Analytical and Toxicological Assessment of Chemicals and Elements in Multiple Generations of Electronic Cigarette Products

Electronic cigarettes (e-cigarettes), which remain popular among consumers, have been associated with attractive flavored products, especially among adolescents and young adults. This dissertation aimed to evaluate the chemical composition of e-cigarettes and determine the toxic effects of e-cigarettes and chemicals used in high amounts. First, high-performance liquid chromatography and gas chromatography-mass spectrometry were used to identify and quantify nicotine, solvents, flavor chemicals, and synthetic coolant in over 400 products. Nicotine concentrations varied in one brand of refill fluids purchased worldwide. Concentrations of total flavor chemicals ranged from 0 - 343 mg/ml and were generally greater than nicotine concentrations. Most frequently occurring flavor chemicals (e.g., ethyl maltol, furaneol, benzyl alcohol, ethyl vanillin, corylone, triacetin, menthol, vanillin, and cinnamaldehyde, were categorized as fruity, floral, caramellic, vanilla and minty. These results showed the flavor chemicals in e-cigarettes, which often exceed levels used in edible or household products, are sufficiently high enough to make them attractive to youth and adolescents. Next, we evaluated the cytotoxicity of e-cigarette liquids, aerosols, and authentic chemicals standards using multiple endpoint assays (MTT, NRU, and live-cell imaging) and cell lines. E-liquid and aerosol cytotoxicities ranged from 0.01 - 10%, and 0.2 - 1.8%, respectively. Lower concentrations of pure flavor chemicals and WS-23 than in e-cigarettes significantly affected cells and correlated with toxicity. In some products, the flavor chemical concentrations were 30 (menthol), 100 (ethyl maltol), and 100,000 (cinnamaldehyde) times greater than their cytotoxic concentration. The WS-23 concentration that produced cytotoxic effects was 90 times lower than in an e-cigarette fluid and exceeded levels used in consumer products. Flavor chemicals have profound cytotoxic effects in acute in vitro assays, emphasizing the potential to impact human health negatively with chronic use. Finally, the Margin of Exposure (MOE) was used to calculate the cancer risk of pulegone and the health risk of synthetic coolants and flavor chemicals. Pulegone and synthetic coolant levels in e-cigarettes present a significantly calculated risk for cancer and health hazard, contributing to increased harm to consumers. The work in this dissertation emphasizes the need for continuous monitoring of e-cigarette constituents and the enactment of effective regulation to reduce unwanted toxicological effects