Abstract:The in vitro toxicity of cigarette mainstream smoke from an electrically heated cigarette (EHC) with controlled combustion was compared with that of the standard University of Kentucky Reference Cigarette 1R4F. In the Salmonella reverse mutation assay, strains TA98, TA100, TA102, TA1535 and TA1537 were used in the absence and presence of a metabolic promutagen activation system (S9) to determine the mutagenic potential of the total particulate matter (TPM), which was collected on a glass-fiber filter. In the n… Show more
“…This 90-day inhalation study on rats was conducted to assess and quantify the relative in vivo activity of EHC smoke compared with 1R4F smoke and to complement the analytical chemistry and cytotoxicity assays, which showed substantially lower yields of several tobacco smoke constituents of concern for the EHC (Stabbert et al, 2003) and a pronounced reduction in cytotoxicity (Tewes et al, 2003). As can be observed from various dose-response curves, several of the effects seen for the low-dose EHC and the lower doses of the 1R4F are only marginally different from the sham control group in this 6 h a day, 7 days per week exposure regimen; however, to use doses much higher than the highest 1R4F dose is not feasible because acute CO toxicity occurs.…”
The biological activity of mainstream smoke from an electrically heated cigarette (EHC) with controlled combustion and from the University of Kentucky Reference Cigarette 1R4F was determined in Sprague Dawley rats exposed nose-only for 90 days, 6 h a day, 7 days per week. For an equivalent response comparison between the two cigarette types, two doses were chosen for the EHC where the anticipated results were in the dynamic range of the 1R4F dose-response curve (four concentrations) for most end points. The number of cigarettes smoked per m(3) of diluted smoke resulted in total particulate matter concentrations of 40 and 90 microg l (-1) for the EHC and 40-170 microg l (-1) for the 1R4F. Biomonitoring indicated achievement of target doses. Mainstream smoke yields were lower for the EHC, with the exception of formaldehyde. No smoke-related mortality, remarkable in-life observations or abnormal gross pathological findings were observed. Smoke- and dose-related clinical pathology and organ weight changes included: increases in segmented neutrophils, some liver parameters and lung and adrenal weight relative to body weight; and decreases in lymphocytes, glucose concentration and spleen weight. Smoke-related histopathological findings in the respiratory tract included epithelial cell hyperplasia, squamous metaplasia, atrophy and accumulation of pigmented alveolar macrophages; they were mostly dose-dependent, more pronounced in the upper than lower respiratory tract and completely or partially reversed by 6 weeks post-inhalation. Qualitatively, the biological effects seen for the EHC and the 1R4F were comparable and similar to those observed in other mainstream smoke inhalation studies. Quantitatively, the biological activity of the EHC mainstream smoke was, on average, 65% lower than that of the 1R4F mainstream smoke on an equal cigarette basis and equivalent activity on an equal TPM basis.
“…This 90-day inhalation study on rats was conducted to assess and quantify the relative in vivo activity of EHC smoke compared with 1R4F smoke and to complement the analytical chemistry and cytotoxicity assays, which showed substantially lower yields of several tobacco smoke constituents of concern for the EHC (Stabbert et al, 2003) and a pronounced reduction in cytotoxicity (Tewes et al, 2003). As can be observed from various dose-response curves, several of the effects seen for the low-dose EHC and the lower doses of the 1R4F are only marginally different from the sham control group in this 6 h a day, 7 days per week exposure regimen; however, to use doses much higher than the highest 1R4F dose is not feasible because acute CO toxicity occurs.…”
The biological activity of mainstream smoke from an electrically heated cigarette (EHC) with controlled combustion and from the University of Kentucky Reference Cigarette 1R4F was determined in Sprague Dawley rats exposed nose-only for 90 days, 6 h a day, 7 days per week. For an equivalent response comparison between the two cigarette types, two doses were chosen for the EHC where the anticipated results were in the dynamic range of the 1R4F dose-response curve (four concentrations) for most end points. The number of cigarettes smoked per m(3) of diluted smoke resulted in total particulate matter concentrations of 40 and 90 microg l (-1) for the EHC and 40-170 microg l (-1) for the 1R4F. Biomonitoring indicated achievement of target doses. Mainstream smoke yields were lower for the EHC, with the exception of formaldehyde. No smoke-related mortality, remarkable in-life observations or abnormal gross pathological findings were observed. Smoke- and dose-related clinical pathology and organ weight changes included: increases in segmented neutrophils, some liver parameters and lung and adrenal weight relative to body weight; and decreases in lymphocytes, glucose concentration and spleen weight. Smoke-related histopathological findings in the respiratory tract included epithelial cell hyperplasia, squamous metaplasia, atrophy and accumulation of pigmented alveolar macrophages; they were mostly dose-dependent, more pronounced in the upper than lower respiratory tract and completely or partially reversed by 6 weeks post-inhalation. Qualitatively, the biological effects seen for the EHC and the 1R4F were comparable and similar to those observed in other mainstream smoke inhalation studies. Quantitatively, the biological activity of the EHC mainstream smoke was, on average, 65% lower than that of the 1R4F mainstream smoke on an equal cigarette basis and equivalent activity on an equal TPM basis.
