The emerging endocrine disruption chemicals organophosphate esters (OPEs) pose high risk of metabolic disruption. However, limited information is available on physiological disturbance of OPEs on adipose, a major endocrine and metabolic organ. In this study, physiological change was investigated after exposing 3T3-L1fully differentiated adipocytes to six OPEs at non-cytotoxic concentrations. We found two chlorinated-OPEs (tris-(2-chloro-1-(chloromethyl) ethyl) phosphate (TDCPP) and tris(2-chloroisopropyl) phosphate (TCPP)) and two alkyl-OPEs (tributyl phosphate (TBP) and tris (2-butoxyethyl) phosphate (TBEP)) induced inflammation-like adipokines (chemoattractant protein 1 and interleukin-6), respectively. Increment of insulin-resistance-related hormones (resistin and leptin) were observed under TDCPP, TCPP, and TBP exposure. Functional and mechanistic investigation revealed that all of the compounds inhibited lipolysis at basal level through dephosphorylated HSLˢᵉʳ⁵⁶³, the rate limiting enzyme of lipolysis. Triphenyl phosphate (TPhP), tricresyl phosphate (TCP), TDCPP, TBP and TBEP enhanced glucose uptake at both basal and insulin-stimulated status. We evidenced that impact was independent of the classical pIRSˢᵉʳ⁶³⁹/pAKTˢᵉʳ⁴⁷³ nor the insulin-independent AMPK pathway. The elevated mRNA of slc2a4 and its transcriptional factor LXRα may, at least partially, explain for the increase of glucose uptake. Given the focus within the endocrine disruption on glands, it would be prudent not to ignore endocrinal impact on adipocytes.

Organophosphate esters (OPEs) are widely added to various industrial and consumer products, and are mainly used as flame retardants and plasticizers. Existing epidemiological studies suggest that OPE exposure may be linked to increased blood pressure (BP) and hypertension risk in adults. However, it remains unclear whether OPE exposure is associated with increased BP in children and adolescents. Here, we investigated the associations between OPE exposure and BP levels in 6–18-year-old children and adolescents from a cross-sectional study in Liuzhou, China. OPE metabolites were determined in spot urine samples (n = 1194) collected between April and May 2018. Three measurements of systolic and diastolic BP for each participant were averaged as study outcomes. Associations of OPE exposure with age-, sex- and height-standardized BP were assessed using linear regression models. We found that each natural log unit increment of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) was associated with a 0.06 standard deviation unit (95% confidant interval (CI): 0.01, 0.11) increase in systolic BP z-score. When conducting stratified analysis based on sex, age, and BMI category, BDCIPP was shown to be positively associated with systolic/diastolic BP z-score in females, but not in males. The associations between bis(2-butoxyethyl) phosphate (BBOEP) and systolic/diastolic BP z-score were pronounced in adolescents, but not in children. Moreover, a significant positive association between 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) and diastolic BP z-score was observed in obese subjects. The present study provides the first evidence that OPE exposure was related to increased BP in children and adolescents. Given the scarcity of high-quality evidence supporting these results, the health effects of OPEs are warrant investigation in well-designed prospective studies.

Organophosphates (OPEs) are manmade organic pollutants that are widely used as flame retardants, plasticizers, and antifoaming and hydraulic agents. In this study, seven OPEs in seawater and sediment from the Yellow Sea and East China Sea were determined to study the distribution and diffusion behavior, and to evaluate the environmental risks. The ΣOPEs in the seawater and sediments ranged from below the method detection limit (<MDL) to 497.40 ng/L and from < MDL to 66.50 ng/g dw, respectively. Tri-n-butyl phosphate (TnBP), tris-(1, 3-Dichloro-2-Propyl) phosphate (TDCPP), and tri-meta-cresyl phosphate (TmCP) were the dominant OPEs in the seawater and sediments. OPEs were mainly distributed in coastal areas and the South Yellow Sea, indicating that they are mainly affected by land-based pollution and ocean currents. Fugacity analysis shows that tri-para-cresyl phosphate (TpCP) was in a state of equilibrium, while TDCPP, TnBP, and TmCP other OPEs tended to diffuse from sediment to water. The diffusion behavior of OPEs is mainly affected by their chemical properties. Hazard quotient (HQ) values of TmCP and TpCP in sediment samples were >1.0, indicating high ecological risks to aquatic organisms.

