Polybrominated Diphenyl Ethers Exposure Research Articles

Exposure to Polybrominated Diphenyl Ethers and Risk of All-Cause and Cause-Specific Mortality

Polybrominated diphenyl ethers (PBDEs) are an important group of persistent organic pollutants with endocrine-disrupting properties. However, prospective cohort studies regarding the association of PBDE exposure with long-term health outcomes, particularly mortality, are lacking. To examine the association of environmental exposure to PBDEs with risk of all-cause and cause-specific mortality. This nationally representative cohort study used data from the National Health and Nutrition Examination Survey 2003 to 2004 and linked mortality information through December 31, 2019. Adults aged 20 years or older with available data on PBDE measurements and mortality were included. Statistical analysis was performed from February 2022 to April 2023. PBDE analytes in serum samples were measured using solid phase extraction and isotope dilution gas chromatography high-resolution mass spectrometry. All-cause mortality, cancer mortality, and cardiovascular mortality. This study included 1100 participants (mean [SE] age, 42.9 [0.6] years; proportion [SE] female, 51.8% [1.6%]; proportion [SE] Hispanic, 12.9% [2.7%]; proportion [SE] non-Hispanic Black, 10.5% [1.6%]; proportion [SE] non-Hispanic White, 70.8% [3.7%]; proportion [SE] other race and ethnicity, 5.8% [1.1%]). During 16 162 person-years of follow-up (median [IQR] follow-up, 15.8 [15.2-16.3] years; maximum follow-up, 17 years), 199 deaths occurred. Participants with higher serum PBDE levels were at higher risk for death. After adjustment for age, sex, and race and ethnicity, lifestyle and socioeconomic factors, and body mass index, participants with the highest tertile of serum PBDE levels had an approximately 300% increased risk of cancer mortality (HR, 4.09 [95% CI, 1.71-9.79]) compared with those with the lowest tertile of serum PBDE levels. No significant association of PBDE exposure with all-cause mortality (HR, 1.43 [95% CI, 0.98-2.07]) or cardiovascular mortality (HR, 0.92 [95% CI, 0.41-2.08]) was observed. In this nationally representative cohort study, PBDE exposure was significantly associated with an increased risk of cancer mortality. Further studies are needed to replicate the findings and determine the underlying mechanisms.

Prenatal exposure to polybrominated diphenyl ether (PBDE) and child neurodevelopment: The role of breastfeeding duration

BackgroundPrenatal and early-life exposure to polybrominated diphenyl ethers (PBDEs) is associated with detrimental and irreversible neurodevelopmental health outcomes during childhood. Breastfeeding may be a child's largest sustained exposure to PBDE— potentially exacerbating their risk for adverse neurodevelopment outcomes. However, breastfeeding has also been associated with positive neurodevelopment. Our study investigates if breastfeeding mitigates or exacerbates the known adverse effects of prenatal exposure to PBDEs and child neurodevelopment. MethodsParticipants included 321 mother-infant dyads from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal birth cohort in California. PBDE concentrations were measured in maternal serum blood samples collected during pregnancy or at delivery. Using generalized estimated equations (GEE), we estimated associations of PBDE concentrations with children's attention, executive function, and cognitive scores assessed longitudinally between 7 and 12 years of age, stratified by duration of exclusive and complementary breastfeeding. ResultsWe observed that higher maternal prenatal PBDE concentrations were associated with poorer executive function among children who were complementary breastfed for a shorter duration compared to children breastfed for a longer duration; preservative errors (β for 10-fold increase in complementary breastfeeding <7 months = −6.6; 95 % Confidence Interval (CI): −11.4, −1.8; β ≥ 7 months = −5.1; 95 % CI: −10.2, 0.1) and global executive composition (β for 10-fold increase <7 months = 4.3; 95 % CI: 0.4, 8.2; β for 10-fold increase ≥7 months = 0.6; 95 % CI: −2.8, 3.9). ConclusionsProlonged breastfeeding does not exacerbate but may mitigate some previously observed negative associations of prenatal PBDE exposure and child neurodevelopment.

