Diphenyl Ethers Research Articles

Development and Biological Evaluation of New Diphenyl Ether Formylhydrazide Compounds as Potent Inhibitors of Succinate Dehydrogenase.

Succinate dehydrogenase (SDH), also recognized as succinate ubiquinone oxidoreductase (SQR), is considered one of the most promising targets for fungicide development, garnering significant international interest. We have focused on the development of highly effective, broad-spectrum-targeted SDH inhibitors. Using an active scaffold combining strategy, we designed and synthesized a series of novel diphenyl ether formylhydrazine derivatives, and most compounds have demonstrated broad-spectrum antifungal activity. Notably, compound M8 exhibited antifungal activity of more than 93% against four tested pathogen types at a concentration of 10 μg/mL, with an EC50 value below 0.3 μg/mL for each pathogen, outperforming boscalid. Additionally, compound M8 exhibited a control efficacy of 83% against Sclerotinia sclerotiorum on rapeseed leaves at a concentration of 200 μg/mL and demonstrated an 87% efficacy in controlling Fusarium graminearum on wheat ears when applied at 400 μg/mL. Structure-activity relationship research suggested that para-substituted benzene rings are more effective, offering stronger and more extensive antifungal potency. Further investigation, including enzyme inhibition assays, mycelial morphology observations, and molecular docking studies, suggests that the antifungal potency of M8 is due to the inhibition of its SDH activity. Therefore, our research positions compound M8 as a highly promising lead compound with broad-spectrum antifungal properties, potentially introducing a new class of fungicide.

Targeting mitochondrial metabolism by the mitotoxin bromoxib in leukemia and lymphoma cells.

Targeting mitochondrial metabolism represents a promising approach for cancer treatment. Here, we investigated the mitotoxic potential of the polybrominated diphenyl ether bromoxib, a natural compound isolated from the marine sponge Dysidea family. We could show that bromoxib comprised strong cytotoxicity in different leukemia and lymphoma cell lines (such as HL60, HPBALL, Jurkat, K562, KOPTK1, MOLT4, SUPB15 and Ramos), but also in solid tumor cell lines (such as glioblastoma cell lines SJ-GBM2 and TP365MG). Bromoxib activated the mitochondrial death pathway as evidenced by the rapid translocation of Bax to the mitochondria and the subsequent mitochondrial release of Smac. Accordingly, bromoxib-induced apoptosis was blocked in caspase 9 deficient Jurkat cells and Jurkat cells overexpressing the antiapoptotic protein Bcl-2. In addition, we could show that bromoxib functioned as an uncoupler of the electron transport chain with similar rapid kinetics as CCCP in terms of dissipation of the mitochondrial membrane potential (ΔΨm), processing of the dynamin-like GTPase OPA1 and subsequent fragmentation of mitochondria. Beyond that, bromoxib strongly abrogated ATP production via glycolysis as well as oxidative phosphorylation (OXPHOS) by targeting electron transport chain complexes II, III, and V (ATP-synthase) in Ramos lymphoma cells. Thus, bromoxib's potential to act on both cytosolic glycolysis and mitochondrial respiration renders it a promising agent for the treatment of leukemia and lymphoma.

Maternal probiotic supplementation protects against PBDE-induced developmental, behavior and metabolic reprogramming in a sexually dimorphic manner: Role of gut microbiome.

