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Many novel tobacco products have been developed in recent years. Although many may emit lower levels of several toxicants, their risk in the long term remains unclear. We previously published a method for the exposure assessment of mixtures that can be used to compare the changes in cumulative exposure to carcinogens among tobacco products. While further developing this method by including more carcinogens or to explore its application to non-cancer endpoints, we encountered a lack of data that are required for better-substantiated conclusions regarding differences in exposure between products. In this special communication, we argue the case for more data on adverse health effects, as well as more data on the composition of the emissions from tobacco products. Such information can be used to identify significant changes in relevance to health using the cumulative exposure method with different products and to substantiate regulatory decisions.

Comparing the harmful health effects related to two different tobacco products by applying common risk assessment methods to each individual compound is problematic. We developed a method that circumvents some of these problems by focusing on the change in cumulative exposure (CCE) of the compounds emitted by the two products considered. The method consists of six steps. The first three steps encompass dose-response analysis of cancer data, resulting in relative potency factors with confidence intervals. The fourth step evaluates emission data, resulting in confidence intervals for the expected emission of each compound. The fifth step calculates the change in CCE, probabilistically, resulting in an uncertainty range for the CCE. The sixth step estimates the associated health impact by combining the CCE with relevant dose-response information. As an illustrative case study, we applied the method to eight carcinogens occurring both in the emissions of heated tobacco products (HTPs), a novel class of tobacco products, and tobacco smoke. The CCE was estimated to be 10- to 25-fold lower when using HTPs instead of cigarettes. Such a change indicates a substantially smaller reduction in expected life span, based on available dose-response information in smokers. However, this is a preliminary conclusion, as only eight carcinogens were considered so far. Furthermore, an unfavorable health impact related to HTPs remains as compared to complete abstinence. Our method results in useful information that may help policy makers in better understanding the potential health impact of new tobacco and related products. A similar approach can be used to compare the carcinogenicity of other mixtures., (© 2020 The Authors. Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.)

Reducing the concentration of reactive carbonyl species (RCS) in e-cigarette emissions represents a major goal to control their potentially harmful effects. Here, we adopted a novel strategy of trapping carbonyls present in e-cigarette emissions by adding polyphenols in e-liquid formulations. Our work showed that the addition of gallic acid, hydroxytyrosol and epigallocatechin gallate reduced the levels of carbonyls formed in the aerosols of vaped e-cigarettes, including formaldehyde, methylglyoxal and glyoxal. Liquid chromatography mass spectrometry analysis highlighted the formation of covalent adducts between aromatic rings and dicarbonyls in both e-liquids and vaped samples, suggesting that dicarbonyls were formed in the e-liquids as degradation products of propylene glycol and glycerol before vaping. Short-term cytotoxic analysis on two lung cellular models showed that dicarbonyl-polyphenol adducts are not cytotoxic, even though carbonyl trapping did not improve cell viability. Our work sheds lights on the ability of polyphenols to trap RCS in high carbonyl e-cigarette emissions, suggesting their potential value in commercial e-liquid formulations., Competing Interests: Authors Bruna de Falco, W. Edryd Stephens and Alberto Fiore are associated with a patent pending on content relating to this manuscript., (This journal is © The Royal Society of Chemistry.)

