Changes in the concentrations of biochemical indicators of diet and nutritional status of pregnant women across pregnancy trimesters in Trujillo, Peru, 2004-2005.

BACKGROUND: In developing countries, deficiencies in essential micronutrients are common, particularly in pregnant women. Although, biochemical indicators of diet and nutrition are useful to assess nutritional status, few studies have examined such indicators throughout pregnancy in women in developing countries. METHODS: The primary objective of this study was to assess the nutritional status of 78 Peruvian women throughout pregnancy for 16 different nutritional indicators including fat-soluble vitamins and carotenoids, iron-status indicators, and selenium. Venous blood samples from which serum was prepared were collected during trimesters one (n = 78), two (n = 65), three (n = 62), and at term via the umbilical cord (n = 52). Questionnaires were completed to determine the demographic characteristics of subjects. Linear mixed effects models were used to study the associations between each maternal indicator and the demographic characteristics. RESULTS: None of the women were vitamin A and E deficient at any stage of pregnancy and only 1/62 women (1.6%) was selenium deficient during the third trimester. However, 6.4%, 44% and 64% of women had ferritin levels indicative of iron deficiency during the first, second and third trimester, respectively. Statistically significant changes (p ≤ 0.05) throughout pregnancy were noted for 15/16 nutritional indicators for this Peruvian cohort, with little-to-no association with demographic characteristics. Three carotenoids (beta-carotene, beta-cryptoxanthin and trans-lycopene) were significantly associated with education status, while trans-lycopene was associated with age and beta-cryptoxanthin with SES (p < 0.05). Concentrations of retinol, tocopherol, beta-cryptoxanthin, lutein + zeaxanthin and selenium were lower in cord serum compared with maternal serum (p < 0.05). Conversely, levels of iron status indicators (ferritin, transferrin saturation and iron) were higher in cord serum (p < 0.05). CONCLUSION: The increasing prevalence of iron deficiency throughout pregnancy in these Peruvian women was expected. It was surprising though not to find deficiencies in other nutrients. The results highlight the importance of continual monitoring of women throughout pregnancy for iron deficiency which could be caused by increasing fetal needs and/or inadequate iron intake as pregnancy progresses.

Personal exposure to PM(2.5) and urinary hydroxy-PAH levels in bus drivers exposed to traffic exhaust, in Trujillo, Peru.

Public transport vehicle drivers, especially in highly polluted or trafficked areas, are exposed to high levels of air pollutants. In this study, we assessed the influence of traffic on levels of hydroxy polycyclic aromatic hydrocarbons (OH-PAHs) in commercial bus drivers in Trujillo, Peru, by measuring the within-shift changes in the urinary whole weight and creatinine-corrected concentrations of the PAH metabolites. We measured personal PM(2.5) as a proxy of exposure to traffic emission. Urine samples were collected daily from two bus drivers and three minivan drivers in Trujillo, pre-, mid-, post-work shift and on days when the drivers were off work (total n = 144). Ten OH-PAH metabolites were measured in the urine samples. Drivers were also monitored for exposure to PM(2.5) (n = 41). Daily work shift (mean = 13.1 ± 1.3 hr) integrated PM(2.5) was measured in the breathing zones of the drivers for an average of 10.5 days per driver. The differences across shift in OH-PAH concentrations were not statistically significant except for urinary 2-hydroxyfluorene (2-FLU) (p = 0.04) and 4-hydroxyphenanthrene (4-PHE) (p = 0.01) and creatinine-corrected 4-hydroxyphenanthrene (p = 0.01). Correlation between pairs of hydroxy-PAHs (ρ = 0.50 to 0.93) were highest for mid-shift samples. Concentrations of PM(2.5) (geometric mean = 64 µg/m(3); 95% confidence limits = 52 µg/m(3), 78 µg/m(3)) is similar to those measured in many other studies of traffic exposure. There was significant change across work shift for concentrations of only two of the OH-PAHs (2-FLU and 4-PHE). Results indicate that the drivers may have had limited time for clearance of PAH exposure from the body between work shifts. Comparisons of the concentrations of creatinine-corrected hydroxy-PAH to those reported in other studies indicate that exposure of public transport drivers to PAH could be similar. By following the subjects over multiple days, this study gives an indication of appropriate exposure situations for the use of hydroxy-PAHs and will be beneficial in designing future occupational studies of PAH exposure.

