Risk Assessment of Multiple Heavy Metal Exposures from Electronic Cigarette Use Among Adults and Adolescents

Abstract

Rising popularity of electronic cigarettes (e-cigs) among adults and adolescents is a public health concern as chronic use of e-cigs is associated with increased risk of cardiovascular and pulmonary morbidity and mortality, including popcorn lungs and bronchiolitis obliterans. Used as an alternative to conventional cigarettes, e-cig users are 1.79 times more likely to experience myocardial infarction. As of February 18, 2020, a total of 2,807 hospitalized e-cig or vaping use-associated lung injury (EVALI) cases had been reported to the CDC in the U.S., with 68 cases resulting in deaths. Although the design and appearance of e-cigs have changed across generations, the contents of e-liquid have not. Heavy metals are a significant hazard associated with smoking conventional cigarettes and e-cigs. However, there are no studies assessing potential human health risks of heavy metal exposure from e-cigs' liquid and aerosol. This risk assessment was aimed at using existing studies to evaluate the exposure of multiple metals: copper (Cu), nickel (Ni), and chromium (Cr), as an inhalation, ingestion, and dermal hazard. Average daily doses (ADD), hazard quotients (HQ), and chronic daily intakes (CDI) and cancer risks (CR) were estimated using the established United States Environmental Protection Agency's deterministic risk assessment framework. Common symptoms of Cu exposure include irritation of eyes, nose, and pharynx; nasal septum perforation; dermatitis; with target organs such as eyes, skin, respiratory system, liver, and kidneys. Frequent symptoms of Ni exposure include sensitization dermatitis, allergic asthma, pneumonitis, potentially a carcinogen; with target organs such as nasal cavities, lungs, and skin. Common symptoms of Cr exposure include irritation of eyes, skin; lung fibrosis, and is considered a carcinogen; with target organs such as eyes, skin, and the respiratory system. A total of 135 exposure scenarios were developed among Cu, Ni, and Cr. Population/exposure route pairings include: 1) Adults (21-77 years) for inhalation based on e-cig use data obtained from e-cig aerosols; 2) Adolescents (16-21 years) for inhalation based on e-cig use data obtained from e-cig aerosols; 3) Children ([less-than-or-equal-to} 5 years) for ingestion based on metal concentrations in e-liquid.; and 4) children ([less-than-or equal-to} 5 years) for dermal exposure based on metal concentrations in e-liquid. Each specific scenario included a low exposure scenario, a default scenario, and a high exposure scenario. Scenarios modeled included adjustments in concentration (inhalation, ingestion, and dermal), body weight (inhalation, ingestion, and dermal), exposure time (inhalation), exposure duration (inhalation), ingestion rate (ingestion), and skin contact surface area (dermal). Scenarios were run to generate estimates for ADD and HI, and CDI and Cumulative Cancer Risk. A considerable non-cancer (systemic) risk and excess lifetime cancer risk from Ni and Cr aerosol exposure from e-cigs for all inhalation scenarios among adults and adolescents were observed. A considerable cancer risk was observed for all dermal scenarios of Ni and Cr in e-liquid among children aged [less-than-or equal-to} 5 years. A considerable non-cancer (systemic) risk from dermal exposures to Cu in e-liquid was observed in children aged [less-than-or equal-to} 5 years when considering the default (154.3833 mg/L), and high concentrations of Cu in e-liquid (308.7665 mg/L), default (0.5 hour) and high (1 hour) exposure time, and all skin surface contact area scenarios (400-1800 cm2). Only the high ingestion rate (0.1183 L/day) from the oral scenarios for Cu ingestion of e-liquid exceeded 1. All e-liquid ingestion scenarios for Ni and Cr, except for the Cr low ingestion rate (0.0002 L/day) among children [less-than-or equal-to} 5 years, resulted in a considerable excess lifetime cancer risk. A considerable non-cancer (systemic) risk from oral exposures to Cu in e-liquid was observed in children under 5 years when considering a high ingestion rate of 0.1183 L/day. Uncertainty analysis of the modelled non-cancer risks (ADD, RfD and HQ values), and the cancer risks (CDI, SF and CR values) using univariate regression with 10,000 bootstrap resampling showed low uncertainty in the modeled parameters. Although the health effects of heavy metals are long well-established, this study for the first time characterized the potential exposure dose rates and health risks under various exposure scenarios for aerosols and e-liquids. Instead of perpetuating the notion that e-cigs are a favorable substitute for smoking, it's crucial to acknowledge the alternative risks they pose. We must redirect our focus towards understanding and mitigating these hazards. This includes implementing tamper-resistant e-cig product, and utilization of proper storage conditions for e-cigs may help mitigate health risks associated with e-cigs. Targeting potential or actual e-cig users to implement weight management, stress and anxiety, and mental health programs may also likely aid in reducing the number of e-cig users.