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Clinical Toxicology (Philadelphia, Pa.) May 2020Current therapeutic options for organophosphorus (OP) insecticide self-poisoning including atropine and oximes are inadequate and case fatality may exceed 20%. An OP...
Current therapeutic options for organophosphorus (OP) insecticide self-poisoning including atropine and oximes are inadequate and case fatality may exceed 20%. An OP hydrolase enzyme, OpdA, has been used for environmental cleansing of OP insecticides and prevented death in rat and non-human primate models of OP insecticide poisoning if given very quickly after exposure. We here tested OpdA's ability to break down OP insecticides in human serum and in clinically relevant minipig models of OP insecticide poisoning. Human serum was spiked with seven diverse WHO Class II OP insecticides (chlorpyrifos, quinalphos, diazinon, dimethoate, fenthion, phenthoate, and profenofos) and the effect of OpdA on degradation measured. The pharmacodynamic and clinical effects of OpdA treatment were studied in Gottingen minipigs orally poisoned with agricultural formulations of dimethoate EC40 or methyl parathion EC60; pharmacodynamic effects were also assessed in profenofos EC50-poisoned pigs. OpdA effectively hydrolysed OP insecticides in human serum, with rates varying from 856 (SD 44) down to 0.107 (SD 0.01) moles of substrate hydrolysed/mole of enzyme/sec (k) for quinalphos and phenthoate, respectively, although at rates 2-3 log orders less than found in buffered solution. It showed clinical benefit in minipig models, reducing the dose of noradrenaline required to sustain an adequate mean arterial pressure after dimethoate (mean 0.149 [SD 0.10] μg/kg/h vs. 1.07 [SD 0.77] μg/kg/h, < .0001) and methyl parathion (mean 0.077 [SD 0.08] μg/kg/h vs. 0.707 [SD 0.49] μg/kg/h, < .0001) poisoning. OpdA reduced blood OP insecticide concentration and acetylcholinesterase inhibition after poisoning by dimethoate, methyl parathion, and profenofos insecticides. incubation of OpdA in human serum showed hydrolysis of diverse OP insecticides, although at lower rates than found in buffer solutions. This activity results in clinical and pharmacodynamic efficacy against several OP insecticides. These results support the testing of OpdA in further animal models before considering human trials to determine whether it may become an urgently required novel therapeutic agent for OP insecticide self-poisoning.
Topics: Animals; Aryldialkylphosphatase; Disease Models, Animal; Humans; Insecticides; Methyl Parathion; Organophosphate Poisoning; Swine; Swine, Miniature
PubMed: 31452424
DOI: 10.1080/15563650.2019.1655149 -
Toxicology Letters Oct 2019Organophosphates are chemical pollutants that are existed widely in the environment, but the reactions of these agents with blood proteins are still not fully clarified....
Organophosphates are chemical pollutants that are existed widely in the environment, but the reactions of these agents with blood proteins are still not fully clarified. The current story was to analyze the static and dynamic interactions between human serum albumin (HSA) and phenthoate and then uncover the impact of the conjugations on the acetylcholinesterase (AChE) activity at the microscopic scale. Experimental results revealed clearly that the bioconjugate of the HSA-phenthoate was yielded and the conformation of HSA can produce autoregulation during the reaction. Dynamic reaction processes suggested that the conformational flexibility of the specific protein domain was changed significantly in equilibrium, and the electrostatic interaction energy played a major role in total energy of the biosystems, which matches the results of wet experiment and molecular docking. We also found that the modes of homologous proteins-phenthoate have obvious distinctions, and this point is related closely to the local dynamic flexibility of biomolecular structures. Additionally, the degree of bioconjugation of the HSA-phenthoate is positively associated with the enzymatic activity of target AChE, which may be attributed to the competitive reactions between HSA and AChE. Evidently, this scenario could provide useful molecular information for the systematic exploration of the toxicokinetics of organophosphorus compounds.
Topics: Acetylcholinesterase; Binding Sites; Binding, Competitive; Cholinesterase Inhibitors; Humans; Insecticides; Models, Biological; Molecular Docking Simulation; Organothiophosphorus Compounds; Protein Binding; Protein Conformation; Protein Domains; Serum Albumin, Human
PubMed: 31362050
DOI: 10.1016/j.toxlet.2019.07.025 -
Environmental Science and Pollution... Dec 2018In this study, a new magnetic adsorbent based on magnetite-sporopollenin/graphene oxide (FeO-SP/GO) was successfully developed. The adsorbent was applied for magnetic...
