Discriminatory power of standard toxicity assays used to evaluate ingredients added to cigarettes

Regulatory Toxicology and Pharmacology

Volumn 62, Issue 1, 2012, Pages 49-61

  Oldham, Michael J ^a   Haussmann, Hans Juergen ^b   Gomm, Willy ^b   Rimmer, Lonnie T ^a   Morton, Michael J ^a   McKinney, Willie J ^a  

^a Altria Client Services   (United States)

^b Toxicology Consultant ^*  (Germany)

Author keywords

Chemical analysis; Discriminatory power; In vitro cytotoxicity; Inter laboratory comparison; Mainstream cigarette smoke; Minimum detectable difference; Ninety day nose only inhalation; Reproducibility; Salmonella mutagenicity

Indexed keywords

CIGARETTE SMOKE;

ARTICLE; CHEMICAL ANALYSIS; CHEMICAL COMPOSITION; CIGARETTE SMOKING; CYTOTOXICITY TEST; HISTOPATHOLOGY; MINIMUM DETECTABLE DIFFERENCES; MUTAGEN TESTING; NONHUMAN; PRIORITY JOURNAL; REPRODUCIBILITY; SEX DIFFERENCE; STATISTICAL ANALYSIS; TOXIC INHALATION; TOXICITY TESTING; WEIGHT GAIN;

ADMINISTRATION, INHALATION; ANIMALS; CELL SURVIVAL; FEMALE; MALE; RATS; REPRODUCIBILITY OF RESULTS; RESPIRATORY MUCOSA; SALMONELLA TYPHIMURIUM; SMOKING; TOBACCO SMOKE POLLUTION; TOXICITY TESTS;

SALMONELLA;

EID: 84856170140     PISSN: 02732300     EISSN: 10960295     Source Type: Journal    
DOI: 10.1016/j.yrtph.2011.11.018     Document Type: Article

References (51)

