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Vaping and Disease Risks: Uncovering the Connections Cynthia Grondin, PhD Comparative Toxicogenomics Database North Carolina State University Introduce Vaping Devices What Chemicals are Involved? Comparative Toxicogenomics Database


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

  6. What chemicals lie beneath?

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

  8. 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

  9. 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

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

  11. Beyond the List of Ingredients 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 nicotine 1-hexanol cyclotene limonene propylene glycol 2,3-pentanedione decan-4-olide linalool glycerin 2,5-dimethylpyrazine decanaldehyde linalyl acetate 2,6-lutidine Diacetyl maltol benzoic acid 2-acetylpyrrole diethyl succinate Menthol flavorings, oils 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

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

  13. 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 Particles from e-cigarette inner/outer fibers SOURCE: Olmedo et. al., 2018 SOURCE: Williams et. al, 2013

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

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

  16. ctdbase.org Genes direct Chemicals Diseases Diseases Chemicals inferred

  17. 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

  18. 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

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

  20. Subset of chemicals in e-cigarette liquids and vapor

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

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

  23. 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

  24. Acknowledgements Carolyn J Mattingly, PhD Cynthia Grondin, PhD Allan Peter Davis, PhD Robin Johnson, PhD Thomas C Wiegers, MS, MBA Daniela Sciaky, PhD Jolene A Wiegers, MS Roy McMorran

  25. 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

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