-
Scandinavian Journal of Work,... 1985After passing toxicity and experimental therapeutic tests, four oxime cholinesterase reactivators [PAM (pyridine aldoxime methiodide), PAC (pralidoxime, pyridine... (Clinical Trial)
Clinical Trial Comparative Study
After passing toxicity and experimental therapeutic tests, four oxime cholinesterase reactivators [PAM (pyridine aldoxime methiodide), PAC (pralidoxime, pyridine aldoxime methylchloride), TMB4 (trimedoxime), and DMO4 (obidoxime, Toxogonin, LüH6)] were compared in clinical trials. All of them proved capable of restoring erythrocyte cholinesterase activity and relieving symptoms and signs of organophosphate insecticide poisoning. Mildly and moderately poisoned patients can be treated by several injections of any one of these drugs alone, but severe cases need the synergistic action of atropine, as well as treatments for two to three consecutive days. Although response to treatment is stronger with TMB4 and DMO4, they are not recommended for routine treatment because of their dangerous adverse side effects.
Topics: Alanine Transaminase; Cholinesterase Reactivators; Cholinesterases; Clinical Trials as Topic; Disulfoton; Erythrocytes; Humans; Insecticides; Obidoxime Chloride; Occupational Diseases; Parathion; Pralidoxime Compounds; Trimedoxime
PubMed: 3914075
DOI: No ID Found -
Toxicological Sciences : An Official... Dec 2004Chronic and acute exposure to organophosphate (OP) pesticides may lead to persistent neurological and neurobehavioral effects, which cannot be explained by...
Chronic and acute exposure to organophosphate (OP) pesticides may lead to persistent neurological and neurobehavioral effects, which cannot be explained by acetylcholinesterase (AChE) inhibition alone. It is suggested that other brain proteins are involved. Effects of commonly used organophosphate pesticides on rat neuronal alpha4beta2 nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus laevis oocytes have been investigated using the two-electrode voltage clamp technique. Several OP pesticides, e.g., parathion-ethyl, chlorpyrifos and disulfoton, inhibited the ACh-induced ion current with potencies in the micromolar range. The potency of inhibition increased with increasing concentrations of the agonist ACh. Comparison of the potency of nAChR inhibition with the potency of AChE inhibition demonstrated that some OPs inhibit nAChRs more potently than AChE. Binding experiments on alpha4beta2 nAChRs showed that the OPs noncompetitively interact with nAChRs. The inhibitory effects on nAChRs are adequately described and explained by a sequential two-step mechanism, in which rapidly reversible OP binding to a separate binding site leads to inhibition followed by a stabilization of the blocked state or receptor desensitization. It is concluded that OPs interact directly with neuronal alpha4beta2 nAChRs to inhibit the agonist-induced response. This implicates that neuronal alpha4beta2 nAChRs are additional targets for some OP pesticides.
Topics: Algorithms; Animals; Binding, Competitive; Brain; Bridged Bicyclo Compounds, Heterocyclic; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Electrophysiology; Humans; Insecticides; Kinetics; Ligands; Male; Models, Biological; Nicotinic Agonists; Nicotinic Antagonists; Oocytes; Organophosphorus Compounds; Patch-Clamp Techniques; Pyridines; Rats; Rats, Wistar; Receptors, Nicotinic; Xenopus laevis
PubMed: 15342957
DOI: 10.1093/toxsci/kfh269 -
The British Journal of Ophthalmology Nov 1974
Topics: Administration, Oral; Animals; Body Weight; Cell Membrane; Ciliary Body; Cytoplasm; Disulfoton; Dogs; Endoplasmic Reticulum; Golgi Apparatus; Insecticides; Microscopy, Electron; Mitochondria; Muscles; Myopia; Organophosphorus Compounds; Refraction, Ocular
PubMed: 4457106
DOI: 10.1136/bjo.58.11.931 -
Ecotoxicology and Environmental Safety Dec 1984The acute toxicities of 13 granular anticholinesterase insecticides were compared with their technical grade active ingredients by administering single oral doses of...
