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Vapingand Disease Risks: Uncovering the Connections
Cynthia Grondin, PhDComparative Toxicogenomics Database
North Carolina State University
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• Introduce Vaping Devices• What Chemicals are Involved?• Comparative Toxicogenomics Database• Disease Risks
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e-liquid
mouthpiece
on/off switch
Lithium battery
atomizer
vape mods
aerosol/vapor
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Suorin DropUltra-Portable SystemElement Vape
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Juuls
ALL Juuls contain NICOTINE
1 pod = nicotine in 1 pack cigarettes
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What chemicals lie beneath?
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Beyond the List of Ingredients
nicotinepropylene glycolglycerinbenzoic acidflavorings, oils
Nicotine Metabolic PathwaysSOURCE: Hukkanen et al. 2005
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Beyond the List of Ingredients
nicotinepropylene glycolglycerinbenzoic acidflavorings, oils
Postulated pathways and by-products of propylene glycol thermal dehydration SOURCE: Sleiman et. al., 2016
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Beyond the List of Ingredients
nicotinepropylene glycolglycerinbenzoic acidflavorings, oils
Postulated pathways and by-products of glycerin thermal dehydration SOURCE: Sleiman et. al., 2016
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Beyond the List of Ingredients
nicotinepropylene glycolglycerinbenzoic acidflavorings, oils
glycerol
propylene glycol
Formation of benzene SOURCE: Pankow et. al., 2017
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Beyond the List of Ingredients
nicotinepropylene glycolglycerinbenzoic acidflavorings, oils
1-hexanol cyclotene limonene
2,3-pentanedione decan-4-olide linalool
2,5-dimethylpyrazine decanaldehyde linalyl acetate
2,6-lutidine Diacetyl maltol
2-acetylpyrrole diethyl succinate Menthol
3,4-dihydrocoumarin ethyl acetoacetate menthone
3-hexen-1-ol ethyl hexanoate methyl acetate
4-Butyrolactone ethyl lactate methyl cinnamate
5-methyl-2-furfural ethyl maltol methyl salicylate
acetoin Ethyl Salicylate methylheptenone
alpha-terpineol ethyl vanillin Nicotine
anisyl acetate Eucalyptol n-pentanol
benzaldehyde Eugenol Pulegone
benzyl acetate Furaldehyde pyridine
Benzyl Alcohol furaneol raspberry ketone
Camphor furfuryl alcohol tetramethylpyrazine
Cinnamaldehyde gamma-valerolactone vanillin
citronellol isoamyl acetate
Alien Blood Double Apple Hookah Oatmeal Cookie
Bad Apple Energy Drink Orange Mint
Bluewater Punch Grape Hookah Peach Schnapps
Carmel Popcorn Iced Berry Pina Colada
Cherry Lava Java Jolt Pomegranate
CooCoo Coconut Just Guava Snap!
Cotton Candy Kick! Tutti Frutti
Cupcake Menthol Vanilla Bean
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Universal System for Analysis of Vaping (U-SAV) machine
Analyzing Vaping Chemicals
SOURCE: Soulet et. al., 2017
• e-liquids and vapor• urine, saliva, blood
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Vaping is NOT just inhaling flavored water vapor
Metals in e-cigarette liquids and vapors Particles from e-cigarette inner/outer fibers
Particles in room air vs. e-cigarette vapor
SOURCE: Olmedo et. al., 2018 SOURCE: Williams et. al, 2013
SOURCE: Williams et. al, 2013
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Diseases
Chemicals
Genes
GO &
Phenotype
Comparative Toxicogenomics
Database (CTD)
Integrate data
Exposures
Pathways
ctdbase.org
• >40 million
toxicogenomic
relationships
• updated monthly
Cellular locationMolecular functionBiological processes
PhD-level scientists
read studies
Health Effects of Chemicals
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Cellular locationMolecular functionBiological processes
Types of e-cig studies curated in CTD
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ctdbase.org
Chemicals Diseasesdirect
Chemicals Diseases
Genes
inferred
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Nicotine Effects on HealthNicotine-DiseasesNicotine-Disease Categories