Polybrominated diphenyl ethers in dust, hair and urine: Exposure, excretion

Polybrominated diphenyl ethers (PBDEs) have been detected in various environmental media and human tissues. PBDEs concentrations in dust from college buildings and homes and in paired hair and urine samples from students were determined. This is of great significance to explore the accumulation and excretion patterns of PBDEs in the human body. The median PBDEs concentrations in the dust (College: 84.59 ng/g; Home: 170.32 ng/g) and hair (undergraduate: 6.16 ng/g; Home: 3.25 ng/g) samples were generally lower than were found in the majority of previous studies. The PBDEs concentrations in the hair and urine samples were subjected to principal component analysis, and the results combined with the PBDEs detection rates confirmed that hair is a useful non-invasive sampling medium for assessing PBDEs exposure and the risks posed. Body mass indices (BMIs) were used to divide students who had not been exposed to large amounts of PBDEs into groups. Body fat percentage is an important factor affecting the accumulation of PBDE in the human body. Environmental factors were found to affect the PBDEs concentrations in the hair and urine samples less for normal-weight students (BMI≤24) than overweight students (BMI>24). Short-term environmental changes to more readily affect the PBDEs concentrations in the tissues of the normal-weight than overweight students. PBDEs with seven or more bromine substituents were found not to be readily excreted in urine. Performing molecular docking simulations of the binding of isomers BDE-99 and BDE-100 to megalin. The binding energy was higher for BDE-100 and megalin than for BDE-99 and megalin, meaning BDE-99 would be more readily excreted than BDE-100.

Chemicals Used in Plastic Materials: An Estimate of the Attributable Disease Burden and Costs in the United States.

Chemicals used in plastics have been described to contribute to disease and disability, but attributable fractions have not been quantified to assess specific contributions. Without this information, interventions proposed as part of the Global Plastics Treaty cannot be evaluated for potential benefits. To accurately inform the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity in the United States, we calculated the attributable disease burden and cost due to chemicals used in plastic materials in 2018. We first analyzed the existing literature to identify plastic-related fractions (PRF) of disease and disability for specific polybrominated diphenylethers (PBDE), phthalates, bisphenols, and polyfluoroalkyl substances and perfluoroalkyl substances (PFAS). We then updated previously published disease burden and cost estimates for these chemicals in the United States to 2018. By uniting these data, we computed estimates of attributable disease burden and costs due to plastics in the United States. We identified PRFs of 97.5% for bisphenol A (96.25-98.75% for sensitivity analysis), 98% (96%-99%) for di-2-ethylhexylphthalate, 100% (71%-100%) for butyl phthalates and benzyl phthalates, 98% (97%-99%) for PBDE-47, and 93% (16%-96%) for PFAS. In total, we estimate $249 billion (sensitivity analysis: $226 billion-$289 billion) in plastic-attributable disease burden in 2018. The majority of these costs arose as a result of PBDE exposure, though $66.7 billion ($64.7 billion-67.3 billion) was due to phthalate exposure and $22.4 billion was due to PFAS exposure (sensitivity analysis: $3.85-$60.1 billion). Plastics contribute substantially to disease and associated social costs in the United States, accounting for 1.22% of the gross domestic product. The costs of plastic pollution will continue to accumulate as long as exposures continue at current levels. Actions through the Global Plastics Treaty and other policy initiatives will reduce these costs in proportion to the actual reductions in chemical exposures achieved.

Ex vivo exposure to polybrominated diphenyl ether (PBDE) selectively affects the immune response in autistic children

Children on the autism spectrum have been shown to have immune dysregulation that often correlates with behavioral deficits. The role of the post-natal environment in this dysregulation is an area of active investigation. We examined the association between plasma levels of polybrominated diphenyl ether (PBDE) and immune cell function in age-matched autistic children and non-autistic controls. Plasma from children on the autism spectrum (n = 38) and typically developing controls (TD; n = 60) were analyzed for 14 major PBDE congeners. Cytokine/chemokine production was measured in peripheral blood mononuclear cell (PBMC) supernatants with and without ex vivo BDE-49 exposure. Total plasma concentration (∑PBDE14) and individual congener levels were also correlated with T cell function. ∑PBDE14 did not differ between diagnostic groups but correlated with reduced immune function in children on the autism spectrum. In autistic children, IL-2 and IFN-γ production was reduced in association with several individual BDE congeners, especially BDE-49 (p = 0.001). Furthermore, when PBMCs were exposed ex vivo to BDE-49, cells from autistic children produced elevated levels of IL-6, TNF-α, IL-1β, MIP-1α and MCP-1 (p < 0.05). Therefore, despite similar plasma levels of PBDE, these data suggest that PBMC function was differentially impacted in the context of several PBDE congeners in autistic children relative to TD children where increased body burden of PBDE significantly correlated with a suppressed immune response in autistic children but not TD controls. Further, acute ex vivo exposure of PBMCs to BDE-49 stimulates an elevated cytokine response in AU cases versus a depressed response in TD controls. These data suggest that exposure to the toxicant BDE-49 differentially impacts immune cell function in autistic children relative to TD children providing evidence for an underlying association between susceptibility to PBDE exposure and immune anomalies in children on the autism spectrum.

