Heterologous expression, biochemical characterization and prospects for insecticide biosensing potential of carboxylesterase Ha006a from Helicoverpa armigera.

Enzymes have attracted considerable scientific attention for their crucial role in detoxifying a wide range of harmful compounds. In today's global context, the extensive use of insecticides has emerged as a significant threat to the environment, sparking substantial concern. Insects, including economically important pests like Helicoverpa armigera, have developed resistance to conventional pest control methods through enzymes like carboxyl/cholinesterases. This study specifically focuses on a notable carboxyl/cholinesterase enzyme from Helicoverpa armigera (Ha006a), with the goal of harnessing its potential to combat environmental toxins. A total of six insecticides belonging to two different classes displayed varying inhibitory responses towards Ha006a, thereby rendering it effective in detoxifying a broader spectrum of insecticides. The significance of this research lies in discovering the bioremediation property of Ha006a, as it hydrolyzes synthetic pyrethroids (fenvalerate, λ-cyhalothrin and deltamethrin) and sequesters organophosphate (paraoxon ethyl, profenofos, and chlorpyrifos) insecticides. Additionally, the interaction studies between organophosphate insecticides and Ha006a helped in the fabrication of a novel electroanalytical sensor using a modified carbon paste electrode (MCPE). This sensor boasts impressive sensitivity, with detection limits of 0.019 µM, 0.15 µM, and 0.025 µM for paraoxon ethyl, profenofos, and chlorpyrifos, respectively. This study provides a comprehensive biochemical and biophysical characterization of the purified esterase Ha006a, showcasing its potential to remediate different classes of insecticides.

Revealing the mechanistic interactions of profenofos and captan pesticides with serum protein via biophysical and computational investigations.

Profenofos (PF) and captan (CT) are among the most utilized organophosphorus insecticides and phthalimide fungicides, respectively. To elucidate the physicochemical and influential toxicokinetic factors, the mechanistic interactions of serum albumin and either PF or CT were carried out in the current study using a series of spectroscopy and computational analyses. Both PF and CT could bind to bovine serum albumin (BSA), a representative serum protein, with moderate binding constants in a range of 103-104 M-1. The bindings of PF and CT did not induce noticeable BSA's structural changes. Both pesticides bound preferentially to the site I pocket of BSA, where the hydrophobic interaction was the main binding mode of PF, and the electrostatic interaction drove the binding of CT. As a result, PF and CT may not only induce direct toxicity by themselves, but also compete with therapeutic drugs and essential substances to sit in the Sudlow site I of serum albumin, which may interfere with the pharmacokinetics and equilibrium of drugs and other substances causing consequent adverse effects.

The looming threat of profenofos organophosphate and microbes in action for their sustainable degradation.

Organophosphates are the most extensively used class of pesticides to deal with increasing pest diversity and produce more on limited terrestrial areas to feed the ever-expanding global population. Profenofos, an organophosphate group of non-systematic insecticides and acaricides, is used to combat aphids, cotton bollworms, tobacco budworms, beet armyworms, spider mites, and lygus bugs. Profenofos was inducted into the system as a replacement for chlorpyrifos due to its lower toxicity and half-life. It has become a significant environmental concern due to its widespread presence. It accumulates in various environmental components, contaminating food, water, and air. As a neurotoxic poison, it inhibits acetylcholinesterase receptor activity, leading to dizziness, paralysis, and pest death. It also affects other eukaryotes, such as pollinators, birds, mammals, and invertebrates, affecting ecosystem functioning. Microbes directly expose themselves to profenofos and adapt to these toxic compounds over time. Microbes use these toxic compounds as carbon and energy sources and it is a sustainable and economical method to eliminate profenofos from the environment. This article explores the studies and developments in the bioremediation of profenofos, its impact on plants, pollinators, and humans, and the policies and laws related to pesticide regulation. The goal is to raise awareness about the global threat of profenofos and the role of policymakers in managing pesticide mismanagement.

Evaluation of biochemical, hematological, and genotoxic parameters in mice exposed to individual and combined ethoprophos and cadmium.

