Organophosphate Flame Retardants Research Articles

Prenatal and postnatal exposure to organophosphate flame retardants and neurodevelopment at 1 and 2 years of age

Prenatal and postnatal exposure to organophosphate flame retardants and neurodevelopment at 1 and 2 years of age

Tris(1-chloro-2-propyl) phosphate enhances the adverse effects of biodegradable polylactic acid microplastics on the mussel Mytilus coruscus

Microplastics (MPs) and organophosphate flame retardants (OPFRs) have recently become ubiquitous and cumulative pollutants in the oceans. Since OPFRs are added to or adsorbed onto MPs as additives, it is necessary to study the composite contamination of OPFRs and MPs, with less focus on bio-based PLA. Therefore, this study focused on the ecotoxicity of the biodegradable MP polylactic acid (PLA) (5 μm, irregular fragments, 102 and 106 particles/L), and a representative OPFRs tris(1-chloro-2-propyl) phosphate (TCPP, 0.5 and 50 μg/L) at environmental and high concentrations. The mussel Mytilus coruscus was used as a standardised bioindicator for exposure experiments. The focus was on examining oxidative stress (catalase, CAT, superoxide dismutase, SOD, malondialdehyde, MDA), immune responses acid (phosphatase, ACP, alkaline phosphatase, AKP, lysozyme, LZM), neurotoxicity (acetylcholinesterase, AChE), energy metabolism (lactate dehydrogenase, LDH, succinate dehydrogenase, SDH, hexokinase, HK), and physiological indices (absorption efficiency, AE, excretion rate, ER, respiration rate, RR, condition index, CI) after 14 days exposure. The results of significantly increased oxidative stress and immune responses, and significantly disturbed energy metabolism and physiological activities, together with an integrated biomarker response (IBR) analysis, indicate that bio-based PLA MPs and TCPP could cause adverse effects on mussels. Meanwhile, TCPP interacted significantly with PLA, especially at environmental concentrations, resulting in more severe negative impacts on oxidative and immune stress, and neurotoxicity. The more severe adverse effects at environmental concentrations indicate higher ecological risks of PLA, TCPP and their combination in the real marine environment. Our study presents reliable data on the complex effects of bio-based MP PLA, TCPP and their combination on marine organisms and the environment.

Structure-dependent destructive adsorption of organophosphate flame retardants on lipid membranes

The widespread use of organophosphate flame retardants (OPFRs), a serious type of pervasive environmental contaminants, has led to a global concern regarding their diverse toxicities to living beings. Using a combination of experimental and theoretical approaches, we systematically studied the adsorption, accumulation, and influence of a series of OPFRs on the lipid membranes of bacteria and cells. Our results revealed that OPFRs can aggregate in lipid membranes, leading to the destruction of membrane integrity. During this process, the molecular structure of the OPFRs is a dominant factor that significantly influences the strength of their interaction with the lipid membrane, resulting in varying degrees of biotoxicity. Triphenyl phosphate (TPHP), owing to its large molecular size and strong hydrophobicity, causes severe membrane disruption through the formation of nanoclusters. The corresponding severe toxicity originates from the phase transitions of the lipid membranes. In contrast, smaller OPFRs such as triethyl phosphate (TEP) and tris(2-chloroethyl) phosphate (TCEP) have weaker hydrophobicity and induce minimal membrane disturbance and ineffective damage. In vivo, gavage of TPHP induced more severe barrier damage and inflammatory infiltration in mice than TEP or TCEP, confirming the higher toxicity of TPHP. Overall, our study elucidates the structure-dependent adsorption of OPFRs onto lipid membranes, highlighting their destructive interactions with membranes as the origin of OPFR toxicity.

Nationwide Investigation on Organophosphate Flame Retardants in Tea from China: Migration from Packaging Materials and Implications for Global Risk Assessment.

