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Canadian Medical Association Journal Oct 1965Because of an increasing incidence of poisoning with the newer organophosphorus anticholinesterase insecticides, these compounds have been reviewed in terms of their...
Because of an increasing incidence of poisoning with the newer organophosphorus anticholinesterase insecticides, these compounds have been reviewed in terms of their history and pharmacology, relationship with other drugs, factors affecting toxicity, mechanism of action, toxic signs and treatment. The modern organophosphorus pesticide requires metabolic conversion before toxicity develops. Insects have a greater propensity for this conversion than humans. Nevertheless, this conversion does occur in humans and can be potentiated by other drugs. Toxicity also varies with age, sex, route and frequency of administration, and previous exposure. The mechanism of toxicity is inhibition of acetylcholinesterase, causing an intoxicating build-up of acetylcholine. Signs and symptoms consist of the clinical manifestations of unopposed parasympathetic and central activity. Treatment must be initiated early. Respiration must be maintained and the effects of acetylcholine must be counteracted by massive doses of atropine. Metaraminol enhances the antagonistic action of atropine against acetylcholine and may also be given. Once acetylcholinesterase is inactivated, restoration is slow. Recovery can be accelerated by enzyme reactivators like the oxime compounds. Pyridine aldoxime (Pralidoxime, Protopam, P(2)S and 2-PAM) can be given in combination with atropine and metaraminol (AMP therapy) and may be the treatment of choice.
Topics: Acetylcholine; Atropine; Cholinesterase Inhibitors; Humans; Insecticides; Metaraminol; Parathion; Pralidoxime Compounds
PubMed: 5831217
DOI: No ID Found -
RSC Advances Jun 2023Organophosphorus (OPs) compounds can endanger human health and the environment by inhibiting the acetylcholinesterase enzyme. But these compounds have been widely used...
Organophosphorus (OPs) compounds can endanger human health and the environment by inhibiting the acetylcholinesterase enzyme. But these compounds have been widely used as pesticides due to their effectiveness against all kinds of pests. In this study, a Needle Trap Device (NTD) packed with mesoporous organo-layered double hydroxide (organo-LDH) material and coupled with gas chromatography-mass spectrometry (GC-MS) was employed for the sampling and analysis of OPs compounds (diazinon, ethion, malathion, parathion, and fenitrothion). In this way, the [magnesium-zinc-aluminum] layered double hydroxide ([Mg-Zn-Al] LDH) modified with sodium dodecyl sulfate (SDS) as a surfactant was prepared and characterized by FT-IR, XRD, BET, and FE-SEM, EDS, and elemental mapping techniques. Then, various parameters such as relative humidity, sampling temperature, desorption time, and desorption temperature were evaluated by the mesoporous organo-LDH:NTD method. The optimal values of these parameters were determined using response surface methodology (RMS) and central composite design (CCD). The optimal temperature and relative humidity values were obtained as 20 °C and 25.0%, respectively. On the other hand, the desorption temperature and time values were in the range of 245.0-254.0 °C and 5 min, respectively. The limit of detection (LOD) and limit of quantification (LOQ) were reported in the range of 0.02-0.05 mg m and 0.09-0.18 mg m, respectively, which shows the high sensitivity of the proposed method compared to the usual methods. The repeatability and reproducibility of the proposed method (by calculating the relative standard deviation) was estimated in the range of 3.8-10.10 which indicates the acceptable precision of the organo-LDH:NTD method. Also, the desorption rate of the stored needles at 25 °C and 4 °C, was determined to be 86.0% and 96.0%, respectively after 6 days. The results of this study proved that the mesoporous organo-LDH:NTD method can be utilized as a fast, simple, environmentally friendly, and effective method for sampling and determining OPs compounds in the air.
PubMed: 37312990
DOI: 10.1039/d3ra01732j -
Environment International Nov 2022Exposure of pet dogs and cats to pesticides used in and around homes (e.g., lawns and gardens) is a significant health concern. Furthermore, some pesticides are directly...
