Association of ambient air pollution and pesticide mixtures on respiratory inflammatory markers in agricultural communities.

Air pollution exposure is associated with adverse respiratory health outcomes. Evidence from occupational and community-based studies also suggests agricultural pesticides have negative health impacts on respiratory health. Although populations are exposed to multiple inhalation hazards simultaneously, multidomain mixtures (e.g. environmental and chemical pollutants of different classes) are rarely studied. We investigated the association of ambient air pollution-pesticide exposure mixtures with urinary leukotriene E4 (LTE4), a respiratory inflammation biomarker, for 75 participants in four Central California communities over two seasons. Exposures included three criteria air pollutants estimated via the Community Multiscale Air Quality model (fine particulate matter, ozone, and nitrogen dioxide) and urinary metabolites of organophosphate (OP) pesticides (total dialkyl phosphates (DAPs), total diethyl phosphates (DE), and total dimethyl phosphates (DM)). We implemented multiple linear regression models to examine associations in single pollutant models adjusted for age, sex, asthma status, occupational status, household member occupational status, temperature, and relative humidity, and evaluated whether associations changed seasonally. We then implemented Bayesian kernel machine regression (BKMR) to analyse these criteria air pollutants, DE, and DM as a mixture. Our multiple linear regression models indicated an interquartile range (IQR) increase in total DAPs was associated with an increase in urinary LTE4 in winter (ß: 0.04, 95% CI: [0.01, 0.07]). Similarly, an IQR increase in total DM was associated with an increase in urinary LTE4 in winter (ß:0.03, 95% CI: [0.004, 0.06]). Confidence intervals for all criteria air pollutant effect estimates included the null value. BKMR analysis revealed potential non-linear interactions between exposures in our air pollution-pesticide mixture, but all confidence intervals contained the null value. Our analysis demonstrated a positive association between OP pesticide metabolites and urinary LTE4 in a low asthma prevalence population and adds to the limited research on the joint effects of ambient air pollution and pesticides mixtures on respiratory health.

Association between organophosphate esters exposure and all-cause and cause-specific mortality: a national population-based cohort study.

Exposure to organophosphate esters (OPEs) is associated with several chronic diseases, but the relationship with mortality risk is unclear. Therefore, we used the National Health and Nutrition Examination Survey 2011-2018 data to evaluate these relationships. 6,869 participants aged 18 years or older were included. Survival status information was obtained through the National Death Index through 31 December 2019. Multivariable COX regression model was adopted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationships of urinary OPEs metabolites with mortality risk. During an average of 5.0 years of follow-up, 406 deaths were documented. After adjusting for confounders, bis(2-chloroethyl) phosphate was associated with an increased risk of all-cause mortality [HR (95%CI) = 1.12(1.05-1.20)] and cardiovascular mortality [HR (95%CI) = 1.15(1.04-1.26)]. Our study found that exposure to OPEs was significantly associated with increased risks of all-cause and cardiovascular mortality. Consequently, controlling OPEs exposure is needed to alleviate the health-related burden.

Associations between co-exposure to per- and polyfluoroalkyl substances and organophosphate esters and erythrogram in Chinese adults.

Erythrogram, despite its prevalent use in assessing red blood cell (RBC) disorders and can be utilized to evaluate various diseases, still lacks evidence supporting the effects of per- and polyfluoroalkyl substances (PFASs) and organophosphate esters (OPEs) on it. A cross-sectional study involving 467 adults from Shijiazhuang, China was conducted to assess the associations between 12 PFASs and 11 OPEs and the erythrogram (8 indicators related to RBC). Three models, including multiple linear regression (MLR), sparse partial least squares regression, and Bayesian kernel machine regression (BKMR) were employed to evaluate both the individual and joint effects of PFASs and OPEs on the erythrogram. Perfluorohexane sulfonic acid (PFHxS) showed the strongest association with HGB (3.68%, 95% CI: 2.29%, 5.10%) when doubling among PFASs in MLR models. BKMR indicated that PFASs were more strongly associated with the erythrogram than OPEs, as evidenced by higher group posterior inclusion probabilities (PIPs) for PFASs. Within hemoglobin and hematocrit, PFHxS emerged as the most significant component (conditional PIP = 1.0 for both). Collectively, our study emphasizes the joint effect of PFASs and OPEs on the erythrogram and identified PFASs, particularly PFHxS, as the pivotal contributors to the erythrogram. Nonetheless, further investigations are warranted to elucidate the underlying mechanisms.

