Organophosphorus Research Articles

Gestational exposure to organophosphate esters and autism spectrum disorder and other non-typical development in a cohort with elevated familial likelihood

BackgroundGestational exposure to organophosphate esters (OPEs) is known to affect offspring neurodevelopment in animal studies. However, epidemiological evidence is inconsistent. MethodsParticipants were 277 mother-child pairs from MARBLES (Markers of Autism Risk in Babies – Learning Early Signs), a cohort with elevated familial likelihood of autism spectrum disorder (ASD). Nine OPE biomarker concentrations were quantified in maternal urine collected during the 2nd or 3rd trimesters of pregnancy. At age 3 years, children underwent clinical assessment for ASD and were classified into ASD, other non-typical development (non-TD), or typical development (TD). Multinomial logistic regression was used to estimate associations between each OPE biomarker and relative risk ratios for ASD and non-TD compared to TD. We examined effect modification by child sex and socioeconomic status. We also conducted a secondary analysis by using a continuous measure of ASD symptom severity as an outcome. Quantile-based g-computation was performed to examine the associations for an OPE mixture. ResultsOverall, no significant association was observed between the concentrations of each OPE biomarker or their mixture and relative risk for either ASD or non-TD. Effect modifications by child sex and maternal education were not observed. When the analysis was stratified by homeownership, among non-homeowners, ASD likelihood was increased with increased levels of bis(1-chloro-2-propyl) phosphate, bis(butoxyethyl) phosphate, and sum of di-n-butyl phosphate and di-iso-butyl phosphate (DBUP/DIBP) (pint < 0.10). Higher DBUP/DIBP were associated with increased ASD symptom severity scores. ConclusionThere was no clear evidence of gestational OPE exposure in association with relative risk for ASD; however, potential effect modification by homeownership was observed. Although our cohort includes children with elevated familial likelihood of ASD, this is the first study investigating the association between gestational OPE exposure and clinically-diagnosed ASD. Further research is needed to confirm our findings in the general population.

Two-dimensional photonic crystal acetylcholinesterase hydrogel and organohydrogel sensors for efficient detection of organophosphorus compounds

Sensors capable of detecting organophosphorus (OP) compounds have attracted the most attention owing to severe OP contamination worldwide. Despite many years of research, the developed OP sensors mainly focused on detecting water-soluble OPs in proper environments and the exploration of OP sensors suitable in resource-limited areas is extremely challenging. Here, a simple two-dimensional photonic crystal (2D PC) hydrogel featuring capabilities of effectively quantitative determination of OP compounds is facilely constructed by immobilizing the enzyme acetylcholinesterase (AChE) onto a bovine serum albumin (BSA) protein hydrogel. Owing to the specific interaction between AChE and OP compounds, the OP compounds are easily bound to the hydrogel, triggering volume phase transition and resulting in apparent Debye diffraction ring variations. The resulting hydrogel sensors show a limit of detection (LoD) of 2.23 nM for trichlorfon and 0.07 nM for diethyl methylphosphonate (DMPP), respectively. On the basis of the hydrogel, a responsive organohydrogel is facilely fabricated utilizing a solvent exchange strategy to meet the requirements of applications in harsh environments and detection of the non-water-soluble OP compounds. The organohydrogel sensors, however, demonstrated a LoD of 0.70 μM for trichlorfon and 4.46 μM for DMPP, respectively. This work provides new light on the development of next-generation stable, low-cost, and portable field sensing devices.

Adipogenic Effects of Cresyl Diphenyl Phosphate (Triphenyl Phosphate Alternative) through Peroxisome Proliferator-Activated Receptor Gamma Pathway: A Comprehensive Study Integrating In Vitro, In Vivo, and In Silico from Molecule to Health Risk.

