Tobacco-Specific Nitrosamines in Current Commercial Large Cigars, Cigarillos, and Little Cigars.

We measured levels of nitrosonornicotine (NNN) and 4-[methyl(nitroso)amino]-1-(3-pyridinyl)-1-butanone (NNK), the two most carcinogenic tobacco-specific nitrosamines, in the filler, binder, and wrapper of 50 cigars: 19 large cigars, 23 cigarillos, and 8 little cigars. The average NNN and NNK levels were 10.6 and 3.70 µg/g, respectively. These levels are 5- and 7-fold higher, respectively, than those of commercial cigarettes. The differences in NNN and NNK levels between cigars and cigarettes reflect differences in tobacco blends and tobacco treatments, such as fermentation. The average tobacco NNN and NNK levels of large cigars were 3- and 5-fold higher than those of cigarillos and little cigars, respectively. Large cigars also exhibited a significantly broader range of NNN and NNK than cigarillos and little cigars. The NNN and NNK levels in cigarillos are comparable to those of little cigars. These results are consistent with earlier studies finding that cigarillos and little cigars have similar tobacco blends with lower NNN and NNK content than large cigar tobacco blends.

Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI.

BACKGROUND: The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung. METHODS: BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes. RESULTS: State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%). CONCLUSIONS: Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States. (Funded by the National Cancer Institute and others.).

Mouth Level Intake of Nicotine from Three Brands of Little Filtered Cigars with Widely Differing Product Characteristics Among Adult Consumers.

Little filtered cigars are tobacco products with many cigarette-like characteristics. However, despite cigars falling under the U.S. Food and Drug Administration regulatory authority, characterizing flavors, which are still allowed in little filtered cigars, and filter design may influence how people use the products and the resulting exposure to harmful and potentially harmful constituents. We estimated nicotine mouth level intake (MLI) from analyses of little cigar filter butt solanesol levels, brand characteristics, carbon monoxide boost, and puff volume in 48 dual cigarette/cigar users during two repeat bouts of ad lib smoking of three little filtered cigar brands. Mean nicotine MLI for the three brands was significantly different with Swisher Sweets (0.1% ventilation) Cherry at 1.20 mg nicotine, Cheyenne Menthol (1.5%) at 0.63 mg, and Santa Fe unflavored (49%) at 0.94 mg. The association between nicotine MLI and puff volume was the same between Cheyenne Menthol and Santa Fe unflavored. However, these were different from Swisher Sweets Cherry. At least five main factors─flavor, ventilation, filter design, nicotine delivery related to tar, and user puff volume─may directly or indirectly impact MLI and its association with other measures. We found that users of little filtered cigars that have different filter ventilation and flavor draw dissimilar amounts of nicotine from the product, which may be accompanied by differences in exposure to other harmful smoke constituents.

Hydrogen Cyanide and Aromatic Amine Yields in the Mainstream Smoke of 60 Little Cigars.

