Tricresyl Phosphate Research Articles

SIRT1-Dependent Neuroprotection by Resveratrol in TOCP-Induced Spinal Cord Injury: Modulation of ER Stress and Autophagic Flux

This study explores the neuroprotective effects of resveratrol (Resv) against tri-o-cresyl phosphate (TOCP)-induced neurotoxicity in the spinal cord of adult hens. It is well documented that TOCP exposure causes significant neurodegeneration via mechanisms that involve endoplasmic reticulum (ER) stress and impaired autophagy. In this experiment, adult hens were assigned to one of four groups: Control, Resv, TOCP, and TOCP + Resv. The spinal cord tissues were examined through transmission electron microscopy, hematoxylin and eosin (HE) staining, Nissl staining, and Western blotting to evaluate key proteins associated with ER stress and autophagy. Additionally, RT-qPCR and immunofluorescence were employed to measure sirtuin1 (SIRT1) expression. The findings revealed that TOCP induced severe ultrastructural damage, including disrupted myelin sheaths, dilated ER, and extensive neurodegeneration, as confirmed by histological evaluations. The expression levels of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, Beclin-1, P62, and LC3-II were also significantly elevated by TOCP. However, Resv treatment markedly attenuated these pathological changes by reducing ER stress, restoring autophagic flux, and upregulating SIRT1 expression, preserving spinal cord integrity. These results indicate that Resv can effectively counteract TOCP-induced neurotoxicity by modulating ER stress and autophagy, underscoring its potential as a therapeutic agent for neuroprotection.

The Effect of Modifiers on the Strength and Impact Toughness of Carbon Fiber Reinforced Plastics

This study utilized epoxy resin, three types of fabric (carbon fiber, glass fiber, and Kevlar), and two plasticizers – tricresyl phosphate (TCP) and oleic acid (OA) – to enhance the impact toughness of carbon fiber-reinforced plastics (CFRP). The polymer matrix used in the experiments was a hot-cured epoxy compound "Etal Inject-T" consisting of two components: A – epoxy resin and B – hardener, in a mass ratio of 100:49.9. For the fabrication of CFRP plates, both manual and vacuum molding techniques were employed. Combined reinforcement of carbon fiber was achieved using one of two types of fabrics: Ortex 360 glass fiber or Kevlar. Accordingly, two compositions were prepared for the experiments: carbon fiber/glass fiber and carbon fiber/Kevlar. Layer stacking in each composition was performed at ratios of 10:10 and 14:6, consisting of 20 layers in total. The greatest strengthening effect for CFRP in the case of carbon fiber/glass fiber was observed with a layer ratio of 14:6 and matrix modification using 10% TCP plasticizer. The strength of the CFRP increased from 425 to 451 MPa, and the impact toughness (α) improved from 192 to 280 kJ/m². A key feature of this technology is the achievement of high-performance dual-purpose CFRP. This enables the reduction of CFRP structures in aerospace applications by 3 to 5 times, while simultaneously enhancing resistance to impact loads.

Association of joint exposure to organophosphorus flame retardants and phthalate acid esters with gestational diabetes mellitus: a nested case-control study

BackgroundOrganic phosphate flame retardants (OPFRs) and phthalate acid esters (PAEs) are common endocrine-disrupting chemicals that cause metabolic disorders. This study aimed to assess the association between joint exposure to OPFRs and PAEs during early pregnancy in women with gestational diabetes mellitus (GDM).MethodsSeven OPFRs and five PAEs were detected in the urine of 65 GDM patients and 100 controls using gas chromatography-tandem triple quadrupole mass spectrometry (GC-MS). The association of OPFRs and PAEs with GDM was assessed using logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models.ResultsLevels of dibutyl phthalate (DBP), di-2-ethylhexyl phthalate (DEHP), diethyl phthalate (DEP), dimethyl phthalate (DMP), tris (2-butoxyethyl) phosphate (TBEP), tributyl phosphate (TBP), tris (2-chloroethyl) phosphate (TCEP), tris (1,3-dichloro-2-propyl) phosphate (TDCPP), tri-ortho-cresyl phosphate (TOCP), and triphenyl phosphate (TPHP) increased in the GDM group, and the OPFRs and PAEs, except for BBP and TMCP, were associated with GDM in the logistic regression analysis. In the WQS model, the mixture of OPFRs and PAEs was significantly positively associated with GDM (OR = 3.29, 95%CI = 1.27–8.51, P = 0.014), with TDCPP having the highest WQS index weight. BKMR analysis reinforced these results, showing that the overall association of joint exposure to the OPFRs and PAEs with GDM increased at exposure levels of the 55th to 75th percentiles. Independent exposure to TDCPP (OR = 1.42, 95%CI = 1.09–1.86, P = 0.011) and TBEP (OR = 1.29, 95%CI = 1.04–1.60, P = 0.023) were associated with an increased risk of GDM.ConclusionsEnvironmental exposure to OPFRs and PAEs is significantly associated with GDM. These findings provide evidence for the adverse effects of exposure to OPFRs and PAEs on the health of pregnant women.