In this study, we measured 15 common organophosphate flame retardants (OPFRs) in six categories of tea samples across China. OPFRs were found in all the tea samples, with the total concentrations of OPFRs (∑OPFRs) at 3.44-432 ng/g [geometric mean (GM): 17.6 ng/g]. Triphenyl phosphate (TPhP) was the dominant OPFR, accounting for 39.0-76.2% of ∑OPFRs across all tea categories. The potential factors influencing the residual OPFRs in tea were thoroughly examined, including the agricultural environment, fermentation, and packaging of teas. Tea packaging materials (TPMs) were then identified as the primary sources of OPFRs in teas. The migration test revealed that OPFRs with lower molecular weights and log Kow values exhibited a higher propensity for facilitating the migration of OPFRs from TPMs to teas. The estimated daily intakes of OPFRs from teas were relatively higher for the general populations in Mauritania, Gambia, Togo, Morocco, and Senegal (3.18-9.79 ng/kg bw/day) than China (3.12 ng/kg bw/day). The health risks arising from OPFRs in Chinese teas were minor. This study established a baseline concentration and demonstrated the contamination sources of OPFRs in Chinese tea for the first time, with an emphasis on enhancing the hygiene standards for TPMs.

Biomonitoring urinary organophosphorus flame retardant metabolites by liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry and their association with oxidative stress.

Organophosphate flame retardants (OPFRs) are widely used as substitutes for traditional brominated flame retardants, necessitating a reliable and sensitive method for biomonitoring their urinary metabolites to assess human exposure. This study conducted biomonitoring of 10 metabolites of OPFRs in 152 adults and assessed their association with oxidative stress biomarkers 8-hydroxydeoxyguanosine and 8-hydroxyguanosine. Urinary metabolites of OPFRs were released via enzymatic deconjugation. The addition of sodium chloride to the urine samples increases the ionic strength, inducing a salting-out effect that reduces the solubility of these compounds, thereby facilitating their extraction with a mixture of ethyl acetate and acetonitrile. Then, the metabolites of OPFRs were quantified by ultra-high performance liquid chromatography-tandem mass spectrometry, and we validated the method for linear range, precision, matrix effect, and method detection limit. The detection limit of the metabolites of OPFRs ranged from 0.01 to 0.2μg/L, and these metabolites were detected with high frequencies ranging from 25.0 to 98.68% in the urine samples. The concentration of bis (2-chloroethyl) phosphate was significantly higher in males than in females, with the geometric mean concentration of 0.88μg/L for males and 0.53μg/L for females, respectively. Spearman correlation analysis revealed weak but statistically significant positive correlations among the urinary metabolites. Bayesian kernel machine regression analysis showed a significant positive association between elevated urinary concentrations of metabolites of OPFRs and increased oxidative stress levels. Di-n-butyl phosphate was identified as the metabolite that significantly contributed to the elevated level of 8-hydroxyguanosine.

Monitoring of OPFRs in WWTPs: Unveiling environmental insights with high resolution mass spectrometry

Exploring the occurrence pattern of organophosphate flame retardants (OPFRs) in environmental samples has attracted increasing attention lately. In the conventional wastewater treatment plants (WWTPs), OPFRs are not sufficiently removed and therefore are discharged to the aquatic environment. However, concerns arise from their release regarding the potential risk posed to organisms. Consequently, closely monitoring this group of emerging contaminants, along with the evaluation of the associated ecological risk are matters of utmost importance. Given the aforementioned information, influents and effluents from two WWTPs (WWTP-A and WWTP-S) in Thessaloniki were gathered during a 36-month sampling initiative spanning from 2020 to 2023 in order to evaluate the occurrence and concentration levels of OPFRs. The collected samples underwent solid-phase extraction and then preceded to analysis with a Q Exactive Focus Orbitrap mass analyzer. In the present study, except for the implementation of the target analysis approach, removal efficiencies and mass loads were further calculated. TBEP (tris-2-butoxyethylphosphate) and TEP (triethyl phosphate) were detected in all influent samples (%DF = 100 %) in WWTP-A while in WWTP-S only TCPP (tris-1-chloro-2-propyl phosphate) was omnipresent. In effluents of both WWTPs, only TEP maintained the same detection frequency (%DF = 100 %). The highest mean concentration levels in WWTP-S influents were calculated for TEP (327 ng/L) followed by TCPP (277 ng/L) while in WWTP-A the highest mean concentrations in influents were detected for TCPP (405 ng/L) and TDCP (Tris(1,3-dichloro-2-propyl)phosphate) (124 ng/L). In effluents, the highest mean concentration was reported for TCPP, in both WWTPs, reaching 295 ng/L and 240 ng/L in WWTP-S and WWTP-A respectively. Generally, OPFRs exhibited low to moderate average removal efficiencies. Positive and negative removal efficiencies were also noticed during the monitoring campaign. The average mass load in WWTP-S was as high as 10.1 mg/day/1000 inhabitants and in WWTP-A, 11 mg/day/1000 inhabitants in effluents. Finally, different mathematical tools were employed for the assessment of the risk posed to algae, invertebrates and fish. For the toxicity assessment in these three trophic levels the worst-case scenario was taken into consideration. Generally, all the target analytes presented low or medium values in all trophic levels for acute and chronic toxicity.