OR06-02 Placental Distribution Of Polybrominated Diphenyl Ethers (Pbdes) And Thyroid Hormones Across Gestation In PBDE-exposed Wistar Rats

Abstract Disclosure: S. Gaballah: None. B. Horman: None. G. St Armour: None. K. Hoffman: None. H.B. Patisaul: None. H. Stapleton: None. In utero exposure to polybrominated diphenyl ethers (PBDEs) has been linked to adverse pregnancy and fetal health outcomes, including altered thyroid hormone (TH) levels. Despite their phase out, PBDEs are still measured in newborn cord blood. While evidence suggests that PBDEs can cross the placental barrier, few studies have assessed differences in PBDE or TH accumulation in the maternally and fetally-derived placental tissue layers or studied fetal sex-differences. To address these gaps, we conducted a controlled exposure study in Wistar rats (n=8 per treatment and gestational day (GD)). From GD2, pregnant dams were exposed daily to sesame oil vehicle, a low dose, or high dose mixture of 10 PBDEs. The low dose represents the 95th percentile of PBDEs measured in U.S. house dust, and the high dose is ∼20X higher. At GD15 and GD20, dams were sacrificed and placental tissues were micro-dissected into maternally and fetally-derived layers. Tissues were analyzed for PBDEs and for T3, rT3, and T4 using mass spectrometry. BDEs 47, 99, 100, and 209 were frequently detected in the fetal and maternal tissues. Higher concentrations of BDEs 99, 100, and 209 were measured in the fetal placenta on GD 15; however, this trend flipped at GD20, with higher maternal concentrations of BDEs 47, 99, and 209. This shift appears to be related to changes in the mass of the maternal and fetal layers during gestation and not to different partioning processes. Only BDE 99 was significantly different between the two layers, in both sexes. At both timepoints, T3 levels were several-fold higher in maternal tissues than fetal, but T3 decreased in maternal tissues by GD20. No sex differences were observed. In general, we observed a significant difference in maternal and fetal T3 levels at GD15 and GD20 in control, low, and high dose-exposed animals. At GD15, there was a significant difference between maternal and fetal female placental T4 levels (p=0.0237) and a suggestive difference in males (p=0.081) in the high dose group, as well as a significant effect of sex between the fetal tissues in the low dose group (p=0.0044). T4 was only detected in the fetal side at GD20, with no significant effects of treatment or sex. These results highlight the rapid developmental changes throughout gestation between the maternal and fetal placenta. Overall, these data highlight that PBDE accumulation in Wistar rats changes across gestation, causing disruption of TH levels in maternal and fetal tissues, and that sex-specific differences may be contributing to differential accumulation patterns in male and female-associated placentas. Coupled with rapid morphological changes in the fetal and maternal layers during placental growth, in utero PBDE exposure may result in adverse impacts on placental TH regulation and fetal health. Presentation: Thursday, June 15, 2023

Higher HDL-C levels attenuated the association of plasma polybrominated diphenyl ethers with prediabetes and type 2 diabetes mellitus in rural Chinese adults

BackgroundPlasma polybrominated diphenyl ethers (PBDE) were used as flame retardants widely, however, epidemiological evidence for the association between PBDEs and type 2 diabetes mellitus (T2DM) is inconsistent. Moreover, the combined effects of PBDEs and blood lipid indicators on impaired fasting glucose (IFG) and T2DM remains largely unknown in rural areas lacking good waste recycling infrastructure. MethodsIn this study, a total of 2607 subjects aged 18–79 years were included from the Henan Rural Cohort. Generalized linear and logistic regression models were applied to evaluate the associations of various PBDE pollutants on IFG and T2DM. Quantile g-computation regression and PBDE pollution score created by the adaptive elastic net were applied to evaluate the impact of PBDEs mixtures on IFG and T2DM. Interaction effects of individual PBDE pollutants and blood lipid indicators on IFG and T2DM were assessed by using Interaction plots. ResultsThe geometric mean concentrations (detection rates) were 0.09 ng/mL (100.0%), 0.12 ng/mL (97.8%), 0.22 ng/mL (94.7%), 0.16 ng/mL (99.2%) and 0.28 ng/mL (100.0%) for PBDE-28, PBDE-47, PBDE-99, and PBDE-153 respectively. However, PBDE-28, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with IFG (odds ratios (ORs) (95% confidence intervals (CIs)): 1.14 (1.06, 1.23), 1.16 (1.04, 1.29), 1.25 (1.14, 1.37), and 1.27 (1.08, 1.50)). Similarly, PBDE-28, PBDE-47, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with T2DM (ORs (95% CIs): 1.30 (1.10, 1.54), 1.13 (1.06, 1.22), 1.27 (1.13, 1.43), 1.27 (1.15, 1.40), and 1.30 (1.10, 1.54)). Moreover, five PBDE mixtures or jointly as PBDE pollution score, were significantly associated with an increased risk of T2DM (P < 0.05 for all). In addition, the harmful effect of PBDE exposure on T2DM was decreased with accompanying high‐density lipoprotein cholesterol (HDL-C) levels increased. ConclusionsOur findings highlight the importance of managing PBDEs contamination and suggest that HDL-C may be a novel way to prevent T2DM.