• Substance-Related Disorders• Lung Cancer• Metastasis• Depression• Colon Cancer• Type 2 Diabetes• Pulmonary Fibrosis• Pancreatic Cancer• Heart Attack• Nerve Degeneration• Atherosclerosis• Stroke• Fatty Liver• Acute Kidney Injury• Hypertension• Panic Disorder
215 direct/1766 inferred disease relationships
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Effects of Acrolein in e-cigarette vapor
interacts with 514 unique genes
Acrolein
involved in 1,294 gene interactions
involved in 433 molecular pathways
associated with 147 phenotypes
directly related to 86 diseases
inferred relationship to 3,455 diseases
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Search for disease associations
Look for chemical-disease associations in CTD
Chemical-Disease Associations in CTD
Input chemicals in e-liquids/vapor
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Subset of chemicals in e-cigarette liquids and vapor
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Vaping convention
Photograph taken during a cloud competition at a vaping convention, April 2016, Maryland SOURCE: Chen et. al., 2017
Chemicals in second-hand and third-hand vape are also toxic
“There is conclusive evidence that e-cigarette use increases airborne concentrations of particulate matter and nicotine in indoor
environments compared with background levels.” NASEM
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Vaping Affects Users Differently
• type of device
• e-liquid
• vaping patterns
• coil resistance, age, composition
• user age, weight, metabolism, health, genetics
• environmental factors
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ctdbase.org connects chemical-gene-disease data
E-liquids AND vapor contain toxic chemicals
Vaping chemicals can cause DNA damage
Vaping impacts genes, pathways, immune system
Vaping increases risks of adverse health outcomes
Take Home Points
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Acknowledgements
Carolyn J Mattingly, PhD
Allan Peter Davis, PhD
Thomas C Wiegers, MS, MBA
Jolene A Wiegers, MS
Cynthia Grondin, PhD
Robin Johnson, PhD
Daniela Sciaky, PhD
Roy McMorran
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Citations
Chen, R., A. Aherrera, C. Isicheye, P. Olmedo, S. Jarmul, J. E. Cohen, A. Navas-Acien, and A. M. Rule. 2018 “Assessment of
indoor air quality at an electronic cigarette (Vaping) convention”. J Expo Sci Environ Epidemiol. 28(6):522-529.
Curated [chemical-gene interactions|chemical-disease|gene-disease] data were retrieved from the Comparative Toxicogenomics
Database (CTD), MDI Biological Laboratory, Salisbury Cove, Maine, and NC State University, Raleigh, North Carolina. World
Wide Web (URL: http://ctdbase.org/). [June, 2018].
Hukkanen J, P Jacob, 3rd, and NL Benowitz. 2005. Metabolism and disposition kinetics of nicotine. Pharmacological Reviews
57(1):79–115.
“Juul| The Smoking Alternative, unlike any e-cigarette or vape”. Juul. Web. 6 Jun 2018.
Olmedo P, Goessler W, Tanda S, Grau-Perez M, Jarmul S, Aherrera A, Chen R, Hilpert M, Cohen JE, Navas-Acien A, Rule AM.
“Metal Concentrations in e-Cigarette Liquid and Aerosol Samples: The Contribution of Metallic Coils”. Environ Health Perspect.
2018 Feb 21;126(2):027010.
Pankow, JF, K Kim, KJ McWhirter, W Luo, JO Escobedo, RM Strongin, AK Duell, and DH Peyton. 2017. Benzene formation in
electronic cigarettes. PLoS ONE 12(3):e0173055.
Sleiman, M., JM Logue, VN Montesinos, ML Russell, MI Litter, LA Gundel, and H Destaillats. 2016. Emissions from electronic
cigarettes: Key parameters affecting the release of harmful chemicals. Environmental Science & Technology 50(17):9644–9651.
Soulet, S. Pairaud, C, Lalo, H. “A Novel Vaping Machine Dedicated to Fully Controlling the Generation of E-Cigarette Emissions”.
Int. J. Environ. Res. Public Health 2017, 14(10): 1225.
Stratton, K, LY Kwan, and DL Eaton. Public health consequences of e-cigarettes. Washington, DC. The National Academies
Press, 2018. doi: https://doi.org/10.17226/24952.
Williams M, Villarreal A, Bozhilov K, Lin S, Talbot P. “Metal and silicate particles including nanoparticles are present in electronic
cigarette cartomizer fluid and aerosol” PLoS One. 2013;8(3):e57987