Polybrominated Diphenyl Ethers Mixture Research Articles

Associations of cord serum polybrominated diphenyl ether (PBDE) mixture with birth outcomes and mediating role of thyroid function: Evidence from the Sheyang Mini Birth Cohort Study

BackgroundPolybrominated diphenyl ethers (PBDEs), a series of worldwide applied flame retardants, may influence fetal growth and interfere with thyroid function. The study intended to explore the relationship between in-utero exposure to PBDE mixture and newborn anthropometric indexes and to further examine the potential mediating role of thyroid function. MethodsDemographics and laboratory measures of 924 mother-infant pairs were obtained from the database of the Sheyang Mini Birth Cohort Study. We applied gas chromatography-mass spectrometry (GC-MS) and electrochemiluminescence immunoassay to measure nine PBDE congeners and seven thyroid function parameters in umbilical cord serum samples, respectively. We fitted generalized linear models and Bayesian kernel machine regression (BKMR) to evaluate associations of lipid-adjusted cord serum PBDEs, as individuals and as a mixture, with newborn anthropometric and cord serum thyroid function parameters. We applied causal mediation analysis to test our hypothesis that thyroid function parameters act as a mediator between PBDEs and birth outcomes. ResultsThe molarity of cord serum ∑9PBDE had a median value of 31.23 nmol/g lipid (IQR 19.14 nmol/g lipid, 54.77 nmol/g lipid). BDE-209 was the most dominant congener. Birth length was positively associated with both single exposure to BDE-28 and cumulative exposure to PBDEs. Correspondingly, ponderal index (PI) was negatively associated with BDE-28 and the total effects of PBDE mixture. Free triiodothyronine had a negative trend with BDE-209 and PBDE mixture. In the sex-stratified analysis, BDE-153 concentrations were positively correlated with PI among males (β = 0.03; 95%CI: 0.01, 0.05; P = 0.01) but not among females. Cord serum thyrotropin mediated 14.92% of the estimated effect of BDE-153 on PI. ConclusionsIn-utero mixture exposure to PBDEs was associated with birth outcomes and thyroid function. Thyroid function might act as a mediator in the process in which PBDEs impact the growth of the fetus.

Trends in flame retardant levels in upholstered furniture and children's consumer products after regulatory action in California

In 2013, California revised its upholstered furniture flammability standard TB 117–2013 to improve fire safety without the need for flame retardant (FR) chemicals. Subsequent legislation (SB 1019) required disclosure of FR content. In 2020 California expanded restriction on FR chemicals to include juvenile products and upholstered furniture (AB 2998). To monitor trends in FR use, and assess the effectiveness of the new regulations, we analyzed 346 samples from upholstered furniture (n = 270) and children's consumer products (n = 76), collected pre- and post-regulatory intervention for added FR chemicals (i.e., ∑FR > 1000 mg/kg). Upholstered furniture samples, collected from products before enactment of the new regulations, had a median FR concentration of 41,600 mg/kg (range: 1360–92,900 mg/kg), with 100% of the foam samples and 13.7% of the textile samples containing ∑FR > 1000 mg/kg. Firemaster formulations (FM 550 and FM 600), a mixture of triphenyl phosphate (TPHP), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), bis(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (BEH-TEBP) and a mixture of isopropyl- or tert-butyl-triphenyl phosphates (ITPs or TBPPs), were the most frequently detected FR (34%), followed by tris(1,3-dichloroisopropyl) phosphate (TDCIPP; 25%), TPHP with a mixture of polybrominated diphenyl ethers (BDE-47, 99, 100, 153 and 154; 20%) and tris(2-chloroethyl) phosphate (TCEP; 11%). Upholstered furniture components collected after enactment of the new legislation had a median FR concentration of 2600 mg/kg (range: 1160–49,800 mg/kg, outlier sample 282,200 mg/kg), with 11.9% of the foam samples and no textile samples containing ∑FR > 1000 mg/kg. Of these samples, tris(1-chloro-2-propyl) phosphate (TCIPP) was the most frequently detected FR (55%), followed by TDCIPP (30%) and Firemaster (FM 550, 15%). No PBDEs were detected in the post-regulatory intervention products. Our initial work on children's products showed 15% of the samples contained ∑FR > 1000 mg/kg. In our post- AB 2998 work, no regulated children's product components failed compliance (i.e., ∑FR > 1000 mg/kg).The data confirm successful adoption of the new regulations with most samples in compliance, demonstrating the efficacy of regulatory intervention. Given these results, environmental FR exposure is expected to decrease as older FR treated consumer products are replaced with FR free products.