In this study, a new magnetic adsorbent based on magnetite-sporopollenin/graphene oxide (FeO-SP/GO) was successfully developed. The adsorbent was applied for magnetic solid phase extraction (MSPE) of three selected polar organophosphorus pesticides (OPPs), namely, dimethoate, phenthoate, and phosphamidon, prior to gas chromatography analysis with electron capture detection (GC-μECD). The FeO-SP/GO adsorbent combines the advantages of superior adsorption capability of the modified sporopollenin (SP) with graphene oxide (GO) and magnetite (FeO) for easy isolation from sample solution. Several MSPE parameters were optimized. Under optimized conditions, excellent linearity (R ≥ 0.9994) was achieved using matrix match calibration in the range of 0.1 to 500 ng mL. The limit of detection (LOD) method (S/N = 3) was from 0.02 to 0.05 ng mL. The developed FeO-SP/GO MSPE method was successfully applied for the determination of these three polar OPPs in cucumber, long beans, bell pepper, and tomato samples. Good recoveries (81.0-120.0%) and good relative standard deviation (RSD) (1.4-7.8%, n = 3) were obtained for the spiked OPPs (1 ng mL) from real samples. This study is beneficial for adsorptive removal of toxic pesticide compounds from vegetable samples.
Topics: Adsorption; Biopolymers; Carotenoids; Chromatography, Gas; Dimethoate; Ferrosoferric Oxide; Graphite; Limit of Detection; Solanum lycopersicum; Magnetics; Magnetite Nanoparticles; Organic Chemicals; Oxides; Pesticides; Solid Phase Extraction; Vegetables
PubMed: 30328041
DOI: 10.1007/s11356-018-3402-3 -
PloS One 2018Deliberate self-poisoning (DSP) using organophosphorus (OP) insecticides are a common clinical problem in Asia. OPs inhibit acetylcholine esterase (AChE), leading to...
BACKGROUND
Deliberate self-poisoning (DSP) using organophosphorus (OP) insecticides are a common clinical problem in Asia. OPs inhibit acetylcholine esterase (AChE), leading to over-activity of muscarinic and nicotinic cholinergic circuits. Intermediate syndrome (IMS) is mediated via prolonged nicotinic receptor stimulation at the neuromuscular junction and its onset is between 24-96 hours post ingestion. The aims of the present study were 1) to investigate whether neuromuscular junction dysfunction within the first 24 hours following exposure, quantified by jitter in single fibre electromyography (SfEMG), can predict IMS, and 2) to compare the changes in SfEMG jitter over the course of the illness among patients who developed IMS (IMS+) and those who did not (IMS-).
METHODS AND FINDINGS
We conducted a prospective cohort study in a tertiary care hospital in Sri Lanka on 120 patients admitted between September 2014 and August 2016 following DSP by OP insecticides viz., profenofos 53, phenthoate 17, diazinon 13, chlorpyrifos 5, others 12, unknown 20. SfEMG was performed every second day during hospitalization. Exposure was confirmed based on the history and red blood cell AChE assays. IMS was diagnosed in patients who demonstrated at least three out of four of the standard IMS criteria: proximal muscle weakness, bulbar muscle weakness, neck muscle weakness, respiratory paralysis between 24-96 hours post ingestion. Respiratory failure requiring intubation occurred in 73 out of 120 patients; 64 of these were clinically diagnosed with IMS. Of the 120 patients, 96 had repeated SfEMG testing, 67 of them being tested within the first 24 hours. Prolonged jitter (>33.4μs) within the first 24 hours was associated with greatly increased risk of IMS (odds ratio = 8.9, 95% confidence intervals = 2.4-29.6, p = 0.0003; sensitivity 86%, specificity 58%). The differences in jitter between IMS+ and IMS- patients remained significant for 72 hours and increased jitter was observed in some patients for up to 216 hours. For intubated patients, the median time for jitter to normalize and median time to extubate were similar, and the two variables had a moderate positive correlation (r = 0.49, P = 0.001).
CONCLUSIONS
Prolonged jitter recorded with SfEMG <24 hours of ingestion of an OP strongly correlates with subsequent occurrence of IMS. The time course of electrophysiological recovery of the NMJ was similar to the time course of respiratory recovery in IMS patients.
Topics: Acetylcholinesterase; Electromyography; Erythrocytes; Humans; Insecticides; Male; Neuromuscular Junction Diseases; Organophosphate Poisoning; Organophosphorus Compounds; Prospective Studies
PubMed: 30261032
DOI: 10.1371/journal.pone.0203596 -
Environmental Health and Preventive... Jun 2018Acetylcholinesterase inhibitor insecticides (AChEIIs) were used extensively in the agrarian region of Anuradhapura for the past few decades. As a result, the region...
