Comparison of Potential Health Risks of Combustible,

Heat-Not-Burn, and Electronic Cigarettes

Charlene Liu, Sc.D. and Kristin Marano, MPH, Ph.D., CPH

RAI Services Company, Winston-Salem, NC

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CORESTA Congress, Kunming, China

October 2018

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Outline

• Introduction

• Problem Formulation

• Hazard Identification

• Toxicity Assessment

• Exposure Assessment

• Risk Characterization

• Conclusions

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Quantitative Risk Assessment (QRA)

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Risk Continuum

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Adapted from Hatsukami DK, Joseph AM, LeSage M, Jensen J, Murphy SE, Pentel PR,

Kotlyar M, Borgida E, Le C, Hecht SS. Developing the science base for reducing tobacco

harm. Nicotine & Tobacco Research. 2007 Dec;9(Suppl_4):S537-53.

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Risk Continuum of Tobacco Products

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Cigarettes E-cigarettesHeat-not-

burn (HNB)

Combustible Noncombustible

This is for illustration purposes only

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Problem Formulation

To estimate the risk of cancer and cardiovascular, respiratory and reproductive or developmental toxic effects for conventional combustible cigarettes, heat-not- burn (HNB) cigarettes, and electronic (E)-cigarettes using QRA

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Hazard Identification

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Harmful and Potentially Harmful Constituents (HPHCs) and Toxic Endpoints1

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HPHC Carcinogen Respiratory Cardiovascular Reproductive or Developmental

Acetaldehyde √ √

Acrolein √ √

Acrylonitrile √ √

2-Aminonaphthalene √

4-Aminobiphenyl √

Benzene √ √ √

Benzo[a]pyrene √

1,3-Butadiene √ √ √

Carbon Monoxide √

Crotonaldehyde √

Formaldehyde √ √

NNK √

NNN √

Cadmium √ √ √

Nickel √ √

1FDA. 2012. Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke;

Established List. Federal Register, Vol. 77, No. 64. April 3, 2012.

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HPHC Data

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(1) Organic HPHC data in tobacco smoke were from Bodnar et al. 2012. Mainstream Smoke Chemistry Analysis of Samples from the 2009 U.S. Cigarette, Regulatory Toxicology and Pharmacology, 64, 35-

42. Metal data in tobacco smoke were from Pappas et al., 2014, Toxic Metal Concentrations in Mainstream Smoke from Cigarettes Available in the USA, Journal of Analytical Toxicology, 38, 204-211. HPHC

data represent cigarettes smoked under Health Canada Intense (HCI) machine smoking: puff volume 55 mL, puff frequency per 30 seconds, 100% vent blocking.

(2) HPHC data in HNB were from Bodnar. LLI Data 2014 US Market Survey of Current Market Product Under HCI Machine Smoking (internal report).

(3) HPHC in e-cigarettes were from Goniewicz ML, et al., 2014. Level of Selected Carcinogens and Toxicants in Vapour from Electronic Cigarettes, Tobacco Control, 23, 133–139.

For a HPHC where there is no bar, it was either not identified or not analyzed.

0.1

1

10

100

1000

10000

Mainstream Cigarette Smoke(1) HNB(2) E-cigarette Vapor (per 15 puffs) (3)

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Toxicity Assessment

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Toxicity Factor Sources

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• USEPA’s IRIS and PPRTVs

• ATSDR

• State: CalEPA, TCEQ, etc.

• International: WHO, RIVM

• Peer-Reviewed Literature

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Toxicity Factors

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na – not applicable

NA – not available

a HPHC is not considered a noncancer toxicant by USFDA and a RfC is not

availableb HPHC is not considered a carcinogen by USFDAC Crotonaldehyde is considered a carcinogen by USFDA; however, an IUR is not

available

ConstituentReference Concentration Inhalation Unit Risk

(mg/m3) (µg/m3)-1

Acetaldehyde 1.4E-01 2.7E-06

Acrolein 2.7E-03 nab

Acrylonitrile 7.1E-03 6.8E-05

2-aminonaphthalene naa 5.1E-04

4-aminobiphenyl naa 6.0E-03

Benzene 3.0E-02 2.2E-06

Benzo(a)pyrene 2.1E-06 6.0E-04

1,3-butadiene 3.3E-02 5.0E-07

Carbon Monoxide 7.0E+00 nab

Crotonaldehyde 1.0E-02 NAc

Formaldehyde 9.0E-03 6.0E-06

NNK naa 5.2E-03

NNN naa 2.4E-04

Cadmium 2.0E-05 1.8E-03

Nickel 1.4E-05 2.4E-04

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Exposure Assessment

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Exposure Assessment

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HPHC YieldConsumption

per day

Exposure Duration

Exposure Frequency

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Exposure Assessment

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HPHC YieldConsumption

per day

Exposure Duration

Exposure Frequency

Lifetime

Exposure

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Exposure Assessment

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• Continuous, chronic

• Steady state

• 100% Retention

• Upper-percentile

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Assumptions: Cigarettes and HNB

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• Initiation: 12.5 years of age1

• Consumption Rate: 1 pack per day2

• Exposure Frequency: 365 days per year

• Exposure Duration: 57.5 years assuming a 70-year lifespan1,2,3

1SAMHSA. 2015. Behavioral Health Trends in the United States: Results for the 2014 National Survey on Drug Use and Health.2CDC. 2018. Current Cigarette Smoking among Adults – United States, 2016. Morbidity and Mortality Weekly Report, 67(2). 3EPA. 2011. Exposure Factors Handbook: 2011 Edition.

