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Cancer-causing chemical formed in e-cigarette users 

The lack of certain toxic and cancer-causing chemicals in e-cigarettes may not necessarily mean that e-cigarette users are not exposed to them anyway, a study from the University of Minnesota found.

While e-cigarettes contain virtually no N-nitrosonornicotine (NNN) – a chemical that can cause oral cavity and esophageal cancer – the chemical can form in an e-cigarette user’s body when they take in nicotine through e-cigarettes.

The study was published recently in Chemical Research in Toxicology.

School of Public Health Associate Professor Irina Stepanov, a Masonic Cancer Center member, led a team of researchers who analyzed NNN in urine and saliva from e-cigarette users, smokers and nonsmokers.

Urine of e-cigarette users was virtually free of NNN. However, their findings showed that 16 out of 20 e-cigarette users had measurable levels of NNN in their saliva. The levels were generally lower than in smokers, but some e-cigarette users had NNN in their saliva at levels comparable to smokers.

"The finding that some e-cigarette users may be forming substantial amounts of NNN in their bodies is significant when considering the long-term risks of prolonged e-cigarette use,” said Stepanov.

“For young e-cigarette users who have never smoked, this is particularly bad news, because they are being exposed to a potent carcinogen that most likely is a key contributor to oral and esophageal cancer in tobacco users. For cigarette smokers, however, it is important to put things into perspective.

Smokers take in significant amounts of NNN from cigarette smoke itself. If they switch to e-cigarettes, their exposure to NNN is reduced dramatically even if some amounts of this chemical are formed in their bodies."

"Our study stresses the importance of taking a thoughtful approach while investigating exposures from e-cigarettes, and not just replicating what has been done in studies with regular cigarettes,” said Gabriela Bustamante, co-author of the study and School of Public Health graduate student.

“Based on the analyses of e-cigarette liquids and aerosols, the common assumption was that there is no exposure to NNN in e-cigarette users. And if we had limited our analyses to urine, and not included saliva, we would not have captured this important process that happens in the oral cavity of e-cigarette users."

Further research should take the study's findings into account when assessing the potential health impact of long-term e-cigarette use. Given that the oral cavity and esophagus are target tissues for NNN carcinogenicity, the presence of this carcinogen in saliva of e-cigarette users is particularly relevant and important.

This study was supported by grants from the National Cancer Institute of the National Institutes of Health.



Many harmful constituents are present in e-cigarettes at much lower levels than in cigarette smoke, and the results of analysis of urinary biomarkers in e-cigarette users are consistent with these findings. However, understanding the health effects of chronic exposures to e-cigarette aerosols may require thinking beyond these comparisons.

In this study, we investigated the endogenous formation of the tobacco-specific oral and esophageal carcinogen N′-nitrosonornicotine (NNN) in e-cigarette users. Salivary NNN, nornicotine, and nicotine as well as urinary tobacco biomarkers, including total NNN, were analyzed in 20 e-cigarette users, 20 smokers, and 19 nonsmokers. Nornicotine and NNN levels in e-cigarettes used by the study participants were also analyzed.

The mean of NNN in saliva of e-cigarette users was 14.6 (±23.1) pg/mL, ranging from nonquantifiable (below the limit of quantitation, LOQ) to 76.0 pg/mL. In smokers, salivary NNN ranged from below LOQ to 739 pg/mL, with 80% of smokers having salivary NNN in the range of levels found in e-cigarette users. Consistent with a previous report, very low levels of urinary total NNN were present in only 5 out of 20 e-cigarette users (ranging from 0.001 to 0.01 pmol/mL urine). Only trace levels of NNN were found in e-cigarette liquids.

Together, our findings demonstrate that NNN is formed endogenously in e-cigarette users.

While the overall exposure to NNN in e-cigarette users is dramatically lower than in smokers, the known carcinogenic potency of NNN warrants further investigations into the potential consequences of its endogenous formation. Salivary NNN, rather than urinary total NNN, which accounts for only 1% to 3% of the NNN dose, should be used to monitor e-cigarette users’ exposure to this carcinogen.

[link url=""]University of Minnesota article[/link]

[link url=""]Chemical Research in Technology article[/link]


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