Cardiopulmonary Toxicity of Electronic Nicotine Delivery Systems Although electronic nicotine delivery systems (ENDS) are widely used by youth and young adults, the toxicity and the health effects of these products remain unclear. Many types of devices with varying constituents have been introduced into the market, making it difficult to ascribe toxicity to a specific class of products or to study their long-term health effects. ENDS produce volatile organic compounds (VOCs) such as formaldehyde and acrolein, which are generated by the thermal degradation of e-liquids containing propylene glycol:vegetable glycerin (PG:VG) and may lead to adverse health effects. Nevertheless, the dependence of VOC generation on e-liquid composition and constituents, nicotine and other ingredients has not been studied, and the contributions of different constituents to the potential harmful effects of e-cigarettes remain unclear. Therefore, within the framework of a regulatory context, we plan to study the cardiovascular and pulmonary toxicity of e-cigarette aerosols over a wide range of operating conditions and use patterns to provide rigorous and comprehensive data pertinent to the regulation of new and emerging devices by the US Food and Drug Administration (FDA). Based on our previous work, we propose that device-specific cardiovascular and pulmonary effects of e-cigarettes are in large part mediated by the extent of VOCs generation and toxicity, which are modified by co-exposure to nicotine and other e-liquid ingredients as well as individual use patterns.