Vapers, Know Your E-Cig Ingredients: Propylene Glycol

A common knock against e-cigarettes is that we don’t know the long-term health effects of consuming nicotine vapor.  The fact is that while it’s impossible to have complete knowledge about a novel form of tobacco use, scientists already know a great deal about propylene glycol (PG), a key ingredient of the vapor in e-cigarettes.

A comprehensive 2012 PG toxicology review, authored by members of the Cosmetics Ingredient Review (CIR) expert panel, appeared in the International Journal of Toxicology (available here). 

The report was an update of a 1994 assessment which concluded that PG was “safe for use in cosmetic products at concentrations up to 50.0%” – the cosmetic industry standard at the time.    By 2012, PG was used in 9,094 of 34,391 cosmetic and personal care formulations.  One of the most interesting passages in the 1994 document was a description of aerosolized PG in hair sprays:

“Propylene glycol is used in hair sprays, and its effects on the lungs that may be induced by aerosolized products containing this ingredient may be of concern.  The aerosol properties that determine deposition in the respiratory system are particle size and density.  The parameter most closely associated with deposition is the aerodynamic diameter, d_a, defined as the diameter of a sphere of unit density possessing the same terminal settling velocity as the particle in question.  In humans, particles with an aerodynamic diameter of < 10 um [micrometers] are respirable.  Particles with a d_a from 0.1 to 10 um settle in the upper respiratory tract and particles with a d_a < 0.1 um settle in the lower respiratory tract.  Particle diameters of 60 to 80 um and > 80 um have been reported for anhydrous hair sprays and pump hairsprays, respectively.  In practice, aerosols

should have at least 99% of their particle diameters in the 10 to 110 um range and the mean particle diameter in a typical aerosol spray has been reported as ~ 38 um.  Therefore, most

aerosol particles are deposited in the nasopharyngeal region and are not respirable.”

In contrast, PG aerosols generated by e-cigarettes appear to be smaller, in the range of 0.1 to 0.4 um, according to a study published last year (abstract here).  So, while it likely that most e-cigarette vapor is settling in the upper respiratory tract, some small aerosol particles are likely reaching deeper lung tissue. 

The 2012 CIR panel also commented about PG as a food additive: “According to the Joint FAO/WHO Expert Committee on Food Additives (JECFA), the acceptable daily intake of PG is 25 milligrams per kilogram of body weight per day.  In Japan, the Ministry of Health, Labour, and Welfare (MHLW) specified that according to the food sanitation law, PG has no potential to cause harm to human health.”

The CIR panel also reviewed numerous animal studies regarding potential problems.  They concluded: “Both PG and PPGs [polypropylene glycols] were not considered to be acute or

chronic toxicants in oral or dermal studies, were not genotoxic or carcinogenic, and were not reproductive or developmental toxicants, supporting that their use in cosmetics would be safe

in regard to these end points.”   

The CIR was established in 1976 by an industry association with the support of the FDA and the Consumer Federation of America; it reviews and assesses the safety of ingredients used in cosmetics.  University faculty, industry representatives and the director of the Office of Cosmetics and Colors at the FDA participate in the reviews, which are conducted according to published procedures (here).  The CIR appears to be an excellent example of cooperation between federal regulators and the industry they regulate; it might serve as a template for cooperation among the FDA Center for Tobacco Products and tobacco manufacturers. 

The FDA has thus far taken an aggressively antagonistic approach in its regulatory procedures, some of which are dictated by the 2009 enabling legislation.  For example, the legislation prohibits members of the FDA Tobacco Product Scientific Advisory Committee (TPSAC) from having any relationship with the tobacco industry in the 18 months preceding their appointment (documented here).  This is in direct contrast to all other federal advisory committees (including expert CIR panels), in which an industry conflict of interest for a qualified candidate is reportable but not prohibited.

The CIR served the public interest in producing an informative PG safety review; it also serves as a role model for constructive government-industry interaction.

What’s the Takeaway from Snus?

A new study from British American Tobacco scientists answers that fascinating question, providing valuable information for consumers and regulators. 

Snus contains nicotine and other constituents that make tobacco satisfying, but it also contains contaminants, albeit in vanishingly small amounts.  It is useful to know how much of these constituents users extract and consume during typical use.

Dr. Helena Digard and colleagues published their research in Chemistry Central Journal (abstract here).  They recruited 21 male snus users in Sweden to use four 1-gram pouched snus products for one hour.  They then compared constituent levels in the used pouches with levels in unused pouches from the same package. 

The researchers found that the percentage extraction of constituents from snus was fairly consistent, even though they were present in concentrations that differed by almost a million-fold.  For example, users extracted about one-quarter of the available salt (sodium and chloride), which was present in milligram quantities in the snus pouches.  Also present in milligram quantities was propylene glycol, the solvent used in many e-cigarettes, of which about 30% was extracted; a third of the available nicotine was consumed.

