(Reuters Health) - Two chemicals commonly used as e-cigarette flavors might harm users’ airway passages, a small experiment suggests.

The results point to the need to further study how the highly popular cigarette alternatives affect human bodies, researchers say.

In test tube experiments, the researchers exposed cells from the lining of human airways to two flavoring compounds: diacetyl - a chemical with a butter-like smell - and its “chemical cousin” 2,3-pentanedione.

In the body, these so-called bronchial epithelial cells work with mucous to clear inhaled germs and particles.

Researchers found that both chemicals induced hundreds of genetic changes in the cells. The chemicals also impaired the ability of the cells to function properly.

“These flavoring chemicals are what we call Generally Regarded As Safe (GRAS) chemicals. That designation, though, only refers to the ingestion pathway,” said study coauthor Joseph Allen, from the Harvard T.H. Chan School of Public Health in Boston.

“They are food grade flavoring chemicals. They have not been tested for inhalation safety. And what we do know about users who inhale these flavoring chemicals is that they can cause severe lung disease,” Allen told Reuters Health by phone.

In food, diacetyl is generally considered safe by experts. But older research going back a decade describes how workers at popcorn factory developed a serious respiratory condition called bronchiolitis obliterans, or “popcorn lung,” after inhaling the butter-flavored compound.

“It’s a good study and it’s a beginning,” said Irfan Rahman, a professor of Environmental Medicine at University of Rochester Medical Center in New York, who was not associated with the study.

“The flavor is causing some changes in the genes, which is a really key point in human lung epithelial cells,” said Rahman, who studies the effects of cigarette smoke on lung inflammation.

“Lungs are not made for flavors to inhale. Our body is not yet ready,” Rahman said.

Test tube experiments may not reflect real human exposure to e-cigarettes, the researchers acknowledge.

Also, they point out, they chose these two flavor chemicals to study based on preliminary investigations conducted in 2016. Today, e-cig manufacturers may have changed formulations.

Indeed, Juul Labs Inc, a popular maker of e-cigarette devices, states on its website that it does not add either of these chemicals to its manufacturing process and lists other ingredients such as natural oils, extracts and flavors as its ingredients.

“Some of the newer e-cigarette companies like Juul are starting to advertise that their products do not contain (these chemicals),” Allen said.

“What is important to ask is: what flavors are they using?” he added

E-cigarette and “vape” makers have come under fire from health regulators and governments as youth e-cigarette use increases, and worries arise about a burgeoning young population of e-cigarette users who may move on to smoking cigarettes.

“Because of the associations of diacetyl inhalation exposure and severe respiratory diseases and increasing popularity of e-cig use among people, further mechanistic studies are warranted to evaluate the effects of diacetyl and related flavoring compounds in e-cig on airway epithelium,” the researchers note in their study published in Scientific Reports.

SOURCE: go.nature.com/2Sgy3D3 Scientific Reports, online February 1, 2019.