Proper appraisal

Assessing the safety and evaluating the risk of novel tobacco and nicotine products

By Marina Murphy

E-cigarettes are expected to be big news this year. India will host the seventh Conference of the Parties (COP) of the Framework Convention on Tobacco Control, which is the World Health Organization’s (WHO) international treaty on tobacco control.

The COP is the governing body of this treaty. The WHO does not support e-cigarettes. This is despite the fact that many in the public health community¹ do, and despite the prediction that around 1 billion people will die from smoking-related disease in the 21st century compared with “just” 100 million in the past century.² This is because, although the percentage of smokers has decreased, the number of smokers has increased due to population growth.³ By contrast, Public Health England (PHE), an agency of the U.K. Department of Health, and others believe that the popularity of e-cigarettes, as well as the fact that they are safer—95 percent safer compared with cigarettes according to PHE—could be the answer to this public health crisis.

E-cigarettes therefore hold great potential for reducing smoking-related disease. But this needs to be scientifically proven. To this end, British American Tobacco (BAT) and others are developing tests to help them understand their products and their biological impact. Such tests will also help better define and further reduce any residual risks to as low a level as possible; help establish appropriate quality control and standards; and further reassure consumers, regulators and public health as to the reduced risk potential of these and other products.

ASSESSING NEXT-GENERATION PRODUCTS

Recent years have seen the emergence of some very high-tech gadgetry and technology in the area of nicotine products. Fresh eyes and new tests are required to ensure that products based on these technologies are as safe as can be. BAT has proposed a new scientific framework⁴ to do just that.

This framework has four basic stages. The first step is understanding how consumers use the products and then using this information to understand the products. Laboratory and clinical testing is then used to determine whether these products emit and deliver fewer toxicants than conventional cigarettes. Testing then moves into the real world to determine what impact, if any, a reduction in toxicants will have on a person’s individual risk, as well as the collective risk of a population using the products.

UNDERSTANDING CONSUMER BEHAVIOR

Understanding how consumers use their products is an essential first step. This helps to ensure that machine testing of e-cigarettes mimics real-life use and therefore gives realistic results. BAT has developed a test, based on a technology called a Smoking Analyzer (SA7), to help it do that. The SA7 was developed initially to measure smokers’ puffing behavior. This is a portable device capable of measuring pressure and flow, and it provides information such as the size and length of a puff and the time between puffs.

The company has observed many different types of vaping behaviors, and by using an average it can program lab-based “vaping robots” to make measurements in the laboratory more accurate and true to life.

CHARACTERIZING VAPOR PRODUCTS

Vaping robots produce vapor in the lab in a similar manner to a consumer, and a series of chemical tests are used to identify and measure the constituents in e-cigarette emissions. For example, a “GC-GC-MS” technology combines gas chromatography, which is used to separate out the component parts of the aerosol, and mass spectroscopy, which then identifies each component part.

The separation technique uses a very long, very narrow column through which the aerosol passes. Different molecules travel through the column at different rates and exit the column at different stages, at which time a mass spectrometer is used to identify each of them. This involves breaking the molecules into smaller fragments and then identifying each fragment according to its mass-to-charge ratio. The results of this and other tests demonstrate that the e-cigarette aerosol is much less complex than cigarette smoke (see Figure 1). BAT has observed reductions of 90 percent and more in the levels of certain toxicants present in e-cigarette vapor compared with cigarettes.

E-CIG VAPOR COMPARISON TO CIGARETTE SMOKE

The biological impact of e-cigarette vapor compared with cigarette smoke can be tested in the lab using cell-based tests. One test uses a 3-D model of human lung tissue to examine the impact of e-cigarette vapor versus smoke on cell health. Also, there is a “scratch test” that examines a tissue’s ability to repair itself (when scratched) after exposure to e-cigarette vapor or cigarette smoke (see Figure 2).

The first test uses a dye to observe the impact of aerosol exposure on the cells. Healthy cells have an enzyme that breaks down the dye so that it changes from purple to yellow. Healthy cells will therefore appear more yellow in color than unhealthy or dead cells. This test reveals that exposure to cigarette smoke for six hours causes near complete death of human airway cells in this test. But even after hours of continuous exposure, the impact of the e-cigarette vapor on the airway tissue was found to be similar to that of air.⁶

In the “scratch test,” a layer of cells is scratched and the cells’ ability to close the scratch/wound is observed. The scratch mimics natural wear and tear in the cardiovascular system. This test can be used to compare the effect of e-cigarette vapor on wound healing compared with cigarette smoke. When the cells were exposed to smoke, they seemed to lose their sense of direction and position relevant to other cells; they appeared “confused” and could not find their way across the gap—the wound did not close. By contrast, when the cells were exposed to e-cigarette vapor, the cells quickly closed the gap in much the same way as they do when just exposed to air.

These early-stage results demonstrate that in comparison to cigarettes, these new products have great potential to demonstrate a reduction in disease-relevant risk.

REAL-WORLD TESTING

Lab tests can be used to study the products to determine whether the aerosol from e-cigarettes contains fewer toxicants than cigarette smoke and to examine the biological impact of e-cigarette vapor on human tissue models, compared with the impact of exposure to cigarette smoke.

Clinical testing with consumers is required to determine exposure to toxicants, using biomarkers of exposure, which could be the toxicant itself or its metabolic breakdown product, which is found in blood, saliva and urine. Or it could be a physiological measurement like cholesterol levels. The higher the levels observed, the higher the exposure. This can give an indication of individual risk, but e-cigarette usage and uptake by consumers must be measured in order to assess their impact for reducing risk at a population level.

This assessment framework will help build the required evidence base needed to demonstrate that novel tobacco and nicotine products can deliver a net population health gain in comparison with cigarette smoking. There is now a great opportunity for the industry, regulators and academia to come together and agree on standards and testing protocols for e-cigarettes and other novel products.

Marina Murphy head of scientific media relations, research & development at British American Tobacco.

References

¹ E-cigarettes: an evidence update. A report commissioned by Public Health England, 2015; [www.gov.uk/government/uploads/system/uploads/attachment_data/file/457102/Ecigarettes_an_evidence_update_A_report_commissioned_by_Public_Health_England_FINAL.pdf, accessed 22nd October 2015]

² WHO Report on the Global Tobacco Epidemic 2008. MPOWER report; [www.who.int/tobacco/mpower/mpower_report_full_2008.pdf]

³ Marie Ng, et al. (2014). Smoking Prevalence and Cigarette Consumption in 187 Countries, 1980-2012. JAMA. Vol. 311(2) p183-192; doi:10.1001/jama.2013.284692.

⁴ F. Lowe, I.M. Fearon, O.M. Camarcho, E. Minet and J. Murphy (2015). A framework for the biological assessment of reduced risk tobacco and nicotine products. Recent Advances in Tobacco Science: Vol. 41, p 51-8.

⁵ C. Proctor, et al. (2014). Integrating chemical, toxicological and clinical research to assess the potential of reducing health risks associated with cigarette smoking through toxicant regulation, Recent Advances in Tobacco Science: Vol. 40, p 1-34.

⁶ L. Neilson, et al. (2015). Development of an in-vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue: application for assessment of e-cigarette aerosol. Toxicol in Vitro, Vol. 29, p 856-86.