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Assumptions: E-Cigarettes

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• Initiation: 12.5 years of age1

• Consumption Rate: – 154 puffs per day (weighted mean of 10 studies)– Puff Volume: 80 mL2

– Daily Total Puff Volume: 12320 mL

• Exposure Frequency: 365 days per year

• Exposure Duration: 57.5 years1,3,4

1SAMHSA. 2015. Behavioral Health Trends in the United States: Results for the 2014 National Survey on Drug Use and Health.2CORESTA. 2018. CORESTA Technical Guide No. 22, Technical Guide for the Selection of Appropriate Intensive Vaping Regime for E-Vapor Devices.3CDC. 2018. Current Cigarette Smoking among Adults – United States, 2016. Morbidity and Mortality Weekly Report, 67(2). 4EPA. 2011. Exposure Factors Handbook: 2011 Edition.

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Exposure Concentration (EC)

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• Cigarettes and HNB:

EC = 𝐻𝑃𝐻𝐶 𝑦𝑖𝑒𝑙𝑑×𝐶𝑝𝐷

𝐼𝑛ℎ𝑎𝑙𝑎𝑡𝑖𝑜𝑛 𝑅𝑎𝑡𝑒=

𝜇𝑔

𝑚3

• E-Cigarettes:

• EC = 𝐻𝑃𝐻𝐶 𝑦𝑖𝑒𝑙𝑑×𝑃𝑢𝑓𝑓 𝐶𝑜𝑢𝑛𝑡×𝑃𝑢𝑓𝑓 𝑉𝑜𝑙𝑢𝑚𝑒

𝐼𝑛ℎ𝑎𝑙𝑎𝑡𝑖𝑜𝑛 𝑅𝑎𝑡𝑒=

𝜇𝑔

𝑚3

Inhalation Rate = 20 m3/day1

1EPA. 2011. Exposure Factors Handbook: 2011 Edition.

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Risk Characterization

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Risk Characterization

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Toxicity

Assessment

Exposure Assessment

Risk

Characterization

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Risk Characterization

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• Noncancer Health Hazard

𝐻𝑎𝑧𝑎𝑟𝑑 𝑄𝑢𝑜𝑡𝑖𝑒𝑛𝑡 =𝐸𝐶

𝑅𝑓𝐶

𝐻𝑎𝑧𝑎𝑟𝑑 𝐼𝑛𝑑𝑒𝑥 = 𝐻𝑎𝑧𝑎𝑟𝑑 𝑄𝑢𝑜𝑡𝑖𝑒𝑛𝑡

• Excess lifetime cancer risk𝐸𝐿𝐶𝑅 = 𝐸𝐶 × 𝐼𝑈𝑅

𝑇𝑜𝑡𝑎𝑙 𝐸𝐿𝐶𝑅 =𝐸𝐿𝐶𝑅EC, exposure concentration

RfC, reference concentration

IUR, inhalation unit risk

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Estimated Overall Cancer Risk

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1E-06 1E-05 1E-04 1E-03 1E-02 1E-01 1E+00

Excess Lifetime Cancer Risk

E-Cigarette HNB Cigarette

69% reduction vs. cigarettes

99.9% reduction vs. cigarettes

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Estimated Noncancer Hazard by Endpoint

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0 20 40 60 80 100 120

Cardiovascular

Respiratory

Reproductive orDevelopmental

Hazard Index

E-Cigarette HNB Cigarette

98% reduction vs. cigarettes

78% reduction vs. cigarettes

99% reduction vs. cigarettes

33% reduction vs. cigarettes

99.9% reduction vs. cigarettes

20% reduction vs. cigarettes

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Results

• Compared with combustible cigarettes and assuming comparable usage patterns:

– HNB vs. combustible cigarettes:

• Cancer Risk – 69% reduction

• Noncancer Hazard – 20% to 78% reduction

– E-cigarettes vs. combustible cigarettes:

• Cancer Risk – 99.9% reduction

• Noncancer Hazard: – 98% to 99.9% reduction

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Conclusion

Estimated risk results are consistent with current views of the tobacco product and nicotine risk continuum.

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Supplemental Information

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E-Cigarette HPHC Data

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Goniewicz ML, et al., 2014. Level of Selected Carcinogens and Toxicants in Vapour from Electronic Cigarettes. Tob

Control 2014;23:133–139.

Puff condition: puffing conditions: puff duration of 1.8 s, intervals between puffs of 10 s, puff volume 70 mL and number of

puffs taken in one puffing session was 15. A total of 150 puffs were taken from each e-cigarette in 10 series of 15 puffs with

intervals between series of 5 min each.

1.0E-07

1.0E-06

1.0E-05

1.0E-04

1.0E-03

1.0E-02

1.0E-01

Formaldehdye (µg) Acetaldedhyde (µg) Acrolein (µg) NNN (ng) NNK (ng) Cd (µg) Ni (µg) Pb (µg)

Per

150 p

uff

s

Mean Level in Vapor Generated from 12 Brands of E-Cigarettes

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