Commentary: Inflammatory and Oxidative Responses Induced by Exposure to Commonly Used e-Cigarette Flavoring Chemicals and Flavored e-Liquids without Nicotine.

Muthumalage et al. (2017) have recently investigated the effects of a range of flavoring chemicals and flavored e-liquids on two monocytic cell lines, MM6 and U937. The authors have shown that by exposing monocytes to flavorings used in e-liquids it is possible to elicit a cytotoxic as well as an inflammatory response mediated by ROS production and conclude that this may provide insights into potential inhalational risk of e-cigarette use.

There is a tendency to exaggerate potential health risks of e-cigarettes with little or no consideration for the emerging health benefits. The current study is no exception. In particular, translating the study’s findings into a real-life setting is questionable.

First, no specific information on the regime used to generate the aerosol was provided; in particular no details on device, voltage, puff volume, puff duration, and puffing profile were reported.

Second, biologic and toxicological responses are normally expected when cells are chronically and continuously exposed to chemicals at high concentrations. Unsurprisingly, cytotoxic as well as non-specific inflammatory and oxidative stress responses were shown in monocytic cell lines exposed for no less than 24 h to (some) chemical flavorings at high concentrations and to a mix of flavorings-containing e-liquids. Furthermore, important consideration must be given to the fact that flavorings gets rapidly degraded in the blood. For example, cinnamaldehyde is oxidized very rapidly to cinnamic acid (Bickers et al., 2005) in rat as well as in humans (Quarto di Palo and Bertolini, 1961; Yuan et al., 1992; Joint Expert Committee on Food Additives, 2000). In a previous study, Yuan et al. determined that the maximum concentration of cinnamaldehyde in the blood reach 7.6 μM after a 250–500 mg/Kg oral dose in rats (Yuan et al., 1992). Muthumalage et al. (2017) exposed monocytes to a range of concentration between 10 and 1000 μM, which is higher than the maximum reported in rats. Moreover, less than 0.1% of cinnamaldehyde remains in the blood, with a high-life ranging from minutes to 2 h (Quarto di Palo and Bertolini, 1961; Lee et al., 2009). So, the exposure system used by Muthumalage et al do not take in account the accelerated metabolism of flavorings and likely to overemphasize their harmful effects. Chronic exposure to high levels of sugar or salt in a water solution would have triggered similar responses (Garland et al., 1989). Moreover, authors exposed monocytes to flavoring chemicals at a range concentration from 10 to 1000 μM when the major international agencies report limits of exposure that are significantly lower (Table 1).