Reactivation by novel pyridinium oximes of rat serum and skeletal muscle acetylcholinesterase inhibited by organophosphates.

The treatment of organophosphate (OP) anticholinesterases currently lacks an effective oxime reactivator of OP-inhibited acetylcholinesterase (AChE) which can penetrate the blood-brain barrier (BBB). Our laboratories have synthesized novel substituted phenoxyalkyl pyridinium oximes and tested them for their ability to promote survival of rats challenged with lethal doses of nerve agent surrogates. These previous studies demonstrated the ability of some of these oximes to promote 24-h survival to rats challenged with a lethal level of highly relevant surrogates for sarin and VX. The reactivation of OP-inhibited AChE in peripheral tissues was likely to be a major contributor to their efficacy in survival of lethal OP challenges. In the present study, twenty of these novel oximes were screened in vitro for reactivation ability for AChE in rat skeletal muscle and serum using two nerve agent surrogates: phthalimidyl isopropyl methylphosphonate (PIMP, a sarin surrogate) and 4-nitrophenyl ethyl methylphosphonate (NEMP, a VX surrogate). The oximes demonstrated a range of 23%-102% reactivation of AChE in vitro across both tissue types. Some of the novel oximes tested in the present study demonstrated the ability to more effectively reactivate AChE in serum than the currently approved oxime, 2-PAM. Therefore, some of these novel oximes have the potential to reverse AChE inhibition in peripheral target tissues and contribute to survival efficacy.

Organophosphate esters and their metabolites in silver pomfret (Pampus argenteus) of the Vietnamese coastal areas: Spatial-temporal distribution and exposure risk.

A large number of studies on organophosphate esters (tri-OPEs) in marine organisms have not assessed the simultaneous occurrence of tri-OPEs and their metabolites (di-OPEs) in these species. This research investigated the concentration and geographical distribution of 15 tri-OPEs and 7 di-OPEs in 172 samples of Pampus argenteus that were collected annually from 2021 to 2023 at three distinct locations along the Vietnamese coast. As a result, tri-OPEs and di-OPEs were detected in numerous fish samples, indicating their widespread spatial and temporal occurrence in marine fish and pointing out the importance of monitoring their levels. The tri-OPEs and di-OPEs ranged within 2.1-38.9 ng g-1 dry weight (dw) and 3.2-263.4 ng g-1 dw, respectively. The mean concentrations of tri-OPEs ranged from 0.4 (TIPrP) to 5.4 ng g-1 dw (TBOEP), with TBOEP and TEHP having the highest mean values. In addition, the profiles of tri-OPEs in fish exhibited a descending order: Σalkyl OPEs > ΣCl-alkyl OPEs > Σaryl OPEs. The di-OPEs, namely BEHP and DMP, had the highest mean levels, measuring 33.4 ng g-1 dw and 23.8 ng g-1 dw, respectively. Furthermore, there have been significant findings of strong positive correlations between di-OPEs and tri-OPE pairs (p < 0.05). It is worth noting that there is a noticeable difference in the composition of tri-OPEs between the North and other regions. Despite these findings, the presence of OPE-contaminated fish did not pose any health risks to Vietnam's coastal population.

Organophosphate esters (OPEs) pollution characteristics, bioaccumulation and human consumption implication in wild marine organisms from the Yellow River Estuary, China.

As the substitutes of polybrominated diphenyl ethers, organophosphate esters (OPEs) with high concentrations have accumulated in the estuaries, bays, and harbors. However, limited information is available about the OPEs in the estuary organism categories, especially under the multiple industrial pressure. This study investigated the occurrence, bioaccumulation and human consumption implication in wild marine organisms from the Yellow River Estuary, where located many petroleum and chemical manufacturing industries. This study found that concentrations of Σ13OPEs ranged from 547 ng/L to 1164 ng/L in seawater (median: 802 ng/L), from 384 to 1366 ng/g dw in the sediment (median: 601 ng/g dw), and from 419 to 959 ng/g dw (median: 560 ng/g dw) in the marine organisms. The congener compositions in the organisms were dominated by alkyl-OPEs (80.7 %), followed by halogenated-OPEs (18.8 %) and aryl-OPEs (0.5 %). Based on the principal component analysis, petrochemical pollution, and industrial wastewater discharge were distinguished as the main plausible sources of OPEs to the YRE ecosystem. Most OPEs had potential or strong bioaccumulation capacity on the organisms, with a positive correlation between log BAF (Bioaccumulation Factor) and log Kow of OPEs. The highest estimated daily intake value of OPEs was tri-n-propyl phosphate, exceeding 300 ng/kg·bw/day via consuming fish. The highest hazard quotients from OPEs ranged from 0.001 to 0.1, indicating a low risk to human health by consuming marine organisms in the YRE. As the consumption of OPEs increases year by year, the risks of OPEs still cannot be ignored.

