Mixture effects of prenatal exposure to polybrominated diphenyl ethers on urinary oxidative stress biomarkers in the Chemicals in Our Bodies Cohort.

Polybrominated diphenyl ethers (PBDEs) exposure is associated with preterm birth. Laboratory studies suggest that PBDEs lead to elevated oxidative stress, a known contributor to preterm birth in epidemiologic studies. We hypothesized that elevated levels of PBDEs would be associated with increased oxidative stress during human pregnancy. Participants in this analysis were enrolled in the Chemicals in Our Bodies cohort and resided in the San Francisco Bay Area (N=201). Four PBDEs (BDE-47, -99, -100, -153) were measured in second trimester serum. Urinary oxidative stress biomarkers were measured at two timepoints (second and third trimester) and included 8-isoprostane-prostaglandin-F2α [8-iso-PGF2α], 2,3-dinor-5,6-dihydro-8-iso-PGF2α, 2,3-dinor-8-iso-PGF2α, and prostaglandin-F2α [PGF2α]. Associations between individual PBDEs and oxidative stress biomarkers (averaged and trimester specific) were examined using linear regression. Quantile g-computation and Bayesian kernel machine regression (BKMR) were used to assess cumulative effects of PBDEs. Quantile g-computation showed that higher concentrations of PBDEs were associated with increasing 8-iso-PGF2α, 2,3-dinor-8-iso-PGF2α, and PGF2α. Associations were greatest in magnitude for second trimester levels of 2,3-dinor-8-iso-PGF2α (mean change per quartile increase=0.25, 95% confidence interval=0.09, 0.41). Associations were similar using BKMR and linear regression. Our findings suggest that oxidative stress may be a plausible biological pathway by which PBDE exposure might lead to preterm birth.

Underexplored Organohalide-Respiring Bacteria in Sewage Sludge Debrominating Polybrominated Diphenyl Ethers.

Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants prevalent in the environment. Organohalide-respiring bacteria (OHRB) can attenuate PBDEs via reductive debromination, but often producing toxic end-products. Debromination of PBDEs to diphenyl ether remains a rare phenomenon and is so far specifically associated with Dehalococcoides isolated from e-waste polluted sites. The occurrence of PBDE debromination in other ecosystems and underpinning OHRB are underexplored. Here we found that debromination of PBDEs is a common trait of sewage sludge microbiota, and diphenyl ether was produced as the end-product at varying quantities (0.6-52.9% mol of the parent PBDEs) in 76 of 84 cultures established with bioreactor sludge. Diverse debromination pathways converting PBDEs to diphenyl ether, including several new routes, were identified. Although Dehalococcoides contributed to PBDE debromination, Dehalogenimonas, Dehalobacter, and uncultivated Dehalococcoidia likely played more important roles than previously recognized. Multiple reductive dehalogenase genes (including bdeA, pcbA4, pteA, and tceA) were also prevalent and coexisted in bioreactor sludge. Collectively, these findings contribute to enhancing our comprehension of the environmental fate of PBDEs, expanding the diversity of microorganisms catalyzing PBDE debromination, and developing consortia for bioremediation application.

Biomarkers of Organophosphate and Polybrominated Diphenyl Ether (PBDE) Flame Retardants of American Workers and Associations with Inhalation and Dermal Exposures.

This study evaluated workers' exposures to flame retardants, including polybrominated diphenyl ethers (PBDEs), organophosphate esters (OPEs), and other brominated flame retardants (BFRs), in various industries. The study aimed to characterize OPE metabolite urinary concentrations and PBDE serum concentrations among workers from different industries, compare these concentrations between industries and the general population, and evaluate the likely route of exposure (dermal or inhalation). The results showed that workers from chemical manufacturing had significantly higher (p <0.05) urinary concentrations of OPE metabolites compared to other industries. Spray polyurethane foam workers had significantly higher (p <0.05) urinary concentrations of bis(1-chloro-2-propyl) phosphate (BCPP) compared to other industries. Electronic scrap workers had higher serum concentrations of certain PBDE congeners compared to the general population. Correlations were observed between hand wipe samples and air samples containing specific flame-retardant parent chemicals and urinary metabolite concentrations for some industries, suggesting both dermal absorption and inhalation as primary routes of exposure for OPEs. Overall, this study provides insights into occupational exposure to flame retardants in different industries and highlights the need for further research on emerging flame retardants and exposure reduction interventions.

