The acceptability of smokeless tobacco products depends on nicotine levels.

Understanding the role nicotine plays in initiating and sustaining addiction has been of interest for the scientific community and general population, with the idea that low levels of nicotine will reduce abuse liability associated with smokeless tobacco products. Previously, research has relied on subjective assessments to determine consumer acceptability, but these measures cannot provide a characterization of the physiological responses associated with nicotine use. Consumer acceptability arises from psychological and neurophysiological factors, thus establishing the need to use subjective and objective measurements in conjunction. This study provides a comprehensive characterization of the subjective and objective effects of smokeless tobacco product use with varying levels of nicotine. EEG data were recorded before and after the use of four different smokeless tobacco products and one control product over five separate visits, with participants arriving to each visit after 12 h of tobacco abstinence. These products have distinct consumer acceptability levels and patterns of use characteristics ranging from starter products to those used primarily by established users. Subjective results showed that smokeless tobacco products with higher levels of nicotine were more successful in reducing craving and more reinforcing than those with lower levels. These results were concordant with the activity present in the EEG recordings where products with high nicotine levels produced larger changes in the amplitude of the event-related signal than those with low levels. This study is fundamental in understanding the relationship between subjective and objective smokeless tobacco acceptability measurements, as mediated by the different levels of nicotine in each product.

Novel Nicotine Delivery Systems.

Electronic nicotine delivery systems (ENDS) are devices that contain a power source, a heating element, and a tank or cartridge containing an "e-liquid," which is a mixture of nicotine and flavoring in a glycerol-propylene glycol vehicle. Their increasing popularity among adolescents might be attributed to aggressive marketing in physical venues, social media outlets, as well as irreversible changes caused by nicotine in the developing brains of youth and young adults, predisposing them to addictive behaviors. Adolescent ENDS users were 4 times more likely to initiate cigarette smoking, and the odds of quitting smoking were lower and, in many instances, delayed for those using ENDS. ENDS also renormalize cigarette-like behaviors, such as inhaling/exhaling smoke. The oral cavity is the initial point of contact of ENDS and the first affected system in humans. Oral health depends on an intricate balance in the interactions between oral bacteria and the human immune system, and dysbiosis of oral microbial communities underlies the etiology of periodontitis, caries, and oral cancer. Emerging evidence from subjects with periodontitis as well as periodontally healthy subjects demonstrates that e-cigarette use is associated with a compositional and functional shift in the oral microbiome, with an increase in opportunistic pathogens and virulence traits.

Effect of cigarette menthol content on mainstream smoke emissions.

The 2009 Family Smoking Prevention and Tobacco Control Act empowered the U.S. Food and Drug Administration to study "the impact of the use of menthol in cigarettes on the public health, including such use among children, African Americans, Hispanics and other racial and ethnic minorities," and develop recommendations. Current scientific evidence comparing human exposures between menthol and nonmenthol smokers shows mixed results. This is largely because of the many differences between commercial menthol and nonmenthol cigarettes other than their menthol content. We conducted an innovative study using two types of test cigarettes: a commercial nonmenthol brand that we mentholated at four different levels, and Camel Crush, a commercial cigarette containing a small capsule in the filter that releases menthol solution into the filter when crushed. Cigarettes were machine-smoked at each of the menthol levels investigated, and the total particulate matter (TPM) was collected on a quartz fiber filter pad and analyzed by gas chromatography/mass spectrometry for menthol, nicotine, tobacco-specific nitrosamines (TSNAs), polycyclic aromatic hydrocarbons (PAHs), cotinine, and quinoline. The mainstream smoke was also monitored continuously in real time on a puff-by-puff basis for seven gas-phase constituents (acetaldehyde, acetonitrile, acrylonitrile, benzene, 1,3-butadiene, isoprene, and 2,5-dimethylfuran), using a proton transfer reaction-mass spectrometer. Average yields (in micrograms/cigarette) for the analytes were determined. Menthol in the TPM samples increased linearly with applied menthol concentration, but the amounts of nicotine along with the target TSNAs, PAHs, cotinine, and quinoline in the cigarettes remained essentially unchanged. Similarly, yields of the targeted volatile organic compounds (VOCs) in whole smoke from the mentholated nonmenthol cigarettes that were measured in real-time were largely unaffected by their menthol levels. In the Camel Crush cigarettes, however, the VOC yields appeared to increase in the presence of menthol, especially in the gas phase. Although we succeeded in characterizing key mainstream smoke constituents in cigarettes that differ only in menthol content, further study is needed to definitively answer whether menthol affects exposure to selected cigarette constituents and thereby influences harm.

Distribution of 2,4-D in air and on surfaces inside residences after lawn applications: comparing exposure estimates from various media for young children.

We collected indoor air, surface wipes (floors, table tops, and window sills), and floor dust samples at multiple locations within 11 occupied and two unoccupied homes both before and after lawn application of the herbicide 2,4-D. We measured residues 1 week before and after application. We used collected samples to determine transport routes of 2,4-D from the lawn into the homes, its subsequent distribution between the indoor surfaces, and air concentration as a function of airborne particle size. We used residue measurements to estimate potential exposures within these homes. After lawn application, 2,4-D was detected in indoor air and on all surfaces throughout all homes. Track-in by an active dog and by the homeowner applicator were the most significant factors for intrusion. Resuspension of floor dust was the major source of 2,4-D in indoor air, with highest levels of 2,4-D found in the particle size range of 2.5-10 microm. Resuspended floor dust was also a major source of 2,4-D on tables and window sills. Estimated postapplication indoor exposure levels for young children from nondietary ingestion may be 1-10 microg/day from contact with floors, and 0.2-30 microg/day from contact with table tops. These are estimated to be about 10 times higher than the preapplication exposures. By comparison, dietary ingestion of 2,4-D is approximately 1.3 microg/day.

