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Journal of Analytical Toxicology Apr 2004Many organophosphate pesticides (OP) such as phosphamidon are unstable in aqueous solutions and especially in blood in the presence of esterases. In a case of...
Many organophosphate pesticides (OP) such as phosphamidon are unstable in aqueous solutions and especially in blood in the presence of esterases. In a case of intoxication, the phosphamidon concentration in serum decreased from 10 mg/L to 4.4 mg/L after storage at -20 degrees C for six months; nearly complete degradation was observed after three years. Dimethyl phosphate (DMP) is a metabolite of phosphamidon, mevinphos, dicrotophos, monocrotophos, dichlorvos, and trichlorfon. A gas chromatographic-mass spectrometric method with deuterated DMP-d6 as internal standard for the determination of DMP in biological material was validated. DMP was found in all of the patient's samples (3.9 and 4.9 mg/L in blood, 33.5 and 50.4 mg/L in urine, and 8.1 mg/L in gastric fluid), even after storage at -20 degrees C for up to 3 years. No hints for a degradation of DMP when spiked in fresh blood and stored at 4 degrees C for 1 week and stored in water over a time period of 10 months. Looking for the stable metabolites like DMP in cases of suspected OP intoxication is recommended.
Topics: Adult; Drug Stability; Female; Fluorobenzenes; Gas Chromatography-Mass Spectrometry; Gastrointestinal Contents; Humans; Insecticides; Organophosphorus Compounds; Phosphamidon; Reproducibility of Results; Suicide, Attempted; Time Factors
PubMed: 15107151
DOI: 10.1093/jat/28.3.198 -
Journal of Economic Entomology Feb 2000The gall wasp Callirhytis cornigera (Osten Sacken) is a cynipid with alternating generations that produce large, woody stem galls and tiny blister-like leaf galls on pin...
The gall wasp Callirhytis cornigera (Osten Sacken) is a cynipid with alternating generations that produce large, woody stem galls and tiny blister-like leaf galls on pin oak, Quercus palustris Muenchhausen, in the United States. We tested 3 approaches to control the leaf-galling generation, and determined their impact on associated parasitoids and effectiveness in reducing numbers of new stem galls. First, trees were sprayed with bifenthrin or chlorpyrifos in late March to kill females emerging from stem galls before they oviposited into buds. Second, concentrated solutions of abamectin, imidacloprid, or bidrin were injected from pressurized containers into tree sapwood to control larvae developing in young leaf galls. Finally, systemic insecticides (acephate, abamectin, dimethoate, or imidacloprid) were sprayed at early leaf expansion (2 May) or to young, expanded leaves (17 May) to target larvae in leaf galls. Parasitoids, mostly eulophids, accounted for approximately 70% mortality of leaf-galling C. cornigera larvae on untreated trees. Whole-canopy sprays during C. cornigera emergence from stem galls reduced overall numbers of galled leaves and leaf galls. Trunk injections of bidrin or abamectin resulted in significant mortality of gall inhabitants, including parasitoids. However, neither of the aforementioned approaches significantly reduced numbers of new stem galls. Sprays of abamectin, dimethoate, or imidacloprid applied on 2 May caused high mortality of all gall inhabitants. There was no net benefit, however, because parasitism caused a similar reduction in C. cornigera survival on unsprayed shoots. Sprays applied later in leaf expansion had little impact on gall inhabitants. Of the treatments tested, bifenthrin sprays at bud break provided the greatest reduction in new leaf galls, whereas bidrin injections provided the greatest reduction in gall wasps emerging from galled leaves. This study suggests that gall wasp outbreaks are unlikely to be controlled by a single treatment, regardless of application method.
Topics: Animals; Chlorpyrifos; Hymenoptera; Imidazoles; Insecticides; Ivermectin; Larva; Neonicotinoids; Nitro Compounds; Organophosphorus Compounds; Plant Diseases; Plant Leaves; Pyrethrins; Quercus
PubMed: 14658527
DOI: 10.1603/0022-0493-93.1.165 -
Journal of Chromatographic Science Jan 2002A simple and rapid procedure for the determination of 22 organophosphorous pesticides (bromophos-ethyl, bromophos-methyl, chlorfenvinphos, chlorpyriphos,...
Simple determination of 22 organophosphorous pesticides in human blood using headspace solid-phase microextraction and gas chromatography with mass spectrometric detection.