Environmental contamination by complex mixtures of pesticides and metals is a major health problem in agriculture and industry. In real life scenarios, we are exposed to mixtures of chemicals rather than single chemicals, and therefore it is critical to assess their toxicity. The current work was conducted to assess the toxic effects of a low dose (2% median lethal dose) of ethoprophos (Etho, 0.16 mg kg-1 bw), and cadmium (Cd, 0.63 mg kg-1 bw); each alone or in combination on hematological, biochemical, and genotoxic parameters in male mice for one or four weeks. The tested toxicants resulted in a decline in body and organs weights, the most hematological indices, acetylcholine esterase activity, and the total protein content, while they significantly increased liver and kidney function parameters. Furthermore, they increased the mitotic index (MI), number of abnormal sperms, and chromosomes. In conclusion, Etho and Cd induce deleterious effects on all tested parameters in male mice which reflect more obvious impacts when both combined, particularly after 28 days of exposure. However, further research is needed to confirm toxicokinetic or toxicodynamic interactions between these two toxic compounds in the organisms.

Peritrophin-like Genes Are Associated with Delousing Drug Response and Sensitivity in the Sea Louse Caligus rogercresseyi.

Caligus rogercresseyi is the main ectoparasite that affects the salmon industry in Chile. The mechanisms used by the parasite to support its life strategy are of great interest for developing control strategies. Due to the critical role of insect peritrophins in host-parasite interactions and response to pest control drugs, this study aimed to identify and characterize the peritrophin-like genes present in C. rogercresseyi. Moreover, the expression of peritrophin-like genes was evaluated on parasites exposed to delousing drugs such as pyrethroids and azamethiphos. Peritrophin genes were identified by homology analysis among the sea louse transcriptome database and arthropods peritrophin-protein database obtained from GenBank and UniProt. Moreover, the gene loci in the parasite genome were located. Furthermore, peritrophin gene expression levels were evaluated by RNA-Seq analysis in sea louse developmental stages and sea lice exposed to delousing drugs deltamethrin, cypermethrin, and azamethiphos. Seven putative peritrophin-like genes were identified in C. rogercresseyi with high homology with other crustacean peritrophins. Differences in the presence of signal peptides, the number of chitin-binding domains, and the position of conserved cysteines were found. In addition, seven peritrophin-like gene sequences were identified in the C. rogercresseyi genome. Gene expression analysis revealed a stage-dependent expression profile. Notably, differential regulation of peritrophin genes in resistant and susceptible populations to delousing drugs was found. These data are the first report and characterization of peritrophin genes in the sea louse C. rogercresseyi, representing valuable knowledge to understand sea louse biology. Moreover, this study provides evidence for a deeper understanding of the molecular basis of C. rogercresseyi response to delousing drugs.

Organophosphorus insecticides exposure and sex hormones in general U.S. population: A cross-sectional study.

BACKGROUND: Evidence showed organophosphorus (OPs) insecticide exposure is common in general population with endocrine-disrupting effects. However, the association between OPs metabolites and sex hormones remains unclear. OBJECTIVE: To investigate the association between OPs metabolites and sex hormones. METHODS: Data of 1438 participants from NHANES 2015-2016 was applied. Urinary OPs metabolites, dialkyl phosphates (DAPs), and serum sex hormones (total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG)) were measured. Free androgen index (FAI) and TT/E2 ratio were also calculated. The generalized linear regression model and restricted cubic spline (RCS) model were employed to evaluate the association and exposure-response curve of DAPs and sex hormones in males and females. The modulation effect of age on their associations in female participants was also explored. RESULTS: After adjusting for confounding factors, DETP was negatively associated with E2 (ß = -0.03; 95% CI: -0.05, -0.01) and FAI (ß = -0.03; 95% CI: -0.06, -0.001) in males. In females, all the four DAP metabolites (DMP, DEP, DMTP, and DETP) were negatively associated with FAI (DMP: ß = -0.06, 95% CI: -0.11, -0.01; DEP: ß = -0.06, 95% CI: -0.12, -0.01; DMTP: -0.05, 95% CI: -0.09, -0.02; DETP: -0.09, 95% CI: -0.14, -0.04). DETP was also found negatively associated with TT and TT/E2 ratio in females. The associations between DETP and TT, FAI, and TT/E2 ratio were modified by gender (Pinteraction<0.05). RCS analysis found these associations were in linear decreased exposure-response curves. For females of different age groups, the inverse associations of DETP with TT and FAI remained stable. Decreased FAI with DMP and DMTP was also found in females ≤50 years old. CONCLUSIONS: Our study indicates OPs metabolites had negative associations with androgen indicators, which was characterized as decreased FAI and E2 in males and decreased TT, FAI, and TT/E2 ratio in females, particularly among females ≤50 years old. Further studies are warranted in larger-scale populations.