Polybrominated diphenyl ethers (PBDEs) are endocrine-disrupting persistent organic pollutants (POPs) used as flame retardants in a wide range of commercial applications. We have previously reported neurobehavioral and metabolic reprogramming produced by developmental PBDEs. PBDEs perturb the microbiome, an influencer of life-long health, while probiotic supplementation with Limosilactobacillus reuteri (LR) can avert neurobehavioral and endocrine disruption. We, therefore, tested the hypothesis that perinatal maternal LR supplementation would protect gut microbiome richness and diversity, developmental milestones, adult neurobehavior and metabolic homeostasis in PBDE-exposed offspring. C57BL/6N dams were orally exposed to a commercial penta-mixture of PBDEs, DE-71, at 0.1mg/kg/day, or corn oil vehicle (VEH/CON) during gestation and lactation. Mice offspring received DE-71 or VEH/CON with or without co-administration of LR (ATCC-PTA-6475) indirectly via their mother from gestational day (GD) 0 until postnatal day (P)21 (Cohort 1), or continued to receive LR directly from P22 through adulthood (Cohort 2). Results of fecal 16S rRNA sequencing indicated age- and sex-dependent effects of DE-71 on gut microbial communities. Maternal LR treatment protected against DE-71-induced reduction in α-diversity in P22 females and against β-diversity alterations in P30 males. In females, DE-71 changed the relative abundance of specific bacterial taxa, such as Tenericutes and Cyanobacteria (elevated) and Deferribacterota (reduced). In males, several Firmicutes taxa were elevated, while Proteobacteria, Chlamydiae, and several Bacteroidota taxa were reduced. The number of disrupted taxa normalized by maternal LR supplementation wasas follows: 100% in P22 females and 33% in males at P22 and 25% at P30. Maternal LR treatment protected against DE-71-induced delay of postnatal body weight gain in males and ameliorated the abnormal timing of incisor eruption in both sexes. Further, DE-71 produced exaggerated digging in both sexes as well as locomotor hyperactivity in females, effects that were mitigated by maternal LR only in females. Other benefits of LR therapy included normalization of glucose tolerance, insulin-to-glucose ratio and plasma leptin in adult DE-71 females(Cohort 2). This study provides evidence that probiotic supplementation can mitigate POP-induced reprogramming of neurodevelopment, adult neurobehavior, and glucose metabolism in association with modified gut microbial community structure in a sex-dependent manner.

Comprehensive evaluation of skin exposure to PBDEs and PCBs in diverse South China populations via dermal wipe sampling.

This study analyzed skin wipe samples from the forehead, palm, forearm, and lower leg of 120 volunteers across different age groups-preschoolers, thresholders, middle-aged, and elderly-with each group comprising 30 individuals with a balanced sex ratio from a city in South China. The research aimed to assess the occurrence, concentration, and associated health risks of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) adsorbed onto human skin from environmental sources. We identified 13 PBDE congeners and 10 PCB congeners across all samples, with average detection frequencies of 48% for PBDEs and 16% for PCBs, with concentrations ranging from non-detectable (ND) to 4200 and ND to 2300ng/m2, respectively. Skin concentrations of both PBDEs and PCBs decreased in the order of face > hand > arm > shank (ANOVA, P < 0.001), suggesting higher exposure to uncovered skin areas than to those covered by clothing, regardless of age or sex. The daily average dose of dermal (DADderm) and oral (DADoral) for PBDEs spanned from 7.0 × 10-4-0.19ng/kg/d and ND-15 ng/kg/d, respectively, whereas the PCB exposure doses ranged from ND-7.8ng/kg/d (DADderm) and ND-2.0ng/kg/d (DADoral), respectively. Preschool children displayed notably higher DADoral levels than the other groups (P < 0.0001), which was attributed to their more frequent hand-to-mouth activity. Preschool boys exhibiting a higher DADderm (P < 0.05) and both preschool boys and university women showing elevated DADoral levels (P < 0.01 and P < 0.05, respectively). Health risk assessments concluded that the carcinogenic risks from BDE209 and PCBs were within acceptable limits (10-4) for all sampled populations.

Study on association between human plasma polybrominated diphenyl ethers (PBDEs) and thyroid homeostasis and carcinoma.