Polybrominated diphenyl ethers and gestational weight gain: a multi-center prospective cohort study.

OBJECTIVE: To evaluate the associations of plasma polybrominated diphenyl ether (PBDE) concentrations in early pregnancy with gestational weight gain (GWG). DESIGN: Prospective cohort study. SETTING: US-based, multicentre cohort of pregnant women. POPULATION: We used data from 2052 women without obesity and 397 women with obesity participating in the NICHD Fetal Growth Studies - Singleton Cohort, with first-trimester plasma PBDE concentrations and weight measurements throughout pregnancy. METHODS: We applied generalised linear models and Bayesian kernel machine regression (BKMR) to evaluate both the individual and joint associations of PBDEs with measures of GWG, adjusting for potential confounders. MAIN OUTCOME MEASURES: Total GWG (kg), total and trimester-specific GWG velocities (kg/week), and GWG categories and trajectory groups. RESULTS: Mean pre-pregnancy BMIs were 23.6 and 34.5 kg/m2 for women without and with obesity, respectively. Among women without obesity, there were no associations of PBDEs with any GWG measure. Among women with obesity, one standard deviation increase in log-transformed PBDE 47 was associated with a 1.87 kg higher total GWG (95% CI 0.39-3.35) and a 0.05 kg/week higher total GWG velocity (95% CI 0.01-0.09). Similar associations were found for PBDE 47 in BKMR among women with obesity, and PBDE 47, 99 and 100 were associated with lower odds of being in the low GWG trajectory group. CONCLUSIONS: PBDEs were not associated with GWG among individuals without obesity. Among those with obesity, only PBDE 47 showed consistent positive associations with GWG measures across multiple statistical methods. Further research is needed to validate this association and explore potential mechanisms.

Exposure levels and determinants of placental polybrominated diphenyl ethers in Chinese pregnant women.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are a group of widely used chemicals and humans are exposed to them in their daily life. PBDEs exposure during pregnancy may have adverse effects on pregnant women and their fetuses. Nevertheless, limited information is available on the levels and determinants of PBDEs exposure in Chinese pregnant women. METHODS: The internal exposure levels of eight PBDEs (BDE-28, 47, 99, 100, 153, 154, 183, and 209) in placental samples of 1280 pregnant women from Zunyi birth cohort were analyzed using gas chromatography tandem mass spectrometry. All PBDEs concentrations were lipid adjusted (ng/g lw). Determinants of exposure were assessed by multivariable logistic regression model. RESULTS: Eight PBDE homologues were quantifiable in more than 70% of the samples. The highest median concentrations were found for BDE-209 (2.78 ng/g lw), followed by BDE-153 (1.00 ng/g lw) and BDE-183 (0.93 ng/g lw). The level of ΣPBDEs ranged from 0.90 to 308.78 ng/g lw, with a median concentration of 10.02 ng/g lw. Multivariate logistic regression analysis showed that maternal age older than 30 years old (OR: 1.59; 95% CI: 1.14, 2.23), pre-pregnancy obesity (1.51; 1.08, 2.10), home renovation within 2 years (1.43; 1.08, 1.91), spending more time outdoors during pregnancy (0.70; 0.55, 0.89), high consumption of fish/seafood (1.46; 1.13, 1.90) and eggs (1.44; 1.04, 2.00), male infant sex (1.69; 1.18, 2.42) were associated with PBDEs exposure. CONCLUSION: The study population is generally exposed to PBDEs, of which BDE-209 is the dominant congener, indicating extensive application of products containing deca-BDE mixtures. Maternal age, pre-pregnancy BMI, home decoration, average outdoor time during pregnancy, fish, seafood, eggs consumption, and fetal sex were exposure-determinning factors. This study contributes to the knowledge on region-specific PBDEs contamination in pregnant women and related risk factors.

