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.

Diethyl ethylphosphonate retardants disturbed the gut microbiome and metabolite SCFAs in vitro based on simulator of the human intestinal microbial ecosystem.

Diethyl ethylphosphonate (DEEP) as a novel organophosphorus flame retardant received increasing attention and its structure was discovered. But there are currently insufficient studies on how DEEP exposure affects the gut microbiome. In this study, the effects of DEEP on the structure and function of the human gut microbiota were examined using the SHIME system. Results from high-throughput sequencing of the 16S rRNA gene show that the high dose DEEP exposure reduced the Shannon and Simpson index in the transverse and descending colon. The Bacillota had the highest proportion while the proportion of Proteobacteria gradually decreased at the phylum level. The abundance of Escherichia, Prevotella, and Bilophila at the genus level increased with increasing doses of DEEP exposure. On the contrary, the abundance of Megasphaera, Klebsiella, and Phascolarctobacterium decreased. The short-chain fatty acids had a significant shift. With increasing doses of DEEP exposure, the concentration of acetic acid and propionic acid increased, while the concentration of butyric acid reached the highest at the medium dose of exposure. In addition, Bilophila, Psychrobacter, Escherichia, and Nostoe showed strong beneficial associations with acetic and propionic acids under DEEP exposure. Phocaeicola, Agathobacter, Klebsiella, Megasphaera, Phascolarctobacterium, and Bacteroides were negatively association with acetic and propionic acids. In a word, the study verified that exposure to different doses of DEEP can cause changes in the composition of the gut microbiome and metabolite SCFAs, which provides ideas for the investigation of other potential hazards of DEEP on human beings.

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

BACKGROUND: Organophosphate-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 REPORT: A 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. CONCLUSION: This patient achieved long-term relief using sacral neuromodulation.

Comparative transcriptional analysis between susceptible and resistant populations of Aedes (Stegomyia) aegypti (Linnaeus, 1762) after malathion exposure.

Aedes aegypti is an important vector of arboviruses, including dengue, chikungunya and Zika. The application of synthetic insecticides is a frequently used strategy to control this insect. Malathion is an organophosphate insecticide that was widely used in Brazil in the 1980s and 1990s to control the adult form of A. aegypti. In situations where resistance to currently used insecticides is detected, the use of malathion may be resumed as a control measure. Many studies have confirmed resistance to malathion, however, comparative studies of differential gene expression of the entire transcriptome of resistant and susceptible insects are scarce. Therefore, understanding the molecular basis of resistance to this insecticide in this species is extremely important. In this paper, we present the first transcriptomic description of susceptible and resistant strains of A. aegypti challenged with malathion. Guided transcriptome assembly resulted in 39,904 transcripts, where 2133 differentially expressed transcripts were detected, and three were validated by RT-qPCR. Enrichment analysis for these identified transcripts resulted in 13 significant pathways (padj < 0.05), 8 associated with down-regulated and 5 with up-regulated transcripts in treated resistant insects. It was possible to divide the transcripts according to the mechanism of action into three main groups: (i) genes involved in detoxification metabolic pathways; (ii) genes of proteins located in the membrane/extracellular region; and (iii) genes related to DNA integration/function. These results are important in advancing knowledge of genes related to resistance mechanisms in this insect, enabling the development of effective technologies and strategies for managing insecticide resistance.

Legacy and emerging flame retardants in sediments and wastewater treatment plant-derived biosolids.

