Tuesday, November 20, 2018

Detoxing the Heavy Metal Vape Scare


Jonathan Swift 300 years ago observed that “Falsehood flies, and the Truth comes limping after it; so that when Men come to be undeceiv’d, it is too late; the Jest is over, and the Tale has had its Effect.” (here)  That is the story of e-cigarettes and vaping today. 

Billions of dollars have been transferred from tobacco consumers to companies to the FDA in the form of user fees (here).  The FDA, via the NIH, has transferred hundreds of millions to fund university research on tobacco use and effects, in order to provide a “scientific basis” for FDA regulations (here).  With NIH making no attempt to hide our government’s objective – “a world free of tobacco use” (expressed here) – it is not surprising that much of the funded research and attendant publicity is biased to support the announced policy objective.

In March, anti-vaping researchers published a study claiming that metals in e-cigarette vapor are toxic when inhaled.  While the media headlined the findings “dangerous” and “alarming”, and termed vape products “brain-damaging,” I explained in this blog that the metal doses delivered by e-cigarette liquids in this study are trivial.  I estimated that an e-cigarette user could be exposed to excessive metal levels only by consuming high volumes of vape liquids.  For example, vapers would have to use 15.4 liters (nearly four gallons) of liquid per day to achieve exposure to 2 micrograms of cadmium. (here

I worked with Dr. Konstantinos Farsalinos, a prestigious vaping researcher at Greece’s Onassis Cardiac Surgery Center, the University of Patras and the National School of Public Health.  The findings of our risk assessment analysis of the metals study were just published in the journal Inhalation Toxicology (abstract here).

The original study referenced U.S. Environmental Protection Agency safety limits that apply to 24-hour air exposure, or to workers breathing factory air for 8 to 10 hours.  This standard is entirely invalid for e-cigarette analysis, as users do not inhale vapor continuously for such long periods of time. 

Dr. Farsalinos and I applied more realistic federal standards, such as established regulatory safety limits for inhaled medicines.  We calculated total daily exposure to metals by using an average daily vape liquid consumption of 3 to 5 milliliters (e.g., 3 to 5 grams, around 1 teaspoon).

The chart demonstrates that vapers would need to consume impossibly large volumes of liquid in order to exceed the safety limits for almost all metals.  The one exception is nickel, which requires only 17 grams of liquid, but even that is over three times normal daily consumption.

In this case, truth is limping in eight months after widespread false alarms flew about metals in e-cigarette vapor.  The Tale has had its Effect, but in the end, as Shakespeare assures us, truth will out.




Monday, November 12, 2018

Tobacco Control Special Issue Yields Smoke But No Hazard for IQOS Aerosol


Recently a special issue of the journal Tobacco Control offered 22 articles on Philip Morris International’s (PMI) IQOS heat-not-burn tobacco product (here), aiming to dissuade the FDA from allowing IQOS sales as reduced risk products for smokers.  In the words of editor Stanton Glantz: “Policy makers should give greater weight to the advice provided by public health scientists than to submissions from industry when it comes to regulating tobacco products such as heated tobacco products.”



Dr. Glantz’s advice has been inaccurate in the past. A year ago, when he argued that “PMI’s own data fails to support a modified risk claim in people who are actually using [IQOS],”  I detailed the errors in his analysis (here).  This new collection of anti-IQOS articles deserves the same scrutiny.



One treatise, by UCSF’s Gideon St. Helen and colleagues, acknowledges that “All substances in PMI’s list of 58 constituents (PMI-58) were lower in IQOS emissions compared with mainstream smoke of reference cigarettes.”  That accurate statement is followed by the suggestion that PMI ignored that “levels of 56 other constituents, which are not included in the PMI-58 list or FDA’s list of [harmful and potentially harmful constituents], were higher in IQOS emissions.”  The authors criticize PMI for not undertaking “non-targeted chemical analysis” to identify these compounds.



Dr. St. Helen et al. are mistaken.  The chart above, taken from PMI’s presentation to the FDA advisory committee last January (here), documents that the company performed that analysis.  PMI’s extensive investigation of “other” substances is confirmed on the FDA website, where a chart labeled “non-targeted screening” appears in a document submitted by PMI on December 8, 2017, and published by FDA on January 12, 2018 (here). 



The December filing acknowledged that “80 compounds were found to be of higher concentration or new in [IQOS] aerosols…compared to cigarette smoke.  A toxicological assessment was performed and identified 68 of those that do not present specific toxicological concern. 8 compounds present potential genotoxic concerns based on structure-activity computational alerts and 4 compounds are classified mutagens/carcinogens.” 



PMI scientists did not dismiss the findings: “Although a minor subset of compounds identified in this study show intrinsic (potential) toxicological hazards, overall toxicity of the THS generated aerosol was lower compared to cigarette [smoke]. In vitro studies demonstrated a marked decreased biological activity of [IQOS] aerosol compared to smoke. An in vivo 90 days inhalation study showed in general a lower biological activity of the mainstream aerosol from [IQOS] when compared to mainstream smoke.”



Importantly, PMI is undertaking more research: “Additional investigations are ongoing to further characterize the impact of the [mutagens/carcinogens] on the overall toxicity of [IQOS] products.”        

Wednesday, November 7, 2018

Truth Initiative Stumbles in JUUL Study


It’s surprising how many fundamentally flawed e-cigarette studies are aggressively promoted by their authors and allied organizations as grounds for FDA regulatory action.  It is also concerning when authors refuse to acknowledge or respond to honest scientific inquiries about their research.  Here is a representative case involving researchers associated with Truth Initiative, a non-profit anti-tobacco organization.

Researchers led by Donna Vallone, Ph.D., recently published a study in Tobacco Control on the “prevalence and correlates of JUUL [e-cigarette] use among a national sample of youth and young adults (here).”  While they reported that the overall prevalence of ever and current (past 30-day) JUUL use was 6.0% and 3.3% respectively, they failed to disclose information about the most important correlate of JUUL use – other e-cigarette use.

The authors noted that among underage children (15-17 years), current JUUL use was 6% and current use of combustible tobacco was 7%.  They connected these, finding that children who were currently smoking were five times more likely to use JUUL than non-smokers.  However, 11% of children in that age group currently used e-cigarettes.  They ignored this important correlate in their analyses.  Instead, they inexplicably included e-cig use among other members of the youths’ households.

There are other significant problems with this study.  First, youths and young adults were asked: “…on how many days did you smoke a Juul vape?” (emphasis added)  That wording likely confused participants. 

Second, the authors didn’t define current use of e-cigarettes, nor did they even give any description of the question in their survey. 

Third, the survey flow for JUUL and e-cigarette questions was not provided.  Were separate questions about these products asked of all participants, or did researchers ask first about e-cigarettes, and then only ask current e-cig users if they used JUULs? 

Fourth, Vallone et. al. defined JUUL “regular use” as 10-30 days in the past month, and they reported that 25% of youth fell into this category.  That percentage is grossly inflated.  The CDC and other authorities use a more credible “frequent” category of 20+ days (here and here), which would generate a lower percentage of users at risk.    

In summary, Vallone et. al. produced an error-ridden study focused on JUUL “smoking,” while ignoring the effect of other e-cigarette use.  The obvious problems ought to have been resolved in peer review.  Additional questions remain, owing to the fact that the authors used a private dataset.  When Truth Initiative posted the study on the Society for Nicotine and Tobacco Research listserv, I asked the authors to resolve some of these problems; they did not acknowledge my listserv post.