*1.2. E-Liquids Contamination*

The attention of scientists to the chemical composition of e-liquids has not only been aimed at the identification of flavoring chemicals, but also to address the issue concerning the potential presence of compounds of toxicological concern, such as volatile organic compounds (VOCs), due to main component contamination and low purity level of nicotine and flavors [11,27–30]. Among VOCs, aromatic hydrocarbons have attracted remarkable attention in view of a toxicity assessment of refill liquids due to the recognized carcinogenic properties of benzene, classified as carc. 1A according to EU CLP regulation [31]. Specific investigations were carried out to perform both qualitative and quantitative characterization in terms of VOCs of e-liquids commercially available on the EU market prior to the EU TPD implementation and after 2016, in order to verify the compliance of e-liquids distributed over EU countries with the TPD in force, in terms of both chemical composition and classification/labelling [24,32]. With specific regard to aromatic hydrocarbons, BTEX contamination has been detected in e-liquids available on extra-EU markets. Lim et al. highlighted the potential health hazards for e-cig users reporting the results of investigations made on 283 flavored liquids, 21 nicotine-content liquids, and 12 disposable cartridges [33]. BTEX coexisted in most of the investigated samples at relevant concentrations (e.g., benzene concentration ranging from 0.008 to 2.28 mg/L) and the contamination was hypothetically related to the use of petrogenic hydrocarbons in the extraction process of nicotine and flavors from natural plants. BTEX contamination of liquid formulations was also previously observed by Han et al. in a study aiming to assess VOCs levels in 55 refill liquids of 17 different brands available on the Chinese market [34]. Benzene and m,p-xylenes were found in all of the samples investigated, whilst ethylbenzene and toluene were detected with different frequencies. They all were present at comparable levels in the concentration range 1.10–17.31 μg/g. In view of the findings obtained to date on e-liquids composition in terms of a broad range of chemicals, reported above, it appears clear that the attention on the issue has to remain high to ensure that consumers' health is safeguarded and that compliance to safety and quality standards is guaranteed. On one hand there is the need for a comprehensive database referred to e-liquids both manufactured and imported in EU member states before the implementation of the TPD allowing us to define a pre-TPD baseline reference useful for comparison. On the other hand, ongoing investigations into e-liquids currently on the market are necessary to evaluate the effectiveness of TPD provisions in EU member states with regard to the manufacture and labelling of e-liquids, and to formulate further recommendations to policymakers.