Cresyl diphenyl phosphate (CDP), a novel organophosphate ester (OPE), has been detected in various environmental and human samples. However, there is very limited knowledge regarding its toxicity, mechanisms of action, and potential health risks. Using new alternative methods (NAMs), across the molecular interactions, signaling pathways, cell functions, animal effects, and population risks, we investigated the potential adipogenic effects and associated risks of CDP and legacy OPE triphenyl phosphate (TPHP) by acting on peroxisome proliferator-activated receptor gamma (PPARγ). Among the 19 screened OPEs, CDP bound to PPARγ with the highest binding potency, followed by TPHP. CDP activated PPARγ through fitting into the binding pocket with strong hydrophobicity and hydrogen bond interactions; CDP exhibited higher potency compared to TPHP. In 3T3-L1 cells, CDP enhanced the PPARγ-mediated adipogenesis activity, exhibiting greater potency than TPHP. The intracellular concentration and receptor-bound concentrations (RBC) of CDP were also higher than those of TPHP in both HEK293 cells and 3T3-L1 cells. In mice, exposure to CDP activated the PPARγ-mediated adipogenic pathway, leading to an increased white adipose tissue weight gain. Overall, CDP could bind to and activate PPARγ, thereby promoting preadipocyte differentiation and the development of white adipose tissue. Its potential obesogenic risks should be of high concern.

Development of enzyme-based biosensor for residual detection of organophosphate pesticides using functionalized nanocellulose-modified silver nanoparticles

Excessive use of pesticides to satisfy the demand of a rapidly increasing population has posed numerous problems for human health and the environment. Therefore, we developed a nanocomposite comprised of rice husk-derived dialdehyde nanocellulose capped silver nanoparticles (AgNP@DANC) as an efficient immobilizing material for acetylcholinesterase (AChE) to develop a novel biosensor. This revolutionary enzyme-based biosensor was used for the rapid detection of organophosphate pesticides (OPs) using chlorpyrifos (CPF) and malathion (MLT) as representative pesticides in food stuffs. The detection of OPs is based on the inhibition of the catalytic activity of AChE in the presence of CPF and MLT coupled with the aggregation of silver nanoparticles (AgNPs) due to thiocholine that can be analyzed for rapid screening. The developed biosensor for CPF and MLT shows ultrasensitive behaviour over a linear range of 1 × 10−3 to 1 × 10-19 M and 1 × 10−3 to 1 × 10−17 M, respectively. Further, the sensitivity of the developed biosensor was also studied for real spiked samples. The developed biosensor shows great potential and sensitivity; thus, it could be a promising biosensor for the rapid and on-site detection of many OPs.

Insecticide binding mode analysis and biological effects of acetylcholinesterase target-site resistance mutations in Spodoptera frugiperda

It is urgent to solve insecticide resistance issues for fall armyworm (FAW), Spodoptera frugiperda. Some acetylcholinesterase-1 (Ace-1) mutations (A201S, G227A and F290V) have been identified as a cause of FAW resistance to organophosphates (OPs) and carbamates insecticides (CXs). However, the structural biological mechanisms on the relationship between the Ace-1 mutations and resistance to OPs and CXs still remain elusive. In this study, the A201S and F290V mutaions were found in eight fields populations of FAW except the G227A. Molecular docking revealed that the four Ace-1 proteins (Ace1-WT, Ace1-A201S, Ace1-G227A and Ace1-F290V) had the same binding modes and the same binding energies with acetylcholine (Ach), trichlorfon, chlorpyrifos, methomyl, carbaryl and chlorpyrifos oxide. The structural biological analysis revealed that the A201S mutations can enhance enzyme catalytic efficiency by introducing the hydroxyl group (-OH) from serine which performed the same function as the main-chain -NH and enhanced the interaction with the carboxy oxygen of acetylcholine (Ach), and the F290V mutation can effectively improve FAW resistance to insecticides by increasing the likelihood of Ach to enter the enzyme's active center for phenylalanine replaced by smaller valine under insecticide inhibition conditions. The bioassays and age-stage-specific life table analysis of FAW-SS and FAW-F290V populations revealed that F290V mutation effectively contributed to FAW resistance with a low fitness cost. This study provides a theoretical basis for future pest resistance management.

Occurrence Characteristics and Health Risk Assessment of Organophosphate Esters in Tap Water of Shanghai

