Plasma concentration of brominated flame retardants and postmenopausal breast cancer risk: a nested case-control study in the French E3N cohort.

BACKGROUND: Brominated flame retardants (BFRs) are lipophilic substances with endocrine-disrupting properties. To date, only few investigations, mainly retrospective case-control studies, have explored the link between internal levels of BFRs and the risk of breast cancer, leading to conflicting results. We investigated the associations between plasma concentrations of two main groups of BFRs, PBDEs (pentabromodiphenyl ethers) and PBBs (polybrominated biphenyls), and the risk of breast cancer in a nested case-control study. METHODS: A total of 197 incident breast cancer cases and 197 controls with a blood sample collected in 1994-1999 were included. Plasma levels of PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, BDE153, BDE-154) and of PBB-153 were measured by gas chromatography coupled to high-resolution mass spectrometry. Conditional logistic regression models, adjusted for potential confounders, were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Women were aged 56 years on average at blood draw. All cases, except for one, were diagnosed after menopause, with an average age at diagnosis of 68 years. Overall, we found no evidence of an association between plasma levels of PBDEs and PBB-153 and postmenopausal breast cancer risk (log-concentrations of BFRs yielding non-statistically significant ORs of 0.87 to 1.07). The analysis showed a non-linear inverse association for BDE-100 and BDE-153 and postmenopausal breast cancer risk; nevertheless, these findings were statistically significant only when the exposure was modeled as ng/L plasma (third vs. first quintile: OR = 0.42, 95%CI = 0.19-0.93 and OR = 0.42, 95%CI = 0.18-0.98, respectively) and not when modeled as ng/gr of lipids (OR = 0.58, 95%CI = 0.27-1.25 and OR = 0.53, 95%CI = 0.25-1.17). These results were unchanged in stratified analyses by tumor hormone receptor expression or body mass index. CONCLUSIONS: Our results suggest no clear association between internal levels of PBDEs and PBB-153 and the risk of breast cancer in postmenopausal women. However, these findings need to be carefully interpreted, taking into account limitations due to the limited number of women included in the study, the lack of information concerning genetic susceptibility of cases, and the unavailability of exposure assessment during critical windows of susceptibility for breast cancer. More studies are warranted to further investigate the relationships between PBDE and PBB exposure and breast cancer risk.

Serum concentrations of polybrominated biphenyls (PBBs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in the Michigan PBB Registry 40 years after the PBB contamination incident.

Widespread polybrominated biphenyls (PBBs) contamination occurred in Michigan from 1973 to 1974, when PBBs were accidentally substituted for a nutritional supplement in livestock feed. People who lived in the state were exposed to PBBs via several routes including ingestion, inhalation and skin absorption. PBBs sequestered in lipid-rich matrices such as adipose tissue, are slowly eliminated after entering the human body, and can also be transferred from a mother to her offspring through the placenta and breastfeeding. Due to the long biological half-lives of PBBs, as well as concerns from the exposed community, biomonitoring measurements were conducted from 2012 to 2015. Because of their similar structures, serum PBBs, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) were all measured 40 years after the PBB contamination incident (N = 862). The serum PBB-153 levels among the original highly-exposed groups (i.e., chemical workers, the family of chemical workers, and individuals who lived on or received food from the contaminated farms) remains significantly higher than other Michigan residents. Several predictors such as sampling age, sex, and smoking status were significantly associated with the serum levels of some persistent organic pollutants (POPs). Higher average values and also wider ranges of serum POP levels were found in this study compared to the National Health and Nutrition Examination Survey (NHANES), with the most substantial difference in serum PBB-153. This was true for all groups of Michigan residents including those who were not part of the above-described highly-exposed groups. Moreover, the people born after the contamination incident began also have higher serum PBB-153 levels when compared with more recent NHANES data (2010-2014), which suggests potential intergenerational exposure and/or continued environmental exposure following the contamination period.

Polybrominated Diphenyl Ethers, Polybrominated Biphenyls, and Risk of Papillary Thyroid Cancer: A Nested Case-Control Study.