A baseline assessment of legacy and emerging flame retardant chemicals was performed in inland and transitional sediments as well as biosolids emanating from a selection of wastewater treatment plants (WWTPs) in Ireland. A selection of 24 polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and chlorinated organophosphate esters (Cl-OPEs) were quantified in: 81 inland and transitional sediment samples collected during 2023; 39 transitional sediments collected between 2018 and 2022; and 21 biosolid samples collected from 7 WWTPs over 4-month intervals in January, May, and September 2023. Highest concentrations of BDE-209 and several Cl-OPEs were detected in both sediment and biosolid samples, while most PCBs and penta-/octa-BDEs were comparatively low. Moderate levels of PBDEs and Cl-OPEs were detected in Irish sediments compared to similar studies conducted internationally. In biosolid samples, levels of BDE-209 were on the higher end of figured reported worldwide while levels of Σ8Cl-OPEs were the highest relative to comparable international studies. PCBs meanwhile are on the lower end of international levels for both biosolids and sediments. Based on available predicted no-effect concentrations (PNECs), the majority of compounds assessed were found to be of low-risk based on their levels in sediments with the exception of TCIPP (Risk Quotient - RQ = 1.354 = high risk) as well as EHDPP, TEHP, PCB-118, and PCB-52 (RQ = 0.948, 0.576, 0.446, and 0.257 respectively = moderate risk). Similar risk assessment could not be performed on contaminants in biosolids, though levels of BDE-209 were on the higher end of figured reported worldwide (avg = 3155 ng/g) while levels of Σ8Cl-OPEs were the highest relative to comparable international studies (avg8 = 3290 ng/g). As the legacy PBDEs and PCBs have been listed as persistent organic pollutants (POPs) and replacement flame retardants such as Cl-OPEs have been flagged by programmes such as human biomonitoring for EU (HBM4EU) and the NORMAN Network as chemicals of emerging concern, continued monitoring of these moderate and high-risk contaminants in sediments, as well as an investigation of potential contamination of the food chain through land-spreading of biosolids on agricultural lands, would be warranted.

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 the best 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 0.1-113 pg/mL, 0.1-22 pg/mL, and 0.2-22 pg/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.

Assessment of the Potential Phytotoxicity of Chlorpyrifos in the Wetland Macrophyte Bidens laevis (L.).

Chlorpyrifos (CPF) has been used worldwide, but its possible negative effects on macrophytes have been scarcely studied. The main goal of the present work was to assess the potential phytotoxic effects of CPF on different stages (seed and seedling) of the wetland macrophyte Bidens laevis. During the germination of seeds, stimulation of radicle growth at low concentrations of CPF (10 µg/L) and inhibition of its elongation at 80 µg/L CPF were observed. In seedlings, concentrations ≤ 160 µg/L CPF did not exhibit adverse effects on growth after 7 days of exposure, despite the decrease of photosynthetic pigments and carotenoids observed at 40 µg/L CPF compared to the control. Environmentally relevant concentrations of CPF altered neither oxidative stress biomarkers nor pigment contents in seedlings exposed for 48 h, suggesting CPF would be non-toxic to B. laevis in natural scenarios.

Role of paraoxonase 1 in organophosphate G-series nerve agent poisoning and future therapeutic strategies.

Chemical warfare nerve agents (CWNA) are neurotoxic chemicals unethically used as agents of mass destruction by terrorist outfits and during war. The available antidote against CWNA-mediated toxicity is not sufficiently effective and possesses several limitations. As a countermeasure, paraoxonase 1 (PON1), a catalytic bioscavenger, is being developed as a prophylactic treatment. However, the catalytic activity and substrate specificity of human PON1 are insufficient to be used as a potential antidote. Several laboratories have made different approaches to enhance the CWNA hydrolytic activity against various nerve agents. This review explores the holistic view of PON1 as a potential prophylactic agent against G-series CWNA poisoning, from its initial development to recent advancements and limitations. Apart from this, the review also provides an overview of all available PON1 variants that could be used as a potential prophylactic agent and discusses several possible ways to counteract immunogenicity.

Plasticizers levels in four fish species from the Ligurian Sea and Central Adriatic Sea (Mediterranean Sea) and potential risk for human consumption.