Electrochemical degradation of aromatic organophosphate esters: Mechanisms, toxicity changes, and ecological risk assessment

Aromatic organophosphate esters (AOPEs), including triphenyl phosphate (TPHP), tricresyl phosphate (TCP), and 2-ethylhexyl diphenyl phosphate (EHDPP), pose significant health and ecological risks. Electrochemical advanced oxidation process (EAOP) is effective in removing refractory pollutants. In this study, the degradation performance and detoxication ability of AOPEs by EAOP were investigated. Hydroxylation, oxidation, and bond cleavage products were identified as major degradation products (DPs) due to the reaction with ·OH and O₂·-. Toxicity assessments using ecological structure activity relationship (ECOSAR) model and flow cytometry (FCM) revealed the cytotoxicity and aquatic toxicity for DPs were significantly decreased. 16S rRNA gene sequencing of sediment exposure to AOPEs and DPs were applied to assess ecological toxicity, and results showed reduced bacterial richness and diversity with EHDPP and TCP, while TPHP slightly enhanced richness. AOPEs and DPs altered bacterial genera involved in carbon, nitrogen, sulfur cycling and organic compound degradation. Bacterial community assembly suggested elevated stochastic processes and reduced ecotoxicity, confirming AOPEs can be effectively detoxified by 10-min EAOP treatment. Molecular ecological network analysis indicated increased complexity and stability of bacterial communities with DPs. These findings comprehensively revealed the toxicity of AOPEs and their DPs and provided the first evidence of effective degradation and detoxification by EAOP from ecotoxicological perspective.

Organophosphorus Flame Retardants and Metabolic Disruption: An in Silico, in Vitro, and in Vivo Study Focusing on Adiponectin Receptors.

Environmental chemical exposures have been associated with metabolic outcomes, and typically, their binding to nuclear hormone receptors is considered the molecular initiating event (MIE) for a number of outcomes. However, more studies are needed to understand the influence of such exposures on cell membrane-bound adiponectin receptors (AdipoRs), which are critical metabolic regulators. We aimed to clarify the potential interactions between AdipoRs and environmental chemicals, specifically organophosphorus flame retardants (OPFRs), and the resultant effects. Employing in silico simulation, cell thermal shift, and noncompetitive binding assays, we screened eight OPFRs for interactions with AdipoR1 and AdipoR2. We tested two key events underlying AdipoR modulation upon OPFR exposure in a liver cell model. The Toxicological Prioritization Index (ToxPi)scoring scheme was used to rank OPFRs according to their potential to disrupt AdipoR-associated metabolism. We further examined the inhibitory effect of OPFRs on AdipoR signaling activation in mouse models. Analyses identified pi-pi stacking and pi-sulfur interactions between the aryl-OPFRs 2-ethylhexyl diphenyl phosphate (EHDPP), triphenyl phosphate (TPhP), and tricresyl phosphate (TCP) and the transmembrane cavities of AdipoR1 and AdipoR2. Cell thermal shift assays showed a rightward shift in the AdipoR proteins' melting curves upon exposure to these three compounds. Although the binding sites differed from adiponectin, results suggest that aryl-OPFRs noncompetitively inhibited the binding of the endogenous peptide ligand ADP355 to the receptors. Analyses of key events underlying AdipoR modulation revealed that glucose uptake was notably lower, whereas lipid content was higher in cells exposed to aryl-OPFRs. EHDPP, TCP, and TPhP were ranked as the top three disruptors according to the ToxPi scores. A noncompetitive binding between these aryl-OPFRs and AdipoRs was also observed in wild-type (WT) mice. In db/db mice, the finding of lower blood glucose levels after ADP355 injection was diminished in the presence of a typical aryl-OPFR (TCP). WT mice exposed to TCP demonstrated lower AdipoR1 signaling, which was marked by lower phosphorylated AMP-activated protein kinase (pAMPK) and a higher expression of gluconeogenesis-related genes. Moreover, WT mice exposed to ADP355 demonstrated higher levels of pAMPK protein and peroxisome proliferator-activated receptor- messenger RNA. This was accompanied by higher glucose disposal and by lower levels of long-chain fatty acids and hepatic triglycerides; these metabolic improvements were negated upon TCP co-treatment. In silico, in vitro, and invivo assays suggest that aryl-OPFRs act as noncompetitive inhibitors of AdipoRs, preventing their activation by adiponectin, and thus function as antagonists to these receptors. Our study describes a novel MIE for chemical-induced metabolic disturbances and highlights a new pathway for environmental impact on metabolic health. https://doi.org/10.1289/EHP14634.

