Search Results (43)

The maternal–fetal environment is influenced by multiple factors, including nutrition and environmental contaminants, which can impact long-term development. Perinatal exposure to organophosphate flame retardants (OPFRs) disrupts energy homeostasis and causes maladaptive behaviors in mice. Maternal obesity affects development by impairing blood–brain barrier (BBB) formation, influencing brain regions involved in energy regulation and behavior. This study examined the combined effects of maternal obesity and perinatal OPFR treatment on offspring development. Female mice were fed either a low-fat (LFD) or a high-fat diet (HFD) for 8 weeks, mated, and treated with either sesame oil or an OPFR mixture (tris(1,3-dichloro-2-propyl)phosphate, tricresyl phosphate, and triphenyl phosphate, 1 mg/kg each) from gestational day 7 to postnatal day 14. Results showed that both maternal diet and OPFR treatment disrupted blood–brain barrier integrity, energy balance, and reproductive gene expression in the hypothalamus of neonates. The expression of hepatic genes related to lipid and xenobiotic metabolism was also altered. In adulthood, LFD OPFR-treated female offspring exhibited increased avoidance behavior, while HFD OPFR-treated females demonstrated memory impairments. Metabolic assessments revealed decreased energy expenditure and nighttime activity in LFD OPFR-treated females. These findings suggest that maternal diet and OPFR treatment alter hypothalamic and liver gene expression in neonates, potentially leading to long-term metabolic and behavioral changes. Full article

Organophosphate flame retardants (OPFRs) have increasingly replaced polybrominated diphenyl ethers (PBDEs) in various consumer products and raw materials, due to regulatory restrictions on PBDEs. However, concerns about the toxicity and environmental persistence of OPFRs are growing. This review summarizes current research on the toxicity of OPFRs, with a focus on New Approach Methodologies (NAMs) that aim to eliminate the need for animal testing. NAMs, including in vitro models, omics technologies, and computational methods, provide valuable insights into the cellular and molecular effects of OPFR exposure. Evidence suggests that OPFRs may disrupt multiple organ systems, including the nervous, hepatic, pulmonary, reproductive, and endocrine systems. Additionally, the metabolic transformation of OPFRs can increase their toxicity, raising concerns about long-term exposure risks. While NAM studies provide valuable insights, further research is needed to refine risk-assessment frameworks and improve our understanding of the long-term effects of OPFR exposure, particularly at concentrations found in the environment. This new knowledge will help develop more accurate regulatory guidelines and ensure the better protection of public and environmental health. Full article

Tris(2-chloroethyl) phosphate (TCEP) is a representative chlorinated organophosphate flame retardant (OPFR) that demonstrates greater persistence than other non-halogenated alkyl or aryl OPFRs. Although TCEP has been shown to accumulate significantly in the environment and contribute to testicular toxicity and spermatogenic dysfunction, the precise underlying factors and mechanisms of action remain unclear. Herein, male ICR mice were gavaged with corn oil, 50 mg/kg body weight (bw) TCEP, or 100 mg/kg bw TCEP from postnatal day (PND) 22 to PND 35. TCEP exposure resulted in the disruption of blood-testis barrier (BTB) integrity and in abnormal testicular development. Considering that Sertoli cells constitute the primary target of toxicants and that TCEP induces oxidative stress in the testis and other organs, we focused on ferroptosis in Sertoli cells. Our findings revealed a significant increase in ferroptosis in the testes and Sertoli cells following TCEP exposure, and we observed functional restoration of Sertoli cell junctions upon treatment with the ferroptosis inhibitor ferrostatin-1. Furthermore, ferritin heavy chain 1 (FTH1) was markedly reduced in TCEP-exposed testes and Sertoli cells. Since nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy is essential for the degradation of FTH1, we assessed ferritinophagic activity and found significant upregulation of NCOA4, ATG5, ATG7, and LC3B II/I in TCEP-exposed testes and Sertoli cells. These results strongly suggest that TCEP triggers Sertoli cell ferroptosis by activating ferritinophagy that leads to reduced expression of BTB-associated proteins, ultimately causing BTB disruption and testicular developmental toxicity. Full article