Exposure of pet dogs and cats to pesticides used in and around homes (e.g., lawns and gardens) is a significant health concern. Furthermore, some pesticides are directly used on dogs and cats for flea, lice, and tick control. Despite this, little is known regarding the extent of pesticide exposure in pets. In this study, we determined the concentrations of 30 biomarkers of pesticide exposure in urine collected from dogs and cats in New York State, USA: 6 dialkylphosphate (DAP) metabolites of organophosphates (OPs); 14 neonicotinoids (neonics); 3 specific metabolites of OPs; 5 pyrethroids (PYRs); and 2 phenoxy acids (PAs). The sum median concentrations of these 30 pesticide biomarkers (ΣPesticides) in dog and cat urine were 35.2 and 38.1 ng/mL, respectively. Neonics were the most prevalent in dogs (accounting for 43% of the total concentrations), followed by DAPs (17%), PYRs (16%), OPs (13%), and PAs (∼10%). In cat urine, neonics alone accounted for 83% of the total concentrations. Elevated concentrations of imidacloprid were found in the urine of certain dogs (max: 115 ng/mL) and cats (max: 1090 ng/mL). Some pesticides showed gender- and sampling location- related differences in urinary concentrations. We calculated daily exposure doses of pesticides from the measured urinary concentrations through a reverse dosimetry approach. The estimated daily intakes (DIs) of chlorpyrifos, diazinon, and cypermethrin were above the chronic reference doses (cRfDs) in 22, 76, and 5%, respectively, of dogs. The DIs of chlorpyrifos, parathion, diazinon, and imidacloprid were above the cRfDs in 33, 14, 100, and 29%, respectively, of cats. This study thus provides evidence that pet dogs and cats are exposed to certain pesticides at levels that warrant immediate attention.
Topics: Animals; Biomarkers; Cat Diseases; Cats; Chlorpyrifos; Diazinon; Dog Diseases; Dogs; Environmental Exposure; Neonicotinoids; New York; Nitro Compounds; Parathion; Pesticides; Pyrethrins; United States
PubMed: 36155914
DOI: 10.1016/j.envint.2022.107526 -
Toxicological Sciences : An Official... Jan 2013Exposure to organophosphates (OPs) can lead to cognitive deficits and oxidative damage. Little is known about the relationship between behavioral deficits and oxidative...
Exposure to organophosphates (OPs) can lead to cognitive deficits and oxidative damage. Little is known about the relationship between behavioral deficits and oxidative stress within the context of such exposures. Accordingly, the first experiment was carried out to address this issue. Male Wistar rats were administered 250 mg/kg of chlorpyrifos (CPF), 1.5 mg/kg of diisopropylphosphorofluoridate (DFP), or 15 mg/kg of parathion (PTN). Spatial learning in the water maze task was evaluated, and F(2)-isoprostanes (F(2)-IsoPs) and prostaglandin (PGE(2)) were analyzed in the hippocampus. A second experiment was designed to determine the degree of inhibition of brain acetylcholinesterase (AChE) activity, both the soluble and particulate forms of the enzyme, and to assess changes in AChE gene expression given evidence on alternative splicing of the gene in response to OP exposures. In addition, brain acylpeptide hydrolase (APH) activity was evaluated as a second target for OP-mediated effects. In both experiments, rats were sacrificed at various points to determine the time course of OPs toxicity in relation to their mechanism of action. Results from the first experiment suggest cognitive and emotional deficits after OPs exposure, which could be due to, at least in part, increased F(2)-IsoPs levels. Results from the second experiment revealed inhibition of brain AChE and APH activity at various time points post OP exposure. In addition, we observed increased brain read-through splice variant AChE (AChE-R) mRNA levels after 48 h PTN exposure. In conclusion, this study provides novel data on the relationship between cognitive alterations and oxidative stress, and the diverse mechanisms of action along a temporal axis in response to OP exposures in the rat.