Structural, spectroscopic, and biological properties of an asymmetric Cu (II) Schiff-base complex: Synthesis, DNA/BSA interactions, and antimicrobial potential with experimental and computational insights

A copper (II) complex with the asymmetric bidentate Schiff-base ligand (E)-2-(((4-chlorophenyl) imino) methyl) phenol was synthesized and characterized using FTIR and UV–VIS spectroscopy. Photoluminescence studies were conducted on both the copper (II) complex and the free ligand. XRD analysis revealed the copper (II) complex crystallizes in the monoclinic system, space group P21/c. The complex structure was optimized using DFT calculations with B3LYP/6-31G+(d,p) and Lanl2dz basis sets, with QTAIM and NBO analyses confirming complex formation. The energy gap of the copper (II) complex was determined to be 3.701 eV (alpha state) and 2.764 eV (beta state). MEP analysis of the optimized structure indicated a hydrophobic environment around the nitrogen atom, with the molecule exhibiting overall hydrophobicity. The chlorine atoms were identified as potential nucleophilic sites. The antimicrobial efficacy of a Schiff base copper (II) complex was evaluated against selected pathogenic bacteria (B. subtilis, B. megaterum, K. pneumoniae, E. coli) and the fungus Candida albicans. Among these C. albicans for complex showed larger zones (11–15.5 mm) at higher concentrations such as 2 and 2.5 mg/mL. Molecular docking studies suggested strong binding affinity between the complex and the target protein, this was further supported by obtained root means square deviations, root means square fluctuations, radius of gyration and hydrogen bond values during simulations. The binding free energy between BSA and the copper (II) complex was calculated as −8.7 kcal/mol, indicating significant interaction. However, only weak van der Waals interactions were observed between the complex and DNA. Toxicity studies revealed the copper (II) complex had minimal irritant effects on ocular and cutaneous tissues, with a low lethal dose. In comparison, Tricresyl phosphate showed moderate to severe ocular irritancy and modest cutaneous irritancy.

Aryl phosphate ester-induced pericardial edema in zebrafish embryos is influenced by the ionic composition of exposure media

