PBPK modeling characterization of potential acute impairment effects from inhalation of ethanol during e-cigarette use
Creators: name: Sharlee L. More
name: Thornton, Stephanie A.
name: Maskrey, Joshua R.
name: Apurva Sharma
name: Gandiaga, Elise De
name: Thales J. Cheng
name: Fung, Ernest S.
name: Bernal, Autumn J.
name: Madl, Amy K.
Publisher: name: Taylor & Francis
Year: 2020
Subjects: subject: Biophysics
subject: Biochemistry
subject: Microbiology
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Genetics
subject: Pharmacology
subject: Biotechnology
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: FOS: Earth and related environmental sciences
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: FOS: Chemical sciences
subject: 69999 Biological Sciences not elsewhere classified
subject: Plant Biology

description: <b>Objective:</b> Ethanol is used as a solvent for flavoring chemicals in some electronic cigarette (e-cigarette) liquids (e-liquids). However, there are limited data available regarding the effects of inhalation of ethanol on blood alcohol concentration (BAC) during e-cigarette use. In this study, a modified physiologically based pharmacokinetic (PBPK) model for inhalation of ethanol was used to estimate the BAC time-profile of e-cigarette users who puffed an e-liquid containing 23.5% ethanol. <b>Materials and Methods:</b> A modified PBPK model for inhalation of ethanol was developed. Use characteristics were estimated based on first-generation and second-generation e-cigarette topography parameters. Three representative use-case puffing profiles were modeled: a user that took many, short puffs; a typical user with intermediate puff counts and puff durations; and a user that took fewer, long puffs. <b>Results and Discussion:</b> The estimated peak BACs for these three user profiles were 0.22, 0.22, and 0.30 mg/L for first-generation devices, respectively, and 0.85, 0.58, and 0.34 mg/L for second-generation devices, respectively. Additionally, peak BACs for individual first-generation users with directly measured puffing parameters were estimated to range from 0.06 to 0.67 mg/L. None of the scenarios modeled predicted a peak BAC result that approached toxicological or regulatory thresholds that would be associated with physiological impairment (roughly 0.01% or 100 mg/L). <b>Conclusions:</b> The approach used in this study, combining a validated PBPK model for a toxicant with peer-reviewed topographical parameters, can serve as a screening-level exposure assessment useful for evaluation of the safety of e-liquid formulations. <b>Abbreviations:</b> BAC: blood alcohol concentration; e-cigarette: electronic cigarette; e-liquid: e-cigarette liquid or propylene glycol and/or vegetable glycerin-based liquid; HS-GC-FID: headspace gas chromatography with flame-ionization detection; HS-GC-MS: headspace gas chromatography-mass spectrometry; PBPK: physiologically based pharmacokinetic; C<sub>air</sub>: puff concentration expressed as ppm; C<sub>air,mass</sub>: ethanol air concentration expressed on a mass basis; C<sub>v</sub>: ethanol concentration in the venous blood; ρ: density; EC: ethanol concentration in the liquid; PLC: liquid consumption per puff; PAV: air volume of the puff; C<sub>air,mass</sub>: puff concentration expressed as ppm; MW: molecular weight; P: pressure; T: temperature; PK: pharmacokinetic