Partition of environmental chemicals between maternal and fetal blood and tissues.

Passage of environmental chemicals across the placenta has important toxicological consequences, as well as for choosing samples for analysis and for interpreting the results. To obtain systematic data, we collected in 2000 maternal and cord blood, cord tissue, placenta, and milk in connection with births in the Faroe Islands, where exposures to marine contaminants is increased. In 15 sample sets, we measured a total of 87 environmental chemicals, almost all of which were detected both in maternal and fetal tissues. The maternal serum lipid-based concentrations of organohalogen compounds averaged 1.7 times those of cord serum, 2.8 times those of cord tissue and placenta, and 0.7 those of milk. For organohalogen compounds detectable in all matrices, a high degree of correlation between concentrations in maternal serum and the other tissues investigated was generally observed (r(2) > 0.5). Greater degree of chlorination resulted in lower transfer from maternal serum into milk. Concentrations of pentachlorbenzene, γ-hexachlorocyclohexane, and several polychlorinated biphenyl congeners with low chlorination were higher in fetal samples and showed poor correlation with maternal levels. Perfluorinated compounds occurred in lower concentrations in cord serum than in maternal serum. Cadmium, lead, mercury, and selenium were all detected in fetal samples, but only mercury showed close correlations among concentrations in different matrices. Although the environmental chemicals examined pass through the placenta and are excreted into milk, partitions between maternal and fetal samples are not uniform.

In-vitro oxidation of bisphenol A: Is bisphenol A catechol a suitable biomarker for human exposure to bisphenol A?

The extensive use of bisphenol A (BPA) in the manufacture of consumer products results in widespread human exposure to the chemical. In the body, BPA undergoes first-pass metabolism to form BPA glucuronide, considered to be a major BPA byproduct. Concentrations of total (free plus conjugated) urinary species of BPA are used to assess human exposure to BPA. However, because BPA can be present in numerous consumer and household products, potential contamination with parent BPA during collection and handling may pose a challenge when measuring BPA in such biological samples as blood or urine. In this study we investigated the in-vitro phase I metabolism of BPA in rat and human liver microsomes by using on-line solid-phase extraction-high-performance liquid chromatography-tandem mass spectrometry to identify phase I metabolites (e.g., BPA oxidation products) that could be used as potential alternative biomarkers of BPA exposure. We unambiguously identified 5-hydroxy BPA (BPA catechol) as an in-vitro oxidative metabolite of BPA, but human microsomes oxidized only about 10% of BPA to BPA catechol. We evaluated the usefulness of BPA catechol as a potential biomarker of human exposure to BPA by measuring total concentrations of BPA catechol and BPA in 20 urine samples. We detected BPA catechol at much lower concentrations and frequency than those of BPA. Furthermore, we found that free BPA catechol was rather unstable in urine, which highlights the importance of sampling techniques to adequate interpretation of biomonitoring data. Together, these findings suggest that BPA catechol may not be a suitable biomarker of environmental exposure to BPA, but could be used to confirm BPA exposure in special populations or in situations when urine specimens were potentially contaminated with BPA.

Phthalate exposure associated with self-reported diabetes among Mexican women.

