Tobacco Documents Online

1W_ 8 The 28 non-tobacco ingredients that are present at the highest levels in cigarettes occur at levels ranging from 0.05% to 11.58$ by weight. These ingredients, along with processing aids, comprise 99% of the total poundage of ingredients added to tobacco in the manufacture of cigarettes, and have been exten- sively tested for safety. All remaining ingredients occur at lower levels, with many below 0.0001% (1 ppm). Approximately 94% of all ingredients are approved as food additives, or are generally recognized as safe (GRAS) by expert committees, and exposure to these ingredients is generally higher in food than through smoking. The authors of this report independently examined extensive published and unpublished toxicologic, metabolic, and pyrolysis data on the ingredients added to cigarette tobacco, and found none to be potentially toxic at levels of use. It is concluded that the ingredients added to tobacco in the manufacture of cigarettes by United States manufacturers are not hazardous under the conditions of use. . ~ :~

APPENDIX Curricula Vitae of Authors a z A. John Doull, Ph.D., M.D. B. .Tohn P. Frawley, Ph.D. C. William George, Ph.D. D. Ted Loomis, Ph.D., M.D. E. Robert A. Squire, Ph.D., D.V.M. . 't

ANDREWS OFFICE PRODUCTS CAPITOL HEIGHTS, MD (K) D

CURRICULUM VITAE John Doull, Ph.D., M.D. OFFICE: University of Kansas Medical Center Department of Pharmacology, Toxicology and Therapeutics 39th & Rainbow Blvd. Kansas City, KS 66103 Phone: 913-588-7140 HOME: 6305 West 125th Street Overland Park, KS 66209 Phone: 913-345-1907 SOCIAL SECURITY NUMBER: 513-22-5613 DATE/PLACE OF BIRTH: September 13, 1922, Baker, Montana USA MARITAL STATUS: Married to Vera M. Orsborn, March 1, 1958 CHILDREN: Ellen Jane, 1959; John Kelling, 1961; James Douglas, 1961 EDUCATION: B.S.,-Chemistry, Montana State College, Bozeman, Mont., 1944 US Navy, Electronics, 1944-1946 Ph.D., Pharmacology, Univ. of Chicago, Chicago, Ill., 1950 M.D., Medicine, Univ. of Chicago, Chicago, Ill., 1953 I PROFESSIONAL EXPERIENCE: ~ University of Chicago Medical School Research Assistant, Univ. of Chicago Toxicity Laboratory, 1946-1950 Research Associate, US Air Force Radiation Laboratory and Univ. of Chicago Toxicity Laboratory, 1951-1953 Assistant Director, US Air Force Radiation Laboratory & Toxicity Laboratory, 1954-1967 Assistant Professor, Department of Pharmacology, 1956-1957 Associate Professor, Department of Pharmacology, 1957-1967 University of Kansas Medical Center Professor of Pharmacology and Toxicology, Department of Pharmacology, Toxicology and Therapeutics, 1967- Co-Director, Clinical Pharmacology-Toxicology Center, 1967-1968 Director, Univ. of Kansas Medical Center Safety Office, 1978-1985 Director, Center for Environmental and Occupational Health, Y986- M 1

PROFESSIONAL SOCIETY MEMBERSHIPS: In ; American Chemical Society, 1949- Kansas City Regional Chapter, 1967- American Industrial Hygiene Association, 1950- Radiation Research Society, 1953-1980 American Society for Pharmacology and Experimental Therapeutics, 1953- Environmental Pharmacology Committee, 1975-1978 Soc.iety for Experimental Biology and Medicine, 1954- New York Academy of Sciences, 1954-1975 American Association for the Advancement of Science, 1954- (Fellow, 1958-. Society of Toxicology (Charter Member), 1961 Technical Committee, 1967-1968 Education Committee, 1974-1976 Membership Requirement Revision Committee, 1975-1976 Biomed Research Oversight Committee, 1977-1978 Central States Regional Chapter, 1986- Program Committee (Chairman), 1985-1986 Finance Committee, 1986-1987 Awards Committee (Chairman), 1987-1988 Nominating Committee (Chairman), 1988-1989 Council Member, 1981-1988 Vice President Elect, 1984-1985 Vice President, 1985-1986 President, 1986-1987 Past-President, 1987-1988 American Academy of Clinical Toxicology, 1970- Board of Trustees, 1972-1977 Canadian Academy of Clinical Toxicology, 1976- Program Committee, 1976-1977 The Toxicology Forum, 1979- Board of Directors, 1981-1982 American Board bf Toxicology, 1979-1983 Chairman Examination Committee, 1979-1982 Vice President, 1981-1982 President, 1982-1983 American Water Works Association, 1983- Kansas Regional Section, 1983- EDITORIAL BOARDS: Toxicology and Applied Pharmacology, 1970-1982 Forum for the Advancement of Toxicology, 1973-1983 AACTION (American Academy of Clinical Toxicology), 1974-1977 Environmental Health Sciences, 1976- Archives Internationales de Pharmacodynamie et de Therapie, 1976- Journal of Environmental Pathology and Toxicology, 1977- Health & Environment Digest, 1987- F 2

