Urinary Biomarkers of Exposure to Volatile Organic Compounds from the Population Assessment of Tobacco and Health Study Wave 1 (2013-2014).

Volatile organic compounds (VOCs) are ubiquitous in the environment. In the United States (U.S.), tobacco smoke is the major non-occupational source of exposure to many harmful VOCs. Exposure to VOCs can be assessed by measuring their urinary metabolites (VOCMs). The Population Assessment of Tobacco and Health (PATH) Study is a U.S. national longitudinal study of tobacco use in the adult and youth civilian non-institutionalized population. We measured 20 VOCMs in urine specimens from a subsample of adults in Wave 1 (W1) (2013-2014) to characterize VOC exposures among tobacco product users and non-users. We calculated weighted geometric means (GMs) and percentiles of each VOCM for exclusive combustible product users (smokers), exclusive electronic cigarette (e-cigarette) users, exclusive smokeless product users, and tobacco product never users. We produced linear regression models for six VOCMs with sex, age, race, and tobacco user group as predictor variables. Creatinine-ratioed levels of VOCMs from exposure to acrolein, crotonaldehyde, isoprene, acrylonitrile, and 1,3-butadiene were significantly higher in smokers than in never users. Small differences of VOCM levels among exclusive e-cigarette users and smokeless users were observed when compared to never users. Smokers showed higher VOCM concentrations than e-cigarette, smokeless, and never users. Urinary VOC metabolites are useful biomarkers of exposure to harmful VOCs.

Nitromethane Exposure from Tobacco Smoke and Diet in the U.S. Population: NHANES, 2007-2012.

Nitromethane is a known toxicant and suspected human carcinogen. Exposure to nitromethane in a representative sample of the civilian, noninstitutionalized population in the United States ≥12 years old was assessed using 2007-2012 National Health and Nutritional Examination Survey (NHANES) data. Nitromethane was detected in all 8000 human blood samples collected, of which 6730 were used for analyses reported here. Sample-weighted median blood nitromethane was higher among exclusive combusted tobacco users (exclusive smokers; 774 ng/L) than nonusers of tobacco products (625 ng/L). In stratified sample-weighted regression analysis, smoking 0.5 pack of cigarettes per day was associated with a statistically significant increase in blood nitromethane by 150 ng/L, and secondhand smoke exposure (serum cotinine >0.05 ng/mL and <10 ng/mL) was statistically significant with a 31.1 ng/L increase in blood nitromethane. Certain dietary sources were associated with small but statistically significant increases in blood nitromethane. At median consumption levels, blood nitromethane was associated with an increase of 7.55 ng/L (meat/poultry), 9.32 ng/L (grain products), and 14.5 ng/L (vegetables). This is the first assessment of the magnitude and relative source apportionment of nitromethane exposure in the U.S. population.

Ethylbenzene and styrene exposure in the United States based on urinary mandelic acid and phenylglyoxylic acid: NHANES 2005-2006 and 2011-2012.

Ethylbenzene and styrene are air toxicants with widespread nonoccupational exposure sources, including tobacco smoke and diet. Ethylbenzene and styrene (EB/S) exposure was quantified from their common metabolites measured in spot urine samples obtained from participants (≥6 years old) in the 2005-2006 and 2011-2012 cycles of the National Health and Nutrition Examination Survey (NHANES; N = 4690). EB/S metabolites mandelic acid (MA) and phenylglyoxylic acid (PGA) were measured using ultra-high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). MA and PGA were detected in 98.9% and 90.6% of tested urine specimens, respectively. Exclusive smokers had 2-fold and 1.6-fold higher median urinary MA and PGA, respectively, compared with non-users. Sampleweighted regression analysis among exclusive smokers showed that smoking 0.5 pack cigarettes per day significantly increased MA (+97.9 µg/L) and PGA (+69.3 µg/L), controlling for potential confounders. In comparison, exposure from the median daily dietary intake of grain products increased MA by 1.95 µg/L and was not associated with statistically significant changes in urinary PGA levels. Conversely, consuming vegetables and fruit was associated with decreased MA and PGA. These results confirm tobacco smoke as a major source of ethylbenzene and styrene exposure for the general U.S. population.

Quantification of 19 Aldehydes in Human Serum by Headspace SPME/GC/High-Resolution Mass Spectrometry.

Sources of human aldehyde exposure include food additives, combustion of organic matter (tobacco smoke), water disinfection byproducts via ozonation, and endogenous processes. Aldehydes are potentially carcinogenic and mutagenic, and chronic human aldehyde exposure has raised concerns about potential deleterious health effects. To aid investigations of human aldehyde exposure, we developed a novel method to measure 19 aldehydes released from Schiff base protein adducts in serum using controlled acid hydrolysis, solid-phase microextraction (SPME), gas chromatography (GC), and high-resolution mass spectrometry (HRMS). Aldehydes are released from Schiff base protein adducts through acid hydrolysis, and are quantified in trace amounts (µg/L) using stable isotope dilution. Detection limits range from 0.1 to 50 µg/L, with calibration curves spanning 3 orders of magnitude. The analysis of fortified quality control material over a three-month period showed excellent precision and long-term stability (3-22% CV) for samples stored at -70 °C. The intraday precision is also excellent (CV, 1-10%). The method accuracy ranges from 89 to 108% for all measured aldehydes, except acrolein and crotonaldehyde, two aldehydes present in tobacco smoke; their analysis by this method is not considered robust due in part to their reactivity in vivo. However, results strongly suggest that propanal, butanal, isobutanal, and isopentanal levels in smokers are higher than levels in nonsmokers, and thus may be useful as biomarkers of tobacco smoke exposure. This method will facilitate large epidemiological studies involving aldehyde biomonitoring to examine nonoccupational environmental exposures.

A regioselective Huisgen reaction inside a Keplerate polyoxomolybdate nanoreactor.

A 1,3-dipolar cycloaddition reaction taking place quantitatively between propiolic acid "guests" and azide functions previously attached to binding sites within the cavity of a {Mo(132)}-type Keplerate reproducibly gives a 2 : 1 ratio of 1,4- and 1,5-triazoles.