BACKGROUND: Phthalates are ubiquitous industrial chemicals used as plasticizers in plastics made of polyvinyl chloride (PVC) to confer flexibility and durability. They are also present in products used for personal-care, industry and in medical devices. Phthalates have been associated with several adverse health effects, and recently it has been proposed that exposure to phthalates, could have an effect on metabolic homeostasis. This exploratory cross-sectional study evaluated the possible association between phthalate exposure and self-reported diabetes among adult Mexican women. METHODS: As part of an on-going case-control study for breast cancer, only controls were selected, which constituted 221 healthy women matched by age (±5 years) and place of residence with the cases. Women with diabetes were identified by self-report. Urinary concentrations of nine phthalate metabolites were measured by online solid phase extraction coupled to high performance liquid chromatography-isotope-dilution tandem mass spectrometry. RESULTS: Participants with diabetes had significantly higher concentrations of di(2-ethylhexyl) pththalate (DEHP) metabolites: mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) but lower levels of monobenzyl phthalate (MBzP) a metabolite of benzylbutyl phthalate, compared to participants without diabetes. A marginally significant positive associations with diabetes status were observed over tertiles with MEHHP (OR(T3 vs. T1)=2.66; 95% CI: 0.97-7.33; p for trend=0.063) and MEOHP (OR(T3 vs. T1)=2.27; 95% CI; 0.90-5.75; P for trend=0.079) even after adjusting for important confounders. CONCLUSIONS: The results suggest that levels of some phthalates may play a role in the genesis of diabetes.

Biomarker measurements of concurrent exposure to multiple environmental chemicals and chemical classes in children.

Concern is mounting that children from disadvantaged, low-income neighborhoods are likely to be both more exposed to chemical hazards and more susceptible to related adverse health effects. This article reports measurements of >75 individual biomarkers spanning 7 chemical/pollutant classes in blood and urine from more than 100 children living in a socioeconomically disadvantaged and ethnically diverse area of south Minneapolis, MN. Results indicate that a significant proportion of children in the study were at the high end of the exposure distribution compared to national reference ranges for a variety of environmental chemicals and/or their metabolites, including phthalates, organochlorine pesticides, organophosphate pesticides, metals, polychlorinated biphenyls, and volatile organic compounds. In addition, levels of cotinine in urine indicate that more than half the children were regularly exposed to environmental tobacco smoke, with the upper 10th percentile exposed to relatively high concentrations.

High-throughput sample preparation for the quantitation of acephate, methamidophos, omethoate, dimethoate, ethylenethiourea, and propylenethiourea in human urine using 96-well-plate automated extraction and high-performance liquid chromatography-tandem mass spectrometry.

Acephate, methamidophos, o-methoate, and dimethoate are organophosphorus pesticides, and ethylenethiouria and propylenethiourea are two metabolites from the bisdithiocarbamate fungicide family. They are some of the most widely used pesticides and fungicides in agriculture both domestically and abroad. The existing high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS) method for the measurement of these compounds in human urine was improved by using a 96-well plate format sample preparation; the use of HPLC-MS/MS was comparable with a concentration range of 0.125 to 50 ng/ml. Deuterium-labeled acephate, ethylenethiouria, and methamidophos were used as internal standards. The sample preparation procedure, in the 96-well format with a 0.8-ml urine sample size, uses lyophilization of samples, followed by extraction with dichloromethane. The analytes were chromatographed on a Zorbax SB-C3 (4.6 × 150 mm, 5.0-µm) column with gradient elution by using 0.1% formic acid in aqueous solution (solvent A) and 0.1% formic acid in methanol (solvent B) mobile phase at a flow rate of 1 ml/min. Quantitative analysis was performed by atmospheric pressure chemical ionization source in positive ion mode using multiple-reaction monitoring of the precursor-to-product ion pairs for the analytes on a TSQ Quantum Ultra HPLC-MS/MS. Repeated analyses of urine samples spiked with high (15 ng/ml), medium (5 ng/ml), and low (1 ng/ml) concentrations of the analytes gave relative SDs of <13%. The limits of detection were in the range of 0.004-0.01 ng/ml. The method also has high accuracy, high precision, and excellent extraction recovery. Furthermore, the improved sample preparation method decreased the cost and labor required while effectively doubling the analytic throughput with minimal matrix effect.

Prenatal environmental tobacco smoke exposure and early childhood body mass index.

