Role of testing standards in smoke-free product assessments.

Testing standards for tobacco and related products are an important basis for product science-based regulation. The recent emergence and rapid growth of products offering an alternative to continued smoking for adult smokers who would otherwise continue to smoke, urgently calls for the establishment of quality and assessment standards relevant for these products. The two main categories of products under consideration are electronic cigarettes and heated tobacco products, which both deliver nicotine in the aerosol that is not smoke, because tobacco is not burned in the process, and in particular no solid particles are generated as a result. In the case of electronic cigarettes the need for new testing and product standards is well recognized and relevant initiatives are underway, whereas no testing standards specific for heated tobacco products are currently under development. In the present manuscript, a critical review of the applicability of existing testing standards - which were mainly developed for cigarettes, is provided, and a framework approach is proposed toward developing relevant testing standards to be able to compare aerosol yields across different product categories (cigarettes, e-cigarettes, heated tobacco products).

Comparative assessment of HPHC yields in the Tobacco Heating System THS2.2 and commercial cigarettes.

There has been a sustained effort in recent years to develop products with the potential to present less risk compared with continued smoking as an alternative for adult smokers who would otherwise continue to smoke cigarettes. During the non-clinical assessment phase of such products, the chemical composition and toxicity of their aerosols are frequently compared to the chemical composition and toxicity of the smoke from a standard research cigarette - the 3R4F reference cigarette. In the present study, it is demonstrated that results of these analytical comparisons are similar when considering commercially available cigarette products worldwide. A market mean reduction of about 90% is observed on average across a broad range of harmful and potentially harmful constituents (HPHC) measured in the aerosol of a candidate modified risk tobacco product, the Tobacco Heating System 2.2 (THS2.2), compared against the levels of HPHC of cigarettes representative of selected markets; this mean reduction is well in line with the reduction observed against 3R4F smoke constituents in previous studies.

Considerations for comparative tobacco product assessments based on smoke constituent yields.

Cigarette smoke is a complex mixture of more than 8000 smoke constituents. The quantification of selected mainstream smoke constituent yields is one of the methods to evaluating and comparing the performance of different products. Numerous regulatory and scientific advisory bodies have used cigarette smoke constituent yield data for reporting and product comparison purposes. For more than a decade limitations of the indiscriminate application of traditional statistical methods such as the t-test for differences in comparative smoke constituent yield assessments lacking a specific study design, have been highlighted. In the present study, the variability of smoke constituent yields is demonstrated with data obtained under the ISO smoking regime for the Kentucky reference cigarette 3R4F and one commercial brand, analyzed on several occasions between 2007 and 2014. Specifically it is shown that statistically significant differences in the yields of selected smoke constituents do not readily translate to differences between products, and that tolerances need to be defined. To this end, two approaches have been proposed in the literature--minimal detectable differences, and the statistical equivalence. It is illustrated how both approaches provide more meaningful comparison outcomes than the statistical t-test for differences. The present study provides considerations relevant for comparative tobacco product assessments both in the scientific and regulatory contexts.

Investigating predictability of in vitro toxicological assessments of cigarettes: analysis of 7 years of regulatory submissions to Canadian regulatory authorities.

A wealth of in vitro toxicological information on different types of tobaccos and tobacco products has been acquired and published, although the link between in vitro data and impact on human health remains elusive. The present study investigates the possibility of establishing quantitative models for the in vitro toxicological endpoint responses to cigarette smoke. To this end, it relies on information submitted to Canadian health authorities during the period 2006-2012. To our knowledge, this is the first time that published results concerning the influence of such factors as cigarette blend, diameter and filter type on in vitro toxicity are confirmed at the level of a representative range of products on a market. Taking these cigarette design features into account and adding a limited amount of quantitative mainstream smoke composition information, it is shown that, within the boundaries of the considered cigarette design parameters, the in vitro toxicological response can be effectively predicted. In vitro tests of tobacco products are an invaluable initial comparative product assessment tool. The present results reveal the limited value of data from repeated tests on products which do not undergo significant modifications.

Menthol addition to cigarettes using breakable capsules in the filter. Impact on the mainstream smoke yields of the health Canada list constituents.

