Ecotoxicological screening of an e-liquid mixture using computational tools

Abstract

E-liquids used in electronic nicotine delivery systems (ENDS) are mixtures composed of a variety of chemicals, with nicotine, propylene glycol, and glycerol typically representing the primary ingredients. The U.S. Food and Drug Administration requires manufacturers to evaluate the environmental impacts of manufacture, use, and disposal of ENDS, e-liquids, and other tobacco products as a component of the premarket tobacco product application (PMTA). Environmental impacts may be assessed by examining the potential ecotoxicological risks of e-liquid ingredients in National Environmental Policy Act of 1969 Environmental Assessments as part of the PMTA. Although ecotoxicological characteristics have been assessed for myriad industrial chemicals, pharmaceuticals, and personal care products, to date, no published study has evaluated the ecotoxicological characteristics of e-liquids. Hence, this study describes a novel framework to screen complex e-liquid mixtures for chemicals that exhibit the greatest potential ecological risk. Specifically, the U.S. Environmental Protection Agency (USEPA) Ecological Structure Activity Relationships (ECOSAR) program was used to predict toxicity of e-liquid ingredients to several aquatic organisms; the relative toxicity of each chemical was then calculated, accounting for toxicity thresholds and chemical concentration. The potential environmental fate of seven chemicals exhibiting the greatest toxicity was then evaluated using the USEPA Exposure and Fate Assessment Screening Tool (E-FAST). Concentrations of chemicals released to the environment under hypothetical manufacturing and end-use release scenarios were estimated in surface water and compared to toxicological benchmarks to determine the potential impacts to aquatic organisms. The described framework is a robust, high-throughput method to screen the chemicals of greatest ecological concern in complex chemical mixtures, including, but not limited to, e-liquids to enable a targeted assessment of potential ecological impacts.