Analyzing harmful constituents in e-cigarette aerosols typically involves adopting a methodology used for analyzing tobacco smoke. Cambridge filter pads (CFP) are the basis of numerous protocols for analyzing the various classes of compounds representing 93 harmful and potentially harmful constituents identified in tobacco smoke by the FDA. This paper describes a simplified method for trapping the low volatility components of e-cigarette aerosols using a single trapping procedure followed by physical extraction. The trap is a plug of amorphous silica fibers (0.75 g of 4 μm diameter) within a 10 mL syringe inserted between the e-cigarette mouthpiece and the pump of the vaping machine. The method is evaluated for emissions from three generations of e-cigarette device (Kangertech CE4, EVOD, and Subox Mini-C). On average, the silica wool traps about 94% of the vaporized liquid mass in the three devices and higher levels of condensate is retained before reaching saturation compared with CFP. The condensate is then physically extracted from the silica wool plug using a centrifuge. Condensate is then available for use directly in multiple analytical procedures or toxicological experiments. The method is tested by comparison with published analyses of carbonyls, among the most potent toxicants and carcinogens in e-cigarette emissions. Ranges for HPLC-DAD analyses of carbonyl-DNPH derivatives in a laboratory formulation of e-liquid are formaldehyde (0.182 ± 0.023 to 9.896 ± 0.709 μg puff -1 ), acetaldehyde (0.059 ± 0.005 to 0.791 ± 0.073 μg puff -1 ), and propionaldehyde (0.008 ± 0.0001 to 0.033 ± 0.023 μg puff -1 ); other carbonyls are identified and quantified. Carbonyl concentrations are also consistent with published experiments showing marked increases with variable power settings (10W to 50W). Compared with CFPs, e-cigarette aerosol collection by silica wool requires only one vaping session for multiple analyte groups, traps more condensate per puff, and collects more condensate before saturation.

Background: Quantifying relative harm caused by inhaling the aerosol emissions of vapourised nicotine products compared with smoking combustible tobacco is an important issue for public health., Methods: The cancer potencies of various nicotine-delivering aerosols are modelled using published chemical analyses of emissions and their associated inhalation unit risks. Potencies are compared using a conversion procedure for expressing smoke and e-cigarette vapours in common units. Lifetime cancer risks are calculated from potencies using daily consumption estimates., Results: The aerosols form a spectrum of cancer potencies spanning five orders of magnitude from uncontaminated air to tobacco smoke. E-cigarette emissions span most of this range with the preponderance of products having potencies<1% of tobacco smoke and falling within two orders of magnitude of a medicinal nicotine inhaler; however, a small minority have much higher potencies. These high-risk results tend to be associated with high levels of carbonyls generated when excessive power is delivered to the atomiser coil. Samples of a prototype heat-not-burn device have lower cancer potencies than tobacco smoke by at least one order of magnitude, but higher potencies than most e-cigarettes. Mean lifetime risks decline in the sequence: combustible cigarettes >> heat-not-burn >> e-cigarettes (normal power)≥nicotine inhaler., Conclusions: Optimal combinations of device settings, liquid formulation and vaping behaviour normally result in e-cigarette emissions with much less carcinogenic potency than tobacco smoke, notwithstanding there are circumstances in which the cancer risks of e-cigarette emissions can escalate, sometimes substantially. These circumstances are usually avoidable when the causes are known., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Illicit tobacco products have a disproportionately negative effect on public health. Counterfeits and cheap whites as well as legal brands smuggled from countries not adopting track and trace technologies will require novel forensic tools to aid the disruption of their supply chains., Methods: Data sets of trace element concentrations in tobacco were obtained using X-ray fluorescence spectrometry on samples of legal and illicit products mainly from Europe. Authentic and counterfeit products were discriminated by identifying outliers from data sets of legal products using Mahalanobis distance and graphical profiling methods. Identical and closely similar counterfeits were picked out using Euclidean distance, and counterfeit provenance was addressed using chemometric methods to identify geographical affinities., Results: Taking Marlboro as an exemplar, the major brands are shown to be remarkably consistent in composition, in marked contrast to counterfeits bearing the same brand name. Analysis of 35 illicit products seized in the European Union (EU) indicates that 18 are indistinguishable or closely similar to Marlboro legally sold in the EU, while 17 are sufficiently different to be deemed counterfeit, among them being 2 counterfeits so closely similar that their tobaccos are likely to come from the same source. The tobacco in the large majority of counterfeits in this data set appears to originate in Asia., Conclusions: Multivariate and graphical analysis of trace elements in tobacco can effectively authenticate brands, crossmatch illicit products across jurisdictions and may identify their geographical sources., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objectives: The current study examines physical cigarette design characteristics and tobacco metal content of cigarettes obtained from 5 countries to determine how these properties vary for cigarette brands, both within and across countries with different dominant manufacturers., Methods: Cigarette packs were collected from International Tobacco Control Policy Evaluation Survey (ITC) participants in the U.S., the U.K., Mauritius, Mexico, and Thailand. Cigarettes were assessed for physical and design properties (eg, ventilation, pressure drop, rod density, weight) by published methods, and for metal content (As, Cd, Ni, Pb) by X-ray fluorescence spectrometry., Results: Significant differences in cigarette design and toxic metal concentrations were observed between countries and between manufacturers within countries. Filter ventilation, which is strongly predictive of machine-measured tar and nicotine levels, varied most widely across countries. Ni and Cd were highest in Thailand (2.23ug/g and 1.64ug/g, respectively); As was highest in Mexico (0.29ug/g) and Pb was highest in the U.K. (0.43 ug/g)., Conclusions: Parties to the FCTC should consider the adoption of uniform product standards related to cigarette design, emissions, and tobacco content that would reduce population health risks., Competing Interests: Conflict Of Interest Statement RJO is a member of the Tobacco Products Scientific Advisory Committee, U.S. Food and Drug Administration. KMC has provided expert testimony on behalf of plaintiffs in cases against the tobacco industry. JFT and GTF have provided expert testimony on behalf of governments in legal proceedings involving the tobacco industry. WES, RVC, and BVF declare they have no conflicts.

