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.

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.

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-n­butyl 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.

GC/MS-Based Metabolomic Analysis of A549 Cells Exposed to Emerging Organophosphate Flame Retardants.

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.

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

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.

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.

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 0.2 µg/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 0.88 µg/L for males and 0.53 µg/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.

Biodegradation pathway and mechanism of tri (2-chloropropyl) phosphate by Providencia rettgeri.

Tri (2-chloropropyl) phosphate (TCPP) was an emerging contaminant of global concern because of its frequent occurrence, potential toxic effects, and persistence in the environment. Microbial degradation might be an efficient and safe removal method, but limited information was available. In this study, Providencia rettgeri was isolated from contaminated sediment and showed it could use TCPP as unique phosphorus source to promote growth, and decompose 34.7% of TCPP (1 mg/L) within 5 days. The microbial inoculation and the initial concentration of TCPP could affect the biodegradation efficient. Further study results indicated that TCPP decomposition by Providencia rettgeri was mainly via phosphoester bond hydrolysis, evidenced by the production of bis (2-chloropropyl) phosphate (C6H13Cl2PO4) and mono-chloropropyl phosphate (C3H8ClPO4). Both intracellular and extracellular enzymes could degrade TCPP, but intracellular degradation was dominant in the later reaction stage, and the presence of Cu2+ ions had a promoting effect. These findings developed novel insights into the potential mechanism of TCPP microbial degradation.

Rapid and Comprehensive Analysis of 41 Harmful Substances in Multi-Matrix Products by Gas Chromatography-Mass Spectrometry Using Matrix-Matching Calibration Strategy.

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.

Personal environmental exposure to plasticizers and organophosphate flame retardants using silicone wristbands and urine: Patterns, comparisons, and correlations.

Plasticizers (PLs) and organophosphate flame retardants (OPFRs) are ubiquitous in the environment due to their widespread use and potential for leaching from consumer products. Environmental exposure is a critical aspect of the human exposome, revealing complex interactions between environmental contaminants and potential health effects. Silicone wristbands (SWBs) have emerged as a novel and non-invasive sampling device for assessing personal external exposure. In this study, SWBs were used as a proxy to estimate personal dermal adsorption (EDdermal) to PLs and OPFRs in Belgian participants for one week; four morning urine samples were also collected and analyzed for estimated daily intake (EDI). The results of the SWBs samples showed that all the participants were exposed to these chemicals, and the exposure was found to be highest for the legacy and alternative plasticizers (LP and AP), followed by the legacy and emerging OPFRs (LOPFR and EOPFR). In urine samples, the highest levels were observed for metabolites of diethyl phthalate (DEP), di-isobutyl phthalate (DiBP) and di-n-butyl phthalate (DnBP) among LPs and di(2-ethylhexyl) terephthalate (DEHT) for APs. Outliers among the participants indicated that there were other sources of exposure that were not identified. Results showed a significant correlation between EDdermal and EDI for DiBP, tris (2-butoxyethyl) phosphate (TBOEP) and triphenyl phosphate (TPhP). These correlations indicated their suitability for predicting exposure via SWB monitoring for total chemical exposure. The results of this pilot study advance our understanding of SWB sampling and its relevance for predicting aggregate environmental chemical exposures, while highlighting the potential of SWBs as low-cost, non-invasive personal samplers for future research. This innovative approach has the potential to advance the assessment of environmental exposures and their impact on public health.

Organophosphate esters in water and air: A minireview of their sources, occurrence, and air-water exchange.

Organophosphate esters (OPEs) have received considerable attention in environmental research due to their extensive production, wide-ranging applications, prevalent presence, potential for bioaccumulation, and associated ecological and health concerns. Low efficiency of OPE removal results in the effluents of wastewater treatment plants emerging as a significant contributor to OPE contamination. Their notable solubility and mobility give OPEs the potential to be transported to coastal ecosystems via river discharge and atmospheric deposition. Previous research has indicated that OPEs have been widely detected in the atmosphere and water bodies. Atmospheric deposition across air-water exchange is the main input route for OPEs into the environment and ecosystems. The main processes that contribute to air-water exchange is air-water diffusion, dry deposition, wet deposition, and the air-water volatilization process. The present minireview links together the source, occurrence, and exchange of OPEs in water and air, integrates the occurrence and profile data, and summarizes their air-water exchange in the environment.

