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Neurotoxicology May 2009Epidemiologic studies have suggested that organophosphate exposure is associated with an increased risk of depression and suicide. Considering that the neurobiological...
Epidemiologic studies have suggested that organophosphate exposure is associated with an increased risk of depression and suicide. Considering that the neurobiological basis of this association is not well understood, in the present study we evaluated the depressive-like behavior of Swiss mice subchronically exposed to the organophosphate methamidophos at adulthood. From postnatal days 60 to 89 (PN60-PN89), one of two concentrations of methamidophos [higher dose (HiD): 5.25 microg/ml; lower dose (LoD): 1.31 microg/ml] or vehicle was administered in the drinking water. Immobile behavior, an animal model of depressive behavior, was assessed in the forced swimming and tail suspension tests either during (PN88) or after (PN99) the exposure period. On the subsequent day (PN89 or PN100), the Rota-rod and endurance swimming tests were used to evaluate motor performance. Brain acetylcholinesterase activity was quantified. During exposure, the LoD group presented increased immobility in the tail suspension test when compared to controls. The HiD group presented increased immobility in the forced swimming test when compared to LoD and control groups, an effect that emerged after cessation of exposure. There were no motor performance alterations. During exposure, acetylcholinesterase activity was inhibited in the HiD (43%) and LoD (15%) groups. After exposure, enzyme activity was reduced (25%) only in the HiD group. There were no signs of systemic toxicity. There were no correlations between acetylcholinesterase activity and behavioral measures. Our results indicate that methamidophos at doses below the threshold for systemic toxicity induces depressive-like behavior in adult mice.
Topics: Acetylcholinesterase; Animals; Body Weight; Brain; Depression; Disease Models, Animal; Drinking; Hindlimb Suspension; Insecticides; Male; Mice; Motor Activity; Organothiophosphorus Compounds; Swimming
PubMed: 19442833
DOI: 10.1016/j.neuro.2009.01.009 -
Journal of Medical Toxicology :... Jun 2009Acephate (AP) is a widely available organophosphorus (OP) insecticide considered to have low mammalian toxicity. In plants and insects, AP is metabolized extensively to...
INTRODUCTION
Acephate (AP) is a widely available organophosphorus (OP) insecticide considered to have low mammalian toxicity. In plants and insects, AP is metabolized extensively to methamidophos (MP), a more potent OP insecticide. The limited mammalian metabolism of AP to MP has been studied in laboratory rat models and suggests that initial formation of MP from AP may inhibit further formation. No case reports of human ingestion with urine AP and MP levels have been previously published.
CASE REPORT
A 4-year-old male being evaluated for altered mental status and head trauma was noted to have muscarinic and nicotinic cholinergic signs. Further history suggested possible ingestion of a commercial AP product at an unknown time. Ingestion of AP was confirmed by the presence of urinary AP and MP and severely depressed red blood cell (RBC) cholinesterase and pseudocholinesterase activity levels. The patient initially received atropine in two 0.02 mg/kg IV boluses, then was started on 0.05 mg/kg IV per hour and titrated accordingly to clinical signs of cholinergic toxicity. Pralidoxime was also given at 20 mg/kg IV bolus, followed by an infusion of 10 mg/kg per hour. The patient required mechanical ventilation for 18 days and atropine infusion for 20 days. After a complicated intensive care unit course, he recovered and was discharged after a total of 32 days of hospitalization.
METHODS
Four urine samples collected at different times were analyzed for AP and MP by using high-performance liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry. Kinetic calculations were performed by using standard equations.
RESULTS
Suspected ingestion was confirmed by the presence of AP and MP in urine. The amount of MP found in urine suggests some limited human metabolism to this more toxic compound.
CONCLUSIONS
Urinary elimination kinetics of AP demonstrates low metabolic conversion of AP to MP in humans.