Design and evaluation of a breath-analysis system for biological monitoring of volatile compound.

To ensure the health and safety of workers, integrated industrial hygiene methodologies often include biological monitoring of the workers to help understand their exposure to chemicals. To this end, a field-portable breath-analysis system was developed and tested to measure selected solvents in exhaled air. The exhaled breath data were evaluated using a physiologically based pharmacokinetic (PBPK) model to relate exposure to tissue dose. The system was designed to monitor workers every time they entered or left a work environment--a vast improvement over current 8-hour integrated monitoring strategies. The system combines (1) chemical dosimeters to measure airborne contaminant levels (analyzed in the field/ workplace); (2) real-time breath analysis to quantitate exposure; and 3) PBPK models to estimate internal target tissue dose. To evaluate the system, field tests were conducted at two locations: (1) at an incinerator in Tennessee monitoring benzene and toluene exposures; and (2) a waste repackaging facility in Washington State where hexane, trimethylbenzene, and methylene chloride was monitored. Exhaled breath was sampled and analyzed before and after each specific job task, which ranged from 15 min to 8 hours in duration. In both field studies several volunteers had posttask breath levels higher than pretask levels. The greatest increase corresponded to 573 ppb for methylene chloride and 60 ppb for toluene. Compared with breath analysis, the chemical dosimeters underpredicted the dosimetry, particularly for longer sampling intervals when the volume of air sampled may have diluted exposures. The results of the field studies illustrate the utility of monitoring workers for exposures throughout the day, particularly when job-specific tasks may indicate a potential for exposure.

Residential environmental measurements in the national human exposure assessment survey (NHEXAS) pilot study in Arizona: preliminary results for pesticides and VOCs.

A major objective of the National Human Exposure Assessment Survey (NHEXAS) performed in Arizona was to conduct residential environmental and biomarker measurements of selected pesticides (chlorpyrifos, diazinon), volatile organic compounds (VOCs; benzene, toluene, trichloroethene, formaldehyde, 1,3-butadiene), and metals for total human exposure assessments. Both personal (e.g., blood, urine, dermal wipes, 24 h duplicate diet) and microenvironmental (e.g., indoor and outdoor air, house dust, foundation soil) samples were collected in each home in order to describe individual exposure via ingestion, inhalation, and dermal pathways, and to extrapolate trends to larger populations. This paper is a preliminary report of only the microenvironmental and dermal wipe data obtained for the target pesticides and VOCs, and provides comparisons with results from similar studies. Evaluations of total exposure from all sources and pathways will be addressed in future papers. The pesticides and VOCs all showed log-normal distributions of concentrations in the Arizona population sampled, and in most cases were detected with sufficient frequency to allow unequivocal description of the concentration by media at the 90th, 75th, and 50th (median) percentiles. Those combinations of pollutant and media, in which a large fraction of the measurements were below the detection limit of the analysis method used, included trichloroethene, 1,3-butadiene, and formaldehyde in outdoor air; chlorpyrifos and diazinon in outdoor air; and diazinon in dermal and window sill wipes. In general, indoor air concentrations were higher than outdoor air concentrations for all VOCs and pesticides investigated, and VOC levels were in good agreement with levels reported in other studies. In addition, the agreement obtained between co-located VOC samplers indicated that the low-cost diffusional badges used to measure concentrations are probably adequate for use in future monitoring studies. For the pesticides, the median levels found in indoor samples agreed well with other studies, although the levels corresponding to the upper 0.1-1% of the population were considerably higher than levels reported elsewhere, with indoor air levels as high as 3.3 and 20.5 microg/m3 for chlorpyrifos and diazinon, respectively. These data showed excellent correlation (Pearson and Spearman correlation coefficients of 0.998 and 0.998, respectively) between chlorpyrifos in indoor air and in the corresponding dermal wipes, and relatively poor correlation between chlorpyrifos in dust (microg/g or microg/ml) and dermal wipes (Pearson=0.055 microg/g and 0.015 microg/m2; Spearman=0.644 microg/g and 0.578 microg/m2). These data suggest the importance of dermal penetration of semi-volatiles as a route of residential human exposure.

Effect of water temperature on dermal exposure to chloroform.

We have developed and applied a new measurement methodology to investigate dermal absorption of chloroform while bathing. Ten subjects bathed in chlorinated water while breathing pure air through a face mask. Their exhaled breath was delivered to a glow discharge source/ion trap mass spectrometer for continuous real-time measurement of chloroform in the breath. This new method provides abundant data compared to previous discrete time-integrated breath sampling methods. The method is particularly well suited to studying dermal exposure because the full face mask eliminates exposure to contaminated air. Seven of the 10 subjects bathed in water at two or three different temperatures between 30 degrees C and 40 degrees C. Subjects at the highest temperatures exhaled about 30 times more chloroform than the same subjects at the lowest temperatures. This probably results from a decline in blood flow to the skin at the lower temperatures as the body seeks to conserve heat forcing the chloroform to diffuse over a much greater path length before encountering the blood. These results suggest that pharmacokinetic models need to employ temperature-dependent parameters. Two existing models predict quite different times of about 12 min and 29 min for chloroform flux through the stratum corneum to reach equilibrium. At 40 degrees C, the time for the flux to reach a near steady-state value is 6-9 min. Although uptake and decay processes involve several body compartments, the complicating effect of the stratum corneum lag time made it difficult to fit multiexponential curves to the data; however, a single-compartment model gave a satisfactory fit.