Mainstream smoke yields of hydrogen cyanide (HCN) and three aromatic amines, 1-aminonaphthalene, 2-aminonaphthalene, and 4-aminobiphenyl, from 60 little cigar brands currently on the US market were measured for both International Organization for Standardization (ISO) and Canadian Intense (CI) smoking regimens. The smoke yields are compared with those from 50 cigarette products measured by Counts et al. of Philip Morris USA (PMUSA) in 2005 [Counts et al. Regul. Toxicol. Pharmacol. 2005 41, 185-227] and 50 cigarette products measured by the Centers for Disease Control and Prevention (CDC) in cooperation with the Food and Drug Administration (FDA) in 2012 [Tynan et al. Consumption of Cigarettes and Combustible Tobacco: United States, 2000-2011. In Morbidity and Mortality Weekly Report; Centers for Disease Control and Prevention, 2012; 565-580]. For the little cigars, the average HCN yield with the ISO smoking regimen is 335 µg/cigar (range: 77-809 µg/cigar), which is 332% higher than the average of 50 PMUSA 2005 cigarettes and 243% higher than the average of 50 CDC/FDA 2012 cigarettes. For the CI smoking regimen, the average HCN yield is 619 µg/cigar (range: 464-1045 µg/cigar), which is 70.5% higher than the average of 50 PMUSA 2005 cigarettes and 69% higher than the average of the 50 CDC/FDA 2012 cigarettes. For aromatic amines, the average ISO smoking regimen smoke yields are 36.6 ng/cigar (range: 15.9-70.6 ng/cigar) for 1-aminonaphthalene, 24.6 ng/cigar (range: 12.3-36.7 ng/cigar) for 2-aminonaphthalene, and 5.6 ng/cigar (range: 2.3-17.2 ng/cigar) for 4-aminobiphenyl. The average ISO yields of aromatic amines from little cigars are 141% to 210% higher compared to the average yields of 50 PMUSA cigarettes. The average CI smoke regimen yields are 73.0 ng/cigar (range: 32.1-112.2 ng/cigar) for 1-aminonaphthalene, 45.2 ng/cigar (range: 24.6-74.8 ng/cigar) for 2-aminonaphthalene, and 12.7 ng/cigar (range: 5.5-37.5 ng/cigar) for 4-aminobiphenyl. The average CI aromatic amine yields are 143% to 220% higher compared to the average yields of 50 PMUSA cigarettes, almost identical to the relative yields under the ISO smoking regimen. Both HCN and aromatic amine yields are 1.5× to 3× higher for the tested little cigars than for the conventional cigarettes; however, there are notable differences in the relationships of these yields to certain product characteristics, such as weight, ventilation, and tobacco type. The higher smoke yields of these compounds from little cigars indicates that cigar smokers may be at risk of a higher exposure to HCN and aromatic amines on a per stick basis and thus increased health concerns.

Early Changes in Puffing Intensity When Exclusively Using Open-Label Very Low Nicotine Content Cigarettes.

INTRODUCTION: In response to reducing cigarette nicotine content, people who smoke could attempt to compensate by using more cigarettes or by puffing on individual cigarettes with greater intensity. Such behaviors may be especially likely under conditions where normal nicotine content (NNC) cigarettes are not readily accessible. The current within-subject, residential study investigated whether puffing intensity increased with very low nicotine content (VLNC) cigarette use, relative to NNC cigarette use, when no other nicotine products were available. AIMS AND METHODS: Sixteen adults who smoke daily completed two four-night hotel stays in Charleston, South Carolina (United States) in 2018 during which only NNC or only VLNC cigarettes were accessible. We collected the filters from all smoked cigarettes and measured the deposited solanesol to estimate mouth-level nicotine delivery per cigarette. These estimates were averaged within and across participants, per each 24-h period. We then compared the ratio of participant-smoked VLNC and NNC cigarette mouth-level nicotine with the ratio yielded by cigarette smoking machines (when puffing intensity is constant). RESULTS: Average mouth-level nicotine estimates from cigarettes smoked during the hotel stays indicate participants puffed VLNC cigarettes with greater intensity than NNC cigarettes in each respective 24-h period. However, this effect diminished over time (p < .001). Specifically, VLNC puffing intensity was 40.0% (95% CI: 29.9, 53.0) greater than NNC puffing intensity in the first period, and 16.1% (95% CI: 6.9, 26.0) greater in the fourth period. CONCLUSION: Average puffing intensity per cigarette was elevated with exclusive VLNC cigarette use, but the extent of this effect declined across four days. IMPLICATIONS: In an environment where no other sources of nicotine are available, people who smoke daily may initially attempt to compensate for cigarette nicotine reduction by puffing on individual cigarettes with greater intensity. Ultimately, the compensatory behavior changes required to achieve usual nicotine intake from VLNC cigarettes are drastic and unrealistic. Accordingly, people are unlikely to sustain attempts to compensate for very low cigarette nicotine content.

Comparison of Mainstream Smoke Yields between Linear and Rotary Smoking Machines and Evaluation of "Super Pad" Extraction for Linear Smoking Machines.

Two-tail t test statistical analyses of International Organization for Standardization nonintense and Canadian Intense mainstream smoke yields of total particulate matter, tar, nicotine, and carbon monoxide from cigarettes show that mean quantities are generally higher for a linear smoking machine at a 95% confidence level but a rotary smoking machine has better precision. A novel "super pad" analysis concept combines four smaller filter pads from a linear smoking machine, resulting in increased mean constituent yields and reduced variability. Although measurement variability is still greater than that of rotary machines, super padding may be useful to reduce the variance caused by linear smoking machines.

Volatile Organic Compounds in Mainstream Smoke of Sixty Domestic Little Cigar Products.