Background: Metals of primary health concern can accumulate in the tobacco plant and contribute to smokers' exposures to carcinogens, a significant cause of the millions of smoking-related deaths in China each year. These exposures are due to the smoker's addiction to nicotine., Objective: This study sought to explore toxic heavy metal and nicotine concentrations in the tobacco of Chinese cigarette brands purchased in 2009 and 2012, as well as its regional variation., Methods: Cigarette packs for this study were purchased from seven Chinese cities in 2009 and 2012, and 91 pairs of cigarettes were matched based on UPC for comparison. Ten cigarette sticks were randomly selected from each pack and tested using polarised energy dispersive X-ray fluorescence (XRF) for arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni) and lead (Pb) concentrations. Nicotine analysis was conducted following Coresta's Recommended Method N°62. Data analysis was conducted using SPSS, encompassing descriptive statistics, correlations and generalised estimating equations to observe changes in brand varieties overtime., Findings: On average, from 2009 to 2012, As, Cd, Cr and Pb concentrations have decreased in Chinese tobacco. Of the seven cities where the cigarette brands were purchased, only four cities showed significant differences of the selected metals from 2009 to 2012. However, there was no significant change in the tobacco nicotine content from 2009 to 2012., Conclusions: Tobacco in Chinese cigarettes purchased in seven geographically disbursed cities contains consistently high levels of metals, including carcinogens like Cd. One source may be the improper use of fertilisers. These numbers should be monitored more carefully and regulated by health officials., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Introduction: While U.S. cigarette consumption has declined, cigar use has steadily increased, for reasons including price compared to cigarettes and the availability of filtered varieties resembling cigarettes, and flavors that have been banned in cigarettes (excluding menthol). Little published data exists on the design characteristics of such cigars., Methods: A variety of filtered cigar brands were tested for design characteristics such as whole cigar weight, ventilation, and per-cigar tobacco weight. Cigar sticks were then sent to the University of St. Andrews for metal concentration testing of As, Pb, Cr, Ni, and Cd., Results: Large and small cigars were statistically different between cigar weight (p ≤ .001), per-cigar tobacco weight (p = .001), rod diameter (p = .006), and filter diameter (p = .012). The differences in mean ventilation (overall mean = 19.6%, min. = 0.84%, max. = 57.6%) across filtered cigar brands were found to be statistically significant (p = .031), and can be compared to the ventilation of the average of 2013 U.S. Marlboro Red, Gold, and Silver packs at 29% ventilation. There were no significant differences for metal concentrations between cigar types (p = .650), with Pb and As levels being similar to U.S. 2009 cigarette concentrations, Cd cigar levels being slightly higher, and Cr and Ni levels much lower than cigarette levels., Conclusions: With cigar use rising, and filtered cigars displaying substantial similarities to filtered cigarettes, more research on product characteristics is warranted. Future plans include testing tobacco alkaloid and more observation of cigar weight for tax bracket purposes., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Tobacco smoke is a major risk to the health of its users and arsenic is among the components of smoke present at concentrations of toxicological concern. There are significant variations in human toxicity between inorganic and organic arsenic species and the aim of this study was to determine whether there are predictable relationships among major arsenic species in tobacco that could be useful for risk assessment., Methods: 14 samples of tobacco were studied spanning a wide range of concentrations in samples from different geographical regions, including certified reference materials and cigarette products. Inorganic and major organic arsenic species were extracted from powdered tobacco samples by nitric acid using microwave digestion. Concentrations of arsenic species in these extracts were determined using HPLC-ICPMS., Results: The concentrations of total inorganic arsenic species range from 144 to 3914 μg kg(-1), while organic species dimethylarsinic acid (DMA) ranges from 21 to 176 μg As kg(-1), and monomethylarsonic acid (MA) ranges from 30 to 116 μg kg(-1). The percentage of species eluted compared to the total arsenic extracted ranges from 11.1 to 36.8% suggesting that some As species (possibly macro-molecules, strongly complexed or in organic forms) do not elute from the column. This low percentage of column-speciated arsenic is indicative that more complex forms of arsenic exist in the tobacco. All the analysed species correlate positively with total arsenic concentration over the whole compositional range and regression analysis indicates a consistent ratio of about 4:1 in favour of inorganic arsenic compared with MA + DMA., Conclusions: The dominance of inorganic arsenic species among those components analysed is a marked feature of the diverse range of tobaccos selected for study. Such consistency is important in the context of a WHO expert panel recommendation to regulate tobacco crops and products using total arsenic concentration. If implemented more research would be required to develop models that accurately predict the smoker's exposure to reduced inorganic arsenic species on the basis of leaf or product concentration and product design features.