Vi ,, CONSULTANTSHIPS ChemAgro Corp., Kansas City, MO, 1950-1980 Walter Reed Army Institute for Research, 1960-1963 Radiation Protection Panel, 1962-1963 Atomic Defense Support Agency, Group N-3, 1961-1962 White House Evaluation Study (Woolridge Report), 1962-1963 NIH Special Grants Program Advisory Panel, 1962 NIH Toxicology Study Section, 1965-1970 HEW Secretary's Commission on Pesticides (Mrak Report), 1968-1969 Subcommittee on Interactions, 1968-1969 Midwest Research Institute, 1969- Institute for Clinical Toxicology, Houston, Texas, 1969-1973 National Academy of Sciences, National Research Council, 1970- Toxicology Information Program (Chairman), 1970-1975 Food Protection Committee, 1974-1979 Committee on Non-nutritive Sweeteners, 1974-1975 Safe Drinking Water Committee, 1975-1978 (Chairman, 1976-1978) Pesticides Subcommittee (Chairman), 1975-1977 Committee to Revise Publication 1138, 1976-1977 Chronic Toxicity Subcommittee (Chairman), 1976-1977 Board on Toxicology and Environmental Health Hazards, 1978-1986 Board on Environmental Sciences and Toxicology, 1986- IOM Food Safety Policy Subcommittee, 1978-1979 Committee to study Saccharin and Food Safety Policy, 1978-1979 IOM Advisory Committee on CDC Study of Vietnam Veteran Health, 1985- 1988 - _ Committee on Toxicity Testing Strategies (Chairman), 1982-1984 Committee on Mixtures (Chairman), 1986-1988 Committee on Toxicology (Chairman), 1987- Environmental Protection Agency, Washington, D.C., 1976- FIFRA Science Advisory Panel, 1976-1980 Worktr Re-entry Protocol Group, 1977-1978 Commi:ttee on Tolerances, 1978-1979 Science Advisory Board, Environmental Health Committee, 1980- Organics Subcommittee (Chairman), 1986- Estimating Risks from Dioxins/Dibenzofurans, 1986-1987 Severity of Effects Ranking Schemes, 1985-1986 Acute Toxics Committee, 1986-1987 Hazard Ranking System Committee, 1987-1988 National Institute of Environmental Health Sciences, 1975-1978 NIEHS Advisory Council, 1975-1978 Uiiversity-Based Centers Subcommittee (Chairman), 1975-1978 Second Task Force on Human Health and the Environment, 1976-1977 Biologic Mechanisms and Toxicity Subcommittee, 1976-1977 F.E.M.A., Washington, D.C., Expert Panel Member, 1977- National Advisory Committee, California Primate Center, Davis, 1977-1980 CPC International, Englewood Cliffs, Toxicology Assessment Group, 1978 Best foods, Union, NJ, Food Safety and Nutrition Board, 1978- OTA, Washington, Panel on Assessment of Environmental Contaminants, 1978 Rohm and Haas, Philadelphia (Medical Dept.), 1980- Stauffer Chemical Corp., Pesticide Advisory Group, 1980-1984 National Toxicology Program, Board of Scientific Counselors Ad Hoc Panel on ChemicalYCarcinogenesis Testing & Evaluation, 1982- 1984 3

