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 • Disease Risks vape mods

aerosol/vapor

mouthpiece atomizer e-liquid on/off switch

Lithium battery Suorin Drop Ultra-Portable System Element Vape

Juuls 1 pod = nicotine in 1 pack cigarettes

ALL Juuls contain NICOTINE What chemicals lie beneath? Beyond the List of Ingredients

nicotine propylene glycol glycerin benzoic acid flavorings, oils

Nicotine Metabolic Pathways SOURCE: Hukkanen et al. 2005 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 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 Beyond the List of Ingredients

glycerol

propylene glycol

nicotine propylene glycol glycerin benzoic acid flavorings, oils

Formation of benzene SOURCE: Pankow et. al., 2017 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 nicotine Cupcake Menthol Vanilla Bean 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 Analyzing Vaping Chemicals

Universal System for Analysis of Vaping (U-SAV) machine

• e-liquids and vapor • urine, saliva, blood

SOURCE: Soulet et. al., 2017 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 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 Types of e-cig studies curated in CTD

Cellular location Molecular function Biological processes ctdbase.org

Genes

Chemicals direct Diseases Chemicals Diseases inferred 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 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 Chemical-Disease Associations in CTD

Look for chemical-disease associations in CTD

Input chemicals in e-liquids/vapor

Search for disease associations Subset of chemicals in e-cigarette liquids and vapor 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 Vaping Affects Users Differently

• type of device

• e-liquid

• vaping patterns

• coil resistance, age, composition

• user age, weight, metabolism, health, genetics

• environmental factors 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 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 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