Yan S. Ding

Levels of Tobacco-Specific Nitrosamines and Polycyclic Aromatic Hydrocarbons in Mainstream Smoke from Different Tobacco Varieties

It has been estimated that one in every five cancer deaths worldwide are related to tobacco use. According to the IARC, 10 polycyclic aromatic hydrocarbons (PAH) and 8 tobacco-specific nitrosamines (TSNA), as well as at least 45 other compounds or substances found in tobacco smoke, are potential human carcinogens. The levels of these carcinogens in contents of tobacco and smoke emissions vary between different tobacco products. We evaluated mainstream smoke emissions from cigarettes made with different types of tobacco to examine the relation between their deliveries of TSNAs and PAHs and any possible influence from tobacco nitrate content. To investigate the contribution of tobacco content to mainstream cigarette smoke deliveries without confounders such as filter design, filter ventilation, and paper porosity, we used custom-made, research-grade, unfiltered cigarettes that contained bright, burley, oriental, reconstituted, or mixtures of these tobaccos. Our findings confirm results from other researchers that tobacco type can influence the mainstream smoke delivery of nicotine, TSNAs, and PAHs. However, we found that the effect varies among individual compounds. In addition, we observed a statistically significant relationship between nitrate content and mainstream smoke 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK); nitrate level also influenced the mainstream smoke deliveries of the summed total of the 10 PAHs identified by IARC as potential human carcinogens. The influence of nitrate on mainstream smoke NNK and PAH levels were of different magnitude and direction. Our results tend to indicate an inverse relation exists between NNK and PAH deliveries when considering different tobacco blends. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3366–71)

Simultaneous determination of six mercapturic acid metabolites of volatile organic compounds in human urine.

The widespread exposure to potentially harmful volatile organic compounds (VOCs) merits the development of practical and accurate exposure assessment methods. Measuring the urinary concentrations of VOC mercapturic acid (MA) metabolites provides noninvasive and selective information about recent exposure to certain VOCs. We developed a liquid chromatography-tandem mass spectrometry method for quantifying urinary levels of six MAs: N-acetyl-S-(2-carboxyethyl)-L-cysteine (CEMA), N-acetyl-S-(3-hydroxypropyl)-L-cysteine (HPMA), N-acetyl-S-(2-hydroxy-3-butenyl)-L-cysteine (MHBMA), N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA), N-acetyl-S-(2-hydroxyethyl)-L-cysteine (HEMA), and N-acetyl-S-(phenyl)-L-cysteine (PMA). The method provides good accuracy (102% mean accuracy) and high precision (3.5% mean precision). The sensitivity (limits of detection of 0.01-0.20 microg/L) and wide dynamic detection range (0.025-500 microg/L) make this method suitable for assessing VOC exposure of minimally exposed populations and those with significant exposures, such as cigarette smokers. We used this method to quantify MA levels in urine collected from smokers and nonsmokers. Median levels of creatinine-corrected CEMA, HPMA, MHBMA, DHBMA, HEMA, and PMA among nonsmokers (n = 59) were 38.1, 24.3, 21.3, 104.7, 0.9, and 0.5 microg/g creatinine, respectively. Among smokers (n = 61), median levels of CEMA, HPMA, MHBMA, DHBMA, HEMA, and PMA were 214.4, 839.7, 10.2, 509.7, 2.2, and 0.9 microg/g creatinine, respectively. All VOC MAs measured were higher among smokers than among nonsmokers, with the exception of MHBMA.

Polycyclic Aromatic Hydrocarbons in the Mainstream Smoke of Popular U.S. Cigarettes.

The mainstream smoke yields of 14 polycyclic aromatic hydrocarbons (PAHs) were determined for 50 commercial U.S. cigarettes using a validated GC/MS method with the International Organization of Standardization (ISO) and Canadian Intense (CI) smoking machine regimens. PAH mainstream smoke deliveries vary widely among the commercial cigarettes with the ISO smoking regimen primarily because of differing filter ventilation. The more abundant, lower molecular weight PAHs such as naphthalene, fluorene, and phenanthrene predominantly comprise the total PAH yields. In contrast, delivery yields of high molecular weight PAHs such as benzo[b]fluoranthene, benzo[e]pyrene, benzo[k]fluoranthene, and benzo[a]pyrene (BaP) are much lower. Comparative analysis of PAHs deliveries shows brand specific differences. Correlation analysis shows strong positive associations between BaP and most of the other PAHs as well as total PAHs. The results suggest that BaP may be a representative marker for other PAH constituents in cigarette smoke generated from similarly blended tobacco, particularly those PAHs with similar molecular weights and chemical structures.

