# Integrated risk assessment and molecular characterization of pulmonary response to e-cigarette exposure

> **NIH NIH R01** · BATTELLE PACIFIC NORTHWEST LABORATORIES · 2020 · $576,908

## Abstract

PROJECT ABSTRACT
E-cigarette (e-cig) aerosol/vapor is a complex mixture of the original components of the e-liquid (propylene
glycol (PG), vegetable glycerol (VG), nicotine, water, and flavoring additives), and of other constituents (such
as aldehydes, metals, nanoparticles, and some unknown compounds) produced by chemical transformation of
the original components exposed to the electrically heated metal wire in the presence of oxygen. Emerging
research is beginning to challenge the “relatively safe” perception of e-cigarettes. Recent studies suggest e-cig
aerosol/vapor provokes an inflammatory response and oxidative stress (reminiscent of cigarette smoke where
oxidative stress and inflammation are among the first clinically defined events associated with toxicity and
disease due to cigarette smoking) however details of the underlying molecular mechanisms remain unclear.
Furthermore the contributions that specific e-liquid constituents have in mediating them as well as the impact of
oxidation products of e-liquid constituents generated by the e-cigarette heating process, are poorly understood.
Focusing on oxidative stress and inflammation as intermediate measures of biological responses predictive of
tissue dysfunction leading to disease initiation we will assess the hazard potential of e-liquid main components
(PG, VG, nicotine, and flavorings). We hypothesize that individual components of e-liquid produce distinct
signatures of early oxidative/nitrative damage in cells and tissue. Our objectives are to elucidate the signatures
of reversible and irreversible oxidative modifications induced by e-cig aerosol and use them to evaluate the
relative hazards of different e-liquid constituents in conjunction with computational fluid dynamic-
physiologically-based pharmacokinetic (CFD/PBPK) models for comparative respiratory dosimetry. Most
commonly used measures of cell redox state (i.e., GSH content) provide little insight into the types or sites of
damage induced critical for a mechanistic understanding. Recent advances in quantitative redox proteomics at
PNNL make it feasible to identify these modifications and determine their site-specific occupancies at a
proteome-wide scale. The Research Grade E-cigarette (REC) device developed at Battelle provides a unique
capability to generate and characterize aerosol/vapor from individual e-liquid components with or without the
use of a heated coil, allowing effects of both the major e-liquid components as well as potential toxicants that
result from (coil) heating of the e-liquid in the presence of oxygen to be identified and quantified. Using these
novel enabling technologies, we will define what compounds or aerosol size fraction are most harmful and how
they contribute to the effects of inhalation of e-cig aerosol and individual aerosolized e-liquid components on
pulmonary response. We will accomplish our goal through the following aims: (1) Characterize aerosol/vapor of
e-cigarette generated at moderate a...

## Key facts

- **NIH application ID:** 10003385
- **Project number:** 5R01HL139335-03
- **Recipient organization:** BATTELLE PACIFIC NORTHWEST LABORATORIES
- **Principal Investigator:** Vladimir B Mikheev
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $576,908
- **Award type:** 5
- **Project period:** 2018-09-13 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003385

## Citation

> US National Institutes of Health, RePORTER application 10003385, Integrated risk assessment and molecular characterization of pulmonary response to e-cigarette exposure (5R01HL139335-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10003385. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*