Global responses to tris(1-chloro-2-propyl) phosphate and tris(2-butoxyethyl) phosphate in Escherichia coli: Evidences from biomarkers, and metabolic disturbance using GC-MS and LC-MS metabolomics analyses.

Tris(1-chloro-2-propyl) phosphate (TCPP) and tris(2-butoxyethyl) phosphate (TBEP) as pollutants of emerging concern have aroused the rising attention due to their potential risks on aquatic ecosystem and public health. Nevertheless, there is a lack of toxicological mechanisms exploration of TCPP and TBEP at molecular levels. Herein, the toxicity effects and molecular mechanism of them were fully researched and summarized on Escherichia coli (E.coli). Acute exposure to them significantly activated antioxidant defense system and caused lipid peroxidation, as proved by the changes of antioxidant enzymes and MDA. The ROS overload resulted in the drop of membrane potential as well as the downregulated synthesis of ATPase, endorsing that E. coli cytotoxicity was ascribed to oxidative stress damage induced by TCPP and TBEP. The combination of GC-MS and LC-MS based metabolomics validated that TCPP and TBEP induced metabolic reprogramming in E.coli. More specifically, the responsive metabolites in carbohydrate metabolism, lipids metabolism, nucleotide metabolism, amino acid metabolism, and organic acids metabolism were significantly disturbed by TCPP and TBEP, confirming the negative effects on metabolic functions and key bioprocesses. Additionally, several biomarkers including PE(16:1(5Z)/15:0), PA(17:1(9Z)/18:2(9Z,12Z)), PE(19:1(9Z)/0:0), and LysoPE(0:0/18:1(11Z)) were remarkably upregulated, verifying that the protection of cellular membrane was conducted by regulating the expression of lipids-associated metabolites. Collectively, this work sheds new light on the potential molecular toxicity mechanism of TCPP and TBEP on aquatic organisms, and these findings using GC-MS and LC-MS metabolomics generate a fresh insight into assessing the effects of OPFRs on target and non-target aquatic organisms.

Prenatal exposure to a mixture of organophosphate flame retardants and infant neurodevelopment: A prospective cohort study in Shandong, China.

BACKGROUND: Previous studies have suggested that prenatal exposure to organophosphate flame retardants (OPFRs) may have adverse effect on early neurodevelopment, but limited data are available in China, and the overall effects of OPFRs mixture are still unclear. OBJECTIVE: This study aimed to investigate the association between prenatal exposure to OPFR metabolites mixture and the neurodevelopment of 1-year-old infants. METHODS: A total of 270 mother-infant pairs were recruited from the Laizhou Wan (Bay) Birth Cohort in China. Ten OPFR metabolites were measured in maternal urine. Neurodevelopment of 1-year-old infants was assessed using the Gesell Developmental Schedules (GDS) and presented by the developmental quotient (DQ) score. Multivariate linear regression and weighted quantile sum (WQS) regression models were conducted to estimate the association of prenatal exposure to seven individual OPFR metabolites and their mixture with infant neurodevelopment. RESULTS: The positive rates of seven OPFR metabolites in the urine of pregnant women were greater than 70% with the median concentration ranged within 0.13-3.53 µg/g creatinine. The multivariate linear regression model showed significant negative associations between bis (1-chloro-2-propyl) phosphate (BCIPP), din-butyl phosphate (DnBP), and total OPFR metabolites exposure and neurodevelopment in all infants. Results from the WQS model consistently revealed that the OPFR metabolites mixture was inversely associated with infant neurodevelopment. Each quartile increased in the seven OPFR metabolites mixture was associated with a 1.59 decrease (95% CI: 2.96, -0.21) in gross motor DQ scores, a 1.41 decrease (95% CI: 2.38, -0.43) in adaptive DQ scores, and a 1.08 decrease (95% CI: 2.15, -0.02) in social DQ scores, among which BCIPP, bis (1, 3-dichloro-2-propyl) phosphate (BDCIPP) and DnBP were the main contributors. CONCLUSION: Prenatal exposure to a mixture of OPFRs was negatively associated with early infant neurodevelopment, particularly in gross motor, adaptive, and social domains.

