Species-specific metabolism of triphenyl phosphate and its mono-hydroxylated product by human and rat CYP2E1 and the carp ortholog.

Organophosphorus flame retardants (PFRs) are a class of flame retardants and environmental pollutants with various biological effects. Recentstudies have evidenced activation of some PFRs by human CYP enzymes (including CYP2E1) for genotoxic effects. However, the activity of CYPs in fish species toward PFR metabolism remains unclear. This study was aimed on comparing the metabolism of triphenyl phosphate (TPHP) and 4-OH-TPHP in human, rat, and common carp, and the involvement of human CYP2E1 and its orthologs in the metabolism, by using fomepizole (4-MP, CYP2E1 inhibitor) as a modulator, in silico molecular docking and dynamics analyses. The rate of TPHP metabolism was apparently faster with human and rat, microsomes than with fish microsomes, the major metabolites were phosphodiester and hydroxylated phosphate, with 30-80 % of TPHP forming unidentified metabolites in the system of each species. 4-OH-TPHP was readily metabolized by both human and rat microsomes, whereas it was hardly metabolized in carp assays. Meanwhile, with 4-MP the transformation of TPHP to 4-OH-TPHP was enhanced in the human/rat systems while suppressed in the carp system. Moreover, the formation of unidentified metabolites in human and rat systems was mostly inhibited by 4-MP. Through molecular dynamics analysis TPHP and its primary metabolites showed high affinity for human and rat CYP2E1, as well as the carp ortholog (CYP2G1-like enzyme), however, the 4-OH-TPHP bond to the latter was too far from the heme to permit a biochemical reaction. This study suggests that the metabolism/activation of TPHP might be favored in mammals rather than carp, a fish species.

Fragmentation Pathway of Organophosphorus Flame Retardants by Liquid Chromatography-Orbitrap-Based High-Resolution Mass Spectrometry.

Organophosphorus flame retardants (OPFRs) have been widely used in polymeric materials owing to their flame retardant and plasticizing effects. Investigating the fragmentation pathway of OPFRs is of great necessity for further discovering and identifying novel pollutants using orbitrap-based high-resolution mass spectrometry (HRMS). A total of 25 OPFRs, including alkyl, halogenated, and aromatic types, were analyzed in this study. The fragmentation pathways of the OPFRs were investigated using orbitrap-based HRMS with high-energy collision dissociation (HCD) in positive mode. The major fragmentation pathways for the three types of OPFRs are greatly affected by the substituents. In detail, the alkyl and halogenated OPFRs underwent three McLafferty hydrogen rearrangements, wherein the substituents were gradually cleaved to form the structurally stable [H4PO4]+ (m/z = 98.9845) ions. In contrast, the aromatic OPFRs would cleave not only the C-O bond but also the P-O bond, depending on the substituents, to form fragment ions such as [C6H7O]+ (m/z = 95.0495) or [C7H7]+ (m/z = 91.0530), among others. Using HRMS improved the accuracy of fragment ion identification, and the pathway became more evident. These fragmentation laws can provide identification information in pollutant screening work and theoretical references for the structural characterization of compounds with diverse substituent structures.

Computational Insight into Biotransformation Profiles of Organophosphorus Flame Retardants to Their Diester Metabolites by Cytochrome P450.

Biotransformation of organophosphorus flame retardants (OPFRs) mediated by cytochrome P450 enzymes (CYPs) has a potential correlation with their toxicological effects on humans. In this work, we employed five typical OPFRs including tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), tris(1-chloro-2-propyl) phosphate (TCIPP), tri(2-chloroethyl) phosphate (TCEP), triethyl phosphate (TEP), and 2-ethylhexyl diphenyl phosphate (EHDPHP), and performed density functional theory (DFT) calculations to clarify the CYP-catalyzed biotransformation of five OPFRs to their diester metabolites. The DFT results show that the reaction mechanism consists of Cα-hydroxylation and O-dealkylation steps, and the biotransformation activities of five OPFRs may follow the order of TCEP ≈ TEP ≈ EHDPHP > TCIPP > TDCIPP. We further performed molecular dynamics (MD) simulations to unravel the binding interactions of five OPFRs in the CYP3A4 isoform. Binding mode analyses demonstrate that CYP3A4-mediated metabolism of TDCIPP, TCIPP, TCEP, and TEP can produce the diester metabolites, while EHDPHP metabolism may generate para-hydroxyEHDPHP as the primary metabolite. Moreover, the EHDPHP and TDCIPP have higher binding potential to CYP3A4 than TCIPP, TCEP, and TEP. This work reports the biotransformation profiles and binding features of five OPFRs in CYP, which can provide meaningful clues for the further studies of the metabolic fates of OPFRs and toxicological effects associated with the relevant metabolites.