Racial and ethnic disparities in preterm birth: a mediation analysis incorporating mixtures of polybrominated diphenyl ethers.

Racial and ethnic disparities persist in preterm birth (PTB) and gestational age (GA) at delivery in the United States. It remains unclear whether exposure to environmental chemicals contributes to these disparities. We applied recent methodologies incorporating environmental mixtures as mediators in causal mediation analysis to examine whether racial and ethnic disparities in GA at delivery and PTB may be partially explained by exposures to polybrominated diphenyl ethers (PBDEs), a class of chemicals used as flame retardants in the United States. Data from a multiracial/ethnic US cohort of 2008 individuals with low-risk singleton pregnancies were utilized, with plasma PBDE concentrations measured during early pregnancy. We performed mediation analyses incorporating three forms of mediators: (1) reducing all PBDEs to a weighted index, (2) selecting a PBDE congener, or (3) including all congeners simultaneously as multiple mediators, to evaluate whether PBDEs may contribute to the racial and ethnic disparities in PTB and GA at delivery, adjusted for potential confounders. Among the 2008 participants, 552 self-identified as non-Hispanic White, 504 self-identified as non-Hispanic Black, 568 self-identified as Hispanic, and 384 self-identified as Asian/Pacific Islander. The non-Hispanic Black individuals had the highest mean ∑PBDEs, the shortest mean GA at delivery, and the highest rate of PTB. Overall, the difference in GA at delivery comparing non-Hispanic Black to non-Hispanic White women was -0.30 (95% CI: -0.54, -0.05) weeks. This disparity reduced to -0.23 (95% CI: -0.49, 0.02) and -0.18 (95% CI: -0.46, 0.10) weeks if fixing everyone's weighted index of PBDEs to the median and the 25th percentile levels, respectively. The proportion of disparity mediated by the weighted index of PBDEs was 11.8%. No statistically significant mediation was found for PTB, other forms of mediator(s), or other racial and ethnic groups. PBDE mixtures may partially mediate the Black vs. White disparity in GA at delivery. While further validations are needed, lowering the PBDEs at the population level might help reduce this disparity.

The endocrine disruptor DE-79 alters oxytocinergic transmission and sexual behavior expression in male rats

Polybrominated diphenyl ethers (PBDEs), used as flame retardants are persistent organic pollutants exerting important health effects. PBDEs with >5 bromide substitutions were considered less harmful and therefore extensively used commercially. DE-79 was a widely used PBDE mixture of hexa-, hepta-, octa- and nona-brominated compounds that increases vasopressin (AVP) production. AVP and oxytocin (OT) are both produced in neurons of the supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei projecting to the neurohypophysis and to brain regions involved in copulatory behavior. OT plays an important role in male copulation. Since DE-79 alters AVP expression in the SON and PVN, it might also modify OT content and alter male sexual behavior. We analyzed if repeated DE-79 exposure of adult male rats affected OT content and OT receptor (OTR) density in the SON, PVN, medial preoptic area (mPOA), ventral tegmental area, nucleus accumbens, and amygdala, and if male copulatory behavior was affected. We show that DE-79 exposure produces a generalized decrease in brain OT immunoreactivity, increases OTR density in all brain regions analyzed but the mPOA, and reduces the ejaculatory threshold after a first ejaculation. The documented ejaculation-induced OT release might participate in this last effect. Thus, one-week DE-79 exposure alters the OT-OTR system and modifies male rat sexual performance. Based on the literature it could be speculated that these effects are related to the putative endocrine disrupting actions of DE-79, ultimately altering brain OT levels and OTR expression that might affect copulation and other important OT-mediated brain functions.

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.

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.

