Reduced Toxicological Activity of Cigarette Smoke by the Addition of Ammonia Magnesium Phosphate to the Paper of an Electrically Heated Cigarette: Subchronic Inhalation Toxicology

Abstract

Cigarette smoke is a complex chemical mixture that causes a variety of diseases, such as lung cancer. With the electrically heated cigarette smoking system (EHCSS), temperatures are applied to the tobacco below those found in conventional cigarettes, resulting in less combustion, reduced yields of some smoke constituents, and decreased activity in some standard toxicological tests. The first generation of electrically heated cigarettes (EHC) also resulted in increased formaldehyde yields; therefore, a second generation of EHC was developed with ammonium magnesium phosphate (AMP) in the cigarette paper in part to address this increase. The toxicological activity of mainstream smoke from these two generations of EHC and of a conventional reference cigarette was investigated in two studies in rats: a standard 90-day inhalation toxicity study and a 35-day inhalation study focusing on lung inflammation. Many of the typical smoke exposure-related changes were found to be less pronounced after exposure to smoke from the second-generation EHC with AMP than to smoke from the first-generation EHC or the conventional reference cigarette, when compared on a particulate matter or nicotine basis. Differences between the EHC without AMP and the conventional reference cigarette were not as prominent. Overall, AMP incorporated in the EHC cigarette paper reduced the inhalation toxicity of the EHCSS more than expected based on the observed reduction in aldehyde yields.

Effect of filtration by activated charcoal on the toxicological activity of cigarette mainstream smoke from experimental cigarettes

“…In the current study, the major effect was goblet cell hyperplasia in the respiratory epithelia of the trachea and bronchus, which was markedly lower in the rats exposed to AC filtered MS than in those exposed to the control MS without AC filtration. A similar concordance in decreased severity of findings between the nose and the trachea/bronchus was also described for rats exposed to a less irritating modification of an electrically heated cigarette smoking system, compared to its control MS generated from cigarettes without this modification (Moennikes et al, 2008).…”

“…An increased peak inspiratory flow rate was indeed found for the female rats in the current study, which may result in more pronounced particle impaction at the sensitive laryngeal epithelium. A similar laryngeal response was observed in rats which were exposed to the less irritating MS of an electrically heated cigarette smoking system operated with modified cigarettes, compared to that with unmodified cigarettes (Moennikes et al, 2008). As a hypothesis, it may be suggested that the trend toward more pronounced effects in the larynx of rats exposed to AC filtered MS compared to those observed in rats exposed to MS without AC filtration resulted from altered inspiratory patterns.…”

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.…”

Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 1: Non-clinical and clinical insights

“…The impact of AMP on smoke composition, in vitro cytotoxicity and genotoxicity has been reported in detail . Reduced toxicological activity of mainstream smoke was also determined in both a 90-day sub-chronic rat inhalation study and a 35-day study focusing on lung inflammation in rats (Moennikes et al, 2008). Clinical evaluations also confirmed reduced exposure to selected HPHC and reduced excretion of mutagenic material in urine .…”