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.

BACKGROUND: Polybrominated 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. METHODS: Demographics 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. RESULTS: The 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 (ß = 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. CONCLUSIONS: In-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.

Per- and polyfluoroalkyl substances, polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers and dysregulation of MicroRNA expression in humans and animals-A systematic review.

BACKGROUND: Persistent organic pollutants (POPs) are chemicals characterized by their environmental persistence. Evidence suggests that exposure to POPs, which is ubiquitous, is associated with microRNA (miRNA) dysregulation. miRNA are key regulators in many physiological processes. It is thus of public health concern to understand the relationships between POPs and miRNA as related to health outcomes. OBJECTIVES: This systematic review evaluated the relationship between widely recognized, intentionally manufactured, POPs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (dichlorodiphenyltrichloroethane [DDT], dichlorodiphenyldichloroethylene [DDE], hexachlorobenzene [HCB]), with miRNA expression in both human and animal studies. METHODS: We used PubMed and Embase to systematically search the literature up to September 29th, 2023. Search results for human and animal studies were included if they incorporated at least one POP of interest in relation to at least one miRNA. Data were synthesized to determine the direction and significance of associations between POPs and miRNA. We utilized ingenuity pathway analysis to review disease pathways for miRNA that were associated with POPs. RESULTS: Our search identified 38 eligible studies: 9 in humans and 29 in model organisms. PFAS were associated with decreased expression of miR-19, miR-193b, and miR-92b, as well as increased expression of miR-128, miR-199a-3p, and miR-26b across species. PCBs were associated with increased expression of miR-15a, miR-1537, miR-21, miR-22-3p, miR-223, miR-30b, and miR-34a, as well as decreased expression of miR-130a and let-7b in both humans and animals. Pathway analysis for POP-associated miRNA identified pathways related to carcinogenesis. DISCUSSION: This is the first systematic review of the association of POPs with miRNA in humans and model organisms. Large-scale prospective human studies are warranted to examine the role of miRNA as mediators between POPs and health outcomes.

Design and Synthesis of Marine Polybrominated Diphenyl Ether Derivatives as Potential Anti-Inflammatory Agents.

Natural polybrominated diphenyl ethers are generally isolated from sponges and possess a broad range of biological activities. Through screening of our marine natural product library, we discovered that polybrominated diphenyl ethers 5 and 6 exhibit considerable anti-inflammatory activity. In order to expand our repertoire of derivatives for further biological activity studies, we designed and synthesized a series of 5-related polybrominated diphenyl ethers. Importantly, compound 5a showed comparable anti-inflammatory activity while much lower cytotoxicity on lipopolysaccharide (LPS)-induced RAW264.7 cells. Additionally, western blotting analysis showed that 5a reduced the expression of phosphorylated extracellular signal-regulated kinase (p-ERK). Besides, molecular docking experiments were conducted to predict and elucidate the potential mechanisms underlying the varying anti-inflammatory activities exhibited by compounds 5a, 5, and 6.

Gestational Exposure to Common Endocrine Disrupting Chemicals and Their Impact on Neurodevelopment and Behavior.

