Vapingand Disease Risks: Uncovering the Connections

Cynthia Grondin, PhDComparative Toxicogenomics Database

North Carolina State University

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

e-liquid

mouthpiece

on/off switch

Lithium battery

atomizer

vape mods

aerosol/vapor

Suorin DropUltra-Portable SystemElement Vape

Juuls

ALL Juuls contain NICOTINE

1 pod = nicotine in 1 pack cigarettes

What chemicals lie beneath?

Beyond the List of Ingredients

nicotinepropylene glycolglycerinbenzoic acidflavorings, oils

Nicotine Metabolic PathwaysSOURCE: Hukkanen et al. 2005

Beyond the List of Ingredients

nicotinepropylene glycolglycerinbenzoic acidflavorings, oils

Postulated pathways and by-products of propylene glycol thermal dehydration SOURCE: Sleiman et. al., 2016

Beyond the List of Ingredients

nicotinepropylene glycolglycerinbenzoic acidflavorings, oils

Postulated pathways and by-products of glycerin thermal dehydration SOURCE: Sleiman et. al., 2016

Beyond the List of Ingredients

nicotinepropylene glycolglycerinbenzoic acidflavorings, oils

glycerol

propylene glycol

Formation of benzene SOURCE: Pankow et. al., 2017

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

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

Analyzing Vaping Chemicals

SOURCE: Soulet et. al., 2017

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

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

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

Cellular locationMolecular functionBiological processes

Types of e-cig studies curated in CTD

ctdbase.org

Chemicals Diseasesdirect

Chemicals Diseases

Genes

inferred

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

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

Search for disease associations

Look for chemical-disease associations in CTD

Chemical-Disease Associations in CTD

Input chemicals in e-liquids/vapor

Subset of chemicals in e-cigarette liquids and vapor

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

Vaping Affects Users Differently

• type of device

• e-liquid

• vaping patterns

• coil resistance, age, composition

• user age, weight, metabolism, health, genetics

• environmental factors

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

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

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