Association between brominated flame retardants (PBDEs and PBB153) exposure and hypertension in U.S. adults: results from NHANES 2005-2016.

BACKGROUND: Brominated Flame Retardants (BFRs) have attracted widespread concern due to their environmental persistence and potential toxicity. This study aims to examine the association between BFRs exposure and hypertension. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2016 for the cross-sectional analysis. To evaluate the individual and combined impacts of BFRs exposure on hypertension, we utilized multivariate models, including generalized additive models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models. RESULTS: 9882 individuals (48% male) aged ≥ 20 were included in the final analysis, of whom 4114 had hypertension. After controlling for potential covariates, higher serum concentrations of PBDE100 (OR: 1.26; 95% CI: 1.01, 1.57) and PBDE153 (OR: 1.50; 95% CI: 1.18, 1.88) were significantly associated with hypertension. A nonlinear relationship between PBDE28 and hypertension was observed (P = 0.03). Moreover, BFRs mixture were positively associated with the prevalence of hypertension in both the WQS (ß:1.09; 95% CI: 1.02, 1.17; P = 0.02) and BKMR models. CONCLUSION: Our study suggested that BFRs exposure is positively associated with hypertension in the general population. To confirm this association and elucidate the mechanisms, further research is required.

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 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.

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.

Retention of polybrominated diphenyl ethers and hydroxylated metabolites in paired human serum and milk in relation to CYP2B6 genotype.

Polybrominated diphenyl ethers (PBDEs) and their hydroxylated metabolites (OH-BDEs) are endocrine disrupting compounds prevalent in human serum and breast milk. Retention of PBDEs and OH-BDEs in humans may be affected by differences in PBDE metabolism due to variants in cytochrome P450 2B6 (CYP2B6). The objectives of this study are to assess the partitioning profiles of PBDEs and OH-BDEs in forty-eight paired human serum and milk samples, and to evaluate the relationship between variants in CYP2B6 genotype and PBDE and OH-BDE accumulation in humans. Results show that the geometric mean (GM) concentrations of PBDEs are similar in serum (GM = 43.4 ng/g lipid) and milk samples (GM = 52.9 ng/g lipid), while OH-BDEs are retained primarily in serum (GM = 2.31 ng/g lipid), compared to milk (GM = 0.045 ng/g lipid). Participants with CYP2B6*6 genotype had a greater relative retention of PBDEs in serum and milk, and significant relationships (p <  0.05) were also observed for PBDE-47, 5-OH-BDE-47 and 6-OH-BDE-47 concentrations relative to CYP2B6*5 and CYP2B6*6 genotypes. These results are the first to show that CYP2B6 genotype is significantly related to the relative retention of PBDEs in humans, which may have direct implications for variability in the susceptibility of individuals to the potential adverse effects of these contaminants.

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.

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.

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 (

Thyroid hormone levels associate with exposure to polychlorinated biphenyls and polybrominated biphenyls in adults exposed as children.

BACKGROUND: Michigan residents were directly exposed to endocrine-disrupting compounds, polybrominated biphenyl (PBB) and polychlorinated biphenyl (PCB). A growing body of evidence suggests that exposure to certain endocrine-disrupting compounds may affect thyroid function, especially in people exposed as children, but there are conflicting observations. In this study, we extend previous work by examining age of exposure's effect on the relationship between PBB exposure and thyroid function in a large group of individuals exposed to PBB. METHODS: Linear regression models were used to test the association between serum measures of thyroid function (total thyroxine (T4), total triiodothyronine (T3), free T4, free T3, thyroid stimulating hormone (TSH), and free T3: free T4 ratio) and serum PBB and PCB levels in a cross-sectional analysis of 715 participants in the Michigan PBB Registry. RESULTS: Higher PBB levels were associated with many thyroid hormones measures, including higher free T3 (p = 0.002), lower free T4 (p = 0.01), and higher free T3: free T4 ratio (p = 0.0001). Higher PCB levels were associated with higher free T4 (p = 0.0002), and higher free T3: free T4 ratio (p = 0.002). Importantly, the association between PBB and thyroid hormones was dependent on age at exposure. Among people exposed before age 16 (N = 446), higher PBB exposure was associated with higher total T3 (p = 0.01) and free T3 (p = 0.0003), lower free T4 (p = 0.04), and higher free T3: free T4 ratio (p = 0.0001). No significant associations were found among participants who were exposed after age 16. No significant associations were found between TSH and PBB or PCB in any of the analyses conducted. CONCLUSIONS: This suggests that both PBB and PCB are associated with thyroid function, particularly among those who were exposed as children or prenatally.