Embryonic Exposure to Organophosphate Flame Retardants (OPFRs) Differentially Induces Cardiotoxicity in Rare Minnow (Gobiocypris rarus).

Organophosphorus flame retardants (OPFRs) such as triphenyl phosphate (TPHP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) were reported to impair cardiac function in fish. However, limited information is available regarding their cardiotoxic mechanisms. Using rare minnow (Gobiocypris rarus) as a model, we found that both TPHP and TDCIPP exposures decreased heart rate at 96 h postfertilization (hpf) in embryos. Atropine (an mAChR antagonist) can significantly attenuate the bradycardia caused by TPHP, but only marginally attenuated in TDCIPP treatment, suggesting that TDCIPP-induced bradycardia is independent of mAChR. Unlike TDCIPP, although TPHP-induced bradycardia could be reversed by transferring larvae to a clean medium, the inhibitory effect of AChE activity persisted compared to 96 hpf, indicating the existence of other bradycardia regulatory mechanisms. Transcriptome profiling revealed cardiotoxicity-related pathways in treatments at 24 and 72 hpf in embryos/larvae. Similar transcriptional alterations were also confirmed in the hearts of adult fish. Further studies verified that TPHP and TDCIPP can interfere with Na+/Ca2+ transport and lead to disorders of cardiac excitation-contraction coupling in larvae. Our findings provide useful clues for unveiling the differential cardiotoxic mechanisms of OPFRs and identifying abnormal Na+/Ca2+ transport as one of a select few known factors sufficient to impair fish cardiac function.

Association between exposure to organophosphate flame retardants and epidermal growth factor receptor expression in lung cancer patients.

Organophosphate flame retardants (OPFRs) are extensively distributed in our environment, prompting concerns about potential health hazards, including lung injuries resulting from OPFR exposure. The present study recruited 125 lung cancer patients, assessing their exposure to 10 OPFR compounds through urine samples. The final analysis comprised 108 participants after excluding those lacking epidermal growth factor receptor (EGFR) status and those with chronic kidney disease. Demographic and clinical characteristics, as well as urinary OPFR concentrations, were compared based on OPFR detection. Spearman correlation was conducted to explore the relationship between OPFR compounds, while logistic regression was used to identify OPFR compounds associated with EGFR mutation. The study revealed widespread OPFR exposure among lung cancer patients, with an overall detection frequency of 99.07%. Tris(2-butoxyethyl) phosphate (TBEP) exhibited a strong correlation to its metabolite bis(2-butoxyethyl) phosphate (r = 0.88, p < 0.01). Patients with TBEP in their urine had higher percentage of wild-type EGFR and the detection of TBEP was associated with a reduced likelihood of mutant EGFR expression. OPFR exposure was prevalent in lung cancer patients, with TBEP detection identified as a factor with lower EGFR mutation expression. This study contributes to the understanding of OPFR exposure in lung cancer patients and underscores the significance of TBEP in evaluating EGFR mutation in this population.