Holistic assessment of dimethoate toxicity in Carcinus aestuarii's muscle tissues.

Dimethoate (DMT) is one of the most harmful and commonly used organophosphate pesticides in agricultural lands to control different groups of parasitic insects. However, this pesticide is considered a dangerous pollutant for aquatic organisms following its infiltration in coastal ecosystems through leaching. Yet, our investigation aimed to gain new insights into the toxicity mechanism of DMT in the muscles of the green crab Carcinus aestuarii, regarding oxidative stress, neurotransmission impairment, histological aspects, and changes in lipid composition, assessed for the first time on the green crab's muscle. Specimens of C. aestuarii were exposed to 50, 100, and 200 µg DMT L-1 for 24 h. Compared to the negative control group, the higher the DMT concentration, the lower the saturated fatty acids (SFA), and the higher the monounsaturated fatty acids (MUFA). The significant increase in polyunsaturated fatty acid n-6 (PUFA n-6) was related to the high release, mainly, of linoleic acid (LA, C18: 2n6) and arachidonic acid (ARA, C20: 4n6) levels. Biochemical biomarkers showed that DMT exposure promoted oxidative stress, highlighted by increased levels of hydrogen peroxide (H2O2), malondialdehyde (MDA), advanced oxidation protein product levels (AOPP), and protein carbonyl (PCO). Furthermore, the antioxidant defense system was activated, as demonstrated by the significant changes in the enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) levels associated with an adaptation process of C. aestuarii to cope with the DMT exposure. This pesticide significantly impairs the neurotransmission process, as evidenced by the inhibition of acetylcholinesterase (AChE) activity. Finally, several histopathological changes were revealed in DMT-treated crabs, including vacuolation, and muscle bundle loss.This research offered new insights into the toxic mechanism of DMT, pointing to the usefulness of fatty acid (FA) composition as a sensitive biomarker in littoral crabs.

A smartphone-assisted portable on-site detection system for organophosphorus pesticides in vegetables and fruits based on all-in-one paper-based sensors: 2,2-Dichlorovinyl dimethyl phosphate as a model.

The improper use of organophosphate pesticides (OPs) can lead to residue posing a serious threat to human health and environment. Therefore, the development of a simple, portable, and sensitive detection method is crucial. Herein, a bioenzyme-nanozyme-chromogen all-in-one paper-based sensor was synthesized. Initially, the Ce/Zr-MOF with peroxidase-like activity was grown on filter paper (FP) using in-situ solvent thermal method, resulting in Ce/Zr-MOF@FP. Subsequently, the AChE-ChO-TMB system was immobilized onto Ce/Zr-MOF@FP using biocompatible gelatin, which enhanced cascade catalysis efficiency through the proximity effect. Based on the inhibition principle of OPs on AChE, we integrated this sensor with Python-based image recognition algorithm to achieve detection of OPs. Using 2,2-dichlorovinyl dimethyl phosphate (DDVP) as a model of OPs, it has good detection performance with a detection limit of 0.32 ng mL-1 and a recovery rate range of 95-107%. The potential for on-site detection of DDVP residues in vegetables and fruit samples is highly promising.

Integrated biomarker-based ecological risks assessment of tadpole responses to tris(2-chloroethyl) phosphate, tris(1-chloro-2-propyl) phosphate, and their combined environmental exposure.