Endocrine disrupting chemicals are common in our environment and act on hormone systems and signaling pathways to alter physiological homeostasis. Gestational exposure can disrupt developmental programs, permanently altering tissues with impacts lasting into adulthood. The brain is a critical target for developmental endocrine disruption, resulting in altered neuroendocrine control of hormonal signaling, altered neurotransmitter control of nervous system function, and fundamental changes in behaviors such as learning, memory, and social interactions. Human cohort studies reveal correlations between maternal/fetal exposure to endocrine disruptors and incidence of neurodevelopmental disorders. Here, we summarize the major literature findings of endocrine disruption of neurodevelopment and concomitant changes in behavior by four major endocrine disruptor classes:bisphenol A, polychlorinated biphenyls, organophosphates, and polybrominated diphenyl ethers. We specifically review studies of gestational and/or lactational exposure to understand the effects of early life exposure to these compounds and summarize animal studies that help explain human correlative data.

Decabromodifenyl Ether (BDE-209) in Surface Soils from Warsaw and Surrounding Areas: Characterization of Non-Carcinogenic Risk Associated with Oral and Dermal Exposure.

Polybrominated diphenyl ethers (PBDEs) have been used for many years as flame retardants. Due to their physicochemical and toxicological properties, they are considered to be persistent organic pollutants (POPs). BDE-209 is the main component of deca-BDE, the one PBDE commercial mixture currently approved for use in the European Union. The aim of this study was to analyse BDE-209 in surface soil samples from Warsaw and surrounding areas (Poland) as an indicator of environmental pollution with PBDEs, and to characterise the associated health risk. A total of 40 samples were analysed using gas chromatography with electron capture detection (GC-µECD). Concentrations of BDE-209 in soil ranged from 0.4 ng g-1 d.w. (limit of quantification) to 158 ng g-1 d.w. Overall, 52.5% of results were above the method's limit of quantification. The highest levels were found at several locations with heavy traffic and in the vicinity of a CHP plant in the city. The lowest concentrations were observed in most of the samples collected from low industrialized or green areas (<0.4 to 1.68 ng g-1 d.w.). Exposure to BDE-209 was estimated for one of the most sensitive populations, i.e., young children. The following exposure routes were selected: oral and dermal. No risk was found to young children's health.

Levels, Distribution and Ecological Risk Assessment of PBDEs in Soils and Plants Around the Engineering Plastics Factory.

This study systematically investigated the pollution levels and migration trends of PBDEs in soils and plants around engineering plastics factory, and identified the ecological risks of PBDEs in the environment around typical pollution sources.The results showed that 13 kinds of PBDEs were widely detected in the surrounding areas, and the concentration level was higher than the general environmental pollution level. The total PBDE concentrations (∑13PBDEs) in soils ranged from 14.6 to 278.4 ng/g dry weight (dw), and in plants ranged from 11.5 to 176 ng/g dw. Both soil and plant samples showed that BDE-209 was the most important congener, the pollution level in soil and plant was similar, and the composition of PBDEs congener was similar. In the soil column (50 cm), the radial migration of PBDEs was mainly concentrated in the 0-30 cm section. Except for BDE-66, which was mainly located in the 20-30 cm soil layer, the concentration of PBDEs was the highest in the 0-10 cm region. Furthermore, the environmental risks of PBDEs in soil and plants were evaluated by hazard quotient method, and the HQ values were all < 1, which did not exhibit any ecological risk. The evaluation results also showed that the ecological risk of PBDEs in soil was higher than that of plants, especially penta-BDE, which should be paid more attention.

[Research progress on the developmental toxicity and mechanism of brominated flame retardants during pregnancy exposure on offspring].

Brominated flame retardants (BFRs) are a kind of brominated compounds widely used in electronic and electrical appliances, textiles, construction materials and other industrial products to improve the flame retardant property. Because of its strong chemical stability, environmental persistence, long-distance transmission, biological accumulation, the exposure of humans and organisms in the ecosystem is increasing, and its potential biological effects are of great concern. Now BFRs can be detected in breast milk, serum, placenta and cord blood. Studies have shown that exposure to BFRs during pregnancy can lead to adverse birth outcomes such as low birth weight, malformation, gestational age changes and impairment of neurobehavioral development. This article summarizes the pollution and population exposure of three traditional BFRs, polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA), as well as the impact and mechanism of prenatal exposure on offspring birth outcomes and growth and development. It explores the harm of prenatal exposure to BFRs to offspring and proposes preventive measures for occupational populations for reference.