To explore the occurrence characteristics and health risk levels of the new pollutants organophosphate esters （OPEs） in tap water in Shanghai, based on the water supply areas of the Qingcaosha Reservoir, Chenhang Reservoir, Dongfeng Xisha Reservoir, and Upstream Huangpu River water sources, a total of 52 large shopping malls in Shanghai were selected as tap water sampling sites. Solid phase extraction and gas chromatography-triple quadrupole mass spectrometry were used to determine eight types of OPEs in tap water from shopping malls, including three types of chlorinated OPEs, two types of alkyl OPEs, and three types of aryl OPEs. On this basis, the health risk assessment of the substances with high detection frequency and concentration was carried out. The results showed that six types of OPEs were generally detected, and the average levels of eight types of OPEs in tap water collected in summer and winter were 64.3 ng·L-1 and 60.5 ng·L-1, respectively. The concentration levels and detection rates of different types of OPEs in tap water followed the order of： chlorinated OPEs &gt; alkyl OPEs &gt; aryl OPEs. From the perspective of water sources, the average concentration of OPEs in tap water with Upstream Huangpu River water sources as the water source was the highest （132 ng·L-1 in summer and 170 ng·L-1 in winter）, and OPEs in tap water with Dongfeng Xisha Reservoir as the water source was the lowest （25.1 ng·L-1 in summer and 6.62 ng·L-1 in winter）. The average concentration of chlorinated OPEs in summer （62.1 ng·L-1） was higher than that in winter （53.9 ng·L-1）. Based on the reference dose of OPEs, there were no health risks to people of all ages through drinking water exposure. However, the OPE exposure in tap water of Shanghai was higher compared with that of other countries and regions, which requires further attention and research.

Development of a Generic Physiologically Based Kinetic Model for the Prediction of Internal Exposure to Organophosphate Pesticides.

Since their introduction into agriculture, the toxicity of organophosphate (OP) pesticides has been widely studied in animal models. However, next generation risk assessment (NGRA) intends to maximize the use of novel approach methodologies based on in vitro and in silico methods. Therefore, this study describes the development and evaluation of a generic physiologically based kinetic (PBK) model for acute exposure to OP pesticides in rats and humans using quantitative structure property relationships and data from published in vitro studies. The models were evaluated using in vivo studies from the literature for chlorpyrifos, diazinon, fenitrothion, methyl-parathion, ethyl-parathion, dimethoate, chlorfenvinphos, and profenofos. Evaluation was performed by comparing simulated and in vivo observed time profiles for blood, plasma, or urinary concentrations and other toxicokinetic parameters. Of simulated concentration-time profiles, 87 and 91% were within a 5-fold difference from observed toxicokinetic data from rat and human studies, respectively. Only for dimethyl-organophosphates further refinement of the model is required. It is concluded that the developed generic PBK model provides a new tool to assess species differences in rat and human kinetics of OP pesticides. This approach provides a means to perform NGRA for these compounds and could also be adopted for other classes of compounds.

Real-time, specific, and label-free transistor-based sensing of organophosphates in liquid

Organophosphates (OP), commonly used in agriculture and as chemical warfare agents, pose significant environmental risks, necessitating real-time, low-cost OP detection methods. In particular, liquid-phase OP sensing with minimal sample volumes is crucial. While several methods allow rapid detection of low concentrations of OP vapors, they are effective only in the short term, while vapors are still being produced. Many OP compounds are semi-volatile, leading to the contamination of water, soil, and surfaces, posing a risk of secondary, long-term exposure. Detecting this contamination requires methods that can be directly applied to droplets of the affected medium. Currently, no method provides the desired combination of ultra-sensitivity, quantitative detection, rapid response, and low-cost for detecting OPs in liquid samples. This study aims to demonstrate quantitative, low-cost, real-time, specific, and label-free OP sensing in ultra-small samples using a transistor-based approach. The current work employs the 2-(4-Aminophenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (aminophenyl-HFIP) functionalized meta-nano-channel field-effect chemical sensor (MNChem sensor) to monitor the organophosphate, diethyl cyanophosphonate (DCNP), in liquid samples. The silicon component of the MNChem is fabricated using a complementary metal-oxide semiconductor (CMOS) process, and the amine-based chemical functionalization of the sensing area is performed post-fabrication. The MNChem sensor provides electrostatic control over the source-drain current (IDS), allowing an optimized channel configuration that efficiently transduces localized OP recognition events into significant IDS variations. Sensing is performed using 0.5 μL buffer solution to simulate a miniature field-deployable sensor for on-site liquid analysis. We report the sensing of DCNP with a limit-of-detection of 100 fg/mL, a dynamic range of 9 orders of magnitude, and excellent linearity (≥0.97) and sensitivity. Control measurements confirm the specificity and reliability of the sensor's response, validating its applicability. This study introduces a novel method for OP detection in contaminated droplets using a low-cost disposable transistor technology.

Fast determination of organophosphate esters and their metabolites in human matrices by a straightforward cold-induced strategy coupled with HPLC-MS/MS.