Contaminants of Emerging Concern (CECs), including per- and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs), have raised global concerns due to their persistence, bioaccumulation potential, and toxicity. This study presents a comprehensive investigation of the occurrence, spatiotemporal distribution, potential sources, and the ecological and human health risks associated with 18 PFASs and 9 OPFRs in the surface waters of the upper Yangtze River, China. The water samples were collected from the main stream and five major tributaries (Min, Jinsha, Tuo, Jialing, and Wu Rivers) in 2022 and 2023. The total concentration of PFASs and OPFRs ranged from 16.07 to 927.19 ng/L, and 17.36 to 190.42 ng/L, respectively, with a consistently higher concentration observed in the main stream compared to the tributaries. Ultra-short-chain PFASs (e.g., TFMS) and halogenated OPFRs (e.g., TCPP) were the predominant compounds, likely originating from industrial discharges, wastewater effluents, and other anthropogenic sources. Ecological risk assessments indicated low-to-moderate risks at most sampling sites, with higher risks near wastewater discharge points. Human health risk evaluations suggested negligible non-carcinogenic risks but identified potential carcinogenic risks from OPFR exposure for adults at specific locations, particularly in Leshan city. This study highlights the importance of understanding the fate and impacts of PFASs and OPFRs in the upper Yangtze River, and provides valuable insights for developing targeted pollution control strategies and risk management measures. Full article

Emerging pollutants such as organophosphate flame retardants (OPFRs) pose a critical threat to environmental and human health, while conventional wastewater treatments often fail to remove them. This study addresses this issue by evaluating the bioremediation potential of white-rot fungi for the removal of two OPFRs: tris(2-chloroethyl) phosphate (TCEP) and tributyl phosphate (TBP). Three fungal species—Ganoderma lucidum, Trametes versicolor, and Phanerochaete velutina—were screened for their degradation capabilities. Among these, G. lucidum and T. versicolor demonstrated removal efficiencies exceeding 99% for TBP, while removal rates for TCEP were significantly lower, with a maximum of 30%. The exploration of the enzyme role showed that cytochrome P450 is involved in the degradation while the extracellular laccase is not involved. Continuous batch experiments were performed using a trickle-bed reactor (TBR) operating under non-sterile conditions, a setting that closely resembles real-world wastewater treatment environments. G. lucidum was immobilized on oak wood chips, and the removal efficiencies were measured to be 85.3% and 54.8% for TBP and TCEP, respectively, over 10 cycles. Microbial community analysis showed that G. lucidum remained the dominant species in the reactor. These findings demonstrate the efficacy of fungal-based trickle-bed bioreactors, offering a sustainable and efficient alternative for addressing environmental pollution caused by highly recalcitrant pollutants. Full article

Background: The pollution of organophosphate flame retardants (OPFRs) is of global concern, but the site-specific data of OPFR concentrations in drinking water are scarce for many areas of the world outside of Europe and the US. This study aimed to investigate the occurrence and profiles of OPFRs in the tap water treatment and delivery process in Shanghai. Methods: In total, 106 samples were analyzed for 10 OPFRs, which were collected periodically from monitoring points of drinking water treatment plants and piped water between November 2021 and July 2023. The average daily doses of OPFRs through the ingestion of tap water were calculated by multiplying nominal volumes of water ingestion rates with the measured concentrations of OPFRs. Hazard quotients, the hazard index, and the carcinogenic risks of OPFRs via drinking water were used to estimate the health risks. Results: Tributyl phosphate (TBP), tris(2-chloroethyl) phosphate (TCEP), and tris (1-chloro-2-propyl) phosphate (TCIPP) were found in >90% of the tap water samples, whereas triethyl phosphate (TEP) and tris (2,3-dibromopropyl) phosphate (TDBPP) were not found in any samples. The concentrations of Σ₁₀OPFRs were found at part-per-trillion ranges, with average concentrations that ranged from 86.0 ng/L in February 2023 (dry season) to 218 ng/L in July 2022 (wet season). TCIPP was the most abundant compound among the investigated OPFRs. The average daily dose of Σ₁₀OPFRs via the ingestion of tap water was up to 20.4 ng/kg body weight/day. The hazard quotients of OPFRs through drinking water were in the range of 10⁻⁵–10⁻⁴, indicating low risk levels. Moreover, the hazard index of OPFRs indicated that the risk for children (2 × 10⁻⁴) was higher than adults (7 × 10⁻⁵). Conclusion: Tap water intake may be an important source of OPFRs exposure. But the risk of OPFRs for local residents is at a low level through drinking water. Full article