Topics: Antidotes; Atmospheric Pressure; Atropine; Butyrylcholinesterase; Child, Preschool; Chromatography, High Pressure Liquid; Drug Therapy, Combination; Erythrocytes; Humans; Insecticides; Male; Muscarinic Antagonists; Organothiophosphorus Compounds; Phosphoramides; Poisoning; Pralidoxime Compounds; Respiration, Artificial; Tandem Mass Spectrometry; Treatment Outcome
PubMed: 19415590
DOI: 10.1007/BF03161090 -
Journal of Environmental Monitoring :... Feb 2009The development of new sorbents, which are able to trap polar compounds, is a growing research field in solid-phase extraction (SPE). In this study, multi-walled carbon... (Comparative Study)
Comparative Study
The development of new sorbents, which are able to trap polar compounds, is a growing research field in solid-phase extraction (SPE). In this study, multi-walled carbon nanotubes (MWCNTs) and single-walled carbon nanotubes (SWCNTs) were oxidized in air at 600 degrees C and 500 degrees C, respectively, for 2 h. MWCNTs, SWCNTs, air oxidized MWCNTs (OMWCNTs) and SWCNTs (OSWCNTs) (200 mg of each) were packed in SPE cartridges. The four cartridges obtained, together with a commercial Oasis HLB cartridge, were used to extract six polar organophosphorous pesticides (OPPs), i.e., dichlorvos, methamidophos, acephate, omethoate, monocrotophos and dimethoate, from an aqueous sample. The results showed that the oxidation process significantly enhanced the adsorption abilities of both SWCNTs and MWCNTs for polar OPPs. A comparative study indicated that OSWCNTs were more effective than Oasis HLB for the extraction of methamidophos and acephate and as effective as Oasis HLB for the other four OPPs from aqueous samples. When 100 mL of a natural sample was spiked with OPPs and extracted with OSWCNTs, the recoveries of five of the six polar OPPs (methamidophos excepted) ranged from 79.1 to 101.9%. The detection limits of the method based on OSWCNTs was found to be 0.07-0.12 microg L(-1).
Topics: Adsorption; Nanotubes, Carbon; Organothiophosphorus Compounds; Oxidation-Reduction; Pesticides; Seawater; Sensitivity and Specificity; Solid Phase Extraction; Water; Water Pollutants, Chemical
PubMed: 19212604
DOI: 10.1039/b816271a -
International Journal of Clinical and... 2008Tobacco is an important cash crop of Pakistan and tremendous amount of irrational pesticides are being used to control insect growth. The frequency of plasma pesticide...
Tobacco is an important cash crop of Pakistan and tremendous amount of irrational pesticides are being used to control insect growth. The frequency of plasma pesticide residues above acceptable daily intake (ADI) and its correlation with biochemical markers for assessment of adverse health effects in the tobacco farmers at district Sawabi, Pakistan was determined. Total 109 adult males consisting of 55 tobacco farmers exposed to pesticides and 54 controls were included. Pesticides residues in blood were analyzed on HPLC and GC-NPD. Plasma butyrylcholinesterase (BChE) was analyzed by Ellman's method. Biochemical markers including serum calcium, phosphorus, urea, creatinine, bilirubin and liver enzymes were measured on Selectra-E auto analyzer. The tobacco farmers had multiple pesticides residues above ADI in their blood consisting of 35 (63%) methomyl; 31 (56%) thiodicarb; 34(62%) cypermethrin; 27 (49%) Imidacloprid; 18 (32%) Methamidophos and 15 (27%) endosulfan. BChE activity was significantly decreased in the pesticides exposed farmers as compared to controls (P<0.001). Plasma biochemical markers including ALT, AST, CK, LDH and phosphate were significantly raised in the pesticides exposed farmers as compared to control group (P<0.001). Total pesticides residues revealed a significant positive correlation with AST (r=0.42), LDH(r= 0.47), ALT (r=0.20) and phosphorus (r=0.51). Excessive exposure to pesticide caused cytotoxic changes in the hepatic and renal biochemical markers which were positively correlated with pesticide residue. Hence these biomarkers might be used in addition to BChE activity for monitoring of adverse effects of pesticides on the health of farm workers.
PubMed: 19079663
DOI: No ID Found -
The Journal of Toxicological Sciences Oct 2008An outbreak of food poisoning that affected at least ten people in various regions of Japan was traced to exposure to Chinese dumplings contaminated with the...
An outbreak of food poisoning that affected at least ten people in various regions of Japan was traced to exposure to Chinese dumplings contaminated with the organophosphate insecticide Methamidophos. We experienced the most serious case, a five years old girl, who suffered coma. She presented with features of cholinergic overactivity and her serum cholinesterase activity was 9 U/l. We started intravenous treatment with pralidoxime iodide, atropine sulfate, and midazolam. Her symptoms improved gradually and she was discharged on day 25 without any sequelae. Though poisoning attributed to organophosphate insecticides has become less common in recent years, it is even more important to diagnose the problem rapidly based on the characteristic symptoms and to start specific treatment at the earliest possible stage after poisoning.
Topics: Atropine; Child, Preschool; China; Coma; Female; Foodborne Diseases; Humans; Insecticides; Japan; Midazolam; Organothiophosphorus Compounds; Pralidoxime Compounds
PubMed: 18827448
DOI: 10.2131/jts.33.485 -
Current Therapeutic Research, Clinical... Aug 2008Organophosphate (OP) insecticides are widely used in both agricultural and landscape pest control, and the potential for human exposure to these compounds is significant.
Ultrastructural changes in rat thyroid tissue after acute organophosphate poisoning and effects of antidotal therapy with atropine and pralidoxime: A single-blind, ex vivo study.
BACKGROUND
Organophosphate (OP) insecticides are widely used in both agricultural and landscape pest control, and the potential for human exposure to these compounds is significant.
