The objective of the study was to determine the human serum elimination half-life of polybrominated diphenyl ethers (PBDEs) adjusted for ongoing exposure in subjects moving from a higher exposure region (North America) to a lower exposure region (Australia). The study population was comprised of exchange students and long-term visitors from North America moving to Brisbane, Australia (N = 27) and local residents (N = 23) who were followed by repeated serum sampling every other month. The local residents were sampled to adjust for ongoing exposure in Australia. Only one visitor remained in Australia for a period of time similar to the elimination half-life and had a sufficiently high initial concentration of PBDEs to derive a half-life. This visitor arrived in Australia in March of 2011 and remained in the country for 1.5 years. Since the magnitude of PBDE exposure is lower in Australia than in North America we observed an apparent 1st order elimination curve over time from which we have estimated the serum elimination half-lives for BDE28, BDE47, BDE99, BDE100, and BDE153 to be 0.942, 1.19, 1.03, 2.16, and 4.12 years, respectively. Uncertainty in the estimates were estimated using a Monte Carlo simulation. The human serum elimination half-life adjusted for ongoing exposure can allow us to assess the effectiveness and reduction in exposure in the general population following phase out of commercial penta- and octaBDE in 2004 in the United States.

Biomonitoring for heavy metals is important to assess health risks, especially in Arctic communities where rural residents rely on locally harvested foods. However, laboratory testing for blood contaminants is expensive and might not be sustainable for long-term monitoring. We assessed whether pooled specimen biomonitoring could be a part of a plan for blood contaminant surveillance among pregnant women in rural Alaska using existing blood mercury level data from three cross sectional studies of pregnant women. We applied a hypothetical pooled specimen template stratified into 8 demographic groups based on age, coastal or inland residence, and pre-pregnancy weight. The hypothetical geometric mean blood mercury levels were similar to the individual-level geometric means. However, the 95% confidence intervals were much wider for the hypothetical geometric means compared to the true geometric means. Although the variability that resulted from pooling specimens using a small sample made it difficult to compare demographic groups to each other, pooled specimen results could be an accurate reflection of the population burden of mercury contamination in the Arctic in the context of large numbers of biomonitoring samples.

INTRODUCTION: Snus is an oral tobacco product that originated in Sweden. Snus products are available as fine-cut loose tobacco or in pre-portioned porous "pouches." Some snus products undergo tobacco pasteurization during manufacturing, a process that removes or reduces nitrite-forming microbes, resulting in less tobacco-specific nitrosamine content in the product. Some tobacco companies and researchers have suggested that snus is potentially less harmful than traditional tobacco and thus a potential smoking cessation aid or an alternative to continued cigarette consumption. Although snus is available in various countries, limited information exists on snus variants from different manufacturers. METHODS: Moisture, pH, nicotine, and tobacco-specific N'-nitrosamines (TSNAs) were quantified in 64 snus products made by 10 manufacturers in the United States and Northern Europe (NE). Reported means, standard errors, and differences are least-square (LS) estimates from bootstrapped mixed effects models, which accounted for correlation among repeated measurements. Minor alkaloids and select flavors were also measured. RESULTS: Among all product types, moisture (27.4%-59.5%), pH (pH 5.87-9.10), total nicotine (6.81-20.6 mg/g, wet), unprotonated nicotine (0.083-15.7 mg/g), and total TSNAs (390-4,910 ng/g) varied widely. The LS-mean unprotonated nicotine concentration of NE portion (7.72 mg/g, SE = 0.963) and NE loose (5.06 mg/g, SE = 1.26) snus were each significantly higher than US portion snus (1.00 mg/g, SE = 1.56). Concentrations of minor alkaloids varied most among products with the highest total nicotine levels. The LS-mean NNN+NNK were higher in snus sold in the US (1360 ng/g, SE = 207) than in NE (836 ng/g, SE = 132) countries. The most abundant flavor compounds detected were pulegone, eucalyptol, and menthol. CONCLUSION: Physical and chemical characteristics of US and NE products labeled as snus can vary considerably and should not be considered "equivalent". Our findings could inform public health and policy decisions pertaining to snus exposure and potential adverse health effects associated with snus.