Organophosphate esters (OPEs) are commonly used chemicals and are also regarded as emerging environmental pollutants. Recently, it has been proved that metabolites of OPEs (mOPEs) could also cause health concerns. However, analytical methods for the concurrent measurement of OPEs and mOPEs in human matrices are still complicated. In this study, a convenient and efficient analytical method combining a cold-induced strategy and HPLC-MS/MS was developed to simultaneously determine 18 OPEs and 10 mOPEs in human serum, urine, and human milk. In brief, after the sample was extracted with acetonitrile, a "one-step" treatment combining purification and enrichment was accomplished by cold-induced liquid-liquid extraction (CI-LLE), and analytes were then quantified by HPLC-ESI-MS/MS. The ratio of acetonitrile/water, and the temperature and time set in the CI-LLE procedure were optimized for achieving the highest enrichment factors. Under thebest conditions, linearity, limits of detection (LODs), recovery, precision, and matrix effects of OPEs/mOPEs were verified. LODs of OPEs/mOPEs in serum, urine, and human milk were 0.1-113pg/mL, 0.1-22pg/mL, and 0.2-22pg/mL, respectively. Average recoveries ranged from 80 to 123%, with relative standard deviations lower than 15% for most analytes. The matrix effect test showed slight signal enhancement or inhibition, and the use of isotopically labeled internal standards (ISs) could compensate for the effects. In real sample analysis, both OPEs and mOPEs showed high detecting frequency, which indicated their ubiquity in humans.

Long-term organic fertilization increases phosphorus content but reduces its release in soil aggregates

There is currently limited published information on the coupling correlation between phosphorus (P) redistribution and release in soil aggregates. To fulfill this gap, we conducted a 10-year field experiment of soil amended with organic fertilizer to investigate phosphorus transformation and immobilization during the organic fertilization process. Microbial communities, functional genes and enzymes were analyzed to elucidate the multi-mechanisms of the conversion among phosphorus fractions. Phosphorus content in soil aggregates was determined as follows: FeP (34 % ~ 45 %) > Ca-P (16 % ~ 27 %) > Oc-P (15 % ~ 17 %) > Or-P (13 % ~ 19 %) > Al-P (4 % ~ 5 %) ≈ Ex-P (2 % ~ 4 %). Compared to a control with only chemical fertilizer, a 13 % ~ 38 % increase in P availability of experimental treatments mixed with chemical and organic fertilizers was attributed to the mineralization of Or-P, but not to the dissolution of inorganic P. Following organic fertilization, the phnF gene was dominant factor to promote the mineralization of Or-P, because it encodes CP lyases that pyrolyzes the CP bounds in organophosphate esters. Overall, organic fertilization decreased P release risk in soil aggregates, especially for the micro-aggregates that showed a higher capacity to activate non-available P and immobilize endogenous P in farmland soil. These results provide a theoretical guidance for the source control of P pollution in agro-ecosystems.

Sacral neuromodulation for Organophosphate-induced delayed neuropathy neurogenic lower urinary tract dysfunction: a case report

BackgroundOrganophosphate-Induced Delayed Neuropathy (OPIDN) is a rare neurological disorder triggered by exposure to organophosphorus compounds. These compounds exert their neurotoxic effects by impacting the nervous system, leading to systemic manifestations. Urinary system symptoms are infrequently observed in clinical settings. Currently, effective therapeutic interventions for OPIDN-related urinary symptoms are lacking. Sacral nerve modulation therapy, an FDA-approved approach for managing lower urinary tract symptoms, presents as a promising option. Herein, we present a case of OPIDN-induced lower urinary tract obstruction successfully treated with sacral nerve modulation therapy, resulting in substantial symptom relief.Case reportA 27-year-old male patient presented with severe bilateral hydronephrosis, attributed to low bladder compliance and accompanied by a fever persisting for 6 days. The patient’s medical history revealed accidental ingestion of organophosphate pesticide (Dimethoate) with no concomitant underlying diseases. In consideration of the potential for OPIDN, surgical intervention in the form of sacral neuromodulation (phase I) was undertaken. Subsequent evaluation one month post-surgery revealed notable improvements in both bladder compliance and bilateral hydronephrosis, necessitating sacral neuromodulation (phase II). Presently, following a 5-month follow-up period, the patient remains asymptomatic and in favorable health.ConclusionThis patient achieved long-term relief using sacral neuromodulation.

