UK E-Cigarette Summit Relative risks of cancer posed by combustible and vapourising forms of nicotine delivery: Evidence from chemical exposures
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1 UK E-Cigarette Summit 2017 Relative risks of cancer posed by combustible and vapourising forms of nicotine delivery: Evidence from chemical exposures Ed Stephens University of St Andrews
2 Scope of presentation Projected global tobaccoattributable deaths in 2015 Focus on cancer Carcinogenic potential of different nicotine aerosols assessed Use published data from many labs Aim to create a potency spectrum for comparing tobacco smoke, heat-notburn emissions, e-cigarette vapour and other nicotine-delivering aerosols Convert potencies to risk via exposure Use tobacco smoke as basis for comparing relative risk From Tobacco Atlas, 4 th edition
3 Carcinogens in tobacco US Food & Drug Administration (FDA) list of Harmful & Potentially Harmful Constituents (HPHC) in tobacco products 93 chemical compounds in list, including 75 carcinogens 25 respiratory toxicants 12 cardiovascular toxicants Others have added toxicants specifically for e-cigarettes (HPHC+) Full HPHC+ analysis well beyond the capability of most labs (>20 separate analytical procedures) Major tobacco companies use Labstat Inc. for independent analyses of HPHC or HPHC+ suite in their products, along with QA monitors (3R4F). Now publishing results in peer review journals Inhalation unit risk is the increased cancer risk from inhalation exposure to 1 µg/m 3 of a compound for a lifetime Unit risks for 44 HPHC carcinogens found in various sources
4 Prioritising Carcinogens UNIT RISK increasing unit risk CONCENTRATION IN SMOKE increasing concentration Acrylamide Acetaldehyde Acrylonitrile 1,3-Butadiene Benzene Ethylene oxide Formaldehyde Several carcinogens not yet assigned unit risks Several carcinogens not quantifable 3R4F reference cigarettes HPHC data from Margham et al. (2016) Carcinogen unit risk (µg m -3 ) -1 3R4F concentration (µg ml -1 ) Cancer potency % Cancer Potency (individual compound) = Unit risk x Concentration Cancer Potency (aerosol) = sum of individual potencies
5 Ranked potency Comparing Priority Carcinogens COMBUSTED TOBACCO 3R4F HEAT-NOT-BURN TOBACCO c-thp (BAT) THS (PMI) E-CIGARETTE epen (BAT) Acetaldehyde 1,3-Butadiene Acrylamide Acetaldehyde Formaldehyde >5% potency 1,3-Butadiene Acrylonitrile Acetaldehyde Acrylamide Benzene >5% potency Acrylamide Acetaldehyde Chromium >5% potency Acetaldehyde Chromium Formaldehyde >5% potency Formaldehyde Acetaldehyde Carbonyl Volatile Metal Semivolatile Amine Nitrosamine PAH Other HPHC data from Margham et al. (2016) HPHC data from Breheny et al. (2017) HPHC data from Forster et al. (2017) HPHC data from Margham et al. (2017) Cancer potency % Cancer potency % Cancer potency % Cancer potency %
6 Range of Cancer Potency in Tobacco Smoke Cancer potency calculated on basis of concentration, e.g. µg/ml E-cigarettes usually reported as µg/n puffs of fixed volume Tobacco smoke & HnB reported as µg/consumable TOBACCO SMOKE Counts et al. (2005) Pazo et al. (2016) Bodnar et al. (2012) BRANDS PMI: global (n=48) CDC: US (n=52) RJR: US (n=61) PROTOCOL Health Canada Detailed procedures for resolving incompatibilities and for calculating potency & risk described by Stephens, (2017) Tobacco Control (doi: /tobaccocontro l ) -2s 4.5x x x10-5 Cancer potency +2s
7 Outdoor air Indoor air (Oldham et al. 2017) Cancer Potency Spectrum: From Fresh Air to Smoke Ambient air Tobacco smoke Nicotine inhaler Cancer potency (normalised to tobacco smoke) 10 0
