title: Smoke chemistry, in vitro and in vivo toxicology evaluations of the electrically heated cigarette smoking system series K.
abstract: The Electrically Heated Cigarette Smoking System Series K (EHCSS) produces smoke through the controlled electrical heating of tobacco. Evaluation of the EHCSS was accomplished by comparison with commercial and reference cigarettes, using International Organization for Standardization (ISO) and alternative puffing regimens based on nicotine exposures measured in a short-term clinical study. Using the alternative puffing regimen and compared with conventional cigarettes on a per cigarette basis, the EHCSS had 50-60% reductions in tar and nicotine; at least 90% reductions in carbon monoxide, nitrogen oxides, 1,3-butadiene, isoprene, acrylonitrile, polyaromatic hydrocarbons, hydrogen cyanide, aromatic amines, tobacco specific nitrosamines, and phenol; and least a 40% reduction in 2-nitropropane. Other important smoke constituents in EHCSS smoke were reduced as well. The in vitro studies showed similar large reductions in biological activity. Ames mutagenicity of total particulate matter (TPM) from the EHCSS was reduced by 70-90%; cytotoxicity of the TPM was reduced by approximately 82% and 65% for the gas-vapor phase. In vivo testing under ISO smoking conditions in the mouse skin painting assay demonstrated later dermal tumor onset, lower dermal tumor incidence, reduced dermal tumor multiplicity, and a lower proportion of malignant dermal tumors in EHCSS smoke condensate-exposed mice. Thirty-five day and 90-day nose-only inhalation studies in rats showed reductions in pulmonary inflammation and other biological activity, including histopathological endpoints. We conclude that under the conditions of these in vitro and in vivo studies, the EHCSS demonstrated significantly lower biological activity compared to conventional cigarettes, and may suggest the potential for reductions in human smokers.
authors.affiliation: Philip Morris USA, Research Center, 615 Maury Street, Richmond, VA 23234, USA. michael.s.werley@pmusa.com
authors.forename: Michael S
authors.initials: MS
authors.lastname: Werley
authors.forename: Susan A
authors.initials: SA
authors.lastname: Freelin
authors.forename: Susan E
authors.initials: SE
authors.lastname: Wrenn
authors.forename: Birgit
authors.initials: B
authors.lastname: Gerstenberg
authors.forename: Ewald
authors.initials: E
authors.lastname: Roemer
authors.forename: Heike
authors.initials: H
authors.lastname: Schramke
authors.forename: Erik
authors.initials: E
authors.lastname: Van Miert
authors.forename: Patrick
authors.initials: P
authors.lastname: Vanscheeuwijck
authors.forename: Susanne
authors.initials: S
authors.lastname: Weber
authors.forename: Christopher R E
authors.initials: CR
authors.lastname: Coggins
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D015197:Carcinogenicity Tests; D004560:Electricity; D005260:Female; D006358:Hot Temperature; D007390:International Agencies; D008297:Male; D051379:Mice; D018632:Mice, Inbred SENCAR; D009152:Mutagenicity Tests / Q000379:methods; D009538:Nicotine / Q000737:chemistry; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012878:Skin Neoplasms / Q000139:chemically induced; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism*; D013638:Tars / Q000737:chemistry; D014028:Tobacco Smoke Pollution / Q000009:adverse effects / Q000032:analysis*
chemical_list: D052638:Particulate Matter; D013638:Tars; D014028:Tobacco Smoke Pollution; C024746:tobacco tar; D009538:Nicotine