Maternal smoking during pregnancy is associated with increased risk of childhood overweight body mass index (BMI). Less is known about the association between prenatal secondhand tobacco smoke (SHS) exposure and childhood BMI. We followed 292 mother-child dyads from early pregnancy to 3 years of age. Prenatal tobacco smoke exposure during pregnancy was quantified using self-report and serum cotinine biomarkers. We used linear mixed models to estimate the association between tobacco smoke exposure and BMI at birth, 4 weeks, and 1, 2 and 3 years. During pregnancy, 15% of women reported SHS exposure and 12% reported active smoking, but 51% of women had cotinine levels consistent with SHS exposure and 10% had cotinine concentrations indicative of active smoking. After adjustment for confounders, children born to active smokers (self-report or serum cotinine) had higher BMI at 2 and 3 years of age, compared with unexposed children. Children born to women with prenatal serum cotinine concentrations indicative of SHS exposure had higher BMI at 2 (mean difference [MD] 0.3 [95% confidence interval -0.1, 0.7]) and 3 (MD 0.4 [0, 0.8]) years compared with unexposed children. Using self-reported prenatal exposure resulted in non-differential exposure misclassification of SHS exposures that attenuated the association between SHS exposure and BMI compared with serum cotinine concentrations. These findings suggest active and secondhand prenatal tobacco smoke exposure may be related to an important public health problem in childhood and later life. In addition, accurate quantification of prenatal secondhand tobacco smoke exposures is essential to obtaining valid estimates.

Body burdens of brominated flame retardants and other persistent organo-halogenated compounds and their descriptors in US girls.

BACKGROUND: Levels of brominated flame retardants are increasing in US populations, yet little data are available on body burdens of these and other persistent hormonally active agents (HAAs) in school-aged children. Exposures to such chemicals may affect a number of health outcomes related to development and reproductive function. OBJECTIVE: Determine the distribution of biomarkers of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and organo-chlorinated pesticides (OCPs), such as DDT/DDE, in children, and their variation by key descriptor variables. METHODS: Ethnically diverse cohorts of girls 6-8 y old at baseline are being followed for growth and pubertal development in a multi-site, longitudinal study. Nearly 600 serum samples from the California and Ohio sites were analyzed for lipids, 35 PCB congeners, 11 PBDE congeners, and 9 OCPs. The biomarker distributions were examined and geometric means compared for selected analytes across categories of age, race, site, body mass index (BMI), parental education, maternal age at delivery, and breast feeding in adjusted models. RESULTS: Six PBDE congeners were detected among greater than 70% of samples, with BDE-47 having the highest concentration (median 42.2, range 4.9-855 ng/g lipid). Girls in California had adjusted geometric mean (GM) PBDE levels significantly higher than girls in Ohio. Furthermore, Blacks had significantly higher adjusted GMs of all six PBDE congeners than Whites, and Hispanics had intermediate values. GMs tended to be lower among more obese girls, while other variables were not strongly associated. In contrast, GMs of the six PCB congeners most frequently detected were significantly lower among Blacks and Hispanics than Whites. PCBs and the three pesticides most frequently detected were also consistently lower among girls with high BMI, who were not breast-fed, whose mothers were younger, or whose care-givers (usually parents) were less educated. Girls in California had higher GMs than in Ohio for the pesticides and most PCB congeners, but the opposite for CB-99 and -118. CONCLUSIONS: Several of these potential HAAs were detected in nearly all of these young girls, some at relatively high levels, with variation by geographic location and other demographic factors that may reflect exposure pathways. The higher PBDE levels in California likely reflect differences in fire regulation and safety codes, with potential policy implications.

Polyfluoroalkyl chemicals in house dust.

We developed a high throughput analytical method using on-line solid phase extraction coupled with isotope dilution high-performance liquid chromatography-tandem mass spectrometry (on-line SPE-HPLC-MS/MS) to simultaneously determine the concentrations of 17 polyfluoroalkyl chemicals (PFCs) in house dust. The sample preparation includes dispersion of the dust samples in 0.1 M formic acid:MeOH (1:1), followed by agitation and filtration, addition of the isotope-labeled internal standard solution to the filtrate, and analysis by on-line SPE-HPLC-MS/MS. The limits of quantitation were <4.0 ng/g. The method accuracies ranged between 73.2% and 100.2% for the different analytes at two spike levels. We confirmed the validity of the method by analyzing 39 household dust samples collected in 2004. Of the 17 PFCs measured, 6 of them--perfluorobutane sulfonate (PFBuS), N-ethyl-perfluorooctane sulfonamide, 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid (Et-PFOSA-AcOH), 2-(N-methyl-perfluorooctane sulfonamido) ethanol (Me-PFOSA-EtOH), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS)--had detection frequencies >70%. We detected PFOS, PFBuS, and PFHxS at the highest median concentration, followed by Et-PFOSA-AcOH and Me-PFOSA-EtOH.

