Electronic Cigarettes in Context: What we know and still need to find out

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 Oklahoma1 • 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 – 1st 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 1st 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 • 1st 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 (1st 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) 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 2nd generation e-cigs? • What will be the net population effect of e-cigarettes?

22. End Game Scenarios – role of e-cigs

23. End Game Scenarios – role of e-cigs

24. End Game Scenarios – role of e-cigs

25. 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 • Czogolaet al, 2014 • Farsalinoset al, 2014 • Flouriset al, 2013 • Vansickel et al., 2012 Addiction • Vansickel& Eissenberg, 2013 • Farsalinoset al, 2013 Substance Abuse • Vansickelet al, 2013 Nic and TobRes • 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 • Etteret al, 2011, Addiction • Lechner…Wagener, in press • Floyd and Johnson, 2014 unpublished data

30. Questions?