# Research Project 1: In vitro and in vivo assessment of flavorant toxicity

> **NIH NIH U54** · ROSWELL PARK CANCER INSTITUTE CORP · 2020 · $779,820

## Abstract

SUMMARY This project addresses the Center for Tobacco Products (CTP) research priorities under Toxicity
scientific domain as defined in RFA-OD-17-006, and the overarching integrative scientific theme of this
TCORS coalesce for testing the effects of flavorings in tobacco products and characterize the
pulmonary toxicity. Emerging tobacco products (Electronic Nicotine Delivery Systems ENDS/e-cigarettes,
cigarillos, waterpipe tobacco), often sold in flavored varieties, represent a significant and increasing proportion
of tobacco consumption in the United States. Flavoring chemicals are commonly used in ENDS products,
cigarillos and waterpipe tobacco. Commonly marketed flavors include tobacco, mint/menthol, fruits/candy
(grapes, mango, melon, pineapple, apple, peach, banana), coffee/tea, chocolate, berries (strawberry and
blueberry), crème/butter, clove/cinnamon, and alcoholic beverages. Underlying these flavors are chemical
flavorings, some of which have known respiratory toxicity (e.g., diacetyl, cinnamaldehyde). The development of
comparative toxicity data -- based on oxidative stress, DNA damage, and inflammation resulting from exposure
to aerosol/smoke with different flavorings in tobacco products- is urgently needed. We hypothesize that
different chemical flavorings used in emerging flavored tobacco products (e-cigarettes/ ENDS, cigarillos, and
waterpipe) differentially influence toxicity in terms of oxidative, DNA damage, epithelial barrier dysfunction, and
inflammatory responses, and influence toxicity in vitro and in vivo (lungs) with varying intensity and duration of
exposure. Our goal is to determine and compare the effects of various flavorings in emerging tobacco products
(e-cigarettes, cigarillos, and waterpipe) on toxicological and immune-inflammatory responses. Specifically, we
will: Aim 1) Determine comparative in vitro toxicity of selected tobacco product flavorings using the aerosol
exposure system for cell-free reactive oxygen species reactivity, and exposure to human lung epithelial cells by
air-liquid interface system, and in a 3D culture system, Aim 2) Determine comparative oxidative, DNA damage
and immune-inflammatory responses to tobacco product flavorings in commonly used mouse strains C57BL/6J
(Th1 response) and Balb/c (Th2 response), and using the state-of-the-art reporter models (NF- B luciferase
and DNA repair/NHEJ reporter mouse) to determine the predictive nature of flavoring toxicity for adverse
respiratory health outcomes of flavorings, and Aim 3) Determine comparative epigenomics (DNA methylation
and transcriptomics)- epigenetic biomarkers in response to tobacco product flavorings. This will determine the
biological effects on respiratory health by flavoring tobacco products in terms of toxicity, biomarkers, and
hazard ranking of flavorings. Outcomes for Regulatory Science: Assessment of toxicity of the same class of
flavorings across the different types of tobacco products in in vitro and in vivo studies will provi...

## Key facts

- **NIH application ID:** 9999505
- **Project number:** 5U54CA228110-03
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE CORP
- **Principal Investigator:** IRFAN RAHMAN
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $779,820
- **Award type:** 5
- **Project period:** 2018-09-14 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999505

## Citation

> US National Institutes of Health, RePORTER application 9999505, Research Project 1: In vitro and in vivo assessment of flavorant toxicity (5U54CA228110-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999505. Licensed CC0.

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