Abstract
There is a long history of tobacco use, however, the methods of use have changed throughout time. In its early days it was consumed either by chewing or as a leaf burned within a pipe. It was only in the early twentieth century that the use of cigarettes started to predominate. With the high demand for cigarettes that came in the 1920's and the post-war period, there was a strong economic drive towards mass production. The pace at which this new method of tobacco use progressed, and possibly as it was a known item, meant that no one considered the toxic effects of inhaling nearly 7000 chemicals into the deepest parts of the lung. Today the negative effects of tobacco smoking are well recognized and indeed this has driven the industry to seek alternate mechanisms for delivering tobacco related products and the major addictive agent nicotine.
With the increased understanding of the negative consequences of cigarette smoke has come an increased degree of social unacceptability. The use of alternative delivery mechanisms, including electronic heated tobacco products (eHTP) and electronic nicotine delivery systems (ENDS) is therefore on the rise. Often these mechanisms are perceived to be safer than traditional cigarette smoke, and this may be true, but without proper toxicological testing we cannot know. There are numerous aspects of these devices that introduce new potentially toxic elements. These include flavorings, the effects of high temperature on the constituents, novel particulates, and the release of metals and other elements from the electrode. Without proper toxicological testing of these devices and their delivered vapors we run the risk of repeating the mistakes of the past and ignoring a major public health issue.
However, this represents a new technical challenge of how best to conduct such toxicology. In particular, what are the data that regulatory agencies should consider. This novel challenge presents with an old-fashioned problem: How does one properly simulate the in vivo situation in order to test. Classically, genotoxicity and cytotoxicity studies are performed using single compounds in submerged conditions. These studies give one clear and definable data but the applicability to the human situation is less exact. The use of whole aerosols to expose at an air liquid interface represents a more complex but potentially more realistic system. However, it comes with the difficulty of ensuring accurate dosing and in particular, consistency of exposure between systems.
In this issue of Applied In Vitro Toxicology, Keyser et al. have utilized the Vitrocell smoke system with the Ames module to produce a system that offers sufficient replicates to cover OECD guidelines for testing at multiple concentrations. They have utilized multiple metrics within this setup to ensure that accurate and reproducible aerosol deposition can be achieved. Furthermore, they have tested this system across multiple forms of tobacco delivery so that equivalency comparisons can be drawn. The importance of characterizing and understanding aerosol delivery within a test system is highlighted by this work. As mentioned, the study utilized multiple analytes and tailors them to the aerosol being generated. This is a valid approach to producing accurate delivery data, however, the need for a consistent analyte across systems is necessary for comparison. Within the three systems used here nicotine provided that consistent analyte. The authors also used glycerol within the ENDS analytes. This may be a very useful comparison analyte across multiple devices as flavorings, nicotine levels, and even temperature can vary.
As the use of electronic nicotine delivery systems expands, the need for accurate and standardized testing will only increase. Utilizing and characterizing systems as shown by Keyser et al. is essential for accurate toxicological assessment and for providing data to regulatory bodies. This work brings us closer to achieving a reliable platform for testing.