Analysis and Pollution Assessment of Brominated Flame Retardants (PBDEs, DBDPE, and BTPBE) in Settled Dust from E-waste and Vehicle Processing Areas in Northern Vietnam

Polybrominated diphenyl ethers (PBDEs), decabromodiphenyl ethane (DBDPE), and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) are typical brominated flame retardants (BFRs), which were widely added to polymeric and textile materials to meet fire safety requirements. PBDEs (including commercial penta-, octa-, and deca-BDE mixtures) have been classified as persistent organic pollutants (POPs) under the Stockholm Convention, while DBDPE and BTBPE are considered as PBDE replacements. In the present study, concentrations of PBDEs (major congeners of technical PBDE mixtures such as BDE-28, 47, 99, 100, 153, 154, 183, 197, 207, and 209), DBDPE, and BTBPE were simultaneously analyzed in settled dust samples collected from e-waste and end-of-life vehicle (ELV) processing areas in northern Vietnam. The dust samples were extracted by using an ultrasonic processor subsequently by acetone and acetone/hexane (1:1) mixture for 10 min each time. The dust extract was treated with concentrated sulfuric acid and activated silica gel to remove interferences. BFRs were analyzed by using gas chromatography/mass spectrometry (GC/MS) equipped with a DB-5ht column. The mass spectrometer was operated at electron capture negative ionization (ECNI) and selected ion monitoring (SIM) mode. Concentrations of total PBDEs, DBDPE, and BTBPE ranged from 77 to 240,000 (median 6000), from &lt;20 to 240,000 (median 5500), and from &lt;10 to 9200 (median 160) ng/g, respectively. Concentrations of BFRs in the e-waste dust were significantly higher than those measured in the ELV dust, suggesting e-waste processing activities as potential sources of BFRs in dust. Among BFRs analyzed, BDE-209 and DBDPE were the most predominant compounds, implying intensive application of deca-BDE mixtures and alternative formulations.

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.

Simultaneous Method for Selected PBDEs and HBCDDs in Foodstuffs Using Gas Chromatography-Tandem Mass Spectrometry and Liquid Chromatography-Tandem Mass Spectrometry.

Flame retardants are added to consumer products to retard the ignition of combustible materials. Technical mixtures of polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD) were massively used for several decades. They are bioaccumulative, persistent, and have adverse effects on organisms. Recognised as persistent organic pollutants, they are banned almost worldwide. Food is the principal source of human exposure. Yet, no maximum residue limits for food have been established in the EU. Nevertheless, monitoring of specific congeners is recommended. Simultaneous analysis of HBCDDs and PBDEs is rarely encountered, especially including BDE-209, as this thermally unstable congener is particularly challenging for analysis. We have developed a method for the simultaneous determination of all relevant PBDEs and HBCDDs recommended for monitoring by the EU. In the method, single sample preparation is used for different types of foodstuffs, applying ultrasound-assisted extraction, clean-up by gel permeation, and adsorption chromatography. Analyses were performed on the same extract, first by GC-MS/MS(EI) method for PBDEs and followed by LC-MS/MS(ESI) method for HBCDDs. The analytical method was validated on a blank sample of milk formula at 2-3 fortification levels, including recommended LOQ level of 0.01 µg/kg wet weight. Satisfactory accuracy with recoveries 85-119%, intra-day precision (1.5-11.3%), and inter-day precision (4.3-18.4%) was obtained. The method ensures LOQs that are compliant with the EU recommendations for all PBDEs and HBCDDs, including BDE-209. Method applicability was further confirmed on proficiency testing samples of baby food, fish, and citrus.

Developmental exposure to the brominated flame retardant DE-71 reduces serum thyroid hormones in rats without hypothalamic-pituitary-thyroid axis activation or neurobehavioral changes in offspring

Polybrominated diphenyl ethers (PBDEs) are legacy flame retardants for which human exposure remains ubiquitous. This is of concern since these chemicals can perturb development and cause adverse health effects. For instance, DE-71, a technical mixture of PBDEs, can induce liver toxicity as well as reproductive and developmental toxicity. DE-71 can also disrupt the thyroid hormone (TH) system which may induce developmental neurotoxicity indirectly. However, in developmental toxicity studies, it remains unclear how DE-71 exposure affects the offspring's thyroid hormone system and if this dose-dependently relates to neurodevelopmental effects. To address this, we performed a rat toxicity study by exposing pregnant dams to DE-71 at 0, 40 or 60 mg/kg/day during perinatal development from gestational day 7 to postnatal day 16. We assessed the TH system in both dams and their offspring, as well as potential hearing and neurodevelopmental effects in prepubertal and adult offspring. DE-71 significantly reduced serum T4 and T3 levels in both dams and offspring without a concomitant upregulation of TSH, thus inducing a hypothyroxinemia-like effect. No discernible effects were observed on the offspring's brain function when assessed in motor activity boxes and in the Morris water maze, or on offspring hearing function. Our results, together with a thorough review of the literature, suggest that DE-71 does not elicit a clear dose-dependent relationship between low serum thyroxine (T4) and effects on the rat brain in standard behavioral assays. However, low serum TH levels are in themselves believed to be detrimental to human brain development, thus we propose that we lack assays to identify developmental neurotoxicity caused by chemicals disrupting the TH system through various mechanisms.