Polybrominated diphenyl ethers (PBDEs), a category of persistent organic pollutants (POPs), are ubiquitous in the environment and have been reported to have endocrine-disrupting and tumor-promoting activities. However, the evidence for the correlation between plasma PBDEs levels, thyroid homeostasis and thyroid carcinoma in humans remains limited. Herein, we analyzed eight PBDE congeners in 53 patients undergoing thyroid surgery. BDE-209 was identified as the most abundant PBDE congener in plasma (median, 11.36ng/g lipid). BDE-100 concentration was positively associated with free triiodothyronine (FT3), indicating a potential interference with thyroid function. Point-biserial correlation analysis revealed positive associations between certain plasma PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, and BDE-154) and aggressive pathological parameters. There was no significant correlation between PBDEs and BRAF or RAS mutations in PTC patients, indicating that PBDEs may not directly promote the initiation and progression of thyroid cancer through these genetic mutations. It implies the complexity of the relationship between PBDEs exposure and thyroid cancer development. Although not statistically significant, Bayesian kernel-machine regression (BKMR) analysis of single-exposure effects model found that BDE-47 and BDE-99 were positively associated with the risk of malignant neoplasms. The present study not only contributes to the growing evidence regarding the impact of PBDEs on thyroid function but also provides new insights into the association between exposure to certain PBDE congeners and the aggressive pathological parameters of thyroid cancer. Large-scale prospective studies are still needed to support our findings.

Organophosphate Esters and Polybrominated Diphenyl Ethers in Vehicle Dust: Concentrations, Sources, and Health Risk Assessment

Background: The primary flame retardants in vehicles, organophosphates (OPEs) and polybrominated diphenyl ethers (PBDEs), volatilize and accumulate in the enclosed vehicle environment, posing potential health risks. Amidst the rising number of vehicles, the scrutiny of persistent organic pollutants like OPEs and PBDEs in vehicles is increasing. This study investigates occupational and nonoccupational population exposure to specific OPEs (TnBP, TBOEP, TEHP, TCEP, TCiPP, TDCiPP, TPhP, EHDPP) and PBDEs (BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183, BDE-209) in vehicle dust. Methods: Data on OPEs and PBDEs in vehicle dust were sourced from PubMed and Web of Science. We applied PCA and PMF to identify pollutant sources and assessed health risks using the hazard index (HI) and carcinogenic risk (CR) methods. Monte Carlo simulations were conducted for uncertainty analysis, evaluating variable contributions to the results. Results: The predominant OPE in dust samples was TDCiPP (mean value: 4.34 × 104 ng g−1), and the main PBDE was BDE-209 (mean value: 1.52 × 104 ng g−1). Potential sources of OPEs in vehicle dust include polyvinyl chloride (PVC) upholstery, polyurethane foam (PUF) seats, electronics, carpet wear, hydraulic oil, and plastic wear in the brake system. PBDE sources likely include automotive parts, PVC upholstery, seats, carpets, and electronics. The 90th percentile HI and CR values for occupational and nonoccupational populations exposed to OPEs and PBDEs indicate that the noncarcinogenic and carcinogenic risks are relatively low. A sensitivity analysis showed that the pollutant concentration, time in the vehicle, exposure frequency, and duration significantly influence health risks. Conclusions: The health risks to both occupational and nonoccupational populations from exposure to OPEs and PBDEs in vehicle dust are relatively low.

Green Synthesis, Characterization, and Catalytic Applications of CuO Nanoparticles Using Prosopis Cineraria Seed Extract