Impact of dietary exposure to low-dose tris(1,3-dichloro-2-propyl)phosphate in allergic asthmatic mice.

OBJECTIVE: Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) is an organophosphorus flame retardant that is an alternative to brominated flame retardants. Although TDCIPP can adversely affect human health, information about its effects on immune and allergic responses is scarce. We aimed to investigate the effects of dietary exposure to TDCIPP using less than the human tolerable daily intake (TDI) in allergic asthmatic mice. METHODS: Male C3H/HeJSlc mice were fed a chow diet containing TDCIPP equivalent to 0.02 µg/kg/day (low; L), 0.2 µg/kg/day (medium; M), or 2 µg/kg/day (high; H) and were intratracheally administered ovalbumin (OVA, 1 µg/animal) every 2 weeks from 5 to 11 weeks of age. RESULTS: In OVA-treated mice, TDCIPP-H exposure tended to enhance pulmonary inflammation compared with vehicle exposure. TDCIPP dose-dependently decreased mRNA level of G protein-coupled estrogen receptor (GPER) in the lungs with or without OVA. OVA + TDCIPP-H treatment tended to increase the total cell number and promoted CD4+ cell activation compared with OVA alone treatment in mediastinal lymph nodes. In splenocytes, an increase in the fraction of Breg cells, but not of total B and T cells, and an increase in IL-5 in cell culture supernatants following OVA re-stimulation in OVA + TDCIPP-H-treated mice was observed compared with OVA-alone-treated mice. Moreover, OVA + TDCIPP-H exposure decreased Gr-1 expression in bone marrow (BM) cells. DISCUSSION: These results suggested that dietary exposure to TDCIPP at TDI level slightly enhances allergic diseases, such as allergic asthma, via GPER regulation at inflamed sites and secondary lymphoid tissue and BM cell alternations.

[Fate of Organophosphorus Flame Retardants in Polished Rice during the Cooking Process].

The fate of organophosphorus flame retardants (PFRs) in polished rice during the cooking process was examined. After adding PFRs to polished rice (500 ng/g), the rice was washed with water and cooked in a rice cooker. Among the seven kinds of PFRs, approximately 68-86% of the PFRs residues were removed after washing with water three times. In the first washing with water, approximately 50-70% of the PFRs residues were removed from rice. By the subsequent heating in an electric rice cooker or in a microwave rice cooker, the removal rates of PFRs in the cooked rice were 74-94 and 78-96%, respectively. The removal rates in musenmai (500 ng/g) which need not to wash before cooking were lower than those in the washed rice. In the cooked musenmai, 10-50% of the PFRs residues were removed after heating in the electric rice cooker, and 10-70% were removed in the microwave rice cooker. The washing process is effective to reduce the intake of PFRs from rice.

[Adsorption of Airbone Organophosphorus Flame Retardants on Polished Rice Stored in a House].

In order to clarify the actual situation of indoor pollution to polished rice with organophosphorus flame retardants (PFRs) which are ubiquitous in the indoor environment, the pollution of PFRs to polished rice stored in a house for a week was investigated. The survey covered 64 ordinary families in the Osaka region. We analyzed six typical PFRs in 37 rice samples in 2015, and ten typical PFRs in 27 rice samples in 2016. Polished rice was homogenized with acetone-hexane and defatted by hexane-acetonitrile partition. Quantitative analysis for PFRs was performed by GC-FPD. The detection frequency of PFRs in the rice samples was 35/37 in 2015 and 27/27 in 2016. The highest values were 160 ng/g for TCEP, 500 ng/g for TCIPP and 430 ng/g for TBEP. The concentration ratio of each detected PFR in the polished rice samples was different in each house. In the analysis of 16 polished rice samples which were stored in the home, PFRs were detected in ten samples regardless of the storage methods. PFRs were detected from 12 out of 16 commercial brown rice samples. This result suggested that they were polluted during distribution and storage process of them.