PBDE serum concentration and preschool maturity of children from Slovakia.

Polybrominated diphenylethers (PBDEs) are persistent organic pollutants (POPs), they are considered endocrine disruptors and can bioaccumulate in nature, and in living tissue. Human exposure to and the presence of PBDEs in human samples is of concern due to their potential health risks. Young children are one of the most vulnerable populations to PBDE's potential health effects. Ninety-one serum samples of 6-year-old children, residing in a contaminated location, due to former production of polychlorinated biphenyls (PCBs), were analysed to examine children's exposure to PBDEs in Slovakia. Median serum concentrations found for individual PBDE congeners BDE-28+33, -47, -99, -100, -153, -154 and -183 were 0.015, 0.184, 0.079, 0.046, 0.176, 0.014, and 0.097 ng g-1 lipid weight, respectively. Children's preschool maturity was measured using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) test. In multivariate analyses BDE-153 serum concentrations were significantly inversely associated with WPPSI-III composite score (p = 0.011, ß = -23.6), while adjusting for PCB-153 and sex. Significant negative associations were observed for BDE-153 serum concentrations (p = 0.002, ß = -29.8) and WPPSI-III composite score, after controlling for PCB-118 and sex. Negative associations were also observed for BDE-47, BDE-100 and BDE-153, with different individual WPPSI subtest scores, after adjustment with PCB-153 and/or PCB-118 and sex. Serum concentrations of PCB-153 and PCB-118 were not statistically significantly associated with WPPSI-III composite score and individual subtest scores. These findings demonstrate adverse effects of PBDE serum exposure on preschool maturity of children, and PBDEs potentially negative impact on child neuropsychological development.

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.

Exposure to polybrominated diphenyl ethers (PBDEs) during childhood and adiposity measures at age 8 years.

BACKGROUND: Animal studies suggest polybrominated diphenyl ethers (PBDEs) may be obesogens. However, epidemiologic studies investigating childhood exposure to PBDEs and adiposity are limited, with several reporting an inverse association. OBJECTIVES: To investigate associations between repeated childhood PBDE concentrations and adiposity measures at age 8 years. METHODS: We examined 206 children from the Health Outcomes and Measures of the Environment Study, a birth cohort in Cincinnati, OH (2003-2006). Serum PBDEs were measured at ages 1, 2, 3, 5, and 8 years. We used multiple imputation to estimate missing PBDE concentrations. At 8 years, we measured weight, height, waist circumference, and body fat percentage. We used multiple informant models to estimate age-specific associations between PBDEs and adiposity measures. RESULTS: We observed significant inverse associations between BDE-153 with all adiposity measures that became increasingly stronger with later childhood measurements. A 10-fold increase in BDE-153 at ages 1 and 8 years was associated with 2% (95% CI -3.9, -0.1) and 7% (95% CI -9.1, -4.7) lower body fat, respectively. No statistically significant associations were found with BDE-28, -47, -99, or -100. Child sex modified some associations; inverse associations between BDE-153 and body fat were stronger among boys, while positive and null associations were noted among girls. CONCLUSIONS: Childhood BDE-153 concentrations were inversely associated with adiposity measures and these associations became stronger as BDE-153 measurements were more proximal to adiposity measures. Inverse associations could be attributed to reverse causality arising from greater storage of PBDEs in adipose tissue of children with higher adiposity.