Association between organophosphate flame retardant exposure and lipid metabolism: data from the 2013-2014 National Health and Nutrition Examination Survey.

Organophosphate flame retardants (OPFRs) are emerging environmental pollutants that can be detected in water, dust, and biological organisms. Certain OPFRs can disrupt lipid metabolism in animal models and cell lines. However, the effects of OPFRs on human lipid metabolism remain unclear. We included 1,580 participants (≥20 years) from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to explore the relationship between OPFR exposure and lipid metabolism biomarkers. After adjusting for confounding factors, results showed that one-unit increases in the log levels of diphenyl phosphate (DPhP) (regression coefficient = -5.755; S.E. = 2.289; p = 0.023) and log bis-(1-chloro-2-propyl) phosphate (BCPP) (regression coefficient = -4.637; S.E. = 2.019; p = 0.036) were negatively associated with the levels of total cholesterol (TC) in all participants. One-unit increases in the levels of DPhP (regression coefficient = -2.292; S.E. = 0.802; p = 0.012), log bis (1,3-dichloro-2-propyl) phosphate (BDCPP) (regression coefficient = -2.046; S.E. = 0.825; p = 0.026), and log bis-2-chloroethyl phosphate (BCEP) (regression coefficient = -2.604; S.E. = 0.704; p = 0.002) were negatively associated with the levels of high-density lipoprotein cholesterol (HDL-C). With increasing quartiles of urine BDCPP levels, the mean TC levels significantly decreased in all participants (p value for trend = 0.028), and quartile increases in the levels of DPhP (p value for trend = 0.01), BDCPP (p value for trend = 0.001), and BCEP (p value for trend<0.001) were negatively corelated with HDL-C, with approximately 5.9, 9.9, and 12.5% differences between the upper and lower quartiles. In conclusion, DPhP, BDCPP, and BCEP were negatively related to HDL-C concentration, whereas DPhP and BCPP levels were negatively associated with TC level. Thus, exposure to OPFRs may interfere with lipid metabolism.

Trimester-specific effect of maternal co-exposure to organophosphate esters and phthalates on preschooler cognitive development: The moderating role of gestational vitamin D status.

Organophosphate esters (OPEs) and phthalate acid esters (PAEs) are prevalent endocrine-disrupting chemicals (EDCs). Humans are often exposed to OPEs and PAEs simultaneously through multiple routes. Given that fetal stage is a critical period for neurodevelopment, it is necessary to know whether gestational co-exposure to OPEs and PAEs affects fetal neurodevelopment. However, accessible epidemiological studies are limited. The present study included 2, 120 pregnant women from the Ma'anshan Birth Cohort (MABC) study. The concentrations of tris (2-chloroethyl) phosphate (TCEP), 6 OPE metabolites and 7 PAE metabolites were measured in the first, second and third trimester using ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS). Cognitive development of preschooler was assessed based on the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) of the Chinese version. Generalized estimating equations (GEEs), restricted cubic spline (RCS) and generalized additive models (GAMs) were employed to explore the associations between individual OPE exposure and preschooler cognitive development. The quantile-based g-computation (QGC) method was used to estimate the joint effect of PAEs and OPEs exposure on cognitive development. GEEs revealed significant adverse associations between diphenyl phosphate (DPHP) (ß: -0.58, 95% CI: -1.14, -0.01), bis (2-butoxyethyl) phosphate(BBOEP) (ß: -0.44, 95% CI: -0.85, -0.02), bis(1-chloro-2-propyl) phosphate (BCIPP) (ß: -0.81, 95%CI: -1.43, -0.20) and full-scale intelligence quotient (FSIQ) in the first trimester; additionally, TCEP and bis(2-ethylhexyl) phosphate (BEHP) in the second trimester, as well as DPHP in the third trimester, were negatively associated with cognitive development. Through the QGC analyses, mixture exposure in the first trimester was negatively associated with FSIQ scores (ß: -1.70, 95% CI: -3.06, -0.34), mono-butyl phthalate (MBP), BCIPP, and DPHP might be the dominant contributors after controlling for other OPEs and PAEs congeners. Additionally, the effect of OPEs and PAEs mixture on cognitive development might be driven by vitamin D deficiency.