Validation of an SH-SY5Y Cell-Based Acetylcholinesterase Inhibition Assay for Water Quality Assessment.

The acetylcholinesterase (AChE) inhibition assay has been frequently applied for environmental monitoring to capture insecticides such as organothiophosphates (OTPs) and carbamates. However, natural organic matter such as dissolved organic carbon (DOC) co-extracted with solid-phase extraction from environmental samples can produce false-negative AChE inhibition in free enzyme-based AChE assays. We evaluated whether disturbance by DOC can be alleviated in a cell-based AChE assay using differentiated human neuroblastoma SH-SY5Y cells. The exposure duration was set at an optimum of 3 h considering the effects of OTPs and carbamates. Because loss to the airspace was expected for the more volatile OTPs (chlorpyrifos, diazinon, and parathion), the chemical loss in this bioassay setup was investigated using solid-phase microextraction followed by chemical analysis. The three OTPs were relatively well retained (loss <34%) during 3 h of exposure in the 384-well plate, but higher losses occurred on prolonged exposure, accompanied by slight cross-contamination of adjacent wells. Inhibition of AChE by paraoxon-ethyl was not altered in the presence of up to 68 mgc /L Aldrich humic acid used as surrogate for DOC. Binary mixtures of paraoxon-ethyl and water extracts showed concentration-additive effects. These experiments confirmed that the matrix in water extracts does not disturb the assay, unlike purified enzyme-based AChE assays. The cell-based AChE assay proved to be suitable for testing water samples with effect concentrations causing 50% inhibition of AChE at relative enrichments of 0.5-10 in river water samples, which were distinctly lower than corresponding cytotoxicity, confirming the high sensitivity of the cell-based AChE inhibition assay and its relevance for water quality monitoring. Environ Toxicol Chem 2022;41:3046-3057. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

A non-contact system for intraoperative quantitative assessment of bradykinesia in deep brain stimulation surgery.

BACKGROUND AND OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment for a number of neurological diseases, especially for the advanced stage of Parkinson's disease (PD). Objective assessment of patients' motor symptoms is crucial for accurate electrode targeting and treatment. Existing approaches suffer from subjective variability or interference with voluntary motion. This work is aimed to establish an objective assessment system to quantify bradykinesia in DBS surgery. METHODS: Based on the analysis of the requirements for intraoperative assessment, we developed a system with non-contact measurement, online movement feature extraction, and interactive data analysis and visualization. An optical sensor, Leap Motion Controller (LMC), was taken to detect hand movement in three clinical tasks. A graphic user interface was designed to process, compare and visualize the collected data and assessment results online. Quantified movement features include amplitude, frequency, velocity, their decrement and variability, etc. Technical validation of the system was performed with a motion capture system (Mocap), with respect to data-level and feature-level accuracy and reliability. Clinical validation was conducted with 20 PD patients for intraoperative assessments in DBS surgery. Treatment responses with respect to the bradykinesia movement features were analyzed. Single case analysis and group statistical analysis were performed to examine the differences between preoperative and intraoperative performance, and the correlation between the clinical ratings and the quantified assessment was analyzed. RESULTS: For the movements measured by LMC and Mocap, the average Pearson's correlation coefficient was 0.986, and the mean amplitude difference was 2.11 mm. No significant difference was found for all movement features quantified by LMC and Mocap. For the clinical tests, key movement features showed significant differences between the preoperative baseline and intraoperative performance when the brain stimulation was ON. The assessment results were significantly correlated with the MDS-UPDRS clinical ratings. CONCLUSIONS: The proposed non-contact system has established itself as an objective intraoperative assessment, analysis, and visualization tool for DBS treatment of Parkinson's disease.

Colorimetric and fluorescent probes for the rapid detection of profenofos in farmland system.

Colorimetric and fluorescent sensors were developed for the detection of profenofos. The colorimetric assay relied on the aggregation of cysteine modified gold nanoparticles (Au-cys) composite caused by the hydrogen bond and Au-S bond between profenofos and Au-cys. The further addition of S, N-doped carbon quantum dots (CDs) (fluorescence quantum yield up to 98%) into the Au-cys system depended on the change of fluorescence intensity of Au-cys-CDs owing to the inner filter effect between Au-cys and CDs. Under the optimal conditions, the sensor exhibits good linearity within 0.2-1.2 mg L-1 and 20-320 µg L-1, and limit of detection of 21.7 µg L-1 and 5.5 µg L-1 in colorimetry and fluorescence mode, respectively. The developed sensor did not only possess favorable selectivity and sensitivity, but also feasibility of usage in the actual detection of profenofos in farmland system samples.