Diisodecyl phenyl phosphate promotes foam cell formation by antagonizing Liver X receptor alpha.

While the cardiovascular system is a primary target of organophosphorus flame retardants (OPFRs), particularly aryl-OPFRs, it is still exclusive whether the diisodecyl phenyl phosphate (DIDPP), widely used and broadly present in the environment at high concentrations, elicits atherosclerosis effects. Liver X receptors (LXRs) play a direct role in regulating the formation of atherosclerotic lesions. This study was the first to demonstrate that DIDPP acts as an LXRα ligand and functions as an LXRα antagonist with a half-maximal inhibitory concentration of 16.2 µM. We showed that treatment of an in vitro macrophage model with 1 to 10 µM of DIDPP resulted in the downregulation of direct targets of LXRα, namely ABCA1, ABCG1 and SR-B1, thereby leading to a 7.9-13.2 % reduction in cholesterol efflux. This caused dose-dependent, 24.1-43.1 % increases in the staining intensity of foam cells in the macrophage model. This atherosclerotic effect of DIDPP was proposed to be due to its antagonism of LXRα activity, as DIDPP treatment did not alter cholesterol influx. In conclusion, the findings of this study demonstrate that exposure to DIDPP may be a risk factor for atherosclerosis due to the LXRα-antagonistic activity of DIDPP and its ubiquity in the environment.

Uptake mechanism, translocation, and transformation of organophosphate esters in water hyacinth (Eichhornia crassipes): A hydroponic study.

Owing to their dominant wastewater origin, bioavailability, and toxicity, the occurrence and behavior of organophosphate esters (OPEs) in aquatic systems have attracted considerable attention over the past two decades. Aquatic plants can accumulate and metabolize OPEs in water, thereby playing an important role in their behavior and fate in waterbodies. However, their uptake, translocation and transformation mechanisms in plants remain incompletely characterized. We investigated the accumulation and transformation of OPEs in water hyacinth (Eichhornia crassipes) through a series of hydroponic experiments using three representative OPEs, tris(2-chloroethyl) phosphate (TCEP), tris(2-butoxyethyl) phosphate (TBEP), and triphenyl phosphate (TPP). These OPEs can not only be adsorbed onto and enter plant roots via passive diffusion pathways, which are facilitated by anion channels and/or aquaporins, but also can return to the solution when concentration gradients exist. After entry, hydrophilic TCEP showed a dominant distribution in the cell sap, strong acropetal transportability, and rapid translocation rate, whereas hydrophobic TPP was mostly retained in the root cell wall and therefore demonstrated weak acropetal transportability; TBEP with moderate hydrophilicity remained in the middle. All these OPEs can be transformed into diesters, which presented higher proportions in the cell sap and therefore have stronger acropetal transferability than their parent OPEs. TCEP exhibits the lowest biodegradability, followed by TPP and TBEP. These OPEs exerted apparent effects on plant growth, photosynthesis, and the diversity and composition of the rhizosphere microbial community.

The neurotoxicity of organophosphorus flame retardant tris (1,3-dichloro-2-propyl) phosphate (TDCPP): Main effects and its underlying mechanisms.

