Beyond the Headlines: Trace Toxins, Present in All Teens, Improperly Blamed on E-Cigarettes

The University of California San Francisco publicized a study on March 5, asserting that “Adolescents who smoke e-cigarettes are exposed to significant levels of potentially cancer-causing chemicals.” (here)  The study’s lead author, Mark Rubinstein, M.D., said, “Teenagers need to be warned that the vapor produced by e-cigarettes…actually contains some of the same toxic chemicals found in smoke from traditional cigarettes.”

This led to messaging that vaping is just as dangerous as smoking -- “Teens Using E-Cigarette Have the Same Toxic Chemicals Found in Smokers” (here), “E-Cigarette Users Ingest High Levels of Cancer-Causing Chemicals” (here).

In fact, the research, published in Pediatrics, analyzed urine, not vapor.  The study reports the presence of minute amounts of volatile organic compounds (VOCs) in the urine of teens who didn’t smoke or vape (i.e., controls), e-cigarette users, and dual users of e-cigarettes and cigarettes.

Here are the study results:

Median VOC Levels (ng/mg*) in the Urine of Controls, E-Cig Users and Dual Users
Parent Compound	Controls	E-Cig Users	Dual Users
Benzene	0	0	0.2
Butadiene	0	0	0
Ethylene Oxide	1.3	0.5	1.0
Acrylonitrile	0	1.3	59
Acrolein	193	254	440
Propylene Oxide	15	29	40
Acrylamide	35	67	236
Crotonaldehyde	100	149	185

*ng/mg = parts per MILLION (creatinine)

Significantly, there were no cigarette smokers in the study.  Existing research tells us that their VOC levels would have been far higher, undercutting the UCSF anti-e-cigarette narrative.

Note that there are no alarming elevations in benzene or butadiene, and levels of ethylene oxide were actually lower among users than controls.  This data indicates that teens virtually no exposure to these chemicals.

While levels of other agents are higher in e-cigarette users and especially in dual users, levels in controls are not zero. 

The authors are on shaky ground in their attribution of higher toxin levels among e-cigarette users to the vapor.  A previous study (co-authored by one of the current authors, here) that they cite failed to find any acrolein and crotonaldehyde in vapor from 12 e-cigarettes.  A Centers for Disease Control and Prevention study (here) found that nonsmokers’ urine had up to 245 ng/g of acrolein and up to 158 ng/g of propylene oxide (smokers had far higher levels of both).  Thus, toxin levels seen in e-cigarette users in the new UCSF report are not necessarily due to vapor.

The UCSF research ignores a possible alternative source of these contaminants: recent marijuana smoking, as shown in a CDC study that identified elevated VOC levels among tokers (here).  As I recently noted (here), marijuana use is more prevalent among teens than vaping or cigarette smoking; data from one federal survey shows that about 40% of teen vapers are current marijuana users.  These findings increase the odds that toking impacted results in the new study.

The UCSF research was supported by four grants totaling some $32 million from the National Institutes of Health to authors Rubenstein, Neal Benowitz and Stanton Glantz. 

FDA Advisory Committee: Heat-Not-Burn is Lower Exposure Than Smoke

The FDA Tobacco Products Scientific Advisory Committee (TPSAC) on January 25 unanimously endorsed a claim by Philip Morris International that switching completely from cigarettes to its heat-not-burn IQOS system significantly reduces smokers’ exposure to harmful and potentially harmful chemicals (here).  The committee, however, denied two other claims, that switchers “can reduce the risks of tobacco-related diseases” (8 against, 1 abstention) and that switching “presents less risk of harm” than continued smoking (5-4 against).
 

PMI published numerous short-term studies documenting that toxicant levels from IQOS aerosols were substantially lower than those in smoke, and demonstrating the biologic and medical impact of these differences in cells, animals and humans.  The committee’s denial of the diseases claim was understandable: risks manifest after three or four decades of steady smoke exposure, so risk reduction from switching to IQOS “can” occur over longer time periods. 

However, TPSAC’s close vote rejecting the reduced harm claim is problematic.     

In 2012, the FDA published a list of 93 Harmful and Potentially Harmful Constituents (HPHC) in Tobacco Products and Tobacco Smoke (here and here).  The agency declared that the HPHCs variously posed health hazards as carcinogens, respiratory toxicants, cardiovascular toxicants, reproductive or developmental toxicants, and/or addictive agents.  The agency provided no guidance for the levels of exposure that constitute harm.  This is important, as seen in the case of formaldehyde, a weak carcinogen to which nearly everyone is exposed, but smokers significantly more so (discussed here).

TPSAC rejected impressive evidence of HPHCs reduction in IQOS vapor.  I collected the following information from Appendix C of the FDA Briefing Materials (available here), which standardized toxins in IQOS aerosol and smoke according to nicotine intake.    
 
On average, the reduction in the level of all potential and proven carcinogens (n=29) in IQOS aerosol was 90%.  For the most important carcinogens (n=9), the reduction was 96%.  Average reductions in respiratory (n=18) and cardiovascular (n=8) toxicants were 91% and 93% respectively.  The reductions for all of these individual agents are illustrated in the charts that follow. 

The substantial reductions in all tested HPHCs support the claim that switching completely to IQOS “presents less risk of harm” than continuing to smoke.  There is adequate justification for the FDA to set aside TPSAC’s narrow 5-4 rejection of this claim. 

The two-day hearing raised no significant roadblocks to FDA market authorization for IQOS, which would allow U.S. sales.  Given the significant relative health benefits of this smoke-free product, market authorization is the appropriate action.