A simple and rapid procedure for the determination of 22 organophosphorous pesticides (bromophos-ethyl, bromophos-methyl, chlorfenvinphos, chlorpyriphos, demethon-S-methylsulfon, diazinon, dichlorvos, dicrotophos, dimethoate, disulfoton, edifenphos, fenitrothion, fenthion, malathion, methidathion, mevinphos, monocrotophos, omethoate, parathion-ethyl, parathion-methyl, phosphamidon, and quinalphos) in human blood using headspace (HS) solid-phase microextraction (SPME) and gas chromatography (GC)-mass spectrometry (MS) is presented. The effects of various sample additions, incubation temperatures, absorption times, desorption times, and depths of fiber insertion into the injection port of the GC are optimized to enhance the sensitivity of the procedure. The recoveries of spiked blood samples are determined between 70% and 95% compared with samples prepared in water, and absolute recoveries are in the range between 0.1% and 19.6%. For quantitation in the single ion monitoring mode, linearity is established over concentration ranges from 0.025 to 5.0 microg/g with excellent coefficients of correlation (0.991-0.998). The detection limits are in the range between 0.01 and 0.3 microg/g. The time for analysis is 44 min per sample including extraction and GC-MS analysis. HS-SPME in combination with GC-MS is an effective method for the determination of organophosphorous pesticides in human blood and shows a great potential for use in rapid on-site analytical work, which is highly demanded in clinical and forensic toxicology.
Topics: Calibration; Gas Chromatography-Mass Spectrometry; Humans; Insecticides; Organophosphorus Compounds; Reproducibility of Results; Sensitivity and Specificity
PubMed: 11866384
DOI: 10.1093/chromsci/40.1.29 -
Placenta Sep 2000This study investigated the hypothesis that human term placental lipoxygenase (HTPLO) and soybean lipoxygenase (SLO) are capable of mediating N-demethylation of selected...
This study investigated the hypothesis that human term placental lipoxygenase (HTPLO) and soybean lipoxygenase (SLO) are capable of mediating N-demethylation of selected phenothiazines and insecticides in the presence of linoleic acid (LA). In addition to being LA dependent, the N-demethylation reaction mediated by HTPLO and SLO was limited by incubation time, pH of the medium, concentration of the enzyme and the substrate. Using Nash reagent to monitor formaldehyde production, the specific activity for LA-dependent N-demethylation of chlorpromazine, a model phenothiazine, was determined to be 1.7+/-0.3 nmoles/min/mg HTPLO. Besides chlorpromazine, N-demethylation of promazine, promethazine and trimeprazine was also observed. The insecticide, aminocarb, displayed a specific activity of 2.2+/-0.3 nmoles/min/mg HTPLO for N-demethylation. Other insecticides, namely chlordimeform, dicrotophos and zectran, were oxidized in a similar manner. As compared with HTPLO, the rates of N-demethylation of phenothiazines and insecticides mediated by SLO were higher. Classical inhibitors of lipoxygenase, as well as antioxidants and free radical scavengers, caused a dose-dependent reduction in the production of formaldehyde from chlorpromazine and aminocarb by HTPLO. These results clearly demonstrate the ability of polyunsaturated free fatty acids to support N-demethylation of xenobiotics via the lipoxygenase pathway.
Topics: Carbamates; Cations; Chlorpromazine; Female; Formaldehyde; Free Radicals; Humans; Hydrogen-Ion Concentration; Insecticides; Linoleic Acid; Lipoxygenase; Methylation; Phenothiazines; Phenylcarbamates; Placenta; Pregnancy; Substrate Specificity
PubMed: 10985967
DOI: 10.1053/plac.2000.0547 -
Journal of the American Society of... Aug 1999Due to low toxicity to nontarget species and rapid degradation after its application, organophosphate (OP) remains a widely used class of pesticide. Suicidal or...
Due to low toxicity to nontarget species and rapid degradation after its application, organophosphate (OP) remains a widely used class of pesticide. Suicidal or accidental overdose of OP can result in acute tubular necrosis. Experimental evidence shows little correlation between the renal tubular necrosis and the degree of OP-induced acetylcholinesterase inhibition, the main mechanism of OP's toxicity, suggesting the involvement of alternate mechanisms. Since reactive oxygen species (ROS) are known mediators of many toxin-induced renal injuries, this study was conducted to investigate whether ROS play a role in Bidrin (BD)-induced renal tubular epithelial cell (LLC-PK1) toxicity. BD is an OP insecticide formulation with dicrotophos as the active ingredient. LLC-PK1 cell death, determined by lactate dehydrogenase (LDH) release (% of total), rose concentration- and time-dependently after exposure of the cells to 1000, 1250, 1500, 1750, and 2000 ppm of BD for 6, 12, 24, and 48 h. Antioxidants 2-methylaminochroman (2-MAC; 0.3 to 2.5 microM) and desferrioxamine (DFO; 0.25 to 2 mM) reduced cell damage induced by 1250 ppm of BD over a 24-h incubation in a concentration-related manner. The greatest reductions in % LDH were produced by DFO 2 mM and 2-MAC 2.5 microM, both significantly lower than BD alone. H2O2 levels (micromol/mg protein per h) were significantly elevated after exposure to 1250 ppm of BD. Significantly increased malondialdehyde formation (nmol/mg protein) compared with control was also found in BD-exposed cells indicating enhanced lipid peroxidation. Malondialdehyde generation was significantly suppressed by 2-MAC and DFO. These results demonstrate that the organophosphate BD can cause direct tubular cytotoxicity, and implicate, at least in part, a role for ROS and accompanying lipid peroxidation in cytotoxicity. Based on these direct in vitro findings, it is hypothesized that, besides hypotension that often accompanies OP intoxication, OP-induced oxidative stress at the tubular level may play a role in the pathogenesis of acute tubular necrosis.