Temporal stability of eight phthalate metabolites and their glucuronide conjugates in human urine.

Humans are exposed to phthalates due to the ubiquitous use of these chemicals in consumer products. In the body, phthalates metabolize quickly to form hydrolytic and oxidative monoesters which, in turn, can be glucuronidated before urinary excretion. Exposure assessment studies typically report the total urinary concentrations of phthalate metabolites (i.e., free plus glucuronidated species). Nevertheless, because conjugation may potentially reduce the bioactivity of the metabolites by reducing their bioavailability, measuring the concentrations of free species may be of interest. An accurate, quantitative measurement of phthalate monoesters and their conjugated species requires data on the stability of these species in urine after sample collection and before analysis. We studied the stability of eight phthalate metabolites and their glucuronide conjugates at 25, 4, and -70 degrees C. Interestingly, the total concentrations of phthalate metabolites decreased over time at 25 and 4 degrees C, but not at -70 degrees C for up to 1 year and despite several freeze-thaw cycles. We further observed a considerable decrease in the concentrations of the glucuronides of some phthalate metabolites 1 day and 3 days after collection when the samples were stored at 25 and 4 degrees C, respectively. By contrast, the concentrations of the glucuronide conjugates at -70 degrees C remained unchanged for the whole duration of the study (1 year). Based on these findings, we recommend transferring urine specimens to a cooler or a refrigerator immediately after collection followed by permanent storage at subfreezing temperatures within hours of sample collection.

A mass spectrometry-based method to measure dialkylphosphate degradation products of organophosphorous insecticides in dust and orange juice.

Dialkylphosphates (DAPs) are urinary metabolites and breakdown products of organophosphorous (OP) pesticides. Urinary DAPs are widely used to assess exposure to OP pesticides in epidemiologic studies. Recent evidence suggests that preformed DAPs are present in food and that they may also be present in other parts of the environment. Thus, DAP concentrations observed in urine may reflect a person's exposure to both parent OP pesticides and preformed DAPs in food and other environmental media. The presence of preformed DAPs in multiple media may indicate that previous studies have overestimated exposure to OP pesticides and that the use of urinary DAPs as biomarkers of exposure for OP pesticides may not accurately characterize exposure in non-acute settings. To establish the presence of DAPs in environmental and food media, we developed analytical methods to measure six DAPs in dust and orange juice. The limits of detection (LOD) for the dimethyl phosphates (dimethylphosphate (DMP), dimethylthiophosphate, and dimethyldithiophosphate) ranged from 2.8-9.9 ng g(-1) and 0.2-0.4 ng mL(-1) in dust and juice, respectively. The LODs for the diethyl phosphates (diethylphosphate (DEP), diethylthiophosphate, diethyldithiophosphate) ranged from 5.2-10.4 ng g(-1) and 0.5-3.0 ng mL(-1) in dust and juice, respectively. The extraction efficiencies for the analytes ranged from 23% to 91% and from 41% to 85% in dust and orange juice, respectively. DMP was detected in about half of the dust samples whereas DEP was detected in 80% of the dust samples tested. Other DAPs were less frequently detected in dust. Less than 3% of intact pesticide present in the matrices was converted to their respective DAPs during the pre-analytic and analytic process. Evaluation of the conversion of intact pesticides in the samples to DAPs will help us to better understand the contribution of preformed DAPs to urinary DAP concentrations.

Urinary paranitrophenol, a metabolite of methyl parathion, in Thai farmer and child populations.