As a major alternative to the brominated flame retardants, the production and use of organophosphorus flame retardants (OPFRs) are increasing. And tris (1,3-dichloro-2-propyl) phosphate (TDCPP), one of the most widely used OPFRs, is now commonly found in a variety of products, such as building materials, furniture, bedding, electronic equipment, and baby products. TDCPP does not readily degrade in the water and tends to accumulate continuously in the environment. It has been detected in indoor dust, air, water, soil, and human samples. Considered as an emerging environmental pollutant, increasing studies have demonstrated its adverse effects on environmental organisms and human beings, with the nerve system identified as a sensitive target organ. This paper systematically summarized the progress of TDCPP application and its current exposure in the environment, with a focus on its neurotoxicity. In particular, we highlighted that TDCPP can be neurotoxic (including neurodevelopmentally toxic) to humans and animals, primarily through oxidative stress, neuroinflammation, mitochondrial damage, and epigenetic regulation. Additionally, this paper provided an outlook for further studies on neurotoxicity of TDCPP, as well as offered scientific evidence and clues for rational application of TDCPP in daily life and the prevention and control of its environmental impact in the future.

Elucidating the reproductive toxicity mechanisms in female zebrafish: A transcriptomic study of lifetime tris(2-chloroethyl) phosphate exposure.

Tris(2-chloroethyl) phosphate (TCEP), emerging as a predominant substitute for brominated flame retardants (BFRs), is now increasingly recognized as a prevalent contaminant in aquatic ecosystems. The extent of its reproductive toxicity in aquatic species, particularly in zebrafish (Danio rerio), remains insufficiently characterized. This study subjected zebrafish embryos to various concentrations of TCEP (0, 0.8, 4, 20, and 100 µg/L) over a period of 120 days, extending through sexual maturation, to assess its impact on female reproductive health. Notable reductions in body weight (0.59- and 0.76-fold) and length (0.71- and 0.77-fold) were observed at concentrations of 20 and 100 µg/L, with a concomitant decrease by 0.21- to 0.61-fold in the gonadal somatic index across all treatment groups. The reproductive output, as evidenced by egg production and hatchability, was adversely affected. Histopathological analysis suggested that TCEP exposure impedes ovarian development. Endocrine alterations were also evident, with testosterone and 11-ketotestosterone levels significantly diminished by 0.38- and 0.08-fold at the highest concentration tested, while 17ß-estradiol was elevated by 0.09- to 0.14-fold in all exposed groups. Transcriptomic profiling illuminated numerous differentially expressed genes (DEGs) integral to reproductive processes, including hormone regulation, neuroactive ligand-receptor interactions, oocyte meiosis, and progesterone-mediated maturation pathways. Collectively, these findings indicate that lifelong exposure to TCEP disrupts ovarian development and maturation in female zebrafish, alters gene expression within the hypothalamic-pituitary-gonadal axis, and perturbs sex hormone synthesis, culminating in pronounced reproductive toxicity.

Tributyl phosphate can inhibit the feeding behavior of rotifers by altering the axoneme structure, neuronal coordination and energy supply required for motile cilia.

Organophosphorus flame retardants (OPFRs) are frequently detected in aquatic environments and can potentially amplify the food chain, posing a potential risk to organisms. Marine invertebrates have primitive nervous systems to regulate behavior, but how they respond to OPFRs that are potentially neurotoxic substances is unclear. This study assessed changes in the feeding behavior of rotifer Brachionus plicatilis exposed to alkyl OPFRs tributyl phosphate (TnBP) (0.376 nM, 3.76 and 22.53 µM) to elucidate the mechanism of behavioral toxicity. TnBP at 22.53 µM reduced the ingestion and filtration rates of rotifers for Chlorella vulgaris and Phaeocystis globosa in a 24-h test and altered rotifer-P. globosa population dynamics in 15-d coculture. Ciliary beat frequency was also reduced, and the expression of genes encoding the cilia axoneme was downregulated. TnBP could inhibit rotifer acetylcholinesterase activity by binding this protein and reduce the expression of the exocytotic membrane protein syntaxin-4, suggesting a disorder in nervous regulation of cilia beat. Moreover, TnBP induced abnormal shape and dysfunction of mitochondria, which caused insufficient energy required for ciliary movement. This study revealed diverse neurotoxicity mechanisms of TnBP, particularly as a potentially competing acetylcholinesterase ligand for aquatic invertebrates. Our research also provides a meaningful reference for OPFR-induced behavioral toxicity assessments.

