# Neurotoxic and neurodegenerative risks from chronic exposure to metal mixtures in e-cigarette aerosol

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $687,278

## Abstract

PROJECT SUMMARY
Electronic cigarettes (e-cigs), battery-operated devices that heat liquids to generate an inhaled aerosol vapor,
are increasingly popular, especially among younger users. E-cigs are seen as an increasingly attractive
alternative to tobacco cigarettes; however, little is known about the human health effects arising from chronic
exposure to these aerosols. A growing number of studies have examined potential e-cig risks for cancer,
respiratory, and cardiovascular diseases. New data from our laboratory and others, however, raise additional
human health concerns about exposure to potentially neurotoxic metals released from the heated coil wire and
other e-cig components. For example, we found that in a large fraction e-cig aerosol samples we collected,
nickel, chromium, and lead levels exceeded EPA national ambient air quality standards or ATSDR minimum
risk levels (MRL). Notably, this was true for manganese (Mn), a prime suspect in sporadic Parkinson’s disease
(PD) etiology. Others have found that vanadium, copper and selenium (all suspected for a potential role in PD)
were higher in blood of e-cig users as compared to tobacco smokers. We hypothesize that hazardous metals
released by e-cigs may accumulate in the brain and pose significant neurotoxic risk(s) for neurodegenerative
diseases upon chronic exposure. We will test our hypothesis in three ways. First, we will determine the levels
of potentially neurotoxic metals in the aerosol produced by several popular e-cigs operated under different
conditions and with e-liquids differing in flavor and nicotine content. Second, we will examine the neurotoxic
effect of chronic e-cig aerosol exposure in neuronal cell cultures derived from human subjects carrying
incompletely-penetrant mutations linked to PD or from healthy controls, and identify metal mixtures of particular
neurotoxic concern. Third, we will measure metal concentrations in brain tissue of chronically e-cig exposed
mice, which are wildtype controls or knock-in for a mutation that increases the risk for PD; we will also
determine the metals’ potential adverse effects on motor function and cognition in the mouse models. Findings
from this study are likely to provide crucial and heretofore unavailable information to policy makers and will
enable them to evaluate potential neurotoxic health risks arising from second-hand exposure to e-cig aerosol.
We hypothesize that health risks are significantly influenced by genetic susceptibility to neurodegenerative
disease, as well as by e-cig device construction, operating conditions, e-liquid flavoring, and nicotine content.

## Key facts

- **NIH application ID:** 10483159
- **Project number:** 5R01ES032954-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Markus Hilpert
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $687,278
- **Award type:** 5
- **Project period:** 2021-09-08 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10483159

## Citation

> US National Institutes of Health, RePORTER application 10483159, Neurotoxic and neurodegenerative risks from chronic exposure to metal mixtures in e-cigarette aerosol (5R01ES032954-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10483159. Licensed CC0.

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