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.

Toxicological assessment of kretek cigarettes: Part 2: kretek and American-blended cigarettes, smoke chemistry and in vitro toxicity.

Two commercial kretek cigarettes typical for the Indonesian market and a reference kretek cigarette were compared to the American-blended reference cigarette 2R4F by smoke chemistry characterization and in vitro cytotoxicity and mutagenicity assessments. Despite the widely diverse designs and deliveries of the selected kretek cigarettes, their smoke composition and in vitro toxicity data present a consistent pattern when data were normalized to total particulate matter (TPM) deliveries. This confirms the applicability of the studies' conclusions to a wide range of kretek cigarette products. After normalization to TPM delivery, nicotine smoke yields of kretek cigarettes were 29-46% lower than that of the 2R4F. The yields of other nitrogenous compounds were also much lower, less than would be expected from the mere substitution of one third of the tobacco filler by clove material. Yields of light molecular weight pyrolytic compounds, notably aldehydes and hydrocarbons, were reduced, while yields of polycyclic aromatic hydrocarbons were unchanged and phenol yield was increased. The normalized in vitro toxicity was lowered accordingly, reflecting the yield reductions in gas-phase cytotoxic compounds and some particulate-phase mutagenic compounds. These results do not support a higher toxicity of the smoke of kretek cigarettes compared to American-blended cigarettes.

Toxicological assessment of kretek cigarettes Part 3: kretek and American-blended cigarettes, inhalation toxicity.

A typical Indonesian kretek cigarette brand and an experimental kretek reference cigarette were compared to the reference cigarette 2R4F in two 90-day inhalation studies. Male and female rats were exposed nose-only to mainstream smoke for 6 hours daily, for 90 consecutive days. Biological endpoints were assessed according to OECD guideline 413, with special emphasis on respiratory tract histopathology and on lung inflammation (broncho-alveolar lavage fluid levels of neutrophils, macrophages and lymphocytes). Histopathological alterations included: in the nose, hyperplasia and squamous metaplasia of the respiratory epithelium and squamous metaplasia and atrophy of the olfactory epithelium; in the larynx, epithelial squamous metaplasia and hyperplasia; in the lungs, accumulation of macrophages in alveoli and goblet cell hyperplasia in bronchial epithelium. The findings were qualitatively consistent with observations from previous similar studies on conventional cigarettes. Compared to 2R4F cigarette, however, kretek smoke exposure was associated with a pronounced attenuation of pulmonary inflammation and less severe histopathological changes in the respiratory tract. Neutrophilic inflammation was also significantly lower (>70%). These results are consistent with the observations made on smoke chemistry and in vitro toxicology. They do not support any increased toxicity of the smoke of kretek cigarettes compared to conventional American-blended cigarettes.

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.

Formation of mainstream cigarette smoke constituents prioritized by the World Health Organization--yield patterns observed in market surveys, clustering and inverse correlations.

The WHO TobReg proposed mandating ceilings on selected smoke constituents determined from the market-specific median of nicotine-normalized yield distributions. Data validating this regulatory concept were obtained from essentially single-blend surveys. This process is strongly impacted by inverse correlations among yields. In the present study, 18 priority WHO smoke constituent yields (nicotine-normalized) were determined (using two smoking regimens) from 262 commercial brands including American, Virginia and local blends from 13 countries. Principal Component Analysis was used to identify yields patterns, clustering of blend types and the inverse correlations causing these clusters. Three principal components explain about 75% of total data variability. PC1 was sensitive to the relative levels of gas- and particle-phase compounds. PC2 and PC3 cluster American- and Virginia-blends, revealing inverse correlations: Nitrogen oxides and amino- or nitroso-aromatic compounds inversely correlate to either formaldehyde and acrolein, or benzo(a)pyrene and di-hydroxybenzenes. These results can be explained by reviewing the processes determining each components smoke delivery. Regulatory initiatives simultaneously targeting selected smoke constituents in markets with mixed blend styles will be strongly impacted by the inverse correlations described. It is difficult to predict the ultimate impact of such regulations on public health, considering the complex chemistry of cigarette smoke formation.

Chemical studies on tobacco smoke LXVIII. Analysis of volatile and tobacco-specific nitrosamines in tobacco products.

The yields of volatile N-nitrosamines in cigarette smoke are primarily dependent upon the nitrate content of the tobacco and, to some extent, on the protein content. Cellulose acetate tips, such as those found on most commercial filter cigarettes, selectively remove at least 70% of the volatile N-nitrosamines, independently of the pH of the weakly acidic or weakly alkaline smoke. So far, three tobacco-specific N-nitrosamines have been detected in tobacco and tobacco smoke. During tobacco processing and smoking, N'-nitrosonornicotine is formed by nitrosation of nicotine and, to a minor degree, by nitrosation of nornicotine, whereas 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone originates from oxidative nitrosation of nicotine. N'-Nitrosoanatabine is formed by nitrosation of the second most abundant tobacco alkaloid, anatabine. The tobacco-specific N-nitrosamines in the smoke arise partly from the tobacco by transfer and partly by nitrosation of the alkaloids during smoking (pyrosynthesis). Preliminary results indicate that cellulose acetate filter tips may selectively remove considerable amounts of the nonvolatile nitrosamines from the smoke.