Eleven polybrominated diphenyl ether (tri- to deca-BDE) congeners and 2,2',4,4',5,5'-hexabromobiphenyl (BB153) have been measured in pooled serum samples from the National Health and Nutrition Examination Survey (NHANES) for one decade (from survey years 2005/06 through 2013/14). The pools, which are representative of the general noninstitutionalized population of the United States, encompassed thirty-two demographic groups defined by sex, race/ethnicity (Mexican American, non-Hispanic black, non-Hispanic white, and all other race/ethnicities), and age (12-19, >20-39, >40-59, and >/=60 years). The adjusted geometric means were determined in a multiple linear regression model for the six congeners (BDE28, BDE47, BDE99, BDE100, BDE153, and BB153) with detectable concentrations in at least 60% of pools in each of the thirty-two demographic groups; the level of significance for all statistical comparisons thereof were determined. BDE154 and BDE209 were detected in 60% of the NHANES 2011/12 and 2013/14 pools; only these two survey periods were evaluated for these congeners. The percent change in concentration by a 2-year survey period was calculated. All examined PBDEs reported in five survey periods decreased in concentration, except BDE153, for which concentrations increased by 12.0% (95% CI 7.1-16.4) and 8.4% (95% CI 2.9-14.1) for the age groups 40-59 and >/=60 years, respectively; no significant change was observed in younger age groups. Excluding BDE153, we observed larger percentage decreases by a 2-year survey period for the age groups 12-19, 20-39, and >/=60 years compared with the age group 40-59 years. The percentage decrease by a two-year survey period ranged between -19.6% (BDE99, 20-39 years old) and -4.5% (BDE100, 40-59 years old). Although five polybrominated diphenyl ether (PDBE) congeners and BB153 are still frequently detected in the U.S. general population, PBDE concentrations have decreased since 2005-2006, likely, because of changes in manufacturing practices that started in the mid-2000s.

CONTEXT: The Lead and Multielement Proficiency (LAMP) program is an external quality assurance program promoting high-quality blood-lead measurements. OBJECTIVES: To investigate the ability of US laboratories, participating in the Centers for Disease Control and Prevention (CDC) LAMP program to accurately measure blood-lead levels (BLL) 0.70 to 47.5 mug/dL using evaluation criteria of +/-2 mug/dL or 10%, whichever is greater. METHODS: The CDC distributes bovine blood specimens to participating laboratories 4 times per year. We evaluated participant performance over 5 challenges on samples with BLL between 0.70 and 47.5 mug/dL. The CDC sent 15 pooled samples (3 samples shipped in 5 rounds) to US laboratories. The LAMP laboratories used 3 primary technologies to analyze lead in blood: inductively coupled plasma mass spectrometry, graphite furnace atomic absorption spectroscopy, and LeadCare technologies based on anodic stripping voltammetry. Laboratories reported their BLL analytical results to the CDC. The LAMP uses these results to provide performance feedback to the laboratories. SETTING: The CDC sent blood samples to approximately 50 US laboratories for lead analysis. PARTICIPANTS: Of the approximately 200 laboratories enrolled in LAMP, 38 to 46 US laboratories provided data used in this report (January 2017 to March 2018). RESULTS: Laboratory precision ranged from 0.26 mug/dL for inductively coupled plasma mass spectrometry to 1.50 mug/dL for LeadCare instruments. All participating US LAMP laboratories reported accurate BLL for 89% of challenge samples, using the +/-2 mug/dL or 10% evaluation criteria. CONCLUSIONS: Laboratories participating in the CDC's LAMP program can accurately measure blood lead using the current Clinical Laboratory Improvement Amendments of 1988 guidance of +/-4 mug/dL or +/-10%, with a success rate of 96%. However, when we apply limits of +/-2 mug/dL or +/-10%, the success rate drops to 89%. When challenged with samples that have target values between 3 and 5 mug/dL, nearly 100% of reported results fall within +/-4 mug/dL, while 5% of the results fall outside of the acceptability criteria used by the CDC's LAMP program. As public health focuses on lower blood lead levels, laboratories must evaluate their ability to successfully meet these analytical challenges surrounding successfully measuring blood lead. In addition proposed CLIA guidelines (+/-2 mug/dL or 10%) would be achievable performance by a majority of US laboratories participating in the LAMP program.

BACKGROUND: Biomarkers of tobacco exposure have a central role in studies of tobacco use and nicotine intake. The most significant exposure markers are nicotine itself and its metabolites in urine. Therefore, it is important to evaluate the performance of laboratories conducting these biomarker measurements. METHODS: This report presents the results from a method performance study involving 11 laboratories from 6 countries which are currently active in this area. Each laboratory assayed blind replicates of 7 human urine pools at various concentrations on 3 separate days. The samples included 5 pools blended from smoker and nonsmoker urine sources, and 2 additional blank urine samples fortified with pure nicotine, cotinine and hydroxycotinine standards. All laboratories used their own methods, and all were based on some form of liquid chromatography / tandem mass spectrometry. RESULTS: Overall, good agreement was found among the laboratories in this study. Intralaboratory precision was good, and in the fortified pools the mean bias observed was < + 3.5% for nicotine, approximately 1.2% for hydroxycotinine, and less than 1% for cotinine (1 outlier excluded in each case). Both indirect and direct methods for analyzing the glucuronides gave comparable results. CONCLUSIONS: This evaluation indicates that the experienced laboratories participating in this study can produce reliable and comparable human urinary nicotine metabolic profiles in samples from people with significant recent exposure to nicotine. IMPACT: This work supports the reliability and agreement of an international group of established laboratories measuring nicotine and its metabolites in urine in support of nicotine exposure studies.

