1. Electronic Cigarettes in Context: What we know and still need to find out Evan L. Floyd, PhD* # David Johnson, PhD, PE, CIH* Theodore Wagener, PhD +# *Department of Occupational and Environmental Health + Department of Pediatrics, Co-Director OTRC # OUHSC, Oklahoma TSET Research Scholar

2. Overview  Toll of Tobacco  e-cigarettes/vapor products design  Proposed Rule by FDA (April 25, 2014)  Toxicology – mainstream and secondhand vapor  Nicotine delivery and abuse liability  Subjective effects and smoking behavior  What we still need to find out…  e-cigarettes in context of proposed “Tobacco End Game”

3. Tobacco Toll: US and Oklahoma 1  US  19% smoking rate  443,000 deaths per year  $193 billion in medical costs/lost productivity  Oklahoma  23.3% smoking rate  6,500 deaths per year  $2.8 billion in medical costs/lost productivity

4. e-Cigarette Product Designs

5. e-Cigarettes/Vapor products design  “cig-a-like” e-cigarettes  Aka – 1 st generation e-cigs  Look like regular cigarettes  Activated by inhaling; cartridge-based  Tobacco companies have these type of e-cigs  Lorillard – acquired Blu  RJR – developed Vuse  Altria – acquired Green Smoke and developed MarkTen

6. e-Cigarettes/Vapor products design  Tank system e-cigarettes  Do not look like a cigarette  Activated by push button; user refillable e-liquid; some are variable voltage; different resistance atomizers available  Currently none owned (to my knowledge) by Tobacco Industry  Vape shops sell these types

7. e-Cigarettes/Vapor products design  Rebuildable Atomizers (RBAs)  Doesn’t look like a regular cigarette  “Drip Vaping”, 2-3 drops of e-liquid at a time; Push button activated  High Powered; custom coils with low resistance, high voltages  Currently none own by tobacco industry  Vape shops sell these types  Used mostly by experienced users

8. FDA Proposed Rule  To deem all products meeting the statutory definition of “tobacco product” except accessories… to be subject to FDAs tobacco product authorities under chapter IX of the FD&C Act as amended by the Family Smoking Prevention and Tobacco Control Act.”  Currently marketed products meeting the statutory definition of a “tobacco product” are  Dissolvables  Gels  Hookah tobacco  Electronic cigarettes  Cigars  Pipe tobacco

9. FDA Proposed Rule  FDA does not intend to “deem” accessories since they are not intended or expected to be used in the consumption of the tobacco product  hookah tongs, bags, cases, charcoal burners and holders, as well as cigar foil cutters, humidors, carriers, and lighters  FDA does intend to “deem” components and parts of tobacco products to be subject to the TCA  filters, tubes, papers, pouches, flavorings (such as flavored hookah charcoals and hookah flavor enhancers) or cartridges for e-cigarettes

10. Toxicology (only 1 st gen e-cigs)  Preliminary data (20 peer-reviewed articles/reports)  e-cigarette users are exposed to lower levels of carcinogens and toxicants than cigarette smokers.  Levels 9-450x less than cigarettes and some comparable to nicotine inhaler  E-cig aerosols and liquid significantly less cytotoxic than cigarette smoke: human embryonic stem cells, pulmonary fibroblasts, mouse neural stem cells  Quality control issues  Nicotine levels reported ≠ levels contained in the product  Quality of nicotine liquid used is not currently regulated, but will be if the proposed rule goes through  Mixing of e-liquid in vape shops is not regulated  Secondhand vapor contains significantly less nicotine and PM than secondhand smoke by orders of magnitude, but significantly more than clean indoor air. (Czogola et al., 2014)

11. Toxicology – SH Vapor  Implies particles grow while within the lungs and persist longer in the environment when exhaled by a user

12. Nicotine Delivery/Abuse Liability  1 st generation delivery nicotine less effectively than tank system e- cigarettes (Farsalinos et al 2014)  Nicotine delivery by combustible cigarette still the most effective (faster and larger quantities). (Farsalinos et al 2014)  What’s the difference? Dose or Absorption, Both?