Bioactivity assessment of organophosphate flame retardants via a dose-dependent yeast functional genomics approach.

Organophosphate flame retardants (OPFRs) have been widely detected in multiple environment media and have many adverse effects with complex toxicity mechanisms. However, the early molecular responses to OPFRs have not been fully elucidated, thereby making it difficult to assess their risks accurately. In this work, we systematically explored the point of departure (POD) of biological pathways at genome-wide level perturbed by 14 OPFRs with three substituents (alkyl, halogen, and aryl) using a dose-dependent functional genomics approach in Saccharomyces cerevisiae at 24 h exposure. Firstly, our results demonstrated that the overall biological potency at gene level (PODDRG20) ranged from 0.013 to 35.079 µM for 14 OPFRs, especially the tributyl phosphate (TnBP) exhibited the strongest biological potency with the least PODDRG20. Secondly, we found that structural characteristics of carbon number and logKow were significantly negatively correlated with POD, and carbon number and logKow also significantly affected lipid metabolism associated processes. Thirdly, these early biological pathways of OPFRs toxification were found to be involved in lipid metabolism, oxidative stress, DNA damage, MAPK signaling pathway, and amino acid and carbohydrate metabolism, among which the lipid metabolism was the most sensitive molecular response perturbed by most OPFRs. More importantly, we identified one resistant mutant strain with knockout of ERG2 (YMR202W) gene participated in steroid biosynthesis pathway, which can serve as a key yeast strain of OPFRs toxification. Overall, our study demonstrated an effective platform for accurately assessing OPFRs risks and provided a basis for further green OPFRs development.

Identification, semi-quantification and risk assessment of contaminants of emerging concern in Flemish indoor dust through high-resolution mass spectrometry.

Indoor dust can contribute substantially to human exposure to known and contaminants of emerging concern (CECs). Novel compounds with high structural variability and different homologues are frequently discovered through screening of the indoor environment, implying that constant monitoring is required. The present study aimed at the identification and semi-quantification of CECs in 46 indoor dust samples collected in Belgium by liquid chromatography high-resolution mass spectrometry. Samples were analyzed applying a targeted and suspect screening approach; the latter based on a suspect list containing >4000 CECs. This allowed the detection of a total of 55 CECs, 34 and 21 of which were identified with confidence level (CL) 1/2 or CL 3, respectively. Besides numerous known contaminants such as di(2-ethylhexyl) phthalate (DEHP), di(2-ethylhexyl) adipate (DEHA) or tris(2-butoxyethyl) phosphate (TBOEP) which were reported with detection frequencies (DFs) > 90%, several novel CECs were annotated. These included phthalates with differing side chains, such as decyl nonyl and decyl undecyl phthalate detected with DFs >80% and identified through the observation of characteristic neutral losses. Additionally, two novel organophosphate flame retardants not previously described in indoor dust, i.e. didecyl butoxyethoxyethyl phosphate (DDeBEEP) and bis(butoxyethyl) butyl phosphate (BBEBP), were identified. The implementation of a dedicated workflow provided semi-quantitative concentrations for a set of suspects. Such data obtained for novel phthalates were in the same order of magnitude as the concentrations observed for legacy phthalates indicating their high relevance for human exposure. From the semi-quantitative data, estimated daily intakes and resulting hazard quotients (HQs) were calculated to estimate the exposure and potential health effects. Neither of the obtained HQ values exceeded the risk threshold, indicating no expected adverse health effects.