A nested case-control study was carried out using data from the US Department of Defense cohort between 2000 and 2013 to investigate the associations of papillary thyroid cancer (PTC) with serum concentrations of polybrominated diphenyl ethers and polybrominated biphenyls. This study included 742 histologically confirmed PTC cases (in 341 women and 401 men) and 742 matched controls with prediagnostic serum samples from the Department of Defense Serum Repository. Lipid-corrected serum concentrations of 8 congeners were measured. Multivariate conditional logistic regression analyses were performed for classical PTC and follicular variant of PTC, respectively. We also examined effect modification by sex. BDE-28, a polybrominated diphenyl ether congener, was associated with significantly increased risk of classical PTC (for the third tertile vs. below the limit of detection, odds ratio = 2.09, 95% confidence interval: 1.05, 4.15; P for trend = 0.02), adjusting for other congeners, body mass index, and branch of military service. This association was observed mainly for larger classical PTC (tumor size > 10 mm), with a significantly stronger association among women than men (P for interaction = 0.004). No consistent associations were observed for other congeners, including those at higher concentrations. This study found a significantly increased risk of classical PTC associated with increasing levels of BDE-28. The risk varied by sex and tumor size.

Exposure to Polybrominated Diphenyl Ethers and a Polybrominated Biphenyl and Risk of Thyroid Cancer in Women: Single and Multi-Pollutant Approaches.

BACKGROUND: Thyroid cancer incidence is the most rapidly increasing malignancy; rates are three times higher in women than men. Thyroid hormone-disrupting flame-retardant chemicals, including polybrominated diphenyl ethers (PBDE) and polybrominated biphenyls (PBB), may contribute to this trend. METHODS: We investigated the relationship between PBDE/PBB exposure and papillary thyroid cancer (PTC) in 250 incident female papillary thyroid cancer cases and 250 female controls frequency-matched on age. Interviews and postdiagnostic serum samples were collected from 2010 to 2013. Serum samples were analyzed for 11 congeners. We calculated ORs and 95% confidence intervals (95% CI) using single-pollutant logistic regression models for continuous and categorical lipid-adjusted serum concentrations of PBDE/PBB, adjusted for age, alcohol consumption, and education. We applied three multi-pollutant approaches [standard multipollutant regression models, hierarchical Bayesian logistic regression modeling (HBLR), principal components analysis (PCA)] to investigate associations with PBDE/PBB mixtures. RESULTS: In single-pollutant models, a decreased risk was observed at the highest (>90th percentile) versus lowest (

Environmental exposure to polybrominated biphenyl (PBB) associates with an increased rate of biological aging.

Advanced age increases risk for cancer, cardiovascular disease, and all-cause mortality. However, people do not age at the same rate, and biological age (frequently measured through DNA methylation) can be older than chronological age. Environmental factors have been associated with the rate of biological aging, but it is not known whether persistent endocrine-disrupting compounds (EDCs) like polybrominated biphenyl (PBB) would associate with age acceleration. Three different epigenetic age acceleration measures (intrinsic, extrinsic, and phenotypic) were calculated from existing epigenetic data in whole blood from a population highly exposed to PBB (N=658). Association between serum PBB concentration and these measures was tested, controlling for sex, lipid levels, and estimated cell type proportions. Higher PBB levels associated with increased age acceleration (intrinsic: ß=0.24, 95%CI=0.01-0.46, p = 0.03; extrinsic: ß=0.39, 95%CI=0.12-0.65, p = 0.004; and phenotypic: ß=0.30, 95%CI=0.05-0.54, p = 0.01). Neither age when exposed to PBB nor sex statistically interacted with PBB to predict age acceleration, but, in stratified analyses, the association between PBB and age acceleration was only in people exposed before finishing puberty and in men. This suggests that EDCs can associate with the biological aging process, and further studies are warranted to investigate other environmental pollutants' effect on aging.

Molecular Mechanisms of Polybrominated Diphenyl Ethers (BDE-47, BDE-100, and BDE-153) in Human Breast Cancer Cells and Patient-Derived Xenografts.