Tris(2-chloroethyl) phosphate (TCEP) and tris(1-chloro-2-propyl) phosphate (TCPP) are common chlorinated organophosphorus flame retardants (OPFRs) used in industry. They have been frequently detected together in aquatic environments and associated with various hazardous effects. However, the ecological risks of prolonged exposure to these OPFRs at environmentally relevant concentrations in non-model aquatic organisms remain unexplored. This study investigated the effects of long-term exposure (up to 25 days) to TCEP and TCPP on metamorphosis, hepatic antioxidants, and endocrine function in Polypedates megacephalus tadpoles. Exposure concentrations were set at 3, 30, and 90 µg/L for each substance, conducted independently and in equal-concentration combinations, with a control group included for comparison. The integrated biomarker response (IBR) method developed an optimal linear model for predicting the overall ecological risks of TCEP and TCPP to tadpoles in potential distribution areas of Polypedates species. Results showed that: (1) Exposure to environmentally relevant concentrations of TCEP and TCPP elicited variable adverse effects on tadpole metamorphosis time, hepatic antioxidant enzyme activity and related gene expression, and endocrine-related gene expression, with their combined exposure exacerbating these effects. (2) The IBR value of TCEP was consistently greater than that of TCPP at each concentration, with an additive effect observed under their combined exposure. (3) The ecological risk of tadpoles exposed to the combined presence of TCEP and TCPP was highest in China's Taihu Lake and Vietnam's Hanoi than in other distribution locations. In summary, prolonged exposure to environmentally relevant concentrations of TCEP and TCPP presents potential ecological risks to amphibian tadpoles, offering insights for the development of policies and strategies to control TCEP and TCPP pollution in aquatic ecosystems. Furthermore, the methodology employed in establishing the IBR prediction model provides a methodological framework for assessing the overall ecological risks of multiple OPFRs.

Validity of different scoring systems in prediction of intensive care unit admission and mortality in acute organophosphate poisoning.

Background: Organophosphate compounds (OPCs) pose significant health risks, especially in developing countries with limited resources. Predicting outcomes in OPCs poisoning is crucial for guiding clinical management and reducing mortality rates. The aim of this study to evaluate the validity of different scoring systems Rapid Emergency Medicine Score, Multiple Organ Dysfunction Score, Acute Physiology and Chronic Health Evaluation Score, and Poison Severity Score in prediction of intensive care unit (ICU) admission and mortality of acute OPCs poisoning patients. Methods: A cross-sectional study was conducted on 103 patients admitted to Xx Poison Control Center between May 2022 and June 2023. Scoring systems were applied at admission, and their performance in predicting the need for ICU admission and mortality was evaluated using receiver operating characteristic (ROC) curve analysis. Results: Most patients survived (92.2%). Only 13.6% of the patients required ICU admission. Significant differences in median scores were observed between survivors and non-survivors and between patients requiring ICU admission and those who did not. Multiple Organ Dysfunction Score exhibited the highest discriminatory power for predicting both ICU admission (AUC = 0.983) and mortality (AUC = 0.999). Conclusion: The findings highlight the importance of utilizing scoring systems, particularly Multiple organ dysfunction score, for prediction of poor outcomes of acute OPCs poisoning.

Individual and joint effects of organophosphate esters and hypertension or diabetes on renal injury among Chinese adults.

Exposure to environmental contaminants and the development of hypertension and diabetes represent crucial risk factors for chronic kidney disease (CKD). Toxicological studies have revealed that organophosphate esters (OPEs) impair kidney function. However, the joint effects of OPE exposure on kidney injury and the interactions of OPE exposure with hypertension or diabetes on kidney injury remain unclear. Our study aimed to investigate the individual and joint effects of OPE exposure on renal injury, as well as the potential interaction between OPE exposure and hypertension or diabetes on kidney injury. The study enrolled 1938 participants from Wuhan, China. To explore the relationship between OPE exposure and renal injury, we conducted multivariate linear and logistic regression analysis. The results indicated that each unit increase in 4-hydroxyphenyl diphenyl phosphate (4-HO-DPHP), bis(2-butoxyethyl) phosphate (BBOEP), and tris(2-chloroethyl) phosphate (TCEP) (1 µg/L-ln transformed) was associated with a decreased 0.57 mL/min/1.73 m2 (95%CI: -1.05, -0.09), 0.85 mL/min/1.73 m2 (95%CI: -1.52, -0.19) and 1.24 mL/min/1.73 m2 (95%CI: -2.26, -0.23) of estimated glomerular filtration rate (eGFR), while each unit increase in 4-HO-DPHP and BBOEP (1 µg/L-ln transformed) was associated with 14% and 20% elevation of incident impaired renal function (IRF) risk. Notably the highest tertile of BCIPHIPP was positively associated with eGFR, although the p for trend ＞ 0.05. We employed Bayesian kernel machine regression (BKMR) and quartile-based g-computation (qgcomp) models to explore the joint effects of OPE mixtures on eGFR and IRF. Both the results of BKMR and qgcomp model consistently demonstrated negative associations between OPE mixtures and eGFR, and TCEP and 4-HO-DPHP were major contributors. Furthermore, we observed multiplicative interactions of diphenyl phosphate (DPHP), BBOEP, di-ocresyl phosphate (DoCP) & di-p-cresyl phosphate (DpCP), 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) and hypertension or diabetes on kidney injury (all P＜0.05). Those with diabetes or hypertension and higher OPE metabolite concentrations had increased risk of kidney function impairment compared to those who did not have diabetes or hypertension. These findings suggest that specific OPE exposure may elevate the risk of renal injury, particularly among hypertensive and diabetic populations.