Polybrominated diphenyl ethers in early pregnancy and preterm birth: Findings from the NICHD Fetal Growth Studies.

Studies suggest associations between exposure to individual polybrominated diphenyl ethers (PBDEs) with preterm birth (PTB) and shorter gestational age. Little is known about exposure to PBDE mixtures and these outcomes. We evaluated associations of multiple PBDEs in early pregnancy with gestational age at delivery and PTB. Data were collected from 2046 women without obesity and 396 women with obesity from the NICHD Fetal Growth Studies, who had early pregnancy plasma PBDEs concentrations and gestational age at delivery. PTB was defined as < 37 weeks of gestation at delivery and further categorized into subtypes (late or very early/moderate; spontaneous or medically indicated). We applied (1) generalized linear models (GLM); (2) principal component analysis (PCA); and (3) Bayesian Kernel Machine Regression (BKMR) to evaluate the individual and joint associations of log-transformed PBDE concentrations with gestational age at delivery and PTB, adjusting for potential confounders and evaluating effect modifiers. In GLM analyses, a 1-standard deviation (SD) increase in log-PBDE 153 was associated with shorter gestational age at delivery [adjusted β (95% CI)=-0.19 (-0.31, -0.06) weeks] among women without obesity. In PCA analyses, 1-SD increase in the principal component summarizing most of PBDE 153 variability was associated with shorter gestational age at delivery [adjusted β (95% CI)=-0.18 (-0.30, -0.06) weeks], very early/moderate PTB [adjusted OR (95% CI)=1.91 (1.19, 3.07)], and spontaneous PTB [adjusted OR (95% CI)=1.34 (1.00, 1.80)] among women without obesity. Associations were stronger among non-Hispanic Black women, women with BMI ranging between 25 and 30kg/m2, and women who were ≥35 years old among those without obesity. In BKMR analyses, a suggestive inverse association between PBDE 153 and gestational age at delivery, and an inverse U-shaped association between PBDE 154 and gestational age at delivery were observed in women without obesity. No statistically significant association of PBDEs and gestational age or PTB was observed among women with obesity. PBDEs, specifically PBDE 153, were associated with shorter gestation and higher risk of certain PTB subtypes among pregnant women without obesity.

Thyroid Supplementation Reverses the Abnormal Social and Oxytocin Phenotype Produced by Developmental Exposure to PBDEs in a Sex‐Dependent Manner

Polybrominated diphenyl ethers (PBDEs) are endocrine‐disrupting chemicals (EDCs) that are widely used flame retardants added to common household products. In humans, PBDEs are associated with neurodevelopmental deficits including ones associated with social competence and learning. We have previously shown that PBDE‐exposed F1 female progeny display autism‐relevant characteristics such as deficient social novelty preference and social recognition memory (SRM), exaggerated repetitive behavior and deficient social odor discrimination (Kozlova et al 2021). In this study, we show that developmental exposure (via dam GD0‐PND21) to the PBDE mixture, DE‐71 (L‐DE‐71; 0.1 mg/kg/d), reduces oxytocin immunofluorescence density in the paraventricular nucleus of the hypothalamus (PVN) that is critical for social recognition memory in male and female F1 offspring relative to VEH/CON (0 mg/kg/d). One of the well characterized actions of PBDEs is disruption of the hypothalamo‐pituitary‐thyroid axis (HPT). Thyroid hormones (TH) are critical for nervous system development and regulate the transcription of oxytocin. We show for the first time, that L‐DE‐71 alters central thyroid hormone species (T2, rT3, T3, and T4) relative to VEH/CON in F1 offspring but with a different temporal pattern in males (PND30) and females (PND15) as measured using liquid chromatography‐tandem mass spectrometry. This coincides with reduced plasma T4 in PND15 male but not female offspring. Supplementation of pregnant dams with levothyroxine, a synthetic analogue of thyroxine (T4), during gestation and lactation (GD12‐PND21), increased plasma oxytocin in exposed dams. More importantly, supplementation normalized PBDE‐induced deficiency in social recognition memory test, and PVN oxytocin levels in exposed female but not male offspring. These changes are specific to social behavior as were no changes in passive avoidance memory. Interestingly, L‐DE‐71 female but not male F1 also receiving supplementation showed a significant increase in plasma T4. Maternal behavior (retrieval of PND4 pups) was significantly reduced by supplementation with 6‐propyl‐2‐thiouracil, a drug that blocks the production of thyroid hormone by thyroid gland, but not by DE‐71 nor DE‐71 plus levothyroxine supplementation. These results provide novel insight into neuroendocrine disruption of the central oxytocin system by maternal transfer of environmental pollutants and its possible contribution to neurodevelopmental disorders such as autism.