Pericardial edema – fluid accumulation within the pericardium – is a frequently observed malformation in zebrafish embryo-based chemical toxicity screens. We recently discovered that the severity of triphenyl phosphate (TPHP)-induced pericardial edema was dependent on the ionic strength of exposure media. TPHP is an aryl phosphate ester (APE) widely used as a plasticizer and flame retardant. APEs are characterized by having one or more aryl groups bound to a phosphate center, with TPHP containing only unsubstituted aryl groups. Therefore, the objective of this study was to begin investigating whether, similar to TPHP, pericardial edema induced by other structurally related APEs is dependent on the ionic composition of exposure media. We first mined the peer-reviewed literature to identify other APEs that 1) induced pericardial edema in zebrafish embryos within a minimum of three peer-reviewed publications, and 2) demonstrated a statistically significant induction of pericardial edema in at least 70 % of the studies evaluated. Based on this meta-analysis, we identified four other APEs that caused pericardial edema in zebrafish embryos: isopropylated triphenyl phosphate (IPTPP), cresyl diphenyl phosphate (CDP), tricresyl phosphate (TMPP), and 2-ethylhexyl diphenyl phosphate (EDHPHP). Using TPHP as a positive control and pericardial edema as a readout, we developed concentration-response curves for all four APEs based on static exposure from 24 to 72 h post-fertilization (hpf). We then conducted co-exposures with D-Mannitol (an osmotic diuretic) and exposures within reverse osmosis (RO) water determine whether the ionic composition of exposure media mitigated APE-induced pericardial edema at 72 hpf. Using pericardial edema as an endpoint, the approximate EC50s for TPHP (positive control), IPTPP, CDP, TMPP, and EDHPHP were 6.25, 3.125, 3.125, 25, and 100 µM, respectively, based on exposure from 24 to 72 hpf. Interestingly, similar to our findings with TPHP, co-exposure with D-Mannitol and exposure within ion-deficient water significantly mitigated IPTPP- CDP-, TMPP-, and EDHPHP-induced pericardial edema in zebrafish embryos, suggesting that chemically-induced pericardial edema may be 1) dependent on the ionic composition of exposure media and 2) driven by a disruption in osmoregulation across the embryonic epidermis. Therefore, similar to other assay parameters, our findings underscore the need to standardize the osmolarity of exposure media in order to minimize the potential for false positive/negative hits in zebrafish embryo-based chemical toxicity screens conducted around the world.

Triphenyl Phosphate Alters Methyltransferase Expression and Induces Genome-Wide Aberrant DNA Methylation in Zebrafish Larvae.

Emerging environmental contaminants, organophosphate flame retardants (OPFRs), pose significant threats to ecosystems and human health. Despite numerous studies reporting the toxic effects of OPFRs, research on their epigenetic alterations remains limited. In this study, we investigated the effects of exposure to 2-ethylhexyl diphenyl phosphate (EHDPP), tricresyl phosphate (TMPP), and triphenyl phosphate (TPHP) on DNA methylation patterns during zebrafish embryonic development. We assessed general toxicity and morphological changes, measured global DNA methylation and hydroxymethylation levels, and evaluated DNA methyltransferase (DNMT) enzyme activity, as well as mRNA expression of DNMTs and ten-eleven translocation (TET) methylcytosine dioxygenase genes. Additionally, we analyzed genome-wide methylation patterns in zebrafish larvae using reduced-representation bisulfite sequencing. Our morphological assessment revealed no general toxicity, but a statistically significant yet subtle decrease in body length following exposure to TMPP and EHDPP, along with a reduction in head height after TPHP exposure, was observed. Eye diameter and head width were unaffected by any of the OPFRs. There were no significant changes in global DNA methylation levels in any exposure group, and TMPP showed no clear effect on DNMT expression. However, EHDPP significantly decreased only DNMT1 expression, while TPHP exposure reduced the expression of several DNMT orthologues and TETs in zebrafish larvae, leading to genome-wide aberrant DNA methylation. Differential methylation occurred primarily in introns (43%) and intergenic regions (37%), with 9% and 10% occurring in exons and promoter regions, respectively. Pathway enrichment analysis of differentially methylated region-associated genes indicated that TPHP exposure enhanced several biological and molecular functions corresponding to metabolism and neurological development. KEGG enrichment analysis further revealed TPHP-mediated potential effects on several signaling pathways including TGFβ, cytokine, and insulin signaling. This study identifies specific changes in DNA methylation in zebrafish larvae after TPHP exposure and brings novel insights into the epigenetic mode of action of TPHP.

Comparative studies of radio transparency and dielectric characteristics of polymer composites

Aramid-epoxy composites and glass fiber reinforced plastics are widely used in the manufacturing of the fairing design for modern aerospace vehicles due to their excellent mechanical properties combined with radio transparency in wave transfer. In this paper, aramid-epoxy composite and fiberglass were fabricated by the vacuum infusion method for a comparative study on radio transparency and dielectric characteristics. The radio transparency of the studied materials was evaluated by free-space measurements in the frequency range of 1 GHz to 8.5 GHz. According to the radio transparency results, the aramid-epoxy composite undergoes less electromagnetic wave loss than glass fiber reinforced plastic. Modifying the epoxy resin with tricresyl phosphate in aramid-epoxy resin leads to an increase in mechanical properties with a slight decrease in transmittance and a non-significant increase in dielectric characteristics. The dielectric characteristics results have demonstrated low values (ε = 2.87 and tan δ = 0.037) for aramid composites compared to fiberglass.