BACKGROUND
Acetylcholinesterase inhibitor insecticides (AChEIIs) were used extensively in the agrarian region of Anuradhapura for the past few decades. As a result, the region faced a heightened risk of toxicity. Carbaryl, carbofuran, chlorpyrifos, dimethoate, and fenthion were the five hazardous AChEIIs banned from Anuradhapura in 2014. Assessment of post-ban trends in acute poisoning will reveal the impact of the ban. Data on availability and sales of remaining AChEIIs will guide towards preventive measures against related toxicities.
METHODS
Cross-sectional surveys were conducted at Anuradhapura district of Sri Lanka. Details related to acute AChEII poisoning were sorted from the Teaching Hospital Anuradhapura. Main insecticide vendors in Anuradhapura were surveyed to find information on availability and sales of AChEIIs. Chi-square for goodness of fit was performed for trends in acute poisoning and sales.
RESULTS
Hospital admissions related to acute AChEII poisoning have declined from 554 in 2013 to 272 in 2017. Deaths related to acute AChEII poisoning have declined from 27 in 2013 to 13 in 2017. Sales of all five banned AChEIIs had reduced by 100%. Sales of the remaining AChEIIs were declining, except for acephate, phenthoate, and profenofos. However, one of the top selling, most frequently abused carbosulfan, had the highest risk of toxicity. Chi-square for goodness of fit showed a significance (P < 0.001) between the trends of hospital admissions for acute AChEII poisoning and the sales related to AChEIIs.
CONCLUSIONS
Hospital admissions related to acute poisoning was declining along with the overall sales of remaining AChEIIs, during the post-AChEII ban period. Nevertheless, future vigilance is needed on the remaining AChEIIs to predict and prevent related toxicities.
Topics: Agriculture; Cholinesterase Inhibitors; Commerce; Cross-Sectional Studies; Developing Countries; Female; Government Regulation; Health Policy; Hospitalization; Humans; Incidence; Insecticides; Male; Poisoning; Risk Factors; Sri Lanka
PubMed: 29945568
DOI: 10.1186/s12199-018-0716-1 -
Journal of Forensic Sciences Nov 2018Organophosphates are widely used as pesticides. However, organophosphates are occasionally orally ingested to commit suicide. In this case, a man in his late 80s...
Organophosphates are widely used as pesticides. However, organophosphates are occasionally orally ingested to commit suicide. In this case, a man in his late 80s committed suicide by ingesting both dichlorvos and phenthoate. Autopsy findings revealed a characteristic volatile odor from his mouth, stomach, lungs, liver, and kidneys. The esophageal mucosa was denatured and had lost elasticity. Serum cholinesterase activity was 9 IU/L. Toxicological analyses performed using high-performance liquid chromatography-tandem mass spectrometry revealed that dichlorvos concentrations in the left and right cardiac blood samples were 11.6 and 4.6 μg/mL, respectively. Phenthoate concentrations in the left and right cardiac blood samples were 5.8 and 0.51 μg/mL, respectively. The total amounts of dichlorvos and phenthoate in the stomach were 7.35 and 4.55 g, respectively. The case history, autopsy findings, and toxicological analyses indicated that the cause of death was acute fatal poisoning after oral ingestion of both dichlorvos and phenthoate.
Topics: Aged, 80 and over; Dichlorvos; Gastrointestinal Contents; Humans; Male; Organophosphate Poisoning; Organothiophosphorus Compounds; Suicide
PubMed: 29601635
DOI: 10.1111/1556-4029.13781 -
The Science of the Total Environment Oct 2016The objectives of the current study were to determine the occupational health hazards posed by the application of pesticides in rice-prawn concurrent systems of...
The objectives of the current study were to determine the occupational health hazards posed by the application of pesticides in rice-prawn concurrent systems of south-west Bangladesh and to assess their potential risks for the aquatic ecosystems that support the culture of freshwater prawns (Macrobrachium rosenbergii). Information on pesticide use in rice-prawn farming was collected through structured interviews with 38 farm owners held between January and May of 2012. The risks of the pesticide use to human health were assessed through structured interviews. The TOXSWA model was used to calculate pesticide exposure (peak and time-weighted average concentrations) in surface waters of rice-prawn systems for different spray drift scenarios and a simple first tier risk assessment based on threshold concentrations derived from single species toxicity tests were used to assess the ecological risk in the form of risk quotients. The PERPEST model was used to refine the ecological risks when the first tier assessment indicated a possible risk. Eleven synthetic insecticides and one fungicide (sulphur) were recorded as part of this investigation. The most commonly reported pesticide was sulphur (used by 29% of the interviewed farmers), followed by thiamethoxam, chlorantraniliprole, and phenthoate (21%). A large portion of the interviewed farmers described negative health symptoms after pesticide applications, including vomiting (51%), headache (18%) and eye irritation (12%). The results of the first tier risk assessment indicated that chlorpyrifos, cypermethrin, alpha-cypermethrin, and malathion may pose a high to moderate acute and chronic risks for invertebrates and fish in all evaluated spray drift scenarios. The higher tier assessment using the PERPEST model confirmed the high risk of cypermethrin, alpha-cypermethrin, and chlorpyrifos for insects and macro- and micro-crustaceans thus indicating that these pesticides may have severe adverse consequences for the prawn production yields.