Several constituents, including ammonium (28% extracted), nitrate (27%), and flavorings (19-30%), were present in microgram quantities (one thousand times smaller than milligrams).  Tobacco-specific nitrosamines were present in nanogram quantities (one millionth of a milligram); about 36% were extracted.

This study’s results were reasonably consistent with those from research published in 2012 by John Caraway and P.X. Chen of Reynolds American (abstract here), although the latter work showed somewhat lower extraction of TSNAs and slightly higher extraction of nicotine.  As Nigard et al. acknowledged, there is wide variation in the percentage of extraction among different snus users and even by a single user on different occasions.

Truthful “Action” on E-Cigarettes in the United Kingdom

Action on Smoking and Health (ASH), a British “campaigning public health charity that works to eliminate the harm caused by tobacco,” has published a landmark report on e-cigarettes acknowledging that they “provide effective nicotine delivery” and present “little real-world evidence of harm.”  In addition, “ASH supports regulation to ensure the safety and reliability of e-cigarettes but, in the absence of harm to bystanders, does not consider it appropriate to include e-cigarettes under smokefree regulations.” 

I encourage you to read the 9-page report, which is available here.  I’ll highlight some important points, many of which I have made previously (PubMed Links to the original ASH references are provided where possible).

Nicotine Substitution

“In 1976 Professor Michael Russell wrote: ‘People smoke for nicotine but they die from the tar.’ (reference 6).  Indeed, the harm from smoking is caused almost exclusively by toxins present in tobacco released through combustion.  By contrast, pure nicotine products, although addictive, are considerably less harmful.  Electronic cigarettes consequently represent a safer alternative to cigarettes for smokers who are unable or unwilling to stop using nicotine.”

Propylene Glycol

“There is little evidence of harmful effects from repeated exposure to propylene glycol, the chemical in which nicotine is suspended (references 12 , and 13) One study concludes that e-cigarettes have a low toxicity profile, are well tolerated, and are associated with only mild adverse effects. (reference 14).” 

I should add that the investigators in ASH reference 12 also found that propylene glycol vapor killed bacteria and viruses that were suspended in the air of enclosed spaces (here and here), another potentially positive aspect of this agent.

Second-hand Vapor Risks

“Although e-cigarettes do not produce smoke, users exhale a smoke-like vapour which consists largely of water.  Any health risks of secondhand exposure to propylene glycol vapour are likely to be limited to irritation of the throat.  One study exposed animals to propylene glycol for 12 to 18 months at doses 50 to 700 times the level the animal could absorb through inhalation. Compared to animals living in normal room atmosphere, no localised or generalised irritation was found and kidney, liver, spleen and bone marrow were all found to be normal (reference 12).

“The fact that e-cigarettes look similar to conventional cigarettes has been said to risk confusion as to their use in public places, such as on public transport.  However, given that the most distinctive feature of cigarette smoking is the smell of the smoke, which travels rapidly, and that this is absent from e-cigarette use, it is not clear how any such confusion would be sustained.”

In other words, ASH does not buy into indoor e-cigarette bans because these products don’t expose bystanders to toxic agents, and e-cigarette vapor is instantly distinguished from the smoke of combusted cigarettes.    

While ASH has over many years aggressively opposed the tobacco industry, it notes on its website that it “works to eliminate the harm caused by tobacco.  We do not attack smokers or condemn smoking.”  In this case, ASH has honored this sentiment, objectively evaluating e-cigarettes and establishing a credible position.

E-Cigarettes - No Toxic Effects from Inhaled Propylene Glycol Aerosol

One of the key ingredients in many e-cigarette liquids is propylene glycol (PG), described by Wikipedia (here) as a “colorless, nearly odorless, clear, viscous liquid with a faintly sweet taste…” The entry also explains that PG is used “as a moisturizer in medicines, cosmetics, food, toothpaste, shampoo, mouth wash, hair care and tobacco products…, in smoke machines to make artificial smoke for use in firefighters' training and theatrical productions” and “as a moisture stabilizer (humectant) for snus” among many other applications.

A new study provides valuable information about the toxicological profile of inhaled PG aerosols in laboratory animals; it also provides an excellent general review of the agent. The authors are Michael Werley, a scientist at Altria, and colleagues from Charles River Laboratories (Scotland), WIL Research Laboratories, Battelle Memorial Institute and Virginia Commonwealth University. It was published in the journal Toxicology (abstract here).

The investigators exposed rats and dogs to high concentrations of PG aerosol for up to 28 days, followed by comprehensive systemic evaluations, especially involving the respiratory system.