Human exposure to methyl parathion can be assessed by measuring the concentration of its metabolite paranitrophenol (PNP) in urine. Our biologic monitoring study in Chiang Mai, Thailand, measured PNP and dialkylphosphate metabolites (i.e., dimethylphosphate [DMP] and dimethylthiophosphate [DMTP]) of methyl parathion in urine samples collected from 136 farmers (age 20 to 65 years) and 306 school children (age 10 to 15 years) in 2006. Participants came from two topographically different areas: one was colder and mountainous, whereas the other was alluvial with climate fluctuations depending on the monsoon season. Both children and farmers were recruited from each area. Despite methyl parathion's prohibited use in agriculture in 2004, we detected PNP in >90% of all samples analyzed. We applied a nonparametric correlation test (PNP vs. DMP and DMTP) to determine whether the PNP found in most of the samples tested resulted from exposures to methyl parathion. DMP (Spearman's rho = 0.601 [p = 0.001] for farmers and Spearman's rho = 0.263 [p <0.001] for children) and DMTP (Spearman's rho = 0.296 [p = 0.003] for farmers and Spearman's rho = 0.304 [p<0.001] for children) were positively correlated with PNP, suggesting a common source for the three analytes, presumably methyl parathion or related environmental degradates. Although we found a modest correlation between the metabolites, our findings suggest that despite the prohibition, at least a portion (approximately 25% to 60%) of the PNP detected among farmers and children in Thailand may be attributed to exposure from continued methyl parathion use.

Automated solid-phase extraction approaches for large scale biomonitoring studies.

The main value in measuring environmental chemicals in biological specimens (i.e., biomonitoring) is the ability to minimize risk assessment uncertainties. The collection of biomonitoring data for risk assessment requires the analysis of a statistically significant number of samples from subjects with a significant prevalence of detectable internal dose levels. This paper addresses the practical laboratory challenges that arise from these statistical requirements: development of high throughput techniques that can handle, with high accuracy and precision, a large number of samples and can do a trace level analysis of multiple and diverse environmental chemicals (i.e., analytes). We review here examples of high throughput, automated solid-phase extraction methods developed in our laboratory for biomonitoring of analytes with representative hydrophobic properties and for typical biomonitoring matrices. We discuss key aspects of sample preparation, column, and solvent selection for off- and online extractions, and the so-called nuts-and-bolts of online column-switching systems necessary for developing-with minimal sample handling-rugged, automated methods.

Polychlorinated biphenyl levels in peripheral blood and non-Hodgkin's lymphoma: a report from three cohorts.

The incidence of non-Hodgkin's lymphoma (NHL) unrelated to HIV infection has steadily increased over the past several decades and remains substantially unexplained. Limited evidence suggests that increased concentrations of polychlorinated biphenyls (PCB) measured in blood or fat tissue are associated with increased risk of NHL. Although PCB congeners vary in their biological activity, the relation between individual congeners and NHL risk has not been examined previously using prospectively collected biospecimens. We examined congener-specific associations in three prospective cohorts. Prediagnostic serum or plasma concentrations of selected PCB congeners were measured among NHL cases and controls from these cohorts: Janus (190 cases and 190 controls) in Norway and CLUE I (74 cases and 147 controls) and the Nurses' Health Study (30 cases and 78 controls) in the United States. All blood samples were collected in the 1970s or 1980s. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the relations between risk of NHL and lipid-corrected plasma or serum concentrations. Several congeners (i.e., 118, 138, and 153) that were present at higher levels and were moderately to highly correlated with each other showed exposure-response trends with risk of NHL in all three cohorts. These associations were observed primarily among subjects diagnosed closer to the date of blood collection in the two cohorts with sufficient cases to permit stratification by time. Among cases diagnosed within the median years of follow-up (16 years in Janus and 12 years in CLUE I), ORs and 95% CIs for increasing fourths of concentration of congener 118 relative to the lowest fourth were as follows: 2.4 (0.9-6.5), 4.9 (1.6-15.3), and 5.3 (1.5-18.8; P(trend) < 0.005) in Janus and 8.1 (1.0-68.9), 6.6 (0.7-59.0), and 13.0 (1.6-106.8; P(trend) < 0.05) in CLUE I. Similar patterns were seen for congeners 138 and 153 and for total PCBs. Limited evidence of exposure-response trends was also observed for several other congeners. The primary 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane metabolite, p,p'-DDE, was not significantly associated with NHL in most analyses but slightly to moderately confounded the PCB associations. The results from these three cohorts suggest that concentrations of certain PCBs in blood are associated with increased risk of NHL.