The acute toxicities of 13 granular anticholinesterase insecticides were compared with their technical grade active ingredients by administering single oral doses of chemical to adult Northern bobwhites (Colinus virginianus) and evaluating resultant LD50 values and dose-response curves. Similar tests with ringed turtledoves (Streptopelia risoria) were conducted with five of the granular formulations to check for interspecific differences. The test chemicals were Amaze 15G (isofenphos), Counter 15G (terbufos), Dasanit 15G (fensulfothion), Diazinon 14G (diazinon), Di-Syston 15G (disulfoton), Dyfonate 20G (fonofos), Furadan 10G (carbofuran), Lorsban 15G (chlorpyrifos), Nemacur 15G (fenamiphos), Parathion 10G (parathion), Tattoo 10G (bendiocarb), Temik 15G (aldicarb), and Thimet 15G (phorate). Information is also presented on dose-response relations and their use in hazard assessment, granule size and hazard, response patterns, and toxic signs. The general conclusions were: (1) The organophosphates (fenamiphos and fensulfothion) and the carbamate (aldicarb) were the most toxic of the insecticides tested. (2) The granular formulation and its technical grade active ingredient were of equivalent toxicity, or the granular was significantly less toxic. (3) The dose-response curve enhances hazard assessment. (4) Ingestion of a single granule of Temik 15G was shown to be life threatening to bobwhite-sized birds, and ingestion of fewer than five granules could be lethal to sparrow-sized birds for Dasanit 15G, Diazinon 14G, Dyfonate 20G, Furadan 15G, and Nemacur 15G. (5) It is therefore suggested that the hazard associated with granular insecticides may be more dependent on which species (cf. size and feeding behavior) inhabit a treated area than on the actual application rate.
Topics: Animals; Behavior, Animal; Birds; Cholinesterase Inhibitors; Colinus; Coturnix; Dose-Response Relationship, Drug; Female; Insecticides; Lethal Dose 50; Male; Particle Size; Quail; Species Specificity
PubMed: 6510327
DOI: 10.1016/0147-6513(84)90015-0 -
Science (New York, N.Y.) Sep 1980The flavin adenine dinucleotide--dependent monooxygenase in mammalian hepatic microsomes plays a major role in the oxidative metabolism of thioether-containing...
The flavin adenine dinucleotide--dependent monooxygenase in mammalian hepatic microsomes plays a major role in the oxidative metabolism of thioether-containing pesticides. Thirty-four compounds were tested, and it was determined that organophosphorus insecticides such as disulfoton and phorate are rapidly oxidized by the purified enzyme to their corresponding sulfoxides. The enzyme does not catalyze the oxidation of the thiophosphoryl and thiol sulfur atoms of these or other phosphorothioates and phosphorodithioates, or the oxidation of the sulfoxide to the sulfone. Carbamates aldicarb and Croneton are also oxidized, but at a lower rate.
Topics: Aniline Compounds; Animals; Biotransformation; Microsomes, Liver; Oxidation-Reduction; Oxygenases; Pesticides; Substrate Specificity; Sulfur; Swine
PubMed: 7403873
DOI: 10.1126/science.7403873 -
Biodegradation 2000The organophosphorous pesticide, demeton-S-methyl was transformed by Corynebacterium glutamicum in co-metabolism with more readily degradable substrates. Glucose,...
