Toxicological evaluation of an electrically heated cigarette. Part 4: Subchronic inhalation toxicology

Abstract

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.

Toxicological evaluation of an electrically heated cigarette. Part 1: Overview of technical concepts and summary of findings

“…The types of responses in the inhalation assay are essentially the same when animals are exposed to the same amount of TPM from the 1R4F and from the EHC (Terpstra et al, 2003). The same effects, both in the respiratory tract and systemically, were observed in animals exposed to the smoke from either cigarette.…”

Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 2: Smoke chemistry and in vitro toxicological evaluation using smoking regimens reflecting human puffing behavior

“…Results from in vitro and in vivo testing performed on various Electrically Heated Cigarette Smoking System (EHCSS) prototypes and test market versions of the EHCSS have been published that document the basic product construction and an earlier testing strategy (Patskan and Reininghaus, 2003), the smoke constituent analysis Stabbert et al, 2003a;Werley et al, 2008), in vitro testing Schramke et al, 2006;Tewes et al, 2003;Werley et al, 2008), and in vivo testing (Moennikes et al, 2008;Terpstra et al, 2003). Further publications document additional testing on the generation of environmental tobacco smoke (ETS) (Frost-Pineda et al, 2008a;Tricker et al, 2009) and clinical evaluations (Feng et al, 2006;Frost-Pineda et al, 2008b,c;Oey et al, 2003;Roethig et al, 2002Roethig et al, , 2005Roethig et al, , 2007Roethig et al, , 2008Unverdorben et al, 2005aUnverdorben et al, ,b, 2007Unverdorben et al, , 2008.…”

Comparison of Environmental Tobacco Smoke (ETS) Concentrations Generated by an Electrically Heated Cigarette Smoking System and a Conventional 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.…”