Patricia Richter Ph.D., DABT Centers for Disease Control and Prevention Office on Smoking and Health Tobacco Product Con

1. TM Example Lists of Harmful/Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke Patricia Richter Ph.D., DABT Centers for Disease Control and Prevention Office on Smoking and Health Tobacco Product Constituents Subcommittee June 8-9, 2010 Gaithersburg, Maryland

2. Objectives • Relevant terms • Entities requiring or considering constituent reporting • Examples of lists of harmful and potentially harmful constituents • Origin • Rationale • Potential associations with smoking-related disease • Clarifying questions

3. Relevant Terms • Cigarette smoke • Produced by the incomplete combustion of a tobacco cigarette • An aerosol composed of liquid droplets in a gas • More than 5,300 identified constituents • Mainstream smoke • Generated during active puffing and drawn into the smoker’s mouth • Portion exhaled by a smoker and becomes a component of secondhand smoke

4. Relevant Terms, cont. • Sidestream smoke • Generated between puffs • Surrogate for secondhand smoke • Hoffmann Analytes • 44 Chemicals/chemical mixtures • Summary of toxic and carcinogenic chemicals in mainstream smoke • Originally attributed to Dietrich Hoffmann/ American Health Foundation

5. Example of Entities Requiring or Considering Mandated Tobacco or Tobacco Smoke Constituent Reporting • World Health Organization, Framework Convention on Tobacco Control (FCTC) • Brazil • Canada • Australia • New Zealand

6. Constituent Reporting • World Health Organization, FCTC: Article 9 • “…guidelines for testing and measuring the contents and emissions of tobacco products, and for the regulation of these contents and emissions…” • Assessment of toxicants considered animal and human toxicity data (esp. cardiovascular and pulmonary toxicity and carcinogenicity), toxicity indices, variation in toxicants across brands, the potential for the toxicant to be lowered, particulate and gas phase constituents, and from different chemical classes in cigarette smoke

7. Constituent Reporting • World Health Organization, FCTC: Article 9 • 18 Mainstream smoke constituents • 7 “Most hazardous” mainstream smoke constituents

8. Constituent Reporting • Brazil • National Health Monitoring Agency • RDC Resolution No. 90, December 27, 2007 • Registration of smoking products derived from tobacco • Mandatory for all brands of smoking products derived from tobacco • Analytical and reporting format specified

9. Constituent Reporting • Brazil • 27 Tobacco constituents • 45 Mainstream smoke constituents • 44 Sidestream smoke constituents

10. Constituent Reporting • Canada • Health Canada • The 2000 Tobacco Reporting Regulations • Requirements for the reporting of toxic constituents and toxic emissions • Mandatory for cigarettes, cigarette tobacco, leaf tobacco, tobacco sticks, kreteks, bidis • Analytical and reporting format specified

11. Constituent Reporting • Canada • 26 Tobacco constituents • 39 Mainstream smoke constituents • 38 Sidestream smoke constituents

12. Constituent Reporting • Australia • In 2001 three tobacco manufacturers voluntarily provided cigarette smoke chemistry data for selected Australian cigarette brands to the Australian Department of Health and Ageing • 37 Mainstream smoke constituents • Provide evidence of variation in levels of constituents across brands within countries (FCTC/WHO)

13. Constituent Reporting • New Zealand • New Zealand Ministry of Health • 1997 Amendment to the 1990 Smoke-free Environments Act, Sections 33 and 34 • Clarified regulatory powers to limit harmful constituents in tobacco products • 2000 Environmental Health Effects Programme, Environmental Science & Research report to the New Zealand Ministry of Health

14. Constituent Reporting • New Zealand • “Risk-based priority-setting scheme” for cigarette harm reduction • 95 Chemicals in cigarette smoke • Risk assessment • Mainstream and sidestream smoke data • Cancer and non-cancer (cardiovascular, respiratory, reproductive/developmental, neurotoxicity, etc.) health effects potency data

15. Constituent Reporting • New Zealand • 16 Mainstream smoke constituents • 14 Sidestream smoke constituents • Ammonia and 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK)

16. Summary of Constituent Lists • 59 Chemicals/ chemical mixtures • 48 Mainstream smoke • 46 Sidestream smoke • 27 Tobacco products

17. Association with Smoking-related Disease— Cancer • 32 Constituents • International Agency for Research on Cancer, National Toxicology Program, Environmental Protection Agency, peer reviewed literature • 26 Known, probable, possible human carcinogen, tumor promoter

18. Association with Smoking-related Disease— Cancer, cont. • Known human carcinogens • 2-Aminonaphthalene • 4-Aminobiphenyl • Inorganic arsenic • Benzene • Benzo[a]pyrene • 1,3-Butadiene • Cadmium/cadmium compounds • Chlorinated dioxin (TCDD) • Chromium • Nickel compounds • 4-(Methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK) • N-Nitrosonornicotine(NNN)

19. Association with Smoking-related Disease — Non-neoplastic Respiratory Effects • 24 Constituents • Peer reviewed literature • Eye and respiratory tract irritants (e.g., acrolein) • Ciliatoxicants (e.g., cresols) • Chronic obstructive pulmonary disease (e.g., volatile aldehydes, hydrogen cyanide)

20. Association with Smoking-related Disease — Cardiovascular Effects • 17 Constituents • Peer reviewed literature • Atherosclerosis, peripheral artery disease (e.g., benzo[a]pyrene, cadmium) • Elevated blood pressure (e.g., lead, aldehydes) • Reduced oxygen carrying capacity (e.g., carbon monoxide, nitrogen dioxide)

21. Association with Smoking-related Disease — Addiction • 6 constituents • Peer reviewed literature • Nicotine • Reinforcing effects (acetaldehyde) • Pharmacological activity (anabasine, anatabine, myosmine, nornicotine)

22. Association with Smoking-related Disease — To Be Determined • 8 constituents • Glycerol • Menthol • Nitrate • Propylene glycol • Sodium propionate • Sorbic Acid • Triacetin • Triethylene glycol • Peer reviewed literature, reference materials • Hazardous combustion products – e.g., carbon monoxide, aldehydes • Precursor of smoke carcinogens – tobacco-specific nitrosamines (nitrate)

23. Clarifying Questions The findings and conclusions in this presentation are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention.