Polybrominated Diphenyl Ethers and Biphenyl in Serum: Time Trend Study from the National Health and Nutrition Examination Survey for Years 2005/06 through 2013/14.

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.

LAMP: A CDC Program to Ensure the Quality of Blood-Lead Laboratory Measurements.

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 µg/dL using evaluation criteria of ±2 µg/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 µg/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 µg/dL for inductively coupled plasma mass spectrometry to 1.50 µg/dL for LeadCare instruments. All participating US LAMP laboratories reported accurate BLL for 89% of challenge samples, using the ±2 µg/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 µg/dL or ±10%, with a success rate of 96%. However, when we apply limits of ±2 µg/dL or ±10%, the success rate drops to 89%. When challenged with samples that have target values between 3 and 5 µg/dL, nearly 100% of reported results fall within ±4 µg/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 µg/dL or 10%) would be achievable performance by a majority of US laboratories participating in the LAMP program.

Plasma trans-Fatty Acid Concentrations Continue to Be Associated with Serum Lipid and Lipoprotein Concentrations among US Adults after Reductions in trans-Fatty Acid Intake.

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 µmol/L in 1999-2000 to 37.0 µmol/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.

Ultraperformance Liquid Chromatography Tandem Mass Spectrometry Method To Determine Formaldehyde Hemoglobin Adducts in Humans as Biomarker for Formaldehyde Exposure.

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.

Simultaneous measurement of total estradiol and testosterone in human serum by isotope dilution liquid chromatography tandem mass spectrometry.

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.

Serum Total Testosterone Concentrations in the US Household Population from the NHANES 2011-2012 Study Population.

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.

Polybrominated diphenyl ethers, polychlorinated biphenyls, and persistent pesticides in serum from the national health and nutrition examination survey: 2003-2008.

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.

Total and methyl mercury in whole blood measured for the first time in the U.S. population: NHANES 2011-2012.

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, 1.58 µg/L (95% CI 1.29, 1.93) and THg, 1.86 µg/L (1.58, 2.19), followed by non-Hispanic blacks with MeHg, 0.52 µg/L (0.39, 0.68) and THg, 0.68 µg/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 >5.8 µg/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 >5.8 µg/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.

Use of pooled samples from the National Health and Nutrition Examination Survey.

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. Published 2012. This article is a US Government work and is in the public domain in the USA.

Non-HDL cholesterol shows improved accuracy for cardiovascular risk score classification compared to direct or calculated LDL cholesterol in a dyslipidemic population.

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.

Important issues related to using pooled samples for environmental chemical biomonitoring.

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.

Seven direct methods for measuring HDL and LDL cholesterol compared with ultracentrifugation reference measurement procedures.

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.

Semi-volatiles in mainstream smoke delivery from select charcoal-filtered cigarette brand variants.

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.

A comparison of individual-level vs. hypothetically pooled mercury biomonitoring data from the Maternal Organics Monitoring Study (MOMS), Alaska, 1999-2012.

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.

Chemical analysis of snus products from the United States and northern Europe.

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.

Serum elimination half-lives adjusted for ongoing exposure of tri-to hexabrominated diphenyl ethers: Determined in persons moving from North America to Australia.

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.

Standardization of high-sensitivity immunoassays for measurement of C-reactive protein; II: Two approaches for assessing commutability of a reference material.

BACKGROUND: We evaluated the commutability of a proposed reference material (PRM), with a formulation based on dilution of Certified Reference Material 470 (CRM470), for 24 high-sensitivity C-reactive protein (hsCRP) methods. We also investigated whether calibration by use of PRM was effective in harmonizing results. METHODS: A set of 40 native clinical samples was measured along with PRM and 3 dilutions of PRM. We used weighted least-squares polynomial regression (WLS/PR) to perform comparisons between all method combinations and to calculate normalized residuals for the PRM. The PRM was considered noncommutable if any of the normalized residuals for a method pair was >2. Correspondence analysis (CA) was used to explore the multidimensional relationships between methods and samples to evaluate if the PRM had properties similar to native clinical samples. Clinical sample results from the methods for which PRM was commutable were recalibrated based on the PRM results, and ANOVA was used to estimate the CVs before and after recalibration. RESULTS: After omitting data for 9 methods because of poor precision or procedural flaws, we used data from the 15 remaining methods to evaluate commutability. Using both WLS/PR and CA we found that PRM was noncommutable with 1 method. We found modest improvement in total and among-method CVs when PRM was used to harmonize the results from the 14 methods for which it was commutable. CONCLUSIONS: A PRM with a formulation based on dilution of CRM470 was commutable with native clinical samples for 14 of 15 hsCRP methods that had acceptable precision. For those methods the use of PRM may contribute to improved harmonization of results for native clinical samples.

Concentration and profile of 22 urinary polycyclic aromatic hydrocarbon metabolites in the US population.

Urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) are a class of PAH metabolites used as biomarkers for assessing human exposure to PAHs. The Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey (NHANES) uses OH-PAHs to establish reference range concentrations for the US population, and to set benchmarks for future epidemiologic and biomonitoring studies. For the years 2001 and 2002, 22 OH-PAH metabolites were measured in urine specimens from 2748 NHANES participants. Percentages of samples with detectable levels ranged from nearly 100% for metabolites of naphthalene, fluorene, phenanthrene, and pyrene, to less than 5% for metabolites from parent compounds with higher molecular weight such as chrysene, benzo[c]phenanthrene, and benz[a]anthracene. The geometric mean for 1-hydroxypyrene (1-PYR)--the most commonly used biomarker for PAH exposure--was 49.6 ng/L urine, or 46.4 ng/g creatinine. Children (ages 6-11) generally had higher levels than did adolescents (ages 12-19) or adults (ages 20 and older). Model-adjusted, least-square geometric means for 1-PYR were 87, 53 and 43 ng/L for children, adolescents (ages 12-19) and adults (ages 20 years and older), respectively. Log-transformed concentrations for major detectable OH-PAHs were significantly correlated with each other. The correlation coefficients between 1-PYR and other metabolites ranging from 0.17 to 0.63 support the use of 1-PYR as a useful surrogate representing PAH exposure.

Total TEQ reference range (PCDDs, PCDFs, cPCBs, mono-PCBs) for the US population 2001-2002.

We report reference ranges for the total toxic equivalency (TEQ) and TEQ sub-fractions of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), coplanar biphenyls (cPCBs), and mono-ortho-substituted biphenyls (mPCBs) in a statistically designed sampling of the US population in 2001-2002. The TEQ and TEQ sub-fractions have been stratified by age, sex, and race/ethnicity. The TEQ levels are lower using the 2005 toxic equivalency factors (TEFs) compared to using the 1998 TEF values, principally due to the much lower 2005 TEF values assigned to the mPCBs. Mexican Americans (MA) have significantly lower TEQ levels than both non-Hispanic whites (NHW) and non-Hispanic blacks (NHB). Using the 1998 or 2005 TEF values, males and females have nearly the same distribution of TEQ sub-fractions. We found a significant increase in TEQ levels with age for males, females, and NHW. About 80-90% of the total TEQ can be estimated by using seven congeners, namely 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, 1,2,3,6,7,8-HxCDD, 2,3,4,7,8-PeCDF, PCB-126, PCB-118, and PCB-156. We also measured geometric mean TEQ levels in pooled samples from the US population. The geometric mean TEQ levels also increase with age. In the youngest age group (12-19 years), the TEQ levels were higher in males than in females while females had higher TEQ levels than males in all older age groups. In the pools, as age increases the percent contribution of the PCDD TEQ levels increases while the percent contribution of the PCDF TEQ levels decreases for all race/ethnicity and sex strata.

Collaborative Method Performance Study of the Measurement of Nicotine, Its Metabolites, and Total Nicotine Equivalents in Human Urine.

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 that are currently active in this area. Each laboratory assayed blind replicates of seven human urine pools at various concentrations on three separate days. The samples included five pools blended from smoker and nonsmoker urine sources, and two 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. Cancer Epidemiol Biomarkers Prev; 27(9); 1083-90. ©2018 AACR.