Neurotoxicity of an emerging organophosphorus flame retardant, resorcinol bis(diphenyl phosphate), in zebrafish larvae.

Resorcinol bis(diphenyl phosphate) (RDP), an emerging organophosphorus flame retardant and alternative to triphenyl phosphate (TPHP), is a widespread environmental pollutant. The neurotoxicity of RDP has attracted much attention, as RDP exhibits a similar structure to TPHP, a neurotoxin. In this study, the neurotoxicity of RDP was investigated by using a zebrafish (Danio rerio) model. Zebrafish embryos were exposed to RDP (0, 0.3, 3, 90, 300 and 900 nM) from 2 to 144 h postfertilization. After this exposure, the decreased heart rates and body lengths and the increased malformation rates were observed. RDP exposure significantly reduced the locomotor behavior under light-dark transition stimulation and the flash stimulus response of larvae. Molecular docking results showed that RDP could bind to the active site of zebrafish AChE and that RDP and AChE exhibit potent binding affinity. RDP exposure also significantly inhibited AChE activity in larvae. The content of neurotransmitters (γ-aminobutyric, glutamate, acetylcholine, choline and epinephrine) was altered after RDP exposure. Key genes (α1-tubulin, mbp, syn2a, gfap, shhα, manf, neurogenin, gap-43 and ache) as well as proteins (α1-tubulin and syn2a) related to the development of the central nervous system (CNS) were downregulated. Taken together, our results showed that RDP can affect different parameters related to CNS development, eventually leading to neurotoxicity. This study indicated that more attention should be paid to the toxicity and environmental risk of emerging organophosphorus flame retardants.

Uptake, accumulation, and translocation of organophosphate esters and brominated flame retardants in water hyacinth (Eichhornia crassipes): A field study.

Mechanisms underlying the plant uptake, accumulation, and translocation of organophosphate esters (OPEs) and brominated flame retardants (BFRs) in field environments remain ambiguous. To better understand these processes, we selected a typically polluted river with steady flow and rampant water hyacinth (Eichhornia crassipes) and investigated 25 OPEs and 23 BFRs in 24 sets of matched water-plant samples. Both OPEs and BFRs showed high or ultra-high levels in field water hyacinths, statistically positive water-plant/root concentration correlations, and dominant distributions in the roots. Passive root uptake was the dominant route for OPEs and BFRs to enter the water hyacinth. Both OPEs and BFRs in water hyacinth exhibited acropetal translocation from the root and possible basipetal translocation from the leaf. The accumulation and translocation of OPEs in water hyacinth were significantly affected by their substituents and structures, including the chlorination degree, alkyl chain length, side chain, and methylation degree of aryl-substituted OPEs. The translocation of BFRs in water hyacinth also showed close association with their bromination degree, but their accumulation in roots showed anomaly, indicating possible transformations. Overall, the enrichment and behavior of OPEs and BFRs in water hyacinth seemed to be mainly controlled by physicochemical parameters. OPE/BFR concentrations in total suspended particulate (TSP), TSP-associated organic carbon content, TSP concentration, and plant biomass all showed significant effects on their root accumulation and translocations in water hyacinth. This study provides rare field evidences and novel insights into the basipetal translocation of OPEs and BFRs in plants.

Organophosphorus Reinforced Poly(vinyl alcohol) Nanocomposites Doped with Silver-Loaded Zeolite L Nanoparticles as Sustainable Materials for Packaging Applications.