Plastic materials contain additives such as plasticizers and flame retardants, which are not covalently bound to plastic polymers and can therefore be unintentionally released into the marine environment. This study investigated three families of compounds, phthalates (PAEs), organophosphate esters (OPEs), and non-phthalate plasticizers (NPPs) currently used as plastic additives, in 48 muscle samples of bogue (Boops boops), European hake (Merluccius merluccius), red mullet (Mullus barbatus), and European pilchard (Sardina pilchardus) sampled in the Central Adriatic and the Ligurian Seas. The additional goal of this study is to assess the potential risk to human health from fish consumption with the objective of determining whether the detected levels might potentially pose a concern. PAEs represent the majority of the plastic additives detected in the selected species, with ubiquitous distribution across the study areas, whereas for OPEs and NPPs, there is a more pronounced difference between the two study areas, suggesting that these compounds may represent different exposure levels in the two seas. Among PAEs, bis(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and diisobutyl phthalate (DIBP) were the most abundant compounds, reaching levels up to 455 ng/g ww. OPEs were detected at higher concentrations in samples from the Ligurian Sea, and triethyl phosphate (TEP) was the most abundant compound. Among the NPPs, acetyl tributyl citrate (ATBC) was most frequently detected. From the results obtained, fish consumption may not pose a risk to human health (Hazard Quotient<1) but needs to be considered in future studies. Given the limited number of studies on PAEs, OPEs and NPPs in the Mediterranean Sea, further research is necessary to understand their potential bioaccumulation in marine organisms.

Global Gridded Emission Inventory of Organophosphate Flame Retardants from 2010 to 2020.

As a substitute for brominated flame retardants, organophosphate flame retardants (OPFRs) have become a global concern due to their high toxicity and bioaccumulation. To paint an overall picture of OPFRs in the global environment, the present study develops a gridded global emission inventory of OPFRs on a spatial resolution of 1 × 1° from 2010 to 2020. Revealing a 3.31% average annual increase in emissions, totaling 21,324.42 tons. The production process is the primary source, accounting for 55.43% of emissions, with consumption processes making up the rest. Major sources are in Asia, North America, and Europe. The inventory is verified by implementing emission data into a global atmospheric transport model to predict OPFR concentrations in the global environment and comparing modeled concentrations with field sampled data. The results indicate that the inventory is reliable except for the pristine polar region, where the emission inventory and modeled concentrations underestimate OPFR levels in the atmosphere, likely resulting from ignorance of chemical reactions and the secondary derivative of parent OPFRs during their global long-distance atmospheric transport in the model. This comprehensive data set aids in formulating OPFR emission control policies and assessing health risks.

Enzyme-armed nanocleaner provides superior detoxification against organophosphorus compounds via a dual-action mechanism.

By inhibiting acetylcholinesterase (AChE) activity, organophosphate compounds (OPs) can quickly cause severe injury to the nervous system and death, making it extremely difficult to rescue victims after OP exposure. However, it is quite challenging to construct scavengers that neutralize and eliminate these harmful chemical agents promptly in the blood circulation system. Herein, we report an enzyme-armed biomimetic nanoparticle that enables a 'targeted binding and catalytic degradation' action mechanism designed for highly efficient in vivo detoxification (denoted as 'Nanocleaner'). Specifically, the resulting Nanocleaner is fabricated with polymeric cores camouflaged with a modified red blood cell membrane (RBC membrane) that is inserted with the organophosphorus hydrolase (OPH) enzyme. In such a subtle construct, Nanocleaner inherits abundant acetylcholinesterase (AChE) on the surface of the RBC membrane, which can specifically lure and neutralize OPs through biological binding. The OPH enzyme on the membrane surface breaks down toxicants catalytically. The in vitro protective effects of Nanocleaner against methyl paraoxon (MPO)-induced inhibition of AChE activity were validated using both preincubation and competitive regimens. Furthermore, we selected the PC12 neuroendocrine cell line as an experimental model and confirmed the cytoprotective effects of Nanocleaner against MPO. In mice challenged with a lethal dose of MPO, Nanocleaner significantly reduces clinical signs of intoxication, rescues AChE activity and promotes the survival rate of mice challenged with lethal MPO. Overall, these results suggest considerable promise of enzyme-armed Nanocleaner for the highly efficient removal of OPs for clinical treatment.

Adsorptive removal of organophosphate pesticides from aqueous solution using electrospun carbon nanofibers.