Novel Insights into the Dermal Bioaccessibility and Human Exposure to Brominated Flame Retardant Additives in Microplastics.

In this study, we optimized and applied an in vitro physiologically based extraction test to investigate the dermal bioaccessibility of polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD), incorporated as additives in different types of microplastics (MPs), and assess human dermal exposure to these chemicals. The dermal bioaccessibility of PBDEs in polyethylene (PE) MPs was significantly higher (P < 0.05) than in polypropylene (PP) MPs. Both log Kow and water solubility influenced the dermal bioaccessibility of PBDEs. For HBCDDs in polystyrene MPs, the dermally bioaccessible fractions were 1.8, 2.0, and 1.6% of the applied dose for α-, ß-, and γ-HBCDDs, respectively. MP particle size and the presence of cosmetic formulations (antiperspirant, foundation, moisturizer and sunscreen) influenced the bioaccessibility of PBDEs and HBCDDs in MP matrices at varying degrees of significance. Human exposure to ∑PBDEs and ∑HBCDDs via dermal contact with MPs ranged from 0.02 to 22.2 and 0.01 to 231 ng (kg bw)-1 d-1 and from 0.02 to 6.27 and 0.2 to 65 ng (kg bw)-1 d-1 for adults and toddlers, respectively. Dermal exposure to PBDEs and HBCDDs in MPs is substantial, highlighting for the first time the significance of the dermal pathway as a major route of human exposure to additive chemicals in microplastics.

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.

Disentangling Source Profiles and Time Trends of Halogenated Flame Retardants in the Great Lakes.

Thirty-five polybrominated diphenyl ethers (PBDEs) and eight other alternative flame retardants were measured in air samples (vapor plus particles) collected at six sites near the North American Great Lakes between 2005 and 2019 as part of the Integrated Atmospheric Deposition Network (IADN). These data were analyzed using a multiple linear regression model to determine spatial and temporal trends. Overall, the levels of flame retardants remain significantly higher in urban sites compared to rural and remote sites except for pentabromoethylbenzene (PBEB), hexabromobenzene (HBB), and total Dechlorane Plus (ΣDP). Here, we report the first findings of decreasing levels of ΣDP at Sturgeon Point, New York. The atmospheric levels of total PBDEs remain unchanged over time near Lakes Michigan and Superior and declined near Lakes Erie and Ontario, with rate constants at the latter two lakes revealing halving times of approximately 7 to 14 years. This work presents results from the first investigation of PBDE source apportionment in the Great Lakes atmosphere. Source apportionment by use of positive matrix factorization (PMF) identified two legacy commercial technical mixtures (i.e., penta-BDE and deca-BDE mixes) and elucidated a factor representing ambient degradation. Our results show that weathered local sources of technical commercial mixtures, and their photolysis contribute most to the total PBDE burden in the Great Lakes atmosphere.

Amino Acid Transporter as a Potential Carrier Protein for the Root-to-Shoot Translocation of Polybrominated Diphenyl Ethers in Rice.