Liver disease has become a growing health burden, and little is known about the impairment of liver function caused by exposure to organophosphate esters (OPEs) in adolescents aged 12–19 years in the United States. To investigate the relationship between urinary metabolites of OPEs including diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(1-chloroethyl) phosphate (BCPP), bis(2-chloroethyl) phosphate (BCEP), and dibutyl phosphate (DBUP) and liver function in US adolescents aged 12–19 years. Liver function tests (LFTs) include aspartate aminotransferase (AST), albumin (ALB), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin (TBIL), total protein (TP), and AST/ALT. Meanwhile, potential confounding and interaction effects were assessed. The study sample included 592 adolescents aged 12–19 from two consecutive NHANES cycles (2011–2012, 2013–2014). A composite statistical strategy combining traditional linear regression with advanced multi-pollutant models quantile based g-computation (QGC) and eXtreme Gradient Boosting (XGBoost) regression was used to analyze the joint effects of multiple OPEs on liver function indicators, and to describe the interaction between different OPEs in detail. 592 adolescent participants were 15 (14–17) years old, with similar numbers of males and females (304 vs. 288). The analysis results showed that (1) in the linear regression model, individual DPHP, BCEP exposure and ALP changes, BCEP and AST/ALT changes were positively associated. DPHP, BDCPP were negatively associated with TP changes. (2) The combined effects of various OPEs on ALB, ALT, ALP, GGT, TBIL, TP, and AST/ALT were statistically significant. (3) There is no potential interaction between different OPEs. Several OPEs and their combinations are closely related to the 8 LFT indicators. In addition, data suggest that exposure to OPEs in adolescents may be associated with liver damage. Due to limited evidence in the literature and potential limitations of the current study, our findings require more studies to confirm.

In this study, water and sediment samples from the Jiaozhou Bay and surrounding rivers were collected to analyze the seasonal occurrence and allocation of 12 organophosphate esters (OPEs) and the associated ecological risk. The higher contamination of OPEs in the adjacent rivers indicated the impact of terrestrial input. Tris(1-chloropropan-2-yl) phosphate (TCIPP) was the predominant OPE in the four environmental sample groups investigated. The spatial distribution of OPEs in seawater varied greatly seasonally and was mainly affected by terrestrial input, with OPEs being redistributed under the influence of tidal currents. The partition coefficients (log Kₒc) of the OPEs were calculated, and their strong correlation with the log Kₒw (octanol-water) values suggested that the water-sediment allocation was significantly affected by hydrophobicity. The homologous relationships among the 7 OPEs with detection frequencies greater than 40% were identified by principal component analysis (PCA). The partial least squares regression (PLSR) model explicated that ∑OPEs cycling dynamics and principal controlling factors were dissimilar in the bay versus surrounding rivers. The risk quotient (RQ) faced by typical organisms in seawater and river water indicated that short-term OPEs exposure was safe for green algae, daphnia and fish. The organisms in rivers faced the higher ecological risk of OPEs in spring than in summer and winter. Therefore, the terrestrial transport of OPEs in spring should be controlled.

Cresyl diphenyl phosphate (CDP), as a kind of aryl substituted organophosphate esters (OPEs), is commonly used as emerging flame retardants and plasticizers detected in environmental media. Due to the accumulation of CDP in organisms, it is very important to discover the toxicological mechanism and metabolic process of CDP. Hence, liver microsomes of crucian carps (Carassius carassius) were prepared for in vitro metabolism kinetics assay to estimate metabolism rates of CDP. After 140 min incubation, the depletion of CDP accounted for 58.1%–77.1% (expect 0.5 and 2 μM) of the administrated concentrations. The depletion rates were best fitted to the Michaelis-Menten model (R² = 0.995), where maximum velocity (Vₘₐₓ) and Michaelis-Menten constant (Kₘ) were 12,700 ± 2120 pmol min⁻¹·mg⁻¹ protein and 1030 ± 212 μM, respectively. Moreover, the in vitro hepatic clearance (CLᵢₙₜ) of CDP was 12.3 μL min⁻¹·mg⁻¹ protein. Log Kₒw and bioconcentration factor (BCF) of aryl-OPEs were both higher than those of alkyl- and chlorinated-OPEs, indicating that CDP may easily accumulate in aquatic organisms. The results made clear that the metabolism rate of CDP was greater than those of other OPEs detected in liver microsomes in previous research. This paper was first of its kind to comprehensively investigate the in vitro metabolic kinetics of CDP in fish liver microsomes. The present study might provide useful information to understand the environmental fate and metabolic processes of these kinds of substances, and also provide a theoretical basis for the ecological risk assessment of emerging contaminants.