Fluffy ball-like magnetic covalent organic frameworks for adsorption and removal of organothiophosphate pesticides.

Organothiophosphate pesticides (OPPs) are the most commonly used pesticides, and their environmental migration brings serious water pollution and significant danger to human health, and thus it is urgent to develop effective technologies for removal of OPPs from water. Herein, magnetic covalent organic framework (COF) with a triazine skeleton was fabricated for enhanced adsorption and removal of OPPs from water. Magnetic COF has a fluffy ball-like structure, high crystallinity, large BET surface area (1543 m2 g-1), and regular mesopores (~3.1 nm). Therefore, it displayed high adsorption rates and large adsorption capacities for four typical OPPs, pyridafenthion, phoxim, pyrimitate, and phorate. Based on adsorption kinetic and isotherms investigations, the batch experimental data of magnetic COF was effectively modeled by pseudo-second-order kinetics and the Freundlich isothermal model. The equilibrium adsorption capacities of magnetic COF composite for OPPs ranged from 163.9 to 178.6 mg g-1, which were about 10 times higher than the amorphous magnetic composite. The adsorption mechanism was further explored to verify the contributions of π-π, CH⋯π, and CH⋯S interactions to the adsorption of OPPs on the crystalline magnetic COF. Furthermore, the high removal rate of OPPs from the environmental water and reusability further indicated its potential in real applications as an effective adsorption material.

Albicanol modulates oxidative stress and the p53 axis to suppress profenofos induced genotoxicity in grass carp hepatocytes.

The organophosphorus pesticide profenofos (PFF) is widely used as an environmental contaminant, and it can remain in water bodies causing serious harm to aquatic organisms. Albicanol is a sesquiterpenoid with potent antioxidant and antagonistic activities against heavy metal toxicity. However, the mechanism of PFF induced genotoxicity in fish hepatocytes and the role Albicanol can play in this process are unknown. In this study, the model was established by treating grass carp hepatocytes with PFF (150 µM) and/or Albicanol (5 × 10-5 µg mL-1) for 24 h. The results showed that PFF exposure arrested L8824 cells in the G1-S phase. PFF caused the increase of MDA level in L8824 cells, while the decrease of SOD, CAT and T-AOC levels caused oxidative stress. Elevated levels of γH2AX, tail moment, tail length, % DNA and 8-OHdG indicated that PFF caused DNA damage in L8824 cells. PFF inhibited the expression levels of cell cycle related regulatory genes (cyclin A, cyclin D, cyclin E, CDK2 and CDK4) by upregulating p53/p21 genes and activating the p53 signaling pathway. Albicanol was used to significantly reduce the above effects caused by PFF exposure on hepatocytes in grass carp. Albicanol could reduce the increase in the proportion of cells in the G1-S phase caused by PFF. In summary, Albicanol could inhibit the genotoxicity of L8824 cells resulted from PFF exposure by decreasing oxidative stress and the p53 pathway.

Dissipation and gas chromatographic method for the determination of profenofos residues in/on green pea and cucumber.

Herein we report a novel, accurate and cost-effective gas chromatography method for the determination of average deposits of profenofos on green pea and cucumber following good agricultural practices. Additionally the risk assessment, dissipation and waiting period for profenofos were determined. The average initial deposits (2 h after spraying) of profenofos in/on green pea and cucumber were 3.41 and 3.62 mg kg-1 respectively following two applications at a 10 day interval of profenofos 50EC formulation. Profenofos residues on both of the substrates were below the detection limit of 0.05 mg kg-1 after 20 days at the recommended dosage. For risk assessment studies, the 20th day will be safe for consumers for consumption of green peas. The gas chromatography method was validated according to the SANTE guidelines using the various analytical parameters: linearity, accuracy, detection and quantification limits. The developed method is simple, selective and repeatable and can be extended for profenofos-based standardization of pesticide formulations for green pea/cucumber and their use as pesticides.