Arsenic (As) is one of four metals/metalloids in tobacco being considered for regulation. In vitro toxicological response to As varies substantially, determined primarily by valence and compound speciation, and inorganic arsenite (As(III)) compounds are the most toxic to humans. This study uses X-ray absorption near edge structure (XANES) to determine valence states of As from the tobacco plant to the crucial combustion stage that creates respirable smoke. Samples studied include cultivated plants (some burdened with additional As), reference standards, and commercial products, along with smoke condensate and ash from these samples. The relative contributions of As(III) and As(V) to the XANES spectra are analyzed, and a consistent pattern of redox changes emerges. Tobacco leaf and manufactured products tend to be dominated by As(V) whereas combustion produces respirable smoke invariably in As(III) form and ash invariably as As(V). The valence state of precursor tobacco is not a controlling factor because all the As mobilized in smoke is reduced during combustion. This study concludes that tobacco combustion exposes smokers to potentially the most toxic forms of arsenic, and this exposure is magnified in regions where arsenic is present in tobacco crops at relatively high concentrations.

Smoking-related diseases can be attributed to the inhalation of many different toxins, including heavy metals, which have a host of detrimental health effects. The current study reports the levels of arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), and lead (Pb) in cigarettes obtained from adult smokers participating in the 2009 wave of the ITC United States Survey (N = 320). The mean As, Cd, Cr, Ni, and Pb levels were 0.17, 0.86, 2.35, 2.21, and 0.44 µg/g, respectively. There were some differences in metal concentrations of cigarette brands produced by different manufacturers, suggesting differences in the source of tobaccos used by different companies. For Ni, there were significant pairwise differences between Philip Morris U.S. (PMUSA) and R.J. Reynolds (RJR) brands (PMUSA higher; p < 0.001), PMUSA and other manufacturer (OM) brands (PMUSA higher; p < 0.001), and RJR and OM brands (RJR higher; p = 0.006). For Cr, RJR brands had higher levels than did OM brands (p = 0.02). Levels of As, Cd, and Pb did not differ significantly across manufacturer groups (p > 0.10). Because of the variety of toxic heavy metals in cigarette tobacco, and their numerous negative health effects, metal content in cigarette tobacco should be reduced.