Polybrominated diphenyl ethers and their alternatives in soil cores from a typical flame-retardant production park: Vertical distribution and potential influencing factors

With the prohibition on the production and use of polybrominated diphenyl ethers (PBDEs), decabromodiphenyl ethane (DBDPE) and organophosphate flame retardants (OPFRs) have emerged as their alternatives. However, the vertical transport and associated influencing factors of these chemicals into soil are not clearly understood. To clarify the vertical distribution of the pollutants and related influencing factors, surface soil and soil core samples were collected at a depth in the range of 0.10–5.00 m in a typical 20-year-old flame-retardant production park and surrounding area. PBDEs and DBDPE show a clear point source distribution around the production park with their central concentrations up to 2.88 × 104 and 8.46 × 104 ng/g, respectively. OPFRs are mainly found in residential areas. The production conversion of PBDEs to DBDPE has obvious environmental characteristics. The vertical distribution revealed that most of the pollutants have penetrated into the soil 5.00 m or even deeper. The median concentrations of deca-BDE and DBDPE reached 50.9 and 9.85 × 103 ng/g, respectively, even at a depth of 5.00 m. Soil organic matter plays a crucial role in determining the vertical distribution, while soil clay particles have a greater impact on the high molecular weight and/or highly brominated compounds.

Organophosphate flame retardants in air from formal e-waste recycling workshops in China: Size-distribution, gas-particle partitioning and exposure assessment

In order to understand the organophosphate flame retardants (OPFRs) pollution and evaluate the inhalation exposure risk in formal e-waste recycling facilities, the air concentrations, particle size distribution and gas-particle partitioning of OPFRs in four typical workshops were investigated. The total Σ15OPFR concentrations inside workshops were in the range of 64.7–682 ng/m3, with 5.80–23.4 ng/m3 in gas phase and 58.8–658 ng/m3 in particle phase. Triphenyl phosphate (TPHP) and tris(2-chloroisopropyl) phosphate (TCIPP) were main analogs, both of which contributed to 49.0–85.7% of total OPFRs. In the waste printed circuit boards thermal treatment workshop, the OPFRs concentration was the highest, and particle-bound OPFRs mainly distributed in 0.7–1.1 μm particles. The proportions of TPHP in different size particles increased as the decrease of particle size, while TCIPP presented an opposite trend. The gas-particle partitioning of OPFR analogs was dominated by absorption process, and did not reach equilibrium state due to continuous emission of OPFRs from the recycling activities. The deposition fluxes of OPFRs in respiratory tract were 65.7–639 ng/h, and the estimated daily intake doses of OPFRs were 8.52–76.9 ng/(kg·day) in four workshops. Inhalation exposure was an important exposure pathway for e-waste recycling workers, and deposition fluxes of size-segregated OPFRs were mainly in head airways region.

The mechanism of interaction between tri-para-cresyl phosphate and human serum protein: A multispectroscopic and in-silico study

Organophosphate flame retardants (OPFRs) pose the significant risks to the environment and human health and have become a serious public health issue. Tricresyl phosphates (TCPs), a group of aryl OPFRs, exhibit neurotoxicity and endocrine disrupting toxicity. However, the binding mechanisms between TCPs and human serum albumin (HSA) remain unknown. In this study, through fluorescence and ultraviolet–visible (UV–vis) absorption spectroscopy, molecular docking and molecular dynamics (MD), tri-para-cresyl phosphate (TpCP) was selected to explore potential interactions between HSA and TCPs. The results of the fluorescence spectroscopy demonstrated that a decrease in the fluorescence intensity of HSA and a blue shift were observed with the increasing concentrations of TpCP. The binding constant (Ka) was 2.575 × 104 L/mol, 4.701 × 104 L/mol, 5.684 × 104 L/mol and 9.482 × 104 L/mol at 293 K, 298 K, 303 K, and 310 K, respectively. The fluorescence process between HSA and TpCP involved a mix of static and dynamic quenching mechanism. The gibbs free energy (ΔG0) of HSA-TpCP system was −24.452 kJ/mol, −25.907 kJ/mol, -27.363 kJ/mol, and - 29.401 kJ/mol at 293 K, 298 K, 303 K, and 310 K, respectively, suggesting that the HSA-TpCP reaction was spontaneous. The enthalpy change (ΔH0) and thermodynamic entropy change (ΔS0) of the HSA-TpCP system were 60.83 kJ/mol and 291.08 J/(mol·>k), respectively, indicating that hydrophobic force was the major driving force in the HSA-TpCP complex. Furthermore, multispectral analysis also revealed that TpCP could alter the microenvironment of tryptophan residue and the secondary structure of HSA and bind with the active site I of HSA. Molecular docking and MD simulations confirmed that TpCP could spontaneously form a stable complex with HSA, which was consistent with the fluorescence experimental results. This study provides novel insights into the mechanisms of underlying the transportation and distribution of OPFRs in humans.

