Accurate measurement of main aerosol constituents from heated tobacco products (HTPs): Implications for a fundamentally different aerosol.

ISO 4387 Standard determines the main aerosol constituents (total particulate matter, water, nicotine, and nicotine-free-dry-particulate matter, referred to as "tar") in cigarette mainstream smoke (ISO, 2000). Heated Tobacco Products (also called Tobacco Heating Products or Heat-not-Burn Products) are designed to form aerosol by heating tobacco rather than burning like in combustible cigarettes. In this study we have evaluated the suitability of ISO 4387 Standard to be adapted for quantifying main aerosol constituents for HTP aerosol. HTP emissions have much higher levels of water and humectants (e.g., glycerol) in dynamic equilibria between gaseous and particulate phases. Several modifications to ISO 4387 Standard on aerosol collection were tested to improve the accuracy and reliability of aerosol capturing, with minimal deviation to the standard method. The proposed modifications are readily adoptable by laboratories already practicing the Standard for cigarette smoke analyses. Taking collectively with other available aerosol chemistry and biological results on HTPs in the literature, they show a fundamentally different aerosol in HTPs and call for category-specific product standards and terminology.

Assessment of novel tobacco heating product THP1.0. Part 3: Comprehensive chemical characterisation of harmful and potentially harmful aerosol emissions.

For a tobacco heating product (THP), which heats rather than burns tobacco, the emissions of toxicants in the aerosol were compared with those in cigarette smoke under a machine-puffing regimen of puff volume 55 ml, puff duration 2 s and puff interval 30 s. The list of toxicants included those proposed by Health Canada, the World Health Organization Study Group on Tobacco Product Regulation (TobReg), the US Food and Drug Administration and possible thermal breakdown products. In comparison to the University of Kentucky 3R4F reference cigarette the toxicant levels in the THP1.0 emissions were significantly reduced across all chemical classes. For the nine toxicants proposed by TobReg for mandated reduction in cigarette emissions, the mean reductions in THP1.0 aerosol were 90.6-99.9% per consumable with an overall average reduction of 97.1%. For the abbreviated list of harmful and potentially harmful constituents of smoke specified by the US Food and Drug Administration Tobacco Products Scientific Advisory Committee for reporting in cigarette smoke (excluding nicotine), reductions in the aerosol of THP1.0 were 84.6-99.9% per consumable with an overall average reduction of 97.5%.

Chemical Composition of Aerosol from an E-Cigarette: A Quantitative Comparison with Cigarette Smoke.

There is interest in the relative toxicities of emissions from electronic cigarettes and tobacco cigarettes. Lists of cigarette smoke priority toxicants have been developed to focus regulatory initiatives. However, a comprehensive assessment of e-cigarette chemical emissions including all tobacco smoke Harmful and Potentially Harmful Constituents, and additional toxic species reportedly present in e-cigarette emissions, is lacking. We examined 150 chemical emissions from an e-cigarette (Vype ePen), a reference tobacco cigarette (Ky3R4F), and laboratory air/method blanks. All measurements were conducted by a contract research laboratory using ISO 17025 accredited methods. The data show that it is essential to conduct laboratory air/method measurements when measuring e-cigarette emissions, owing to the combination of low emissions and the associated impact of laboratory background that can lead to false-positive results and overestimates. Of the 150 measurands examined in the e-cigarette aerosol, 104 were not detected and 21 were present due to laboratory background. Of the 25 detected aerosol constituents, 9 were present at levels too low to be quantified and 16 were generated in whole or in part by the e-cigarette. These comprised major e-liquid constituents (nicotine, propylene glycol, and glycerol), recognized impurities in Pharmacopoeia-quality nicotine, and eight thermal decomposition products of propylene glycol or glycerol. By contrast, approximately 100 measurands were detected in mainstream cigarette smoke. Depending on the regulatory list considered and the puffing regime used, the emissions of toxicants identified for regulation were from 82 to >99% lower on a per-puff basis from the e-cigarette compared with those from Ky3R4F. Thus, the aerosol from the e-cigarette is compositionally less complex than cigarette smoke and contains significantly lower levels of toxicants. These data demonstrate that e-cigarettes can be developed that offer the potential for substantially reduced exposure to cigarette toxicants. Further studies are required to establish whether the potential lower consumer exposure to these toxicants will result in tangible public health benefits.

Smoking intensity before and after introduction of the public place smoking ban in Scotland.

A study was performed to determine whether cigarettes were smoked more intensely outside of public venues in Scotland, compared to indoors, after introduction of the public place smoking (PPS) ban. It was conducted in three waves: before the ban, immediately after and 6 months after introduction. The study included 322 regular smokers of four cigarette brand variants. Filter analysis measurements were used to estimate the human-smoked yields of tar and nicotine from cigarettes smoked predominantly inside (before the ban) or outside (after the ban) public venues. Self-reported cigarette consumption data were also collected. Numbers of cigarettes smoked indoors in public places fell dramatically after the ban. There was a corresponding rise in smoking incidence in outdoor public locations. The ban did not significantly affect the total number of cigarettes smoked by the subjects over the weekends investigated. Human-smoked yields of tar and nicotine decreased slightly after the introduction of the ban and some reductions were significant. Therefore, smoking outdoors at public venues, following the PPS ban, did not increase smoking intensity. Any changes in smoking behaviour that may have occurred had little effect on mainstream smoke exposure or cigarette consumption for those that continued to smoke.

