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International Journal of Molecular... 2011We have in vitro tested the ability of common, commercially available, cholinesterase reactivators (pralidoxime, obidoxime, methoxime, trimedoxime and HI-6) to...
We have in vitro tested the ability of common, commercially available, cholinesterase reactivators (pralidoxime, obidoxime, methoxime, trimedoxime and HI-6) to reactivate human acetylcholinesterase (AChE), inhibited by five structurally different organophosphate pesticides and inhibitors (paraoxon, dichlorvos, DFP, leptophos-oxon and methamidophos). We also tested reactivation of human butyrylcholinesterase (BChE) with the aim of finding a potent oxime, suitable to serve as a "pseudocatalytic" bioscavenger in combination with this enzyme. Such a combination could allow an increase of prophylactic and therapeutic efficacy of the administered enzyme. According to our results, the best broad-spectrum AChE reactivators were trimedoxime and obidoxime in the case of paraoxon, leptophos-oxon, and methamidophos-inhibited AChE. Methamidophos and leptophos-oxon were quite easily reactivatable by all tested reactivators. In the case of methamidophos-inhibited AChE, the lower oxime concentration (10(-5) M) had higher reactivation ability than the 10(-4) M concentration. Therefore, we evaluated the reactivation ability of obidoxime in a concentration range of 10(-3)-10(-7) M. The reactivation of methamidophos-inhibited AChE with different obidoxime concentrations resulted in a bell shaped curve with maximum reactivation at 10(-5) M. In the case of BChE, no reactivator exceeded 15% reactivation ability and therefore none of the oximes can be recommended as a candidate for "pseudocatalytic" bioscavengers with BChE.
Topics: Acetylcholinesterase; Butyrylcholinesterase; Cholinesterase Inhibitors; Cholinesterase Reactivators; Erythrocytes; Humans; Organophosphorus Compounds; Oximes; Pesticides; Protein Binding; Structure-Activity Relationship
PubMed: 21673941
DOI: 10.3390/ijms12032077 -
Toxicology Letters Dec 2014An oral dose of the organophosphate insecticide methamidophos was administered to six volunteers at the acceptable daily intake (ADI, 0.004 mg/kg). Urine was collected...
An oral dose of the organophosphate insecticide methamidophos was administered to six volunteers at the acceptable daily intake (ADI, 0.004 mg/kg). Urine was collected from the volunteers at timed intervals for 24 h post-exposure. Methamidophos itself was quantified in urine using liquid/liquid extraction and LC-MS-MS analysis (detection limit 7 nmol/L/1 μg/L). Methamidophos exhibited a rapid elimination half-life of 1.1h, (range 0.4-1.5 h). Mean metabolite levels found in 24h total urine collections (normalised for a 70 kg volunteer) were 9.2 nmol/L (range 1.0-19.1). One volunteer was anomalous; excluding this result the range was 6.7-19.1 nmol/L, with a mean of 10.9 nmol/L. Individual urine samples collected during the first 24 h ranged from below the detection limit (ND) to 237 nmol/L. The mean dose recovery excreted as methamidophos in urine was 1.1% (range 0.04-1.71%). Three environmental studies have been reported in the literature with levels ranging from ND to 66 nmol/L. The number of positive results in all three studies was low (<1.5% of total samples analyzed). When compared with our results (ND - 237 nmol/L), the studies suggest general population exposures are within the ADI. However, the very short half-life makes determining intermittent environmental exposures difficult.
Topics: Adult; Environmental Monitoring; Female; Half-Life; Humans; Insecticides; Male; Middle Aged; Organothiophosphorus Compounds; Young Adult
PubMed: 25310994
DOI: 10.1016/j.toxlet.2014.10.008 -
Environment International Sep 2017Organophosphate insecticides (OPs) are used worldwide, yet despite nearly ubiquitous exposure in the general population, few have been studied outside the laboratory....