As typical persistent organic pollutants, polybrominated diphenyl ethers (PBDEs) tend to accumulate in edible parts of rice, posing great ecological and health risks. The translocation of PBDEs from underground to aboveground parts of rice is a crucial procedure to determine the final bioaccumulation level. Herein, this study aimed to identify the transporter proteins for PBDEs in rice plants in order to strengthen our understanding of the bioaccumulation mechanism and the potential prevention strategy of the PBDE risk. Similar time-dependent patterns were observed among the root-to-shoot translocation factors (TFs) of PBDEs, the expression of lysine histidine transporter (LHT) protein, and the relative levels of LHT substrates (phenylalanine or tyrosine), implying the potential co-transport of PBDEs, phenylalanine, and tyrosine by the carrier LHT. Fluorescence spectra and circular dichroism showed that PBDE congeners interfered with LHT via static fluorescence quenching and changes in the protein's secondary structure. The in vitro sorption fraction of LHT to PBDEs, as revealed by sorption equilibrium analysis, was comparable to the in vivo TF values. Knockout of OsLHT1 in rice using CRISPR/Cas9 technology caused a 48.2-78.4% decrease in PBDE translocation. Molecular docking simulation suggested that PBDEs, phenylalanine, and tyrosine were inserted into the same ligand-binding cavity of LHT, substantiating the potential carrier role of LHT for PBDEs from a conformational perspective. Quantitative structure activity relationship analysis demonstrated that the ether-bond oxygen and the carbons at the site 4 and 4' of PBDE molecules are significant determinants of the binding affinity with the LHT protein and in vivo translocation of PBDEs. In summary, this study discovered that LHT acts as the cellular carrier for PBDEs and offered a comprehensive molecular explanation for the bioaccumulation and translocation of PBDEs in rice plants, covering both biological and chemical perspectives. These findings fill in a knowledge gap on the endogenous transporter proteins for exogenous organic pollutants.

Congener Variation of Genetic Dependent-Developmental Toxicology in Two Emerging Classes of Dioxin-like Compounds.

Emerging classes of dioxin-like compounds (DLCs) like hydroxylated/methoxylated polybrominated diphenyl ethers (HO-/MeO-PBDEs) and polychlorinated diphenyl sulfides (PCDPSs) could lead to diverse adverse outcomes in humans and wildlife, yet knowledge gaps exist in their molecular mechanisms associated with different structures following early life environmental exposure. This study integrated a genetic knockout technique and concentration-dependent reduced zebrafish transcriptome approach (CRZT) to unravel the toxicological pathways underpinning developmental toxicity of four HO-/MeO-PBDEs and five PCDPSs at environmentally relevant doses. Generally, the dependence of aryl hydrocarbon receptor (AhR) on the embryotoxicity and transcriptomic potencies induced by the HO-PBDEs and PCDPSs varied across different congeners. The knockout of the ahr2 gene led to 1.02- to 76.48-fold decreases of DLC-induced embryotoxicities and reduced the transcriptome-based potencies ranging from 1.38 to 2124.74 folds in the CRZT test. The fold changes denoting AhR-mediated potentials significantly increased with the increasing chlorination degrees of MeO-PBDEs and PCDPSs (p < 0.05). Moreover, ahr2 knockout primarily affected the DLC-induced early molecular responses relevant to DNA damage, enzyme activation, and organ development. Our integrated approach revealed the differential role of AhR in mediating the developmental toxicity of emerging DLCs possessing varied structures at environmentally relevant doses.

Temporal Trends and Suspect Screening of Halogenated Flame Retardants and Their Metabolites in Blubbers of Cetaceans Stranded in Hong Kong Waters during 2013-2020.

Halogenated flame retardants (HFRs) are a large class of chemical additives intended to meet flammability safety requirements, and at present, they are ubiquitous in the environment. Herein, we conducted the target analysis and suspect screening of legacy and novel HFRs and their metabolites in the blubber of finless porpoises (Neophocaena phocaenoides; n = 70) and Indo-Pacific humpback dolphins (Sousa chinensis; n = 35) stranded in Hong Kong, a coastal city in the South China Sea, between 2013 and 2020. The average concentrations of total target HFRs (ΣHFRs) were 6.48 × 103 ± 1.01 × 104 and 1.40 × 104 ± 1.51 × 104 ng/g lipid weight in porpoises and dolphins, respectively. Significant decreasing temporal trends were observed in the concentrations of tetra-/penta-/hexa-bromodiphenyl ethers (tetra-/penta-/hexa-BDEs) in adult porpoises stranded from 2013-2015 to 2016-2020 (p < 0.05), probably because of their phasing out in China. No significant difference was found for the concentrations of decabromodiphenyl ether and hexabromocyclododecane, possibly due to their exemption from the ban in China until 2025 and 2021, respectively. Eight brominated compounds were additionally identified via suspect screening. A positive correlation was found between the concentrations of tetra-BDE and methyl-methoxy-tetra-BDE (Me-MeO-tetra-BDE) (p < 0.05), indicating that the metabolism of tetra-BDE may be a potential source of Me-MeO-tetra-BDE in marine mammals.