Topics: Agriculture; Animals; Aquaculture; Bangladesh; Farmers; Fungicides, Industrial; Health Knowledge, Attitudes, Practice; Humans; Insecticides; Occupational Exposure; Occupational Health; Oryza; Palaemonidae; Risk Assessment
PubMed: 27328394
DOI: 10.1016/j.scitotenv.2016.06.014 -
Analytical and Bioanalytical Chemistry Dec 2015As the consumption of aquatic products increased, the need for regulation of pesticide residues in aquatic products also emerged. Thus, in this study, a scheduled...
As the consumption of aquatic products increased, the need for regulation of pesticide residues in aquatic products also emerged. Thus, in this study, a scheduled multiple reaction monitoring (sMRM) method employing a novel extraction and purification step based on QuEChERS with EDTA was developed for the simultaneous quantitation of 20 pesticides (alachlor, aldicarb, carbofuran, diazinon, dimethoate, dimethomorph, ethoprophos, ferimzone, fluridone, hexaconazole, iprobenfos, malathion, methidathion, methiocarb, phenthoate, phosalone, phosmet, phosphamidon, pirimicarb, and simazine) in aquatic products. Additionally, the present method was validated in the aspects of specificity, linearity (r ≥ 0.980), sensitivity (the limit of quantitation (LOQ) ≤ 5 ng/g), relative standard deviation, RSD (1.0% ≤ RSD ≤ 19.4%), and recovery (60.1% ≤ recovery ≤ 117.9%). Finally, the validated method was applied for the determination of the 20 pesticide residues in eel and shrimp purchased from local food markets. In the present study, QuEChERS with EDTA was successfully expanded to residual pesticide analysis for the first time. The present method could contribute to the rapid and successful establishment of the positive list system in South Korea.
Topics: Animals; Eels; Food Contamination; Fruit; Mass Spectrometry; Palaemonidae; Pesticide Residues; Seafood; Solid Phase Extraction; Vegetables; Water Pollutants, Chemical
PubMed: 26466578
DOI: 10.1007/s00216-015-9071-x -
Journal of Environmental Science and... 2015In this study, we carried out three bioassays with nine used insecticides in tomato crops to identify their efficiency against tomato leaf miner Tuta absoluta, the...
In this study, we carried out three bioassays with nine used insecticides in tomato crops to identify their efficiency against tomato leaf miner Tuta absoluta, the physiological selectivity and the activity reduction of insecticides by three rain regimes to predatory wasps Protonectarina sylveirae and Polybia scutellaris. We assessed the mortality caused by the recommended doses of abamectin, beta-cyfluthrin, cartap, chlorfenapyr, etofenprox, methamidophos, permethrin, phenthoate and spinosad to T. absoluta and wasps at the moment of application. In addition, we evaluated the wasp mortality due to the insecticides for 30 days on plants that did not receive rain and on plants that received 4 or 125 mm of rain. Spinosad, cartap, chlorfenapyr, phenthoate, abamectin and methamidophos caused mortality higher than 90% to T. absoluta, whereas the pyrethroids beta-cyfluthrin, etofenprox and permethrin caused mortality between 8.5% and 46.25%. At the moment of application, all the insecticides were highly toxic to the wasps, causing mortality higher than 80%. In the absence of rain, all the insecticides continued to cause high mortality to the wasps for 30 days after the application. The toxicity of spinosad and methamidophos on both wasp species; beta-cyfluthrin on P. sylveirae and chlorfenapyr and abamectin on P. scutellaris, decreased when the plants received 4 mm of rain. In contrast, the other insecticides only showed reduced toxicity on the wasps when the plants received 125 mm of rain.
Topics: Animals; Biological Assay; Dose-Response Relationship, Drug; Drug Combinations; Insecticides; Ivermectin; Larva; Lepidoptera; Solanum lycopersicum; Macrolides; Nitriles; Organothiophosphorus Compounds; Permethrin; Plant Leaves; Pyrethrins; Rain; Thiocarbamates; Wasps
PubMed: 25421627
DOI: 10.1080/03601234.2015.965621