High-sensitive detection of organophosphate and carbamate pesticide residues in milk based on bioluminescence method

Organophosphorus pesticides (OPs) and carbamate pesticides (CBs) are the most commonly used pesticides in agricultural cultivation. The pesticide residues in plant products can easily enter dairy cows through feed, resulting in the pesticide low-concentration residues in milk. Traditional acetylcholinesterase (AChE) inhibition-based colorimetric methods have low sensitivity and could not satisfy the detection of low-concentrations of OPs and CBs residues in dairy products. In this study, we combined firefly luciferase (FLuc)-mediated bioluminescence with the inhibition of AChE-catalyzed substrate activity by pesticides to develop a highly sensitive and rapid method for detecting OPs and CBs residues in milk. AChE breaks down D-luciferin acetate to produce D-luciferin, which is recognized by the FLuc and emits luminescence in the presence of ATP. However, the presence of OPs and CBs inhibits AChE, causing the reduction or disappearance of the luminescence signal. The luminescence signal can be detected using a hand-held luminescence photometer, eliminating the need for large instrumentation. The AChE-FLuc system accurately detected OPs and CBs in milk within 30 min, with detection limits of 7.89 ng/mL and 1.75 ng/mL, respectively. The sensitivity of this method is approximately ten times higher than that of traditional AChE inhibition methods, meeting the pesticide residue limits in milk set by China and the European Union.

Structural and morphological studies of non-covalent functionalization carbon nanotubes wrapped poly(3-hexylthiophene-2,5-diyl) nanocomposites

In this study, a simple and efficient non-covalent functionalization method was developed to introduce conducting polymer of P3HT onto pristine MWCNT and hydroxyl MWCNT surfaces without causing significant changes in electrical characteristics, especially if used as a sensing material. Electron microscopy (FE-SEM) and (HR-TEM) were used to examine the surface morphology of nanocomposites, which demonstrated that the MWCNTs were well wrapped by P3HT. EDX analysis showed interactions between MWCNT-OH and P3HT, with a higher sulfur content of 7.77 wt% from P3HT. Additionally, the diameters of both pristine MWCNT (24.46 nm) and MWCNT-OH (27.56 nm) increased significantly when they form nanocomposites (35.35 nm and 39.40 nm respectively). Further characterization of the produced P3HT-MWCNT nanocomposite was performed using FT-IR and Raman spectroscopy. It was discovered that MWCNTs were dispersed uniformly, with a substantial interaction between P3HT and MWCNTs. The introduction of malathion on the surface of the nanocomposites reveals interaction between P3HT and malathion via intermolecular hydrogen bonding of thiophene, as evidenced by inelastic neutron scattering (INS) spectroscopy, suggesting that the P3HT/MWCNT has the potential as a promising sensing material for organophosphate compounds detection.

Improved and Novel Methods for Investigating Organophosphate Esters in Particulate Matter

A pressurized liquid extraction (PLE) method for the extraction of 31 organophosphate esters (OPEs) and novel organophosphate esters (NOPEs) has been developed. Unlike previously published methods, this method utilizes the high-throughput nature of PLE (as opposed to Soxhlet or sonication methods) without using potentially harmful organic solvents like methylene chloride. Combinations of hexane and acetone and hexane and ethyl acetate at various temperatures were examined. Extracts were concentrated and analyzed via gas chromatography–mass spectrometry. The final optimized method utilized 1:1 v/v hexane/ethyl acetate at 100 °C for three static cycles (5 min each) at 80% flush volume and a 100 s N2 purge. This provided average surrogate corrected target analyte percent recoveries in spike and recovery experiments (n = 6) for OPEs and NOPEs of 106 ± 13%, with average surrogate recoveries of 88.6 ± 7.3%. The developed method was further validated using standard reference materials and was then applied to atmospheric particulate matter samples collected in the city of Providence, RI. The dataset reflected ambient concentrations of 16 OPEs and NOPEs (reported in pg m−3) for the first time in the greater Providence metropolitan area, including one of the first reports of NOPEs in atmospheric particulate matter in the U.S.