Association between organophosphorus pesticides and obesity among American adults.

OBJECTIVE: To investigate any connections between urinary organophosphorus pesticide (OPP) metabolites and adiposity measures. METHODS: In this study, data from the National Health and Nutrition Examination Survey (NHANES) projects from 2003 to 2008, 2011 to 2012, and 2015 to 2018 were analysed. Obesity was defined as a body mass index (BMI) of 30 kg/m² or higher. Abdominal obesity was defined as a waist circumference (WC) over 102 cm for men and 88 cm for women. Four urinary OPP metabolites (dimethyl phosphate [DMP], diethyl phosphate [DEP], dimethyl phosphorothioate [DMTP], and diethyl phosphorothioate [DETP]) and adiposity measures were examined using multiple linear regression and logistic regression analyses. The correlations between a variety of urinary OPP metabolites and the prevalence of obesity were investigated using weighted quantile sum regression and quantile g-computation regression. RESULTS: In this analysis, a total of 9,505 adults were taken into account. There were 49.81% of male participants, and the average age was 46.00 years old. The median BMI and WC of the subjects were 27.70 kg/m2 and 97.10 cm, respectively. Moreover, 35.60% of the participants were obese, and 54.42% had abdominal obesity. DMP, DMTP, and DETP were discovered to have a negative correlation with WC and BMI in the adjusted models. DMP (OR = 0.93 [95% CI: 0.89-0.98]), DEP (OR = 0.94 [95% CI: 0.90-0.99]), DMTP (OR = 0.91 [95% CI: 0.86-0.95]), and DETP (OR = 0.85 [95% CI: 0.80-0.90]) exhibited negative associations with obesity prevalence. Similar correlations between the prevalence of abdominal obesity and the urine OPP metabolites were discovered. Moreover, the mixture of urinary OPP metabolites showed negative associations with adiposity measures, with DMTP and DETP showing the most significant effects. CONCLUSION: Together, higher levels of urinary OPP metabolites in the urine were linked to a decline in the prevalence of obesity.

Bioaccumulation mediated by water solubility leads to differences in the acute toxicity of organophosphorus insecticides to zebrafish (Danio rerio).

The use of some organophosphate insecticides is restricted or even banned in paddy fields due to their high toxicity to aquatic organisms. The aim of this study is to elucidate the main pathways and target organs of organophosphate insecticide toxicity to fish exposed via different routes by integrating histopathological and biochemical techniques. Using malathion as the model drug, when the dosage is 20-60 mg/L, the toxicity of whole body and head immersion drugs to zebrafish is much higher than that of trunk immersion drugs. A dose of 21.06-190.44 mg/kg of malathion feed was fed to adult zebrafish. Although the dosage was already high, no obvious toxicity was observed. Therefore, we believe that the drug mainly enters the fish body through the gills. When exposed to a drug solution of 20 mg/L and 60 mg/L, the fish showed significant neurological behavioral abnormalities, and the pathological damage to key organs and brain tissue was the most severe, showing obvious vacuolization and the highest residual amount (8.72-47.78 mg/L). The activity of acetylcholinesterase was the most inhibited (54.69-74.68%). Therefore, brain tissue is the key toxic target organ of malathion in fish. In addition, we compared the bioaccumulation effects of different water-soluble organophosphorus insecticides in fish and their toxic effects. We found that the higher the water solubility of organophosphorus insecticides, the lower their toxicity to fish.