Topics: Animals; Chromans; Deferoxamine; Free Radical Scavengers; Hydrogen Peroxide; Insecticides; Kidney Tubules; L-Lactate Dehydrogenase; LLC-PK1 Cells; Lipid Peroxides; Organophosphate Poisoning; Organophosphorus Compounds; Osmolar Concentration; Piperazines; Pyruvic Acid; Reactive Oxygen Species; Swine; Time Factors
PubMed: 10446942
DOI: 10.1681/ASN.V1081746 -
Archives of Toxicology 1996The new bispyridinium oximes HI 6 and HLö 7 are promising antidotes against poisoning by highly toxic organophosphorus compounds, i.e. nerve agents. Until now, their... (Comparative Study)
Comparative Study
The new bispyridinium oximes HI 6 and HLö 7 are promising antidotes against poisoning by highly toxic organophosphorus compounds, i.e. nerve agents. Until now, their ability to reactivate pesticide inhibited human acetylcholinesterase (AChE) has not been elucidated. For this purpose human erythrocyte AChE (EC 3.1.1.7) was inhibited (30 min) by chlorfenvinphos, dichlorvos, dicrotophos, heptenophos, mevinphos, monocrotophos, paraoxon, phosphamidon, trichlorfon, malaoxon, omethoate, oxydemeton-methyl or methamidophos by 85-98% of control. After removal of excess inhibitor, obidoxime, pralidoxime (2-PAM), HI 6 or HLö 7 (10, 30 or 100 mumol/l) were added and the AChE activity was measured spectrophotometrically at various times thereafter (5-60 min). The oximes significantly, but not completely, reactivated organophosphate inhibited AChE. The velocity and extent of reactivation were dependent on the oxime and its concentration. In all cases obidoxime was superior to the three other oximes, followed by HLö 7, 2-PAM and HI 6. In most cases obidoxime and HLö 7 were most effective at 10 or 30 mumol/l while 2-PAM and HI 6 needed 100 mumol/l. These data suggest that 2-PAM HI 6 and HLö 7 are less patent than obidoxime in reactivating human AChE inhibited by organophosphate pesticides.
Topics: Acetylcholinesterase; Cholinesterase Inhibitors; Cholinesterase Reactivators; Erythrocytes; Humans; Oximes; Pyridines; Pyridinium Compounds
PubMed: 8783813
DOI: 10.1007/s002040050304 -
The International Journal of... Feb 19931. Treatment of rats with carbicron induced a reduction of the phospholipids in both microsomal and plasma membranes. 2. A decrease of the structural order parameter...
1. Treatment of rats with carbicron induced a reduction of the phospholipids in both microsomal and plasma membranes. 2. A decrease of the structural order parameter (SDPH) and an increase of the pyrene excimer-to-monomer fluorescence ratio (IE/IM) was also observed, indicating membrane fluidization. 3. The specific activity of membrane-bound phospholipase A2 and phospholipase C were decreased in both types of membranes, whereas acyl-CoA:lysophosphatidylcholine acyltransferase activity was augmented due to carbicron treatment.
Topics: 1-Acylglycerophosphocholine O-Acyltransferase; Animals; Cell Membrane; Chemical Phenomena; Chemistry, Physical; Intracellular Membranes; Liver; Male; Membrane Fluidity; Microsomes, Liver; Organophosphorus Compounds; Phospholipases A; Phospholipases A2; Phospholipids; Rats; Rats, Wistar; Type C Phospholipases
PubMed: 8444321
DOI: 10.1016/0020-711x(93)90014-6 -
Comparative Biochemistry and... Nov 19921. Intoxication of rats with carbicron (O-([2-butenoic acid)-N,N-dimethylamide-3-yl]-O,O-dimethylphosphate) induced a reduction of the total phospholipids and... (Comparative Study)
Comparative Study
1. Intoxication of rats with carbicron (O-([2-butenoic acid)-N,N-dimethylamide-3-yl]-O,O-dimethylphosphate) induced a reduction of the total phospholipids and phosphatidylcholine in lung alveolar surfactant. 2. The lipid transfer protein activity was inhibited due to carbicron treatment. 3. No alterations were observed in phospholipase A2 activity in the alveolar surfactant of intoxicated animals. The structural order parameter (SDPH) of bilayer liposomes, prepared from surfactant phospholipids of carbicron-treated rats also remained unchanged.