Photosynthetic response mechanism to polybrominated diphenyl ether exposure in Chlorella pyrenoidosa

Polybrominated diphenyl ether (PBDE) contamination is common in aquatic environments and can severely damage aquatic organisms. However, there is a lack of information on the response and self-adaptation mechanisms of these organisms. Chlorella pyrenoidosa was treated with 2,2′,4,4′-tetrabromodiphenyl ether (BDE47), causing significant growth inhibition, pigment reduction, oxidative stress, and chloroplast atrophy. Photosynthetic damage contributed to inhibition, as indicated by Fv/Fm, Chl a fluorescence induction, photosynthetic oxygen evolution activity, and photosystem subunit stoichiometry. Here, Chl a fluorescence induction and quinone electron acceptor (QA−) reoxidation kinetics showed that the PSII donor and acceptor sides were insensitive to BDE47. Quantitative analyses of D1 and PsaD proteins illustrated that PSII and PSI complexes were the main primary targets of photosynthesis inhibition by BDE47. Significant modulation of PSII complex might have been caused by the potential binding of BDE47 on D1 protein, and molecular docking was performed to investigate this. Increased activation of antioxidant defense systems and photosystem repair as a function of exposure time indicated a positive resistance to BDE47. After a 5-day exposure, 23 % of BDE47 was metabolized. Our findings suggest that C. pyrenoidosa has potential as a bioremediator for wastewater-borne PBDEs and can improve our understanding of ecological risks to microalgae.

Proteomic analyses of primary human villous trophoblasts exposed to flame retardant BDE-47 using SWATH-MS

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants and recognized developmental toxicants that are detectable in placental tissues. Higher levels of in utero PBDE exposure have been associated with an increased risk of adverse birth outcomes. During pregnancy, cytotrophoblasts (CTBs) from the placenta play critical roles in the formation of the maternal-fetal interface via uterine invasion and vascular remodeling. The differentiation of these cells towards an invasive phenotype is crucial for proper placental development. We previously have shown that BDE-47 can impact CTB viability and hinder the ability of these cells to migrate and invade. To expand on potential toxicological mechanisms, we utilized quantitative proteomic approaches to identify changes in the global proteome of mid-gestation primary human CTBs after exposure to BDE-47. Using sequential window acquisition of all theoretical fragment-ion spectra (SWATH), we identified 3024 proteins in our CTB model of differentiation/invasion. Over 200 proteins were impacted as a function of BDE-47 exposure (1 μM and 5 μM) across the treatment period (15, 24, and 39 h). The differentially expressed molecules displayed time- and concentration-dependent changes in expression and were enriched in pathways associated with aggregatory and adhesive processes. Network analysis identified CYFIP1, a molecule previously unexplored in a placental context, to be dysregulated at BDE-47 concentrations previously seen to impact CTB migration/invasion. Our SWATH-MS dataset thus demonstrates BDE-47 impacts the global proteome of differentiating CTBs and serves as a valuable resource for further understanding of the relationship between environmental chemical exposures and placental development and function. Availability of data and materialRaw chromatograms are deposited on the MassIVE proteomic database (https://massive.ucsd.edu) under accession number MSV000087870. Normalized relative abundances are also available as Table S1.

Maternal PBDE exposure disrupts gut microbiome and promotes hepatic proinflammatory signaling in humanized PXR-transgenic mouse offspring over time.