Topics: Acetylcholinesterase; Animals; Behavior, Animal; Chlorpyrifos; Dinoprostone; F2-Isoprostanes; Hippocampus; Isoflurophate; Male; Maze Learning; Oxidative Stress; Parathion; Peptide Hydrolases; Rats; Rats, Wistar; Spatial Behavior
PubMed: 22986948
DOI: 10.1093/toxsci/kfs280 -
Journal of Microbiology and... Dec 2009Three parathion-degrading bacteria and eight pairs of bacteria showing syntrophic metabolism of parathion were isolated from rice field soils, and their genetic and...
Three parathion-degrading bacteria and eight pairs of bacteria showing syntrophic metabolism of parathion were isolated from rice field soils, and their genetic and phenotypic characteristics were investigated. The three isolates and eight syntrophic pairs were able to utilize parathion as a sole source of carbon and energy, producing p-nitrophenol as the intermediate metabolite during the complete degradation of parathion. Analysis of 16S rRNA gene sequence indicated that the isolates were related to members of the genera, Burkholderia, Arthrobacter, Pseudomonas, Variovorax, and Ensifer. The chromosomal DNA patterns of the isolates obtained by polymerase-chain-reaction (PCR) amplification of repetitive extragenic palindromic (REP) sequences were distinct from one another. Ten of the isolates had plasmids. All of the isolates and syntrophic pairs were able to degrade parathion-related compounds such as EPN, p-nitrophenol, fenitrothion, and methyl-parathion. When analyzed with PCR amplification and dot-blotting hybridization using various primers targeted for the organophosphorus pesticide hydrolase genes of previously-reported isolates, most of the isolates did not show positive signals, suggesting that their parathion hydrolase genes had no significant sequence homology with those of the previously-reported organophosphate pesticide-degrading isolates.
Topics: Arthrobacter; Biodegradation, Environmental; Burkholderia; DNA, Bacterial; Genes, Bacterial; Genetic Variation; Gram-Negative Aerobic Rods and Cocci; Hydrolases; Insecticides; Oryza; Parathion; Pseudomonas; RNA, Ribosomal, 16S; Sinorhizobium; Soil Microbiology; Species Specificity
PubMed: 20075637
DOI: 10.4014/jmb.0905.05057 -
International Journal of Analytical... 2023Antibiotics and pesticides are widespread in most rivers and lakes due to the overuse of antibiotics and pesticides, but there are few methods for simultaneous analysis...
Antibiotics and pesticides are widespread in most rivers and lakes due to the overuse of antibiotics and pesticides, but there are few methods for simultaneous analysis of antibiotics and pesticides in aquatic environments. To address this knowledge gap, a concise and sensitive analytical method is proposed in which three classes of human and veterinary drugs (sulfonamides, macrolides, and hormones) and two classes of pesticides (organophosphorus and neonicotinoids) are simultaneously extracted and determined in surface water. The solid-phase extraction column with Cleanert PEP-2 was preconditioned sequentially with 6 mL of methanol, ultrapure water, and citric acid buffer (pH 3.0) each for simultaneous extraction and further purification. The forty-seven target analytes were analysed by LC-MS/MS in positive and negative ion modes. The LC separation was performed using a Sigma-Aldrich C column with 0.1% formic acid in water and acetonitrile as a gradient eluting mobile phase in positive ion mode. The internal standard method was used to overcome the inevitable matrix effects in LC-MS/MS analysis. The matrix effects of most target analytes were in the range of 27-151%. The recoveries of forty analytes in the three concentrations (10, 50, and 100 ng L) of surface water spiked samples ranged from 41 to 127%. The method quantitative limits of the analytes were in the range of 0.40-5.49 ng L. Application of the method to analyze samples in the eight runoff outlets of the Pearl River Delta showed that some antibiotics and pesticides were detected, and the concentration of parathion was as high as 154 ng L. A powerful tool for quickly and efficiently screening for contaminants in surface water has been presented.
PubMed: 37877028
DOI: 10.1155/2023/6350669 -
Toxicology and Applied Pharmacology Oct 2015Parathion, a widely used organophosphate insecticide, is considered a high priority chemical threat. Parathion toxicity is dependent on its metabolism by the cytochrome...