1. Altria Client Services, 2009. Product Integrity Toxicological Evaluation Guideline - Cigarette Products. Available at (accessed 5.5.2011). http://pmusa-science.com/Utilites/PdfDisplay.asp?file=53.
2. Appelman L.M., Woutersen R.A., Feron V.J. Inhalation toxicity of acetaldehyde in rats. I. Acute and subacute studies. Toxicology 1982, 23(4):293-307.
3. Appelman L.M., Woutersen R.A., Feron V.J., Hooftman R.N., Notten W.R. Effect of variable versus fixed exposure levels on the toxicity of acetaldehyde in rats. J. Appl. Toxicol. 1986, 6(5):331-336.
4. Ayres P.H., Hayes J.R., Higuchi M.A., Mosberg A.T., Sagartz J.W. Subchronic inhalation by rats of mainstream smoke from a cigarette that primarily heats tobacco compared to a cigarette that burns tobacco. Inhal. Toxicol. 2001, 13(2):149-186.
5. Baker R.R., Massey E.D., Smith G. An overview of the effects of tobacco ingredients on smoke chemistry and toxicity. Food Chem. Toxicol. 2004, 42(Suppl.):S53-S83.
6. Binns R., Beven J.L., Wilton L.V., Lugton W.G. Inhalation toxicity studies on cigarette smoke III. Tobacco smoke inhalation dosimetry study on rats. Toxicology 1976, 6(2):207-217.
7. Binns R., Lugton W.G., Wilton L.V., Dyas B.J. Inhalation toxicity studies on cigarette smoke. V. Deposition of smoke particles in the respiratory system of rats under various exposure conditions. Toxicology 1978, 9(1-2):87-102.
8. Carchman, R.A., 1998. Identification of 'animal or organism-based' short-term tests which are available for the assessment of the potentially harmful properties of tobacco smoke. In: Rickert, W.S. (Ed.), Report of Canada's Expert Committee on Cigarette Toxicity Reduction, Toronto, Canada, pp. 8.1-8.26.
9. Carmines E.L. Evaluation of the potential effects of ingredients added to cigarettes. Part 1: cigarette design, testing approach, and review of results. Food Chem. Toxicol. 2002, 40(1):77-91.
10. Carmines E.L., Gaworski C.L. Toxicological evaluation of glycerin as a cigarette ingredient. Food Chem. Toxicol. 2005, 43(10):1521-1539.
11. Carmines E.L., Lemus R., Gaworski C.L. Toxicologic evaluation of licorice extract as a cigarette ingredient. Food Chem. Toxicol. 2005, 43(9):1303-1322.
12. Coggins C.R., Lam R., Morgan K.T. Chronic inhalation study in rats, using cigarettes containing different amounts of Cytrel tobacco supplement. Toxicology 1982, 22(4):287-296.
13. Coggins C.R.E., Edmiston J.S., Jerome A.M., Langston T.B., Sena E.J., Smith D.C., Oldham M.J. A comprehensive evaluation of the toxicology of cigarette ingredients: essential oils and resins. Inhal. Toxicol. 2011, 23(S1):41-69.
14. Coggins C.R.E., Jerome A.M., Edmiston J.S., Oldham M.J. A comprehensive evaluation of the toxicology of cigarette ingredients: aliphatic carbonyl compounds. Inhal. Toxicol. 2011, 23(S1):102-118.
15. Coggins C.R.E., Liu J., Merski J.A., Werley M.S., Oldham M.J. A comprehensive evaluation of the toxicology of cigarette ingredients: aliphatic and aromatic carboxylic acids. Inhal. Toxicol. 2011, 23(S1):119-140.
16. CORESTA In Vitro Toxicology Task Force, 2004. Report on Interlaboratory Study of the In Vitro Toxicity of Particulate Matter of Four Cigarettes. Available at (accessed 5.10.10). http://www.coresta.org/Reports/IVT_TF_Report_Particulate_Matter_Tox.pdf.
17. Counts M.E., Hsu F.S., Tewes F.J. Development of a commercial cigarette " market map" comparison methodology for evaluating new or non-conventional cigarettes. Regul. Toxicol. Pharmacol. 2006, 46(3):225-242.
18. Dempsey R., Coggins C.R.E., Roemer E. Toxicological assessment of cigarette ingredients. Regul. Toxicol. Pharmacol. 2011, 61(1):119-128.
19. Deutsches Institut für Normung - Working Group Toxicology of Additives Toxicological Evaluation of Additives for Tobacco Products - A Guide 2004, Beuth Verlag, Berlin, Germany.
20. European Parliament and Council of the European Union Directive 2001/37/EC of the European Parliament and of the Council of 5 June 2001 on the approximation of the laws, regulations and administrative provisions of the Member States concerning the manufacture, presentation and sale of tobacco products. Off. J. Eur. Union 2001, L194:26-34.
21. Gaworski C.L., Dozier M.M., Heck J.D., Gerhart J.M., Rajendran N., David R.M., Brennecke L.H., Morrissey R.L. Toxicologic evaluation of flavor ingredients added to cigarette tobacco: 13-week inhalation exposures in rats. Inhal. Toxicol. 1998, 10:357-381.
22. Gaworski C.L., Lemus-Olalde R., Carmines E.L. Toxicological evaluation of potassium sorbate added to cigarette tobacco. Food Chem. Toxicol. 2008, 46(1):339-351.
23. Gaworski C.L., Oldham M.J., Coggins C.R. Toxicological considerations on the use of propylene glycol as a humectant in cigarettes. Toxicology 2010, 269:54-66.
24. Gaworski C.L., Oldham M.J., Wagner K.A., Coggins C.R., Patskan G.J. An evaluation of the toxicity of 95 ingredients added individually to experimental cigarettes: approach and methods. Inhal. Toxicol. 2011, 23(Suppl. 1):1-12.
25. Gaworski C.L., Schramke H., Diekmann J., Meisgen T.J., Tewes F.J., Veltel D., Vanscheeuwijck P.M., Rajendran N., Muzzio M., Haussmann H.-J. Effect of filtration by activated charcoal on the toxicological activity of cigarette mainstream smoke from experimental cigarettes. Inhal. Toxicol. 2009, 21(8):688-704.