Developmental exposure to the persistent environmental pollutant, polybrominated diphenyl ethers (PBDEs), is associated with increased diabetes prevalence. The microbial tryptophan metabolite, indole-3-propionic acid (IPA), is associated with reduced risk of type 2 diabetes and lower-grade inflammation and is a pregnane X receptor (PXR) activator. To explore the role of IPA in modifying the PBDE developmental toxicity, we orally exposed humanized PXR-transgenic (hPXR-TG) mouse dams to vehicle, 0.1 mg/kg/day DE-71 (an industrial PBDE mixture), DE-71+IPA (20 mg/kg/day), or IPA, from 4 weeks preconception to the end of lactation. Pups were weaned at 21 days of age and IPA supplementation continued in the corresponding treatment groups. Tissues were collected at various ages until 6 months of age (n = 5 per group). In general, the effect of maternal DE-71 exposure on the gut microbiome of pups was amplified over time. The regulation of hepatic cytokines and prototypical xenobiotic-sensing transcription factor target genes by DE-71 and IPA was age- and sex-dependent, where DE-71-mediated mRNA increased selected cytokines (Il10, Il12p40, Il1β [both sexes], and [males]). The hepatic mRNA of the aryl hydrocarbon receptor (AhR) target gene Cyp1a2 was increased by maternal DE-71 and DE-71+IPA exposure at postnatal day 21 but intestinal Cyp1a1 was not altered by any of the exposures and ages. Maternal DE-71 exposure persistently increased serum indole, a known AhR ligand, in age- and sex-dependent manner. In conclusion, maternal DE-71 exposure produced a proinflammatory signature along the gut-liver axis, including gut dysbiosis, dysregulated tryptophan microbial metabolism, attenuated PXR signaling, and elevated AhR signaling in postweaned hPXR-TG pups over time, which was partially corrected by IPA supplementation.

Probiotic Therapy with Lactobacillus reuteri Rescues Social and Emotional Recognition Behavior in an Environmental Mouse Model of Autism

Introduction: Polybrominated diphenyl ethers (PBDEs) are neuroendocrine disrupting chemicals with adverse neurodevelopmental effects in children. Our group has previously shown that PBDEs produce autistic-like traits in developmentally exposed mice offspring (Kozlova et al. 2022 Arch Tox; PMID: 34687351). Our pilot data suggests that PBDEs reduce hypothalamic oxytocin expression. Moreover, PBDEs are well established disruptors of thyroid hormones. Lactobacillus reuteri (LR) is a beneficial probiotic that can increase oxytocin and thyroid hormones in other ASD mouse models. Therefore, we hypothesized that LR can restore PBDE-induced deficits in social behavior. Methods: C57BL/6N dams were dosed with a commercial mixture of PBDE congeners, DE-71, at 0.1 mg/kg/d (DE-71), or corn oil vehicle control (VEH/CON) for 10 wk (preconception: 4 wk; gestation: 3 wk; lactation: 3 wk). Dams were gavaged with L. reuteri (LR) ATCC 6475 (gift of Biogaia, Sweeden) at 10 8 CFU/mL. Cohort 1 pups (C1-LR) received LR via dam until weaning (PND 21). Cohort 2 pups (C2-LR) continued to receive gavage of LR post-weaning, daily, through 6 mo of age. Results: PCR analysis showed increased gene expression of fecal LR 6475 in feces collected from LR offspring and dams confirming efficacy of maternal LR supplementation. Compared to VEH/CON neither DE-71 nor LR disrupted normal maternal behavior. In offspring, DE-71 produced deficient short- (SRT, 30 min retention) and long-term social recognition memory (SRMT, 24 h retention) in adult females (short- and long-term) and adult males (short-term). LR normalized these deficits. The social recognition deficit was not present at PND 11 as measured on a maternal attachment homing test. On an emotional recognition test DE-71 exposed male and female offspring did not prefer investigation of stimulus mice subjected to 15 min restraint stress vs neutral conditions (normalized with LR). In a marble burying test, compared to VEH/CON, DE-71 exposed offspring showed abnormally elevated scores, which were normalized by LR treatment only in females. Developmental benchmarks that are likely affected by the TH-disruptive effects of DE-71 showed complex interactions between DE-71 and LR. LR normalized delayed (vs VEH/CON) incisor eruption in DE-71 females and improved latency of righting reflex in DE-71 males. LR normalized DE-71-induced hyperactivity on an open field test in females. Ongoing studies are focused on exploring possible mechanisms underlying the normalization provided by LR. However, our early data suggest a potential role of 1) OXT confirmed by increased plasma OXT in DE-71 male (C1-LR) mice and normalized with LR, and 2) maternal THs since LR supplementation elevated plasma T4 in DE-71 pregnant dams. Conclusions: These results suggest that maternal LR treatment during developmental PBDE exposure provides normalization of autistic-like features in a sex-dependent manner. This work is supported by a Danone North America Gut Microbiome, Yogurt and Probiotics Fellowship Grant and a University of California President's Pre-Professoriate Fellowship to E.V.K. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Environmental signature and health risk assessment of polybrominated diphenyl ethers (PBDEs) emitted from a landfill fire in Santiago de Chile