Firefighters can be exposed to complex mixtures of airborne substances, including hazardous substances released during structural fires. This study employed silicone wristbands (SWBs) as passive samplers to investigate potential exposure to polycyclic aromatic hydrocarbons (PAHs) and flame retardants (FRs). SWBs were deployed at different areas of four fire stations, in four truck cabins, and at an office control location; they were also donned outside the jackets of 18 firefighters who responded to fire calls. Overall, office areas had significantly lower PAHs than fire station areas. Vehicle bays and truck cabins had significantly higher concentrations of low molecular weight (LMW) PAHs than sleeping and living room areas. For organophosphate ester flame retardants (OPFRs), tri-n-butyl phosphate (TnBP) and tris(1-chloro-2-propyl) phosphate (TCPP) were detected in all the samples; 2-ethylhexyl diphenyl phosphate (EHDPP) was more frequently detected in the fire station areas. Triphenyl phosphate (TPP) concentrations were highest in the truck cabin and office areas, and tris(1,3-dichloro-2-propyl)phosphate (TDCPP) was highest in truck cabins. Thirteen of 16 PAHs and nine of 36 OPFRs were detected in all the SWBs worn by firefighters, and tris (2-butoxyethyl) phosphate (TBEP) was the predominant OPFR. Levels of LMW PAHs were significantly lower when firefighters did not enter the fire. LMW PAHs, HMW (high molecular weight) PAHs, and EHDPP were significantly elevated when heavy smoke was reported. This work highlights the potential for occupational exposure to PAHs and flame retardants in some fire station areas; moreover, factors that may influence exposure during fire suppression. Whilst firefighters’ occupational exposure to PAHs is likely related to fire suppression and exposure to contaminated gear and trucks, exposure to OPFRs may be more related to their presence in truck interiors and electronics. Full article

Organophosphorus flame retardants (OPFRs) are abundant and persistent in the environment but have limited toxicity information. Their similarity in structure to organophosphate pesticides presents great concern for developmental neurotoxicity (DNT). However, current in vivo testing is not suitable to provide DNT information on the amount of OPFRs that lack data. Over the past decade, an in vitro battery was developed to enhance DNT assessment, consisting of assays that evaluate cellular processes in neurodevelopment and function. In this study, behavioral data of small model organisms were also included. To assess if these assays provide sufficient mechanistic coverage to prioritize chemicals for further testing and/or identify hazards, an integrated approach to testing and assessment (IATA) was developed with additional information from the Integrated Chemical Environment (ICE) and the literature. Human biomonitoring and exposure data were identified and physiologically-based toxicokinetic models were applied to relate in vitro toxicity data to human exposure based on maximum plasma concentration. Eight OPFRs were evaluated, including aromatic OPFRs (triphenyl phosphate (TPHP), isopropylated phenyl phosphate (IPP), 2-ethylhexyl diphenyl phosphate (EHDP), tricresyl phosphate (TMPP), isodecyl diphenyl phosphate (IDDP), tert-butylphenyl diphenyl phosphate (BPDP)) and halogenated FRs ((Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), tris(2-chloroethyl) phosphate (TCEP)). Two representative brominated flame retardants (BFRs) (2,2′4,4′-tetrabromodiphenyl ether (BDE-47) and 3,3′,5,5′-tetrabromobisphenol A (TBBPA)) with known DNT potential were selected for toxicity benchmarking. Data from the DNT battery indicate that the aromatic OPFRs have activity at similar concentrations as the BFRs and should therefore be evaluated further. However, these assays provide limited information on the mechanism of the compounds. By integrating information from ICE and the literature, endocrine disruption was identified as a potential mechanism. This IATA case study indicates that human exposure to some OPFRs could lead to a plasma concentration similar to those exerting in vitro activities, indicating potential concern for human health. Full article

