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Scientific Reports Nov 2021Toxicity of organophosphorus compounds (OPs) remains a major public health concern due to their widespread use as pesticides and the existence of nerve agents. Their...
Toxicity of organophosphorus compounds (OPs) remains a major public health concern due to their widespread use as pesticides and the existence of nerve agents. Their common mechanism of action involves inhibition of enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) which are crucial for neurotransmission. Both chronic and acute poisoning by OPs can leave long-lasting health effects even when the patients are treated with standard medical therapy. Therefore, an increasing urgency exists to find more effective oxime reactivators for compounds which are resistant to reactivation, especially phosphoramidates. Here, we investigated in silico and in vitro interactions and kinetics of inhibition for human cholinesterases with four organophosphate pesticides-ethoprophos, fenamiphos, methamidophos and phosalone. Overall, ethoprophos and fenamiphos displayed higher potency as inhibitors for tested cholinesterases. Our results show that methamidophos-inhibited hAChE was more susceptible to reactivation than hAChE inhibited by fenamiphos by selected oximes. Molecular modelling enabled an evaluation of interactions important for specificity and selectivity of both inhibition and reactivation of cholinesterases. Two newly developed reactivators-bispyridinium triazole oxime 14A and zwitterionic oxime RS194B possess remarkable potential for further development of antidotes directed against pesticides and related phosphoramidate exposures, such as nerve agents tabun or Novichoks.
Topics: Acetylcholinesterase; Butyrylcholinesterase; Cholinesterase Inhibitors; GPI-Linked Proteins; Humans; Kinetics; Organophosphorus Compounds; Pesticides
PubMed: 34728713
DOI: 10.1038/s41598-021-00953-9 -
Journal of the American Chemical Society Sep 2019Sensors based on graphene are promising devices for chemical and biological detection owing to their high sensitivity, biocompatibility, and low costs. However, for...
Sensors based on graphene are promising devices for chemical and biological detection owing to their high sensitivity, biocompatibility, and low costs. However, for chiral recognition, which is very important in biological systems, graphene sensors remain unable to discriminate enantiomers. Here, using chiral pesticide molecules as an example, we realized a highly sensitive graphene chiral sensor by modification with acetylcholinesterase (AChE). Quantum chemical simulations indicate that the inhibition effect of the enantiomer on AChE was transferred to graphene, which allowed for the electrical detection of chiral molecules. Under an operating voltage of 1 V, the sensitivity of the device reached 0.34 μg/L and 0.32 μg/L for (+)/(-)-methamidophos, respectively, which is much higher than by circular dichroism (6.90 mg/L and 5.16 mg/L, respectively). Furthermore, real-time, rapid detection was realized by combining with smartphones and wireless transmission.
Topics: Acetylcholinesterase; Circular Dichroism; Graphite; Limit of Detection; Organothiophosphorus Compounds; Pesticides; Quantum Theory; Radio Waves; Smartphone; Stereoisomerism
PubMed: 31448915
DOI: 10.1021/jacs.9b05724 -
The Science of the Total Environment Aug 2018The existence of pesticides, such as organochlorine pesticides, parathion-ethyl, methamidophos which is banned globally and some current-use non-banned pesticides of...
Distribution and risk assessment of banned and other current-use pesticides in surface and groundwaters consumed in an agricultural catchment dominated by cocoa crops in the Ankobra Basin, Ghana.
The existence of pesticides, such as organochlorine pesticides, parathion-ethyl, methamidophos which is banned globally and some current-use non-banned pesticides of organophosphorus and synthetic pyrethroids in freshwater sources is an ecological and public health concern in many countries, including Ghana. Prompted by this concern, the exposure levels and risk assessment of these pesticides to humans and non-target organisms via groundwater and surface water sources in an agricultural catchment dominated by cocoa crops in the Ankobra Basin, Ghana, were investigated. The individual concentrations of the banned pesticides in the surface water and groundwater samples varied from < LOD to 0.110 μg/L and < LOD to 0.055 μg/L, respectively, while the concentrations of the non-banned pesticides ranged from < LOD to 0.925 μg/L and < LOD to 2 μg/L, respectively. The mean concentrations of chlorpyrifos, cypermethrin, p,p'-DDT and pirimiphos-methyl in some water sources exceeded the EU limit of 0.1 μg/L. Some surface water sources were more contaminated with DDTs, endrin, dieldrin, methoxychlor, chlorpyrifos, and HCH isomers than were freshwater sources in river basins in some countries of the world. Chlorpyrifos, p,p'-DDT and methoxychlor were ubiquitous in both water sources. The hydrochemical and compositional profiles of the pesticides indicate that water-exchange and secondary porosities in the bedrock likely contributed to the occurrence of the pesticides in the water sources. The pesticides were of low risk to humans that consume the water, but considering the US EPA safe limit for carcinogenic effects of 10, the high levels of DDTs, β-HCH, and dieldrin in some of the surface water and groundwater sources may cause cancer in children or infants. The toxicity of pesticide mixtures to surface water non-target organisms decreased in the order of fish > Daphnia magna > algae. The pesticides in the water sources were anthropogenic in origin and recently used. DDT and HCH in the water were of technical-grade origin.
