Vaping and Disease Risks: Uncovering the Connections. Cynthia Grondin, PhD Comparative Toxicogenomics Database North Carolina State University

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1 Vaping and Disease Risks: Uncovering the Connections Cynthia Grondin, PhD Comparative Toxicogenomics Database North Carolina State University

2 Introduce Vaping Devices What Chemicals are Involved? Comparative Toxicogenomics Database Disease Risks

3 vape mods aerosol/vapor mouthpiece atomizer e-liquid on/off switch Lithium battery

4 Suorin Drop Ultra-Portable System Element Vape

5

6

7 Juuls 1 pod = nicotine in 1 pack cigarettes ALL Juuls contain NICOTINE

8 What chemicals lie beneath?

9 Beyond the List of Ingredients nicotine propylene glycol glycerin benzoic acid flavorings, oils Nicotine Metabolic Pathways SOURCE: Hukkanen et al. 2005

10 Beyond the List of Ingredients nicotine propylene glycol glycerin benzoic acid flavorings, oils Postulated pathways and by-products of propylene glycol thermal dehydration SOURCE: Sleiman et. al., 2016

11 Beyond the List of Ingredients nicotine propylene glycol glycerin benzoic acid flavorings, oils Postulated pathways and by-products of glycerin thermal dehydration SOURCE: Sleiman et. al., 2016

12 Beyond the List of Ingredients glycerol propylene glycol nicotine propylene glycol glycerin benzoic acid flavorings, oils Formation of benzene SOURCE: Pankow et. al., 2017

13 Beyond the List of Ingredients nicotine propylene glycol glycerin benzoic acid flavorings, oils 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 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

14 Analyzing Vaping Chemicals Universal System for Analysis of Vaping (U-SAV) machine e-liquids and vapor urine, saliva, blood SOURCE: Soulet et. al., 2017

15 Vaping is NOT just inhaling flavored water vapor Particles in room air vs. e-cigarette vapor SOURCE: Williams et. al, 2013 Metals in e-cigarette liquids and vapors SOURCE: Olmedo et. al., 2018 SOURCE: Williams et. al, 2013 Particles from e-cigarette inner/outer fibers

16 PhD-level scientists read studies Health Effects of Chemicals Integrate data ctdbase.org Cellular location Molecular function Biological processes GO & Phenotype Chemicals Pathways Genes Diseases Exposures Comparative Toxicogenomics Database (CTD) >40 million toxicogenomic relationships updated monthly

17 Types of e-cig studies curated in CTD Cellular location Molecular function Biological processes

18 ctdbase.org Genes Chemicals direct Diseases Chemicals Diseases inferred

19 Nicotine Effects on Health Nicotine-Disease Categories Nicotine-Diseases 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

20 Effects of Acrolein in e-cigarette vapor interacts with 514 unique genes involved in 1,294 gene interactions involved in 433 molecular pathways Acrolein associated with 147 phenotypes directly related to 86 diseases inferred relationship to 3,455 diseases

21 Chemical-Disease Associations in CTD Look for chemical-disease associations in CTD Input chemicals in e-liquids/vapor Search for disease associations

22 Subset of chemicals in e-cigarette liquids and vapor

23 Vaping convention Chemicals in secondhand 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 Photograph taken during a cloud competition at a vaping convention, April 2016, Maryland SOURCE: Chen et. al., 2017

24 Vaping Affects Users Differently type of device e-liquid vaping patterns coil resistance, age, composition user age, weight, metabolism, health, genetics environmental factors

25 Take Home Points 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

26 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

27 Citations Chen, R., A. Aherrera, C. Isicheye, P. Olmedo, S. Jarmul, J. E. Cohen, A. Navas-Acien, and A. M. Rule Assessment of indoor air quality at an electronic cigarette (Vaping) convention. J Expo Sci Environ Epidemiol. 28(6): 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: [June, 2018]. Hukkanen J, P Jacob, 3rd, and NL Benowitz Metabolism and disposition kinetics of nicotine. Pharmacological Reviews 57(1): Juul The Smoking Alternative, unlike any e-cigarette or vape. Juul. Web. 6 Jun 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 Feb 21;126(2): Pankow, JF, K Kim, KJ McWhirter, W Luo, JO Escobedo, RM Strongin, AK Duell, and DH Peyton Benzene formation in electronic cigarettes. PLoS ONE 12(3):e Sleiman, M., JM Logue, VN Montesinos, ML Russell, MI Litter, LA Gundel, and H Destaillats Emissions from electronic cigarettes: Key parameters affecting the release of harmful chemicals. Environmental Science & Technology 50(17): 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): Stratton, K, LY Kwan, and DL Eaton. Public health consequences of e-cigarettes. Washington, DC. The National Academies Press, doi: 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

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