Background: Organophosphate flame retardants (OPFRs) are compounds with a wide range of industrial and commercial applications and are mainly used as flame retardants and plasticizers. The global consumption of OPFRs has risen rapidly in recent decades, and they have been widely detected in environmental media. Unfortunately, OPFRs have been associated with many adverse health outcomes. The issue of the health risks of OPFRs is attracting increasing attention. Therefore, there is a need to review the current state of research and trends in this field to help researchers and policymakers quickly understand the field, identify new research directions, and allocate appropriate resources for further development of the OPFR health risk research field. Methods: This study statistically analyzed 1162 relevant publications included in the Web of Science Core Collection from 2003–2023. The internal and external features of the literature, such as publication trends, countries, authors, journals, and keywords, were quantitatively analyzed and visually presented to identify the research hotspots, compositions, and paradigms of the field and to horizontally and vertically analyze the development trends and structural evolution of the field. Results: The development of the field can be divided into three stages, and the field entered a period of rapid development in 2016. China (649 papers) is the most prolific country, followed by the United States (188 papers). The authors STAPLETON HM and WANG Y have the highest combined impact. International collaboration between countries and researchers still needs to be strengthened. Science of The Total Environment is the most frequently published journal (162 papers), and Environmental Science and Technology is the most frequently cited journal (5285 citations). Endocrine disruption, developmental toxicity, and neurotoxicity are the health effects of greatest interest. Conclusions: Future research is expected to be multidisciplinary, and research hotspots may involve a comprehensive assessment of OPFR exposure in the population, exploration of the mechanisms of endocrine-disrupting effects and in vivo metabolic processes, and examination of the health effects of OPFR metabolites. Full article

Emerging organophosphate flame retardants (eOPFRs) have attracted attention in recent times and are expected to gain extensive usage in the coming years. However, they may have adverse effects on organisms. Due to their novel nature, there are few relevant articles dealing with toxicological studies of the above eOPFRs, especially their information on the perturbation of cellular metabolism, which is, thus far, marginally understood. Our research initially assessed the cytotoxicity of eOPFRs, which include compounds like cresyl diphenyl phosphate (CDP), resorcinol bis(diphenyl phosphate) (RDP), triallyl phosphate (TAP), and pentaerythritol phosphate alcohol (PEPA). This evaluation was conducted using the methyl thiazolyl tetrazolium (MTT) assay. Subsequently, we utilized a gas chromatography/mass spectrometry (GC/MS)-based metabolomic approach to investigate the metabolic disruptions induced by these four eOPFRs in A549 cells. The MTT results showed that, at high concentrations of 1 mM, their cytotoxicity was ranked as CDP > TAP > RDP > PEPA. In addition, metabolic studies at low concentrations of 10 μM showed that the metabolic interference of CDP, TAP, and PEPA focuses on oxidative stress, amino acid metabolism, and energy metabolism, while RDP mainly affects energy metabolism—galactose metabolism and gluconeogenesis. Therefore, from the perspective of cytotoxicity and metabolic analysis, RDP may be a more promising alternative. Our experiments provide important insights into the possible metabolic effects of potential toxic substances and complement the evidence on the human health risks of eOPFRs. Full article

The occurrence, distribution, removal, and mass loadings of common organophosphate flame retardants (OPFRs) in an advanced municipal wastewater treatment plant (WWTP) were comprehensively investigated. The OPFRs were mainly partitioning in the dissolved phase, and the total concentrations ranged from 1364 to 1701 ng/L in influent, 678~1064 in effluent, and 177~470 ng/g dw in residual sludge. Tributoxyethyl phosphate and tris(2-chloroethyl) phosphate were the abundant compounds in both the dissolved phase and adsorbed phase. The removal frequencies and mechanisms of the OPFRs were highly associated with the properties of compounds. According to the mass balance analysis, 14.9%, 13.0%, and 11.2% of the total OPFR loads were removed in the traditional treatment, tertiary treatment, and to the sludge, respectively. The mass loadings and environmental emissions of the OPFRs were 0.67~291 μg/d/person and 0.57~107 μg/d/person, respectively. The effluent discharged from the WWTP posed ecological risks to the receiving river, which requires being paid more attention. Full article

Understanding the interplay among organophosphorus flame retardants (OPFRs), microplastics, and freshwater organisms is crucial for unravelling the dynamics within freshwater environments and foreseeing the potential impacts of organic pollutants and plastic contamination. For that purpose, the present research assessed the exposure impact of 10 mg L⁻¹ flame-retardant aluminium diethylphosphinate (ALPI), 10 μg mg⁻¹_liver microplastics polyurethane (PU), and the combination of ALPI and PU on the freshwater planarian Girardia tigrina. The exposure to both ALPI and PU revealed a sequential effect, i.e., a decrease in locomotor activity, while oxidative stress biomarkers (total glutathione, catalase, glutathione S-transferase, lipid peroxidation) and metabolic responses (cholinesterase activity, electron transport system, and lactate dehydrogenase) remained unaffected. Despite this fact, it was possible to observe that the range of physiological responses in exposed organisms varied, in particular in the cases of the electron transport system, cholinesterase activity, glutathione S-transferase, catalase, and levels of total glutathione and proteins, showing that the energetic costs for detoxification and antioxidant capacity might be causing a lesser amount of energy allocated for the planarian activity. By examining the physiological, behavioural, and ecological responses of planarians to these pollutants, insights can be gained into broader ecosystem-level effects and inform strategies for mitigating environmental risks associated with OPFRs and microplastic pollution in freshwater environments. Full article