Polybrominated diphenyl ethers (PBDEs) have been used as flame retardants in household materials. Their environmental persistence has led to continuous human exposure and significant tissue levels. Three PBDE congeners (BDE-47, BDE-100, and BDE-153) have been frequently detected in human serum. Although these compounds appear to possess endocrine disrupting activity, studies are largely missing to determine the biological mechanisms of PBDEs in breast cancer cells. Here, we assessed PBDE bioactivities with three complementary strategies: receptor binding/activity assays; nonbiased RNA-sequencing analysis using an estrogen-dependent breast cancer cell line MCF-7aroERE; and in vivo assessments using patient-derived xenograft (PDX) models of human breast cancer. According to the results from in vitro experiments, the PBDE congeners regulate distinct nuclear receptor signaling pathways. BDE-47 acts as a weak agonist of both estrogen receptor α (ERα) and estrogen-related receptor α (ERRα); it could stimulate proliferation of MCF-7aroERE and induced expression of ER-regulated genes (including cell cycle genes). BDE-153 was found to act as a weak antagonist of ERα. BDE-100 could act as (1) an agonist of aryl hydrocarbon receptor (AhR), inducing expression of CYP1A1 and CYP1B1 and (2) as a very weak agonist/antagonist of ERα. In vivo, a mixture of the three congeners with ratios detected in human serum was tested in an ER+ PDX model. The mixture exhibited estrogenic activity through apoptosis/cell cycle regulation and increased the expression of a proliferation marker, Ki-67. These results advance our understanding of the mechanisms of PBDE exposure in breast cancer cells.

Temporal trends and developmental patterns of plasma polybrominated diphenyl ether concentrations over a 15-year period between 1998 and 2013.

Polybrominated diphenyl ethers (PBDEs) were used extensively as flame retardants in furniture containing polyurethane foam until they were phased out of use, beginning in 2004. We examined temporal changes in plasma PBDE concentrations from 1998 to 2013 and characterized patterns of exposure over the early lifecourse among 334 children (903 samples) between birth and 9 years. We examined time trends by regressing PBDE concentration on year of sample collection in age-adjusted models and characterized developmental trajectories using latent class growth analysis (LCGA). Controlling for age, BDE-47 concentrations decreased 5% (95% confidence interval (CI): -9, -2) per year between 1998 and 2013. When considering only postnatal samples, this reduction strengthened to 13% (95% CI: -19, -9). Findings for BDE-99, 100 and 153 were similar, except that BDE-153 decreased to a lesser extent when both prenatal and postnatal samples were considered (-2%, 95% CI: -7, 0). These findings suggest that, on average, pentaBDE body burdens have decreased since the 2004 phase-out of these chemicals. When examining developmental period, PBDE concentrations peaked during toddler years for the majority of children, however, our observation of several unique trajectories suggests that a single measure may not accurately reflect exposure to PBDEs throughout early life.

Biomonitoring Equivalents (BEs) for tetrabromobisphenol A.

Tetrabromobisphenol A (TBBPA) is a flame retardant used in a variety of products, including epoxy and polycarbonate resins. Relevant exposure to TBBPA has been assessed by measuring TBBPA in the blood of humans. Here, we derive Biomonitoring Equivalents (BEs) for TBBPA to interpret these, and future biomonitoring results for TBBPA in humans. The available toxicity risk values (TRVs) for TBBPA were all based on toxicology studies in rats. Several studies have been conducted in which TBBPA in blood of rats were measured following controlled oral doses of TBBPA. These data provide a robust relationship from which to derive BEs. BEs of 5.6 and 13.0 µg total TBBPA/L plasma were calculated for available cancer and non-cancer TRVs, respectively. Several studies have measured TBBPA in serum, with median concentrations less than 0.1 µg/L, indicating considerable margins of safety (MOS) for TBBPA based on the currently available biomonitoring studies.

TBBPA disposition and kinetics in pregnant and nursing Wistar Han IGS rats.

Tetrabromobisphenol-A (TBBPA) is a brominated flame retardant (BFR) commonly used in electronics to meet fire safety standards and has the largest worldwide production of any BFR. TBBPA has been detected in human breast milk and maternal/cord serum, indicating exposure to mothers, fetuses, and breastfeeding newborns although exposure to fetuses and newborns is poorly understood. Pregnant or nursing Wistar Han IGS rats were administered [14C]-TBBPA in a single dose (25 mg/kg, 2.5 µCi/kg) and euthanized between 0.5&24 h post dose to determine disposition in pregnant and nursing rats and their pups. Systemic exposure was largely unchanged between 1&8 h post dose in pregnant rats; [14C]-radioactivity in blood varied only slightly between 0.5&8 h (2.6 ± 0.6 â†’ 2.6 ± 0.8 nmol-eq/mL) but was below the limit of detection at 24 h with an absorption half-life of 16min and elimination half-life of 17 h. Cmax was observed at 30min in lactating rats and concentrations fell steadily through 8 h. Plasma from pregnant rats contained a mixture of TBBPA and TBBPA-conjugates at 30min but only metabolites in subsequent samples. TBBPA was not detected in lactating dam plasma in this study. Placental concentrations increased through 8 h while whole-fetus Cmax occurred at 2 h post dose. In lactating animals, liver, uterus, and mammary time-concentration curves lagged slightly behind blood-concentration curves. It was clear from these studies that TBBPA is available to both the developing fetus and nursing pup following maternal exposure, and nursing pups are continuously exposed via contaminated milk produced by their mother. This research was supported in part by the Intramural Research Program of NIH/NCI.