OBJECTIVES
The aims of this study were to investigate the effects of acute poisoning with the OP methamidophos and the effects of antidotal therapy with atropine and pralidoxime on rat thyroid tissue ultrastructure.
METHODS
In this single-blind, ex vivo study, male Wistar albino rats weighing 220 to 230 g were divided into 4 treatment groups. Group 1 received a median lethal dose of methamidophos (30 mg/kg) via oral gavage. Group 2 received saline via oral gavage and served as the control group for group 1. Group 3 received methamidophos (30 mg/kg) via oral gavage, and after 8 minutes atropine 0.05 mg/kg and pralidoxime chloride (2-FAM) (40 mg/kg) were administered intraperitoneally (IP). Atropine was titrated to reverse signs of cholinergic excess. Group 4 received saline via oral gavage followed by IP injections and served as the control for group 3. Rat thyroid tissues were examined using electron microscopy, and the histologic changes were examined by a histopathologist who was blinded to treatment. All rats were euthanized by intracardiac blood collection. The rats in groups 1 and 2 were euthanized 8 minutes after treatment. The rats in groups 3 and 4 were euthanized 96 hours after treatment.
RESULTS
Thirty-four male rats (aged 16 weeks) were included in the study. The rats were grouped accordingly: group 1 (n = 10); group 2 (n = 7); group 3 (n = 10); and group 4 (n = 7). The mean (SD) pseudocholinesterase (FCE) activity was significantly lower in the methamidophos-treated rats (group 1) compared with the corresponding control group (group 2) (32.6 [17.0] vs 579.4 [59.0] U/L, respectively; P < 0.001). PCE activity was significantly higher in rats treated with atropine and 2-PAM (group 3) (392.5 [39.4] U/L; P < 0.001) compared with those not receiving antidotal therapy (group 1). Group 1 experienced changes in thyrocytes and organelles that were not detected in the antidote-treated rats in group 3. These changes included follicular cell nuclei exhibiting an increase in chromatin content, pyknotic nuclei, mitochondrial degeneration, dilated granular endoplasmic reticulum cisternae, reduced microvilli, and intraluminal cellular debris. Within follicular cells, formation of vacuoles filled with fine granular material was noted.
CONCLUSION
Acute OP poisoning was associated with histopathologic effects in rat thyroid tissue that appeared to be mitigated by antidotal therapy in this small animal study. More extensive studies using immunohistochemical methods are needed.
PubMed: 24692810
DOI: 10.1016/j.curtheres.2008.07.001 -
Environmental Health Perspectives Apr 2008The pesticides monocrotophos, methamidophos, and endosulfan were a very common cause of severe poisoning in Sri Lanka during the 1980s and early 1990s, before they were...
BACKGROUND
The pesticides monocrotophos, methamidophos, and endosulfan were a very common cause of severe poisoning in Sri Lanka during the 1980s and early 1990s, before they were banned in 1995 and 1998. Now, the most commonly used insecticides are the less toxic World Health Organization Class II organophosphorus pesticides and carbamates. These bans were followed by a large reduction in both fatal poisonings and suicide in Sri Lanka.
OBJECTIVE
We aimed to see if these bans adversely affected agricultural production or costs.
METHODS
We used data from the World Resources Institute to compare the yields of the main crop groups in Sri Lanka with those from surrounding South Asian countries for 1980-2005. We also examined data from the Sri Lankan Department of Census and Statistics to examine the yields of 13 specific vegetable crops and rice for 1990-2003, along with the costs of rice production.
RESULTS
We found no drop in productivity in the years after the main bans were instituted (1995, 1998). We observed substantial annual fluctuation in estimated yields in all data sources, but these did not coincide with the bans and were no larger than the fluctuations in other countries. Also, there was no sudden change in costs of rice production coinciding with bans.
CONCLUSIONS
Countries aiming to apply restrictions to reduce deaths from pesticide poisoning should evaluate agricultural needs and develop a plan that encourages substitution of less toxic pesticides. If farmers have an affordable alternative for pest control for each crop, there is no obvious adverse effect on agricultural output.
Topics: Agriculture; Endosulfan; Health Policy; Humans; Insecticides; Monocrotophos; Organothiophosphorus Compounds; Sri Lanka; Suicide Prevention
PubMed: 18414632
DOI: 10.1289/ehp.11029 -
Shokuhin Eiseigaku Zasshi. Journal of... Oct 2006A screening method is described for determining 200 pesticides, except dimethipin, divided into four groups by means of gas chromatography/tandem mass spectrometry...