Metabolic activity of gut microbial enrichment cultures from different marine species and their transformation abilities to plastic additives

The role of the gut microbiota in host physiology has been previously elucidated for some marine organisms, but little information is available on their metabolic activity involved in transformation of environmental pollutants. This study assessed the metabolic profiles of the gut microbial cultures from grouper (Epinephelus coioides), green mussel (Perna viridis) and giant tiger prawn (Penaeus monodon) and investigated their transformation mechanisms to typical plastic additives. Community-level physiological profiling analysis confirmed the utilization profiles of the microbial cultures including carbon sources of carbohydrates, amines, carboxylic acids, phenolic compounds, polymers and amino acids, and the plastic additives of organophosphate flame retardants, tetrabromobisphenol A derivates and bisphenols. Using in vitro incubation, triphenyl phosphate (TPHP) was found to be rapidly metabolized into diphenyl phosphate by the gut microbiota as a representative ester-containing plastic additive, whereas the transformation of BPA (a representative phenol) was relatively slower. Interestingly, all three kinds of microbial cultures efficiently transformed the hepatic metabolite of BPA (BPA-G) back to BPA, thereby increasing its bioavailability in the body. The specific enzyme analysis confirmed the ability of the gut microbiota to perform the metabolic reactions. The results of 16S rRNA sequencing and network analysis revealed that the genera Escherichia-Shigella, Citrobacter, and Anaerospora were functional microbes, and their collaboration with fermentative microbes played pivotal roles in the transformation of the plastic additives. The structure-specific transformations by the gut microbiota and their distinct bioavailability deserve more attention in the future.

Fugacity- and biotransformation-based mechanistic insights into the trophic transfer of organophosphate flame retardants in a subtropical coastal food web from the Northern Beibu Gulf of China

The bioaccumulation and trophic transfer of organophosphate flame retardants (OPFRs) in marine ecosystems have attracted great attention in recent research, but our understanding of the trophic transfer mechanisms involved is limited. In this study, we investigated the trophodynamics of OPFRs and their metabolites in a subtropical coastal food web collected from the northern Beibu Gulf, China, and characterized their trophodynamics using fugacity- and biotransformation-based approaches. Eleven OPFRs and all seven metabolites were simultaneously quantified in the shellfish, crustacean, pelagic fish, and benthic fish samples, with total concentrations ranging from 164 to 4.11 × 104 and 4.56–4.28 × 103 ng/g lipid weight, respectively. Significant biomagnification was observed only for tris (phenyl) phosphate (TPHP) and tris (2-ethylhexyl) phosphate (TEHP), while other compounds except for tris(2-chloroethyl) phosphate (TCEP) displayed biomagnification trends based on Monte Carlo simulations. Using a fugacity-based approach to normalize the accumulation of OPFRs in biota to their relative biological phase composition, storage lipid is the predominant biological phase for the mass distribution of 2-ethylhexyl diphenyl phosphate (EHDPHP) and TPHP. The water content and structure protein are equally important for TCEP, whereas lipid and structure protein are the two most important phases for other OPFRs. The mass distribution of these OPFRs along with TLs can explain their trophodynamics in the food web. The organophosphate diesters (as OPFR metabolites) also displayed biomagnification trends based on bootstrapped estimation. The correlation analysis and Korganism-water results jointly suggested the metabolites accumulation in high-TL organisms was related to biotransformation processes. The metabolite-backtracked trophic magnification factors for tri-n‑butyl phosphate (TNBP) and TPHP were both greater than the values that accounted for only the parent compounds. This study highlights the incorporation of fugacity and biotransformation analysis to characterize the trophodynamic processes of OPFRs and other emerging pollutants in food webs.