13. Nicotine Delivery/Abuse Liability  Naïve e-cigarette users need more puffs to get cotinine blood levels as high as regular cigarettes (Flouris et al., 2013; Vansickel et al.,, 2012)  Experienced users do not (Vansickel & Eissenberg, 2013)  Currently tested models of e-cigarettes suggest e-cigs have lower abuse potential than regular cigs (1 st gen) (Vansickel et al, 2012 Addiction; Farsalinos et al Substance Abuse 2013)

14. Subjective effects and smoking behavior  Effectively reduces cravings (Vansickel et al., 2012 Addiction; Vansickel et al., 2013 Nic and Tob Res)  Improvement in depression and concentration ( Dawkins et al., 2012 Addictive Behaviors)  Men show more improvement in irritability and restlessness than women (Dawkins et al., 2012 Addictive Behaviors)  Experimentation among naïve smokers uninterested in quitting led to increased motivation and confidence to quit smoking. (Wagener et al., 2014)

15. Subjective effects and smoking behavior  Smoking Behavior & cessation  Nicotine free e-cigarettes effective at reducing craving and number of cigarettes smoked (Bullen et al., 2010,Tobacco Control)  Smokers uninterested in quitting (Polosa et al., 2011 BMC Public Health)  e-cigarettes helped a majority of smokers reduce (45%) or completely quit (22.5%) regular cigarettes  Smokers, uninterested in quitting (Caponetto et al., 2013)  At least 50% reduction in 22.3% at 12 weeks and 10.3% at 52 weeks.  10.7% quit regular cigarettes at 12 weeks, and 8.7% at 52 weeks  26.9% of quitters continued to use e-cigarettes at 52 weeks  Smokers, uninterested in quitting (Wagener et al., 2014)  Mean 44% reduction in reg cigs at 1 week after initial e-cig experimentation.

16. Subjective effects and smoking behavior  Smokers interested in quitting (Bullen et al 2013)  E-cigarette versus patch  At 6 months, 7.3% of e-cigarette users versus 5.8% of patch were abstinence (not significantly different)  Smokers with Schizophrenia, uninterested in quitting (Caponnetto, Auditore, Russo et al., 2013)  64.3% participants reduced number of cig/day (52-weeks)  50% of participants reduced number of cig/day by at least 50% (52-weeks)  Surveys of current EC users show abstinence rates from regular cigarettes at rates as high as 74% to 96% (Dawkins et al., 2013, Addiction; Etter et al., 2011, Addiction)

17. Subjective effects and smoking behavior  Preliminary data suggests that a majority of vape store customers are exclusive e-cig users (64%). (Lechner…Wagener, in press)

18. Aerosol Size Distribution of Modern Variable Voltage e-Cigarette (Prelim Data) Floyd and Johnson, 2014 unpublished

19. Vaping aerosol mass evolution (Prelim Data) DC Volts applied Energy applied (Joules) Mass consumed per puff (mg) Aerosol mass per puff (mg) 3.08.820.250.006 3.411.4240.550.030 3.814.4782.070.084 4.217.5142.800.083 4.621.1143.270.105 5.024.753.590.126 5.428.9986.560.146 5.833.4088.200.167 6.035.827.290.155 E-cigarettes consume milligram quantities of e-juice All of which is inhaled (though not necessarily retained) Measured aerosol (<20,000 µm) account for about 2% of the consumed e-juice Suggests the rest is gas phase or particles >20 µm in size Floyd and Johnson, 2014 unpublished

20. Tobacco cigarette vs e-cigarette aerosols (prelim data) Vaping aerosol may greatly exceed tobacco cigarette smoke mass concentrations Nicotine concentrations in the gas and particulate phases have not been compared Floyd and Johnson, 2014 unpublished

21. What we still need to find out…  What are the long-term effects of e-cig use?  How common will dual use be?  What will the research outcomes look like with 2 nd generation e-cigs?  What will be the net population effect of e-cigarettes?

22. End Game Scenarios – role of e-cigs

26. Continuum of Risk

27. End Game Steps – 1 potential way  2009 Tob Control Act – FDA has the authority to issue mandatory product standards to control permissible levels of compounds in tobacco products  Reduce nicotine in all combustible products to very low levels, rendering them non-addictive. (studies already underway).  To help prevent counterfeit tobacco…allow non-combustible products to remain at addictive levels though regulated by the FDA (also with product standards) to allow smokers who are unable or uninterested in quitting nicotine to switch.  First steps taken with the currently proposed rule

28. End Game Scenarios – role of e-cigs

29. References  FDA proposed rule 25 April 2014, section D http://www.regulations.gov/#!documentDetail;D=FDA-2014-N-0189-0001 http://www.regulations.gov/#!documentDetail;D=FDA-2014-N-0189-0001  Czogola et al, 2014  Farsalinos et al, 2014  Flouris et al, 2013  Vansickel et al., 2012 Addiction  Vansickel & Eissenberg, 2013  Farsalinos et al, 2013 Substance Abuse  Vansickel et al, 2013 Nic and Tob Res  Dawkins et al, 2012 Addictive Behaviors  Wagener et al, 2014  Bullen et al, 2010,Tobacco Control  Caponnetto, Auditore, Russo et al., 2013  Dawkins et al, 2013, Addiction  Etter et al, 2011, Addiction  Lechner…Wagener, in press  Floyd and Johnson, 2014 unpublished data

30. Questions?