They report, “In general, these studies confirmed the relatively low toxic potential of [aerosol] PG, administered by various dose routes, including the inhalation route…in the dog, no histopathological effects on the [larynx, trachea and lung] tissues were observed.” The investigators noted decreases in some assessments of red blood cells in dogs treated for 28 days, but “these effects were not clinically significant in the dog and had no effect upon their activity of health”, and “the values still within the normal historical ranges for dogs of this age, strain and sex.”

Werley and colleagues added that, “overall, PG inhalation exposure in rats and dogs produced quite limited toxicological findings, and allowed us to conclude that [aerosol] PG exposures could be conducted safely in man by the inhalation route…”

This study assessed the effects of short-term exposure to PG vapor, but the effects of long-term (months or years) exposure are unknown and unknowable. However, it provides valuable information for e-cigarette users and policy makers. First, even high concentrations of PG vapor don’t have any measurable harmful effects, which is fully consistent with its designation by the FDA as “generally recognized as safe” as a food additive for all food categories up to 2% (here). Just as important, there will be no impact on bystanders from “second-hand” exposure to e-cigarette vapor, if it occurs at all.

Straight Talk About E-Cigarettes

Electronic cigarettes (e-cigarettes) pose important issues relevant to tobacco harm reduction. This post will review the facts about these products, which have been the subject of exaggerated claims by e-cigarette proponents and nicotine prohibitionists alike. As with most complex issues, the truth about e-cigarettes lies somewhere in between.

When users draw on them, battery-powered e-cigarettes vaporize a mixture of water, propylene glycol, nicotine and flavorings. Nicotine is one of the most intensively studied drugs in history; while it is highly addictive, it is not the primary cause of virtually any of the diseases related to smoking. In fact, long-term nicotine consumption is about as safe as that of caffeine. Propylene glycol is approved by the FDA for use in a large number of consumer products; it, too, is sometimes vaporized, forming artificial smoke in theatrical and other productions.

It is almost certain that e-cigarette use (also called vaping) is vastly safer than cigarette smoking, but this is based on limited scientific evidence. Some questions remain unanswered.

The health effects of long-term exposure of the respiratory tract to propylene glycol vapor are unknown, and unknowable. As a health professional, I am more comfortable recommending a product with a defined risk profile, where a clear risk-benefit analysis can be evaluated. That is why I have been a strong supporter of smokeless tobacco products as cigarette substitutes. I recommend these products knowing that we have 50 years of epidemiology documenting the extremely low level of health risks. E-cigarette consumers must understand that the safety of e-cigarettes can not be guaranteed, despite the likelihood that they pose but a tiny fraction of the health risks of regular cigarettes. But given the paucity of legitimate research, specific safety claims for e-cigarettes can not be made.

There is a lot of uncertainty with respect to the reliability of e-cigarettes, essentially all of which are imported from China. One of my colleagues ordered numerous products with the intent of performing some routine tests; many of these products did not function properly right out of the box. According to a recent clinical study of two brands (abstract here), “…neither of the electronic cigarettes exposed users to measurable levels of nicotine or [carbon monoxide]…” Not inhaling carbon monoxide is a good thing, but for addicted smokers, not getting nicotine may be a problem. Many e-cigarette users know that the devices often don’t deliver enough nicotine to satisfy them, so they re-load cartridges with even higher doses from commercially available concentrated solutions. Concentrated nicotine is dangerous, and this kind of experimentation is bound to lead to injuries.

The same study showed that “…both [brands] suppressed nicotine/tobacco abstinence symptom ratings.” This is impressive, because it indicates that e-cigarettes simulate the behavioral aspects of smoking and therefore may be successful in ways that no other smoking cessation product can match.

E-cigarette cartridges may contain hazardous contaminants. Last year, the FDA conducted laboratory tests on a few e-cigarette cartridges. Although the tests were biased and flawed (as I discussed here), they found in one cartridge traces of diethylene glycol, a poisonous impurity found previously in propylene glycol (reported here).

Consumer products should be free of contaminants. Cartridges, as well as the hardware, should be subjected to independent quality control testing. The FDA tests underscored the need for regulatory oversight. This could be accomplished if the FDA regulated e-cigarettes as recreational tobacco products under authority from the Tobacco Act. Instead, the FDA is attempting, inappropriately according to one federal judge, to regulate them as drug-delivery devices (discussed here). That would effectively remove them from the American market, leaving hundreds of thousands of e-cigarette users with no satisfactory alternative to tobacco combustion.

There is no justification or scientific rationale to ban e-cigarettes. Still, anti-tobacco extremists are campaigning against them, claiming, entirely without proof, that they are a starter tobacco product for children. As with all tobacco products, they should not be available to minors.

Another battle rages over whether e-cigarettes can be used safely indoors. Some militant users object to any indoor restrictions, while prohibitionists claim that second-hand vapor is annoying and/or toxic. The latter claim is preposterous, but e-cigarette users who are courteous and respectful toward bystanders are likely to lead longer, healthier and less stressful lives.