Exploring sources of inaccuracy and irreproducibility in the CDC bottle bioassay through direct insecticide quantification.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) bottle bioassay is a commonly used susceptibility test for measuring insect response to insecticide exposure. However, inconsistencies and high variability in insect response when conducting CDC bottle bioassays have been reported in previous publications. We hypothesized that the CDC bottle bioassay results may be compromised when expected and actual insecticide concentrations in the bottles are not equivalent and that inadequate bottle cleaning and/or loss during insecticide introduction and bottle storage steps could be responsible. We explored this hypothesis by quantifying insecticides using gas chromatography tandem mass spectrometry (GC-MS/MS) in bottles that had been cleaned, prepared, and stored according to the CDC guidelines. METHODS: We investigated the bottle cleaning, preparation, and storage methods outlined in the CDC bottle bioassay procedure to identify sources of irreproducibility. We also investigated the effectiveness of cleaning bottles by autoclaving because this method is commonly used in insecticide assessment laboratories. The two insecticides used in this study were chlorpyrifos and lambda-cyhalothrin (λ-cyhalothrin). Insecticides were removed from glass bioassay bottles by rinsing with ethyl-acetate and n-hexane and then quantified using GC-MS/MS. RESULTS: The CDC bottle bioassay cleaning methods did not sufficiently remove both insecticides from the glass bottles. The cleaning methods removed chlorpyrifos, which has higher water solubility, more effectively than λ-cyhalothrin. Chlorpyrifos experienced significant loss during the bottle-coating process whereas λ-cyhalothrin did not. As for bottle storage, no significant decreases in insecticide concentrations were observed for 6 h following the initial drying period for either insecticide. CONCLUSIONS: The CDC bottle bioassay protocol is susceptible to producing inaccurate results since its recommended bottle cleaning method is not sufficient and semi-volatile insecticides can volatilize from the bottle during the coating process. This can lead to the CDC bottle bioassay producing erroneous LC50 values. High levels of random variation were also observed in our experiments, as others have previously reported. We have outlined several steps that CDC bottle bioassay users could consider that would lead to improved accuracy and reproducibility when acquiring toxicity data.

Serum albumin and liver dysfunction mediate the associations between organophosphorus pesticide exposure and hypertension among US adults.

BACKGROUND: Human health is commonly threatened by organophosphorus pesticides (OPPs) due to their widespread use and biological characteristics. However, the combined effect of mixtures of OPPs metabolites on the risk of hypertension and potential mechanism remain limited. OBJECTIVES: To comprehensively investigate the effects between OPPs exposure on hypertension risk and explore and underlying mechanism among US general population. METHODS: This cross-sectional study collected US adults who had available data on urine OPPs metabolites (dialkyl phosphate compounds, DAPs) from the National Health and Nutrition Examination Survey (NHANES) to assess the relationships of DAPs with hypertension risk. Survey-weighted logistic regression, restricted cubic spline (RCS), and mixed exposure analysis models [weighted quantile sum regression (WQS) and Bayesian kernel machine regression (BKMR)] were used to analyze individual, dose-response and combined associations between urinary DAPs metabolites and hypertension risk, respectively. Mediation analysis determined the potential intermediary role of serum albumin and liver function in the above associations. RESULTS: Compared with the reference group, participants with the highest tertile levels of DEP, DMTP, DETP, and DMDTP experienced increased risk of hypertension by 1.21-fold (95%CI: 1.02-1.36), 1.20-fold (95%CI: 1.02-1.42), 1.19-fold (95%CI: 1.01-1.40), and 1.17-fold (95%CI: 1.03-1.43), respectively. RCS curve also showed positive exposure-response associations of individual DAPs with hypertension risk. WQS and BKMR analysis further confirmed DAP mixtures were significantly associated with increased risk of hypertension, with DEP identified as a major contributor to the combined effect. Mediation analysis indicated that serum albumin and AST/ALT ratios played crucial mediating roles in the relationships between individual and mixed urinary DAPs and the prevalence of hypertension. CONCLUSION: Our findings provided more comprehensive and novel perspectives into the individual and combined effects of urinary OPPs matabolites on the increased risk of hypertension and the possible driving mechanism, which would be of great significance for environmental control and early prevention of hypertension.

Organophosphate ester flame retardant chemicals and maternal depression during pregnancy.