Abstract The current study used a seed extract of Prosopis cineraria as a stabilizing and reducing agent to produce CuO nanoparticles via an easy, low-cost, affordable, and environmentally friendly synthesis process. The formation of copper oxide nanoparticles and the maximum absorbance of the CuO nanoparticles produced in the solution at 565 nm were verified by UV-vis. Copper oxide nanoparticles were found to have secondary metabolites on their surface, as shown by a distinctive Cu-O stretching band at 532 cm−1, which confirmed the reduced Cu2+ ions in copper oxide nanoparticles. This was confirmed by FTIR analysis. The XRD analysis confirmed the produced copper oxide nanoparticles’ monoclinic crystalline nanostructure with an average particle size of 34 nm. The phytonutrients in Prosopis cineraria seed extract stabilized and reduced copper, as demonstrated by the existence of copper and oxygen atoms at 85.2% and 12.5%, respectively, as demonstrated by SEM-EDX analysis. According to the HR-TEM study, copper oxide nanoparticles with a mean size of 18 nm are spherical in shape and well distributed. Prosopis cineraria seed extract-derived copper oxide nanoparticles were utilized as a catalyst in the Ullmann process to produce diphenyl ether. CuO nanoparticles produced by Prosopis cineraria seed extraction as a catalyst yielded 91% diphenyl ether. The results showed that a more ecologically friendly way of synthesizing copper oxide nanoparticles with great homogeneity of particle sizes could be achieved using seed extract. This work aims to facilitate heterogeneous catalysis from CuO nanoparticles utilising Prosopis cineraria seed extract. Overall, this technique offers several advantages, like high yields at fast reaction times, and low catalyst loading are just a few of this approach’s many benefits.

Evidence of polybrominated diphenyl ethers (PBDEs) and alternative halogenated flame retardants (AHFRs) in wild fish species from the remote tropical marine environment, South China Sea

Polybrominated diphenyl ethers (PBDEs) and their alternatives (e.g., dechlorane plus (DPs) and decabromodiphenyl ethane (DBDPE)) are ubiquitous in various environmental media. However, limited data is available on these chemicals in edible fish species from the wide-open South China Sea (SCS). In the present study, ten legacy PBDEs and three substitutions (DBDPE and two DPs) were analyzed in 16 wild fish species sampled from the open SCS to investigate their spatial and species-specific variations. The results showed that the total concentrations of PBDEs, DBDPE, and DPs in fish samples were in the range of 1.69 to 47.6, not detected (nd) to 21.0, and nd to 3.80 ng/g lipid weight (lw), respectively. BDEs 47, 209 and 100 were the dominant target PBDE congeners, representing 49.2%, 17.2% and 9.93% of the total PBDE concentrations, respectively. Higher concentrations of PBDEs, DBDPE, and DPs were found in fish species from the Wanshan Archipelago compared to those from the Mischief Reef and the Yongxing Island, suggesting the significant influence of anthropogenic activities. Species-specific differences in levels of PBDEs were observed, with the order of bathydemersal > demersal > pelagic ≈ reef-associated > benthopelagic species. The average fanti value of all fish samples was 0.68, suggesting commercial DP products as a contamination source. The levels of PBDEs, DPs, and DBDPE in fish samples were relatively low compared with those from other locations around the globe. Finally, the health risks concerning the ingestion of BDEs 47, 99, 153 and 209 via fish consumption collected from the SCS are negligible.

Dietary and terrestrial exposure to methoxylated polybrominated diphenoxybenzene contaminants in Great Lakes herring gulls

Methoxylated polybrominated diphenoxybenzenes (MeO-PB-DPBs) are little known contaminants except in North American Great Lakes herring gull tissues and egg samples. MeO-PB-DPBs in gulls originate not via aquatic bioaccumulation pathways but instead likely via transformation of the tetradecabromo-1,4-diphenoxybenzene (TDB-DPB) flame retardant (FR). TDB-DPB was formerly produced as SAYTEX-120 in North America and is still produced in Asia. This study investigates the terrestrial exposure pathway of MeO-PB-DPBs and other FRs in herring gulls. Gull regurgitant and faeces, soil, and earthworms were collected from Channel Shelter Island (Saginaw Bay, Lake Huron), and analyzed for 3 MeO-PB-DPBs, 25 polybrominated diphenyl ethers (PBDEs), and 22 non-PBDE halogenated FRs. MeO-PB-DPBs in soil varied from non-detect to 4 ng/g dw per pentabrominated congener to a remarkably high 53 ng/g dw for the hexabrominated congener and comparable to BDE-209 which accumulates to high levels in Great Lakes sediment. MeO-hexa- to penta-brominated-DPB congener ratios were much greater (> 10x vs. ∼ 2x) than in herring gull tissues or eggs, suggesting possible differences in bioavailability. PB-DPB congeners were detected for the first time in environmental soil samples and confirmed via standard addition of the 2,2′,4,4″- and 2,2′,2″,4-tetrabromodiphenoxybenzene standards. MeO-PB-DPBs were mostly absent from faeces and not detected in earthworm samples. Combined with the finding of detection in regurgitant samples, indicating dietary intake, this suggests that gull exposure is via terrestrial bioaccumulation of MeO-PB-DPBs.