The sustainable development of innovative eco-friendly multifunctional nanocomposites, possessing superior characteristics, is a noteworthy topic. Novel semi-interpenetrated nanocomposite films based on poly(vinyl alcohol) covalently and thermally crosslinked with oxalic acid (OA), reinforced with a novel organophosphorus flame retardant (PFR-4) derived from co-polycondensation in solution reaction of equimolar amounts of co-monomers, namely, bis((6-oxido-6H-dibenz[c,e][1,2]oxaphosphorinyl)-(4-hydroxyaniline)-methylene)-1,4-phenylene, bisphenol S, and phenylphosphonic dichloride, in a molar ratio of 1:1:2, and additionally doped with silver-loaded zeolite L nanoparticles (ze-Ag), have been prepared by casting from solution technique. The morphology of the as prepared PVA-oxalic acid films and their semi-interpenetrated nanocomposites with PFR-4 and ze-Ag was investigated by scanning electron microscopy (SEM), while the homogeneous distribution of the organophosphorus compound and nanoparticles within the nanocomposite films has been introspected by means of energy dispersive X-ray spectroscopy (EDX). It was established that composites with a very low phosphorus content had noticeably improved flame retardancy. The peak of the heat release rate was reduced up to 55%, depending on the content of the flame-retardant additive and the doping ze-Ag nanoparticles introduced into the PVA/OA matrix. The ultimate tensile strength and elastic modulus increased significantly in the reinforced nanocomposites. Considerably increased antimicrobial activity was revealed in the case of the samples containing silver-loaded zeolite L nanoparticles.

Organophosphate esters (OPEs) in a heavily polluted river in South China: Occurrence, spatiotemporal trends, sources, and phase distribution.

In the past decade, organophosphate esters (OPEs) undergo rapid increase in production and use. Meanwhile, owing to their additive property, OPEs exhibit liability to escape from related products and therefore ubiquity in various environments. Moreover, numerous researches verify their bioavailability and negative effects on biota and human, hence their occurrence and associated risks have caught much concern, particularly those in aquatic systems. So far, however, OPEs in water are generally investigated as a whole, their phase distribution and behavior in waterbodies are incompletely characterized. We examined 25 OPEs in water (including dissolved and particulate phases), sediment, and sediment core samples from the Lian River, which flows through the Guiyu e-waste recycling zone and Shantou specific economic zone in South China. Compared to most global waterbodies, the Lian River showed high or ultrahigh OPE levels in both water and sediments, particularly in the reaches surrounded by e-waste recycling and plastic-related industries, which were the top two greatest OPE sources. Non-industrial and agriculture-related anthropogenic activities also contributed OPEs. Sediment core data suggested that OPEs have been present in waters in Guiyu since the 1960s and showed a temporal trend consistent with the local waste-recycling business. The phase distribution of OPEs in the Lian River was significantly correlated with their hydrophobicity and solubility. Owing to their wide range of physicochemical properties, OPE congeners showed significant percentage differences in the Lian River water and sediments. Generally, OPEs in water reflect their dynamic real-time inputs, while those in sediment signify their accumulative deposition, which is another cause of their phase distribution disparities in the Lian River. The physicochemical parameters of OPEs first imposed negative and then positive influences on their dissolved phase-sediment distribution, indicating the involvement of both the adsorption of dissolved OPEs and the deposition of particle-bound OPEs.

Organophosphate esters and synthetic musks in the sediments of the Yangtze River Estuary and adjacent East China Sea: Occurrence, distribution, and potential ecological risks.

Occurrence, distribution, and potential ecological risks of ten organophosphate esters (OPEs) and nine synthetic musks (SMs) were investigated in sediments from the Yangtze River Estuary (YRE) and adjacent East China Sea (ECS). The total concentrations of OPEs in the surface sediments ranged from 0.977 to 19.0 ng/g dry weight (dw) with tris(2-chloro-propyl) phosphate being the dominant component. Total concentrations of SMs ranged from 0.176 to 7.25 ng/g dw, with 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta(g)-2-benzopyran and 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene as the dominant SMs. Higher sedimentary concentrations of ΣOPEs and ΣSMs were found in the river mouths of the YRE, inter face of Hangzhou Bay, and mud area of the ECS; the results suggested that terrestrial discharge might be the main source of OPEs and SMs in the studied region. Risk assessment revealed that low ecological risks were posed by OPEs, and limited to low ecological risks were posed by SMs.

Organophosphorus flame retardants (OPFRs) in the seawater and sediments of the Qinzhou Bay, Northern Beibu Gulf: Occurrence, distribution, and ecological risks.