Cigarettes with menthol capsules embedded in the filter have been introduced recently in many countries. At the same time, concerns have been expressed that filter performance could be affected by the crushing of the capsule therein, altering mainstream smoke constituent yields, ultimately with the potential to impact the toxicity of these products. The present study investigates the possible mechanisms underlying differences in smoke constituent deliveries following the crushing of a menthol capsule in a cigarette filter. It also includes results from a market survey of a selection of commercial cigarette brands with menthol capsules representing the different designs for this type of product available in different markets worldwide. The yields of 46 Health Canada smoke components were determined according to the International Organization for Standardization (ISO) machine-smoking regime. Data obtained from measurements using cigarettes with the capsule crushed and uncrushed were compared. Except for the intended presence of menthol flavors in smoke, no meaningful differences were identified in the yields of the remaining measured particulate-phase smoke constituents. Regarding the gas-phase smoke constituents, it was found that the delivery of lipophilic volatiles was reduced when the capsule was crushed. Delivery of the other measured gas-phase components remained unaffected. The results from investigations performed in this study did not show any meaningful increase in the yield of smoke constituents listed by Health Canada as a result of crushing the menthol capsule in the cigarette filter.

Hydrodynamics and the fluctuation theorem.

The fluctuation theorem is a pivotal result of statistical physics. It quantifies the probability of observing fluctuations which are in violation of the second law of thermodynamics. More specifically, it quantifies the ratio of the probabilities of observing entropy-producing and entropy-consuming fluctuations measured over a finite volume and time span in terms of the rate of entropy production in the system, the measurement volume, and time. We study the fluctuation theorem in computer simulations of planar shear flow. The simulations are performed by employing the method of multiparticle collision dynamics, which captures both thermal fluctuations and hydrodynamic interactions. The main outcome of our analysis is that the fluctuation theorem is verified at any averaging time provided that the measurement volume exhibits a specific dependence on a hydrodynamic time scale.

Differences in cadmium transfer from tobacco to cigarette smoke, compared to arsenic or lead.

Arsenic, cadmium and lead levels in tobacco filler and cigarette smoke were determined in a 568-sample worldwide survey. Median tobacco levels for arsenic, cadmium and lead were 237, 769 and 397 ng/g respectively, comparable to those previously reported albeit somewhat lower for lead and cadmium. Median mainstream smoke yields for arsenic, cadmium and lead were <3.75, 18.2, and <12.8 ng/cig. under ISO, and <8.71, 75.1 and <45.7 ng/cig. under Health Canada Intense (HCI) smoking regime respectively. In the case of cigarettes with activated carbon, a selective retention of cadmium but not lead or arsenic was observed. This effect was more pronounced under ISO than under HCI smoking regimes. Cadmium selective retention by activated carbon was confirmed by testing specially designed prototype cigarettes and the causes for this selective filtration were investigated. The differences between cadmium, arsenic and lead in terms of their speciation in tobaccos and in cigarette smoke could be related to their distribution in the ash, butt, mainstream (in gas-phase and particulate-phase) and sidestream smoke of a smoked cigarette. The possible formation of organometallic cadmium derivatives in the smoke gas-phase is discussed, the presence of which could adequately explain the observed cadmium selective filtration.

Backtracking of colloids: a multiparticle collision dynamics simulation study.

The role of sound in the dynamics of mesoscale systems is typically neglected, since frequently the associated time scales are much smaller than all the other time scales of interest. However, for sufficiently small objects embedded in a solvent with a sufficiently small sound velocity, sound can play a crucial role. In particular, behavior resembling viscoelasticity has been theoretically predicted for nonviscoelastic fluids. This effect is due to the interference of the propagation of sound waves caused by the solute particle's motion and hydrodynamic vortex formation. We demonstrate this effect, known as backtracking, in computer simulations employing the method of multiparticle collision dynamics. We systematically study the influence of sound on the dynamics of the solute particle, and find that it disappears in the long-time limit. Thus, we confirm that sonic effects at the single-particle level can be neglected at sufficiently long times.

Near-surface structure of a bicontinuous microemulsion with a transition region.

The lamellar ordering of bicontinuous microemulsions adjacent to a planar hydrophilic wall is investigated experimentally by grazing-incidence small-angle neutron scattering and theoretically by computer simulations. It is shown that precise depth information in neutron scattering can be obtained by tuning the scattering length density of the overall microemulsion. Neutron reflectometry completes the characterization. The nucleation of a lamellar phase at the wall is observed, and a perforated lamellar transition region is identified at the lamellar-microemulsion interface. The thickness of the lamellar region is about 400 Å, which corresponds to two bilayers.