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Characterization of Potential Harm Caused by Electronic Cigarette Flavor Chemicals and their Reaction Products

Award Number: R01ES029741
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Characterization of Potential Harm Caused by Electronic Cigarette Flavor Chemicals and their Reaction Products - Project Summary Electronic cigarettes (ECs) use heat to aerosolize “e-liquid” mixtures that usually contain high concentrations of flavor chemicals. This project will purchase 650 commercial e-liquids to: a) identify and quantify the flavor chemicals used plus their degradation reaction products (RxPs) formed upon vaping; and b) evaluate the cellular responses to those flavor chemicals often found at >1 mg/ml (viz. “dominant flavor chemicals”, DFCs), and to the aerosols produced on vaping. Tested will be 550 “popular” refill and cartomizer fluids and 100 fluids that have been anecdotally reported to cause sickness in users. Work will be conducted at two campuses: Portland State University for analytical chemistry, and University of California Riverside for human toxicology. Aim 1 (PSU). DFCs and vaping RxPs will be identified and quantified for the 650 fluids. Aerosols made using a range of devices at varied power will be collected in isopropanol and analyzed using gas chromatography/ mass spectrometry (GC/MS) and liquid chromatography/MS/MS. Identification will proceed with standards. RxPs formed from flavor chemicals will be unambiguously distinguished from RxPs from the EC solvents. Aim 2 (UCR). Vape aerosols made using lab-prepared fluids containing the identified DFCs will be made with a range of devices, and screened for cytotoxicity in dose-response experiments using in vitro assays in conjunction with BEAS-2B lung epithelial cells from normal human adults. The aerosols that are most cytotoxic will be studied in depth using an air-liquid interface exposure system with the 3D EpiAirway platform that recapitulates human respiratory epithelium. Individual DFCs will be tested using six cancer-related mode-of- action assays including assays for an epithelial to mesenchymal transition (EMT) that we have observed with some EC products. Alterations in gene expression will be determined using RNA-seq and affected pathways identified. Mixtures of DFCs will be tested at the same relative proportions found in consumer products. Aim 3 (UCR). Since Aim 2 will examine heat generated aerosols, both DFCs and their RxPs products will have been present. Aim 3 will differentiate the DFCs and RxP toxicities by exposing the 3D EpiAirway platform to aerosols generated without heat and containing individual DFCs or the identified RxPs from heating. Endpoint assays will proceed as in Aim 2 to isolate toxicity to individual chemicals. Summary. Little is known about the health effects of flavor chemicals used in ECs. This project will fill an important informational gap with comprehensive new data. Specific toxicants will be identified and the effects of mixing DFCs will be evaluated. Results will be posted on an online database that will be accessible to any interested persons or organization, and will provide foundational information for future understanding of flavor chemicals in tobacco products. The data, the first of their kind, will contribute to a foundation of science upon which the NIH can develop future research directions to protect consumers’ health and protect those exposed by second- and thirdhand means.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Family Smoking Prevention and Tobacco Control Act Regulatory Research	000	5	11/14/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Family Smoking Prevention and Tobacco Control Act Regulatory Research	000	5	8/31/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $681,921 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	900 UNIVERSITY AVE	RIVERSIDE	CA	92521	RIVERSIDE	USA	Family Smoking Prevention and Tobacco Control Act Regulatory Research	001	5	6/30/2022	NON-COMPETING CONTINUATION	$681,921
2022	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	900 UNIVERSITY AVE	RIVERSIDE	CA	92521	RIVERSIDE	USA	Family Smoking Prevention and Tobacco Control Act Regulatory Research	000	4	3/2/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $681,921

Issue Date FY: 2021 ( Subtotal = $683,205 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Family Smoking Prevention and Tobacco Control Act Regulatory Research	001	4	6/25/2021	NON-COMPETING CONTINUATION	$683,205
2021	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Family Smoking Prevention and Tobacco Control Act Regulatory Research	000	3	12/8/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $683,205

Issue Date FY: 2020 ( Subtotal = $870,828 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Family Smoking Prevention and Tobacco Control Act Regulatory Research	001	3	7/13/2020	NON-COMPETING CONTINUATION	$694,308
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Environmental Health	002	3	7/14/2020	SUPPLEMENT FOR EXPANSION	$176,520
2020	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Family Smoking Prevention and Tobacco Control Act Regulatory Research	000	2	11/18/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $870,828

Issue Date FY: 2019 ( Subtotal = $705,062 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Family Smoking Prevention and Tobacco Control Act Regulatory Research	001	2	6/27/2019	NON-COMPETING CONTINUATION	$705,062
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Family Smoking Prevention and Tobacco Control Act Regulatory Research	002	2	7/18/2019	NON-COMPETING CONTINUATION	-$705,062
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Family Smoking Prevention and Tobacco Control Act Regulatory Research	003	2	7/19/2019	NON-COMPETING CONTINUATION	$705,062
2019	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Family Smoking Prevention and Tobacco Control Act Regulatory Research	000	1	11/28/2018	NEW	$0
														Subtotal = $705,062

Issue Date FY: 2018 ( Subtotal = $721,470 )
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Family Smoking Prevention and Tobacco Control Act Regulatory Research	000	1	9/18/2018	NEW	$721,470
														Subtotal = $721,470

Grand Total All Awards = $3,662,486

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Characterization of Potential Harm Caused by Electronic Cigarette Flavor Chemicals and their Reaction Products

Award Number: R01ES029741

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/20/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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