Organophosphate pesticides (OPPs) are widely prevalent in the environment primarily due to their low cost and extensive use in agricultural lands. However, it is estimated that only about 5% of these applied pesticides reach their intended target organisms. The remaining 95% residue linger in the environment as contaminants, posing significant ecological and health risks. This underscores the need for materials capable of effectively removing, recovering, and recycling these contaminants through adsorption processes. In this research, adsorbent materials composed of electro-spun carbon nanofibers (ECNFs) derived from polyacrylonitrile was developed. The materials were characterized through several techniques, including scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier Transform Infrared Spectroscopy (FTIR), Brunauer-Emmett-Teller (BET) analysis, and contact angle measurements. SEM analysis revealed details of the structural properties and inter-fiber spacing variations of the carbon nanofibers. The results revealed that ECNFs possess remarkable uniformity, active surface areas, and high efficiency for adsorption processes. The adsorption studies were conducted using batch experiments with ethion pesticide in aqueous solution. High-Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD) was utilized to quantify the concentrations of the OPP. Various parameters, including adsorbent dosage, pH, contact time, and initial ethion concentration, were investigated to understand their impact on the adsorption process. The adsorption isotherm was best described by the Freundlich model, while the kinetics of adsorption followed a non-integer-order kinetics model. The adsorption capacity of the ECNFs for OPP removal highlights a significant advancement in materials designed for environmental remediation applications. This study demonstrates the potential of ECNFs to serve as effective adsorbents, contributing to the mitigation of pesticide contamination in agricultural environments.

Unveiling the mechanisms of reproductive toxicity induced by full life-cycle exposure to environmentally relevant concentrations of tris(2-chloroethyl) phosphate in male zebrafish.

Tris (2-chloroethyl) phosphate (TCEP), a commonly used organophosphate flame retardant, has garnered considerable concern owing to its pervasive presence in the environment and its toxic effects on living organisms. The perpetuation of populations and species hinges on successful reproduction, yet research into the mechanisms underlying reproductive toxicity remains scant, particularly in aquatic species. In this work, zebrafish embryos were exposed to TCEP (0, 0.8, 4, 20, and 100 µg/L) for 120 days until sexual maturation, and multiple reproductive endpoints were investigated in male zebrafish. Our results showed that the body weight, body length, and gonadal-somatic index (GSI) were remarkably decreased in all TCEP treatment groups (except GSI in the 0.8 µg/L TCEP-treated group). Long-term exposure to TCEP led to reduced reproductive capacity of male zebrafish, as evidenced by decreased fertilization. Histological observation gave an indication of delayed testicular development and inhibited spermatogenesis under TCEP stress. The content of testosterone (T) was significantly elevated in all TCEP treatment group, whereas 17 ß-estradiol (E2) levels remained stable. Transcriptome analysis revealed a lot of downregulated genes involved in steroid hormone biosynthesis, energy metabolism, and sperm motility, which might account for the imbalance of steroid hormone levels, retarded spermatogenesis and declined fertilization success. Overall, these findings offered a thorough understanding of the mechanisms underlying the male reproductive toxicity caused by TCEP, highlight the risk of TCEP on reproductive health of fish.

Exposure to organophosphate ester flame retardants and plasticizers and associations with preeclampsia and blood pressure in pregnancy.