Topics: Agriculture; Cacao; Crops, Agricultural; Dietary Exposure; Geologic Sediments; Ghana; Groundwater; Humans; Hydrocarbons, Chlorinated; Pesticide Residues; Pesticides; Risk Assessment; Rivers; Water Pollutants, Chemical; Water Pollution, Chemical; Water Supply
PubMed: 29597160
DOI: 10.1016/j.scitotenv.2018.03.129 -
Toxics Oct 2021In recent years, the official authorities in Chile have reported transgressions in the maximum residue levels of pesticides in fresh vegetables. There is no official...
In recent years, the official authorities in Chile have reported transgressions in the maximum residue levels of pesticides in fresh vegetables. There is no official information about traceability, pesticide levels, and potential health risks. The aim of this study was to analyse pesticide residues and their corresponding dietary risk assessments in tomatoes from supermarkets in the Metropolitan Region. Pesticides were extracted using the Quick, Easy, Cheap, Effective, Rugged and Safe, QuEChERS method, and their concentrations were determined by using chromatography with HPLC-FL/UV and GC-MS/ECD/NPD, following the Analytical Quality Control and Method Validation Procedures for Pesticides Residues Analysis in Food and Feed, SANTE guide and ISO 17025:2017 standard. In addition, a dietary risk assessment was carried out by comparing Chilean data to international references. The results reported that 9% of the samples had pesticide residue levels above the maximum residue levels permitted in Chile. All the scenarios evaluated revealed the highest estimated daily intake and hazard quotients for methamidophos and chlorpyrifos. Both the active substances used were acetylcholinesterase inhibitors and were neurotoxic under chronic risk assessment. The results showed the highest chronic hazard index in the Chilean scenario for all age groups and genders. The evidence obtained revealed that methamidophos, methomyl, and chlorpyrifos should be restricted for their use in Chilean agriculture.
PubMed: 34678945
DOI: 10.3390/toxics9100249 -
Environmental Science and Pollution... Dec 2014The main objective of the review is to document, assess and analyze the results of the previously reported data on levels of different pesticides in selected fruits and... (Review)
Review
The main objective of the review is to document, assess and analyze the results of the previously reported data on levels of different pesticides in selected fruits and vegetables from Pakistan. The findings of the previous studies clearly indicated that more than 50 % of the samples were contaminated with organophosphate, pyrethroids and organochlorine pesticides. Many studies reported that among fresh fruits and vegetables tomato, apple, melon, mango, grapes, and plum crossed the FAO/WHO permissible limits for these contaminants residual levels. The comparison of other regions showed that observed levels were found above maximum residue limits (MRLs) in 50 % of the samples but were in agreement with the studies from neighboring countries like China and Bangladesh. Higher hazard risk index (HRI) values were calculated for dieldrin, methamidophos, o,p'-DDT, diazinon and p,p'-DDT in apple, mango, banana, melon, potato and onion. The review also highlights that data on pesticide residues in foodstuff is scarce which should be overcome by further extending studies from different areas of Pakistan. In order to ascertain the provision of food suitable for human consumption, it is imperative to monitor pesticides in food commodities by the country's authorities and enforce guidelines based on permissible limits.