The organophosphorous pesticide, demeton-S-methyl was transformed by Corynebacterium glutamicum in co-metabolism with more readily degradable substrates. Glucose, acetate and fructose were tested as growth substrates, and the highest demeton-S-methyl biotransformation average rate (0.78 mg l(-1) h(-1)) and maximum instantaneous rate (1.4 mg l(-1) h(-1)) were achieved on fructose. This higher efficiency seems to be linked to the atypical behavior of C. glutamicum grown on fructose, characterized by a prolonged period of accelerating growth instead of a constant growth rate observed on glucose or acetate. More precisely, for growth rates in the 0.1-0.4 h(-1) range, a direct coupling between the specific demeton-S-methyl consumption rate and the growth rate was demonstrated on fructose during batch-, steady state continuous- or continuous cultures with a controlled transient growth rate (accelerostat technology). The demeton-S-methyl biotransformation was more favoured during an acceleration phase of the growth rate.
Topics: Biodegradation, Environmental; Biotransformation; Corynebacterium; Disulfoton; Fermentation; Insecticides; Oxidation-Reduction
PubMed: 11587440
DOI: 10.1023/a:1011682714928 -
Food Additives & Contaminants. Part A,... 2012Fifteen pesticides including some of their metabolites (disulfoton sulfoxide, ethoprophos, cadusafos, dimethoate, terbufos, disulfoton, chlorpyrifos-methyl, malaoxon,...
Fifteen pesticides including some of their metabolites (disulfoton sulfoxide, ethoprophos, cadusafos, dimethoate, terbufos, disulfoton, chlorpyrifos-methyl, malaoxon, fenitrothion, pirimiphos-methyl, malathion, chlorpyrifos, terbufos sulfone, disulfoton sulfone and fensulfothion) were analysed in milled toasted wheat and maize as well as in wheat flour and baby cereals. The QuEChERS (quick, easy, cheap, effective, rugged and safe) methodology was used and its dispersive solid-phase extraction procedure was optimised by means of an experimental design with the aim of reducing the amount of co-extracted lipids and obtaining a clean extract. Gas chromatography with nitrogen phosphorus detection were used as the separation and detection techniques, respectively. The method was validated in terms of selectivity, recoveries, calibration, precision and accuracy as well as matrix effects. Limits of detection were between 0.07 and 34.8 µg kg(-1) with recoveries in the range of 71-110% (relative standard deviations were below 9%). A total of 40 samples of different origin were analysed. Residues of pirimiphos-methyl were found in six of the samples at concentrations in the range 0.08-0.47 mg kg(-1), which were below the MRLs established for this pesticide in cereal grains. Tandem mass spectrometry confirmation was also carried out in order to identify unequivocally the presence of this pesticide.
Topics: Calibration; Chromatography, Gas; Edible Grain; Limit of Detection; Pesticides; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization
PubMed: 22043870
DOI: 10.1080/19440049.2011.615032 -
Bulletin of Environmental Contamination... Oct 2015A simple, rapid and sensitive spectrofluorimetric method was developed for the determination of di-syston, ethion and phorate in environmental water samples. The...
A simple, rapid and sensitive spectrofluorimetric method was developed for the determination of di-syston, ethion and phorate in environmental water samples. The procedure is based on the oxidation of these pesticides with cerium (IV) to produce cerium (III), and its fluorescence was monitored at 368 ± 3 nm after excitation at 257 ± 3 nm. The variables effecting oxidation of each pesticide were studied and optimized. Under the experimental conditions used, the calibration graphs were linear over the range 0.2-15, 0.1-13, 0.1-13 ng mL(-1) for di-syston, ethion and phorate, respectively. The limit of detection and quantification were in the range 0.034-0.096 and 0.112-0.316 ng mL(-1), respectively. Intra- and inter-day assay precisions, expressed as the relative standard deviation (RSD), were lower than 5.2 % and 6.7 %, respectively. Good recoveries in the range 86 %-108 % were obtained for spiked water samples. The proposed method was applied to the determination of studied pesticides in environmental water samples.
Topics: Disulfoton; Environmental Monitoring; Insecticides; Organothiophosphorus Compounds; Phorate; Spectrometry, Fluorescence; Water Quality
PubMed: 26210825
DOI: 10.1007/s00128-015-1612-7 -
Journal of Environmental Science and... 2015The objective of this study was to determine the levels of pesticides in the fish Prochilodus costatus caught in São Francisco River, one of most important rivers in...