BACKGROUND: Organophosphate esters (OPEs), flame retardants and plasticizers found widely in consumer products, may impact vascularization processes in pregnancy. Yet, the association between maternal exposure to OPEs and both preeclampsia and blood pressure during pregnancy remains understudied. METHODS: Within the LIFECODES Fetal Growth Study (N = 900), we quantified 8 OPE metabolites from maternal urine collected at up to 3 time points during pregnancy and created within-subject geometric means. Outcomes included diagnosis of preeclampsia and longitudinal systolic (SBP) and diastolic (DBP) blood pressure measurements (mean = 14 per participant). Cox proportional hazards models were used to estimate associations between OPE metabolites and preeclampsia. Associations between average OPE metabolite concentrations and repeated blood pressure measurements were estimated using generalized estimating equations. RESULTS: Five OPE metabolites were detected in at least 60% of samples; 3 metabolites detected less frequently (5-39%) were examined in an exploratory analysis as ever vs. never detectable in pregnancy. There were 46 cases of preeclampsia in our study population. Associations between OPE metabolites and preeclampsia were null. We noted several divergent associations between OPE metabolites and longitudinal blood pressure measurements. An interquartile range (IQR) difference in average bis(2-chloroethyl) phosphate concentrations was associated with a decrease in SBP (-0.81 mmHg, 95% confidence interval [CI]: -1.62, 0.00), and, conversely, bis(1-chloro-2-propyl) phosphate was associated with a slight increase in SBP (0.94 mmHg, 95% CI: 0.28, 1.61). We also noted a decrease in SBP in association with several metabolites with low detection frequency. CONCLUSIONS: We observed null associations between OPE metabolites and preeclampsia, but some positive and some inverse associations with blood pressure in pregnancy. While our study was well-designed to assess associations with blood pressure, future studies with a larger number of preeclampsia cases may be better poised to investigate the association between OPE metabolites and phenotypes of this heterogenous hypertensive disorder of pregnancy.

Migration patterns of organophosphate esters from plastic food packaging simulants to foods: Donors, behaviours, and influencing factors.

In recent years, organophosphate esters (OPEs) have been widely produced and used as flame retardants and plasticizer additives, posing significant ecological and health risks. Dietary intake is considered to be the primary route of human exposure to OPEs. Plastic food packaging materials are considered a crucial source for contamination of OPEs in food. However, the migration behaviour of OPEs from plastic food packaging materials into foods has received limited attention. In this study, we employed a novel method to prepare migration donors containing 13 kinds of OPEs. The migration behaviours of OPEs from food packaging simulants (polypropylene) to foods (full-fat milk powder) were simulated, and factors influencing the migration of OPEs were examined, including the properties of the target compounds, migration temperature, fat content of the migration receptors, and mass transfer mode. The results indicated that OPEs exhibited a significant migration tendency. Low molecular weight OPEs (< 300 Da) had faster migration efficiency compared to high molecular weight OPEs. The mean migration efficiencies of various OPEs showed a significant negative correlation with their molecular weights (p < 0.01) and a significant positive correlation with temperature (p < 0.01). Except for resorcinol bis(diphenyl phosphate) (RDP), which showed almost no migration, the mean migration efficiencies of other OPEs at 25 °C, 40 °C, and 60 °C were 3.1-37.5 %, 9.0-60.0 %, and 23.9-80.4 %, respectively. Most of the OPEs demonstrated higher migration efficiency in high-fat content food than low-fat content food. The migration of OPEs from food packaging simulants to foods primarily occurred through contact rather than gas-phase mass transfer. Overall, this study uncovers the migration behaviours of OPEs from food packaging simulants to foods and scrutinized the relevant factors influencing the migration. It is expected that the research in terms of the contamination control of OPEs in food will benefit from this work.

From e-waste to living space: Flame retardants contaminating household items add to concern about plastic recycling.

