Chemicals in e-cigarettes may form toxic compounds
Flavorings combine with solvents in electronic cigarettes to produce unstable chemicals that may cause respiratory effects in users, according to new data presented at the virtual European Respiratory Society International Congress.
“Our co-author and analytical chemist Dr. Hanno Erythropel and colleagues at Yale University found new chemicals in e-liquids and revealed that they are formed when components are mixed by manufacturers. We became concerned about the high levels of these new compounds that had not been studied in the past, and decided to conduct toxicological tests,” Sven-Eric Jordt, PhD, associate professor of anesthesiology, pharmacology and cancer biology at Duke University School of Medicine, said in a press release.
The researchers analyzed what happens when cells that line the bronchi are exposed to flavoring chemicals such as vanillin and ethyl-vanillin, which are responsible for vanilla and other sweet flavors, and benzaldehyde, which is responsible for berry or fruit flavors. Using gas chromatography, mass spectrometry and nuclear magnetic resonance, the researchers analyzed the effect of the new chemicals that formed as a result of mixing the e-cigarette flavors with the solvents propylene glycol and vegetable glycerin, underwent rapid chemical reactions with the solvents after mixing, according to the abstract.
“We observed over 48 hours that these new chemicals are formed. These are not declared by the manufacturers and not reported to regulators. We were concerned that these chemicals might have toxicological effects in the lungs of users. They have not been studied in detail in respiratory exposure experiments,” Jordt said during a press conference.
Following toxicological tests, these compounds caused activations of the sensory irritant receptors transient receptor potential cation channel subfamily V member 1 and subfamily A member 1. This activation caused increased cough, secretions and cardiovascular reflexes from vapor inhalation, according to Jordt.
Researchers obtained nasal epithelial cells and performed a toxicological assay to assess the effect on user bronchi. Few respiratory cells exposed to vanillin or benzaldehyde alone were killed, but when exposed to the newly formed flavor and solvent chemical more cells were killed as the concentrations of the chemical increased, according to Jordt.
Moreover, the unstable chemicals also had an effect on cell metabolism, he said. In an analysis of mitochondria in respiratory cells, these chemicals suppressed oxygen consumption and adenosine triphosphate production, he said.
“This is the first demonstration that these new chemicals formed in e-liquids can damage and kill lung cells and probably do this by damaging their metabolism,” Jordt said. “Although, in some cases, more than 40% of flavor chemical are converted into new chemicals in e-cigarettes, almost nothing was known about their toxicity until now.”
The researchers expressed surprise at the results of this study.
“We actually expected that the observed chemical reactions would inactivate benzaldehyde and other flavoring chemicals, making the products less toxic. However, we observed the opposite, finding the newly formed compounds to be more irritating and toxic,” Jordt said in the release.
The researchers concluded that more research is needed to identify these chemicals. In addition, “[m]anufacturers have to declare chemicals that are formed and investigate their toxicity to make sure that vapers are not exposed to toxic chemicals,” Jordt said.
In a second presentation, Hanno C. Erythropel, PhD, associate research scientist in the department of chemical and environmental engineering at Yale School of Medicine, and colleagues analyzed mint, vanilla and mango e-cigarette liquids in Juul e-cigarettes to compare how the chemicals providing these flavors and the nicotine content varied in Juul products available in different countries.
In the U.S. and Canada, Juul products are sold with 5%, 3% and 1.5% (Canada) nicotine content, whereas the European Union regulation limits 1.7% nicotine content, according to the researchers.
“While the composition of Juul e-liquids was identical in the U.S. and Canada, it differed from the e-liquids available in Europe,” Erythropel said in the release. “Juul e-liquids sold in the U.S. and Canada contain up to 59 mg/mL of nicotine, comprising about 5% of the liquid, but EU regulations limit nicotine content to approximately a third of that amount at 20 mg/mL, about 1.7%, which the company adhered to, based on our results.”
In addition, “[w]e found that along with lower nicotine content, the European products also contained lower amounts of flavoring agents compared to the U.S. and Canadian products with one exception: the reduced amount of menthol in European mint e-liquid was replaced with a synthetic coolant called WS-3, not present in U.S. or Canadian products,” Erythropel said in the release. “The safety of inhaling WS-3 in e-cigarettes is unknown and so we believe that any legislation targeting menthol in tobacco products should be extended to synthetic coolants.”
References:
Erythropel H, et al. From tobacco and vaping health effects to tobacco cessation. Presented at: European Respiratory Society International Congress; Sept. 7-9, 2020 (virtual meeting).