Serum organochlorine pesticide residues and risk of testicular germ cell carcinoma: a population-based case-control study.

Testicular germ cell carcinoma (TGCC) is the most common malignancy among men ages 20 to 34 years. Although the pathogenesis of TGCC is poorly understood, suboptimal androgen levels or impaired androgen signaling may play a role. Some persistent organochlorine pesticides commonly found in human tissue possess antiandrogenic properties. We examined whether the risk of TGCC is associated with serum levels of 11 organochlorine pesticides, including p,p'-DDE, and whether the p,p'-DDE-TGCC association is modified by CAG or GGN repeat polymorphisms in the androgen receptor gene. We conducted a population-based case-control study among 18- to 44-year-old male residents of three Washington State counties. Cases (n = 246) were diagnosed during 1999 to 2003 with a first, primary TGCC. Controls (n = 630) were men of similar age with no history of TGCC from the same population identified through random-digit telephone dialing. Questionnaires elicited information on demographic, medical, and lifestyle factors. A blood specimen provided serum for gas chromatography-high-resolution mass spectrometry analysis of organochlorine pesticide residues and DNA for genotyping. We observed no clear patterns between TGCC risk and concentrations of any of the organochlorines measured, nor did we observe that the risk associated with p,p'-DDE was modified by androgen receptor CAG (<23 versus > or =23 repeats) or GGN (<17 versus > or =17 repeats) genotype. This study does not provide support for the hypothesis that adult exposure to organochlorine pesticides is associated with risk of TGCC. Due to uncertainty regarding how well organochlorine levels measured in adulthood reflect exposures during early life, further research is needed using exposure measurements collected in utero or during infancy.

Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003-2004.

BACKGROUND: Bisphenol A (BPA) and 4-tertiary-octylphenol (tOP) are industrial chemicals used in the manufacture of polycarbonate plastics and epoxy resins (BPA) and nonionic surfactants (tOP). These products are in widespread use in the United States. OBJECTIVES: We aimed to assess exposure to BPA and tOP in the U.S. general population. METHODS: We measured the total (free plus conjugated) urinary concentrations of BPA and tOP in 2,517 participants > or = 6 years of age in the 2003-2004 National Health and Nutrition Examination Survey using automated solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry. RESULTS: BPA and tOP were detected in 92.6% and 57.4% of the persons, respectively. Least square geometric mean (LSGM) concentrations of BPA were significantly lower in Mexican Americans than in non-Hispanic blacks (p = 0.006) and non-Hispanic whites (p = 0.007); LSGM concentrations for non-Hispanic blacks and non-Hispanic whites were not statistically different (p = 0.21). Females had statistically higher BPA LSGM concentrations than males (p = 0.043). Children had higher concentrations than adolescents (p < 0.001), who in turn had higher concentrations than adults (p = 0.003). LSGM concentrations were lowest for participants in the high household income category (> $45,000/year). CONCLUSIONS: Urine concentrations of total BPA differed by race/ethnicity, age, sex, and household income. These first U.S. population representative concentration data for urinary BPA and tOP should help guide public health research priorities, including studies of exposure pathways, potential health effects, and risk assessment.

Urinary concentrations of triclosan in the U.S. population: 2003-2004.

BACKGROUND: Triclosan is a synthetic chemical with broad antimicrobial activity that has been used extensively in consumer products, including personal care products, textiles, and plastic kitchenware. OBJECTIVES: This study was designed to assess exposure to triclosan in a representative sample > or = 6 years of age of the U.S. general population from the 2003-2004 National Health and Nutrition Examination Survey (NHANES). METHODS: We analyzed 2,517 urine samples using automated solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry. RESULTS: We detected concentrations of total (free plus conjugated) triclosan in 74.6% of samples at concentrations of 2.4-3,790 microg/L. The geometric mean and 95th percentile concentrations were 13.0 microg/L (12.7 microg/g creatinine) and 459.0 microg/L (363.8 mug/g creatinine), respectively. We observed a curvilinear relation between age and adjusted least square geometric mean (LSGM) concentrations of triclosan. LSGM concentrations of triclosan were higher in people in the high household income than in people in low (p < 0.01) and medium (p = 0.04) income categories. CONCLUSIONS: In about three-quarters of urine samples analyzed as part of NHANES 2003-2004, we detected concentrations of triclosan. Concentrations differed by age and socioeconomic status but not by race/ethnicity and sex. Specifically, the concentrations of triclosan appeared to be highest during the third decade of life and among people with the highest household incomes.