Occurrence, Bioaccumulation, and Risk Assessment of Organophosphate Esters in Rivers Receiving Different Effluents.

Organophosphate esters (OPEs), as alternatives to brominated flame retardants, are extensively used in both production and daily life, with their environmental contamination and toxic effects being a concern. This study investigated the concentration levels, bioaccumulation, and ecological effects of OPEs in five different effluent-receiving rivers. The results demonstrate that the concentration range of Σ13OPEs across the five rivers was between 142.23 and 304.56 ng/L (mean: 193.50 ng/L). The highest pollution levels of OPEs were found in rivers receiving airport and industrial wastewater, followed by agricultural wastewater, mixed wastewater, and domestic wastewater. Tris(2-chloroisopropyl) phosphate (TCPP), triethyl phosphate (TEP), and tricresyl phosphate (TCrP) were identified as the main pollutants. The accumulation concentrations of OPEs in fish ranged from 54.0 to 1080.88 ng/g dw, with the highest bioaccumulation found in Pelteobagrus fulvidraco, followed by Carassius auratus and Misgurnus anguillicaudatus. The brain was the primary organ of accumulation, followed by the liver, gills, intestine, and muscle. Tri-n-propyl phosphate (TPeP) and TEP exhibited the highest bioconcentration, with log BAF values exceeding three. The bioaccumulation of OPEs was influenced by pollutant concentration levels, hydrophobic properties, and biological metabolism. Ecological risk assessment revealed that the cumulative risk values of Σ13OPEs ranged from 0.025 to 16.76, with TCrP being the major contributor. It posed a medium-low risk to algae but a high risk to crustaceans and fish.

Integrated Approach for Testing and Assessment for Developmental Neurotoxicity (DNT) to Prioritize Aromatic Organophosphorus Flame Retardants.

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

Real-Time Potentiometric Monitoring of Tetrachloroaurate(III) with an Ion-Selective Electrode and Its Applications to HAuCl4 Iodide-Catalyzed Reduction by Hydroxylamine

Ion-selective electrodes for tetrachloroaurate(III) have been developed for potentiometric monitoring of the reduction reaction of tetrachloroaurate(III). Three different plasticized polyvinyl chloride membranes containing tridodecymethylammonium chloride as an anion exchanger were investigated. These membranes differ in the plasticizer used, either 2-nitrophenyl octyl ether (NPOE) or tricresyl phosphate (TCP) or bis-(2-ethylhexyl) sebacate (DOS). The potentiometric response of the electrodes to the tetrachloroaurate(III) concentration was studied by two methods. In the first method, commonly used in the calibration of ion-selective electrodes, successive tetrachloroaurate(III) concentration increments were used and the potential was allowed to stabilize after each concentration step. The second method was developed to mimic the tetrachloroaurate(III) reduction reaction in which there is a continuous decrease in the concentration of tetrachloroaurate(III). This was achieved by continuously diluting an initial concentration of tetrachloroaurate(III) by pumping a diluent solution while keeping the sample volume constant. This method gave an excellent linear response to the tetrachloroaurate(III) concentration. The calibrated electrodes were used for the potentiometric monitoring of the kinetics of a newly observed reaction: the reduction of tetrachloroaurate(III) by hydroxylamine catalyzed by iodide. A mechanism for this reaction is proposed on the basis of the experimental results obtained.

Self-dispersed molybdenum disulfide quantum dot/graphene crumpled ball as efficient high temperature lubricant additive

Inorganic nanoparticles have been proved as powerful lubricant additives at elevated temperature. However, the tribological properties are inevitably impaired due to poor dispersion and insufficient high temperature resistance of organic matter modified nanoparticles. Here, we prepare a self-dispersed molybdenum disulfide quantum dot/graphene crumpled ball (MGCB) comprising molybdenum disulfide quantum dot uniformly interspersed on the wrinkled graphene ball. The crumpled ball composite possesses excellent dispersity in polyalkylene glycol base oil without depending on surface modifiers. Compared with the conventional phosphate esters lubricant, our results indicate MGCB could vastly improve the lubrication performance of polyalkylene glycol with an extremely low concentration (0.05 wt%) at elevated temperature (150 °C), showing a friction reduction of 47% and a wear reduction of 30% compared with the conventional phosphate esters lubricant (tricresyl phosphate, TCP). This is because crumpled ball potentiates synergistic lubrication effect within the boundary lubrication. Overall, we envision our designed self-dispersed MGCB has significant potential in tribological application at elevated temperature.