The mainstream smoke yields of five volatile organic compounds (VOCs) were determined from 60 commercial U.S. little cigar products under ISO 3308 and Canadian Intense (CI) smoking regimens on linear smoking machines using a gas sampling bag collection. The five VOCs, 1,3-butadiene, acrylonitrile, benzene, isoprene, and toluene were analyzed using an automated GC/MS analytical method validated for measuring various VOCs in mainstream smoke. The VOCs range in amounts from micrograms to milligrams per little cigar. VOC deliveries vary considerably among the little cigar products under the ISO smoking regimen primarily due to varying filter ventilation. Under the CI smoking regimen where filter ventilation is blocked, the delivery range narrows, although individual and total VOC yields are approximately 2 fold higher than those under the ISO smoking regimen. Correlation analysis reveals strong associations between acrylonitrile and 1,3-butadiene or toluene under the ISO smoking regimen. Compared to cigarettes, little cigars delivered substantially higher VOC mainstream smoke yields under both ISO and CI smoking regimens. Moreover, little cigar smoke also contains higher VOCs than cigarette smoke when adjusted for mass of tobacco.

Tobacco-Specific Nitrosamines in the Tobacco and Mainstream Smoke of Commercial Little Cigars.

Cigars are among the broad variety of tobacco products that have not been as extensively studied and characterized as cigarettes. Small cigars wrapped in a tobacco-containing sheet, commonly referred to as little cigars, are a subcategory that are similar to conventional cigarettes with respect to dimensions, filters, and overall appearance. Tobacco-specific nitrosamines (TSNAs) are carcinogens in the tobacco used in both little cigars and cigarettes. This study uses a validated high-performance liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) method to measure the TSNAs 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) in the tobacco filler and the nonintense International Organization for Standardization smoking regimen, ISO 3308, and the newer ISO 20778 Cigarette Intensive (CI) smoking regimen mainstream smoke of 60 commercial little cigars. Tobacco filler NNK and NNN quantities ranged from 26 to 2950 and 1440 to 12 100 ng/g tobacco, respectively. NNK and NNN by the ISO nonintense smoking regimen ranged from 89 to 879 and 200 to 1540 ng/cigar, respectively; by the CI regimen, NNK and NNN ranged from 138 to 1570 and 445 to 2780 ng/cigar, respectively. The average transfer (%) for NNK and NNN from tobacco filler to mainstream smoke was 24% and 36% by the ISO nonintense and CI smoking regimens, respectively. By the ISO nonintense and CI smoking regimens, mainstream smoke NNK and NNN yields showed a moderate to strong correlation (ISO nonintense, R2 = 0.60-0.68, p < 0.0001; CI, R2 = 0.78-0.81, p < 0.0001) with tobacco filler NNK and NNN quantities. In addition, the mainstream smoke NNK and NNN yields of little cigars were determined to be 3- to 5-fold higher compared to previously tested commercial cigarettes. The mainstream smoke NNK and NNN yields have wide variation among commercial little cigars and suggest that, despite design similarities to cigarettes, machine-smoke yields of carcinogenic TSNAs are higher in little cigars.

Characterization of Total and Unprotonated (Free) Nicotine Content of Nicotine Pouch Products.

INTRODUCTION: Nicotine pouch products, oral smokeless products that contain nicotine but no tobacco leaf material, have recently entered the US marketplace. Available data indicate sales of these products in the United States have increased since 2018; however, the extent of use among US youth and adults is uncertain. METHODS: To assay the chemistry of these emerging tobacco products, we analyzed 37 nicotine pouch brands from six total manufacturers. Almost all of the products had flavor descriptors (36 of 37), such as mint, licorice, coffee, cinnamon, and fruit. The amount of free nicotine, the form most easily absorbed, was calculated for each product using total nicotine, product pH, the appropriate pKa, and the Henderson-Hasselbalch equation. RESULTS: Nicotine pouch products varied in pouch content mass, moisture content (1.12%‒47.2%), alkalinity (pH 6.86‒10.1), and % free nicotine (7.7%‒99.2%). Total nicotine content ranged from 1.29 to 6.11 mg/pouch, whereas free nicotine ranged from 0.166 to 6.07 mg/pouch. These findings indicate that nicotine and pH levels found in some of these nicotine pouches are similar to conventional tobacco products, such as moist snuff and snus, and that most of these pouch products are flavored. CONCLUSIONS: Although these products likely lack many tobacco-related chemicals, each product analyzed contained nicotine, which is both addictive and can harm human health. Given that nicotine pouches may appeal to a spectrum of users, from novice to experienced users, it is important to include these emerging tobacco products in tobacco control research, policy, and practice. IMPLICATIONS: These "tobacco-free" nicotine pouches have similar pH and nicotine content to conventional tobacco products, such as moist snuff and snus. Although they lack many tobacco-related chemicals, most are highly flavored which could increase experimentation from new users. Given that nicotine pouches may appeal to a spectrum of users, from novice to experienced users, in terms of their flavors and nicotine content, it is important to examine and include these emerging tobacco products as they relate to tobacco control research, policy, and practice.