Polychlorinated biphenyl and polybrominated diphenyl ether profiles in serum from cattle, sheep, and goats across California.

It has been previously been shown by our lab and others that persistent organic pollutants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), are contaminants in milk produced for human consumption. To further this research we determined the concentration of 21 PCB and 14 PBDE congeners in livestock serum, mainly bovine, across California. Congeners were extracted from serum using solid phase extraction (SPE), cleaned up by silica cartridge and quantified using gas chromatography-triple quadruple mass spectrometry. We detected significant differences among species and the production class of cattle (beef or dairy). The sum of all 21 PCB congeners (ΣPCBs) in caprine and ovine sera had a mean value of 9.26 and 9.13 ng/mL, respectively, compared to 3.98 ng/mL in bovine sera. The mean value for the sum of all 14 PBDE congeners (ΣPBDEs) in caprine and ovine sera was 2.82 and 2.39 ng/mL, respectively, compared to 0.91 ng/mL in bovine sera. Mean ΣPCBs in dairy cattle was 5.92 ng/mL compared to 2.70 ng/mL in beef cattle. Mean ΣPBDEs in dairy cattle was 1.33 ng/mL compared to 0.70 ng/mL in beef cattle. There were no regional differences in the ΣPCBs or ΣPBDEs in cattle distributed across California. These results highlight the fact that livestock are still being exposed to these pollutants yet little is known about where this exposure may be coming from.

Temporal Evaluation of Polybrominated Diphenyl Ether (PBDE) Serum Levels in Middle-Aged and Older California Women, 2011-2015.

In response to health concerns and widespread human exposures, two widely used commercial formulations of polybrominated diphenyl ethers (PBDEs) were banned in the United States in 2005. Initial biomonitoring data have provided early indications of reduced human exposures since these bans took effect. Our objective was to evaluate temporal trends in PBDE serum levels among a population of older California women during a four-year period, beginning approximately five years after these formulations were banned. Automated solid phase extraction and gas chromatography/high resolution mass spectrometry were used to measure PBDE levels in blood collected during 2011-2015 among 1253 women (ages 40-94) participating in the California Teachers Study. Only congeners with detection frequencies (DF) ≥ 75% were included in the present analysis: BDE-47 (DF = 88%); BDE-100 (DF = 78%); and BDE-153 (DF = 80%). Results from age- and race/ethnicity-adjusted linear regression analyses indicated modest, but statistically significant, average annual percent increases in the serum concentrations of all three PBDEs over the four-year study period. While not without limitations, these results, in the context of other biomonitoring data, suggest that earlier reported declines in PBDE levels may have plateaued and may now be starting to increase. Further biomonitoring to ascertain current trends and determinants of population exposures is warranted.

Prenatal and postnatal polybrominated diphenyl ether exposure and visual spatial abilities in children.

Polybrominated diphenyl ethers (PBDEs) are associated with impaired visual spatial abilities in toxicological studies, but no epidemiologic study has investigated PBDEs and visual spatial abilities in children. The Health Outcomes and Measures of the Environment Study, a prospective birth cohort (2003-2006, Cincinnati, OH), was used to examine prenatal and childhood PBDEs and visual spatial abilities in 199 children. PBDEs were measured at 16±3 weeks gestation and at 1, 2, 3, 5, and 8 years using gas chromatography/isotope dilution high-resolution mass spectrometry. We used the Virtual Morris Water Maze to measure visual spatial abilities at 8 years. In covariate-adjusted models, 10-fold increases in BDE-47, -99, and -100 at 5 years were associated with shorter completion times by 5.2s (95% Confidence Interval [CI] -9.3, -1.1), 4.5s (95% CI -8.1, -0.9), and 4.7s (95% CI -9.0, -0.3), respectively. However, children with higher BDE-153 at 3 years had longer completion times (ß=5.4s, 95% CI -0.3, 11.1). Prenatal PBDEs were associated with improved visual spatial memory retention, with children spending a higher percentage of their search path in the correct quadrant. Child sex modified some associations between PBDEs and visual spatial learning. Longer path lengths were observed among males with increased BDE-47 at 2 and 3 years, while females had shorter paths. In conclusion, prenatal and postnatal BDE-28, -47, -99, and -100 at 5 and 8 years were associated with improved visual spatial abilities, whereas a pattern of impairments in visual spatial learning was noted with early childhood BDE-153 concentrations.