Many types of contaminants of emerging concern (CECs), including per- and poly-fluoroalkyl substances (PFAS), have been found in leachate of operating municipal landfills. However, there is only limited information on CECs presence in leachate of historic landfills (≥3 decades since closure, often lacking engineered liners or leachate collection systems) at concentrations that may pose a risk to nearby wells and surface water ecosystems. In this study, 48 samples of leachate-impacted groundwater were collected from 20 historic landfills in Ontario, Canada. The CECs measured included artificial sweeteners (ASs), PFAS, organophosphate esters (OPE), pharmaceuticals, bisphenols, sulfamic acid, perchlorate, and substituted phenols. The common presence of the AS saccharin, a known indicator of old landfill leachate, combined with mostly negligible levels of the AS acesulfame, an indicator of modern wastewater, revealed that most samples were strongly influenced by leachate and not cross-contaminated by wastewater (which can contain these same CECs). Several landfills, including ones closed in the 1960s, had total PFAS concentrations similar to those previously measured at modern landfills, with a maximum observed here of 12.7 μg/L. Notably elevated concentrations of several OPE, sulfamic acid, cotinine, and bisphenols A and S were found at many 30-60 year-old landfills. There was little indication of declining concentrations with landfill age, suggesting historic landfills can be long-term sources of CECs to groundwater and that certain CECs may be useful tracers for historic landfill leachate. These findings provide guidance on which CECs may require monitoring at historic landfill sites and wastewater treatment plants receiving their effluent.

Many environmental chemicals have been found to exert estrogenic effects in cells and experimental animals by activating nuclear receptors such as estrogen receptors and estrogen-related receptors. These compounds include bisphenols, pesticides, polybrominated diphenyl ethers (PBDEs), organophosphate flame retardants, phthalates and metalloestrogens. G protein-coupled estrogen receptor (GPER) exists widely in numerous cells/tissues of human and other vertebrates. A number of studies have demonstrated that GPER plays a vital role in mediating the estrogenic effects of environmental pollutants. Even at very low concentrations, these chemicals may activate GPER pathways, thus affect many aspects of cellular functions including proliferation, metastasis and apoptosis, resulting in cancer progression, cardiovascular disorders, and reproductive dysfunction. This review summarized the environmental occurrence and human exposure levels of these pollutants, and integrated current experimental evidence toward revealing the underlying mechanisms of pollutant-induced cellular dysfunction via GPER. The GPER mediated rapid non-genomic actions play an important role in the process leading to the adverse effects observed in experimental animals and even in human beings.

Informal electrical and electronic waste (e-waste) handling activities constitute a potentially important source of halogenated (HFRs) and organophosphate flame retardants (OPFRs) to the environment and humans. In this review, two electronic databases (ScienceDirect and Web of Science Core Collection) were searched for papers that addressed this topic. A total of 82 relevant studies (including 72 studies selected from the two databases and 10 studies located from the references of the first 72 selected studies) were identified that reported on human external and internal exposure to HFRs and OPFRs arising as a result of informal e-waste handling activities. Compared to the general population, higher levels of external exposure (i.e., inhalation, ingestion, and dermal absorption) and internal exposure (i.e., blood serum, hair, breast milk, urine, and other human matrices) to HFRs and OPFRs were identified for e-waste recyclers and residents inhabiting e-waste dismantling and recycling zones, especially for younger adults and children. Food intake and dust ingestion were the dominant exposure pathways for the majority of brominated flame retardants (BFRs) and dechlorane plus (DP); while inhalation was identified as the most significant pathway of human exposure to OPFRs in informal e-waste sites. The majority of research to date has focused on China and thus future studies should be conducted in other regions such as Africa and South Asia. Other suggested foci of future research are: examination of exposure via dermal contact with e-waste, dietary exposure of local populations to OPFRs, confirmation of the existence of and cause(s) of the higher body burdens of females compared with males amongst populations impacted by informal e-waste handling, and characterisation of exposure of such populations to chlorinated paraffins.

We investigated the concentration, composition, and potential risk of organophosphate esters (OPEs) and phthalates (PAEs) in soils and vegetation from rural areas of Dalian, Northeast China. The residues of total OPEs and PAEs in soils were in the range of 33.1–136 ng/g dw (dry weight) and 465–5450 ng/g dw, while the values in plants were 140–2360 ng/g dw and 2440–21800 ng/g dw, respectively. The concentrations of both chemicals in the plant rhizosphere soils were significantly lower than those in the bulk soils, suggesting an enhanced degradation or uptake by plant. The contaminations in soils also varied for different land use types with the concentrations generally higher in paddy soils than those in maize soils. The OPE and PAE concentrations in plant leaves were slightly higher than those in their corresponding roots. The bioconcentration factors of OPEs & PAEs were significantly negatively correlated with their octanol-water partition coefficients. A hazard assessment suggested potential medium to high risks from tricresyl phosphate (TMPP) and di-n-butyl phthalate (DNBP) for the agricultural soils in Dalian of China. Although the ecological risks of OPEs and PAEs in the rhizosphere soils were lower than those in the bulk soils, the relevant risk could still endanger human health via oral intake of these plants. The daily dietary intakes of OPEs and PAEs via vegetable and rice consuming were estimated, and the result suggests a higher exposure risk via ingestion of leafy vegetable than rice.