Comparison of Potential Health Risks of Combustible, Heat-Not-Burn, and Electronic ... · 2018. 11....
Transcript of Comparison of Potential Health Risks of Combustible, Heat-Not-Burn, and Electronic ... · 2018. 11....
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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