Formaldehyde (FA) is an environmental chemical classified as a human carcinogen. It is highly reactive and can bind covalently with hemoglobin (Hb) to produce Hb adducts. Measurement of these Hb adducts provides valuable information about exposure to this chemical. We developed a robust, ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantifying FA-Hb adducts in red blood cells. The method measures the FA-VHLTPEEK peptide after trypic digestion. The peptide is a FA adduct at the N-terminus of the beta chain of human Hb. Method mean (+/-SD) accuracy, determined by recovery in quality control and blank material was 103.2% +/- 8.11. The mean among-day and within-day coefficients of variation determined at three concentration levels (%CV) were 9.2% (range: 7.2-10.2%) and 4.9% (range 3.1-7.3%), respectively. The limit of detection was 3.4 nmol/g Hb. This method was applied to the analysis of 135 human blood samples, and FA-VHLTPEEK was detected in all study samples. FA-VHLTPEEK concentrations were not significantly different between smokers and nonsmokers. This work is the first validated UPLC-MS/MS method in which a FA peptide derived from a FA-Hb adduct could be used to monitor exposure to FA in population studies.

Reliable measurement of total testosterone and estradiol is critical for their use as biomarkers of hormone-related disorders in patient care and translational research. We developed and validated a mass spectrometry method to simultaneously quantify these analytes in human serum without chemical derivatization. Serum is equilibrated with isotopic internal standards and treated with acidic buffer to release hormones from their binding proteins. Lipids are isolated and polar impurities are removed by two serial liquid-liquid extraction steps. Total testosterone and estradiol are measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) in combination of positive and negative electrospray ionization modes. The method shows broad analytical measurement range for both testosterone 0.03-48.5 nM (0.75-1400 ng/dL) and estradiol 11.0-5138 pM (2.99-1400 pg/mL) and excellent agreement with certified reference materials (mean bias less than 2.1% to SRM 971, BCR 576, 577, and 578) and a high order reference method (mean bias 1.25% for testosterone and -0.84% for estradiol). The high accuracy of the method was monitored and certified by CDC Hormone Standardization (HoSt) Program for 2 years with mean bias -0.7% (95% CI -1.6% to 0.2%) for testosterone and 0.1% (95% CI -2.2% to 2.3%) for estradiol. The method precision over a 2-year period for quality control pools at low, medium, and high concentrations was 2.7-2.9% for testosterone and 3.3-5.3% for estradiol. With the consistently excellent accuracy and precision, this method is readily applicable for high-throughput clinical and epidemiological studies.

Background: The consumption of trans fatty acids (TFAs) is associated with an increased risk of cardiovascular disease, and reducing their consumption is a major public health objective. Food intake studies have provided estimates for TFA concentrations in the US population; however, there is a need for data on TFA blood concentrations in the population.Objective: The objective of this study was to determine plasma TFA concentrations in a nationally representative group of fasted adults in the US population in NHANES samples from 1999-2000 and 2009-2010.Design: Four major TFAs [palmitelaidic acid (C16:1n-7t), trans vaccenic acid (C18:1n-7t), elaidic acid (C18:1n-9t), and linoelaidic acid (C18:2n-6t,9t)] were measured in plasma in 1613 subjects from NHANES 1999-2000 and 2462 subjects from NHANES 2009-2010 by gas chromatography-mass spectrometry. Geometric means and distribution percentiles were calculated for each TFA and their sum by age, sex, and race/ethnicity (non-Hispanic white, non-Hispanic black, Mexican American), and covariate-adjusted geometric means were computed by using a model that included these demographic and other dietary factors, as well as survey year and any significant interaction terms.Results: These nationally representative data for the adult US population show that TFA concentrations were 54% lower in NHANES 2009-2010 than in NHANES 1999-2000. Covariate-adjusted geometric means for the sum of the 4 TFAs were 81.4 mumol/L (95% CI: 77.3, 85.6 mumol/L) and 37.8 mumol/L (95% CI: 36.4, 39.4 mumol/L) in NHANES 1999-2000 and 2009-2010, respectively. Even with the large decline in TFA concentrations, differences between demographic subgroups were comparable in the 2 surveys.Conclusion: The results indicate an overall reduction in TFA concentrations in the US population and provide a valuable baseline to evaluate the impact of the recent regulation categorizing TFAs as food additives.

Background: High intakes of trans-fatty acids (TFAs), especially industrially produced TFAs, can lead to unfavorable lipid and lipoprotein concentrations and an increased risk of cardiovascular disease. It is unknown how this relation might change in a population after significant reductions in TFA intake.Objective: This study, which used a new analytical method for measuring plasma TFA concentrations, clarified the association between plasma TFA and serum lipid and lipoprotein concentrations before and after the US FDA enacted TFA food-labeling regulations in 2006.Methods: Data were selected from the NHANES of 1999-2000 and 2009-2010. Findings on 1383 and 2155 adults, respectively, aged ≥20 y, were evaluated. Multivariable linear regressions were used to examine the associations between plasma TFA concentration and lipid and lipoprotein concentrations. The outcome measures were serum concentrations of total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triglycerides and the ratio of TC to HDL cholesterol.Results: The median plasma TFA concentration decreased from 80.6 mumol/L in 1999-2000 to 37.0 mumol/L in 2009-2010. Plasma TFA concentration continued to be associated with serum lipid and lipoprotein concentrations after significant reductions in TFA intake in the population. For example, by comparing the lowest with the highest quintiles of TFA concentration in 1999-2000, adjusted mean (95% CI) LDL-cholesterol concentrations increased from 118 mg/dL (112, 123 mg/dL) to 135 mg/dL (130, 141 mg/dL) (P-trend < 0.001). The corresponding values for 2009-2010 were 102 mg/dL (97.4, 107 mg/dL) and 129 mg/dL (125, 133 mg/dL) for LDL cholesterol (P-trend < 0.001). Differences between the highest and lowest quintiles were consistent across age groups, sexes, races/ethnicities, and other covariates.Conclusions: Despite a 54% reduction in plasma TFA concentrations in US adults from 1999-2000 to 2009-2010, concentrations remained significantly associated with serum lipid and lipoprotein concentrations. There does not appear to be a threshold under which the association between plasma TFA concentration and lipid profiles might become undetectable.

BACKGROUND: Limited information is available about testosterone concentrations representative of the general US population, especially children, women, and non-Hispanic Asians. METHODS: We obtained nationally representative data for total testosterone (totalT), measured with standardized LC-MS/MS, for the US population age 6 years and older from the 2011-2012 National Health and Nutrition Examination Survey (NHANES). We analyzed 6746 serum samples and calculated the geometric means, distribution percentiles, and covariate-adjusted geometric means by age, sex, and race/ethnicity. RESULTS: The 10th-90th percentiles of totalT values in adults (≤20 years) was 150-698 ng/dL (5.20-24.2 nmol/L) in men, 7.1-49.8 ng/dL (0.25-1.73 nmol/L) in women, and 1.0-9.5 ng/dL (0.04-0.33 nmol/L) in children (6-10 years old). Differences among race/ethnic groups existed in children and men: covariate-adjusted totalT values in non-Hispanic Asians were highest among children (58% compared to non-Hispanic black children) and lowest among men (12% compared to Mexican-American men). Covariate-adjusted totalT values in men were higher at age 55-60 years compared to ages 35 and 80 years, a pattern different from that observed in previous NHANES cycles. CONCLUSIONS: TotalT patterns were different among age groups in men compared with previous NHANES cycles. Covariate-adjusted totalT values peaked at age 55-60 years in men, which appeared to be consistent with the increased use of exogenous testosterone. Differences among race/ethnic groups existed and appeared more pronounced in children than adults.

The National Centers for Disease Control and Prevention (CDC) is using a weighted pooled-sample design to characterize concentrations of persistent organic pollutants (POPs) in the U.S. POPULATION: Historically, this characterization has been based on individual measurements of these compounds in body fluid or tissue from representative samples of the population using stratified multistage selection. Pooling samples before making analytical measurements reduces the costs of biomonitoring by reducing the number of analyses. Pooling samples also allows for larger sample volumes which can result in fewer left censored results. But because samples are pooled across the sampling design cells of the original survey, direct calculation of the design effects needed for accurate standard error and confidence interval (CI) estimation is not possible. So in this paper I describe a multiple imputation (MI) method for calculating design effects associated with pooled-sample estimates. I also evaluate the method presented, by simulating NHANES individual sample data from which artificial pools are created for use in a comparison of pooled-sample estimates with estimates based on individual samples. To further illustrate and evaluate the method proposed in this paper I present geometric mean and various percentile estimates along with their 95% CIs for two chemical compounds from NHANES 2005-2006 pooled samples and compare them to individual-sample based estimates from NHANES 1999-2004.

Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and persistent pesticides have been measured in serum pools from participants 3-5, 6-11, 12-19, 20-39, 40-59, and ≥60 years of age from the 2001-2002 National Health and Nutrition Examination Survey. For 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47), the unweighted (not adjusted for sampling weights) arithmetic mean concentration (±95% confidence interval) was 3.4 times higher in 3-5-year-olds (216 ± 30 ng/g of lipid) than in 12-19-year-olds (64 ± 11 ng/g of lipid), with no apparent change with increasing age for adults ≥20 years of age. By contrast, unweighted arithmetic mean concentrations of traditional persistent organic pollutants (POPs) such as hexachlorobenzene (HCB) and 2,2',3,3',4,4',5,5'-octachlorobiphenyl (PCB194) were 2- and 20-fold higher, respectively, in persons ≥60 years than in 12-19-year-old adolescents. Findings suggest higher exposures to PBDEs but lower exposures to traditional POPs in 3-5-year-old children than in adults.

BACKGROUND: Despite the public health and toxicologic interest in methyl mercury (MeHg) and ethyl mercury (EHg), these mercury species have been technically difficult to measure in large population studies. METHODS: Using NHANES 2011-2012 data, we calculated reference ranges and examined demographic factors associated with specific mercury species concentrations and the ratio of MeHg to THg. We conducted several multiple regression analyses to examine factors associated with MeHg concentrations and also with the ratio of MeHg to THg. RESULTS: Asians had the highest geometric mean concentrations for MeHg, 1.58microg/L (95% CI 1.29, 1.93) and THg, 1.86microg/L (1.58, 2.19), followed by non-Hispanic blacks with MeHg, 0.52microg/L (0.39, 0.68) and THg, 0.68microg/L (0.54, 0.85). Greater education attainment in adults and male sex were associated with higher MeHg and THg concentrations. Race/ethnicity, age, and sex were significant predictors of MeHg concentrations, which increased with age and were highest in Asians in all age categories, followed by non-Hispanic blacks. Mexican Americans had the lowest adjusted MeHg concentrations. The ratio of MeHg to THg was highest in Asians, varied by racial/ethnic group, and increased with age in a non-linear fashion. The amount of increase in the MeHg to THg ratio with age depended on the initial ratio, with a greater increase as age increased. Of the overall population, 3.05% (95% CI 1.77, 4.87) had MeHg concentrations >5.8microg/L (a value that corresponds to the U.S. EPA reference dose). The prevalence was highest in Asians at 15.85% (95% CI 11.85, 20.56), increased with age, reaching a maximum of 9.26% (3.03, 20.42) at ages 60-69 years. Females 16-44 years old had a 1.76% (0.82-3.28) prevalence of MeHg concentrations >5.8microg/L. CONCLUSIONS: Asians, males, older individuals, and adults with greater educational attainment had higher MeHg concentrations. The ratio of MeHg to THg varied with racial/ethnic group, increased with age, and was nonlinear. U.S. population reference values for MeHg and the ratio of MeHg to THg can assist in more precise assessment of public health risk from MeHg consumed in seafood.

Techniques for conducting hypothesis testing on the median and other quantiles of two or more subgroups under complex survey design are limited. In this paper, we introduce programs in both SAS and R to perform such a test. A detailed illustration of the computations, macro variable definitions, input and output for the SAS and R programs are also included in the text. Urinary iodine data from National Health and Nutrition Examination Survey (NHANES) are used as examples for comparing medians between females and males as well as comparing the 75th percentiles among three salt consumption groups.

Reliable measurement of total testosterone is essential for the diagnosis, treatment and prevention of a number of hormone-related diseases affecting adults and children. A mass spectrometric method for testosterone determination in human serum was carefully developed and thoroughly validated. Total testosterone from 100muL serum is released from proteins with acidic buffer and isolated by two serial liquid-liquid extraction steps. The first extraction step isolates the lipid fractions from an acidic buffer solution using ethyl acetate and hexane. The organic phase is dried down and reconstituted in a basic buffer solution. The second extraction step removes the phospholipids and other components by hexane extraction. Liquid chromatography - isotopic dilution tandem mass spectrometry is used to quantify the total testosterone. The sample preparation is automatically conducted in a liquid-handling system with 96-deepwell plates. The method limit of detection is 9.71 pmol/L (0.280ng/dL) and the method average percent bias is not significantly different from reference methods. The performance of this method has proven to be consistent with the method precision over a 2-year period ranging from 3.7-4.8% for quality control pools at the concentrations 0.527, 7.90 and 30.7nmol/L (15.2, 228, and 886ng/dL), respectively. This method provides consistently high accuracy and excellent precision for testosterone determination in human serum across all clinical relevant concentrations.