Brominated flame retardants (BFRs) and organophosphate flame retardants (OPFRs) are commonly used in electric and electronic products in high concentrations to prevent or retard fire. Health concerns related to flame retardants (FRs) include carcinogenicity, endocrine disruption, neurotoxicity, and reproductive and developmental toxicity. Globally, a lack of transparency related to chemicals in products and limited restrictions on use of FRs in electronics have led to widespread use and dissemination of harmful FRs. Despite the lack of transparency and restrictions, plastics from electronics are often recycled and can be incorporated in household items that do not require flame retardancy, resulting in potentially high and unnecessary exposure. This study sought to determine whether black plastic household products sold on the U.S. market contained emerging and phased-out FRs and whether polymer type was predictive of contamination. A total of 203 products were screened for bromine (Br), and products containing >50 ppm Br were analyzed for BFRs, OPFRs, and plastic polymers (e.g. acrylonitrile butadiene styrene, high impact polystyrene, polypropylene). FRs were found in 85% of analyzed products, with total FR concentrations ranging up to 22,800 mg/kg. FRs detected include the restricted compound deca-BDE, which was used widely in electronics casings, as well as its replacements decabromodiphenyl ethane (DBDPE) and 2,4,6-Tris(2,4,6-tribromophenoxy)-1,3,5-triazine (TBPP-TAZ) along with associated compound 2,4,6-tribromophenol (2,4,6-TBP), recently detected in breast milk. Plastic typically used in electronics (styrene-based) contained significantly higher levels of ∑FRs than plastics less typically used for electronics (polypropylene and nylon). Estimation of exposure to BDE-209 from contaminated kitchen utensils indicated users would have a median intake of 34,700 ng/day, exceeding estimates for intake from dust and diet. The detection of FRs in collected household products indicates that recycling, without the necessary transparency and restrictions to ensure safety, is resulting in unexpected exposure to toxic flame retardants in household items.

Biphasic response of human iPSC-derived neural network activity following exposure to a sarin-surrogate nerve agent.

Organophosphorus nerve agents (OPNA) are hazardous environmental exposures to the civilian population and have been historically weaponized as chemical warfare agents (CWA). OPNA exposure can lead to several neurological, sensory, and motor symptoms that can manifest into chronic neurological illnesses later in life. There is still a large need for technological advancement to better understand changes in brain function following OPNA exposure. The human-relevant in vitro multi-electrode array (MEA) system, which combines the MEA technology with human stem cell technology, has the potential to monitor the acute, sub-chronic, and chronic consequences of OPNA exposure on brain activity. However, the application of this system to assess OPNA hazards and risks to human brain function remains to be investigated. In a concentration-response study, we have employed a human-relevant MEA system to monitor and detect changes in the electrical activity of engineered neural networks to increasing concentrations of the sarin surrogate 4-nitrophenyl isopropyl methylphosphonate (NIMP). We report a biphasic response in the spiking (but not bursting) activity of neurons exposed to low (i.e., 0.4 and 4 µM) versus high concentrations (i.e., 40 and 100 µM) of NIMP, which was monitored during the exposure period and up to 6 days post-exposure. Regardless of the NIMP concentration, at a network level, communication or coordination of neuronal activity decreased as early as 60 min and persisted at 24 h of NIMP exposure. Once NIMP was removed, coordinated activity was no different than control (0 µM of NIMP). Interestingly, only in the high concentration of NIMP did coordination of activity at a network level begin to decrease again at 2 days post-exposure and persisted on day 6 post-exposure. Notably, cell viability was not affected during or after NIMP exposure. Also, while the catalytic activity of AChE decreased during NIMP exposure, its activity recovered once NIMP was removed. Gene expression analysis suggests that human iPSC-derived neurons and primary human astrocytes resulted in altered genes related to the cell's interaction with the extracellular environment, its intracellular calcium signaling pathways, and inflammation, which could have contributed to how neurons communicated at a network level.

Identification and biophysical characterization of potential phytochemical inhibitors of carboxyl/choline esterase from Helicoverpa armigera for advancing integrated pest management strategies.

In the realm of disease vectors and agricultural pest management, insecticides play a crucial role in preserving global health and ensuring food security. The pervasive use, particularly of organophosphates (OPs), has given rise to a substantial challenge in the form of insecticide resistance. Carboxylesterases emerge as key contributors to OP resistance, owing to their ability to sequester or hydrolyze these chemicals. Consequently, carboxylesterase enzymes become attractive targets for the development of novel insecticides. Inhibiting these enzymes holds the potential to restore the efficacy of OPs against which resistance has developed. This study aimed to screen the FooDB library to identify potent inhibitory compounds targeting carboxylesterase, Ha006a from the agricultural pest Helicoverpa armigera. The ultimate objective is to develop effective interventions for pest control. The compounds with the highest scores underwent evaluation through docking studies and pharmacophore analysis. Among them, four phytochemicals-donepezil, protopine, 3',4',5,7-tetramethoxyflavone, and piperine-demonstrated favorable binding affinity. The Ha006a-ligand complexes were subsequently validated through molecular dynamics simulations. Biochemical analysis, encompassing determination of IC50 values, complemented by analysis of thermostability through Differential Scanning Calorimetry and interaction kinetics through Isothermal Titration Calorimetry was conducted. This study comprehensively characterizes Ha006a-ligand complexes through bioinformatics, biochemical, and biophysical methods. This investigation highlights 3',4',5,7-tetramethoxyflavone as the most effective inhibitor, suggesting its potential for synergistic testing with OPs. Consequently, these inhibitors offer a promising solution to OP resistance and address environmental concerns associated with excessive insecticide usage, enabling a significant reduction in their overuse.