The objective of this study was to determine the levels of pesticides in the fish Prochilodus costatus caught in São Francisco River, one of most important rivers in Brazil. Thirty-six fish were captured in three different areas, and samples of the dorsal muscle and pooled viscera were collected for toxicological analysis. We evaluated the presence of 150 different classes of insecticides, fungicides, herbicides and acaricides by multiresidue analysis technique using liquid chromatography-tandem mass spectrometry (LC-MS/MS), with the limit of detection of 5 ppb. In this study, organophosphorus and carbamate pesticides were detected at the highest levels in the caught fish. Among the 41 organophosphorus pesticides surveyed, nine types were detected (chlorpyrifos, diazinon, dichlorvos, disulfoton, ethion, etrimfos, phosalone, phosmet and pyrazophos) in the muscle, viscera pool, or both in 22 (61.1%) fish. Sampled tissues of 20 (55.6%) fish exhibited at least one of the eight evaluated carbamate pesticides and their metabolites: aldicarb, aldicarb sulfoxide, carbaryl, carbofuran, carbosulfan, furathiocarb, methomyl and propoxur. Fungicides (carbendazim, benalaxyl, kresoxim-methyl, trifloxystrobin, pyraclostrobin and its metabolite BF 500 pyraclostrobin), herbicides (pyridate and fluasifop p-butyl), acaricide (propargite) and pyrethroid (flumethrin) were also detected. In conclusion, P. costatus fish caught in the São Francisco River contained residues of 17 different pesticides, in both muscles and the viscera pool, indicating heavy environmental contamination by pesticides in the study area.
Topics: Animals; Brazil; Characiformes; Environmental Monitoring; Muscle, Skeletal; Pesticide Residues; Pesticides; Rivers; Water Pollutants, Chemical
PubMed: 25844860
DOI: 10.1080/03601234.2015.1011946 -
General Pharmacology 19911. The effect of various commonly used membrane solubilizing detergents on the activity of the microsomal xenobiotic metabolizing enzyme, the flavin-containing...
1. The effect of various commonly used membrane solubilizing detergents on the activity of the microsomal xenobiotic metabolizing enzyme, the flavin-containing monooxygenase (FMO) purified from mouse liver, kidney and lungs was determined. 2. Regardless of the type of detergent used, the effect on the enzyme activity was variable depending on the type of substrate used. 3. Emulgen 911 concentrations of up to 10% had very little effect on thiobenzamide-S-oxidation by liver, kidney or lung FMO. 4. While Emulgen 911 increased substrate dependent NADPH oxidation rate by thiourea and thioacetamide, it drastically reduced the activity toward the organophosphorous compounds, disulfoton, fenthion, fonofos and phorate at low concentrations. 5. Activities of fenthion, phorate and fonofos were decreased by 80, 65 and 55% by the inclusion of 0.25% Emulgen 911 in the assay mixture. 6. This decline in FMO activity for phorate was evident regardless of the type of detergent used. In contrast, thiourea dependent NADPH oxidation rate in the presence of various detergents was variable. 7. Thiourea oxidation rate was decreased by cholate and Zwittergent 3-12, whereas it was increased in the presence of Emulgen 911, Triton X-100 and Tween 20. 8. This study shows that before FMO activity is determined in the presence of detergents their effects should be carefully evaluated.
Topics: Animals; Cytochrome P-450 Enzyme Inhibitors; Detergents; In Vitro Techniques; Kidney; Kinetics; Liver; Lung; Male; Mice; NADP; Nonoxynol; Oxidation-Reduction; Oxygenases; Polyethylene Glycols; Thiourea
PubMed: 1651268
DOI: 10.1016/0306-3623(91)90022-x