Albicanol inhibits the toxicity of profenofos to grass carp hepatocytes cells through the ROS/PTEN/PI3K/AKT axis.

Profenofos (PFF) as an environmental pollutant seriously harms the health of aquatic animals, and even endangers human safety through the food chain. Albicanol, a sesquiterpenoid extraction from the Dryopteris fragrans, has previously been shown to effectively exhibit anti-aging, anti-oxidant, and antagonize the toxicity of heavy metals. However, the mechanism of hepatocyte toxicity caused by PFF and the role that Albicanol plays in this process are still unclear. In this study, a PFF poisoning model was established by treating grass carp hepatocytes cells with PFF (150 µM) for 24 h The results of AO/EB staining, Tunel staining and flow cytometry showed that the proportion of apoptotic liver cells increased significantly after exposure. The results of ROS staining show that compared with the control group, ROS levels and PTEN/PI3K/AKT-related gene expression were up-regulated after PFF exposure. RT-qPCR and Western blotting results showed that the expression of PTEN/PI3K/AKT related genes was up-regulated. These results indicate that PFF can induce oxidative stress in hepatocytes and inhibit the phosphorylation of AKT. We further found that the expressions of Bax, CytC, Caspase-3, Caspase-9, Caspase-8 and TNFR1 after PFF exposure were significantly higher than those of the control group, and Bcl-2/Bax was significantly lower than that of the control group. These results indicate that PFF can induce oxidative stress in hepatocytes and inhibit the phosphorylation of AKT and activate mitochondrial apoptosis. Using Albicanol (5 × 10-5 µg mL-1) can significantly reduce the above-mentioned effects of PFF exposure on grass carp hepatocytes cells. In summary, Albicanol inhibits PFF-induced apoptosis by regulating the ROS/PTEN/PI3K/AKT pathway.

Effects of simulated environmental discharges of the salmon lice pesticides deltamethrin and azamethiphos on the swimming behaviour and survival of adult Northern shrimp (Pandalus borealis).

Swimming behaviour was investigated in adult egg-carrying northern shrimp (Pandalus borealis) exposed to dilute concentrations of the pesticides Alpha Max® (active ingredient deltamethrin) and Salmosan® (active ingredient azamethiphos) used to control parasitic copepods in salmon aquaculture. These treatments are applied topically within fish nets or well boats. Following a short treatment period, the pesticides are directly discharged to sea, exposing non-target organisms such as P. borealis to diluted concentrations of these chemicals. Locomotor activity was measured continuously in individual shrimp over several days within which they were exposed to treatments of diluted AlphaMax® or Salmosan®. Dilutions were based on modelling and dispersion studies from the literature and were considered environmentally realistic for greater than 1 km from point of discharge. 24 h continuous flow treatments were delivered within a 3.5-day monitoring period to observe the timeline of events following the release of treatment water, addressing questions of temporal responses in locomotor activity, recognising key time points of significant events and assessing the survival capacity of the shrimp. Exposure of shrimp to 1 ng l-1 deltamethrin triggered an immediate increase in swimming activity which reduced in intensity over the following 22 h leaving all shrimp either moribund or dead. A further exposure trial exposing shrimp to 0.2 ng l-1 deltamethrin (nominal) showed an increase in activity at the start of exposure that continued throughout the 24 h delivery, returning to previous levels by the end of the 3.5-day monitoring period. All these shrimps survived for at least four weeks after exposure, putting the threshold concentration of deltamethrin leading to immobility or death in adult P. borealis within this study at greater than 0.2 ng l-1 (nominal) and less than 1 ng l - 1 (measured). Exposure of P. borealis to azamethiphos at 30 ng l-1 induced several periods of significantly increased activity within the first 10 h of exposure and an extended period of reduced activity during post exposure, though no morbidity was observed with this treatment. No significant increase in activity or morbidity was observed in shrimp during a water vehicle control assessment. Shrimps exposed to a combination of 30 ng l-1 azamethiphos and 1 ng l-1 deltamethrin broadly followed the response pattern shown by shrimp exposed to 1 ng l-1 deltamethrin alone. Pesticide residues were not detected in post exposure tissue analyses for either chemical. The potential ecological significance of increased swimming activity at the start of pesticide exposures is discussed.

A sensitive bio-barcode immunoassay based on bimetallic Au@Pt nanozyme for detection of organophosphate pesticides in various agro-products.