Polybrominated diphenyl ethers (PBDEs) have been used as flame retardants in building materials, electronics, furnishings, vehicles, airplanes, plastics, polyurethane foams, and textiles for many years. Currently, the primary commercial mixtures, penta-, octa-, and deca-BDE, are globally restricted. Still, products containing PBDEs are expected to impact waste management and the environment for many years. In January 2016, an open fire in the Santa Marta landfill close to Santiago de Chile affected the city and surroundings. The fire caused several acute health effects and an increase in emergency hospitalizations. We measured PBDE levels in the areas affected by the fire in the air (gaseous and particulate) and soil, and PBDE emissions were estimated using a dispersion model. The results showed an increase in PBDE concentrations by a factor of 2–4 one day after the start of the fire. However, PBDE concentrations measured after the fire in PM10 and the gas phase were considered low compared to other regions. Interestingly, PBDEs’ patterns differed across the sites; however, BDE209 was the dominant congener for all environmental matrices. A preliminary risk assessment was conducted using the daily exposure dose (DED) by air inhalation estimation. The results showed low DED values for adults and children and suggested no direct health risk due to PBDE exposure. This study brings new data useful for future solid waste management initiatives in the country.

Serum polybrominated diphenyl ether exposure and influence factors in blood donors of Wuxi adults from 2013 to 2016

Polybrominated diphenyl ethers (PBDEs) have been used as brominated flame retardants worldwide and are correlated with extensive environmental pollution and human health concerns. This study is aimed at analyzing the concentrations of PBDEs and at evaluating their temporal trends among a population of blood donors (n = 33) over a 4-year period. A total of 132 serum samples were used for PBDE detection. Nine PBDE congeners were quantified in serum samples by gas chromatography with mass spectrometry (GC-MS). The median concentrations of Σ9PBDEs in each year were 33.46, 29.75, 30.85, and 35.02ng/g lipid, respectively. Most of the PBDE congeners showed a downward trend from 2013 to 2014 and then increased after 2014. No correlations between age and PBDE congener concentrations were observed, while concentrations of each congener and Σ9PBDE were nearly always lower in females than in males, especially in BDE-66, BDE-153, BDE-183, BDE-190, and Σ9PBDE. We also found that the intake of fish, fruit, and eggs in the daily diet was related to the exposure level of PBDEs. Our results suggest that, as deca-BDE is still produced and used in China, diet is an important exposure pathway for PBDEs, and follow-up studies will be required to improve our understanding of the behaviors of PBDE isomers in humans and the exposure levels.

Dietary exposure and risk assessment of polybrominated diphenyl ethers in the Republic of Korea: A nationwide study

In this study, the dietary exposure to seven polybrominated diphenyl ethers (PBDEs) congener groups, including 22 types of PBDEs compounds, through consumption of 80 food items in Korean diets along with their risk assessment has been investigated. To process this, the concentrations of the target PBDEs in samples of food items were measured. The consumption amounts of the target food items were derived from the results of the 24 h food recall interview of subjects who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) from 2015 to 2019. Thereafter, the estimated daily intake and risk of exposure for each PBDEs congener group were assessed. Results indicate that although exposure to the target PBDEs was not significant enough to cause a potential health risk, deca-BDE (BDE-209) was the dominant congener in terms of both exposure and risk for consumers in all age groups. Furthermore, while eating seafood was the dominant path for dietary exposure to PBDEs, exposure to octa-BDEs was mostly through livestock products. Accordingly, to protect all consumers, especially those aged below 2 years and over 65 years, more accurate food quality management is required for controlling the dietary intake of PBDEs.

2,2',4,4',5,5'-Hexabromophenyl ether (BDE-153) causes abnormal insulin secretion and disorders of glucose and lipid metabolism in mice.