Topics: Animals; Carrier Proteins; Fluorescence Polarization; Insecticides; Male; Organophosphorus Compounds; Phospholipases A; Phospholipases A2; Phospholipids; Pulmonary Alveoli; Pulmonary Surfactants; Rats; Rats, Wistar
PubMed: 1363304
DOI: 10.1016/0742-8413(92)90180-f -
Fundamental and Applied Toxicology :... May 1991An optical sensor for anticholinesterases (AntiChEs) was constructed by immobilizing fluorescein isothiocyanate (FITC)-tagged eel electric organ acetylcholinesterase...
An optical sensor for anticholinesterases (AntiChEs) was constructed by immobilizing fluorescein isothiocyanate (FITC)-tagged eel electric organ acetylcholinesterase (AChE) on quartz fibers and monitoring enzyme activity. The pH-dependent fluorescent signal generated by FITC-AChE, present in the evanescent zone on the fiber surface, was quenched by the protons produced during acetylcholine (ACh) hydrolysis. Analysis of the fluorescence response showed Michaelis-Menten kinetics with a Kapp value of 420 microM for ACh hydrolysis. The reversible inhibitor edrophonium (0.1 mM) inhibited AChE and consequently reduced fluorescence quenching. The biosensor response immediately recovered upon its removal. The carbamate neostigmine (0.1 mM) also inhibited the biosensor response but recovery was much slower. In the presence of ACh, the organophosphate (OP) diisopropylfluorophosphate (DFP) at 0.1 mM did not interfere with the ACh-dependent fluorescent signal quenching, but preexposure of the biosensor to DFP in absence of ACh inhibited totally and irreversibly the biosensor response. However, the DFP-treated AChE biosensor recovered fully after a 10-min perfusion with pralidoxime (2-PAM). Echothiophate, a quaternary ammonium OP, inhibited the ACh-induced fluorescence quenching in the presence of ACh and the phosphorylated biosensor was reactivated with 2-PAM. These effects reflected the mechanism of action of the inhibitors with AChE and the inhibition constants obtained were comparable to those from colorimetric methods. The biosensor detected concentrations of the carbamate insecticides bendiocarb and methomyl and the OPs echothiophate and paraoxon in the nanomolar to micromolar range. Malathion, parathion, and dicrotophos were not detected even at millimolar concentrations; however, longer exposure or prior modification of these compounds (i.e., to malaoxon, paraoxon) may increase the biosensor detection limits. This AChE biosensor is fast, sensitive, reusable, and relatively easy to operate. Since the instrument is portable and can be self-contained, it shows potential adaptability to field use.
Topics: Acetylcholinesterase; Animals; Biosensing Techniques; Cholinesterase Inhibitors; Eels; Enzymes, Immobilized; Fiber Optic Technology; Fluorescein-5-isothiocyanate; Fluoresceins; Hydrogen-Ion Concentration; Kinetics; Neostigmine; Optical Fibers; Thiocyanates
PubMed: 1909249
DOI: 10.1016/0272-0590(91)90166-2 -
Journal of Wildlife Diseases Oct 1989Blood plasma cholinesterase (ChE) activity is a sensitive indicator of exposure to organophosphorus and carbamate insecticides. Effects of sex and storage of samples... (Comparative Study)
Comparative Study
Blood plasma cholinesterase (ChE) activity is a sensitive indicator of exposure to organophosphorus and carbamate insecticides. Effects of sex and storage of samples were studied as sources of variability by treating breeding Japanese quail (Coturnix japonica) with 3 mg of dicrotophos or carbofuran per kg of body weight and comparing blood plasma ChE activities for samples collected at 1 hr postdosage and assayed fresh, after 1 and 2 days of refrigeration (4 C), and after 1, 7 and 28 days of freezing (-25 C). ChE activity of fresh control plasma was 34% (P less than 0.01) higher in males than females. Male ChE activity remained essentially unchanged during storage while female ChE activity increased (P less than 0.05) gradually over time under both storage conditions. In contrast, when plasma ChE activity was inhibited by either antiChE, male plasma ChE activity was depressed further than female ChE (P less than 0.01) and remained constant during storage while female ChE activity continued to decrease (P less than 0.05). These divergent effects of exposure to antiChE compounds and sample storage indicate extreme care should be exercised in use of blood plasma for evaluation of antiChE exposure in wild birds.
Topics: Animals; Blood Preservation; Brain; Carbofuran; Cholinesterases; Cold Temperature; Coturnix; Cryopreservation; Female; Insecticides; Male; Organophosphorus Compounds; Quail; Random Allocation; Sex Factors
PubMed: 2810558
DOI: 10.7589/0090-3558-25.4.580