PBPK modeling characterization of potential acute impairment effects from inhalation of ethanol during e-cigarette use
| Autor: | Amy K. Madl, Apurva Sharma, Stephanie A Thornton, Autumn J Bernal, Sharlee L More, Joshua R. Maskrey, Ernest S Fung, Elise de Gandiaga, Thales J. Cheng |
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| Rok vydání: | 2020 |
| Předmět: |
Physiologically based pharmacokinetic modelling
Health Toxicology and Mutagenesis Cigarette use 010501 environmental sciences Pharmacology Electronic Nicotine Delivery Systems Toxicology 01 natural sciences Models Biological law.invention 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine law Humans 0105 earth and related environmental sciences Inhalation exposure Inhalation Exposure Ethanol Inhalation Vaping food and beverages 030228 respiratory system chemistry Electronic cigarette |
| DOI: | 10.6084/m9.figshare.11961510.v1 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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