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.

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.

Association between serum polybrominated diphenyl ethers, new flame retardants and thyroid hormone levels for school students near a petrochemical complex, South China.

As surrogates of polybrominated diphenyl ethers (PBDEs), new flame retardants (NFRs) include a series of chlorinated and brominated flame retardants. Though the NFRs are thought to induce similar thyroid hormone (TH) disrupting effects as PBDEs, few studies have focused on them. Given the increasing levels of NFRs in the environment, more in depth investigation of the potential TH disrupting effects of NFRs is warranted. This research involved a health survey to collect data and examine the associations between PBDEs, NFRs and TH. 174 school students lived near a petrochemical complex in South China participated in the survey, completing questionnaires and providing blood samples. Thirteen congeners of PBDEs, eight species of NFRs, TH and thyroid-stimulating hormone (TSH) were measured. The median levels of ΣPBDE (sum of thirteen congeners of PBDEs) and ΣNFR (sum of eight species of NFRs) for students were 140 and 240 ng g-1 lipid, respectively. Nonmonotonic relationships were observed between quartile levels of PBDEs, NFRs and corresponding TH. In contrast to ΣPBDE that was positively associated with triidothyrine (T3) level, ΣNFR was not statistically associated with TH. ΣPBDE + NFR (sum of thirteen congeners of PBDEs and eight species of NFRs) was significantly associated with T3 level.

Polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDEs in human serum from Shanghai, China: a study on their presence and correlations.

Polybrominated diphenyl ethers (PBDEs) are becoming a public health concern because of their potential toxicity, from endocrine disruption system to neurodevelopmental impairments. Nonetheless, information on their levels in human blood is scarce. In this study, human serum samples collected in Shanghai, China, were analyzed for the concentrations of PBDEs and their hydroxylated metabolites (OH-PBDEs). Eight PBDE congeners and six OH-PBDE congeners were quantified in serum samples by gas chromatography with mass spectrometry (GC-MS) and high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). As a result, total PBDE concentration ranged from 0.280 to 12.330 ng g-1 on a lipid weight basis lw (median: 1.100 ng g-1 lw) and the total OH-PBDE level ranged from 0.045 to 0.363 ng g-1 (lw) (median: 0.187 ng g-1 lw). Among them, BDE-47 and 6-OH-BDE-47 were the predominant PBDEs and OH-PBDEs, respectively. In addition, based on the results of the Bartelett X 2 test, BDE-47 significantly (p < 0.05) correlated with BDE-28, BDE-100, BDE-85, and BDE-154, whereas 3'-OH-BDE-7 significantly (p < 0.01) correlated with 3-OH-BDE-47, 2-OH-BDE-68, and 6'-OH-BDE-99. Among all donors, no significant association between age and PBDEs (or OH-PBDEs) was found. Further research on the exposure routes in the environment and metabolic processing of PBDEs in human blood is necessary.

Polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDE metabolites (OH-PBDEs): A six-year temporal trend in Northern California pregnant women.

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants. Technical mixtures PentaBDE and OctaBDE were phased out in 2004 through voluntary and regulatory actions with DecaBDE remaining in limited use until 2013. Biomonitoring studies have shown widespread presence of PBDEs in the US and worldwide population. While some studies suggest that human serum concentrations are declining over time, it is unclear whether this trend will continue. Our objective was to examine temporal trends of PentaBDEs and their hydroxylated metabolites (OH-PBDEs) between 2008 and 2014 in populations of ethnically diverse, pregnant women residing in Northern California (n = 111). Serum samples were collected and analyzed by high resolution mass spectrometry for five PentaBDE congeners and two OH-PBDEs. We found widespread exposures in participants from all three time points (2008/09, 2011/12, 2014). Temporal patterns varied substantially by congener. BDE-47, -99 and the OH-PBDEs decreased between 2008/09-2011/12 but plateaued between 2011/12-2014. In contrast, BDE-100 decreased across all years, BDE-153 decreased in the latter years, and BDE-28 decreased initially and then increased. These findings indicate that while policies to remove PBDEs from the marketplace have successfully lead to declines in exposures to some PBDE congeners, human exposures to these legacy pollutants could plateau and remain ubiquitous in human populations.