Introduction: Distributed Data Networks (DDNs) offer infrastructure solutions for sharing electronic health data from across disparate data sources to support comparative effectiveness research. Data sharing mechanisms must address technical and governance concerns stemming from network security and data disclosure laws and best practices, such as HIPAA., Methods: The Scalable Architecture for Federated Translational Inquiries Network (SAFTINet) deploys TRIAD grid technology, a common data model, detailed technical documentation, and custom software for data harmonization to facilitate data sharing in collaboration with stakeholders in the care of safety net populations. Data sharing partners host TRIAD grid nodes containing harmonized clinical data within their internal or hosted network environments. Authorized users can use a central web-based query system to request analytic data sets., Discussion: SAFTINet DDN infrastructure achieved a number of data sharing objectives, including scalable and sustainable systems for ensuring harmonized data structures and terminologies and secure distributed queries. Initial implementation challenges were resolved through iterative discussions, development and implementation of technical documentation, governance, and technology solutions.

Background: China is the home to the world's largest cigarette maker, China National Tobacco Company (CNTC), yet little is known publicly about the design and emissions of Chinese cigarettes. CNTC is currently in the process of consolidating its brands and has ambitions to export its cigarettes. Machine-measured tar yields of many of its cigarette brands have also been reduced, similar to what occurred in Western countries from the 1970s through the 1990s with so-called 'low-tar' cigarettes introduced to address consumer concerns about health risks from smoking., Method: The current study examines the design and physical characteristics, labelled smoke emissions and tobacco metals content of leading brands of Chinese cigarettes from seven cities purchased in 2005-6 and in 2007., Results: Findings suggest that similar to most countries, tar levels of Chinese cigarettes are predicted primarily by tobacco weight and filter ventilation. Ventilation explained approximately 50% of variation observed in tar and 60% variation in carbon monoxide yields. We found little significant change in key design features of cigarettes purchased in both rounds. We observed significant levels of various metals, averaging 0.82 μg/g arsenic (range 0.3-3.3), 3.21 μg/g cadmium (range 2.0-5.4) and 2.65 μg/g lead (range 1.2-6.5) in a subsample of 13 brands in 2005-6, substantially higher than contemporary Canadian products., Conclusion: Results suggest that cigarettes in China increasingly resemble those sold in Western countries, but with tobacco containing higher levels of heavy metals. As CNTC looks to export its product around the world, independent surveillance of tobacco product characteristics, including tobacco blend characteristics, will become increasingly important.

The global trade in counterfeit tobacco products is increasingly taking market share from legal brands in many parts of the developed world, with attendant adverse economic, health, criminal, and other societal impacts. Knowing the geographical source is central to developing new strategies for curbing this illicit trade, and here, the potential of environmental pollen extracted from manufactured cigarettes is examined. Two samples representing U.S. and Chinese brands were investigated for their pollen content. Results indicate that tobacco leaf very efficiently captures environmental pollen (about 1800 and 12,600 grains per cigarette, respectively) with no detectable self-contamination by the tobacco plant. In both cases, the flora is typical of open space environments, but pollen type counts indicate very different distributions of species. This preliminary investigation indicates that palynology has the potential to constrain geographical source(s) of tobacco, particularly if regionally localized species can be recognized among the pollen.

An exploratory XPS and FTIR investigation of the surfaces of bulk quartz powders widely used in toxicological studies (DQ12 and Min-U-Sil 5) was carried with the aim of correlating surface features with toxicity as reflected by indicators of biological response. Some patches of amorphous silica were identified as well as varying amounts of calcium but none of these features correlated with biological response. No evidence of widely-quoted surface silanol (SiOH) structures was found in this investigation and the possibility that FTIR artefacts have been previously misidentified as silanol structures is discussed.