Effect of charcoal-containing cigarette filters on gas phase volatile organic compounds in mainstream cigarette smoke

Of the chemicals identified to date in mainstream cigarette smoke with known toxicological properties, the volatile organic compounds (VOCs) are considered the most hazardous group owing to their high abundance and toxicity. In this research we evaluate a recently introduced line of cigarettes that contain charcoal in their filters. The amount of charcoal in these filters ranged from 45 mg to 180 mg and were either dispersed among the filter material or contained in a small cavity in the filter segment. Charcoal has long been used for removing VOCs from both water and air. Our findings indicate that these cigarettes reduce machine generated mainstream smoke deliveries of a wide range of VOCs compared to a similar, non-charcoal filtered, cigarette. However, this reduction is dependent not only on the amount of charcoal present but also on the volume of smoke being drawn through the filter. While a brand with 45 mg charcoal reduces VOC delivery under ISO smoking conditions, charcoal saturation and breakthrough occur under more intense smoking conditions. Breakthrough is minimised for brands with the most charcoal. Overall, the brands with the most charcoal are effective at reducing VOC deliveries under even intense smoking conditions.

Semi-volatiles in mainstream smoke delivery from select charcoal-filtered cigarette brand variants

Background It has been reported that charcoal added to cigarette filters selectively removes many of the more volatile chemicals, but it is not clear to what extent charcoal may reduce the delivery of important less volatile chemical constituents in mainstream cigarette smoke. Methods We analysed machine-derived mainstream smoke deliveries (under three smoking regimens) for variants of a charcoal-filtered cigarette commercially test-marketed in the USA, focusing on selected polycyclic aromatic hydrocarbons (PAHs), phenols and tobacco-specific nitrosamines (TSNAs). Results While charcoal-containing filters selectively removed lower molecular weight PAHs from mainstream smoke, they did not significantly remove the heavier and more toxic PAHs studied, such as benzo[a]pyrene, a known carcinogen. Likewise, charcoal-containing filters removed phenols and TSNAs from mainstream smoke to differing amounts depending on the compound, filter design and the smoking regimen. Conclusions The addition of sufficient charcoal to cigarette filters is known to remove many volatile compounds and can potentially reduce deliveries of certain semi-volatile compounds under some machine smoking regimens. Less volatile compounds, with a significant portion in the particulate phase, are less available for selective filtration by charcoal-containing filters than the more volatile compounds that reside predominantly in the gas phase.

Mouth-Level Intake of Benzo[a]pyrene from Reduced Nicotine Cigarettes

Cigarette smoke is a known source of exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), especially benzo[a]pyrene (BaP). Exposure to BaP in cigarette smoke is influenced by how a person smokes and factors, such as tobacco blend. To determine whether sustained use of reduced-nicotine cigarettes is associated with changes in exposure to nicotine and BaP, levels of BaP in spent cigarette filter butts were correlated with levels of BaP in cigarette smoke to estimate mouth-level intake (MLI) of BaP for 72 daily smokers given three progressively reduced nicotine content cigarettes. Urinary cotinine, a marker of nicotine exposure, and urinary 1-hydroxypyrene (1-HOP), a marker of PAH exposure, were measured throughout the study. Median daily BaP MLI and urine cotinine decreased in a similar manner as smokers switched to progressively lower nicotine cigarettes, despite relatively constant daily cigarette consumption. 1-HOP levels were less responsive to the use of reduced nicotine content cigarettes. We demonstrate that spent cigarette filter butt analysis is a promising tool to estimate MLI of harmful chemicals on a per cigarette or per-day basis, which partially addresses the concerns of the temporal influence of smoking behavior or differences in cigarette design on exposure.