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.

Serum Polybrominated Biphenyls (PBBs) and Polychlorinated Biphenyls (PCBs) and Thyroid Function among Michigan Adults Several Decades after the 1973-1974 PBB Contamination of Livestock Feed.

BACKGROUND: In 1973-1974, Michigan residents were exposed to polybrominated biphenyls (PBBs) through an accidental contamination of the food supply. Residents were enrolled in a registry assembled after the incident, and they and their children participated in follow-up studies to assess subsequent health outcomes. OBJECTIVES: We evaluated associations between serum PBBs and polychlorinated biphenyls (PCBs) and markers of thyroid function among Michigan adults. METHODS: Serum concentrations of four PBB and four PCB congeners were measured at least once in 753 adults, including 79 women who participated in a 2004-2006 study and 683 women and men with follow-up during 2012-2015. Participants completed questionnaires on health conditions (including physician-diagnosed thyroid disease), behaviors, and demographics. Thyroid hormones were measured in a subset without thyroid disease (n=551). In multivariable linear regression models, PBB and PCB congener concentrations, on both the volume (nanogram/milliliter) and lipid (nanogram/gram lipid) basis, were assessed in relation to thyroid hormones. Logistic regression models were used to estimate associations between serum PBBs and PCBs and thyroid disease. RESULTS: Thyroid disease was common (18% overall; 25% among women). Among women, all odds ratios (ORs) for PBB-153 and thyroid disease were positive for quintiles above the reference level, but estimates were imprecise and were without a monotonic increase. For an interquartile range (IQR) increase in PBB-153 (0.43 ng/mL), the OR (any thyroid disease)=1.12; (95% CI: 0.83, 1.52) (n=105 cases); for hypothyroidism, OR=1.35 (95% CI: 0.86, 2.13) (n=49 cases). There were 21 cases of thyroid disease in men [OR=0.69 (95% CI: 0.33); 1.44 for an IQR increase (0.75 ng/mL) in serum PBB-153]. PCB congeners were statistically significantly associated with greater total and free thyroxine and total triiodothyronine among women and with total and free triiodothyronine among men in lipid-standardized models. CONCLUSIONS: We found some evidence to support associations of PBBs and PCBs with thyroid disease and thyroid hormone levels. https://doi.org/10.1289/EHP1302.

Anthropogenic and Naturally Produced Brominated Phenols in Pet Blood and Pet Food in Japan.

Present study determined concentrations and residue patterns of bromophenols (BPhs) in whole blood samples of pet cats and pet dogs collected from veterinary hospitals in Japan. BPhs concentrations were higher in cat blood than in dog blood, with statistically insignificant differences (p = 0.07). Among the congeners, 2,4,6-tribromophenol (TBPh) constituted the majority of BPhs (>90%) detected in both species. Analysis of commercial pet food to estimate exposure routes showed that the most abundant congener in all pet food samples was 2,4,6-TBPh, accounting for >99% of total BPhs. This profile is quite similar to the blood samples of the pets, suggesting that diet might be an important exposure route for BPhs in pets. After incubation in polybrominated diphenyl ether (PBDE) mixtures (BDE-47, BDE-99 and BDE-209), 2,4,5-TBPh was found in dog liver microsomes but not in cat liver microsomes, implying species-specific metabolic capacities for PBDEs. Formation of 2,4,5-TBPh occurred by hydroxylation at the 1' carbon atom of the ether bond of BDE-99 is similar to human study reported previously. Hydroxylated PBDEs were not detected in cats or dogs; therefore, diphenyl ether bond cleavage of PBDEs can also be an important metabolic pathway for BPhs formation in cats and dogs.