Environmental polybrominated diphenyl ether (PBDE) exposure may be associated with diabetes and obesity. 2,2',4,4',5,5'-Hexabromodiphenyl ether (BDE-153) is one of the most abundant and widely distributed homologs of PBDEs detected in humans. This study investigated the effects of BDE-153 on the expression of adipokines and glucose and lipid metabolism. Adult male C57BL/6 mice were divided into five BDE-153 groups and one control group. After BDE-153 exposure for 4 weeks, the levels of biochemical indexes and the mRNA and protein expression levels of leptin, adiponectin, peroxisome proliferators activated receptors gamma (PPARγ), and AMPKα were measured. The histomorphological changes of liver and pancreas tissues were observed. After BDE-153 exposure, the weight of mice in the medium-high-dose group at different exposure times was lower than that in the control group ( p all <0.05), and the body weight decreased slightly with the increase of the dose of BDE-153. BDE-153 caused the disorder of glucose and lipid metabolism in mice, the weight of liver and pancreas increased, lipid droplets accumulated in liver cells, and the positive rate of insulin staining increased in a dose-dependent manner. BDE-153 also interfered with the expression of PPARγ, AMPKα, and adipokines. The results of restrictive cubic splines (RCS) showed that there were a nonlinear dose-response relationship between the exposure dose of BDE-153 and the expression levels of PPARγ, AMPKα, and adipokines. Our results suggest that BDE-153 may interfere with the expression of adipokines and the secretion of insulin by affecting the expression of PPARγ and AMPKα, which play a key role in glucose and lipid metabolism, leading to the occurrence of glucose and lipid metabolism disorder.

Current status of indoor dust PBDE pollution and its physical burden and health effects on children.

Polybrominated diphenyl ethers (PBDEs) are widely detected in indoor dust, which has been identified as a more important route of PBDE exposure for children than food intake. The physical burden and health hazards to children of PBDE exposure in house dust have not been adequately summarized; therefore, this article reviews the current status of PBDE pollution in indoor dust associated with children, highlighting the epidemiological evidence for physical burden and health risks in children. We find that PBDEs remain at high levels in indoor dust, including in homes, schools, and cars, especially in cars showing a significant upward trend. There is a trend towards an increase in the proportion of BDE-209 in household dust, which is indicative of recent PBDE contamination. Conversely, PBDE congeners in car and school indoor dust tended to shift from highly brominated to low brominated, suggesting a shift in current pollution patterns. Indoor dust exposure causes significantly higher PBDE burdens in children, especially infants in early life, than in adults. Exposure to dust also affects breast milk, putting infants at high risk of exposure. Although evidence is limited, available epidemiological studies suggest that exposure to indoor dust PBDEs promotes neurobehavioral problems and cancer development in children.

A meta-analysis of randomized controlled studies on the hepatoxicity induced by polybrominated diphenyl ethers (PBDEs) in rats and mice

Several toxicological studies were conducted to evaluate the hepatoxicity of PBDEs using different animal models, congeners, duration of exposure, and other parameters. These variations in different animal models and conditions might have an impact on extrapolating experimental results to humans. Hence, by the meta-analysis, we aimed to clarify and elucidate the species differences in hepatoxicity induced by PBDE exposure in rats and mice across different conditions and moderators. Fourteen in vivo studies that utilized rats and mice models were identified, and data such as author names, year of publication, type of PBDE congeners, rodent species, life stage of exposure, dosage, duration, and hepatoxicity indicators were extracted. The pooled standard mean difference (SMD) with a 95% confidence interval (95% CI) was used to evaluate the association between hepatoxicity and PBDE exposure across multiple approaches of measurement. Subgroup analysis, meta-regression, and interaction analysis were utilized to elucidate the species-related differences among the results of the involved studies. The pooled SMD of hepatoxicity of PBDE exposure in the involved in vivo studies was 1.82 (p = 0.016), indicating exposure to PBDE congeners and mixtures is associated with a significant increase in liver toxicity in rodents. Moreover, findings showed that rats were more sensitive to PBDEs than mice with the BDE-209 had the highest SMD value. Among the life stages of exposure, embryonic stage was found to be the most sensitive to hepatoxicity induced by PBDE congeners. Positive relationships were found between the incidence of hepatoxicity with dosage and duration of exposure to PBDE. Interaction analyses showed significant interactions between rodent species (rats or mice), dosage, length of exposure, and hepatotoxicity endpoints. Rats demonstrated an increased susceptibility to variations in organ weight, histopathological changes, mitochondrial dysfunction, and oxidative stress markers. Conversely, mice showed pronounced lipid accumulation and modifications in liver enzyme expression levels. However, significant differences were not found in terms of endoplasmic reticular stress as a mechanistic endpoint for hepatotoxicity. In conclusion, this meta-analysis showed that there might be some species-related differences in hepatoxicity induced by PBDE exposure in rats and mice depending on the parameters used. This study highlights the importance of cross-species extrapolation of results from animal models to accurately assess the potential risks to human health from exposure to PBDEs.