A review of the UK methodology used for monitoring cigarette smoke yields, aspects of analytical data variability and their impact on current and future regulatory compliance.

The European Union (EU) requires that tobacco products are regulated by Directive 2001/37/EC through testing and verification of results on the basis of standards developed by the International Organization for Standardization (ISO). In 2007, the European Commission provided guidance to EU Member States by issuing criteria for competent laboratories which includes accreditation to ISO 17025:2005. Another criterion requires regular laboratory participation in collaborative studies that predict the measurement tolerance that must be observed to conclude that test results on any particular product are different. However, differences will always occur when comparing overall data across products between different laboratories. A forum for technical discussion between laboratories testing products as they are manufactured and a Government appointed verification laboratory gives transparency, ensures consistency and reduces apparent compliance issues to the benefit of all parties. More than 30years ago, such a forum was set up in the UK that continued until 2007 and will be described in this document. Anticipating further testing requirements in future product regulation as proposed by the Framework Convention on Tobacco Control, cooperation between accredited laboratories, whether for testing or verification, should be established to share know-how, to ensure a standardised level of quality and to offer competent technical dialogue in the best interest of regulators and manufacturers alike.

A study to estimate and correlate cigarette smoke exposure in smokers in Germany as determined by filter analysis and biomarkers of exposure.

A clinical study, conducted in Germany, compared two methods of estimating exposure to cigarette smoke. Estimates of mouth level exposure (MLE) to nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), pyrene and acrolein were obtained by chemical analysis of spent cigarette filters for nicotine content. Estimates of smoke constituent uptake were achieved by analysis of corresponding urinary biomarkers: for nicotine; total nicotine equivalents (nicotine, cotinine, trans-3'-hydroxycotinine plus their glucuronide conjugates), for NNK; (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) plus glucuronide, for pyrene; 1-hydroxy pyrene (1-OHP) plus glucuronide and for acrolein; 3-hydroxylpropyl-mercapturic acid (3-HPMA) plus the nicotine metabolite cotinine in plasma and saliva. Two hundred healthy volunteer subjects were recruited; 50 smokers of each of 1-2 mg, 4-6 mg and 9-10 mg ISO tar yield cigarettes and 50 non-smokers (NS). Smokers underwent two periods of home smoking, each followed by residence in a clinic. Smoking was permitted ad libitum, and spent cigarette filters, cigarette consumption data, 24h urine, as well as plasma and saliva samples were collected. Significant correlations (p<0.001) were found between MLE and the relevant biomarker for each smoke constituent. The Pearson correlation coefficients (r) were 0.83 (nicotine), 0.76 (NNK), 0.82 (acrolein) and 0.63 (pyrene). Mean MLE estimates for nicotine, NNK and pyrene showed a dose response in line with ISO tar yield smoked, with 10 mg > 4 mg >1 mg, and for acrolein 10 mg> 4 mg > *1mg (where * indicates not significant at 95% confidence level). The mean exposure estimates from biomarkers for nicotine, NNK and acrolein also showed a dose response in line with ISO tar yield with 10 mg > 4 mg > 1 mg > NS, and for pyrene 10 mg > *4 mg> 1 mg> NS. This study shows that estimates of exposure obtained by filter analysis and biomarkers of exposure correlate significantly over a wide range of smoke exposures and that filter analysis may provide a simple and effective alternative to biomarkers for estimating smokers' exposure.

The effect of tobacco blend additives on the retention of nicotine and solanesol in the human respiratory tract and on subsequent plasma nicotine concentrations during cigarette smoking.

The influence of the tobacco additives diammonium hydrogen phosphate (DAP) and urea on the delivery and respiratory tract retention of nicotine and solanesol and on the uptake of nicotine into venous blood was investigated in 10 smokers under mouth-hold and 75 and 500 mL inhalation conditions. Three cigarettes with identical physical specifications were produced from a common lamina tobacco blend. The control cigarette contained nonammoniated reconstituted tobacco sheet (RTS), whereas DAP and other ammonia compounds were added to the RTS of the second cigarette. Urea was added to the tobacco of the third cigarette. The presence of DAP or urea in the test cigarettes did not significantly influence solanesol retention within the mouth during the mouth-hold condition. Nicotine retention within the mouth during the mouth-hold condition was, however, significantly higher for the DAP cigarette (64.3 +/- 10.5%) than for the urea (53.3 +/- 11.3%) or control cigarette (46.3 +/- 8.6%), but this did not result in an increase in nicotine uptake into venous blood. Solanesol retentions during the 75 and 500 mL inhalation volume conditions and nicotine retentions during the 75 mL inhalation volume condition were not significantly different for the three cigarette types. Although the nicotine retention approached 100% with each cigarette type during the 500 mL inhalation condition, the nicotine retention for the urea-treated cigarette (99.6 +/- 0.2%) was marginally, but statistically, significant, higher than for the control (99.1 +/- 0.5%) and DAP-treated cigarettes (98.8 +/- 0.6%). There were no statistically significant differences between the indices of nicotine uptake into venous blood for the three cigarette types in any of the inhalation conditions.