Parathion, a widely used organophosphate insecticide, is considered a high priority chemical threat. Parathion toxicity is dependent on its metabolism by the cytochrome P450 system to paraoxon (diethyl 4-nitrophenyl phosphate), a cytotoxic metabolite. As an effective inhibitor of cholinesterases, paraoxon causes the accumulation of acetylcholine in synapses and overstimulation of nicotinic and muscarinic cholinergic receptors, leading to characteristic signs of organophosphate poisoning. Inhibition of parathion metabolism to paraoxon represents a potential approach to counter parathion toxicity. Herein, we demonstrate that menadione (methyl-1,4-naphthoquinone, vitamin K3) is a potent inhibitor of cytochrome P450-mediated metabolism of parathion. Menadione is active in redox cycling, a reaction mediated by NADPH-cytochrome P450 reductase that preferentially uses electrons from NADPH at the expense of their supply to the P450s. Using human recombinant CYP 1A2, 2B6, 3A4 and human liver microsomes, menadione was found to inhibit the formation of paraoxon from parathion. Administration of menadione bisulfite (40mg/kg, ip) to rats also reduced parathion-induced inhibition of brain cholinesterase activity, as well as parathion-induced tremors and the progression of other signs and symptoms of parathion poisoning. These data suggest that redox cycling compounds, such as menadione, have the potential to effectively mitigate the toxicity of organophosphorus pesticides including parathion which require cytochrome P450-mediated activation.
Topics: Acetylcholinesterase; Activation, Metabolic; Animals; Cholinesterase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Female; GPI-Linked Proteins; Humans; Insecticides; Liver; Microsomes, Liver; NADP; Organophosphate Poisoning; Oxidation-Reduction; Paraoxon; Parathion; Rats, Long-Evans; Recombinant Proteins; Time Factors; Vitamin K 3
PubMed: 26212258
DOI: 10.1016/j.taap.2015.07.023 -
Global Challenges (Hoboken, NJ) Sep 2022Glyphosate is a globally applied herbicide yet it has been relatively undetectable in-field samples outside of gold-standard techniques. Its presumed nontoxicity toward...
Glyphosate is a globally applied herbicide yet it has been relatively undetectable in-field samples outside of gold-standard techniques. Its presumed nontoxicity toward humans has been contested by the International Agency for Research on Cancer, while it has been detected in farmers' urine, surface waters and crop residues. Rapid, on-site detection of glyphosate is hindered by lack of field-deployable and easy-to-use sensors that circumvent sample transportation to limited laboratories that possess the equipment needed for detection. Herein, the flavoenzyme, glycine oxidase, immobilized on platinum-decorated laser-induced graphene (LIG) is used for selective detection of glyphosate as it is a substrate for GlyOx. The LIG platform provides a scaffold for enzyme attachment while maintaining the electronic and surface properties of graphene. The sensor exhibits a linear range of 10-260 m, detection limit of 3.03 m, and sensitivity of 0.991 nA m . The sensor shows minimal interference from the commonly used herbicides and insecticides: atrazine, 2,4-dichlorophenoxyacetic acid, dicamba, parathion-methyl, paraoxon-methyl, malathion, chlorpyrifos, thiamethoxam, clothianidin, and imidacloprid. Sensor function is further tested in complex river water and crop residue fluids, which validate this platform as a scalable, direct-write, and selective method of glyphosate detection for herbicide mapping and food analysis.
PubMed: 36176938
DOI: 10.1002/gch2.202200057 -
American Journal of Physiology. Lung... Apr 2013Organophosphorus pesticides (OPs) are implicated in human asthma. We previously demonstrated that, at concentrations that do not inhibit acetylcholinesterase activity,...