Elevated intracellular Ca2+ functions downstream of mitodysfunction to induce Wallerian-like degeneration and necroptosis in organophosphorus-induced delayed neuropathy

Neurotoxic organophosphorus compounds can induce a type of delayed neuropathy in humans and sensitive animals, known as organophosphorus-induced delayed neuropathy (OPIDN). OPIDN is characterized by axonal degeneration akin to Wallerian-like degeneration, which is thought to be caused by increased intra-axonal Ca2+ concentrations. This study was designed to investigate that deregulated cytosolic Ca2+ may function downstream of mitodysfunction in activating Wallerian-like degeneration and necroptosis in OPIDN. Adult hens were administrated a single dosage of 750 mg/kg tri-ortho-cresyl phosphate (TOCP), and then sacrificed at 1 day, 5 day, 10 day and 21 day post-exposure, respectively. Sciatic nerves and spinal cords were examined for pathological changes and proteins expression related to Wallerian-like degeneration and necroptosis. In vitro experiments using differentiated neuro-2a (N2a) cells were conducted to investigate the relationship among mitochondrial dysfunction, Ca2+ influx, axonal degeneration, and necroptosis. The cells were co-administered with the Ca2+-chelator BAPTA-AM, the TRPA1 channel inhibitor HC030031, the RIPK1 inhibitor Necrostatin-1, and the mitochondrial-targeted antioxidant MitoQ along with TOCP. Results demonstrated an increase in cytosolic calcium concentration and key proteins associated with Wallerian degeneration and necroptosis in both in vivo and in vitro models after TOCP exposure. Moreover, co-administration with BATPA-AM or HC030031 significantly attenuated the loss of NMNAT2 and STMN2 in N2a cells, as well as the upregulation of SARM1, RIPK1 and p-MLKL. In contrast, Necrostatin-1 treatment only inhibited the TOCP-induced elevation of p-MLKL. Notably, pharmacological protection of mitochondrial function with MitoQ effectively alleviated the increase in intracellular Ca2+ following TOCP and mitigated axonal degeneration and necroptosis in N2a cells, supporting mitochondrial dysfunction as an upstream event of the intracellular Ca2+ imbalance and neuronal damage in OPIDN. These findings suggest that mitochondrial dysfunction post-TOCP intoxication leads to an elevated intracellular Ca2+ concentration, which plays a pivotal role in the initiation and development of OPIDN through inducing SARM1-mediated axonal degeneration and activating the necroptotic signaling pathway.

Inhibition kinetics of acetylcholinesterase and butyrylcholinesterase from various species by 2-(2-cresyl)-4H-1,3,2-benzodioxaphosphorin-2-oxide (CBDP)

The aerotoxic syndrome has been associated with exposure to tricresyl phosphate (TCP), which is used as additive in hydraulic fluids and engine lubricants. The toxic metabolite 2-(2-cresyl)-4H-1,3,2-benzodioxaphosphorin-2-oxide (CBDP) is formed from the TCP isomer tri-ortho-cresyl phosphate (TOCP) in vivo and is known to react with the active site serine in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) resulting in the inhibition of the enzymes. Previous in vitro studies showed pronounced species differences in the inhibition kinetics of cholinesterases by organophosphorus compounds (OP), which must be considered in the development of relevant animal models for the investigation of OP poisoning and the aerotoxic syndrome. The present study was designed to investigate the inhibition kinetics of human, Cynomolgus monkey, pig, mini pig, guinea pig, mouse, and rat AChE as well as BChE by CBDP under standardized conditions. There were similar rate constants for the inhibition (ki) of human, Cynomolgus monkey and mouse AChE by CBDP. In contrast, the ki values obtained for guinea pig, mini pig, pig, and rat AChE were 2.8- to 5.9-fold lower than that of human AChE. The results of the present study confirmed CBDP as one of the most potent inhibitors of human BChE, indicating a ki value of 3.24 ± 0.33 ×108M−1min−1, which was about 1,140-fold higher than that of human AChE. Accordingly, a markedly more pronounced inhibition rate of BChE from the species guinea pig, mini pig, pig, rat, Cynomolgus monkey, and mouse by CBDP was found as compared to those of AChE from the respective sources, indicating 2.0- to 89.6-fold higher ki values.