Associations between environmental exposure to polybrominated diphenyl ethers and nodular goiter risk: A case-control study

Polybrominated diphenyl ethers (PBDEs) are widespread and persistent environmental contaminants, but their association with nodular goiter (NG) remains unknown. The present case-control study of 179 NG cases and 358 matched normal controls aimed to investigate the association between PBDEs and risk of NG. The plasma concentrations of 8 PBDEs congeners (BDE-28, -47, −99, −100, −153, −154, −183, and −209) were determined by gas chromatograph-mass spectrometer. Conditional logistic regression model was used to evaluate the odds ratio (OR) and 95% confidence interval (CI) for the association between each PBDEs congener and NG. Bayesian kernel machine regression (BKMR) was used to evaluate the association between overall levels of 8 PBDEs mixture and NG. The results of logistic model suggested that increased risk of NG was associated with elevated concentrations of all PBDEs congeners, except for BDE-209. In BKMR model, the risk of NG increased with the increase in overall exposure level of 8 PBDEs mixture. Compared to when all PBDEs mixture were at their median value, the risk of exposure-response function for NG increased by 0.34 units when all PBDEs were at their 75th percentile. In women, the results showed similar trends after additional adjustment for age at menarche and menopausal status. These findings provide novel epidemiological evidence for the prevention of NG. However, larger prospective studies are required to address the associations between PBDEs exposure and NG risk.

Per-and polyfluoroalkyl substances (PFAS) and persistent chemical mixtures in dust from U.S. colleges

Indoor spaces contain several classes of persistent organic chemicals, including per- and polyfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs). However, concentrations of PFAS and persistent chemical mixtures and their associations with building characteristics on college campuses are understudied. We collected dust from 43 nonresidential spaces on four U.S. college campuses in 2016 and evaluated associations of room characteristics (carpeting, upholstered furniture, and years since last furnished) with dust concentrations of PFAS, PBDEs, PCBs, and OCPs. Nine PFAS, twelve PBDEs, two PCBs, and four OCPs were each detected in at least 75% of the spaces, including several chemicals (e.g., DDT) that have been banned for decades. Concentrations were correlated within and, in some cases, between chemical classes. Wall-to-wall carpeting (compared to rooms without wall-to-wall carpeting) was associated with higher concentrations of six individual PFAS and a mixture of PFAS, and the number of pieces of upholstered furniture was associated with increased concentrations of a mixture of PBDEs. These findings indicate that carpeting and furniture are current sources of PFAS and PBDEs, respectively. Building and finish materials should be carefully selected to avoid exposure to persistent chemicals.

Recycling plastics containing decabromodiphenyl ether into new consumer products including children's toys purchased in Japan and seventeen other countries

Polybrominated diphenyl ethers (PBDEs) are flame retardants widely used to manufacture several commercial plastic products. The major homologue in commercial PBDE mixtures are listed in the Stockholm Convention on Persistent Organic Pollutants and are scheduled for global elimination. Hence, to understand more about unintentional contamination of plastic recycling stream by restricted PBDEs, we examined 540 small plastic consumer products (1139 components after dismantling), including children's toys, purchased in 18 countries (mainly Japan) between 2015 and 2019. Handheld X-ray fluorescence analysis revealed that 219 plastic components (19% of the total samples) contained bromine at a concentration of ≥30 mg kg−1. Chemical analysis of these bromine-positive components revealed that 109 pieces (9.6% of the total), mainly those made of black-colored plastic, contained PBDEs at concentrations ranging between 35 and 10,000 mg kg−1, with the maximum contribution from decabromodiphenyl ether (decaBDE). These PBDE concentrations were insufficient to impart flame retardancy, suggesting that the recycled plastic used to manufacture these consumer products probably originated from electronic waste, the manufacture of which was the primary use of commercial decaBDE mixtures. PBDEs were also found in secondary raw plastic materials and their final products obtained in India in 2019, demonstrating that plastics containing decaBDE end up in products where they serve no functional purpose. To contribute to the circular economy, the recycling of plastic waste in end-of-life products should be promoted. However, urgent action is needed to prevent plastic additives of concern, including PBDEs, from entering new products used in daily lives, particularly those used by children.

Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71

Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring. C57Bl6/N mouse dams (F0) were exposed to DE-71 via oral administration of 0 (VEH/CON), 0.1 (L-DE-71) or 0.4 (H-DE-71) mg/kg bw/d from 3 wk prior to gestation through end of lactation. Mass spectrometry analysis indicated in utero and lactational transfer of PBDEs (in ppb) to F1 female offspring brain tissue at postnatal day (PND) 15 which was reduced by PND 110. Neurobehavioral testing of social novelty preference (SNP) and social recognition memory (SRM) revealed that adult L-DE-71 F1 offspring display deficient short- and long-term SRM, in the absence of reduced sociability, and increased repetitive behavior. These effects were concomitant with reduced olfactory discrimination of social odors. Additionally, L-DE-71 exposure also altered short-term novel object recognition memory but not anxiety or depressive-like behavior. Moreover, F1 L-DE-71 displayed downregulated mRNA transcripts for oxytocin (Oxt) in the bed nucleus of the stria terminalis (BNST) and supraoptic nucleus, and vasopressin (Avp) in the BNST and upregulated Avp1ar in BNST, and Oxtr in the paraventricular nucleus. Our work demonstrates that developmental PBDE exposure produces ASD-relevant neurochemical, olfactory processing and behavioral phenotypes that may result from early neurodevelopmental reprogramming within central social and memory networks.

Prenatal exposure to environmentally relevant levels of PBDE-99 leads to testicular dysgenesis with steroidogenesis disorders

Polybrominated diphenyl ethers (PBDEs) are a widely used class of brominated flame retardants. Exposure to PBDEs could induce testicular damage in mammals, but the effects and potential mechanism of action of prenatal exposure to environmentally relevant PBDEs on testicular development remain unclear. For the in vivo study, pregnant ICR mice were exposed to environmentally relevant levels of 2,2′,4,4′,5-pentabromodiphenyl ether (PBDE-99), a major component of commercial PBDE mixtures. We found that the anogenital index and testicular organ coefficient were significantly decreased, the incidence of cryptorchidism was increased, and testicular histology was disturbed in male offspring. Transcriptomic profiling showed that steroidogenesis disorders were significant in all PBDE-99 exposure groups. The testosterone levels, expressions of testosterone regulators, and the number of CYP11A1-positive and 11β-HSD1-positive Leydig cells were significantly decreased after PBDE-99 exposure. For the in vitro study, TM3 Leydig cells were exposed to PBDE-99 at gradient concentrations. Transcriptomic profiling and validation experiments showed that PBDE-99 upregulated reactive oxygen species, activated the ERK1/2 pathway, inhibited the ubiquitination degradation pathway, and finally induced Leydig cell apoptosis. Cumulatively, these findings revealed that prenatal exposure to environmentally relevant levels of PBDE-99 leads to steroidogenesis disorders by inducing the apoptosis of Leydig cells, causing testicular dysgenesis.

Contamination status, emission sources, and human health risk of brominated flame retardants in urban indoor dust from Hanoi, Vietnam: the replacement of legacy polybrominated diphenyl ether mixtures by alternative formulations.