BACKGROUND
Organophosphate insecticides (OPs) are used worldwide, yet despite nearly ubiquitous exposure in the general population, few have been studied outside the laboratory. Fetal brains undergo rapid growth and development, leaving them susceptible to long-term effects of neurotoxic OPs. The objective here was to investigate the extent to which prenatal exposure to OPs affects infant motor development.
METHODS
30 OPs were measured in umbilical cord blood using gas chromatography tandem mass spectrometry in a cohort of Chinese infants. Motor function was assessed at 6-weeks and 9-months using Peabody Developmental Motor Scales 2nd edition (PDMS-2) (n=199). Outcomes included subtest scores: reflexes, stationary, locomotion, grasping, visual-motor integration (V-M), composite scores: gross (GM), fine (FM), total motor (TM), and standardized motor quotients: gross (GMQ), fine (FMQ), total motor (TMQ).
RESULTS
Naled, methamidophos, trichlorfon, chlorpyrifos, and phorate were detected in ≥10% of samples. Prenatal naled and chlorpyrifos were associated with decreased 9-month motor function. Scores were 0.55, 0.85, and 0.90 points lower per 1ng/mL increase in log-naled, for V-M (p=0.04), FM (p=0.04), and FMQ (p=0.08), respectively. For chlorpyrifos, scores were 0.50, 1.98, 0.80, 1.91, 3.49, 2.71, 6.29, 2.56, 2.04, and 2.59 points lower for exposed versus unexposed infants, for reflexes (p=0.04), locomotion (p=0.02), grasping (p=0.05), V-M (p<0.001), GM (p=0.007), FM (p=0.002), TM (p<0.001), GMQ (p=0.01), FMQ (p=0.07), and TMQ (p=0.008), respectively. Girls appeared to be more sensitive to the negative effects of OPs on 9-month motor function than boys.
CONCLUSIONS
We found deficits in 9-month motor function in infants with prenatal exposure to naled and chlorpyrifos. Naled is being aerially sprayed to combat mosquitoes carrying Zika virus, yet this is the first non-occupational human study of its health effects. Delays in early-motor skill acquisition may be detrimental for downstream development and cognition.
Topics: China; Chlorpyrifos; Cohort Studies; Developmental Disabilities; Female; Fetal Blood; Humans; Infant; Infant, Newborn; Insecticides; Male; Motor Skills; Naled; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 28602489
DOI: 10.1016/j.envint.2017.05.015 -
Brazilian Journal of Otorhinolaryngology Jun 2012Pesticides are widely used in agriculture, despite the risk of hearing loss related to the exposure to their chemical components. This study looks into protective drugs...
UNLABELLED
Pesticides are widely used in agriculture, despite the risk of hearing loss related to the exposure to their chemical components. This study looks into protective drugs to counteract the ototoxicity of pesticides.
OBJECTIVE
This study aims to analyze the effect ginkgo biloba extract may have in protecting against possible cochlear damage caused by organophosphate pesticides (methamidophos). Anatomic changes are assessed through surface and electron microscopy.
MATERIALS AND METHODS
This is a prospective experimental study. Twenty-one guinea pigs were given saline solution, pesticide, and ginkgo biloba alone or combined for seven consecutive days. Then their cochleas were removed and examined in a scanning electron microscope.
RESULTS
Pesticide-exposed guinea pigs had morphological alterations in their cochleas and injuries in the three turns analyzed through electron microscopy. Injury intensity varied according to the dosages of the agents given to the test subjects. Guinea pigs treated with pesticide and ginkgo biloba maintained the architecture of their outer hair cells in all cochlear turns.
CONCLUSION
The antioxidant properties found in the ginkgo biloba extract protected guinea pigs from pesticide ototoxicity.
Topics: Animals; Cochlea; Ginkgo biloba; Guinea Pigs; Microscopy, Electron, Scanning; Organothiophosphorus Compounds; Pesticides; Plant Extracts; Prospective Studies
PubMed: 22714857
DOI: 10.1590/S1808-86942012000300020 -
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 -
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 -
Bulletin of the World Health... 2003To assess in a developing Asian country the impact of pesticide regulation on the number of deaths from poisoning. These regulations, which were implemented in Sri Lanka...