BACKGROUND: Depression substantially contributes to pregnancy-related morbidity, and pregnancy is increasingly recognized as a vulnerable window for exposure effects on maternal mental health. Exposures to organophosphate esters (OPEs) are ubiquitous and may have neurotoxic effects; however, their impacts on prenatal depression remain unknown. We evaluated associations of third trimester OPE metabolites on maternal depressive symptoms during pregnancy. METHODS: This study included 422 participants in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort, a prospective pregnancy cohort of primarily low-income and Hispanic participants residing in Los Angeles, California. We measured concentrations of nine OPEs in third trimester spot urine samples (mean gestational age = 31.5 ± 2.0 weeks). Using the Center for Epidemiologic Studies-Depression (CES-D) scale, we classified participants as having probable depression during pregnancy (N = 137) or not (N = 285) if one or more CES-D scores administered at each trimester met the suggested cutoff score for clinically significant depressive symptoms (≥16). We estimated associations of prenatal OPE metabolite concentrations in tertiles and risk of prenatal depression using modified Log-Poisson regression. We examined associations of the OPE mixture on depression during pregnancy using Bayesian kernel machine regression (BKMR). RESULTS: Participants with the highest tertiles of DPHP and BDCIPP exposure had a 67% (95% CI: 22%, 128%) and 47% (95% CI: 4%, 108%) increased risk of maternal depressive symptoms during pregnancy, respectively. No associations between other OPE metabolites and maternal depression symptoms were observed. In mixture analyses, we observed a positive and linear association between higher exposure to the OPE metabolite mixture and odds of prenatal maternal depression, primarily driven by DPHP. CONCLUSIONS: Our findings provide new evidence of associations between frequently detected OPE metabolites on maternal depression symptoms during pregnancy. Results could inform future intervention efforts aimed at reducing perinatal maternal depression.

Evaluation of suitability and biodegradability of the organophosphate insecticides to mitigate insecticide pollution in onion farming.

Organophosphates constitute a major class of pesticides widely employed in agriculture to manage insect pests. Their toxicity is attributed to their ability to inhibit the functioning of acetylcholinesterase (AChE), an essential enzyme for normal nerve transmission. Organophosphates, especially chlorpyrifos, have been a key component of the integrated pest management (IPM) in onions, effectively controlling onion maggot Delia antiqua, a severe pest of onions. However, the growing concerns over the use of this insecticide on human health and the environment compelled the need for an alternative organophosphate and a potential microbial agent for bioremediation to mitigate organophosphate pesticide pollution. In the present study, chloropyrifos along with five other organophosphate insecticides, phosmet, primiphos-methyl, isofenphos, iodofenphos and tribuphos, were screened against the target protein AChE of D. antiqua using molecular modeling and docking techniques. The results revealed that iodofenphos showed the best interaction, while tribuphos had the lowest interaction with the AChE based on comparative binding energy values. Further, protein-protein interaction analysis conducted using the STRING database and Cytoscap software revealed that AChE is linked with a network of 10 different proteins, suggesting that the function of AChE is disrupted through interaction with insecticides, potentially leading to disruption within the network of associated proteins. Additionally, an in silico study was conducted to predict the binding efficiency of two organophosphate degrading enzymes, organophosphohydrolase (OpdA) from Agrobacterium radiobacter and Trichoderma harzianum paraoxonase 1 like (ThPON1-like) protein from Trichoderma harzianum, with the selected insecticides. The analysis revealed their potential to degrade the pesticides, offering a promising alternative before going for cumbersome onsite remediation.

Partitioning of an Enzyme-Polymer Surfactant Nanocomplex into Lipid-Rich Cellular Compartments Drives In Situ Hydrolysis of Organophosphates.

Most organophosphates (OPs) are hydrophobic, and after exposure, can sequester into lipophilic regions within the body, such as adipose tissue, resulting in long term chronic effects. Consequently, there is an urgent need for therapeutic agents that can decontaminate OPs in these hydrophobic regions. Accordingly, an enzyme-polymer surfactant nanocomplex is designed and tested comprising chemically supercharged phosphotriesterase (Agrobacterium radiobacter; arPTE) electrostatically conjugated to amphiphilic polymer surfactant chains ([cat.arPTE][S-]). Experimentally-derived structural data are combined with molecular dynamics (MD) simulations to provide atomic level detail on conformational ensembles of the nanocomplex using dielectric constants relevant to aqueous and lipidic microenvironments. These show the formation of a compact admicelle pseudophase surfactant corona under aqueous conditions, which reconfigures to yield an extended conformation at a low dielectric constant, providing insight into the mechanism underpinning cell membrane binding. Significantly, it demonstrated that [cat.arPTE][S-] spontaneously binds to human mesenchymal stem cell membranes (hMSCs), resulting in on-cell OP hydrolysis. Moreover, the nanoconstruct can endocytose and partition into the intracellular fatty vacuoles of adipocytes and hydrolyze sequestered OP.