Urban mangroves at risk: Understanding organophosphate flame retardant pollution at different urban function zones in shenzhen

Organophosphate flame retardants (OPFRs) have become a ubiquitous environmental contaminant due to their extensive usage in various applications such as electronics, electrical equipment, building materials, automobiles, textiles, and cables. It have been detected in water bodies and sediment worldwide, indicating their global presence and potential environmental impact. Mangrove forests in the marine-terrestrial ecotone serve as the primary repository for terrestrial pollutants. However, the distribution of OPFRs and the underlying factors driving their presence are not yet well understood. In this study, three urban mangroves in Shenzhen were selected based on urban functional zoning: Shajing (SJ) mangrove, located in an industrial district; Futian (FT) mangrove and Baguang (BG) mangrove, located in the central business district and ecological preserve, respectively. This study revealed that the total concentrations of the seven OPFRs ranged from 30.0 to 418.3 ng L−1 in surface seawater and from 53.1 to 151.6 ng g−1 dry weight in sediment. Triethyl phosphate-TEP and tributyl phosphate-TnBP were detected in surface seawater from SJ and in all sediment samples. The dominant OPFRs varied between surface seawater (tris(1-chloro-2-propyl) phosphate-TCPP and triphenylphosphine oxide-TPPO) and sediments (TCPP and triphenyl phosphate-TPhP). Further analysis showed transfer of OPFRs was relatively weak in SJ but improved in BG and FT, suggesting varying degrees of contamination and accumulation across the different functional zones. Ecological risk assessment indicated that only TPHP exhibited moderate risk in surface seawater and sediment. This study provides a comprehensive understanding of the spatial distribution (surface seawater and sediment) of OPFRs in urban mangroves characterized by diverse functional zoning. It emphasizes the necessity of reducing OPFRs emissions into the environment and effectively managing OPFRs contamination in urban mangroves.

Nephrotoxicity of organophosphate flame retardants in patients with chronic kidney disease: A 2-year longitudinal study

Humans are extensively exposed to organophosphate flame retardants (OPFRs), an emerging group of organic contaminants with potential nephrotoxicity. Nevertheless, the estimated daily intake (EDI) and prognostic impacts of OPFRs have not been assessed in individuals with chronic kidney disease (CKD). In this 2-year longitudinal study of 169 patients with CKD, we calculated the EDIs of five OPFR triesters from urinary biomonitoring data of their degradation products and analyzed the effects of OPFR exposure on adverse renal outcomes and renal function deterioration. Our analysis demonstrated universal OPFR exposure in the CKD population, with a median EDIΣOPFR of 360.45 ng/kg body weight/day (interquartile range, 198.35–775.94). Additionally, our study revealed that high tris(2-chloroethyl) phosphate (TCEP) exposure independently correlated with composite adverse events and composite renal events (hazard ratio [95 % confidence interval; CI]: 4.616 [1.060–20.096], p = 0.042; 3.053 [1.075–8.674], p = 0.036) and served as an independent predictor for renal function deterioration throughout the study period, with a decline in estimated glomerular filtration rate of 4.127 mL/min/1.73 m2 (95 % CI, −8.127–−0.126; p = 0.043) per log ng/kg body weight/day of EDITCEP. Furthermore, the EDITCEP and EDIΣOPFR were positively associated with elevations in urinary 8-hydroxy-2’-deoxyguanosine and kidney injury molecule-1 during the study period, indicating the roles of oxidative damage and renal tubular injury in the nephrotoxicity of OPFR exposure. To conclude, our findings highlight the widespread OPFR exposure and its possible nephrotoxicity in the CKD population.

EGFR and Hippo signaling pathways are involved in organophosphate esters-induced proliferation and migration of triple-negative breast cancer cells.

The widespread application of organophosphate flame retardants has led to pervasive exposure to organophosphate esters (OPEs), prompting considerable concerns regarding their potential health risk to humans. Despite hints from previous research about OPEs' association with breast cancer, their specific effects and underlying mechanisms of triple-negative breast cancer (TNBC) remain unclear. In this study, we investigated the effects of four representative OPEs on cell proliferation, cell cycle regulation, migration, and the expression of genes and proteins associated with the epidermal growth factor receptor (EGFR) and Hippo signaling pathways in TNBC (MDA-MB-231) cells. Our findings revealed that treatment with 1-25μM triphenyl phosphate (TPHP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) induced TNBC cell proliferation and accelerated cell cycle progression, with upregulation in MYC, CCND1, and BRCA1 mRNA. Moreover, exposure to 1-25μM TPHP, 10-25μM TDCIPP, and 1-10μM tris (2-chloroethyl) phosphate (TCEP) induced MMP2/9 mRNA expression and enhanced migratory capacity, except for 2-ethylhexyl diphenyl phosphate (EHDPP). Mechanistically, four OPEs treatments activated the EGFR-ERK1/2 and EGFR-PI3K/AKT signaling pathways by increasing the transcript of EGFR, ERK1/2, PI3K, and AKT mRNA. OPEs treatment also suppressed the Hippo signaling pathway by inhibiting the expression of MST1 mRNA and phosphorylation of LATS1, leading to the overactivation of YAP1 protein, thereby promoting TNBC cell proliferation and migration. In summary, our study elucidated that activation of the EGFR signaling pathway and suppression of the Hippo signaling pathway contributed to the proliferation, cell cycle dysregulation, and migration of TNBC cells following exposure to OPEs.