Organophosphorus pesticides (OPs) are implicated in human asthma. We previously demonstrated that, at concentrations that do not inhibit acetylcholinesterase activity, the OP parathion causes airway hyperreactivity in guinea pigs as a result of functional loss of inhibitory M2 muscarinic receptors on parasympathetic nerves. Because macrophages are associated with asthma, we investigated whether macrophages mediate parathion-induced M2 receptor dysfunction and airway hyperreactivity. Airway physiology was measured in guinea pigs 24 h after a subcutaneous injection of parathion. Pretreatment with liposome-encapsulated clodronate induced alveolar macrophage apoptosis and prevented parathion-induced airway hyperreactivity in response to electrical stimulation of the vagus nerves. As determined by qPCR, TNF-α and IL-1β mRNA levels were increased in alveolar macrophages isolated from parathion-treated guinea pigs. Parathion treatment of alveolar macrophages ex vivo did not significantly increase IL-1β and TNF-α mRNA but did significantly increase TNF-α protein release. Consistent with these data, pretreatment with the TNF-α inhibitor etanercept but not the IL-1β receptor inhibitor anakinra prevented parathion-induced airway hyperreactivity and protected M2 receptor function. These data suggest a novel mechanism of OP-induced airway hyperreactivity in which low-level parathion activates macrophages to release TNF-α-causing M2 receptor dysfunction and airway hyperreactivity. These observations have important implications regarding therapeutic approaches for treating respiratory disease associated with OP exposures.
Topics: Animals; Apoptosis; Bronchial Hyperreactivity; Clodronic Acid; Etanercept; Female; Guinea Pigs; Humans; Immunoglobulin G; Insecticides; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Macrophage Activation; Macrophages, Alveolar; Parathion; RNA, Messenger; Receptor, Muscarinic M2; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha
PubMed: 23377347
DOI: 10.1152/ajplung.00381.2012 -
Biochemical Pharmacology Mar 2013The glutathione S-transferases (GSTs) provide cellular protection by detoxifying xenobiotics, maintaining redox status, and modulating secondary messengers, all of which...
The glutathione S-transferases (GSTs) provide cellular protection by detoxifying xenobiotics, maintaining redox status, and modulating secondary messengers, all of which are critical to maintaining olfaction in salmonids. Here, we characterized the major coho salmon olfactory GSTs (OlfGSTs), namely omega, pi, and rho subclasses. OlfGST omega contained an open reading frame of 720bp and encoded a protein of 239 amino acids. OlfGST pi and OlfGST rho contained open reading frames of 627 and 681nt, respectively, and encoded proteins of 208 and 226 amino acids. Whole-protein mass spectrometry yielded molecular weights of 29,950, 23,354, and 26,655Da, respectively, for the GST omega, pi, and rho subunits. Homology modeling using four protein-structure prediction algorithms suggest that the active sites in all three OlfGST isoforms resembled counterparts in other species. The olfactory GSTs conjugated prototypical GST substrates, but only OlfGST rho catalyzed the demethylation of the pesticide methyl parathion. OlfGST pi and rho exhibited thiol oxidoreductase activity toward 2-hydroxyethyl disulfide (2-HEDS) and conjugated 4-hydroxynonenal (HNE), a toxic aldehyde with neurodegenerative properties. The kinetic parameters for OlfGST pi conjugation of HNE were K(M)=0.16 ± 0.06mM and V(max)=0.5 ± 0.1μmolmin⁻¹mg⁻¹, whereas OlfGST rho was more efficient at catalyzing HNE conjugation (K(M)=0.022 ± 0.008 mM and V(max)=0.47 ± 0.05μmolmin⁻¹mg⁻¹). Our findings indicate that the peripheral olfactory system of coho expresses GST isoforms that detoxify certain electrophiles and pesticides and that help maintain redox status and signal transduction.
Topics: Amino Acid Sequence; Animals; Base Sequence; Blotting, Western; Catalysis; Cloning, Molecular; DNA Primers; Electrophoresis, Polyacrylamide Gel; Glutathione Transferase; Humans; Kinetics; Models, Molecular; Molecular Sequence Data; Oncorhynchus kisutch; Phylogeny; Polymerase Chain Reaction; Sequence Homology, Amino Acid
PubMed: 23261526
DOI: 10.1016/j.bcp.2012.11.018