Rapid screening of polybrominated diphenyl ethers in water by solid-phase microextraction coupled with ultrahigh-resolution mass spectrometry.

Polybrominated diphenyl ethers (PBDEs) are considered emerging organic contaminants that attract more attention in the environment. Herein, online coupling of solid-phase microextraction and ultrahigh-resolution mass spectrometry was developed for rapid screening of eight PBDEs in water samples. This procedure was completed in 22 min, about 6 times faster than the routine workflow such as solid-phase extraction coupled with gas chromatography-mass spectrometry. Thermal desorption and solvent-assisted atmospheric pressure chemical ionization were developed for the effective coupling of solid-phase microextraction (SPME) with ultrahigh-resolution mass spectrometry (UHRMS), which contributed to the signal enhancement and made the methodology feasible for environmental screening. The limits of detection and quantification were 0.01-0.50 ng/mL and 0.05-4.00 ng/mL, respectively. The recoveries were 57.2-75.2% for quality control samples at spiking levels of 0.8-10 ng/mL (4-50 ng/mL for BDE209), with relative standard deviation less than 19.0%. Twelve water samples from different river sites near industrial areas were screened using the developed method. The results showed that BDE-209 was the dominant PBDE (1.02-1.28 ng/mL in positive samples), but its amount was lower than the human health ambient water quality criteria. Consequently, the developed method provides a rapid and reliable way of evaluating contamination status and risks of PBDEs in aqueous environment.

Prenatal exposure to polybrominated diphenyl ethers and birth outcomes.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) were used as flame retardants and from their end-use products they can be released to accumulate within indoor environments. This may result in exposures to pregnant women with potential adverse effects on the developing fetus. While studies have shown associations between prenatal PBDE exposure and poor birth outcomes, research has mainly focused on birth weight and gestational age and may miss important indicators of newborn size. METHODS: The sample included a cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners (BDE-47, BDE-99, BDE-100, and BDE-153) were measured in cord serum at birth and dichotomized into low (<80th percentile) and high (>80th percentile) categories. Weight, length, head circumference, and gestational age were measured at birth and the ponderal index (birth weight/length x 100), size for gestational age, and population-based z-scores were calculated (n = 305). Separate regression analyses were conducted to estimate associations between PBDEs or PBDE sum (ng/g lipid) and birth outcomes. Quantile g-computation was performed to estimate the effect of total PBDE mixture. We also assessed effect modification by sex and ethnicity. RESULTS: Adjusting for relevant covariates, the high exposure category of BDE-153 was associated with lower birth weight z-score (-0.25, 95% CI: -0.5, 0.0) and longer gestation (0.43 weeks, 95% CI: 0.07, 0.79). The high exposure category of BDE-99 was associated with lower birth length z-score (-0.55, 95% CI: -0.98, -0.12). There was a negative association between the overall PBDE mixture and birth length z-score (-0.10, 95% CI: -0.21, 0.00) per 1 quintile increase in PBDEs. There was no effect modification by sex or ethnicity. CONCLUSIONS: These results suggest that prenatal exposures to BDE-153, BDE-99, and total PBDE mixture are associated with birth outcomes in a cohort of Dominican and African American newborns.