BACKGROUND: Adsorption of albumin onto urine collection and analysis containers may cause falsely low concentrations. METHODS: We added 125I-labeled human serum albumin to urine and to phosphate buffered solutions, incubated them with 22 plastic container materials and measured adsorption by liquid scintillation counting. RESULTS: Adsorption of urine albumin (UA) at 5-6mg/l was <0.9%; and that at 90mg/l was <0.4%. Adsorption was generally less at pH8 than pH5 but only 3 cases had p<0.05. Adsorption from 11 unaltered urine samples with albumin 5-333mg/l was <0.8%. Albumin adsorption for the material with greatest binding was extrapolated to the surface areas of 100ml and 2l collection containers, and to instrument sample cups and showed <1% change in concentration at 5mg/l and <0.5% change at 20mg/l or higher concentrations. Adsorption of albumin from phosphate buffered solutions (2-28%) was larger than that from urine. CONCLUSIONS: Albumin adsorption differed among urine samples and plastic materials, but the total influence of adsorption was <1% for all materials and urine samples tested. Adsorption of albumin from phosphate buffered solutions was larger than that from urine and could be a limitation for preparations used as calibrators.

Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and persistent pesticides have been measured in pooled samples representative of the general noninstitutionalized population of the United States. The pools were made from individual sera from the National Health and Nutrition Examination Survey (NHANES) during 2005/06 and 2007/08. The pooled concentrations have been contrasted to NHANES 2003/04 individual measurements to evaluate changes in concentration over time and within survey period differences among age groups, race/ethnicity groups (Mexican American, non-Hispanic Black, non-Hispanic White), and sex. The arithmetic mean serum concentrations of several PCB congeners decreased from NHANES 2003/04 through 2007/08. Larger percentage reductions were seen for younger subjects (12-19 years) compared with older subjects (≥60 years). For example, the arithmetic mean concentration of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) was 36% lower in 12-19 year old adolescents when comparing NHANES 2007/08 with 2003/04; while for subjects over the age of 60 a 14% lower concentration was seen, although, the 95% confidence intervals overlapped. Similarly, the arithmetic mean serum concentrations of tri- to hexaBDEs were lower in NHANES 2007/08 than in 2003/04; however, most confidence intervals of the arithmetic means overlapped. These findings suggest that a reduction in PBDE serum concentrations cannot yet be detected following the discontinuation of pentaBDE in 2004.

To reduce the variability in estradiol (E2) testing and to assure better patient care, standardization of E2 measurements has been recommended. This study aims to assess the accuracy and variability of E2 measurements performed by 11 routine immunological methods and 6 mass spectrometry methods using single donor serum materials and to compare the results to a reference method. The contribution of calibration bias, specificity or matrix effects, and imprecision on the overall variability of individual assays was evaluated. This study showed substantial variability in serum E2 measurements in samples from men and pre- and post-menopausal women. The mean bias across all samples, for each participant, ranged between -2.4% and 235%, with 3 participants having a mean bias of over 100%. The data suggest that calibration bias is the major contributor to the overall variability for nine assays. The analytical performances of most assays measuring E2 concentrations do not meet current needs in research and patient care. Three out of 17 assays would meet performance criteria derived from biological variability of +12.5% bias at concentrations >20pg/mL, and a maximum allowable bias of +2.5pg/mL at concentrations <20pg/mL. The sensitivity differs highly between assays. Most assays are not able to measure E2 levels below 10pg/mL. Standardization, specifically calibration to a common standard by using panels of individual patient samples, can reduce the observed variability and improve the utility of E2 levels in clinical settings.

The National Centers for Disease Control and Prevention (CDC) provides an ongoing assessment of the US population's exposure to environmental chemicals by using biomonitoring in conjunction with CDC's National Health and Nutrition Examination Survey (NHANES). Characterizing the distributions of concentrations of environmental compounds or their metabolites in the US population is a primary objective of CDC's biomonitoring program. Historically, this characterization has been based on individual measurements of these compounds in body fluid or tissue from representative samples of the population. Pooling samples before making analytical measurements can reduce the costs of biomonitoring by reducing the number of analyses. For the first time in NHANES 2005-2006, a weighted pooled-sample design was implemented to facilitate pooling samples before making analytical measurements. This paper describes this design and the estimation method being developed in the National Center for Environmental Health, Division of Laboratory Sciences (NCEH/DLS) to characterize concentrations of polychlorinated and polybrominated compounds. We present percentile estimates for 2,2',4,4',5,5' -hexachlorobiphenyl (PCB153) in specific subpopulations of the US based on the NHANES 2005-2006 pooled-sample design. We also compare estimates based on individual samples from NHANES 2003-2004 with estimates based on artificially created pools from NHANES 2003-2004 using a pooled-sample design similar to the one used for NHANES 2005-2006. For NHANES 2005-2006 the number of analyses required to characterize the levels of 61 polychlorinated and 13 polybrominated compounds in the US population was reduced from 2201 to 228. At a cost of $1400 per analytical measurement, this represents a savings of approximately $2.78 million. (Copyright (c) 2012 John Wiley & Sons, Ltd.)