Pollution status, phase partitioning, potential sources, and health impacts of polybrominated diphenyl ethers in Hangzhou offices

Pollution status, phase partitioning, potential sources, and health impacts of polybrominated diphenyl ethers in Hangzhou offices

Human Biomonitoring of Serum Polybrominated Diphenyl Ethers by Supported Liquid Extraction and Gas Chromatography Coupled With Tandem Mass Spectrometry.

This study aims to develop and validate a robust analytical method for the quantification of polybrominated diphenyl ethers (PBDEs) in human serum using gas chromatography-tandem mass spectrometry. We compared procedural blanks, recoveries, and operational convenience of liquid-liquid extraction and supported liquid extraction for the determination of serum PBDEs. We evaluated different extraction solvents for their effect on PBDE recoveries. Supported liquid extraction was selected for method validation due to its operational convenience. The method demonstrated satisfactory linearity, sensitivity, and reproducibility, with the range of 0.10-5.00µg/L for most PBDE congeners and 0.20-10.0µg/L for PBDE-154 and PBDE-183, with limits of detection ranging from 2 to 48ng/L, and with matrix effects ranging from 94% to 113%. Quality control assessments indicated that recoveries ranged from 85% to 110% and relative standard deviations of less than 11%. The proposed method was applied to biomonitoring of 111 healthy adults, revealing detectable levels of PBDEs in over 90% of the samples. BDE-47 and BDE-183 were the most prevalent, with mean concentrations of 4.13 and 22.1ng/L, respectively. Detection frequencies ranged from 0.90% for BDE-17 and BDE-85 to 25.2% for BDE-47. Males had higher mean concentrations of BDE-183 than females.

Northern Fur Seal Whisker Bioaccumulation and Partitioning of Polybrominated Diphenyl Ethers and Organochlorines

Northern Fur Seal Whisker Bioaccumulation and Partitioning of Polybrominated Diphenyl Ethers and Organochlorines

Xylose Acetals - a New Class of Sustainable Solvents and Their Application in Enzymatic Polycondensation.

The use of organic solvents in academic research and industry applications is facing increasing regulatory pressure due to environmental and health concerns. Consequently, there is a growing demand for sustainable solvents, particularly in the enzymatic synthesis and processing of polyesters. Biocatalysts offer a sustainable method for producing these materials; however, achieving high molecular weights often necessitates use of solvents. In this work, we introduce a new class of alternative aprotic solvents with medium polarity produced directly from agricultural waste biomass in up to 83 mol% yield (on xylan basis). The new solvents have a largely unmodified xylose core and acetal functionality, yet they show no peroxide formation and provide reduced flammability risk. We also demonstrate their successful application in enzymatic polycondensation reactions with Candida antarctica lipase B (CaLB). In particular, the solvent dibutylxylose (DBX) outperformed the hazardous solvent diphenyl ether and facilitated polycondensation of the lignin-derived diester pyridine-2,4-dicarboxylate, yielding polyesters with a Mn of >15 kDa. Computational modelling studies provided further insight into the molecular structure and dynamics of CaLB in the presence of new solvents. Lastly, up to 98 wt% of the new xylose acetals were successfully recovered and recycled, further contributing to the sustainability of the overall process.

Design, synthesis and antifungal activity of arylhydrazine analogs containing diphenyl ether fragments.