Quantification of Polybrominated and Polychlorinated Biphenyls in Human Matrices by Isotope-Dilution Gas Chromatography-Tandem Mass Spectrometry.

We have developed a highly sensitive and selective analytical method capable of quantifying a total of 15 polybrominated and polychlorinated biphenyls (11 PBBs and 4 PCBs) in human serum. Samples were subjected to liquid-liquid extraction followed by solid-phase extraction prior to measurement using gas chromatography-tandem mass spectrometry in multiple reaction monitoring mode. Quantification was performed using isotope-dilution calibration covering a concentration range of 0.005-12.5 ng/mL. Limits of detection for all target compounds were in the low range (0.7-6.5 pg/mL). The method was validated using in-house pooled human serum fortified at two concentrations (0.5 ng/mL and 1.0 ng/mL), whole semen fortified at one concentration (0.25 ng/mL), and NIST Standard Reference Material (SRM) 1958, which includes five of the target compounds. Method accuracies for all target compounds ranged from 84 to 119% with relative standard deviations (RSDs) of <19%. The measured values for the five target compounds present in the SRM agreed with the certified reference values (89-119% accuracy with RSDs <9%). As this method was developed to support ongoing epidemiologic investigations, we evaluated its suitability by analyzing subsets of serum and whole semen samples from the Michigan PBB Registry cohort. PBB-153, PCB-118, PCB-138, PCB-153 and PCB-180 were detected in all serum samples analyzed, with PBB-77 and PBB-101 detected less frequently in serum. PBB-153, PCB-118, PCB-138, PCB-153 and PCB-180 were detected in at least one whole semen sample.

Validation of the analytical method for the simultaneous determination of selected polybrominated diphenyl ethers, polychlorinated biphenyls and organochlorine pesticides in human blood serum by gas chromatography with microelectron capture detector.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) as other persistent organic pollutants like polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) pose a significant hazard to human health, mainly due to interference with the endocrine system and carcinogenetic effects. Humans are exposed to these substances mainly through a food of animal origin. These pollutants are globally detected in human matrices which requires to dispose reliable and simple analytical method that would enable further studies to assess the exposure of specific human populations to these compounds. OBJECTIVE: The purpose of this study was to modify and validate of the analytical procedure for the simultaneous determination of selected PBDEs, PCBs and OCPs in human blood serum samples. MATERIAL AND METHODS: The analytical measurement was performed by GC-µECD following preparation of serum samples (denaturation, multiple extraction, lipid removal). Identity of the compounds was confirmed by GC-MS. RESULTS: The method was characterised by the appropriate linearity, good repeatability (CV below 20%). The recoveries ranged from 52.9 to 125.0% depending on compound and level of fortification. The limit of quantification was set at 0.03 ng mL(-1) of serum. CONCLUSIONS: The modified analytical method proved to be suitable for the simultaneous determination of selected PBDEs, PCBs and OCPs in human blood serum by GC-µECD with good precision.

Breast cancer among women in Michigan following exposure to brominated flame retardants.

In this updated follow-up, we investigated the breast cancer experience among women in Michigan exposed to brominated flame retardants, some 30 years following exposure. Michigan residents were enrolled in a study cohort after exposure to polybrominated biphenyls (PBBs) through the consumption of contaminated food products. PBB concentrations were measured in serum at the time of enrolment. Cancer experience was determined by linkage to the Michigan Cancer Registry. We conducted a nested case-control study that included 51 women diagnosed with breast cancer during 1974-2004 and 202 age-matched controls. While the data suggest an increase in breast cancer risk with higher PBB exposure, this did not reach statistical significance. The OR of having breast cancer among women with PBB concentrations ≥10 ng/mL compared to women with PBB concentrations at or below the limit of detection of 1 ng/mL was 2.60, 95% CI 0.93 to 7.27, (p=0.07), when adjusted for age and family history of cancer in a first-degree female relative. It remains important to examine exposure to brominated chemicals and possible health effects, and to continue following the cancer experience of participants in this study.