Topics: DDT; Dieldrin; Food Contamination; Fruit; Humans; Hydrocarbons, Chlorinated; Solanum lycopersicum; Pakistan; Pesticide Residues; Pesticides; Risk; Vegetables
PubMed: 24958529
DOI: 10.1007/s11356-014-3117-z -
Neurotoxicity Research Oct 2017Although evidence indicates that exposure to organophosphorus (OP) pesticides induces neurobehavioral disorders, little is known about the effects of OP on aggressive...
Although evidence indicates that exposure to organophosphorus (OP) pesticides induces neurobehavioral disorders, little is known about the effects of OP on aggressive behaviour. Our study investigated the effects of repeated exposure to an OP pesticide, methamidophos, on the isolation-induced aggressive behaviour in mice. Forty seven male mice were individually housed for a month. Socially isolated animals were then confronted with a standard non-isolated opponent for 15 min (pre-treatment trial), and the latency and frequency of aggressive and general exploratory behaviours were recorded. Based on the presence of attack behaviour in the pre-treatment trial, mice were classified as isolation-induced aggressive and non-aggressive. All mice were then treated for 7 days with methamidophos (3.5 mg/kg/day, n = 22, intraperitoneal (i.p.)) or saline (1 mL/kg/day, control group, n = 25, i.p.), and a second trial was performed. Repeated exposure to methamidophos induced attack behaviour in non-aggressive mice. The treatment with methamidophos also decreased plasma butyrylcholinesterase and brain acetylcholinesterase activity. These results suggest that methamidophos has a pro-aggressive effect on socially isolated mice.
Topics: Acetylcholinesterase; Aggression; Animals; Brain; Butyrylcholinesterase; Injections, Intraperitoneal; Insecticides; Male; Mice; Motor Activity; Organothiophosphorus Compounds; Psychological Tests; Social Isolation
PubMed: 28540662
DOI: 10.1007/s12640-017-9750-9 -
Food Chemistry May 2022A method for the determination of 80 pesticides (including five metabolites) in passion fruit using ethyl acetate extraction and dispersive solid-phase extraction...
A method for the determination of 80 pesticides (including five metabolites) in passion fruit using ethyl acetate extraction and dispersive solid-phase extraction followed by LC-MS/MS and GC-MS/MS was validated at LOQ of 0.005 or 0.010 mg kg (70 to 120% recovery; RSD ≤ 20%). Fifty-five passion fruit samples were obtained from producers, and 30 samples of frozen pulp and 12 samples of flour purchased. About 27% of the pesticides were detected; at least one in 60% of the peel samples, mainly imidacloprid and carbendazim (max. of 0.274 mg kg). Median processing factor was 0.5 for washed peel and 6.5 for dried peel (flour). About 63% of frozen pulp samples were positive, and 4 flour samples contained residues, mainly methamidophos. About 70% of the detected pesticides are not authorized in passion fruit in Brazil. Chronic and acute exposure from the consumption of passion fruit products did not indicate a health concern.
Topics: Chromatography, Liquid; Fruit; Gas Chromatography-Mass Spectrometry; Passiflora; Pesticide Residues; Risk Assessment; Tandem Mass Spectrometry
PubMed: 34836670
DOI: 10.1016/j.foodchem.2021.131643 -
Environmental Science and Pollution... Apr 2023Pesticides use increased worldwide with a record in Brazil. Although several works addressed the effects of pesticides on living organisms, only a few considered their...
Pesticides use increased worldwide with a record in Brazil. Although several works addressed the effects of pesticides on living organisms, only a few considered their mixture, and even fewer tried to unravel their role in tumoral progression. Due to the relevance of cancer, in the present study, the effects of the mixture of pesticides widely used in Brazil (Glyphosate, 2,4-dichlorophenoxyacetic acid, Mancozeb, Atrazine, Acephate, and Paraquat) and their main metabolites (Aminomethylphosphonic Acid, 2,4-diclorophenol, Ethylenethiourea, Desethylatrazine, Methamidophos, and Paraquat) were investigated on the malignancy phenotype of murine melanoma B16-F1 cells after acute (24 h) and chronic (15 days) exposures. The tested concentrations were based on the Acceptable Daily Intake (ADI) value established by Brazilian legislation. The set of results showed that these chemicals modulate important parameters of tumor progression, affecting the expression of genes related to tumor aggressiveness (Mmp14 and Cd44) and multidrug resistance (Abcb1, Abcc1, and Abcc4), as well as tissue inhibitors of metalloproteinases (Timp1, Timp2, and Timp3). These findings revealed an absence of cytotoxicity but showed modulation of migration, invasion, and colonization capacity of B16-F1 cells. Together, the results point to some negative ways that exposure to pesticides can affect the progression of melanoma and raise a concern related to the increasing trend in pesticide use in Brazil, as the country is one of the major world food suppliers.