DHHS Advisory Committee on Long-term Health Effects of Phenoxy Herbicides and Contaminants, 1982-1985 National Sanitation Foundation, Ann Arbo:, 1983- Council of Public Health Consultants, 1983- Health Advisory Board, 1983- Drinking Water Additives Peer Review Group, 1987- Nutrition Foundation, Washington Predictive Role of Mc:use Liver Tumors Committee, 1982-1983 UAREP, Panel on Health Aspects of Waste Chemical Disposal, 1983-1984 Kansas Dept. Health and Environment, Topeka, 1983- Toxicology Advisory Committee, 1983- Governors Advisory Committee on Radon (Chairman), 1987- National Institute of Occupational Safety and Health, 1984-1987 Board of Scientific Counselors, 1984-1987 Pillsbury Corp., Minneapolis, 1984- White House Advisory Panel on Ranchhand Veterans, 1984-1986 Clean Sites Inc., Alexandria, Technical Advisory Panel, 1984- Naylor Dana Institute, Advisory Panel on Acetaminophen, 1986-1987 Black and Veatch Engineering Corp., Kansas City, 1986-1987 Denver Water Department Reuse Demo. Project Advisory Committee, 1986- Scientific Advisory Panel on Ground Water Recharge (California), 1987 Water Resource Recovery Pilot Plant Project (Tampa, FL), 1987- Health Effects Group (Chairman), 1987- Monsanto Chemical Corp., St. Louis Alachlor Review Panel, 1987-1988 International Life Sciences Institute, Risk Science Institute, 1988- LOCAL COMMITTEES: Poison Control Center Committee (Chairman), 1968-1980 Pharmacy and Therapy Committee (Chairman), 1969-1984 Basic Science'Lectureship Committee, 1970-1972 Health Care Delivery systems Committee, 1971-1972 Research Commi~tee, 1971-1973 Animal Care Committee, 1972-1974 Computer Committee (Chairman), 1972-1974 Search Committee for Chair of Biochemistry, 1975 Search Committee for Dean of School of Nursing (Chairman), 1975 Education Committee, 1976-1977 Faculty Promotion and Tenure Committee, 1976-1977 Curriculum Implementation Committee, 1976 Ad Hoc Ethics Committee, 1976 Long Range Planning Committee, 1976 Information Systems Advisory Committee, 1977 Medical Center Safety Committee (Chairman), 1978-1983 Radiation Safety Committee, 1978-1983 Biohazards Committee, 1978-1983 Engineering Safety Committee, 1978-1983 Committee for Intercampus Liaison (Chairman), 1978-1980 Search Committee for Director of Biomedical Engineering (Chairman), 1980 Search Committee for Graduate School Dean (Chairman), 1980 Task Force on Need for School of Public Health, 1980 Education and Curriculum Committee, 1984-1987 Center for Environmental and Occupational Health, 1986- Executive Advisory Committee, 1986- External Advisory Committee, 1986- 4

HONORS/AWARDS: Sigma Xi, 1960 Alpha Omega Alpha, 1973 The Kenneth P. DuBois Award, 1985 BOOKS/BOOK CHAPTERS: Essays in Toxicology (F. Blood, ed.), Academic Press, New York, Effect of Physical Environmental Factors on Drug Response, 1972. Casarett and Doull's Toxicology: The Basic Science of Poisons, Macmillan Publishing Co., Inc., New York. First Edition (L. J. Casarett and J. Doull, eds.), 1975 Second Edition (C. D. Klaassen, M. 0. Amdur and J. Doull, eds.), 1980 Third Edition (C. D. Klaassen, M. 0. Amdur and J. Doull, eds.), 1986 J Insecticide Biochemistry and Physiology (C. Wilkinson, ed.), Plenum Press, NY, The Treatment of Insecticide Poisoning, 1976. Information Technology in Health Science Education (E. Deland, ed.), Plenum Pub. Co., Use of CATS in Pharmacology, 1978. Food Safety (H. Roberts, ed.), Wiley & Sons, New York, Chapter 7, and Toxicology, 1981. Complex Mixtures, National Academy Press, Washington, D.C., 1988. M 5 i Food Safety