Optimization and pharmacological evaluation of phytochemical-rich Cuscuta reflexa seed extract for its efficacy against chlorpyrifos-induced hepatotoxicity in murine models

The popular organophosphorus (OP) compound chlorpyrifos (CP) has recently gained significant attention due to its health risks, particularly among farmers exposed to OP pesticides. This study aimed to evaluate the acute toxicity of Cuscuta reflexa seed extract (CRSE) and its efficacy of mitigating the adverse effects of CP in albino male mice. For acute toxicity analysis, the first group was served as the control group, while the second group was received CRSE (200 mg/kg/bw) on the first day of the 14-day experiment. For hepatotoxicity analysis, the first group was the control group, the second group (vehicle control) received corn oil (CO) (2 mL/kg/bw), the third group was given CP (20 mg/kg/bw) dissolved in corn oil and the fourth group was given CP (20 mg/kg/bw) along-with CRSE (200 mg/kg/bw) orally via gavage once daily for 21 days. The acute toxicity examination revealed no statistically significant differences between the CRSE-treated and control groups in serum biochemical indicators and histopathological analyses of various organs, suggesting that CRSE as safe at a dosage of 200 mg/kg/bw, with an oral LD50 in mice higher than 200 mg/kg. The hepatotoxicity study demonstrated that the CP administration resulted in liver damage and oxidative stress, while CRSE acted as an antioxidant and attenuated the signs of oxidative stress in liver damage. Hence, a promising therapeutic approach for lowering CP hepatotoxicity is co-treatment with CRSE.

High-performance metal-organic frameworks for efficient adsorption, controlled release, and membrane separation of organophosphate pesticides

Metal-organic frameworks (MOFs) are considered good choices for the absorption, separation, and release of various substances. The rapid increase in the number of MOFs being produced makes it impractical to conduct experimental research to identify the most promising candidates in these areas. Therefore, computational screening has emerged as a robust approach. We employed this approach to identify the most efficient MOFs for the removal, separation, and controlled release of organophosphorus pesticides, including diazinon, chlorpyrifos, and chlorpyrifos-methyl. From a database of approximately 14,000 MOFs, 584 MOFs with the largest cavity diameters were used in the screening process to evaluate promising candidates for each pesticide. Monte Carlo simulations were used to estimate the pesticide uptake capacities and isosteric heats of the selected MOFs. The structural properties of MOFs were correlated with their adsorption capacities and isosteric heats. Computational screening identified 325, 330, and 450 MOFs as potential absorbents and carriers for diazinon, chlorpyrifos-methyl, and chlorpyrifos, respectively. Additionally, it proposed 235, 254, and 135 MOFs as membranes for the effective separation of these organophosphorus pesticides. The reactivity of the pesticides was explored using quantum mechanics calculations. Molecular dynamics simulations of the top three MOFs with high uptake capacities for each pesticide were performed and analyzed to understand the interactions between the MOF, pesticide, and water molecules. The solvation-free energies of the pesticides were calculated for various solvents to identify the most effective solvent for desorbing pesticides from the MOFs, thereby enabling MOF regeneration.

Nationwide Profiling and Source Identification of Organophosphate Esters in Korean Surface Waters Using Target, Suspect, and Non-Target HRMS Analysis

Organophosphate esters (OPEs) are emerging contaminants that serve as alternatives to regulated substances in aquatic environments. A nationwide large-scale assessment for OPEs, including point sources, remains insufficient. To address this issue, we aimed to investigate OPEs occurrence and novel OPEs via comprehensive target, suspect and non-target analysis. Among the 11 target OPEs, 10 were detected at sampling sites distributed evenly nationwide. The highest mean concentrations were measured for tris-(2-butoxyethyl) phosphate (TBOEP) and tris(2-chloroisopropyl) phosphate (TCIPP). The multivariate statistical analysis revealed that TBOEP and TCIPP are essential components for assessing total OPEs pollution. The systematic risk assessment results evaluated the overall risk contribution of TBOEP and the significant risk impact of 2-ethylhexyl diphenyl phosphate. Promising suspect and non-target analysis enabled frequent detection and identification of 6 antioxidant transformation products (TPs), as well as the tentative identification of 14 OPEs and TPs, including 3 di-OPEs. Based on sampling site classification, we confirmed that major OPEs are significantly discharged near point sources. We believe that this is the first attempt to assess the nationwide risk and potential sources of OPEs in Korean surface waters, providing insights that could support further prioritization and regulation efforts.