Nicotinamide mononucleotide maintains cytoskeletal stability and fortifies mitochondrial function to mitigate oocyte damage induced by Triocresyl phosphate

Triocresyl phosphate (TOCP) was commonly used as flame retardant, plasticizer, lubricant, and jet fuel additive. Studies have shown adverse effects of TOCP on the reproductive system. However, the potential harm brought by TOCP, especially to mammalian female reproductive cells, remains a mystery. In this study, we employed an in vitro model for the first time to investigate the effects of TOCP on the maturation process of mouse oocytes. TOCP exposure hampered the meiotic division process, as evidenced by a reduction in the extrusion of the first polar body from oocytes. Subsequent research revealed the disruption of the oocyte cell cytoskeleton induced by TOCP, resulting in abnormalities in spindle organization, chromosome alignment, and actin filament distribution. This disturbance further extended to the rearrangement of organelles within oocytes, particularly affecting the mitochondria. Importantly, after TOCP treatment, mitochondrial function in oocytes was impaired, leading to oxidative stress, DNA damage, cell apoptosis, and subsequent changes of epigenetic modifications. Supplementation with nicotinamide mononucleotide (NMN) alleviated the harmful effects of TOCP. NMN exerted its mitigating effects through two fundamental mechanisms. On one hand, NMN conferred stability to the cell cytoskeleton, thereby supporting nuclear maturation. On the other hand, NMN enhanced mitochondrial function within oocytes, reducing the excess reactive oxygen species (ROS), restoring meiotic division abnormalities caused by TOCP, preventing oocyte DNA damage, and suppressing epigenetic changes. These findings not only enhance our understanding of the molecular basis of TOCP induced oocyte damage but also offer a promising avenue for the potential application of NMN in optimizing reproductive treatment strategies.

Occurrence and potential risks of organophosphate esters in agricultural soils: A case study of Fuzhou City, Southeast China

Fifty agricultural soil samples collected from Fuzhou, southeast China, were first investigated for the occurrence, distribution, and potential risks of twelve organophosphate esters (OPEs). The total concentration of OPEs (ΣOPEs) in soil ranged from 1.33 to 96.5 ng/g dry weight (dw), with an average value of 17.1 ng/g dw. Especially, halogenated-OPEs were the predominant group with a mean level of 9.75 ng/g dw, and tris(1-chloro-2-propyl) phosphate (TCIPP) was the most abundant OPEs, accounting for 51.1% of ΣOPEs. The concentrations of TCIPP and ∑OPEs were found to be significantly higher (P < 0.05) in soils of urban areas than those in suburban areas. In addition, the use of agricultural plastic films and total organic carbon had a positive effect on the occurrence of OPE in this study. The positive matrix factorization model suggested complex sources of OPEs in agricultural soils from Fuzhou. The ecological risk assessment demonstrated that tricresyl phosphate presented a medium risk to land-based organisms (0.1 ≤ risk quotient < 1.0). Nevertheless, the carcinogenic and non-carcinogenic risks for human exposure to OPEs through soil ingestion and dermal absorption were negligible. These findings would facilitate further investigations into the pollution management and risk control of OPEs.

Biodegradation of aryl-organophosphate flame retardants by Rhodococcus pyridinivorans YC-MTN: Performance, pathway and potential in environmental remediation