BACKGROUND: Our objective was to evaluate the accuracy of cardiovascular disease (CVD) risk score classification by direct LDL cholesterol (dLDL-C), calculated LDL cholesterol (cLDL-C), and non-HDL cholesterol (non-HDL-C) compared to classification by reference measurement procedures (RMPs) performed at the CDC. METHODS: We examined 175 individuals, including 138 with CVD or conditions that may affect LDL-C measurement. dLDL-C measurements were performed using Denka, Kyowa, Sekisui, Serotec, Sysmex, UMA, and Wako reagents. cLDL-C was calculated by the Friedewald equation, using each manufacturer's direct HDL-C assay measurements, and total cholesterol and triglyceride measurements by Roche and Siemens (Advia) assays, respectively. RESULTS: For participants with triglycerides <2.26 mmol/L (<200 mg/dL), the overall misclassification rate for the CVD risk score ranged from 5% to 17% for cLDL-C methods and 8% to 26% for dLDL-C methods when compared to the RMP. Only Wako dLDL-C had fewer misclassifications than its corresponding cLDL-C method (8% vs 17%; P < 0.05). Non-HDL-C assays misclassified fewer patients than dLDL-C for 4 of 8 methods (P < 0.05). For participants with triglycerides ≥2.26 mmol/L (≥200 mg/dL) and <4.52 mmol/L (<400 mg/dL), dLDL-C methods, in general, performed better than cLDL-C methods, and non-HDL-C methods showed better correspondence to the RMP for CVD risk score than either dLDL-C or cLDL-C methods. CONCLUSIONS: Except for hypertriglyceridemic individuals, 7 of 8 dLDL-C methods failed to show improved CVD risk score classification over the corresponding cLDL-C methods. Non-HDL-C showed overall the best concordance with the RMP for CVD risk score classification of both normal and hypertriglyceridemic individuals.

Pooling samples for analysis was first proposed in the 1940s to reduce analytical measurement costs associated with screening World War II recruits for syphilis. Later, it progressed to more complex screening strategies, to population prevalence estimation for discrete quantities, and to population mean estimation for continuous quantities. Recently, pooled samples have also been used to provide efficient alternatives for gene microarray analyses, epidemiologic studies of biomarkers of exposure, and characterization of populations regarding environmental chemical exposures. In this study, we address estimation and bias issues related to using pooled-sample variance information from an auxiliary source to augment pooled-sample variance estimates from the study of interest. The findings are illustrated by using pooled samples from the National Health and Nutrition Examination Survey 2001-2002 to assess exposures to perfluorooctanesulfonate and other polyfluoroalkyl compounds in the U.S. population. Published in 2011 by John Wiley & Sons, Ltd.

BACKGROUND: Methods from 7 manufacturers and 1 distributor for directly measuring HDL cholesterol (C) and LDL-C were evaluated for imprecision, trueness, total error, and specificity in nonfrozen serum samples. METHODS: We performed each direct method according to the manufacturer's instructions, using a Roche/Hitachi 917 analyzer, and compared the results with those obtained with reference measurement procedures for HDL-C and LDL-C. Imprecision was estimated for 35 runs performed with frozen pooled serum specimens and triplicate measurements on each individual sample. Sera from 37 individuals without disease and 138 with disease (primarily dyslipidemic and cardiovascular) were measured by each method. Trueness and total error were evaluated from the difference between the direct methods and reference measurement procedures. Specificity was evaluated from the dispersion in differences observed. RESULTS: Imprecision data based on 4 frozen serum pools showed total CVs <3.7% for HDL-C and <4.4% for LDL-C. Bias for the nondiseased group ranged from -5.4% to 4.8% for HDL-C and from -6.8% to 1.1% for LDL-C, and for the diseased group from -8.6% to 8.8% for HDL-C and from -11.8% to 4.1% for LDL-C. Total error for the nondiseased group ranged from -13.4% to 13.6% for HDL-C and from -13.3% to 13.5% for LDL-C, and for the diseased group from -19.8% to 36.3% for HDL-C and from -26.6% to 31.9% for LDL-C. CONCLUSIONS: Six of 8 HDL-C and 5 of 8 LDL-C direct methods met the National Cholesterol Education Program total error goals for nondiseased individuals. All the methods failed to meet these goals for diseased individuals, however, because of lack of specificity toward abnormal lipoproteins.

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.