Organophosphate pesticides (OPs) are often used as insecticides and acaricides in agriculture, thus improving yields. OP residues may pose a serious threat, duetoinhibitionof the enzymeacetylcholinesterase(AChE). Therefore, a competitive bio-barcode immunoassay was designed for simultaneous quantification of organophosphate pesticide residues using AuNP signal amplification technology and Au@Pt catalysis. The AuNP probes were labelled with antibodies and corresponding bio-barcodes (ssDNAs), MNP probes coated with ovalbumin pesticide haptens and Au@Pt probes functionalized with the complementary ssDNAs were then prepared. Subsequently, pesticides competed with MNP probes to bind the AuNP probes. The recoveries of the developed assay were ranged from 71.26 to 117.47% with RSDs from 2.52 to 14.52%. The LODs were 9.88, 3.91, and 1.47 ng·kg-1, for parathion, triazophos, and chlorpyrifos, respectively. The assay was closely correlated with the data obtained from LC-MS/MS. Therefore, the developed method has the potential to be used as an alternative approach for detection of multiple pesticides.

Triazophos and its metabolite diethyl phosphate have different effects on endocrine hormones and gut health in rats.

Organophosphorus pesticide (OP) residues present in food can be metabolized into diethylphosphate (DEP) in vivo. Epidemiological studies of OPs have usually focused on these metabolites, while animal studies mainly assessed the OPs. Here, we compared the health risks of a frequently detected OP, triazophos (TAP), and its major metabolite, DEP, in rats. Levels of serum lipids and, sex hormones were measured using immunoassay kits. Gut hormones and inflammatory cytokines were assessed using a multiplexing kit, and the gut microbiota was evaluated by 16S rRNA gene sequencing. After a 24-week exposure period, both TAP and DEP significantly decreased serum levels of triglycerides, cholesterol, low-density lipoprotein cholesterol, and IL-6 (p < 0.05). However, DEP exposure had a stronger effect on serum estradiol (p < 0.05) than TAP, whereas only TAP inhibited the secretion of gut hormones. Both TAP and DEP enriched the pathogenic genera Oscillibacter, Peptococcus and Paraprevotella in the gut, and TAP also enriched enteritis-related genera Roseburia and Oscillibacter, which may affect the secretion of gut hormones. These findings indicate that the use of dialkyl phosphates as markers of OPs to examine the correlations of OP exposure with diseases may only provide partial information, especially for diseases related to gut health and the endocrine system.

Three widely used pesticides and their mixtures induced cytotoxicity and apoptosis through the ROS-related caspase pathway in HepG2 cells.

Difenoconazole, cypermethrin and triazophos are widely used pesticides in agricultural production and frequently detected in foods. The aim of this study was to determine the effect of these pesticides and their mixtures on cell viability, reactive oxygen species (ROS), lactate dehydrogenase (LDH) content, apoptosis rate and DNA fragmentation and synthesis in human hepatocellular carcinoma cells (HepG2). The order of inhibitory effects for the individual pesticides was ranked as difenoconazole > cypermethrin > triazophos. The enhanced expression of caspase-3, caspase-7 and PARP activity was observed in HepG2 cells, which was 1.7, 1.3 and 1.6-fold higher than the control, respectively, along with significant protein cleavage; and induced apoptosis in a concentration-dependent manner. Further, the pesticide mixtures significantly increased ROS level (up to 1.3-fold), induced DNA fragmentation (up to 1.8-fold), inhibited DNA synthesis (up to 53%), and damaged the cells by destroying the cell membrane and producing a large amount of LDH at concentration range of 10-30 µM. Specifically, mixtures containing difenoconazole showed stronger toxicities than individual pesticides, implying higher health risks associated with mixtures. Our results show that three widely used pesticides exhibited cytotoxicity and apoptosis through the ROS-related caspase pathway, providing a basis for evaluation of health risks from pesticide mixtures via food consumption.

Prediction of dose-dependent in vivo acetylcholinesterase inhibition by profenofos in rats and humans using physiologically based kinetic (PBK) modeling-facilitated reverse dosimetry.