Association between Serum Polybrominated Diphenyl Ether Levels and Residential Proximity to Solid-Waste Facilities.

As consumer products treated with polybrominated diphenyl ethers (PBDEs) reach the end of their life cycle, they often are discarded into solid-waste facilities, offering a potential reservoir for exposure. The likelihood of exposures to PBDEs by residents living near those sites rarely has been explored. This study collected blood samples from 923 female participants in the California Teachers Study in 2011-2013 and examined the association between participants' residential proximity to solid-waste facilities with potential release of PBDEs and serum levels of three congeners (BDE-47, BDE-100, and BDE-153). General linear regression analysis was used to examine the association, adjusting for age, race, body-mass index, neighborhood socioeconomic status, and urban residency. Compared to participants living >10 km from any selected site, those living within 2 km had 45% higher BDE-47 (95% CI: 5-100%) and BDE-100 (95% CI: 0-109%) levels, and those living between 2 and 10 km had 35% higher BDE-47 (95% CI: 0-82%) and 29% higher BDE-100 (95% CI: -9 to 82%) levels. No associations were found for BDE-153. Living close to some solid waste sites may be related to higher serum BDE-47 and BDE-100 levels. Studies with comprehensive exposure assessments are needed to confirm these initial observations.

Persistent organic pollutants and pregnancy complications.

We sought to investigate the relationship between maternal preconception exposures to persistent organic pollutants (POPs) and pregnancy complications, gestational diabetes (GDM) and gestational hypertension. Data from 258 (51%) women with human chorionic gonadotropin (hCG) confirmed pregnancies reaching ≥24weeks gestation, from a prospective cohort of 501 couples who discontinued contraception to attempt pregnancy, were analyzed. Preconception concentrations of 9 organochlorine pesticides (OCPs) and 10 polybrominated diphenyl ethers (PBDEs) were quantified in serum. In separate multiple logistic regression models of self-reported physician diagnosed outcomes: GDM (11%) and gestational hypertension (10%), chemicals were natural log-transformed and rescaled by their standard deviation (SD). Models were adjusted for serum lipids, and then adjusted for age, body mass index, race, and smoking. Models were additionally adjusted for the sum of the remaining POPs in each chemical class. Women's serum concentration of PBDE congener 153 (PBDE-153) was positively associated with an increased odds of GDM per SD increase in log-transformed concentration, for unadjusted (OR=1.36, 95%CI: 1.02-1.81), a priori adjusted (OR=1.38, 95% CI: 1.03-1.86) and with the sum of remaining PBDEs (OR=1.79, 95% CI: 1.18, 2.74) models. Our findings suggest that at environmentally relevant concentrations, maternal exposure to POPs prior to conception may contribute to increased chance of developing GDM.

Determinants of plasma PCB, brominated flame retardants, and organochlorine pesticides in pregnant women and 3 year old children in The Norwegian Mother and Child Cohort Study.

BACKGROUND: Exposure to persistent organic pollutants (POPs) during prenatal and postnatal life has been extensively studied in relation to adverse health effects in children. OBJECTIVES: The aim was to identify determinants of the concentrations of polychlorinated biphenyls (PCBs), brominated flame retardants (polybrominated diphenyl ethers, PBDEs; polybrominated biphenyl, PBB), and organochlorine pesticides (OCPs) in blood samples from pregnant women and children in The Norwegian Mother and Child Cohort Study (MoBa). METHODS: Blood samples were collected from two independent subsamples within MoBa; a group of women (n=96) enrolled in mid-pregnancy during the years 2002-2008 and a group of 3 year old children (n=99) participating during 2010-2011. PCB congeners (74, 99, 138, 153, 180, 170, 194, 209, 105, 114, 118, 156, 157, 167, and 189), brominated flame retardants (PBDE-28, 47, 99, 100, 153, 154, and PBB-153), as well as the OCPs hexachlorobenzene (HCB), oxychlordane, 4,4'dichlorodiphenyltrichloroethane (DDT), and 4,4'dichlorodiphenyldichloroethylene (DDE) were measured in both pregnant women and children. RESULTS: Age, low parity, and low pre-pregnant BMI were the most important determinants of increased plasma concentrations of POPs in pregnant women. In 3 year old children, prolonged breastfeeding duration was a major determinant of increased POP concentrations. Estimated dietary exposure to PCBs during pregnancy was positively associated with plasma concentrations in 3 year old children, but not in pregnant women. Plasma concentrations were approximately 40% higher in children compared to pregnant women. CONCLUSIONS: Several factors associated with exposure and toxicokinetics, i.e. accumulation, excretion and transfer via breastmilk of POPs were the main predictors of POP levels in pregnant women and children. Diet, which is the main exposure source for these compounds in the general population, was found to predict PCB levels only among children. For the PBDEs, for which non-dietary sources are more important, toxicokinetic factors appeared to have less predictive impact.