Concentrations of the sunscreen agent benzophenone-3 in residents of the United States: National Health and Nutrition Examination Survey 2003--2004.

BACKGROUND: The capability of benzophenone-3 (BP-3) to absorb and dissipate ultraviolet radiation facilitates its use as a sunscreen agent. BP-3 has other uses in many consumer products (e.g., as fragrance and flavor enhancer, photoinitiator, ultraviolet curing agent, polymerization inhibitor). OBJECTIVES: Our goal was to assess exposure to BP-3 in a representative sample of the U.S. general population > or = 6 years of age. METHODS: Using automated solid-phase extraction coupled to high-performance liquid chromatography-tandem mass spectrometry, we analyzed 2,517 urine samples collected as part of the 2003--2004 National Health and Nutrition Examination Survey. RESULTS: We detected BP-3 in 96.8% of the samples. The geometric mean and 95th percentile concentrations were 22.9 microg/L (22.2 microg/g creatinine) and 1,040 microg/L (1,070 microg/g creatinine), respectively. Least-square geometric mean (LSGM) concentrations were significantly higher (p < or = 0.04) for females than for males, regardless of age. LSGM concentrations were significantly higher for non-Hispanic whites than for non-Hispanic blacks (p < or = 0.01), regardless of age. Females were more likely than males [adjusted odds ratio (OR) = 3.5; 95% confidence interval (95% CI), 1.9-6.5], and non-Hispanic whites were more likely than non-Hispanic blacks (adjusted OR = 6.8; 95% CI, 2.9-16.2) to have concentrations above the 95th percentile. CONCLUSIONS: Exposure to BP-3 was prevalent in the general U.S. population during 2003--2004. Differences by sex and race/ethnicity probably reflect differences in use of personal care products containing BP-3.

Birth delivery mode modifies the associations between prenatal polychlorinated biphenyl (PCB) and polybrominated diphenyl ether (PBDE) and neonatal thyroid hormone levels.

BACKGROUND: Developing infants may be especially sensitive to hormone disruption from chemicals including polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). OBJECTIVE: We investigated relationships between cord serum levels of PCBs and PBDEs and thyroid hormones measured in cord blood serum and neonatal blood spots. METHODS: We measured PCBs and PBDEs, thyrotropin (TSH), thyroxine (T4) and free T4 (FT4) in cord blood serum from 297 infants who were delivered at the Johns Hopkins Hospital in 2004-2005. We abstracted results of total T4 (TT4) measured in blood spots collected in the hospital and at neonatal visits. We used delivery mode (augmented vaginal deliveries and nonelective cesarean deliveries) as a surrogate for intrapartum stress, which is known to alter cord blood thyroid hormones. RESULTS: In the full study population, no compounds were associated with a change in average TSH, FT4, or TT4. BDE-100 was associated with increased odds of low cord TT4, BDE-153 with increased odds of low cord TT4 and FT4, and no compounds were associated with increased odds of high TSH. For infants born by spontaneous, vaginal, unassisted deliveries, PCBs were associated with lower cord TT4 and FT4 and lower TT4 measured in neonatal blood spots. PBDEs showed consistent but mainly nonsignificant negative associations with TT4 and FT4 measurements. CONCLUSIONS: Prenatal PCB and PBDE exposures were associated with reduced TT4 and FT4 levels among infants born by spontaneous, unassisted vaginal delivery. Intrapartum stress associated with delivery mode may mask hormonal effects of PCBs and PBDEs.