“…The cytotoxicity assay evaluates cell death and inhibition of cell growth in BALB/c 3T3 cells by measuring the uptake of neutral red (Tewes et al, 2003). This assay assesses the effects of the gas/vapor phase and the particulate phase separately and is considered to be an indicator of irritation in vivo.…”
This series of papers provides a description of the toxicological evaluation of an electrically heated cigarette (EHC). With this novel cigarette design the tobacco is heated by a series of electric heating elements, which allows for greater control of the available heat and results in lower temperatures and less combustion compared with conventional lit-end cigarettes. This design was subjected to testing, including an evaluation of smoke chemistry, in vitro bacterial genotoxicity, in vitro mammalian cell cytotoxicity and a 90-day smoke inhalation study in rats. A conventional lit-end cigarette, the University of Kentucky Reference Cigarette 1R4F, was used as a point of comparison in these experiments. When adjusted for the yield of total particulate matter, the EHC delivered 50% lower amounts of about two-thirds of the 69 smoke constituents measured. Mutagenic activity (Salmonella reverse mutation assay) of the particulate phase material in the presence of metabolic activation was ca. 90% lower, with a slight reduction of activity in the absence of metabolic activation. Cytotoxic activity (neutral red assay) of the particulate phase material was ca. 40% lower, with about equal activity of the gas/vapor-phase material. Equal activity was noted between cigarette types in a whole smoke rat inhalation assay. The results from this series of tests demonstrate that the EHC produces a much different smoke--with an at least partially reduced yield of smoke constituents and biological activity--from that of a standard reference cigarette.
“…The technical concept of the EHCSS and the chemical and biological properties have been described in earlier publications Stabbert et al, 2003;Terpstra et al, 2003;Tewes et al, 2003). A distinct feature of the EHCSS is that it only produces mainstream smoke and no sidestream smoke is emitted.…”
Smoking conventional lit-end cigarettes results in exposure of nonsmokers to potentially harmful cigarette smoke constituents present in environmental tobacco smoke (ETS) generated by sidestream smoke emissions and exhaled mainstream smoke. ETS constituent concentrations generated by a conventional lit-end cigarette and a newly developed electrically heated cigarette smoking system (EHCSS) that produces only mainstream smoke and no sidestream smoke emissions were investigated in simulated "office" and "hospitality" environments with different levels of baseline indoor air quality. Smoking the EHCSS (International Organisation for Standardization yields: 5 mg tar, 0.3 mg nicotine, and 0.6 mg carbon monoxide) in simulated indoor environments resulted in significant reductions in ETS constituent concentrations compared to when smoking a representative lit-end cigarette (Marlboro: 6 mg tar, 0.5 mg nicotine, and 7 mg carbon monoxide). In direct comparisons, 24 of 29 measured smoke constituents (83%) showed mean reductions of greater than 90%, and 5 smoke constituents (17%) showed mean reductions between 80% and 90%. Gas-vapor phase ETS markers (nicotine and 3-ethenylpyridine) were reduced by an average of 97% (range 94-99%). Total respirable suspended particles, determined by online particle measurements and as gravimetric respirable suspended particles, were reduced by 90% (range 82-100%). The mean and standard deviation of the reduction of all constituents was 94 ± 4%, indicating that smoking the new EHCSS in simulated "office" and "hospitality" indoor environments resulted in substantial reductions of ETS constituents in indoor air.
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