Evaluation of Bronchoalveolar Lavage Fluid from Patients in an Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injury - 10 States, August-October 2019.

CDC, the Food and Drug Administration (FDA), state and local health departments, and multiple public health and clinical partners are investigating a national outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). Based on data collected as of October 15, 2019, 86% of 867 EVALI patients reported using tetrahydrocannabinol (THC)-containing products in the 3 months preceding symptom onset (1). Analyses of THC-containing product samples by FDA and state public health laboratories have identified potentially harmful constituents in these products, such as vitamin E acetate, medium chain triglyceride oil (MCT oil), and other lipids (2,3) (personal communication, D.T. Heitkemper, FDA Forensic Chemistry Center, November 2019). Vitamin E acetate, in particular, might be used as an additive in the production of e-cigarette, or vaping, products; it also can be used as a thickening agent in THC products (4). Inhalation of vitamin E acetate might impair lung function (5-7).

Development of a Cigarette Tobacco Filler Standard Reference Material.

A new tobacco filler Standard Reference Material (SRM) has been issued by the National Institute of Standards and Technology (NIST) in September 2016 with certified and reference mass fraction values for nicotine, N-nitrosonornicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and volatiles. The constituents have been determined by multiple analytical methods with measurements at NIST and at the Centers for Disease Control and Prevention, and with confirmatory measurements by commercial laboratories. This effort highlights the development of the first SRM for reduced nicotine and reduced tobacco-specific nitrosamines with certified values for composition.

Caffeine Concentrations in Coffee, Tea, Chocolate, and Energy Drink Flavored E-liquids.

INTRODUCTION: Most electronic cigarettes (e-cigarettes) contain a solution of propylene glycol/glycerin and nicotine, as well as flavors. E-cigarettes and their associated e-liquids are available in numerous flavor varieties. A subset of the flavor varieties include coffee, tea, chocolate, and energy drink, which, in beverage form, are commonly recognized sources of caffeine. Recently, some manufacturers have begun marketing e-liquid products as energy enhancers that contain caffeine as an additive. METHODS: A Gas Chromatography-Mass Spectrometry (GC-MS) method for the quantitation of caffeine in e-liquids was developed, optimized and validated. The method was then applied to assess caffeine concentrations in 44 flavored e-liquids from cartridges, disposables, and refill solutions. Products chosen were flavors traditionally associated with caffeine (ie, coffee, tea, chocolate, and energy drink), marketed as energy boosters, or labeled as caffeine-containing by the manufacturer. RESULTS: Caffeine was detected in 42% of coffee-flavored products, 66% of tea-flavored products, and 50% of chocolate-flavored e-liquids (limit of detection [LOD] - 0.04 µg/g). Detectable caffeine concentrations ranged from 3.3 µg/g to 703 µg/g. Energy drink-flavored products did not contain detectable concentrations of caffeine. Eleven of 12 products marketed as energy enhancers contained caffeine, though in widely varying concentrations (31.7 µg/g to 9290 µg/g). CONCLUSIONS: E-liquid flavors commonly associated with caffeine content like coffee, tea, chocolate, and energy drink often contained caffeine, but at concentrations significantly lower than their dietary counterparts. Estimated daily exposures from all e-cigarette products containing caffeine were much less than ingestion of traditional caffeinated beverages like coffee. IMPLICATIONS: This study presents an optimized and validated method for the measurement of caffeine in e-liquids. The method is applicable to all e-liquid matrices and could potentially be used to ensure regulatory compliance for those geographic regions that forbid caffeine in e-cigarette products. The application of the method shows that caffeine concentrations and estimated total caffeine exposure from e-cigarette products is significantly lower than oral intake from beverages. However, because very little is known about the effects of caffeine inhalation, e-cigarette users should proceed with caution when using caffeine containing e-cigarette products. Further research is necessary to determine associated effects from inhaling caffeine.