26. Gaworski C.L., Wagner K.A., Morton M.J., Oldham M.J. Insights from a multi-year program designed to test the impact of ingredients on mainstream cigarette smoke toxicity. Inhal. Toxicol. 2011, 23(S1):172-183.
27. Hatsukami D.K., Biener L., Leischow S.J., Zeller M.R. Tobacco and nicotine product testing. Nicotine Tob. Res. 2011, 10.1093/ntr/ntr027.
28. Higuchi M.A., Sagartz J., Shreve W.K., Ayres P.H. Comparative subchronic inhalation study of smoke from the 1R4F and 2R4F reference cigarettes. Inhal. Toxicol. 2004, 16(1):1-20.
29. Intorp M., Purkis S., Whittacker M., Wright W. Determination of " Hoffmann Analytes" in cigarette mainstream smoke. The Coresta 2006 joint experiment. Beitr. Tabakforsch. Int. 2009, 23:161-202.
30. Lemus R., Carmines E.L., Van Miert E., Coggins C.R., Anskeit E., Gerstenberg B., Meisgen T.J., Schramke H., Stabbert R., Völkel H., Terpstra P.M. Toxicological comparisons of cigarettes containing different amounts of vanillin. Inhal. Toxicol. 2007, 19(7):683-699.
31. Life Sciences Research Office The LSRO report on review of ingredients added to cigarettes. Phase two: Scientific criteria for the evaluation of ingredients added to cigarettes 2004, Life Science Research Office, Bethesda, MD.
32. Organization for Economic Co-operation, Development OECD Guideline for Testing of Chemicals. Test No. 471: Bacterial Reverse Mutation Test 1997, OECD Publishing, Paris, France.
33. Paschke T., Scherer G., Heller W.D. Effects of ingredients on cigarette smoke composition and biological activity: a literature overview. Beitr. Tabakforsch. Int. 2002, 20(3):107-247.
34. Patskan G.J., Podraza K.F., Meurrens K., Coggins C.R.E., Friedrichs B., Gerstenberg B., Gomm W., Schnell P., Stabbert R., Veltel D., Weber S., Terpstra P. Toxicological comparisons of three styles of a commercial U.S. cigarette (Marlboro®) with the 1R4F reference cigarette. Inhal. Toxicol. 2008, 20(7):695-721.
35. Rasch D., Herrendoerfer G., Bock J., Victor N. Verfahrensbibliothek, Oldenbourg Wissenschaftsverlag 1998, München, Germany.
36. Renne R.A., Yoshimura H., Yoshino K., Lulham G., Minamisawa S., Tribukait A., Dietz D.D., Lee K.M., Westerberg R.B. Effects of flavoring and casing ingredients on the toxicity of mainstream cigarette smoke in rats. Inhal. Toxicol. 2006, 18(9):685-706.
37. Roemer E., Carchman R.A. Limitations of cigarette machine smoking regimens. Toxicol. Lett. 2011, 203(1):20-27.
38. Roemer, E., Teredesai, A., Terpstra, P.M., Vanscheeuwijck, P.M., Haussmann, H.-J., 1998. The discriminative power of rat inhalation studies investigating the irritative property of inhalants. Available at (accessed on 25.11.10). http://www.pmusa-science.com/Utilites/PdfDisplay.sap?file=72.
39. Roemer E., Wittke S., Trelles Sticken E., Piade J.J., Bonk T., Schorp M.K. The addition of cocoa, glycerol, and saccharose to the tobacco of cigarettes: implications for smoke chemistry, in vitro cytotoxicity, mutagenicity and further endpoints. Beitr. Tabakforsch. Int. 2010, 24:117-138.
40. SAS Institute, 2003. SAS Stat User's Guide, SAS Version 9.1.3, SAS Institute Inc.
41. Stavanja M.S., Curtin G.M., Ayres P.H., Bombick E.R., Borgerding M.F., Morgan W.T., Garner C.D., Pence D.H., Swauger J.E. Safety assessment of diammonium phosphate and urea used in the manufacture of cigarettes. Exp. Toxicol. Pathol. 2008, 59(6):339-353.
42. Terpstra P.M., Teredesai A., Vanscheeuwijck P.M., Verbeeck J., Schepers G., Radtke F., Kuhl P., Gomm W., Anskeit E., Patskan G. Toxicological evaluation of an electrically heated cigarette. Part 4: subchronic inhalation toxicology. J. Appl. Toxicol. 2003, 23(5):349-362.
43. Tobacco Manufacturers Association and UK Department of Health, 1997. Voluntary Agreement on the Approval and Use of New Additives in Tobacco Products in the UK. Available at (accessed on 9.02.10). http://legacy.library.ucsf.edu/tid/hlv11c00/pdf?search=%22voluntary%20agreement%20new%20additives%20in%20tobacco%20products%22.
44. US Congress, 2009. Family Smoking Prevention and Tobacco Control Act. Available at (accessed on 18.03.10). http://frwebgate.accessgpo.gov/cgi-bin/getdoc.cgi?dbname=111_cong_public_laws&docid=f:publ031.111.pdf.
45. US Consumer Product Safety Commission, 1993. Toxicity testing plan for low ignition-potential cigarettes. Washington, DC.
46. US Department of Health and Human Services, 2010. How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease - a report of the Surgeon General. Available at (accessed on 9.12.10). http://www.surgeongeneral.gov/library/tobaccosmoke/report/index.html.
47. US Food and Drug Administration Harmful and potentially harmful constituents in tobacco products and tobacco smoke; request for comments. Fed. Regist. 2011, 76(156):50226-50230.
48. US Institute of Medicine Clearing the smoke: assessing the science base for tobacco harm reduction 2001, National Academy Press, Washington, DC.
49. Werley M.S., Freelin S.A., Wrenn S.E., Gerstenberg B., Roemer E., Schramke H., Van Miert E., Vanscheeuwijck P., Weber S., Coggins C.R. Smoke chemistry, in vitro and in vivo toxicology evaluations of the electrically heated cigarette smoking system series K. Regul. Toxicol. Pharmacol. 2008, 52:122-139.
50. Woolson R.F. Statistical methods for the analysis of biomedical data 1987, John Wiley & Sons, New York, NY.
51. Woutersen R.A., Appelman L.M., Wilmer J.W., Falke H.E., Feron V.J. Subchronic (13-week) inhalation toxicity study of formaldehyde in rats. J. Appl. Toxicol. 1987, 7(1):43-49.