Organophosphate pesticides (OPs) are known to inhibit acetylcholine esterase (AChE), a critical effect used to establish health-based guidance values. This study developed a combined in vitro-in silico approach to predict AChE inhibition by the OP profenofos in rats and humans. A physiologically based kinetic (PBK) model was developed for both species. Parameter values for profenofos conversion to 4-bromo-2-chlorophenol (BCP) were derived from in vitro incubations with liver microsomes, liver cytosol, and plasma from rats (catalytic efficiencies of 1.1, 2.8, and 0.19 ml/min/mg protein, respectively) and humans (catalytic efficiencies of 0.17, 0.79, and 0.063 ml/min/mg protein, respectively), whereas other chemical-related parameter values were derived using in silico calculations. The rat PBK model was evaluated against literature data on urinary excretion of conjugated BCP. Concentration-dependent inhibition of rat and human AChE was determined in vitro and these data were translated with the PBK models to predicted dose-dependent AChE inhibition in rats and humans in vivo. Comparing predicted dose-dependent AChE inhibition in rats to literature data on profenofos-induced AChE inhibition revealed an accurate prediction of in vivo effect levels. Comparison of rat predictions (BMDL10 of predicted dose-response data of 0.45 mg/kg bw) and human predictions (BMDL10 of predicted dose-response data of 0.01 mg/kg bw) suggests that humans are more sensitive than rats, being mainly due to differences in kinetics. Altogether, the results demonstrate that in vivo AChE inhibition upon acute exposure to profenofos was closely predicted in rats, indicating the potential of this novel approach method in chemical hazard assessment.

Simultaneous detection and identification of thiometon, phosalone, and prothioconazole pesticides using a nanoplasmonic sensor array.

In this work, a colorimetric sensor array has been designed for the identification and discrimination of thiometon (TM) and phosalone (PS) as organophosphate pesticides and prothioconazole (PC) as a triazole pesticide. For this purpose, two different plasmonic nanoparticles including unmodified gold nanoparticles (AuNPs) and unmodified silver nanoparticles (AgNPs) were used as sensing elements. The principle of the proposed strategy relied on the aggregation AuNPs and AgNPs through the cross-reactive interaction between the target pesticides and plasmonic nanoparticles. Therefore, these aggregation-induced UV-Vis spectra changes were utilized to discriminate the target pesticides with the help of linear discriminant analysis (LDA). Besides, we have employed the bar plots and the heat maps as visual non-statistical methods to differentiate the pesticides in a wide range of concentrations (i.e., 20-5000 ng mL-1). Multivariate calibration plots from partial least squares (PLS)- regression indicated that the responses linearly depend on the pesticide concentrations in the range of 100-1000 ng mL-1 with the limit of detections (LOD) of 66.8, 68.3, and 41.4 ng mL-1, for TM, PS, and PC, respectively. Finally, the potential applicability of the proposed sensor array has been evaluated for the detection and identification of the pesticides in the mixtures, water samples, and cucumber fruit.

Biodegradation pathway of the organophosphate pesticides chlorpyrifos, methyl parathion and profenofos by the marine-derived fungus Aspergillus sydowii CBMAI 935 and its potential for methylation reactions of phenolic compounds.

The indiscriminate use of organophosphate pesticides causes serious environmental and human health problems. This study aims the biodegradation of chlorpyrifos, methyl parathion and profenofos with the proposal of new biodegradation pathways employing marine-derived fungi as biocatalysts. Firstly, a growth screening was carried out with seven fungi strains and Aspergillus sydowii CBMAI 935 was selected. For chlorpyrifos, 32% biodegradation was observed and the metabolites tetraethyl dithiodiphosphate, 3,5,6-trichloropyridin-2-ol, 2,3,5-trichloro-6-methoxypyridine, and 3,5,6-trichloro-1-methylpyridin-2(1H)-one were identified. Whereas 80% methyl parathion was biodegraded with the identification of isoparathion, methyl paraoxon, trimethyl phosphate, O,O,O-trimethyl phosphorothioate, O,O,S-trimethyl phosphorothioate, 1-methoxy-4-nitrobenzene, and 4-nitrophenol. For profenofos, 52% biodegradation was determined and the identified metabolites were 4-bromo-2-chlorophenol, 4-bromo-2-chloro-1-methoxybenzene and O,O-diethyl S-propylphosphorothioate. Moreover, A. sydowii CBMAI 935 methylated different phenolic substrates (phenol, 2-chlorophenol, 6-chloropyridin-3-ol, and pentachlorophenol). Therefore, the knowledge about the fate of these compounds in the sea was expanded, and the marine-derived fungus A. sydowii CBMAI 935 showed potential for biotransformation reactions.