We hear a lot about how the ingredients in vape juice might be bad for us: the nicotine is addictive, for example, and the flavorings could be bad for lungs. But new research says that there are chemicals in e-liquids that we didn’t even know to worry about, because they form in the e-liquid bottle or pod after all the ingredients are mixed together.

Scientists have discovered that cinnamon, vanilla, and cherry flavors react with propylene glycol, a main ingredient in many vape juices, to create entirely new chemicals, according to a study published today in the journal Nicotine & Tobacco Research. Those same chemicals carry over into the vapor that people inhale, the new study says. Early investigations led by Sven-Eric Jordt, a professor of anesthesiology, pharmacology, and cancer biology at Duke University, suggest that these modified flavorings might be able to irritate lungs over the long term. And people don’t even know they’re inhaling them.

“There are things that are being vaped and inhaled that people don’t really know about.”

There are more than 7,000 e-liquid flavors out there, and they’re pretty controversial. Right now, regulators and lawmakers are weighing how to regulate them, and there’s an ongoing debate about whether flavored e-liquids lure in kids or help adults switch away from cigarettes (or both). But there are also health impacts to consider: while the FDA says many of these flavors are safe for eating, we don’t actually know if they’re safe for breathing, according to the massive National Academies report about vaping that came out earlier this year. Some research, for example, suggests cinnamon flavors can harm lung cells, The New York Times reports.

And now, it turns out that there’s more than just the flavor ingredients themselves to worry about: there are also the chemicals the flavorings can produce as they continue reacting in vape juice. That’s why this study is important, says Robert Strongin, an organic chemist at Portland State University who was not involved in the research. It looks at the risks unique to the soup of chemicals in e-cigarettes. “There are things that are being vaped and inhaled that people don’t really know about.”

“...like the elephant in the room.”

Vape juices are typically made by mixing nicotine and flavorings with a solvent — often propylene glycol, vegetable glycerine, or a mixture of the two. That solvent, Strongin says, is “like the elephant in the room. That’s the main chemical in the e-liquid,” he says. But there’s not enough known about how these solvents could mix and react with other ingredients in a little bottle of cherry-flavored vape juice, for example.

Scientists analyzing commercial vape juices have detected new chemicals in the mixtures that aren’t listed on the ingredients label (when there is one). And based on the compounds’ chemical structures, it looked like they formed when flavorings reacted with the propylene glycol — but no one knew what exactly was going on, or whether these compounds made it from the vape juice and into vapers’ lungs.

So to watch the chemistry in action, Jordt’s team made their own e-liquid based on the formulations they’d found in the literature and by analyzing vape juices they bought from AmericanEliquidStore.com. They mixed propylene glycol, vegetable glycerine, and a handful of different flavors, including cherry, cinnamon, and vanilla. And they watched the concentration of these new compounds rise. When they analyzed the vapor their e-liquids produced, they found that roughly 50 to 80 percent of the new chemicals showed up in the vapor, too.

“We think the public and the medical community needs to be aware.”

The real question, though, is what those new chemicals do to human body. And today’s study takes the first steps toward answering it: the team tested the compounds on cells sporting irritant receptors known to be triggered by things like cigarette smoke and chili peppers. And they found that these modified flavorings triggered them more effectively, and at lower concentrations, than the flavors themselves.

That’s weird because there isn’t an epidemic of people with burning airways. “Obviously, if this would be very severely irritating, people would stop using the e-cigarettes,” Jordt says. Instead, he’s worried about what chronic, low-level stimulation of these irritation receptors could do to people’s lungs. “If they are more continuously activated they can lead to inflammation, chronic cough, they also promote asthma. That’s why we are concerned,” he says. The study shows that these e-liquids aren’t stable, he says: that’s why there needs to be additional research on what happens when these ingredients are mixed and left in an e-liquid bottle or pod for months at a time.

“You don’t want harm replacement.”

And it’s key for vapers to know that the ingredients companies say are in their vape juice don’t necessarily reflect what people are inhaling. “Once you mix them all together, what’s present in the liquid is not what you put in originally,” Jordt says. “We think the public and the medical community needs to be aware of that.”

Strongin, too, says that these risks need to be investigated further. “We’d love for these to be totally harmless,” he says. And he doesn’t want to discourage anyone from quitting tobacco smoking. But, he says, to say vaping is perfectly safe also isn’t true. “If you’re really interested in harm reduction, which I think we’re all interested in, you don’t want harm replacement.”