Chronic exposure to tris (2-chloroethyl) phosphate (TCEP) induces brain structural and functional changes in zebrafish (Danio rerio): A comparative study on the environmental and LC50 concentrations of TCEP.

Tris (2-chloroethyl) phosphate (TCEP) is a crucial organophosphorus flame retardant widely used in many industrial and commercial products. Available reports reported that TCEP could cause various toxicological effects on organisms, including humans. Unfortunately, toxicity data for TCEP (particularly on neurotoxicity) on aquatic organisms are lacking. In the present study, Danio rerio were exposed to different concentrations of TCEP for 42 days (chronic exposure), and oxidative stress, neurotoxicity, sodium, potassium-adenosine triphosphatase (Na+, K+-ATPase) activity, and histopathological changes were evaluated in the brain. The results showed that TCEP (100 and 1500 µg L-1) induced oxidative stress and significantly decreased the activities of antioxidant enzymes (SOD, CAT and GR) in the brain tissue of zebrafish. In contrast, the lipid peroxidation (LPO) level was increased compared to the control group. Exposure to TCEP inhibited the acetylcholinesterase (AChE) and Na+,K+-ATPase activities in the brain tissue. Brain histopathology after 42 days of exposure to TCEP showed cytoplasmic vacuolation, inflammatory cell infiltration, degenerated neurons, degenerated purkinje cells and binucleate. Furthermore, TCEP exposure leads to significant changes in dopamine and 5-HT levels in the brain of zebrafish. The data in the present study suggest that high concentrations of TCEP might affect the fish by altering oxidative balance and inducing marked pathological changes in the brain of zebrafish. These findings indicate that chronic exposure to TCEP may cause a neurotoxic effect in zebrafish.

Investigation of alkyl, aryl, and chlorinated OPFRs in sediments from estuarine systems: Seasonal variation, spatial distribution and ecological risks assessment.

Estuaries in South Africa are very important for biodiversity conservation and serve as focal points for leisure and tourism activities. The organophosphate flame retardants (OPFRs) levels in these aquatic systems haven't been documented in any studies as of yet. Due to the negative effects of persistent organic pollutants in South African estuaries, we examined the occurrence of eight OPFRs in sediments of two estuaries by studying their spatiotemporal distribution, season variation, and ecological risks. The Sundays Estuary (SDE), a semi-urbanized agricultural surrounding system, recorded an ∑8OPFR concentration in sediments that ranged from 0.71 to 22.5 ng/g dw, whereas Swartkops Estuary, a largely urbanized system, recorded a concentration that ranged from 0.61 to 119 ng/g dw. Alkyl-OPFRs were the prevalent homologue in both estuaries compared to the chlorinated and aryl groups. While TBP, TCPP, and TCrP were the most abundant compounds among the homologue groups. There was no distinct seasonal trend of ∑8OPFR concentration in either estuary, with summer and autumn seasons recording the highest concentrations in SDE and SWE, respectively. Ecological risks in the majority of the study sites for the detected compounds were at low (RQ < 0.1) and medium levels (0.1 ≤ RQ < 1) for certain species of fish, Daphnia magna and algae. However, the cumulative RQs for all the compounds had ∑RQs ≥1 for most sites in both estuaries, indicating that these organisms, if present in both estuaries, may be exposed to potential ecological concerns due to accumulated OPFR chemicals. The scope of future studies should be broadened to include research areas that are not only focus on the bioaccumulation patterns of these compounds but also find sustainable ways to reduce them from these estuarine environments.