BACKGROUND: Acrolein is a highly reactive alpha, beta unsaturated aldehyde and respiratory irritant. Acrolein is formed during combustion (e.g. burning tobacco or biomass), during high-temperature cooking of foods, and in vivo as a product of oxidative stress and polyamine metabolism. No biomonitoring reference data has been reported to characterize acrolein exposure of the U.S. population. OBJECTIVES: Our goals were to: a) evaluate two acrolein metabolites in urine - N-Acetyl-S-(3-hydroxypropyl)-L-cysteine (3HPMA) and N-acetyl-S-(2-carboxyethyl)-L-cysteine (CEMA) - as biomarkers of exposure to acrolein for the U.S. population by age, sex, race, and smoking status; and b) assess tobacco smoke as a predictor of acrolein exposure. METHODS: We analyzed urine from National Health and Nutrition Examination Survey (NHANES 2005-2006) participants ≥ 12 years-old (n = 2,866) for 3HPMA and CEMA using ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC/ESI-MSMS). Sample-weighted linear regression models stratified for non-tobacco users vs. tobacco smokers (as defined by serum cotinine and self-report) characterized the association of urinary 3HPMA and CEMA with tobacco smoke exposure, adjusting for urinary creatinine, sex, age, and race/ethnicity. RESULTS: 3HPMA and CEMA levels were higher among tobacco smokers (cigarettes, cigars and pipe users) compared with non-tobacco users. The median 3HPMA levels for tobacco smokers and non-tobacco were 1089 and 219 microg/g creatinine respectively. Similarly, median CEMA levels were 203 microg/g creatinine for tobacco smokers and 78.8 microg/g creatinine for non-tobacco users. Regression analysis showed that serum cotinine was a significant positive predictor (p <0.0001) of both 3HPMA and CEMA among tobacco smokers. CONCLUSIONS: Tobacco smoke was a significant predictor of acrolein exposure in the U.S. population.

Tobacco use is a major contributor to premature morbidity and mortality. The measurement of nicotine and its metabolites in urine is a valuable tool for evaluating nicotine exposure and for nicotine metabolic profiling-i.e., metabolite ratios. In addition, the minor tobacco alkaloids-anabasine and anatabine-can be useful for monitoring compliance in smoking cessation programs that use nicotine replacement therapy. Because of an increasing demand for the measurement of urinary nicotine metabolites, we developed a rapid, low-cost method that uses isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneously quantifying nicotine, six nicotine metabolites, and two minor tobacco alkaloids in smokers' urine. This method enzymatically hydrolyzes conjugated nicotine (primarily glucuronides) and its metabolites. We then use acetone pretreatment to precipitate matrix components (endogenous proteins, salts, phospholipids, and exogenous enzyme) that may interfere with LC-MS/MS analysis. Subsequently, analytes (nicotine, cotinine, hydroxycotinine, norcotinine, nornicotine, cotinine N-oxide, nicotine 1'-N-oxide, anatabine, and anabasine) are chromatographically resolved within a cycle time of 13.5 minutes. The optimized assay produces linear responses across the analyte concentrations typically found in urine collected from daily smokers. Because matrix ion suppression may influence accuracy, we include a discussion of conventions employed in this procedure to minimize matrix interferences. Simplicity, low cost, low maintenance combined with high mean metabolite recovery (76-99%), specificity, accuracy (0-10% bias) and reproducibility (2-9% C.V.) make this method ideal for large high through-put studies.

Perchlorate is ubiquitous in the environment, leading to human exposure and potential impact on thyroid function. Nitrate can also competitively inhibit iodide uptake at the sodium-iodide symporter and thus reduce thyroid hormone production. This study investigates the intake of perchlorate, nitrate, and iodide attributable to direct and indirect tap water consumption. The National Health and Nutrition Examination Survey collected tap water samples and consumption data from 3262 U.S. residents during the years 2005-2006. The median perchlorate, nitrate, and iodide levels measured in tap water were 1.16, 758, and 4.55 mug/L, respectively. Measured perchlorate levels were below the United States Environmental Protection Agency (U.S. EPA) drinking water equivalent level for perchlorate (24.5 mug/L). Significant correlations were found between iodide and nitrate levels (r = 0.17, p < 0.0001) and perchlorate and nitrate levels (r = 0.25, p < 0.0001). On the basis of 24 h recall, 47% of the study participants reported drinking tap water; 89% reported either direct or indirect consumption of tap water. For the adult population (age ≥ 20 yrs) the median tap water consumption rate was 11.6 mL/kg-day. Using individual tap water consumption data and body weight, we estimated the median perchlorate, nitrate, and iodide dose attributable to tap water as 9.11, 11300, and 43.3 ng/kg-day, respectively, for U.S. adults. This perchlorate exposure dose from tap water is relatively small compared to the total perchlorate exposure dose previously characterized for the U.S. adults (median 64 ng/kg-day) and the U.S. EPA reference dose (700 ng/kg-day).