Objective: To estimate the extent to which tar, nicotine and carbon monoxide (TNCO) yields are dependent on cigarette design features such as burn rate, filter ventilation and paper porosity, and to consider the implications for human exposure and the regulation of TNCO emissions. A related aim is to determine whether accurate prediction of TNCO yields is possible using only simple physical parameters., Design and Methods: Datasets that include quantitative design parameters as well as measurements of TNCO yields collected under standard conditions with vents unblocked (International Organization for Standardization) and under intense conditions with vents fully blocked (Health Canada) were compiled from the literature (primarily US and UK brands). Forward stepwise multiple regression analysis is used to assess the relative importance of each design feature in explaining variability in the observed emissions. Using randomly split data subsets, multiple linear regression is used to model the dependence of TNCO yields on design features in the training subset and validated against the test subset. Tar and carbon monoxide correlate with many of the particulate- and volatile-phase toxins in smoke, and brand values normalised to nicotine yield are used as surrogate measures of exposure within the bounds defined by non-intense and intense smoking protocols., Results and Conclusions: Filter ventilation is the dominant control on measured TNCO emissions, but other factors including burn rate, amount of tobacco and paper porosity also contribute. Yields are predictable with reasonable accuracy and precision using only measured physical parameters. Surrogate exposure indicators suggest that filter ventilation does not lead to any reduction in exposure and that highly ventilated (low-yield) brands may actually increase exposure to the more volatile toxins.

A significant flux of heavy metals, among other toxins, reaches the lungs through smoking. Consequently, contaminated soil is usually avoided for tobacco cultivation. Here we compare the heavy metal concentrations in tobacco from a sample of 47 counterfeit products, representative of the substantial market for these products in the U.K., with their genuine equivalents and find significantly higher concentrations of heavy metals in the counterfeits. Trace element patterns suggest that over-application of fertilizers (phosphate and/or nitrate) is the most likely cause. Nitrogen isotopes showed no significant enrichment in 15N (delta15N range from +1.1 to +4.6% in counterfeits and from +2.5 to +3.3% in genuine tobaccos) as might be expected from a sewage or manure source of nitrate, and a mineral phosphate source is considered the more likely source of metals. Stable carbon isotopes in the same tobaccos have a wide range (delta13C -18.3 to -26.4%), indicating the influence of multiple controls during cultivation and possibly post-harvesting. A review of the health effects of heavy metal transfer from tobacco via smoke to the lungs indicates that habitual smokers of counterfeits may be risking additional harm from high levels of cadmium and possibly other metals.

Munchausen syndrome by proxy is the act of one person fabricating or inducing an illness in another to meet his or her own emotional needs through the treatment process. The diagnosis is poorly understood and controversial. We report here the case of a 6-year-old boy who presented with possible pneumonia, nausea, vomiting, and diarrhea and whose mother was suspected of Munchausen syndrome by proxy.

An electrooptical realization of an optimal phase estimator for phase modulated communication signals is described in this work. The realization uses an electrooptical processor to perform a 1-D convolution in a 2-D space and a computer to complete the calculations. The processor is a realization of the time domain recursive nonlinear filter. This paper describes the nonlinear filter theory, the electrooptical realization,and the performance of the processor.

In equivalence-formation tasks, retarded children have been ovserved to use fewer action concepts than expected on the basis of their MA. When tasks were structured and praise for performance was introduced, mildly retarded children performed like nonretarded children in most respects, except for total number of responses. Moderately retarded children of the same MA showed improved performance but still performed more poorly than either of the other two groups. The implications of these findings were discussed.

The inadequate use of action concepts by mentally retarded children has been reported in several recent studies, but little is yet known concerning the level of performance that might be expected to result from direct instruction designed to remedy this deficit. In the present study, it was found that three different instructional approaches yielded higher adjusted posttest scores. The highest adjusted posttest score was yielded by an instructional program in which motion picture sequences were used. This program was significantly more effective than two paralled programs, one using photographic slides, and the other using live demonstration by a teacher. An explanation for these findings was suggested.

An error in calculation of MAs of the moderately retarded subjects in the above study raises significant questions about the findings that their use of action concepts is less than that of mildly retarded subjects of the same MA. Their reduced performance may instead be attributable to some unknown extent to their lower MA.