PBPK modeling characterization of potential acute impairment effects from inhalation of ethanol during e-cigarette use. (2nd January 2020)

• Record Type: Journal Article
• Authors: More, Sharlee L.; Thornton, Stephanie A.; Maskrey, Joshua R.; Sharma, Apurva; de Gandiaga, Elise; Cheng, Thales J.; Fung, Ernest S.; Bernal, Autumn J.; Madl, Amy K.
• Is Part Of: Inhalation toxicology. Volume 32:Number 1(2020)
• Page Start: 14
• Page End: 23
• Publication Date: 2020-01-02
• Subjects: BAC -- e-cigarette -- ethanol -- inhalation exposure -- physiologically based pharmacokinetic modeling -- topography; Pulmonary toxicology -- Animal models -- Periodicals; Pulmonary toxicology -- Periodicals; Air -- Pollution -- Health aspects -- Periodicals; 616.200471
• DOI: 10.1080/08958378.2020.1720867
• Languages: English
• ISSNs: 0895-8378

Abstract

Abstract: Objective: 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. Materials and Methods: 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. Results and Discussion: 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). Conclusions: 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. Abbreviations: 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; Cair : puff concentration expressed as ppm; Cair, mass : ethanol air concentration expressed on a mass basis; Cv : 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; Cair, mass : puff concentration expressed as ppm; MW: molecular weight; P: pressure; T: temperature; PK: pharmacokinetic