Quantification of three chlorinated dialkyl phosphates, diphenyl phosphate, 2,3,4,5-tetrabromobenzoic acid, and four other organophosphates in human urine by solid phase extraction-high performance liquid chromatography-tandem mass spectrometry.

Polybrominated diphenyl ethers (PBDEs), produced as flame retardants worldwide, have been phased-out in many countries, and chlorinated and non-chlorinated organophosphates and non-PBDE brominated formulations (e.g., Firemaster 550 (FM550)) have entered the consumers' market. Recent studies show that components of organophosphate esters and FM550 are frequently detected in many products common to human environments. Therefore, urinary metabolites of these compounds can be used as human exposure biomarkers. We developed a method to quantify nine compounds in 0.4 mL urine: diphenyl phosphate (DPhP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis-(1-chloro-2-propyl) phosphate, bis-2-chloroethyl phosphate, di-p-cresylphosphate, di-o-cresylphosphate (DoCP), di-n-butyl phosphate, dibenzyl phosphate (DBzP), and 2,3,4,5-tetrabromobenzoic acid. The method relies on an enzymatic hydrolysis of urinary conjugates of the target analytes, automated off-line solid phase extraction, reversed phase high performance liquid chromatography separation, and isotope dilution-electrospray ionization tandem mass spectrometry detection. The method is high-throughput (96 samples/day) with detection limits ranging from 0.05 to 0.16 ng mL-1. Spiked recoveries were 90-113 %, and interday imprecision was 2-8 %. We assessed the suitability of the method by analyzing urine samples collected from a convenience sample of adults (n = 76) and from a group of firefighters (n = 146). DPhP (median, 0.89; range, 0.26-5.6 ng mL-1) and BDCPP (median, 0.69; range, 0.31-6.8 ng mL-1) were detected in all of the non-occupationally exposed adult samples and all of the firefighter samples (DPhP [median, 2.9; range, 0.24-28 ng mL-1], BDCPP [median, 3.4; range, 0.30-44 ng mL-1]); DBzP and DoCP were not detected in any samples.

Maternal perchlorate exposure in pregnancy and altered birth outcomes.

BACKGROUND: At high medicinal doses perchlorate is known to decrease the production of thyroid hormone, a critical factor for fetal development. In a large and uniquely exposed cohort of pregnant women, we recently identified associations between environmental perchlorate exposures and decreased maternal thyroid hormone during pregnancy. Here, we investigate whether perchlorate might be associated with birthweight or preterm birth in the offspring of these women. METHODS: Maternal urinary perchlorate, serum thyroid hormone concentrations, birthweight, gestational age, and urinary nitrate, thiocyanate, and iodide were collected in 1957 mother-infant pairs from San Diego County during 2000-2003, a period when the county's water supply was contaminated with perchlorate. Associations between perchlorate exposure and birth outcomes were examined using linear and logistic regression analyses adjusted for maternal age, weight, race/ethnicity, and other factors. RESULTS: Perchlorate was not associated with birth outcomes in the overall population. However, in analyses confined to male infants, log10 maternal perchlorate concentrations were associated with increasing birthweight (ß=143.1gm, p=0.01), especially among preterm births (ß=829.1g, p<0.001). Perchlorate was associated with male preterm births ≥2500g (odds ratio=3.03, 95% confidence interval=1.09-8.40, p-trend=0.03). Similar associations were not seen in females. CONCLUSIONS: This is the first study to identify associations between perchlorate and increasing birthweight. Further research is needed to explore the differences we identified related to infant sex, preterm birth, and other factors. Given that perchlorate exposure is ubiquitous, and that long-term impacts can follow altered birth outcomes, future research on perchlorate could have widespread public health importance.

Thyroid antagonists and thyroid indicators in U.S. pregnant women in the Vanguard Study of the National Children's Study.

