So…are they safe?

That’s the question on everyone’s minds.

There’s little concrete data on the safety of ingredients in e-cigarettes. In the US, to legally sell vapes and e-juice, companies have to provide an ingredient list to the FDA—but they don’t have to make those lists public. As long as the ingredients are generally regarded as safe by the FDA for use in food, drugs, and cosmetics, the organization then authorizes those products for sale. It doesn’t actually approve any tobacco product, vapes included, in acknowledgement that they are all inherently risky.

“Generally regarded as safe” is an official designation which literally means “there is no evidence in the available information on [substance] that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.” However, in the case of e-cigarettes, whose compounds are being inhaled instead of consumed or included in makeup, that designation may not be appropriate.

A recent review of the safety of all components in e-cigarettes states in the abstract: “We conclude that current knowledge of these effects is insufficient to determine whether the respiratory health effects of e-cigarettes are less than those of combustible tobacco products.”

Here’s what we know about each product instead:

Vegetable glycerin was originally a plant-based product—there are now synthetic forms—that’s been used for centuries in a huge range of products, from cosmetics to dynamite. More recently, it’s been added to “low-fat” foods to absorb water and prevent freezer burn.

Propylene glycol is found naturally in low concentrations in some foods like eggs and flavorings (no more than 15%) and shows up in some medications administered through an IV. It’s also used in polyester production, as well as some forms of antifreeze. The US military and theater groups also uses it to make smokeless smoke bombs.

Are they safe? Both glycerin and propylene glycol are generally recognized as safe by the FDA, but just because something is safe to eat, it doesn’t mean it’s safe to inhale, says Robert Tarran, a cell biologist at the University of North Carolina who co-authored the above review. (Water, for example, is safe to ingest, but not safe to inhale.)

Existing cell, animal, and clinical studies suggest that glycerin and propylene glycol irritate the lining of the lungs. One small clinical study from 2018 that found that the compounds changed vapers’ sputum—the mucosal lining that covers the internal respiratory tract—to express different immune proteins. Some of these protein changes have been linked to asthma.

Nicotine is the addictive substance found in tobacco plants. Benzoic acid is also naturally found in plants, and is used commercially in dyes, perfumes, insect repellants, and food preservatives.

Are they safe? Nicotine has always been viewed as the lesser of two evils when it comes to cigarettes. Burning tobacco releases hundreds of chemicals, including nicotine. Some of these other chemicals lead to cancer—and while nicotine may make some cancers worse, there’s little data suggesting it causes cancer.

The chemical is best known as a stimulant that raises the heart rate and blood pressure. It’s also a mood booster because of the way it stimulates dopamine transmission in the brain, and blocks other receptors from dampening dopamine’s signal. In high doses, nicotine can cause nausea and other forms of GI distress, plus a jittery sensation—but the effects are temporary.

Scientists have found that in the long term, nicotine can damage parts of the heart, lungs, and circulatory systems, and can hurt fetal development in pregnant people who smoke. But the biggest drawback of nicotine is how addictive it is. The US surgeon general has classified nicotine as just as addictive as cocaine or heroin. Teenagers, whose brains are still developing, are at a heightened risk of getting hooked on nicotine, and early research has shown that nicotine addiction may result in lifelong problems concentrating.

The health effects of nicotine as a salt with benzoic acid is also relatively unknown.

For this analysis, we used a 5% nicotine Juul pod, which claims to contain 5% nicotine by weight, or about 59 mg of nicotine per mL of fluid (It also makes 3% nicotine pods). It’s not clear how much of the pod is benzoic acid, and a spokesperson for Juul referred us back to the pod ingredients page when asked for this story.

Juul does not list specific flavor ingredients on its website, and as of Oct. 17, it produces pods flavored to taste like tobacco, Virginia tobacco, menthol, and mint. (It used to sell creme, mango, fruit, and cucumber flavored pods, but have suspended sales until the FDA reviews them under a premarket tobacco product application.)

But Juul’s four flavors are just a fraction of all the e-juice flavors available for purchase. E-juice comes in over 7,000 different flavors, which are largely unregulated and undocumented. A public policy group over at UNC has a database of some of these flavors and their chemical constituents, but Juul pods haven’t been included.

Are they safe? It’s unclear—like all other ingredients in e-cigarettes, many of these flavors are generally recognized as safe in food products, but there’s limited research on what happens when they’re brought into the lungs. Some chemical analyses of e-cigarettes have found that flavors can harm the white blood cells in the lungs, which could lead to inflammation.

Another chemical analysis from 2017 found that out of 24 popular flavored e-juice pods, every one contained at least one chemical listed as a High Priority Chemical by the US Federal Emergency Management, or harmful or potentially harmful constituents by the FDA. It also found that as these chemicals break down, they produce aldehydes—a class of compounds that includes formaldehyde—which are known toxins for humans.

In addition to the e-juice, there’s the vape itself. There’s a risk that the metal wick that heats e-juice may be releasing tiny bits of metals like nickel, lead, and chromium into the aerosolized puff as well—which wouldn’t be great for lungs. And when a vape’s ingredients combine under heat, they may interact with each other and produce yet another set of chemicals of unknown safety.

Legally sold nicotine vapes are just the tip of the iceberg: The majority of the nearly 1,300 cases of e-cigarette or vaping product use-associated lung injury, or EVALI, have been associated with THC or “street” nicotine e-juice, which can include any ingredients they want. It’s possible that some users are mixing their own flavors with potentially dangerous chemicals.

As Quartz has reported, studying the safety of e-cigarettes is daunting because of the sheer variety of e-cigarettes. It’s a huge number of variables to contend with, especially compared to the essential uniformity of combustible tobacco cigarettes. And because they’re relatively new, scientists haven’t had time to do all the research necessary to prove—or disprove—that they’re entirely safe.

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