Long-Term Monitoring of Polybrominated Diphenyl Ethers (PBDEs) in Indo-Pacific Humpback Dolphins (Sousa chinensis) from the Pearl River Estuary Reveals High Risks for Calves due to Maternal Exposure.

Although many studies have documented the wide occurrence of polybrominated diphenyl ethers (PBDEs) in cetaceans, little evidence exists regarding the detrimental effects of PBDE exposure on calf death rates for free-ranging cetaceans. This study analyzed life-history-associated PBDE bioaccumulation patterns in 128 stranding Indo-Pacific humpback dolphin (Sousa chinensis) samples over an 18-year timespan from the Pearl River Estuary (PRE). In comparison to the records of PBDE levels in cetaceans worldwide, the median levels of PBDEs (median = 10600 ng g-1 lw, range = 721-50900 ng g-1 lw) in all samples were the highest to date. One-way analysis of variance (ANOVA) showed that adult males (median = 16100 ng g-1 lw, range = 4070-50900 ng g-1 lw) and calves (12000 ng g-1 lw, range = 1250-35300 ng g-1 lw) both had the highest levels of PBDEs compared to the rest of the age/sex groups (p < 0.05). Concentrations of PBDEs in noncalves significantly decreased over the studied period, while those in calves had a slightly increasing trend, which may be due to different exposure routes via fish or milk, respectively. A significant and positive relationship was found between annual calf stranding death rates and body-length-adjusted PBDE concentrations in calves (r = 0.62, p < 0.05), suggesting that maternal exposure of calves to elevated levels of PBDEs may have contributed to the high annual stranding death rates of calves in the last two decades.

New insights into mechanism of emerging pollutant polybrominated diphenyl ether inhibiting sludge dark fermentation

Polybrominated diphenyl ethers (PBDEs), derived from electronics, furniture, etc., are detected with high level in excess sludge (ES). In this work, the influence of PBDEs on ES dark fermentation (ESDF) hydrogen production and the related key mechanisms were explored. The result shows PBDEs exposure reduced hydrogen production, and hydrogen accumulation decreased from 17.6 mL/g in blank to 12.3 mL/g with 12.0 mg/Kg PBDEs. PBDEs induced the reactive oxygen species production, which directly led to cell inactivation and reduced hydrogen production. Furthermore, PBDEs decreased ES disintegration, hydrolysis, acidification and homoacetogenic processes and inhibited the activities of enzymes related to hydrogen production. PBDEs also affected the diversity and richness of microbial communities in dark fermentation systems, especially high doses of PBDEs reduced the relative abundance of microorganisms associated with hydrogen production. In conclusion, PBDEs reduce hydrogen generation from ES.

Prenatal exposure to phthalates and polybrominated diphenyl ethers on neonatal health: A birth cohort study in Guangxi, China

Few epidemiological studies have focused on prenatal phthalates (PAEs) and polybrominated diphenyl ethers (PBDEs) exposure to neonatal health in China. This study aimed to assess the associations between prenatal PAEs and PBDEs exposure and neonatal health in Guangxi, a Zhuang autonomous region of China. Concentrations of 4 PAEs metabolites (mPAEs) and 5 PBDEs congeners were measured in the serum of 267 healthy pregnant women. Birth outcomes and clinical data of neonates were collected after delivery. Mono-(2-Ethylhexyl) phthalate (MEHP) (81.52%) and BDE47 (35.21%) were the mPAEs and PBDEs congeners with the highest detection rate in serum. Prenatal exposures to mono-n-butyl phthalate (MBP), MEHP, and ΣmPAEs were negatively associated with birth weight (BW), birth length (BL), and gestational age (GA). Higher exposures to MBP, MEHP, and ΣmPAEs were associated with an increased odds ratio (OR) for low birth weight (LBW), but exposure to BDE28 exhibited the opposite effect. Moreover, higher exposures to MBP, MEHP, ΣmPAEs, BDE99, and ΣPBDEswere associated with an increased OR for premature birth (PTB) (P < 0.05). In contrast to MBP exposure, BDE28 exposure was associated with a higher OR for neonatal jaundice (NNJ) (P < 0.05). The interaction analysis showed a positive interaction between monoethyl phthalate (MEP) and BDE28 on the risk of NNJ and positive interaction between ΣmPAEs and BDE47 on the risk of NNJ. In addition, there are ethnicity-specific associations of prenatal PBDEs exposure with neonatal health in individuals of Zhuang and Han nationalities, and boy neonates were more sensitive to prenatal PBDEs exposure than girl neonates. The results revealed that prenatal exposure to mPAEs and PBDEs might have adverse effects on neonatal development, and the effects might be ethnicity- and sex-specific.