggests that even inhaling the drug via either conventional cigarettes or e-cigs may contribute to heart disease.

Also there is evidence that e-cigs deliver some toxic stuff of their own such as formaldehyde (a known carcinogen), nitrosamines (linked to cancer) and lead (a neurotoxin). Though the toxicant levels of e-cigs may be "9-450 times lower than in cigarette smoke," as this study suggests, levels of formaldehyde and metalshave been found to be comparable to or higher than those found in conventional cigarettes.* Silicate particles, which are a cause of lung disease, have also been found in e-cigarette vapors.
The 'Second-Hand Smoke' Question
A number of e-cig enthusiasts I have spoken to believe that the ban on smoking cigarettes in public places should not apply to e-cigs. And some are acting on that belief. I've even seen a woman confidently doing her e-cig thing on the subway in New York. Another in a restaurant.

And why not? Electronic cigarettes don't burn and so there is no smoke. And no smoke means no second-hand smoke. And no second-hand smoke means no health worries for the non-e-cig public who happen to be in the vicinity. Sounds reasonable and what a boon for nicotine addicts. Relegated, lo all these years, to standing outside in the freezing cold or blistering heat to get their fix and unable to inhale while in flight, now e-cig users can reenter conventional society.

But is there really no second-hand "smoke"?

Don't be so sure. A small studyby Wolfgang Schober of the Bavarian Health and Food Safety Authority and colleagues published in the International Journal of Hygiene and Environmental Health in December found that vaping worsened indoor air quality, specifically by increasing the concentration of nicotine, particulate matter, PAHs and aluminum - compounds that have been linked to lung and cardiovascular diseaseand cancer among other health effects.

The upshot? Probably won't be long before the nicotine-inhaling e-cig users of the world find themselves legislated back out into the cold to hang with their conventional nicotine-smoking addicts.
End Note
* Comparable levels of some metals have been reported for FDA-approved nicotine inhalers as well.Depending upon your view of FDA regulations, you could take this as an "all clear" on metals and e-cigs. One difference between inhalers and e-cigs that may impact exposure is that the vapors from FDA inhalers are absorbed in the mouth rather than the lungs like e-cigs.

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Is it safe to bogart that e-cig or even be in the same room with an e-cig bogarter? OK, in this post we're going to clue you in on some of the potential issues with electronic cigarettes or e-cigs, as they're diminutively known. But before we do, we need to get one thing straight: Smoking cigarettes kills.

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E cigarette manufacturers make vaping fluid look like kid's candy

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San Francisco tried to ban candy-flavored vape cigarettes, but a tobacco industry-funded campaign has put that ban on the ballot for public vote.

LULU GARCIA-NAVARRO, HOST:

San Francisco wants to ban the sale of flavored tobacco products. Included in the potential ban, a high-tech vaping device called a JUUL. It's marketed to help adult smokers quit regular cigarettes. But as Shia Levitt reports, the flavors and sleek design have become wildly popular among teens.

SHIA LEVITT, BYLINE: JUUL uses nicotine salts to deliver a hit that closely replicates that of a cigarette. JUULing - it's a verb now - started just three years ago but already makes up more than half of the multibillion-dollar e-cigarette market. In San Francisco, 14-year-olds Emma (ph) and Jaclyn (ph) say there are lots of reasons why their friends love JUUL. We're not using their last names because JUULing is illegal here, if you're under 21.

JACLYN: It's easier to hide. And it doesn't taste bad. And there's no tobacco.

EMMA: It also doesn't - the smell doesn't stick on you, the nicotine smell.

LEVITT: Their friends put stickers or engravings on the devices so they can tell them apart. The head rush and sweet fruity taste of the flavor pods are appealing, too.

JACLYN: Almost everyone I know, I think, is a little bit or a lot addicted because it's not...

LEVITT: Public health advocates have long known that flavors attract young people. April Roeseler is with California's Department of Public Health.

APRIL ROESELER: Eighty percent of kids who use tobacco products start with a flavored tobacco product.

LEVITT: And a lot of kids who would never have tried a cigarette are using e-cigarettes, like JUUL. There's also a documented gateway effect. If you start with e-cigs, you're more likely to go on to old-fashioned cigarettes. But all of this has flown under the radar.

ROESELER: It doesn't smell like a pack of cigarettes. It doesn't look like a pack of cigarettes. There's really some deception going on here. And parents and school teachers need to be aware.

LEVITT: Last year, San Francisco banned the sale of all flavored vaping liquids and tobacco products. But a petition forced the voter referendum set for June. The measure is known as Prop E. And the main opponents - the tobacco industry. RJ Reynolds is the sole funder of the No on E campaign, to the tune of nearly $12 million so far. Slogans include bans and prohibitions don't work and that voting no preserves adult choice.

GREGORY CONLEY: We know that adults like flavors.

LEVITT: Gregory Conley is with the American Vaping Association, a one-man operation speaking for the No on Prop E campaign. R.J. Reynolds sent us to him. Conley says fruit- and dessert-flavored cigarettes are helping adult smokers quit traditional smoking.

CONLEY: As long as you have people switching and as long as you have the smoking rate dramatically declining, you are going to see positive public health effects almost regardless of how many people actually end up using the product.

LEVITT: But it's a bit more complicated. There's mounting evidence that e-cigarettes cause many of the same health problems as old-fashioned smoking. And if you look at the total amount of kids using nicotine products, that's actually gone up in recent years. Stan Glantz directs the Center for Tobacco Control Research and Education.

STAN GLANTZ: Simply shifting people from cigarettes to e-cigarettes or to some of these other new products is just going to prolong the tobacco epidemic.

LEVITT: The FDA began a crackdown in April on vaping sales to teens, including warning retailers who sell JUULs to minors. In response, JUUL Labs announced they'd be investing $30 million to combat underage use of their products. San Francisco's flavored vaping ban, if upheld, would be the toughest restrictions in the nation. It could set a precedent for flavored tobacco restrictions elsewhere in the country.

For NPR News, I'm Shia Levitt in San Francisco.

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San Francisco To Vote On Ban Of Flavored E-Cigarettes And Tobacco

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San Francisco tried to ban candy-flavored vape cigarettes, but a tobacco industry-funded campaign has put that ban on the ballot for public vote. LULU GARCIA-NAVARRO, HOST: San Francisco wants to ban the sale of flavored tobacco products. Included in the potential ban, a high-tech vaping device called a JUUL.