A strain capable of efficiently degrading aryl-organophosphate flame retardants (aryl-OPFRs) was isolated and identified as Rhodococcus pyridinivorans YC-MTN. The strain demonstrated high degradation efficiency within a wide range of pH (7.0–10.0), temperature (25–45 °C), and salinity (0–2%). Strain YC-MTN effectively utilized aryl-OPFRs as the sole carbon source, facilitating their rapid degradation. The estimated half-lives for four aryl-OPFRs, namely triphenyl phosphate (TPhP), tricresyl phosphate (TCrP), 2-ethylhexyl diphenyl phosphate (EHDPP), and resorcinol bis (diphenyl phosphate) (RBDPP), were found to be 8.73, 10.82, 30.28, and 16.14 h, respectively. Additionally, half of the aryl-OPFRs underwent mineralization after 7 d of incubation. In particular, hydrolysis played a dominant role in the metabolism of TPhP, EHDPP, and RBDPP by strain YC-MTN, while P–O bond cleavage generally occurred in the presence of phenol as the leaving group. In addition to hydrolysis, methylation participated in the biotransformation of TCrP. Strain YC-MTN exhibited significant degradability towards TPhP at various concentrations ranging from 1 to 1000 mg L−1. The remediation of TPhP was simulated in both freshwater and seawater, and within a span of 5 d, strain YC-MTN completely degraded the exogenous TPhP. Strain YC-MTN holds potential as a viable microbial agent in the bioremediation of aryl-OPFRs contamination.

Occurrence, potential sources, and ecological risks of traditional and novel organophosphate esters in facility agriculture soils: A case study in Beijing, China

Although traditional organophosphate esters (OPEs) in soils have attracted widespread interest, there is little information on novel OPEs (NOPEs), especially in facility agriculture soils. In this work, we surveyed 11 traditional OPEs, four NOPEs, and four corresponding organophosphite antioxidant precursors (OPAs) for the NOPEs in soil samples collected from facility greenhouses and open fields. The median summed concentrations of traditional OPEs and NOPEs were 14.1 μg/kg (range: 5.38–115 μg/kg) and 702 μg/kg (range: 348–1952 μg/kg), respectively, in film-mulched soils from greenhouses. These concentrations were much higher than those in soils without mulch films, which suggests that OPEs in soils are associated with plastic mulch films. Tris(2,4-di-tert-butylphenyl) phosphate, which is a NOPE produced by oxidation of (2,4-di-tert-butylphenyl) phosphite, was the predominant congener in farmland soils, with concentrations several orders of magnitude greater than those of traditional OPEs. Comparisons of OPEs in different mulch films and the corresponding mulched soils revealed that degradable and black films caused more severe pollution than polyethylene and white films. Traditional OPEs, including tris(2-ethylhexyl) phosphate and tricresyl phosphate, exhibited moderate risks in farmland soils, especially in film-mulched soils. NOPEs, including trisnonylphenol phosphate, posed high ecological risks to the terrestrial ecosystem. Risk evaluations should be conducted for a broad range of NOPEs in the environment.

Determination of potential dermal exposure rates of phosphorus flame retardants via the direct contact with a car seat using artificial skin

Dermal exposure to phosphorus flame retardants (PFRs) has received much attention as a major alternative exposure route in recent years. However, the information regarding dermal exposure via direct contact with a product is limited. In addition, in the commonly used dermal permeability test, the target substance is dissolved in a solvent, which is unrealistic. In this study, a dermal permeability test of PFRs in three car seats was performed using artificial skin. The PFR concentrations in the car seats are 0.12 wt% tris(2-chloroethyl) phosphate (TCEP), 0.030–0.25 wt% tris(2-chloroisopropyl) phosphate (TCPP), 0.15 wt% triphenyl phosphate (TPhP), 0.89 wt% cresyl diphenyl phosphate (CsDPhP), 0.074 wt% tricresyl phosphate (TCsP), and 0.46–4.7 wt% diethylene glycol bis [di (2-chloroisopropyl) phosphate (DEG-BDCIPP). The mean skin permeation rates for a contact time of 24 h are 14 (TCEP), 5.4–160 (TCPP), 0.67 (CsDPhP), 0.38 (TPhP), and 3.3–58 ng cm−2 h−1 (DEG-BDCIPP). The concentrations of TCsP in receptor liquid were lower than the limit of quantification at the contact time of 24 h. The skin permeation rates were significantly affected by the type of car seat (e.g., fabric or non-fabric). The potential dermal TCPP exposure rate for an adult via direct contact with the car seat during the average daily contact time (1.3 h), which was the highest value assessed in this study, was estimated to be 16,000 ng kg−1 day−1, which is higher than that related to inhalation and dust ingestion reported as significant exposure route of PFRs in previous studies. These facts reveal that dermal exposure associated with direct contact with the product might be an important exposure pathway for PFRs.