Personalization of Electronic Nicotine Delivery Systems Toxicological impact in in-vivo model

Electronic nicotine delivery systems (ENDS) use has recently grown. E-cig generates carcinogenic chemical compounds and reactive oxygen species (ROS). Carbonyls and ROS are formed when the liquid comes into contact with the heating element. In this study the chemical and biological effects of coil resistance applied on the same device were investigated. A preliminary in-vivo study the new heat-not-burn devices (IQOS®) has been conducted to evaluate the effect of the device on antioxidant biomarkers. The amount of formaldehyde, acetaldehyde, acrolein was measured by GC-MS analysis. The two e-liquids used for carbonyls detection differed only for the presence of nicotine. The nicotine-free liquid was then used for the detection of ROS in the aerosol. The impact of the non-nicotine vapor on cell viability in H1299 human lung carcinoma cells, as well as the biological effects in a rat model of e-cig aerosol exposure, were also evaluated. After the exposure of Sprague Dawley rats to e-cig and IQOS® aerosol, the effect of 28-day treatment was examined on enzymatic and non-enzymatic antioxidant response, lung inflammation, blood homeostasis and tissue damage by using scanning electron microscope (SEM) technique. The results show a significant correlation between the low resistance and the generation of higher concentrations of the selected carbonyls and ROS in aerosols. Cell viability was reduced with an inverse relation to coil resistance. The experimental model highlighted an impairment of the pulmonary antioxidant and detoxifying machinery. Frames from SEM show disorganization of alveolar and bronchial epithelium. IQOS® exposed animals shows a significant production of ROS related to the unbalance of antioxidant defense and alteration of macromolecule integrity. This research demonstrates how several toxicological aspects can potentially occur in e-cig consumers who use low resistance device coupled with nicotine-free liquid. ENDS may expose users to hazardous compounds, which, may promote chronic pathologies and degenerative diseases.

Toxicological effects related to a novel heated tobacco product

The tobacco epidemic is a public health burden. Nicotine-Delivery-Systems(NDS) are devices designed to help people replace conventional cigarette(CC) and among these devices we find electronic cigarettes(e-cig), which are classified as Electronic-NDS(ENDS). E-cigs use different technologies to vaporize a liquid or to heat the tobacco avoiding the combustion phenomenon(IQOS). The US Food and Drug Administration(FDA) has labelled IQOS as modified risk tobacco products(MRTPs), indirectly encouraging the perception of safety in the consumers, but IQOS smoke, although to a lesser extent than conventional, still presents a great deal of harmful or potentially harmful compounds. My PhD thesis aims to study the toxic effects related to IQOS exposure. I sought to answer the question of whether the toxic compounds released by IQOS, albeit in reduced concentrations, could lead to genotoxicity and damage to the airways and liver in vivo. At the University of Nottingham, I have investigated in vitro the effects generated by the IQOS, e-cigs and CC exposure on PBMCs and human lung epithelial cell line. Finally, at University of Milano–Bicocca, I have developed a in vivo Positron Emission computed Tomography(PET) imaging procedure meant to be applied to the monitoring of ENDS toxicity, particularly in the brain. These results indicate that IQOS is not a low-risk product in vivo, for primary target organs but also for secondary organs, although we have observed a small impact in vitro. Labelling as MRTP may mislead consumers who interpret “a lower level of toxic compounds” as an indication of “harmlessness” when there is a health risk for users. In the last part, I set up a methodology for studying temporal fluctuations of regional brain metabolism and connectivity derived from mice of different ages allowing researchers to obtain normative values in investigations of the efficacy or toxicity of substances at the functional level of the CNS.