Has the mist been peered through? Revisiting the building blocks of human health risk assessment for electronic cigarette use.

Background: Electronic cigarettes, battery-powered nicotine delivery devices, have been increasingly used in the past decade. However, human health risks associated with E-vapor inhalation have not been fully characterized. Aims: This critical review aims at revisiting the building blocks of human health risk assessment, summarizing the state of the science, and identifying major knowledge gaps in exposure assessment and toxicity assessment. Approach: A qualitative research synthesis was conducted based on scientific findings reported to date in peer-reviewed publications and our own preliminary experimental results. Results: There are a limited number of studies across all lines of evidence on E-vapor exposure and the health impacts of E-vapor inhalation. E-cigarette may be as efficient as traditional cigarettes in nicotine delivery, especially for experienced users, and studies suggest lower emissions of air toxics from E-cigarette vapor and lower second- and third-hand vapor exposures. But some toxic emissions may surpass those of traditional cigarettes, especially under high voltage vaping conditions. Experimentally, E-vapor/E-liquid exposures reduce cell viability and promote pro-inflammatory cytokine release. User vulnerability to concomitant environmental agent exposures, such as viruses and bacteria, may potentially be increased. Conclusion: While evidence to date suggests that e-cigarettes release fewer toxins and carcinogens and compared to cigarettes, E-vapor is not safe and might adversely affect human immune functions. Major knowledge gaps hinder risk quantification and effective regulation of E-cigarette products including: 1) lack of long-term exposure studies; 2) lack of understanding of biological mechanisms associated with exposure; and 3) lack of integration of exposure and toxicity assessments.,. Better data are needed to inform human health risk assessments and to better understand the public health impact of E-vapor exposures.