Gestational exposure to organophosphate ester flame retardants and risk of childhood obesity in the environmental influences on child health outcomes consortium

Introduction: Organophosphate esters (OPEs) are increasing in use as flame retardants and plasticizers and concerns have been raised given their endocrine-disrupting activities and possible obesogenic consequences. However, longitudinal studies on gestational OPE exposure and childhood obesity are scarce. This study examined whether OPE levels in maternal urine during pregnancy were associated with the risk of childhood obesity. Methods: OPEs were analyzed in pregnancy urine samples of 5,087 individuals from 14 studies contributing to the Environmental influences on Child Health Outcomes (ECHO) Cohort. BDCPP, DBUP/DIBP, and DPHP, detected in > 80 % of the samples, were modeled continuously and by tertiles; whereas BCPP, BBOEP, and BCETP, detected in 50–80 % of samples, were modeled categorically (not-detected, low, and high). Childhood obesity was defined by BMI z-score ≥ 95th percentile according to WHO (<2 years) and the CDC (≥2 years) metrics. Adjusted modified Poisson regression models assessed childhood obesity risk and the mixture effect was assessed using Bayesian kernel machine regression (BKMR). Results: BMI measurements were available for 3,827 children in infancy (0.5–1.9 years), 3,921 children in early childhood (2.0–4.9 years), and 2,541 children in mid-childhood (5.0–10.0 years). Obesity was present in 16–21 % of children across age groups. In mid-childhood DBUP/DIBP second and third versus first tertiles were associated with increased obesity risk (RR 1.14; 95 % CI: 1.02, 1.28; and RR 1.11; 95 % CI: 0.97, 1.27; respectively); whereas BDCPP second and third versus first tertiles reflected an inverse association with obesity risk (RR 0.85; 95 % CI: 0.80, 0.91 and RR 0.91; 95 % CI: 0.77, 1.07; respectively). No association with obesity risk was observed for DPHP, BCPP, BBOEP, and BCETP. Directions observed were consistent with those seen in BKMR models. Conclusions: This study identified mixed associations between gestational OPE exposure and childhood obesity. Further investigation across a comprehensive range of OPE exposures is warranted.

A green approach coupled with molecular dynamics simulations and toxicity assays to infer the mode of action for organophosphate esters

Organophosphate esters (OPEs) have attracted extensive attention due to their toxic effects on human health and biological systems as plasticizers and flame retardants. This study focused on exploring a green approach to get toxicity mechanisms that used less solvents or organisms. The toxicity values of selected organophosphate esters including tri (2-chloroethyl) phosphate (TCEP), tri (1, 3-dichloro-2-propyl) phosphate (TDCP), tripropyl phosphate (TPrP), tri-n-butyl phosphate (TnBP), and tritolyl Phosphate (TCrP) to Photobacterium phosphoreum were determined. Their EC50 range was between 7.27 × 10−8–5.12 × 10−6 mol/L. Based on molecular dynamics simulation the data of binding affinity between OPEs and n-octanol / phospholipid bilayer were calculated respectively. Coupling with binding affinity energies and toxicity values, the mode of action (MOA) of OPEs including types of reactive or anesthetic mechanism could be fast deduced. The proposed hypothesis of n-octanol (C8H18O) as a virtual biofilm to replace phospholipid bilayer was verified. The alternative green approach could simplify toxicity assay and realize fast predicting MOA for different chemicals and model organisms.

Responsive release of guest aqueous droplet in liquid crystal droplet assists the detection of organophosphorus using commercial pregnancy test strip

Here, we report a liquid crystal (LC) double-emulsion based system for organophosphorus (OPs) sensing by controllable release of guest aqueous droplets (GADs) cargo. First, double liquid crystal emulsion, water in liquid crystal in water (W/LC/W), with size between 4∼ 20 μm was prepared with GADs loaded at the center of liquid crystal droplet (LCD) through elasticity trap. The LCDs were monodispersed and response sensitively to amphiphilic surfactant with opposite charge. With the capability of ejecting GADs with human chorionic gonadotropin (hCG) as cargo located in LCD to continuous aqueous phase, responsive vehicles are obtained and applied in the repurposing of commercial pregnancy test strip (PTS). With hydrophobic alkyl chain and hydrophilic head, myristoylcholine (Myr) is a good amphiphilic surfactant to trigger the release of hCG, and substrate for the enzymatic hydrolysis of acetylcholine esterase (AChE). Provided with the inhibition effect of OPs to the hydrolysis ability of AChE, OPs correlate positively with the concentration of Myr, thus correlate well with the release of hCG in W/LC/W emulsion. Thus, OPs residue in river or food is readily visualized using commercial PTS.