Potential Adverse Outcome Pathways of Chlorinated Organophosphate Flame Retardants.

Chlorinated organophosphate flame retardants (Cl-OPFRs) are frequently detected chemicals in the environment and biological samples, yet there is a lack of systematic evaluation regarding the adverse effects and toxicological mechanisms of Cl-OPFRs. This study utilizes the adverse outcome pathway (AOP) framework to assess the health implications and mechanisms of Cl-OPFRs, identifying multi-system toxicity, with a particular emphasis on reproductive issues and the possible toxic mechanisms. These results enhance knowledge of the health hazards linked to Cl-OPFRs, supporting the creation of focused risk evaluations and suitable regulatory actions.

Covalent adduct formation of histone with organophosphorus pesticides in vitro

It is established that organophosphorus pesticide (OPP) toxicity results from modification of amino acids in active sites of target proteins. OPPs can also modify unrelated target proteins such as histones and such covalent histone modifications can alter DNA-binding properties and lead to aberrant gene expression. In the present study, we report on non-enzymatic covalent modifications of calf thymus histones adducted to selected OPPs and organophosphate flame retardants (OPFRs) in vitro using a bottom-up proteomics method approach. Histones were not found to form detectable adducts with the two tested OPFRs but were avidly modified by a few of the seven OPPs that were tested in vitro. Dimethyl phosphate (or diethyl phosphate) adducts were identified on Tyr, Lys and Ser residues. Most of the dialkyl phosphate adducts were identified on Tyr residues. Methyl and ethyl modified histones were also detected. Eleven amino residues in histones showed non-enzymatic covalent methylation by exposure of dichlorvos and malathion. Our bottom-up proteomics approach showing histone-OPP adduct formation warrants future studies on the underlying mechanism of chronic illness from exposure to OPPs.

Distribution, traceability, and risk assessment of organophosphate flame retardants in agricultural soils along the Yangtze River Delta in China.

Severe pollution threatens the ecosystem and human health in the Yangtze River Delta (YRD) in China because of the rapid development of industry in this area. This study examines the types, distribution, concentration, and origin of fourteen typical organophosphate flame retardants (OPFRs) in agricultural soils within the YRD region to offer insights for pollutant control and policy-making. The total concentration of OPFRs (ΣOPFRs) varied between 79.19 and 699.58 μg/kg dry weight (dw), averaging at 209.61 μg/kg dw. Among the OPFRs detected, tributoxyethyl phosphate (TBEP) was identified as the main congener, followed by tri-n-butyl phosphate (TnBP), tris(2-chloroisopropyl) phosphate (TCPP), and trimethyl phosphate (TMP). Source analysis, conducted through correlation coefficients and PCA, indicated that OPFRs in agricultural soils within the YRD region mainly originate from emissions related to plastic products and transportation. The health risk exposure to ΣOPFRs in agricultural soil was considered negligible for farmers, with values below 1.24 × 10-2 and 1.76 × 10-9 for noncarcinogenic and carcinogenic risks, respectively. However, the ecological risk of ΣOPFRs in all the samples ranged from 0.08-1.08, indicating a medium to high risk level. The results offer a comprehensive understanding of OPFR pollution in agricultural soils in the YRD region and can be useful for pollution control that mitigates ecological and health risks in this region.

Global Trends and Hotspots in Research on the Health Risks of Organophosphate Flame Retardants: A Bibliometric and Visual Analysis.

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. 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. 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. 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.