8 Tobacco smoke Cancer Potency Spectrum: Tobacco Products Ambient air Tobacco blends for THS THS Schaller et al. (2017) THS Forster et al. (2017) THP Forster et al. (2017) Nicotine inhaler Cancer potency (normalised to tobacco smoke) 10 0
9 Ambient air Heat-not-Burn Tobacco smoke Cancer Potency Spectrum: E-Cigarettes Analyses of E-cigarette emissions collected from 16 publications epen has full HPHC, others have fewer analytes (mainly carbonyls) Nicotine inhaler epen: Margham et al. (2016) Cancer potency (normalised to tobacco smoke) 10 0
10 Cancer poetncy relative to tobacco smoke Cancer Potency of E-cigarettes by Generation GENERATION 1 st potency of tobacco smoke 2 nd rd th st 2nd 3rd e-cigarette generation 4th
11 Formaldehyde (µg/ml) Formaldehyde power user experience 1 Experiment: 26 former smokers now e-cigarette users recruited Same device & liquid vaped (CE4, Innokin itaste VV, 6 mg/ml nicotine) Voltage increased in steps and users reported taste responses 1 Total aversion Some aversion No aversion (r 2 = 0.98) Farsalinos et al. (2017) Food and Chemical Toxicology 109, data from Farsalinos et al. (2017) Volts
12 Heat-not-Burn emission Tobacco smoke Formaldehyde power user experience 2 Nicotine inhaler Ambient air No aversion Some aversion Total aversion Cancer potency (normalised to tobacco smoke) 10 0
13 Heat-not-Burn Tobacco smoke Unexplained Potency Variation in Same Brand & Flavour Solid lines connect the same brand & flavour in 2 nd generation disposable cartomisers (US). Voltage/power was not varied. (data from Klager et al., 2017) Ambient air Vivid Vanilla Berry Pina Colada Original Tobacco Java Jolt Menthol Cancer potency (normalised to tobacco smoke) 10 0
14 Other factors? METALS IN EMISSIONS E-cigarette devices of all generations are largely constructed of metal Coils most commonly nichrome (NiCr alloy) or kanthal (FeAlCr) Very few measurements of metals in vapour No studies of metal speciation in e-cigarette emissions, e.g. Cr(0), Cr(III) & Cr(IV) have low toxicities whereas Cr(VI) is highly carcinogenic AEROSOL SIZE DISTRIBUTIONS Mikheev et al. (2016) Real-Time Measurement of Electronic Cigarette Aerosol Size Distribution and Metals Content Analysis. Nicotine & Tobacco Research 18, Scungio et al. (2018) Measurements of electronic cigarette-generated particles for the evaluation of lung cancer risk of active and passive users. Journal of Aerosol Science 115, 1-11
15 Heat-not-Burn Tobacco smoke From Potency to Risk Risk = Potency x Exposure In this model exposure is a simple function of the volume of aerosol inhaled Cigarettes: 15 cigs/day x 10 puffs x 50 ml/puff = 7.5 L smoke/day e-cigarettes: Robinson et al. (2015) report 30L/day as the mean inhaled vapour across a sample (n=21) i.e. x4 greater exposure - consistent with Behar et al. (2014) Ambient air Nicotine inhaler POTENCY x4 No aversion Some aversion Total aversion POTENCY Cancer potency (normalised to tobacco smoke)
16 Effect of emissions on other medical conditions RESPIRATORY & CARDIOVASCULAR DISEASE Cancer potential appears to be dominated by carbonyls - most studies of emissions have focused on carbonyls (aldehydes) Carbonyls are implicated in respiratory but not CV disease. Also volatiles (VOCs), metals, carbonyls, PAHs and other compounds involved Applying analogous approaches to respiratory and cardiovascular diseases is currently limited by the very small number of studies with e-cigarette emissions data for the wider range of HPHC+ toxicants
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