A screening method is described for determining 200 pesticides, except dimethipin, divided into four groups by means of gas chromatography/tandem mass spectrometry (GC/MS/MS) using an ion trap mass spectrometer equipped with automated gain control (AGC). The quantitation limit for 194 pesticides was 0.01 mg/kg on a crop basis, except for allidochlor, dimethoate, hexythiazox, methamidophos and triadimenol. The calibration curve of each pesticide was linear in the range of 0.04-5.0 microg/mL. One hundred and ninety-nine pesticides were added to matrix of potato, spinach, cabbage, apple, orange, soybean and unpolished rice at twice the limits of quantitation. The recoveries of 194 pesticides from all crops were satisfactory (50-150%) for screening purposes. Although some pesticides in apple and orange were not determined by selected ion monitoring (SIM) analysis at the limits of quantitation, all of them were identified by ion-trap GC/MS/MS at the same concentration. Thus, the ion trap GC/MS/MS technique is useful for the screening of residual pesticides present at low levels in agricultural products.
Topics: Brassica; Citrus sinensis; Crops, Agricultural; Food Analysis; Gas Chromatography-Mass Spectrometry; Malus; Oryza; Pesticide Residues; Solanum tuberosum; Glycine max; Spinacia oleracea; Tandem Mass Spectrometry
PubMed: 17128871
DOI: 10.3358/shokueishi.47.213 -
Genetics and Molecular Research : GMR Dec 2005We examined the cytogenetic and genotoxic effects of the neonicotinoid insecticide imidacloprid and the organophosphate insecticide methamidophos, when administered...
We examined the cytogenetic and genotoxic effects of the neonicotinoid insecticide imidacloprid and the organophosphate insecticide methamidophos, when administered alone or in combination. These insecticides were tested with the bone marrow chromosome aberration assay and micronucleus test in rats and by the bacterial mutation assay (Salmonella/microsome mutagenicity assay). Wistar albino rats were orally fed daily with laboratory chow treated with various concentrations of insecticides, 50 and 100 mg/kg imidacloprid, 2.5 and 5 mg/kg methamidophos, and 2.5 and 5 mg/kg imidacloprid plus methamidophos, respectively, for 90 days. Numerical and structural chromosomal aberrations were evaluated. Significant differences were detected between all the insecticide-administered groups versus the control group and between the two concentrations of the pesticide-treated groups. Both concentrations of the insecticides induced a dose-related increase in the micronucleus frequency (P < 0.05). Dose-related increases in the number of revertants were observed with the two Salmonella strains (TA98 and TA100). All tested doses of the insecticides demonstrated mutagenic activity in the presence of S9 mix. These results lead us to the conclusion that the synergistic effect of methamidophos and imidacloprid causes an increase in potential damage to non-target organisms.
Topics: Animals; Bone Marrow Cells; Chromosome Aberrations; Dose-Response Relationship, Drug; Drug Synergism; Imidazoles; Insecticides; Male; Mutagenicity Tests; Neonicotinoids; Nitro Compounds; Organothiophosphorus Compounds; Rats; Rats, Wistar
PubMed: 16475109
DOI: No ID Found -
Industrial Health Apr 2005We examined the effects of pesticides on the central and peripheral nervous system in the setting of a tobacco farm at a developing country. Maximal motor and sensory...
Effects of pesticides on the peripheral and central nervous system in tobacco farmers in Malaysia: studies on peripheral nerve conduction, brain-evoked potentials and computerized posturography.
We examined the effects of pesticides on the central and peripheral nervous system in the setting of a tobacco farm at a developing country. Maximal motor and sensory nerve conduction velocities (MCV and SCV, respectively) in the median, sural and tibial nerves, postural sway, and brain-evoked potentials (auditory event-related and visual-evoked potentials) were measured in 80 male tobacco farmers and age- and sex-matched 40 controls in Kelantan, Malaysia. Median SCV (finger-wrist) in farmers using Delsen (mancozeb, dithiocarbamate fungicide), who showed significant decrease of serum cholinesterase activities, were significantly lower compared with the controls. Sural SCV in farmers using Fastac (alpha-cypermethrin, pyrethroid insecticide) and median MCV (elbow-wrist) in farmers using Tamex (butralin, dinitroaniline herbicide) were significantly slowed compared with their respective controls. In Delsen (mancozeb, dithiocarbamate) users, the power of postural sway of 0-1 Hz was significantly larger than that in the controls both in the anterior-posterior direction with eyes open and in the right-left direction with eyes closed. The former type of sway was also significantly increased in Tamaron (methamidophos, organophosphorus insecticide) users. In conclusion, nerve conduction velocities and postural sway seem to be sensitive indicators of the effects of pesticides on the central and peripheral nervous system.
Topics: Adult; Agriculture; Case-Control Studies; Central Nervous System; Cholinesterases; Evoked Potentials; Humans; Malaysia; Male; Middle Aged; Neural Conduction; Occupational Exposure; Peripheral Nervous System; Pesticides; Postural Balance; Nicotiana
PubMed: 15895843
DOI: 10.2486/indhealth.43.285