This study investigated the occurrence, distribution of several additive brominated flame retardants (BFRs) such as polybrominated diphenyl ethers (PBDEs) and some novel brominated flame retardants (NBFRs) in urban indoor dust collected from ten inner districts of Hanoi, Vietnam to assess the contamination status, emission sources, as well as their associated human exposure through indoor dust ingestion and health risks. Total concentrations of PBDEs and NBFRs in indoor dust samples ranged from 43 to 480 ng g-1 (median 170 ng g-1) and from 56 to 2200 ng g-1 (median 180 ng g-1), respectively. The most abundant PBDE congener in these dust samples was BDE-209 with concentrations ranging from 29 to 360 ng g-1, accounting for 62.6-86.5% of total PBDE levels. Among the NBFRs analyzed, decabromodiphenyl ethane (DBDPE) was the predominant compound with a mean contribution of 98.6% total NBFR amounts. Significant concentrations of DBDPE were detected in all dust samples (median 180 ng g-1, range 54-2200 ng g-1), due to DBDPE as a substitute for deca-BDE. Other NBFRs such as 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE), pentabromoethylbenzene (PBEB) and 2,2',4,4',5,5'-hexabromobiphenyl (BB-153) were found at very low levels. Based on the measured BFR concentrations, daily intake doses (IDs) of PBDEs and NBFRs via dust ingestion at exposure scenarios using the median and 95th percentile levels for both adults and children were calculated for risk assessment. The results showed that the daily exposure doses via dust ingestion of all compounds, even in the high-exposure scenarios were also lower than their reference dose (RfD) values. The lifetime cancer risks (LTCR) were much lower than the threshold level (10-6), which indicated the acceptable health risks resulting from indoor BFRs exposure for urban residents in Hanoi.

Polybrominated Diphenyl Ether Serum Concentrations and Depressive Symptomatology in Pregnant African American Women.

(1) Polybrominated diphenyl ethers (PBDEs) were widely produced in the United States until 2004 but remain highly persistent in the environment. The potential for PBDEs to disrupt normal neuroendocrine pathways resulting in depression and other neurological symptoms is largely understudied. This study examined whether PBDE exposure in pregnant women was associated with antenatal depressive symptomatology. (2) Data were collected from 193 African American pregnant women at 8–14 weeks gestation. Serum PBDEs and depressive symptoms were analyzed and a mixture effect was calculated. (3) Urban pregnant African American women in the Southeastern United States had a high risk of depression (27%) compared to the National average. Increased levels of PBDEs were found. BDE-47 and -99 exposures are significantly associated with depressive symptomatology in the pregnant cohort. The weighted body burden estimate of the PBDE mixture was associated with a higher risk of mild to moderate depression using an Edinburgh Depression Scale cutoff score of ≥10 (OR = 2.93; CI 1.18, 7.82). (4) Since antenatal depression may worsen in postpartum, reducing PBDE exposure may have significant clinical implications.

Gulls foraging in landfills: Does atmospheric exposure to halogenated flame retardants result in bioaccumulation?

Several bird species have adapted to foraging in landfills, although these sites are known to represent significant sources of emissions of toxic semi-volatile chemicals including the halogenated flame retardants (HFRs) (e.g., polybrominated diphenyl ethers (PBDEs) and emerging compounds). The objective of this study was to investigate the association between atmospheric exposure to PBDEs and selected emerging HFRs and their bioaccumulation in landfill-foraging birds. We determined HFR concentrations in liver of 58 GPS-tagged ring-billed gulls (Larus delawarensis) breeding in a colony near Montreal (Canada) as well as their atmospheric exposure determined using a miniature bird-borne passive air sampler. PBDE mixtures were the most abundant HFRs determined in passive air samplers (daily exposure rates of ∑9PentaBDE: 47.4 ± 6.5 pg/day; DecaBDE: 36.0 ± 6.3 pg/day, and ∑3OctaBDE: 3.4 ± 0.5 pg/day) and liver (∑9PentaBDE: 68.1 ± 8.9 ng/g ww; DecaBDE: 52.3 ± 8.1 ng/g ww, and ∑3OctaBDE: 12.8 ± 2.1 ng/g ww), and their concentrations increased with the presence probability of gulls in landfills. We found a spatial relationship between the local sources of atmospheric exposure to PBDEs and the sites associated with greatest PBDE concentrations in liver. Specifically, the atmospheric exposure index was correlated with the bioaccumulation index (Pearson r for ∑9PentaBDE: r = 0.63, p < 0.001; DecaBDE: r = 0.66, p < 0.001, and ∑3OctaBDE: r = 0.42, p < 0.001). However, we found no correlation at the individual level between daily exposure rates of HFRs in passive air samplers and their liver concentrations. This suggests that complex exposure pathways combined with toxicokinetic factors shaped HFR profiles in gull liver, potentially confounding the relationships with atmospheric exposure.