BACKGROUND: The lifelong exposure of the population to acrylamide has raised concerns about the possible health effects of the chemical. Data on the extent of exposure to acrylamide and its primary metabolite, glycidamide, are needed to aid in the assessment of potential health effects. OBJECTIVES: The aim of this study was to assess human exposure to acrylamide and glycidamide in the general U.S. population through the measurement of hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA). METHODS: HbAA and HbGA were measured in 7,166 subjects from the National Health and Nutrition Examination Survey. Stratified HbAA and HbGA data were reported by sex, age groups, race/ethnicity (Mexican American, non-Hispanic black, non-Hispanic white), and smoking status based on serum cotinine levels. Covariate-adjusted geometric means for each demographic group were calculated using multiple regression analysis. RESULTS: HbAA and HbGA levels ranged from 3 to 910 and from 4 to 756 pmol/g hemoglobin, respectively, with smokers having the highest levels overall. Tobacco smoke exposure in nonsmokers had a small but significant effect on HbAA and HbGA levels. Adjusted geometric mean levels for children 311 years of age were higher than for adults ≥ 60 years of age [mean (95% confidence interval): HbAA, 54.5 (49.151.5) and HbGA, 73.9 (71.376.6) vs. HbAA, 46.2 (44.348.2) and HbGA, 41.8 (38.745.2)]. Levels were highest in Mexican Americans [HbAA: 54.8 (51.957.8), HbGA: 57.9 (53.762.5)], whereas non-Hispanic blacks had the lowest HbGA levels [43.5 (41.145.9)]. CONCLUSIONS: U.S. population levels of acrylamide and glycidamide adducts are described. The high variability among individuals but modest differences between population subgroups suggest that sex, age, and race/ethnicity do not strongly affect acrylamide exposure. Adduct concentration data can be used to estimate relative exposure and to validate intake estimates. EDITOR'S SUMMARY: Human exposure to acrylamide, a neurotoxin and suspected human carcinogen, occurs via dietary sources, tobacco smoke, and occupational production or use. Carcinogenic effects are attributed to DNA adducts formed with the phase I metabolite glycidamide, and body burdens and risks may be partly determined by factors that influence acrylamide metabolism, including genetic variants and factors that induce metabolism gene expression (e.g., medications and alcohol). Vesper et al. (p. 278) measured hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) in blood samples from 7,166 participants in the National Health and Nutrition Examination Survey, and estimated HbGA:HbAA ratios to assess variation in metabolic conversion. The authors report that smokers had the highest adjusted geometric mean levels of HbAA and HbGA and that adduct levels in nonsmokers were associated with tobacco smoke exposure (based on serum cotinine levels). In addition, adduct levels and HbGA:HbAA ratios were higher in children 311 years of age than in adults ≥ 60 years of age, and in Mexican Americans compared with other participants. The authors note that differences among population subgroups were modest relative to differences among individuals within subgroups, and suggest that factors other than sex, age, and race/ethnicity may be primarily responsible for variation in acrylamide exposure and metabolism.

Biomonitoring involves the assessment of human or animal populations by measuring organic or biological compounds or their metabolites in the body fluids or tissues of individuals in those populations. Pooling samples before making analytical measurements can reduce the costs of biomonitoring by reducing the number of analyses. By proper choice of pooled-sample design, population means can be estimated without measuring individual samples. I present a statistical method for characterizing an entire population distribution of such compounds by exploiting the theoretic relationship between interindividual-sample variance and the variation between pooled samples. I use simulation experiments to determine an optimum pooled-sample design as a function of the number of subpopulations and the number of available samples. Using pooled samples to characterize populations is not only more cost-efficient, but also in some cases it can lead to more precise and less biased parameter estimation than that occurs with individual samples.

We describe the distribution and demographic characteristics of total blood Hg levels in the U.S. general population among persons ages 1 year and older who participated in the 2003-2006 National Health and Nutrition Examination Survey (NHANES). We also describe trends in the total blood Hg of children ages 1-5 (n=3456) and females ages 16-49 during 1999-2006 (n=7245). In the combined 2003-2006 survey periods, the geometric means for non-Hispanic blacks, 0.853microg/L (95% confidence interval [CI], 0.766-0.950microg/L), and non-Hispanic whites, 0.833microg/L (95% CI, 0.752-0.922microg/L), were higher than the geometric mean for Mexican Americans, 0.580microg/L (95% CI, 0.522-0.645microg/L). Also in 2003-2006, regression analysis of log total blood Hg with age, race/ethnicity and gender showed that total blood Hg levels in the population exhibited a quadratic increase with age (p<0.0001), peaking at ages 50-59 in non-Hispanic blacks and whites, at ages 40-49 in Mexican Americans, and then declining at older ages. Over the four survey periods (1999-2006), regression analysis showed that total blood Hg levels increased slightly for non-Hispanic white children and decreased slightly for non-Hispanic black and Mexican American children. Over the same four survey periods, female children had slightly higher total blood Hg levels than males (0.356 vs. 0.313microg/L, p=0.0050) and total blood Hg levels in non-Hispanic black women aged 16-49 years were significantly higher than in non-Hispanic white women (1.081 vs. 0.850microg/L, p<0.0001) and in Mexican American women (1.081 vs. 0.70microg/L, p<0.0001).