The occurrence, distributions, and ecological risks of 11 organophosphate flame retardants (OPFRs) were investigated in the seawater and sediment samples from the Qinzhou Bay. The Σ11OPFRs in the surface seawater and sediments ranged from 150 to 885 ng/L and from

Embryotoxicity characterization of the flame retardant tris(1-chloro-2-propyl)phosphate (TCPP) in the invertebrate chordate Ciona intestinalis.

Tris(1-chloro-2-propyl)phosphate (TCPP) is the most common chlorinated organophosphorus flame retardant in seawater. Due to its chemical features and abundance, TCPP has been classified as a high hazard, and restrictions of use have been set in multiple countries. Despite TCPP being highly present in the marine environment, only a few studies have explored the TCPP impact on the development of marine invertebrates. Ascidians are important invertebrate members of benthic marine communities and reliable model systems for ecotoxicological research. The aim of this study was to assess the adverse effects of TCPP exposure on the embryogenesis of the ascidian Ciona intestinalis. Our results showed that this pollutant affected both muscles and nervous system development. Malformations appeared similar to those reported in other animal models for other flame retardants, suggesting that these molecules could share a common mechanism of action and induce a mixture effect when simultaneously present in the aquatic environment even at sub-teratogenic concentrations.

Graphene oxide nanosheets mitigate the developmental toxicity of TDCIPP in zebrafish via activating the mitochondrial respiratory chain and energy metabolism.

Graphene oxide (GO), a novel two-dimension carbon nanomaterial, has showed tremendous potential for utilization in intelligent manufacturing and environmental protection. In parallel, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is widely distributed in the water environment and represents a great threat to ecosystem health. However, the related knowledge remained absent regarding the impact of GO on the biological risks of TDCIPP. Herein, GO significantly reduced the mortality and malformation rates of zebrafish induced by TDCIPP maximumly by 28.6% and 41.8%, respectively. Decreased mitochondrial respiratory chain (MRC) enzyme and ATP activity induced by TDCIPP were mitigated by GO. Integrating proteomics and metabolomics revealed TDCIPP obviously induced the downregulation of the proteins and metabolites involved in the cytoskeleton, mitochondrial function, carbohydrate and amino acid metabolism, and the TCA cycle, but the alterations were attenuated by GO. GO primarily promoted MRC activity, carbohydrate metabolism, and fatty acid ß-oxidation, thus activating the energy metabolism of zebrafish and leading to antagonistic effects on the developmental toxicity of TDCIPP. These results provide a novel view on the co-exposure of GO with other pollutants and promote the reconsideration of the environmental risks of GO.

Organophosphorus flame retardants in a typical freshwater food web: Bioaccumulation factors, tissue distribution, and trophic transfer.

Water, sediment, and wild aquatic species were collected from an electronic waste (e-waste) polluted pond in South China. This study aimed to investigate the bioaccumulation, tissue distribution, and trophic transfer of organophosphorus flame retardants (PFRs) in these aquatic organisms. The concentrations of PFRs detected in the analyzed organisms were between 1.7 and 47 ng/g wet weight (ww). Oriental river prawn and snakehead exhibited the highest and lowest levels, respectively. Tri-n-butyl phosphate (TnBP), tris(2-chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCPP) and triphenyl phosphate (TPhP) were dominant contaminants, accounting for approximately 86% of the total sum. The mean values of bioaccumulation factors (BCFs) and logarithmic biota-sediment accumulation factors (log BSAFs) for individual PFRs varied from 6.6 to 1109 and from -2.0 to 0.41, respectively. Both log BCFs and log BSAFs of PFRs were significantly and positively correlated with their octanol-water partitioning coefficient (log KOW). The concentrations of PFRs in tissues of large mud carp and snakehead were significantly and positively correlated with the lipid content (each p < 0.05) and the liver, kidney, and gill exhibited high PFR levels. When the concentration was expressed on a lipid basis, liver exhibited the lowest level, indicating the probable effects of metabolism. Significantly positive correlation was also found between lipid content and total PFR concentration in muscle of all aquatic organisms, given the strong correlation between lipid content and the concentration of TnBP. Trophic magnification factors (TMF) of TnBP and TPhP were lower than 1 (0.57 and 0.62), indicating that these PFRs undergo trophic dilution in this aquatic food web.