Topics: Animals; Mice; Pesticides; Paraquat; Melanoma; Phenotype; Complex Mixtures
PubMed: 36738412
DOI: 10.1007/s11356-023-25603-7 -
Methamidophos induces cytotoxicity and oxidative stress in human peripheral blood mononuclear cells.Environmental Toxicology Jan 2017Previous studies have shown that organophosphate pesticide (OP) exposure is associated with oxidative stress. Methamidophos (MET) is an OP widely used in agriculture,...
Previous studies have shown that organophosphate pesticide (OP) exposure is associated with oxidative stress. Methamidophos (MET) is an OP widely used in agriculture, which is regarded as a highly toxic pesticide and it is a potent inhibitor of acetylcholinesterase. The aim of this study was to evaluate whether MET can induce oxidative stress at low concentrations in primary cultures of human peripheral blood mononuclear cells (PBMCs). PBMCs from healthy individuals were exposed to MET (0-80 mg/L) for 0-72 h. We performed the MTT and neutral-red assays to assess the cytotoxicity. As indicators of oxidative stress, the levels of reactive oxygen species (ROS) were assessed using flow cytometry, and the malondialdehyde (MDA) and reduced glutathione (GSH) levels were determined. MET decreased the viability of PBMCs in a dose-dependent manner. At concentrations of 3, 10, or 20 mg/L for 24 h, MET increased the ROS production significantly compared with the vehicle control. Similarly, MET increased the levels of MDA at the same concentrations that increased ROS (10 and 20 mg/L); however, no changes in GSH levels were observed. These results suggest that MET increased the generation of oxidative stress in PBMCs. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 147-155, 2017.
Topics: Cell Survival; Dose-Response Relationship, Drug; Glutathione; Humans; Insecticides; Lipid Peroxidation; Male; Malondialdehyde; Monocytes; Organothiophosphorus Compounds; Oxidative Stress; Primary Cell Culture; Reactive Oxygen Species; Young Adult
PubMed: 26589457
DOI: 10.1002/tox.22220 -
Environmental Pollution (Barking, Essex... Oct 2021Studies have shown that the mixture toxicity of compounds with similar modes of action (MOAs) is usually predicted by the concentration addition (CA) model. However, due...
Studies have shown that the mixture toxicity of compounds with similar modes of action (MOAs) is usually predicted by the concentration addition (CA) model. However, due to the lack of toxicological information on compounds, more evidence is needed to determine whether the above conclusion is generally applicable. In general, the same type of compounds with similar chemical structures have similar MOAs, so whether the toxicities of the mixture of these compounds are additive needs to be further studied. In this paper, three types of pesticides with similar chemical structures (three organophosphoruses, two carbamates and two neonicotinoids) that may have similar MOAs were selected and five binary mixture systems were constructed. For each system, five mixture rays with different concentration ratios were designed by the direct equipartition ray design (EquRay) method. The mortality of Caenorhabditis elegans was regarded as the endpoint for the toxicity exposure to single pesticides and binary mixtures. The combined toxicities were evaluated simultaneously using the CA model, isobologram and combination index. The structural similarity of the same type of pesticides was quantitatively analyzed according to the MACCS molecular fingerprint and the slope of dose-response curve at pEC. The results show that the toxicities of neonicotinoid mixtures and carbamate mixtures are almost antagonistic. The entire mixture system of dichlorvos and dimethoate produced synergism, and four of the five mixture rays of dimethoate and methamidophos induced antagonism, while among the mixture rays of dichlorvos and methamidophos, different concentrations showed different interaction types. The results of structural similarity analysis show that the size of structural similarity showed a certain quantitative relationship with the toxicity interaction of mixtures, that is, the structural similarity of the same type of pesticides may show an additive action in a certain range.
Topics: Animals; Caenorhabditis elegans; Dichlorvos; Dimethoate; Neonicotinoids; Pesticides
PubMed: 33975210
DOI: 10.1016/j.envpol.2021.117207