Polybrominated Diphenyl Ether Exposure and Thyroid Function Tests in North American Adults.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are flame-retardant chemicals that are added to many consumer products. Multiple animal studies have shown PBDEs to be thyroid hormone (TH) disruptors. Epidemiologic evidence of PBDE exposure associated with TH disruption has been inconclusive. OBJECTIVES: We used repeated measures to estimate associations between serum PBDE concentrations and THs in a North American adult cohort. METHODS: From 2010 to 2011, we collected ≤ 3 serum samples at approximately 6-month intervals from 52 healthy adult office workers from Boston, Massachusetts, for analysis of PBDE congeners and THs. RESULTS: The geometric mean sum concentrations of the most prevalent PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, and BDE-153) were 22 ng/g lipid in winter 2010, 23 ng/g lipid in summer 2010, and 19 ng/g lipid in winter 2011. BDE-47 was the predominant congener. Based on a multivariable mixed regression model, we estimated that on average, a 1-ng/g serum increase in BDE-47 was associated with a 2.6-µg/dL decrease in total thyroxine (T4) (95% CI: -4.7, -0.35). Total T4 was inversely associated with each PBDE congener. Serum concentrations of PBDEs were not strongly associated with total triiodothyronine (T3), free T4, or thyroid-stimulating hormone (TSH). CONCLUSION: These results are consistent with those from animal studies showing that exposure to PBDEs is associated with a decrease in serum T4. Because the other TH concentrations did not appear to be associated with BDE exposures, our findings do not indicate effects on the pituitary-thyroid axis. Taken together, our findings suggest that PBDE exposure might decrease the binding of T4 to serum T4 binding proteins. CITATION: Makey CM, McClean MD, Braverman LE, Pearce EN, He XM, Sjödin A, Weinberg JM, Webster TF. 2016. Polybrominated diphenyl ether exposure and thyroid function tests in North American adults. Environ Health Perspect 124:420-425; http://dx.doi.org/10.1289/ehp.1509755.

Concentrations of Persistent Organic Pollutants in California Children's Whole Blood and Residential Dust.

We evaluated relationships between persistent organic pollutant (POP) levels in the blood of children with leukemia and POP levels in dust from their household vacuum cleaners. Blood and dust were collected from participants of the California Childhood Leukemia Study at various intervals from 1999 to 2007 and analyzed for two polybrominated diphenyl ethers (PBDEs), two polychlorinated biphenyls (PCBs), and two organochlorine pesticides using gas chromatography-mass spectrometry. Due to small blood sample volumes (100 µL), dichlorodiphenyldichloroethylene (DDE) and BDE-153 were the only analytes with detection frequencies above 70%. For each analyte, depending on its detection frequency, a multivariable linear or logistic regression model was used to evaluate the relationship between POP levels in blood and dust, adjusting for child's age, ethnicity, and breastfeeding duration; mother's country of origin; household annual income; and blood sampling date. In linear regression, concentrations of BDE-153 in blood and dust were positively associated; whereas, DDE concentrations in blood were positively associated with breastfeeding, maternal birth outside the U.S., and Hispanic ethnicity, but not with corresponding dust-DDE concentrations. The probability of PCB-153 detection in a child's blood was marginally associated with dust-PCB-153 concentrations (p = 0.08) in logistic regression and significantly associated with breastfeeding. Our findings suggest that dust ingestion is a source of children's exposure to certain POPs.