Some E-Cigarette Flavors May Be More Harmful Than Others

In the 1990s, several employees of a Missouri popcorn factory began reporting mysterious symptoms. They were always tired, wheezing, and out of breath. After doctors found scar tissue inside the factory workers’ lungs, they diagnosed the workers with an irreversible lung disease: bronchiolitis obliterans, which would later be nicknamed “popcorn lung.” Its cause was traced back to the chemical behind popcorn’s buttery flavor.

While the FDA recognizes this chemical, diacetyl, as “generally safe to eat,” the case of the factory workers revealed that inhaling heated diacetyl particles day in and day out takes a harsh toll. What was safe to swallow wasn’t safe to inhale.

Years later, reports of diacetyl in e-cigarette vapors led to panicky headlines about vapers, too, being at risk of “popcorn lung.” Vaping advocates were quick to object, pointing out that spending years breathing in buttery-flavored factory air is very different from taking a few quick puffs from an e-cig. But the incident underscored the motley assortment of chemicals that go into different vape flavors. There can be hundreds of flavor additives in any given vape juice, with concentrations that range from trace amounts to large fractions of the whole e-liquid. Their toxicity profiles vary widely as well.

Many of these chemicals have never been tested on whether they’re safe to breathe in. And that makes vaping’s already unclear effects on health even murkier, because different flavors could be more or less dangerous. “Just because vanilla flavor or crème flavor is okay in your cookies doesn’t mean it’s okay when you heat it and then inhale it,” says Amanda Dickinson, a developmental biologist at Virginia Commonwealth University. “It seems that it’s a roll of the dice.”

A recent study coauthored by Dickinson investigated the effects of six different e-cig vapors on tadpoles, as a proxy test for how vaping while pregnant might affect human embryos. Some of the exposed tadpoles developed “clefts” in the bone behind the upper lip, somewhat similar to cleft palate in humans. These clefts only appeared in tadpoles exposed to two particular flavors out of six tested. When the researchers exposed tadpoles to nicotine-free versions of the same flavors, those tadpoles still developed clefts in the same ratios.

The flavors that correlated with the tadpoles’ facial defects weren’t “tobacco” and “menthol,” but rather flavors with fruit and cream overtones. These two flavors also had the most complex flavor descriptions: About 20 percent of tadpoles exposed to a flavor of “strawberry, almond, caramel, vanilla, biscuit, Vienna cream” and 70 percent of those exposed to a flavor of “cereal, berries, cream, citrus” developed clefts.

Dickinson and her colleagues pointed out that it may not be the fruity or creamy flavor additives per se, but the complexity of the flavor—or the number of chemical components in the vapor—that correlates with the cleft formation.

The tadpole study isn’t the first to note e-liquid flavors vary in toxicity. Robert Tarran, a cell biologist at University of North Carolina, has analyzed the composition of more than 100 e-liquids and tested their toxicity against human kidney cells in petri dishes by diluting the e-liquids and then slowly increasing their concentrations. The concentration needed to kill half the cells ranged from 5.997 percent for some flavors down to .002 percent for others, and could vary by as much as an order of magnitude between flavors mixed by the same vape shop. So far, Tarran hasn’t singled out any specific flavor ingredients as uniquely dangerous, but he has noticed a pattern. “The more chemicals there tended to be in the e-liquid, the more toxic it tended to be,” he says.

Tarran points out that these toxicity assays in kidney cells don’t necessarily predict overall health effects in humans, and that at this point, direct comparisons to the toxicity of conventional cigarettes aren’t feasible. It’s also possible that the effects of e-cigarettes in lungs could predispose people to a different set of ailments than tobacco smoke.

If a vaper wanted to avoid a particular chemical, they’d have a hard time figuring out which flavors contain certain chemicals and which ones don’t. E-cig manufacturers are required to file their full ingredients list for each e-liquid on the market with the FDA, and they list the amounts of three chemicals that make up the bulk of most e-liquids—nicotine, glycerin, and propylene glycol—on the label. But they stop short of listing out all the chemicals that contribute to flavor. “The commercial success of a product is in its formulation (that is, its taste) and this is preciously hidden by the manufacturer,” Emanuele Ferri, the scientific director of a Milan-based vaping R&D company called TRUSTiCERT, said in an email.

Ferri says that his team has studied toxicology profiles for more than 1,000 e-liquid ingredients and that no two chemicals’ effects are completely identical. They’ve posted toxicology data online from some e-liquids made by the company FlavourArt that tested as safe.

Still, this lack of transparency frustrates many researchers. “If you look at a bottle of e-liquid or the websites where they sell these things, the descriptions of the ingredients are like, ‘cookies,’” says Allyson Kennedy, a policy fellow at the American Association for the Advancement of Science and a coauthor on the tadpole paper. “You didn’t crush up cookies and put them in there. What are the chemicals that you used to create that flavor? That information I can’t seem to find anywhere.”

These initial studies are “just small steps,” says René Olivares-Navarrete, a bioengineering assistant professor at VCU and another coauthor on the tadpole study. As with Tarran’s cell lines, results in tadpoles and mice may or may not translate to humans. Olivares-Navarette says he hopes that e-cigarettes are as safe as vaping advocates claim, but first, “people need to have the information about what is possible.”