The sodium iodide-symporter (NIS) mediates uptake of iodide into thyroid follicular cells. This key step in thyroid hormone synthesis is inhibited by perchlorate, thiocyanate (SCN) and nitrate (NO3) anions. When these exposures occur during pregnancy the resulting decreases in thyroid hormones may adversely affect neurodevelopment of the human fetus. Our objectives were to describe and examine the relationship of these anions to the serum thyroid indicators, thyroid stimulating hormone (TSH) and free thyroxine (FT4), in third trimester women from the initial Vanguard Study of the National Children's Study (NCS); and to compare urine perchlorate results with those in pregnant women from the National Health and Nutritional Examination Survey (NHANES). Urinary perchlorate, SCN, NO3, and iodine, serum TSH, FT4, and cotinine were measured and a food frequency questionnaire (FFQ) was administered to pregnant women enrolled in the initial Vanguard Study. We used multiple regression models of FT4 and TSH that included perchlorate equivalent concentration (PEC, which estimates combined inhibitory effects of the anions perchlorate, SCN, and NO3 on the NIS). We used multiple regression to model predictors of each urinary anion, using FFQ results, drinking water source, season of year, smoking status, and demographic characteristics. Descriptive statistics were calculated for pregnant women in NHANES 2001-2012. The geometric mean (GM) for urinary perchlorate was 4.04µg/L, for TSH 1.46mIU/L, and the arithmetic mean for FT4 1.11ng/dL in 359 NCS women. In 330 women with completed FFQs, consumption of leafy greens, winter season, and Hispanic ethnicity were significant predictors of higher urinary perchlorate, which differed significantly by study site and primary drinking water source, and bottled water was associated with higher urinary perchlorate compared to filtered tap water. Leafy greens consumption was associated with higher urinary NO3 and higher urinary SCN. There was no association between urinary perchlorate or PEC and TSH or FT4, even for women with urinary iodine <100µg/L. GM urinary perchlorate concentrations in the full sample (n=494) of third trimester NCS women (4.03µg/L) were similar to pregnant women in NHANES (3.58µg/L).

Perchlorate Exposure Through Water and Milk in Istanbul.

Perchlorate is a chemical pollutant that inhibits iodide uptake and may possibly impair thyroid function. Our previous study found widespread perchlorate exposure in non-pregnant, non-lactating, healthy women residing in Istanbul. The aim of this study is to assess the relative amounts of perchlorate exposure attributable to consumption of municipal water, bottled water and boxed milk available in Istanbul. Only trace levels of perchlorate were found in treated municipal water (58 % detectable, mean = 0.13 µg/L, maximum = 0.75 µg/L) and bottled water (7.4 % detectable, mean = 

A High Throughput Method for Estimating Mouth-Level Intake of Mainstream Cigarette Smoke.

INTRODUCTION: We developed a high throughput method for estimating smoker's mainstream smoke intake on a per-cigarette basis by analyzing discarded cigarette butts. This new method utilizes ultraviolet/visible (UV-Vis) spectrophotometric analysis of isopropanol-soluble smoke particulate matter extracted from discarded cigarette filters. METHODS: When measured under a wide range of smoking conditions for a given brand variant, smoking machine delivery of nicotine, benzene, polycyclic aromatic hydrocarbons, and tobacco-specific nitrosamines can be related to the overall filter extract absorbance at 360 nm. Once this relationship has been established, UV-Vis analysis of a discarded cigarette filter butt gives a quantitative measure of a smoker's exposure to these analytes. RESULTS: The measured mainstream smoke constituents correlated closely (correlation coefficients from 0.9303 to 0.9941) with the filter extract absorbance. These high correlations held over a wide range of smoking conditions for 2R4F research cigarettes as well as popular domestic cigarette brands sold in the United States. CONCLUSIONS: This low cost, high throughput method is suitable for high volume analyses (hundreds of samples per day) because UV-Vis spectrophotometry, rather than mass spectrometry, is used for the cigarette filter butt analysis. This method provides a stable and noninvasive means for estimating mouth-level delivery of many mainstream smoke constituents. The ability to gauge the mouth-level intake of harmful chemicals and total mainstream smoke for cigarette smokers in a natural setting on a cigarette-by-cigarette basis can provide insights on factors contributing to morbidity and mortality from cigarette smoking, as well as insights on strategies related to smoking cessation.

CO-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women.

BACKGROUND: Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy OBJECTIVES: We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. METHODS: We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (±2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. RESULTS: Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4-0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. CONCLUSIONS: Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy.