Dioxins, PFOS, and 20 other Persistent Organic Pollutants in Eggs of Nine Wild Bird Species from the Vaal River, South Africa.

The Vaal River catchment drains the largest and most populated industrial and mining region in Southern Africa. Heron, ibis, cormorant, egrets, and darter eggs, representing three habitats and four feeding guilds, were collected at four locations in 2009/10 to identify hotspots and hazards associated with persistent organic pollutants (POPs). The POPs included 21 organochlorine pesticides, five polybrominated diphenyl ether (PBDE) classes, 18 polychlorinated biphenyls (PCBs including six non-dioxin-like PCBs; NDL-PCB), and 12 dioxin-like PCBs (DL-PCBs), 17 polychlorinated dibenzo-p-dioxins and dibenzo-p-furans (PCDD/Fs), and perfluorooctane sulfonate (PFOS). Aquatic predators had higher PFOS and PCDD/F concentrations, while PCBs dominated in terrestrial eggs. Organochlorine pesticides, PBDEs, and PCBs were strongly associated with eggs from the industrial regions, while PCDD/F concentrations were evenly distributed. PCDD/F and PCB toxic equivalency quotient concentrations were low with no adverse effects expected. PFOS peaked at Bloemhof Dam with a maximum of 2300 ng/g wm in an African Darter egg, indicating an unexpected PFOS hotspot, the source of which is unknown. Despite order of differences in compound class concentrations, there was no association with egg size. To the best of our knowledge, this is the only study that analysed all 2010 POPs in bird eggs on a large geographic scale. This study highlighted the importance of multi-species studies sampling from multiple locations to assess the risk that POPs pose to avian populations as hotspots and species at risk may be missed by studies looking at one or few species.

Mitigation of PBDE net discharge in hazardous waste thermal treatment system through reintroducion of sludge and fly ash into GASMILD operations.

The presence of polybrominated diphenyl ethers (PBDEs) in consumer products, waste treatment processes, and treated ashes poses a significant environmental threat. Due to the lack of research on the removal of PBDEs during waste incineration, this study investigated the effectiveness of a Hazardous Waste Thermal Treatment System (HAWTTS) utilizing reburning of sludge and fly ash (SFA) with gasification-moderate or intense low-oxygen dilution (GASMILD) combustion for PBDE removal. The closed-loop treatment of sludge and ash within the HAWTTS provides a potential pathway for near-zero PBDE emissions. The GASMILD combustion addresses potential combustion issues associated with fly ash recirculation. The system achieved an impressive overall removal efficiency of 98.4% for PBDEs, with minimal stack emissions (2.45 ng/Nm³) and a negative net discharge rate (-1.02 µg/h). GASMILD combustion played a crucial role (92.7%-97.6% destruction) in addressing challenges associated with high-moisture feedstocks and SFA residues. Debromination of highly brominated PBDEs occurred within the incinerator, resulting in an increased proportion of lower brominated PBDEs in the bottom slag compared to the feedstock. Air Pollution Control Devices (APCDs) achieved a total PBDE removal efficiency of 74.4%. However, the hydrophobic nature of PBDEs limited removal efficiency in scrubbers (36.0%) and cyclonic demisters (37.86%). This study demonstrates that reintroducing SFA into the GASMILD combustion process offers an effective and environmentally sustainable strategy for reducing net PBDE levels in hazardous waste. This approach also provides additional benefits such as energy conservation, reduced carbon emissions, and lower operating costs associated with secondary treatment of thermally treated byproducts.

Contaminant levels versus toxicity bioassays in ecological risk assessment of sediments from the southern Baltic Sea.

Surface sediments collected in 2021 from six locations in the southern Baltic Sea (Polish district) were examined by chemical and toxicological methods. Chemical analyses included polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and their alkylated derivatives, butyltin compounds and 16 major and trace elements. The toxicity was measured using Ostracodtoxkit F and Microtox. The ecological risk of sediment was estimated by hazard quotient (HQ) calculation. Some PAHs, alkylated PAHs and metals (Zn, Hg, Cd and As) could pose a moderate risk in the sediments from the Gdansk Deep and in the vicinity of the wrecks, but the risk resulting from the presence of all analyzed compounds was considered high for these sediments. In studies using biotests, sediments from the vicinity of the t/s Franken wreck and the Slupsk Furrow were highly toxic to test organisms. Ostracodtoxkit F, compared to Microtox, appeared a more sensitive test for measured compounds.

2,2',4,4'-Tetrabromodiphenyl ether exposure disrupts blood-testis barrier integrity through CMA-mediated ferroptosis.

2,2',4,4'-Tetrabromodiphenyl ether (PBDE-47), being the most prevalent congener of polybrominated diphenyl ethers (PBDEs), has been found to accumulate greatly in the environment and induce spermatogenesis dysfunction. However, the specific underlying factors and mechanisms have not been elucidated. Herein, male Sprague-Dawley (SD) rats were exposed to corn oil, 10 mg/kg body weight (bw) PBDE-47 or 20 mg/kg bw PBDE-47 by gavage for 30 days. PBDE-47 exposure led to blood-testis barrier (BTB) integrity disruption and aberrant spermatogenesis. Given that Sertoli cells are the main toxicant target, to explore the potential mechanism involved, we performed RNA sequencing (RNA-seq) in Sertoli cells, and the differentially expressed genes were shown to be enriched in ferroptosis and lysosomal pathways. We subsequently demonstrated that ferroptosis was obviously increased in testes and Sertoli cells upon exposure to PBDE-47, and the junctional function of Sertoli cells was restored after treatment with the ferroptosis inhibitor ferrostatin-1. Since glutathione peroxidase 4 (GPX4) was dramatically reduced in PBDE-47-exposed testes and Sertoli cells and considering the RNA-sequencing results, we examined the activity of chaperone-mediated autophagy (CMA) and verified that the expression of LAMP2a and HSC70 was upregulated significantly after PBDE-47 exposure. Notably, Lamp2a knockdown not only inhibited ferroptosis by suppressing GPX4 degradation but also restored the impaired junctional function induced by PBDE-47. These collective findings strongly indicate that PBDE-47 induces Sertoli cell ferroptosis through CMA-mediated GPX4 degradation, resulting in decreased BTB-associated protein expression and eventually leading to BTB integrity disruption and spermatogenesis dysfunction.

Tyrosinase inhibition prevents non-coplanar polychlorinated biphenyls and polybrominated diphenyl ethers-induced hyperactivity in developing zebrafish: Interaction between pigmentation and neurobehavior.

Non-coplanar polychlorinated biphenyl (PCB) mixture Aroclor 1254 and polybrominated diphenyl ether (PBDE) BDE-47 are known to impede neurogenesis and neuronal development. We previously reported that exposure to PCB and PBDE leads to increased embryonic movement in zebrafish by decreasing dopamine levels. In this study, we studied the connection between the melanin and dopamine synthesis pathways in this context. Both genetic and chemical inhibition of tyrosinase, the rate-limiting enzyme in melanin synthesis, not only led to reduced pigmentation but also inhibit PCB/PBDE-induced embryonic hyperactivity. Furthermore, PCB and PBDE rarely affected tyrosinase expression in the potential pigment cells, suggesting that these compounds reduce dopamine through enzymatic regulation, including a competitive interaction for the substrate tyrosine. Our results provide new insights into the interactions between melanogenesis and dopaminergic neuronal activity, which may contribute to understanding the mechanisms underlying PCB/PBDE toxicity in developing organisms.

Defective ferritinophagy and imbalanced iron metabolism in PBDE-47-triggered neuronal ferroptosis and salvage by Canolol.

The brominated flame retardant 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) is a ubiquitous environmental pollutant that causes neurotoxicity. However, incomplete understanding of the underlying mechanisms has hampered the development of effective intervention strategies. Oxidative stress and related cell death are the modes of action for PBDE-47 neurotoxicity, which are also the characteristics of ferroptosis. Nonetheless, the role of ferroptosis in PBDE-47-induced neurotoxicity remains unclear. In the present study, we found that PBDE-47 triggered ferroptosis in neuron-like PC12 cells, as evidenced by intracellular iron overload, lipid peroxidation, and mitochondrial damage. This was confirmed by ferroptosis inhibitors including the lipid reactive oxygen species scavenger ferrostatin-1 and iron chelator deferoxamine mesylate. Mechanistically, PBDE-47 impaired ferritinophagy by disrupting nuclear receptor coactivator 4-mediated lysosomal degradation of the iron storage protein ferritin. Moreover, PBDE-47 disturbed iron metabolism by increasing cellular iron import via upregulation of transferrin receptor 1 and decreasing cellular iron export via downregulation of ferroportin 1 (FPN1). Intriguingly, rescuing lysosomal function by overexpressing cathepsin B (CatB) mitigated PBDE-47-induced ferroptosis by partially restoring dysfunctional ferritinophagy and enhancing iron excretion via the upregulation of FPN1. However, FPN1 knockdown reversed the beneficial effects of CatB overexpression on the PBDE-47-induced iron overload. Finally, network pharmacology integrated with experimental validation revealed that Canolol, the main phenolic compound in canola oil, protected against PBDE-47-evoked iron overload, resulting in ferroptosis by restoring defective ferritinophagy and improving abnormal iron metabolism via lowering iron uptake and facilitating iron excretion. Overall, these data suggest that ferroptosis is a novel mechanism of PBDE-47-induced neuronal death and that manipulation of ferritinophagy and iron metabolism via Canolol represents a promising therapeutic strategy.

ZLN005 alleviates PBDE-47 induced impairment of mitochondrial translation and neurotoxicity through PGC-1α/ERRα axis.

Recent studies are identified the mitochondria as critical targets of 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47) induced neurotoxicity. This study aimed at examining the impact of PBDE-47 exposure on mitochondrial translation, and its subsequent effect on PBDE-47 neurotoxicity. The Sprague-Dawley (SD) rat model and neuroendocrine pheochromocytoma (PC12) cells were adopted for the measurements of mitochondrial ATP levels, mitochondrial translation products, and expressions of important mitochondrial regulators, such as required meiotic nuclear division 1 (RMND1), estrogen-related receptor α (ERRα), and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α). To delve into the role of PGC-1α/ERRα axis in mitochondrial translation, 2-(4-tert-butylphenyl) benzimidazole (ZLN005) was employed. Both cellular and animal model results shown that PBDE-47 impeded PGC-1α/ERRα axis and mitochondrial translation. PBDE-47 suppressed mitochondrial function in rat hippocampus and PC12 cells by decreasing relative mitochondrial DNA (mtDNA) content, mitochondrial translation products, and mitochondrial ATP levels. Particularly, ZLN005 reversed PBDE-47 neurotoxicity by enhancing mitochondrial translation through activation of PGC-1α/ERRα axis, yet suppressing PGC-1α with siRNA attenuates its neuroprotective effect in vitro. In conclusion, this work highlights the importance of mitochondrial translation in PBDE-47 neurotoxicity by presenting results from cellular and animal models and suggests a potential therapeutic approach through activation of PGC-1α/ERRα axis. ENVIRONMENTAL IMPLICATION: PBDEs have attracted extensive attention because of their high lipophilicity, persistence, and detection levels in various environmental media. Increasing evidence has shown that neurodevelopmental disorders in children are associated with PBDE exposure. Several studies have also found that perinatal PBDE exposure can cause long-lasting neurobehavioral abnormalities in experimental animals. Our recent studies have also demonstrated the impact of PBDE-47 exposure on mitochondrial biogenesis and dynamics, leading to memory and neurobehavioral deficits. Therefore, we explore whether the pathological mechanism of PBDE-47-induced neurotoxicity involves the regulation of mitochondrial translation through the PGC-1α/ERRα axis.

Toxicity of persistent organic pollutants: a theoretical study.

CONTEXT: Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are two families of persistent organic pollutants that are dangerous as they remain in the atmosphere for long periods and are toxic for humans and animals. They are found all over the world, including the penguins of Antarctica. One of the mechanisms that explains the toxicity of these compounds is related to oxidative stress. The main idea of this theoretical research is to use conceptual density functional theory as a theory of chemical reactivity to analyze the oxidative stress that PCBs and PBDEs can produce. The electron transfer properties as well as the interaction with DNA nitrogenous bases of nine PCBs and ten PBDEs found in Antarctic penguins are investigated. From this study, it can be concluded that compounds with more chlorine or bromine atoms are more oxidizing and produce more oxidative stress. These molecules also interact directly with the nitrogenous bases of DNA, forming hydrogen bonds, and this may be an explanation for the toxicity. Since quinone-type metabolites of PCBs and PBDEs can cause neurotoxicity, examples of quinones are also investigated. Condensed Fukui functions are included to analyze local reactivity. These results are important as the reactivity of these compounds helps to explain the toxicity of PCBs and PBDEs. METHODS: All DFT computations were performed using Gaussian16 at M06-2x/6-311 + g(2d,p) level of theory without symmetry constraints. Electro-donating (ω-) and electro-accepting (ω +) powers were used as global response functions and condensed Fukui functions as local parameters of reactivity.

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.

Quantifying the removal of polybrominated diphenyl ethers (PBDEs) in physical, chemical, and biological sludge treatment systems.

Polybrominated diphenyl ethers (PBDE) are priority contaminants historically used as flame retardants. PBDEs are known to occur in wastewater biosolids posing potential concerns with the beneficial land application of the biosolids. This study evaluated the removal of 21 congeners in nine full-scale sludge treatment systems including pelletization (P), alkaline stabilization (AS), and aerobic (AE) and anaerobic (AN) digestion. It is the first study to conduct a mass balance analysis of a broad spectrum of PBDEs during physical, chemical, and biological sludge treatment. The PBDE congener pattern in raw sludge and biosolids samples was consistent with commercial formulations. The fully brominated congener BDE-209 dominated biosolids from all sites with an average concentration of 620 ng/g dry weight (dw), followed by BDE-99 (173 ng/g dw) and BDE-47 (162 ng/g dw). Mass balance analysis on the P and AS processes showed no change in PBDE mass flows with treatment. However, aerobic and anaerobic digestion processes reported significant levels of removal and formation of individual congeners, though the results were not consistent between facilities. One aerobic digestion process (AE2) reported an overall average removal of 48%, whereas the other (AE1) reported very high levels of accumulation of tri- and tetraBDE congeners. Similarly, there were significant variations in PBDE behavior across the five anaerobic digestion plants studied. The plant with the longest solids retention time (SRT) (AN1) reported a moderate removal (50%) of overall PBDE loading and lower congeners, whereas other plants (AN2-AN5) showed significant low (-19%) to high (-166%) levels of formation of lower congeners. The results suggest that reduced SRTs result in formation of lower congeners while extended SRTs can lead to moderate removal of some PBDEs. Conventional sludge treatment result in low to moderate PBDE removal and advanced thermal conversion technologies may be needed to improve the contaminant removal during sludge treatment.

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.

Inflammation and cardiometabolic diseases induced by persistent organic pollutants and nutritional interventions: Effects of multi-organ interactions.

The development and outcome of inflammatory diseases are associated with genetic and lifestyle factors, which include chemical and nonchemical stressors. Persistent organic pollutants (POPs) are major groups of chemical stressors. For example, dioxin-like polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFASs), and polybrominated diphenyl ethers (PBDEs) are closely associated with the incidence of inflammatory diseases. The pathology of environmental chemical-mediated inflammatory diseases is complex and may involve disturbances in multiple organs, including the gut, liver, brain, vascular tissues, and immune systems. Recent studies suggested that diet-derived nutrients (e.g., phytochemicals, vitamins, unsaturated fatty acids, dietary fibers) could modulate environmental insults and affect disease development, progression, and outcome. In this article, mechanisms of environmental pollutant-induced inflammation and cardiometabolic diseases are reviewed, focusing on multi-organ interplays and highlighting recent advances in nutritional strategies to improve the outcome of cardiometabolic diseases associated with environmental exposures. In addition, advanced system biology approaches are discussed, which present unique opportunities to unveil the complex interactions among multiple organs and to fuel the development of precision intervention strategies in exposed individuals.

Polybrominated Diphenyl Ethers (PBDEs) and Human Health: Effects on Metabolism, Diabetes and Cancer.

There is increasing evidence of the role of endocrine disruptors (EDs) derived from commonly employed compounds for manufacturing and processing in altering hormonal signaling and function. Due to their prolonged half-life and persistence, EDs can usually be found not only in industrial products but also in households and in the environment, creating the premises for long-lasting exposure. Polybrominated diphenyl ethers (PBDEs) are common EDs used in industrial products such as flame retardants, and recent studies are increasingly showing that they may interfere with both metabolic and oncogenic pathways. In this article, a multidisciplinary panel of experts of the Italian Association of Medical Diabetologists (AMD), the Italian Society of Diabetology (SID), the Italian Association of Medical Oncology (AIOM), the Italian Society of Endocrinology (SIE) and the Italian Society of Pharmacology (SIF) provides a review on the potential role of PBDEs in human health and disease, exploring both molecular and clinical aspects and focusing on metabolic and oncogenic pathways.

2,2',4,4'-tetrabromodiphenyl ether causes depigmentation in zebrafish larvae via a light-mediated pathway.

Polybrominated diphenyl ethers (PBDEs) are organic pollutants widely detected in various environmental media due to their high persistence and bioaccumulation. PBDE-induced visual impairment and neurotoxicity were previously demonstrated using zebrafish (Danio rerio) models, and recent research reported the phenotypic depigmentation effect of PBDEs at high concentrations on zebrafish, but whether those effects are still present at environment-relevant levels is still unclear. Herein, we performed both phenotypic examination and mechanism investigation in zebrafish embryos (48 hpf) and larvae (5 dpf) about their pigmentation status when exposing to PBDE congener BDE-47 (2,2',4,4'-tetrabrominated diphenyl ether) at levels from 0.25 to 25 µg/L. Results showed that low-level BDE-47 can restrain the relative melanin abundance of zebrafish larvae to 70.47% (p < 0.05) and 61.54% (p < 0.01) respectively under 2.5 and 25 µg/L BDE-47 compared with control, and the thickness of retinal pigment epithelium (RPE) remarkably reduced from 571.4 nm to 350.3 nm (p < 0.001) under 25 µg/L BDE-47 exposure. We also observed disrupted expressions of melanin synthesis genes and disorganized mitfa differentiation patterns based on Tg(mifta:EGFP), as well as visual impairment resulting from thinner RPE. Considering both processes of visual development and melanin synthesis are highly sensitive to ambient light conditions, we prolonged the light regime of maintaining zebrafish larvae from 14 hours light versus 10 hours dark (14L:10D) to 18 hours light versus 6 hours dark (18L:6D). Lengthening photoperiod successfully rescued the fluorescent level of mitfa in zebrafish epidermis and most gene expressions associated with melanin synthesis under 25 µg/L BDE-47 exposure to the normal level. In conclusion, our work reported the effects of low-level PBDEs on melanin production using zebrafish embryos and larvae, and identified the potential role of a light-mediated pathway in the neurotoxic mechanism of PBDEs.

Derivation and application of indoor air screening values for inhalation exposure to semi-volatile organic compounds.

Semi-volatile organic compounds (SVOCs) are being increasingly studied in indoor air. The absence of health-based inhalation exposure guidelines for most SVOCs impedes the interpretation of indoor air concentrations from a health risk context. To accelerate the derivation of screening values for a large number of SVOCs, a tiered framework was developed to evaluate and adjust published hazard assessments for SVOCs to calculate benchmarks relevant for evaluation of inhalation risk. Inhalation screening values were derived for 43 SVOCs considered in this study, most of which required extrapolation from oral exposure guidelines. The screening values were compared to published SVOC concentrations in homes in Canada to evaluate the potential health risks of chronic exposure to SVOCs in indoor residential environments. SVOCs that could be prioritized for further evaluation were dibutyl phthalates (DBP), di(2-ethylhexyl) phthalate (DEHP) and polybrominated diphenyl ethers (PBDEs). The framework could be applied more broadly in the future to derive screening values for other non-traditional indoor air contaminants with limited inhalation hazard data or assessments.

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, Il1ß [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.

Feed as a source of polybrominated diphenyl ethers (PBDEs).

One of the most important routes for human exposure to polybrominated diphenyl ethers (PBDEs) is the ingestion of contaminated food. Food of animal origin safety is strongly related to feed quality. The aim of the study was the assessment of feeds and feed materials quality associated with ten PBDE congeners (BDE-28, 47, 49, 99, 100, 138, 153, 154, 183 and 209) contamination. The quality of 207 feed samples divided into eight categories (277/2012/EU) was checked using the gas chromatography-high resolution mass spectrometry (GC-HRMS). At least one congener was identified in 73% of the samples. All investigated fish oil, animal fat, and feed for fish were contaminated, and 80% of plant-origin feed samples were free of PBDEs. The highest median content of ∑10PBDE was found in fish oils (2260 ng kg-1) followed by fishmeal (530 ng kg-1). The lowest median was found in mineral feed additives, plant materials excluding vegetable oil and compound feed. BDE-209 was the most frequently detected congener (56%). All congeners except BDE-138 and BDE-183 were detected in 100% of the fish oil samples. Except for BDE-209, the congener detection frequencies did not exceed 20% in compound feed, feed of plant origin, and vegetable oils. Excluding BDE-209, similar congener profiles were found for fish oils, fishmeal and feed for fish, with BDE-47 in the highest concentration, followed by BDE-49 and BDE-100. Another pattern appeared in animal fat, with a higher median concentration of BDE-99 than BDE-47. Time-trend analysis of PBDE concentrations in fishmeal (n = 75) showed a 63% decrease in ∑10PBDE (p = 0.077) and a 50% decrease in the ∑9PBDE (p = 0.008) between 2017 and 2021. It proves the international legislation implemented to reduce PBDE environmental levels has been effective.

Polybrominated diphenyl ethers isolated from the marine sponge Lendenfeldia chondrodes collected in Mayotte.

CDK7 and FynB protein kinases have been recognized as relevant targets for cancer and brain diseases treatment due to their pivotal regulatory roles in cellular functions such as cell cycle and neural signal transduction. Several studies demonstrated that the inhibition of these proteins could be useful in altering the onset or progression of these diseases. Based on bioassay-guided approach, the extract of the marine sponge Lendenfeldia chondrodes (Thorectidae), which exhibited interesting kinase inhibitory activities, was fractionated. The investigation led to the isolation of five known 1-5 and one new 6 polybrominated diphenyl ethers (PBDEs). Their structure elucidation was established based on spectroscopic data (NMR and HRMS) and comparison with literature data.

BDE-47 Induces Immunotoxicity in RAW264.7 Macrophages through the Reactive Oxygen Species-Mediated Mitochondrial Apoptotic Pathway.

Polybrominated diphenyl ethers (PBDEs) are classic and emerging pollutants that are potentially harmful to the human immune system. Research on their immunotoxicity and mechanisms suggests that they play an important role in the resulting pernicious effects of PBDEs. 2,2',4,4'-Tetrabrominated biphenyl ether (BDE-47) is the most biotoxic PBDE congener, and, in this study, we evaluated its toxicity toward RAW264.7 cells of mouse macrophages. The results show that exposure to BDE-47 led to a significant decrease in cell viability and a prominent increase in apoptosis. A decrease in mitochondrial membrane potential (MMP) and an increase in cytochrome C release and caspase cascade activation thus demonstrate that cell apoptosis induced by BDE-47 occurs via the mitochondrial pathway. In addition, BDE-47 inhibits phagocytosis in RAW264.7 cells, changes the related immune factor index, and causes immune function damage. Furthermore, we discovered a significant increase in the level of cellular reactive oxygen species (ROS), and the regulation of genes linked to oxidative stress was also demonstrated using transcriptome sequencing. The degree of apoptosis and immune function impairment caused by BDE-47 could be reversed after treatment with the antioxidant NAC and, conversely, exacerbated by treatment with the ROS-inducer BSO. These findings indicate that oxidative damage caused by BDE-47 is a critical event that leads to mitochondrial apoptosis in RAW264.7 macrophages, ultimately resulting in the suppression of immune function.

An additional threat to populations predicted to collapse: Organobromine compounds of natural and anthropogenic sources in rough-toothed dolphins from the Southwestern Atlantic Ocean.

Organic contaminants with toxic effects, like the conventional brominated flame retardants (BFRs) and BFRs of emergent concern, and their synergistic effects with other micropollutants, can be an additional threat to delphinids. Rough-toothed dolphins (Steno bredanensis) populations strongly associated with coastal environments already face a potential risk of decline due to high exposure to organochlorine pollutants. Moreover, natural organobromine compounds are important indicators of the environment's health. Polybrominated diphenyl ethers (PBDEs), pentabromoethylbenzene (PBEB), hexabromobenzene (HBB) and the methoxylated PBDEs (MeO-BDEs) were determined in the blubber of rough-toothed dolphins from three ecological populations from the Southwestern Atlantic Ocean (Southeastern, Southern and Outer Continental Shelf/Southern populations, SE, S, and OCS/S, respectively). The profile was dominated by the naturally produced MeO-BDEs (mainly 2'-MeO-BDE 68 and 6-MeO-BDE 47), followed by the anthropogenic BFRs PBDEs (mainly BDE 47). Median ΣMeO-BDE concentrations varied between 705.4 and 3346.0 ng g-1 lw among populations and ΣPBDE from 89.4 until 538.0 ng g-1 lw. Concentrations of anthropogenic organobromine compounds (ΣPBDE, BDE 99 and BDE 100) were higher in SE population than in OCS/S, indicating a coast - ocean gradient of contamination. Negative correlations were found between the concentration of the natural compounds and age, suggesting their metabolization and/or biodilution and maternal transference. Conversely, positive correlations were found between the concentrations of BDE 153 and BDE 154 and age, indicating low biotransformation capability of these heavy congeners. The levels of PBDEs found are concerning, particularly for SE population, because they are similar to concentrations known for the onset of endocrine disruption in other marine mammals and may be an additional threat to a population in a hotspot for chemical pollution.