Fugacity- and biotransformation-based mechanistic insights into the trophic transfer of organophosphate flame retardants in a subtropical coastal food web from the Northern Beibu Gulf of China.

The bioaccumulation and trophic transfer of organophosphate flame retardants (OPFRs) in marine ecosystems have attracted great attention in recent research, but our understanding of the trophic transfer mechanisms involved is limited. In this study, we investigated the trophodynamics of OPFRs and their metabolites in a subtropical coastal food web collected from the northern Beibu Gulf, China, and characterized their trophodynamics using fugacity- and biotransformation-based approaches. Eleven OPFRs and all seven metabolites were simultaneously quantified in the shellfish, crustacean, pelagic fish, and benthic fish samples, with total concentrations ranging from 164 to 4.11 × 104 and 4.56-4.28 × 103 ng/g lipid weight, respectively. Significant biomagnification was observed only for tris (phenyl) phosphate (TPHP) and tris (2-ethylhexyl) phosphate (TEHP), while other compounds except for tris(2-chloroethyl) phosphate (TCEP) displayed biomagnification trends based on Monte Carlo simulations. Using a fugacity-based approach to normalize the accumulation of OPFRs in biota to their relative biological phase composition, storage lipid is the predominant biological phase for the mass distribution of 2-ethylhexyl diphenyl phosphate (EHDPHP) and TPHP. The water content and structure protein are equally important for TCEP, whereas lipid and structure protein are the two most important phases for other OPFRs. The mass distribution of these OPFRs along with TLs can explain their trophodynamics in the food web. The organophosphate diesters (as OPFR metabolites) also displayed biomagnification trends based on bootstrapped estimation. The correlation analysis and Korganism-water results jointly suggested the metabolites accumulation in high-TL organisms was related to biotransformation processes. The metabolite-backtracked trophic magnification factors for tri-n­butyl phosphate (TNBP) and TPHP were both greater than the values that accounted for only the parent compounds. This study highlights the incorporation of fugacity and biotransformation analysis to characterize the trophodynamic processes of OPFRs and other emerging pollutants in food webs.

The mechanism of interaction between tri-para-cresyl phosphate and human serum protein: a multispectroscopic and in-silico study.

Organophosphate flame retardants (OPFRs) pose the significant risks to the environment and human health and have become a serious public health issue. Tricresyl phosphates (TCPs), a group of aryl OPFRs, exhibit neurotoxicity and endocrine disrupting toxicity. However, the binding mechanisms between TCPs and human serum albumin (HSA) remain unknown. In this study, through fluorescence and ultraviolet-visible (UV-vis) absorption spectroscopy, molecular docking and molecular dynamics (MD), tri-para-cresyl phosphate (TpCP) was selected to explore potential interactions between HSA and TCPs. The results of the fluorescence spectroscopy demonstrated that a decrease the fluorescence intensity of HSA and a blue shift were observed with the increasing concentrations of TpCP. The binding constant (Ka) was 2.575 × 104 L/mol, 4.701 × 104 L/mol, 5.684 × 104 L/mol and 9.482 × 104 L/mol at 293 K, 298 K, 303 K, and 310 K, respectively. The fluorescence process between HSA and TpCP involved a mix of static and dynamic quenching mechanism. The gibbs free energy (ΔG0) of HSA-TpCP system was -24.452, -25.907, 27.363, and 29.401 kJ/mol at 293 K, 298 K, 303 K, and 310 K, respectively, suggesting that the HSA-TpCP reaction was spontaneous. The enthalpy change (ΔH0) and thermodynamic entropy change (ΔS0) of the HSA-TpCP system were 291.08 J/K mol and 60.83 kJ/mol, respectively, indicating that hydrophobic force was the major driving forces in the HSA-TpCP complex. Furthermore, multispectral analysis also revealed that TpCP could alter the microenvironment of tryptophan residue and the secondary structure of HSA and bind with the active site I of HSA. Molecular docking and MD simulations confirmed that TpCP could spontaneously form a stable complex with HSA, which was consistent with the fluorescence experimental results. This study provides novel insights into the mechanisms of underlying the transportation and distribution of OFPRs in humans.