BIBLIOGRAPHY 1. Dubois, K. P., Doull, J., Salerno. P. R., and Coon, J. *i. Studies on the toxicity and mechanism of action of p-nitrophenyl diethyl thionophosphate (Parathion). J. Pharmacol. Exp. Ther. 95: 79 (1949). 2. DuBois, K. P., Doull, J., and Cochran, K. W. Effects of acute beryllium poisoning on carbohydrate metabolism. Proc. 116th Meeting Arner. Chem. Soc., p. 57 (1949). 3. DuBois, K. P., Doull, J., and Coon, J. M. The cholinergic action of alkyl pyrophosphoramide. J. Pharmacol. Exp. Ther. 98: 6 (1950). 4. Cochran, K. W., Doull, J., Mazur, M., and DuBois, K. P. Acute toxicity of zirconium, columbium, strontium „ lanthanum, cesium, tantalum and yttrium. J. Ind. Hyg. Occup. Med. 1: 637 (1950). 5. DuBois, K. P., Doull, J., and Coon, J. M. Studies on the toxicity and pharmacological actions of octamethyl pyrophosphoramide (OMPA, Pestox III). J. Pharmacol. Exp. Ther. 99: 376 (1950). 6. DuBois, K. P., Cochran, K. W., and Doull, J. Inhibition of citric acid synthesis in vitro by x-irradiation. Proc. Soc. Exp. Bfo1. Med. 76: 422 (1951). 7. Doull', J., DuBois, K. P., and Geiling, E. M. K. The biosynthesis of radioactive bufagin. Arch. Int. Pharmacodyn. 86: 454 (1951). 8. Doull, J., Hermann, R. G., Geiling, E. M. K., and DuBois, K. P. Effects of bufagin on the respiration of cardiac muscle and other tissues. Arch. Int. PharmacodXn. 86: 487 (1951). 9. Doull, J., and DuBois, K. P. Toxicity and anticholinesterase action of tetra-n-propyl dithionopyrophosphate. J. Pharmacol. Exp. Ther. 106: 382 (1952). 10. DuBois, K. P., Doull, J., Deroin, J., and Cummings, 0. K. Studies on the toxicity and mechanism of action of some new insecticidal thionophos- phates. Arch. Ind. flyg. Occup. Med. 8: 350 (1953). 11. DuBois, K. P., Doull, J., Okinaka, A. J., and Coon, J. M. S:-udies on the toxicity and pharmacological actions of symmetrical and unsymmetrical diethyl bis(dimethylamido) pyrophosphate. J. Pharmacol. Exp. Ther. 107: 464 (1953). 12. Doull, J., and DuBois, K. P. Influence of hibernation on survival time and weight loss of x-irradiated ground squirrels. Proc. Soc. Exp. Biol. Med. 84: 367 (1953). Doull, J. Studies on the cholinesterase activity of tissues of irradiated animals. J. Pharmacol. Exp. Ther. 110: 14 (1954). w 14. Okinaka, A. J., Doull, J., Coon, J. M., and DuBois, K. P. Studies on the toxicity and pharmacological actions of bis(dimethylamido) fluorophos- phate (BFP). J. Pharmacol. Exp. Ther. 112: 231 (1954). 13. 6

15. 16. 17. 18. 19. 20. 21. 22. 23. _W 24. 25. 0 26. ~ 27. 28. 29. 30. Fitch, F. W., Doull, J., and Wissler, R. W. Histopathology of the irradiated hibernating ground squirrel (Citellus tridecemlineatus). A.M.A. Arch. Path. 60: 644 (1955). Hallesy, D. W., and Doull, J. Acute and chronic toxicity of orange B and orange 1 in rats. J. Pharmacol. Exp. Ther. 116: 26 (1956). Doull, J. Irradiation and survival in hibernating animals. Med. Sci. 1: 27 (1956). Landahl, H. D., Hasegawa, A. T., and Doull, J. Effect of whole body x- irradiation on the heat production and temperature regulation of rats and mice. Radiat. Res. 5: 488 (1956). Doull, J., Plzak, V., and Noble, J. F. Synthesis and radioprotective properties of chlorinated 0-dialkylaminopropionamideo- and 0-dialkyl- aminopropylaminodiphenyl sulfide derivatives. J. Med. Pharm. Chem. 1: 171 (1959). Doull, J., Plzak, V., and Brois, S. J. Protective effects of various phenone derivatives against radiation lethality in x-irradiated mice. Radiat. Res. 11: 439 (1959). Noble, J. F., Hasegawa, A. T., Landahl, H. D., and Doull, J. Effect of fractionation on survival of mice following chronic exposure to x- irradiation. Radiat. Res. 11: 457 (1959). Doull, J. Chemical antidotes for radiation injury. Arch. Environ. Health 2: 284 (1961). Vesselinovitch, D., DuBois, K. P., Fitch, F. W., and Doull, J. Mammalian toxicity and histopathologic effects of 2,6-dibutyl-4-nitrophenol. Toxicol. Appi. Pharmacol. 3: 713 (1961). Doull, J., Plzak, V., and Root, M. Protection against chronic radiation lethality in mice. Radiat. Res. 16: 578 (1962). Doull, J., Plzak, V., and Brois, S. J. A survey of compounds for radia- tion protection. USAF School of Aerospace Med. Report, No. 62-29: 1 (1962). Doull, J., Plzak, V., and Root, M. Toxicity and radioprotective activity of p-aminopropiophenone in mice. Radiat. Res. 16: 588 (1962). Plzak, V., and Doull, J. Toxicity and radioprotective effects of acetyl p-aminopropiophenone in mice. Radiat. Res. 19: 228 (1963). Oldfield, D. G., Doull, J., Plzak, V., Hasegawa, A., and Sandberg, A. Protection of proton-irradiated mice with p-aminopropiophenone (PAPP) and 2-mercaptoethylamine (MEA). Radiat. Res. 19: 229 (1963). Pizak, V., Hasegawa, A. T., and Doull, J. Radioprotective effects of cyclobutane derivatives in mice. Radiat. Res. 22: 224 (1964). Vesselinovitch, D., and Doull, J. Effect'of adding Co-ral to the diet of rats and mice. Lab. Anim. Care 14: 325 (1964). 7