Succinate dehydrogenase (SDH) represents a critical target in the development of novel fungicides. To address the growing issue of resistance and safeguard the economic viability of agricultural production, the pursuit of new succinate dehydrogenase inhibitors (SDHIs) has emerged as a significant focus of contemporary research. In this project, 32 arylhydrazine derivatives containing diphenyl ether structural units were synthesized and evaluated for their fungicidal activities against Rhizoctonia solani, Sclerotinia sclerotiorum, Alternaria alternata, Gibberella zeae, Alternaria solani and Colletotrichum gloeosporioides. In an in vitro fungicidal activity assay, compound D6 showed significant inhibitory activity against R. solani with a half-maximum effective concentration (EC50) of 0.09 mg L-1. The in vivo fungicidal activity demonstrated that compound D6 inhibited R. solani by 95.39% in rice leaves, which was significantly better than that of boscalid (85.76%). The results of SDH enzyme assay, molecular docking simulation, mitochondrial membrane potential assay, cytoplasmic release studies and morphological observations demonstrated that the target compound D6 not only had significant SDH inhibitory activity, but also affected the membrane integrity of mycelium. Bioactivity screening and validation of the mechanism of action indicated that compound D6 was a potentially unique SDHI, acting on SDH while also affecting cell membrane permeability, which deserved further study. © 2024 Society of Chemical Industry.

PBDEs and dechlorane plus contamination in community e-waste recycling: Environmental and health implications in Northeastern Thailand

Electronic waste (e-waste) poses significant environmental and health risks in Thailand due to both domestic production and international imports. A notable portion of this waste is processed in small-scale, community-based workshops, often located in poorer regions, where safety regulations are improperly enforced or entirely ignored. This study focuses on the Kalasin province in Northern Thailand, a region with numerous such workshops, where no comprehensive analysis of exposure to polybrominated diphenyl ethers (PBDEs) and dechlorane plus (DP) has been conducted. The study's objective was to quantify these toxic substances in environmental and biological samples to assess its contamination and human health risks. Environmental samples, including soil, dust, sediment, ash, eggs, crabs, snails, fish, and rice, were collected from e-waste processing sites and compared with control areas. Blood samples from e-waste workers and a control group were also analysed. Gas chromatography coupled with mass spectrometry operated in negative ion chemical ionization (GC-NCI-MS) was used to quantify PBDEs and DP isomers. Results showed significantly higher concentrations of these toxic compounds in e-waste sites compared to control areas. E-waste workers also had elevated levels of these substances in their blood, suggesting exposure through contaminated dust and food. These findings underscore the severe environmental contamination and health risks associated with improper e-waste management, highlighting the urgent need for regulatory measures and improved recycling practices to safeguard both environmental and public health.

Effects of Mixtures of Emerging Pollutants and Drugs on Modulation of Biomarkers Related to Toxicity, Oxidative Stress, and Cancer.

Background/Objectives: Over time, the scientific community has developed a growing interest in the effects of mixtures of different compounds, for which there is currently no established evidence or knowledge, in relation to certain categories of xenobiotics. It is well known that exposure to pollutants causes oxidative stress, resulting in the overproduction of reactive oxygen species (ROS), which can affect signaling pathways that regulate the cell cycle, apoptosis, energy balance, and cellular metabolism. The aim of this study was to investigate the effects of sub-lethal concentrations of mixtures of emerging pollutants and pharmaceuticals on the modulation of biomarkers related to toxicity, oxidative stress, and cancer. Methods: In this study, the hepatoma cell line HepG2 was exposed to increasing concentrations of polybrominated diphenyl ether 47 (BDE-47), cadmium chloride (CdCl2), and carbamazepine (CBZ), both individually and in mixtures, for 72 h to assess cytotoxicity using the MTT assay. The subsequent step, following the identification of the sub-lethal concentration, was to investigate the effects of exposure at the gene expression level, through the evaluation of molecular markers related to cell cycle and apoptosis (p53), oxidative stress (NRF2), conjugation and detoxification of xenobiotics (CYP2C9 and GST), DNA damage (RAD51 and γH2AFX), and SUMOylation processes (SUMO1 and UBC9) in order to identify any potential alterations in pathways that are normally activated at the cellular level. Results: The results showed that contaminants tend to affect the enzymatic detoxification and antioxidant system, influencing DNA repair defense mechanisms involved in resistance to oxidative stress. The combined effect of the compounds at sub-lethal doses results in a greater activation of these pathways compared to exposure to each compound alone, thereby exacerbating their cytotoxicity. Conclusions: The biomarkers analyzed could contribute to the definition of early warning markers useful for environmental monitoring, while simultaneously providing insight into the toxicity and hazard levels of these substances in the environment and associated health risks.

Decoding Adverse Effects of Organic Contaminants in the Aquatic Environment: A Meta-analysis of Species Sensitivity, Hazard Prediction, and Ecological Risk Assessment.

Aquatic organisms in the environment are frequently exposed to a variety of organic chemicals, while these biological species may show different sensitivities to different chemical groups present in the environment. This study evaluated species sensitivity, hazards, and risks of six classes of organic chemicals in the aquatic environment. None of the taxonomic groups were the most sensitive or tolerant to all chemicals, as one group sensitive to one class of chemicals might possess adaptations to other chemical groups. Polychlorinated biphenyls were generally the most toxic chemical group, followed by polybrominated diphenyl ethers, polycyclic aromatic hydrocarbons, and pharmaceuticals and personal care products, while per- and polyfluoroalkyl substances and phthalate esters were the less toxic chemical groups. The hazard of organic chemicals was closely related to their physicochemical properties, including hydrophobicity and molecular weight. It was shown that 20% of the evaluated chemicals exhibited medium or high ecological risks with the worst-case scenario in the Pearl River Estuary. This novel work represented a comprehensive comparison of chemical hazards and species sensitivity among different classes of organic chemicals, and the reported results herein have provided scientific evidence for ecological risk assessment and water quality management to protect aquatic ecosystems against organic chemicals.

Extremely high levels of PBDEs in children’s toys from European markets: causes and implications for the circular economy

BackgroundWith the high influx of low-cost plastic toys on the market, there is growing concern about the safety of such toys. Some of these plastic toys contains hazardous chemicals like polybrominated diphenyl ethers (PBDEs) due to the use of recycled plastics in new toy manufacturing. Here, we investigated if toys marketed in Europe are compliant with EU directives to assess the safety of currently used children's toys and identify implications of PBDE content in toys.ResultsEighty-four toys purchased from international toy retailers were screened for bromine using X-ray fluorescence (XRF), and 11 of those with bromine content higher than 500 µg/g were analyzed for ten PBDEs using GC–HRMS. PBDEs were detected in all 11 toys. Ʃ10PBDE concentrations ranged up to 23.5 mg/g (with a median concentration of 8.61 mg/g), with BDE-209 being the most abundant compound (4.40 mg/g). Eight samples exceeded the EU’s Low POP Content Limit (LPCL) of 500 µg/g for the Ʃ10PBDEs by 6–47 times and the Unintentional Trace Contaminant (UTC) limits of 10 µg/g for Deca-BDE by 12–800 times.ConclusionsPBDEs were up to percent levels, suggesting direct recycling of flame retarded plastic, e.g., e-waste plastics, into toy components. This is a call for concern and requires intervention from all stakeholders involved in the toy market. Overall, the occurrence of non-compliant toys in the EU market, as indicated in this study is primarily attributed to gaps in regulations, inadequate legislation for recycled plastics, the rise of online sales, complexities in global and national supply chains, and economic challenges. Failure to address these issues will hinder the efforts of the plastics industry to transition into a circular economy. This suggests that more actions are needed to address gaps in cross-border enforcement, and stricter sanctions are required for toy manufacturers who fail to adhere to regulations and safety standards.

The Interplay of Persistent Organic Pollutants and Mediterranean Diet in Association With the Risk of Gestational Diabetes Mellitus.

Certain foods characterizing the alternate Mediterranean diet (aMED) are high in persistent organic pollutants (POPs), which are related to greater gestational diabetes mellitus (GDM) risk. We examined the associations of combined aMED and POP exposure with GDM. aMED score of 1,572 pregnant women was derived from food frequency questionnaires at early pregnancy within the U.S. Fetal Growth Study and plasma concentrations of 76 POPs, including organochlorine pesticides, polybrominated diphenyl ethers, polychlorinated biphenyls (PCBs), and per- and polyfluoroalkyl substances, were measured. Associations of combined aMED score and exposure to POPs with GDM risk were examined by multivariable logistic regression models. In 61 of 1,572 (3.88%) women with GDM, 25 of 53 included POPs had a detection rate >50%. Higher POP levels appeared to diminish potential beneficial associations of aMED score with GDM risk, with the lowest GDM risk observed among women with both high aMED score and low POP concentrations. Specifically, adjusted log-odds ratios of GDM risk comparing women with low PCB and high aMED score with those with low aMED score and high PCB concentrations was -0.74 (95% CI -1.41, -0.07). Inverse associations were also observed among women with low aMED score and high TransNo_chlor, PCB182_187, PCB196_203, PCB199, and PCB206. These associations were more pronounced among women with overweight or obesity. Pregnant women who consumed a healthy Mediterranean diet but had a low exposure to POP concentrations had the lowest GDM risk. Future endeavors to promote a healthy diet to prevent GDM may consider concurrent POP exposure.

Analysis of brominated flame retardants exposure-associated chronic kidney disease risk in the US population from the NHANES

BackgroundExposure to brominated flame retardants (BFRs) may contribute the advancement of chronic kidney disease (CKD). The objective is to evaluate the renal effects of BFRs in patients with CKD. MethodsTotally 7235 US participants of whom 1187 (16.41 %) were diagnosed with CKD were screened for this investigation from the National Health and Nutrition Examination Survey (NHANES) database spanning from 2005 to 2016. The isotope dilution gas chromatography high-resolution mass spectrometry (GC/IDHRMS) was employed for identification of 11 polybrominated diphenyl ethers (PBDEs) and PBB153 serving as the exposure factor. A set of covariates concerning basic characteristics, renal function indicators and suffering from diseases of these participants was considered as potential confounding factors. Subgroup analyses to examine the impact of age and gender on the relationship between serum BFRs and CKD, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), serum creatinine (Scr), and blood urea nitrogen (BUN). Weighted Quantile Sum (WQS) regression and Quantile G-computation (QGC) analyses were applied to identify relationship of individual BFRs and other anthropometric indicators in CKD. ResultsAfter adjusting for available confounding factors, PBDE100, PBDE28, PBDE85, PBDE47, PBDE99, and PBDE154 were positively correlated with CKD. PBDE28, PBDE66, PBDE47, PBDE183, PBDE100, PBDE99, PBDE85, PBDE154, and PBB153 were significantly negatively correlated with eGFR. PBDE66 and PBDE183 were positively correlated with UACR. PBDE28, PBDE17, PBDE66, PBDE100, PBDE47, PBDE85, PBDE154, PBDE99, PBDE183 and PBB153 were positively correlated with Scr. PBDE17, PBDE28, PBDE154, PBDE66, PBDE47, PBDE99, and PBDE209 were negatively associated with BUN. PBB153 was positively correlated with BUN. The subgroup results gender and age are key factors affecting the relationship of PBDEs and renal function indicators. Both WQS and QGS analyses revealed that exposure to mixed BFR was negatively correlated with eGFR and BUN, of which PBB153 and PBDE66 contributed the most, respectively, as well as positively correlated with Scr, in which PBDE66 contributed the most. ConclusionSpecific BFRs exposure was significantly correlated with renal function indicators, enhancing the potential risk of CKD. This pioneer investigation shed light on an overlooked impact of BFR exposure on CKD in US.