# Measuring Anatalline and Nicotelline to Differentiate Non-combusted Tobacco Use Using the PATH Study

> **NIH NIH R21** · WESTAT, INC. · 2020 · $256,368

## Abstract

PROJECT SUMMARY
Although tobacco use remains the leading preventable cause of disease and death in the United States, all
tobacco products do not confer similar public health risk. Specifically, combusted products tend to be viewed
as more harmful than non-combusted products. One research priority for the Food and Drug Administration
(FDA) is to better understand product toxicity including the development and validation of new biomarkers
related to non-cigarette tobacco exposure, harm, or toxicity. Biomarkers that are able to distinguish between
types of product use are vital to track the impact of regulatory action and associated proximal and distal health
effects related to product use. The goal of this study is to measure nicotelline, a minor tobacco alkaloid
associated with tobacco smoker particulate matter, in urine biospecimens from Wave 1 of the Population
Assessment of Tobacco and Health (PATH) Study. Aims include to validate nicotelline and its utility (alone or in
combination with other biomarkers of tobacco exposure) to distinguish combusted product use (i.e., cigarettes)
from non-combusted product use (i.e., smokeless tobacco [SLT] and electronic cigarettes [e-cigarettes]).
Previous research has shown when taken as a ratio with its parent compound (anatalline), nicotelline has
shown promise in distinguishing SLT use from combusted tobacco use. Therefore, we propose to expand on
this existing literature by measuring these compounds in a large sample (N= 140 each) of exclusive daily SLT
users, exclusive daily cigarette smokers, and dual SLT + cigarette users to: (1a) validate anatalline/nicotelline
ratio to distinguish exclusive SLT users from exclusive cigarette smokers, and (1b) determine
anatalline/nicotelline ratio cut-points to distinguish exclusive SLT, dual SLT + cigarette use, and exclusive
cigarette use. In addition, we propose exploring if this biomarker may also be able to differentiate other non-
combusted product use, specifically e-cigarettes, from combusted product use. We propose additional specific
aims among exclusive e-cigarette users (N= 140), and dual e-cigarette + cigarette users (N= 140):
(2a) measure nicotelline to distinguish exclusive e-cigarette users from exclusive cigarette smokers, and
(2b) determine cut-points of nicotelline and ratios of nicotelline-to-traditional tobacco biomarkers (i.e., 4-
(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL]) to distinguish exclusive e-cigarette, dual e-cigarette +
cigarette use, and exclusive cigarette use. All aims will be evaluated by comparing levels of exposure using
nonparametric Kruskal-Wallace analysis of variance (Aim 1a, 2a) and calculating Receiver Operating Curve
(ROC) characteristics (Aim 1b, 2b) to determine cut-points for distinguishing different tobacco product use.
Based on biospecimen availability online, https://www.icpsr.umich.edu/icpsrweb/content/NAHDAP/pathstudy-
biospec-index.html, these specimens should be available in sufficient quantities. Given...

## Key facts

- **NIH application ID:** 10037666
- **Project number:** 1R21DA051491-01
- **Recipient organization:** WESTAT, INC.
- **Principal Investigator:** Kathryn Claire Edwards
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $256,368
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10037666

## Citation

> US National Institutes of Health, RePORTER application 10037666, Measuring Anatalline and Nicotelline to Differentiate Non-combusted Tobacco Use Using the PATH Study (1R21DA051491-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10037666. Licensed CC0.

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