Harmful substances in consumer goods pose serious hazards to human health and the environment. However, due to the vast variety of consumer goods and the complexity of their substrates, it is difficult to simultaneously detect multiple harmful substances in different materials. This paper presents a method for the simultaneous determination of 41 harmful substances comprising 17 phthalates (PAEs), 8 organophosphate flame retardants (OPFRs), and 16 polycyclic aromatic hydrocarbons (PAHs) in five types of products using the matrix-matching calibration strategy. The method employs an efficient ultrasonic extraction procedure using a mixture of dichloromethane and methylbenzene, followed by dissolution–precipitation and analysis through gas chromatography–mass spectrometry. Compared with previous experiments, we established a universal pretreatment method suitable for multi-matrix materials to simultaneously determine multiple harmful substances. To evaluate the effects of the matrix on the experimental results, we compared neat standard solutions and matrix-matching standard solutions. The results demonstrated that all compounds were successfully separated within 30 min with excellent separation efficiency. Additionally, the linear relationships of all analytes showed strong correlation coefficients (R²) of at least 0.995, ranging from 0.02 mg/L to 20 mg/L. The average recoveries of the target compounds (spiked at three concentration levels) were between 73.6 and 124.1%, with a relative standard deviation (n = 6) varying from 1.2% to 9.9%. Finally, we tested 40 different materials from consumer products and detected 16 harmful substances in 31 samples. Overall, this method is simple and accurate, and it can be used to simultaneously determine multiple types of hazardous substances in multi-matrix materials by minimizing matrix effects, making it an invaluable tool for ensuring product safety and protecting public health. Full article

Cyclodextrins (CDs) were used as green char promoters in the formulation of organophosphorus flame retardants (OPFRs) for polymeric materials, and they could reduce the amount of usage of OPFRs and their release into the environment by forming [host:guest] inclusion complexes with them. Here, we report a systematic study on the inclusion complexes of natural CDs (α-, β-, and γ-CD) with a representative OPFR of DOPO using computational methods of molecular docking, molecular dynamics (MD) simulations, and quantum mechanical (QM) calculations. The binding modes and energetics of [host:guest] inclusion complexes were analyzed in details. α-CD was not able to form a complete inclusion complex with DOPO, and the center of mass distance [host:guest] distance amounted to 4–5 Å. β-CD and γ-CD allowed for a deep insertion of DOPO into their hydrophobic cavities, and DOPO was able to frequently change its orientation within the γ-CD cavity. The energy decomposition analysis based on the dispersion-corrected density functional theory (sobEDAw) indicated that electrostatic, orbital, and dispersion contributions favored [host:guest] complexation, while the exchange–repulsion term showed the opposite. This work provides an in-depth understanding of using CD inclusion complexes in OPFRs formulations. Full article

A widely used organophosphate flame retardant (OPFR), triphenyl phosphate (TPP), is frequently detected in various environmental media and humans. However, there is little known on the human corneal epithelium of health risk when exposed to TPP. In this study, human normal corneal epithelial cells (HCECs) were used to investigate the cell viability, morphology, apoptosis, and mitochondrial membrane potential after they were exposed to TPP, as well as their underlying molecular mechanisms. We found that TPP decreased cell viability in a concentration-dependent manner, with a half maximal inhibitory concentration (IC50) of 220 μM. Furthermore, TPP significantly induced HCEC apoptosis, decreased mitochondrial membrane potential in a dose-dependent manner, and changed the mRNA levels of the apoptosis biomarker genes (Cyt c, Caspase-9, Caspase-3, Bcl-2, and Bax). The results showed that TPP induced cytotoxicity in HCECs, eventually leading to apoptosis and changes in mitochondrial membrane potential. In addition, the caspase-dependent mitochondrial pathways may be involved in TPP-induced HCEC apoptosis. This study provides a reference for the human corneal toxicity of TPP, indicating that the risks of OPFR to human health cannot be ignored. Full article