Ethion food poisoning outbreak in Pereira, Colombia, 2022.

INTRODUCTION: Ethion is an organophosphate used as an acaricide and insecticide, that is restricted worldwide. In Colombia, pesticide poisoning is the third most common cause of chemical intoxication. On 9 October 2022, an outbreak of ethion poisoning occurred in Pereira. The aim of this study was to describe the clinical and epidemiological characteristics of the outbreak. METHODS: This is a descriptive study of an outbreak of organophosphate poisoning. The onset of symptoms occurred on 9 October 2022, following the consumption of empanadas. Information was collected on sociodemographic characteristics and clinical manifestations, as well as from paraclinical examinations. Data were obtained from clinical histories, field epidemiological investigations, and inspection visits. Food samples were collected for analysis by gas chromatography-mass spectrometry. Attack rates, proportions, and measures of central tendency, dispersion, and position were calculated. RESULTS: The case definition was met by 37 individuals with a median age of 30 years; all presented with muscarinic symptoms, 29 patients presented with nicotinic symptoms, and 20 patients presented with neurological symptoms. Males were the most affected (57%), and the most common time of symptom onset was 10:00 am. Twenty-three patients (62%) required intensive care unit admission, of whom 14 (38%) required mechanical ventilation. No deaths were reported. Erythrocyte acetylcholinesterase activity was reduced in all patients. Ethion was detected in mass-prepared maize and empanadas at concentrations greater than 0.1 mg/kg. The consumption of empanadas was identified as the common source. DISCUSSION: In Colombia, pesticide poisonings are the third most common type of poisoning caused by chemical substances reported to the National Health Institute through the National Public Health Surveillance System. In the present outbreak, ethion was in empanadas, likely due to contamination of cooking oil. CONCLUSIONS: We describe a large ethion-contaminated food poisoning outbreak reported in Colombia. The main symptoms were muscarinic, and the main treatment measures employed were atropine and respiratory support. Increased awareness of pesticide poisoning and training for food handlers are needed.

Mediated self-assembled gold nanoclusters with mesoporous silica particles to boost fluorescence for enhanced on-site monitoring of organophosphate pesticides.

Accurate detection of organophosphate pesticides (OPs) is paramount for ensuring food safety. Dendritic mesoporous silica sphere was employed to confine gold nanoclusters (AuNCs@dmSiO2) to ameliorate fluorescent property of AuNCs. A AuNCs@dmSiO2-based fluorescent method was developed for OPs sensing. Identification of Cu2+ by AuNCs quenched AuNCs@dmSiO2 fluorescence. Interaction between Cu2+ and generated thiocholine in catalysis of acetylcholinesterase (AChE) caused fluorescence enhancement. OPs, an inhibitor of AChE, suppressed thiocholine production to cause fluorescence quenching. Based on fluorescent variation, a fluorescent method was proposed for OPs by selecting paraoxon as a model within range of 0.05-25.0 ng/mL with a limit of detection (LOD) of 0.032 ng/mL. Besides, a portable test swab was prepared for on-site monitoring OP paraoxon with a smartphone-based 3D-printing portable device with a LOD of 0.65 ng/mL. This work is highlighted by the inspiration of designing highly fluorescent AuNCs, and the provision of a viable avenue for OPs-related food analysis.