Development of a Method to Estimate Mouth-Level Benzo[a]pyrene Intake by Filter Analysis

Background: Benzo[a]pyrene (BaP) is one of the most potent carcinogens generated in cigarette smoke. During smoking, cigarette filters trap a significant portion of mainstream smoke benzo[a]pyrene. This trapped portion is proportional to what exits the end of the filter and is drawn into the mouth of smokers. Methods: We developed a new method to estimate mouth-level BaP intake using filter analysis. In this analysis, cigarettes are smoked by a smoking machine using a variety of conditions to yield a range of mainstream smoke deliveries, which approximate a range of human puffing characteristics. Mainstream smoke BaP collected on Cambridge filter pads and the corresponding 1-cm mouth-end cigarette filter butts is extracted, purified by solid-phase extraction, and quantified by high-performance liquid chromatography coupled with a fluorescence detector. On the basis of the amount of BaP retained in cigarette butts and the amount collected on pads, we can relate them using a linear regression model. Results: Using this model and subsequently analyzing cigarette filters collected from smokers, we are able to estimate their mouth-level intakes, which smokers received when they consumed cigarettes. We made a series of measurements using research cigarettes and select commercial cigarettes having a wide range of machine smoke “tar” and nicotine deliveries. Conclusions: In all cases, results indicate a linear relation of BaP between cigarette filter butts and Cambridge filter pads, with R2 ranging from 0.93 to 0.98. Impact: This technique provides a noninvasive means to examine intake on a per cigarette basis to examine both exposure and behavioral aspects of smoking. Cancer Epidemiol Biomarkers Prev; 21(1); 39–44. ©2011 AACR.

In Situ Derivatization and Quantification of Seven Carbonyls in Cigarette Mainstream Smoke

Carbonyls, especially aldehydes, are a group of harmful volatile organic compounds that are found in tobacco smoke. Seven carbonyls are listed on the FDAs harmful and potential harmful constituents list for tobacco or tobacco smoke. Carbonyls have reactive functional groups and thus are challenging to quantitatively measure in cigarette smoke. The traditional method of measuring carbonyls in smoke involves solvent-filled impinger trapping and derivatization. This procedure is labor-intensive and generates significant volumes of hazardous waste. We have developed a new method to efficiently derivatize and trap carbonyls from mainstream smoke in situ on Cambridge filter pads. The derivatized carbonyls are extracted from the pads and subsequently quantified by ultra-high-pressure liquid chromatography coupled with tandem mass spectrometry. The new method has been validated and applied to research and commercial cigarettes. Carbonyl yields from research cigarettes are comparable to those from other published literature data. With a convenient smoke collection apparatus, a 4 min sample analysis time, and a low- or submicrogram detection limit, this new method not only simplifies and speeds the detection of an important class of chemical constituents in mainstream smoke but also reduces reactive losses and provides a more accurate assessment of carbonyl levels in smoke. Excellent accuracy (average 98%) and precision (14% average relative standard deviation in research cigarettes) ensure this new methods sufficient fidelity to characterize conventional combusted tobacco products, with potential application toward new or emerging products.

The use of charcoal in modified cigarette filters for mainstream smoke carbonyl reduction

&NA; Carbonyls are harmful and potentially harmful constituents (HPHCs) in mainstream cigarette smoke (MSS). Carbonyls, including formaldehyde and acrolein, are carcinogenic or mutagenic in a dose‐dependent manner. Past studies demonstrate significant reduction of HPHCs by charcoal filtration. However, limits of charcoal filtration and cigarette design have not yet been investigated in a systematic manner. Objective data is needed concerning the feasibility of HPHC reduction in combustible filtered cigarettes. This systematic study evaluates the effect of charcoal filtration on carbonyl reduction in MSS. We modified filters of ten popular cigarette products with predetermined quantities (100–400 mg) of charcoal in a plug‐space‐plug configuration. MSS carbonyls, as well as total particulate matter, tar, nicotine, carbon monoxide (TNCO), and draw resistance were quantified. Significant carbonyl reductions were observed across all cigarette products as charcoal loading increased. At the highest charcoal loadings, carbonyls were reduced by nearly 99%. Tar and nicotine decreased modestly (<20%) compared to reductions in carbonyls. Increased draw resistance was significant at only the highest charcoal loadings. This work addresses information gaps in the science base that can inform the evaluation of charcoal filtration as an available technological adaptation to cigarette design which reduces levels of carbonyls in MSS. HighlightsEffect of charcoal load on carbonyl removal from smoke was systematically assessed.100 mg charcoal reduced most carbonyls investigated by between 48% and 95%.300 mg and 400 mg charcoal reduced most carbonyls studied by at least 90%.Modest changes to tar, nicotine, and draw resistance occurred with charcoal filters.Data gathered may inform strategies for exposure reduction.