OBJECTIVES
To assess in a developing Asian country the impact of pesticide regulation on the number of deaths from poisoning. These regulations, which were implemented in Sri Lanka from the 1970s, aimed to reduce the number of deaths - the majority from self-poisoning - by limiting the availability and use of highly toxic pesticides.
METHODS
Information on legislative changes was obtained from the Ministry of Agriculture, national and district hospital admission data were obtained from the Sri Lanka Health Statistics Unit, and individual details of deaths by pesticide poisoning were obtained from a manual review of patients' notes and intensive care unit records in Anuradhapura.
FINDINGS
Between 1986 and 2000, the total national number of admissions due to poisoning doubled, and admissions due to pesticide poisoning increased by more than 50%. At the same time, the case fatality proportion (CFP) fell for total poisonings and for poisonings due to pesticides. In 1991_92, 72% of pesticide-induced deaths in Anuradhapura were caused by organophosphorus (OP) and carbamate pesticides - in particular, the WHO class I OPs monocrotophos and methamidophos. From 1991, the import of these pesticides was reduced gradually until they were banned for routine use in January 1995, with a corresponding fall in deaths. Unfortunately, their place in agricultural practice was taken by the WHO class II organochlorine endosulfan, which led to a rise in deaths from status epilepticus - from one in 1994 to 50 in 1998. Endosulfan was banned in 1998, and over the following three years the number of endosulfan deaths fell to three. However, at the end of the decade, the number of deaths from pesticides was at a similar level to that of 1991, with WHO class II OPs causing the most deaths. Although these drugs are less toxic than class I OPs, the management of class II OPs remains difficult because they are, nevertheless, still highly toxic, and their toxicity is exacerbated by the paucity of available facilities.
CONCLUSION
The fall in CFP amidst a rising incidence of self-poisoning suggests that Sri Lanka's programmes of pesticide regulation were beneficial. However, a closer inspection of pesticide-induced deaths in one hospital revealed switching to other highly toxic pesticides, as one was banned and replaced in agricultural practice by another. Future regulation must predict this switching and bear in mind the ease of treatment of replacement pesticides. Furthermore, such regulations must be implemented alongside other strategies, such as integrated pest management, to reduce the overall pesticide availability for self-harm.
Topics: Acute Disease; Carbamates; Commerce; Developing Countries; Government Regulation; Health Policy; Hospitals, General; Humans; Incidence; Insecticides; Organophosphorus Compounds; Poisoning; Sri Lanka
PubMed: 14758405
DOI: No ID Found -
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 -
Confirmed organophosphorus and carbamate pesticide poisonings in South African wildlife (2009-2014).Journal of the South African Veterinary... Dec 2015During a six-year period (from January 2009 to December 2014), specimens collected from 344 cases of suspected organophosphorus and carbamate pesticide poisonings in...
During a six-year period (from January 2009 to December 2014), specimens collected from 344 cases of suspected organophosphorus and carbamate pesticide poisonings in wildlife, including birds, were submitted to the Toxicology Laboratory (ARC-OVI) for analysis. A positive diagnosis was made in 135 (39%) of these cases. The majority of cases were from birds, which included Cape vultures (Gyps coprotheres) and African white-backed vultures (Gyps africanus) and bateleur eagles (Terathopius ecaudatus). In one incident 49 vultures were killed when a farmer intentionally laced carcasses with carbofuran in an attempt to control jackal predation. There were 22 incidents of poisoning in helmeted guineafowl (Numida meleagris). On nine different occasions blue cranes (Anthropoides paradiseus) were poisoned, in one incident 14 birds were reported to have been killed. Over the period of investigation, there were 20 cases of poisoning involving mammalian species, the majority being vervet monkeys (Chlorocebus pygerythrus). The carbamate pesticides were responsible for 57 incidents of poisoning. Aldicarb, carbofuran and methomyl were detected in 26, 18 and 12 cases respectively. The majority of organophosphorus pesticide poisonings were caused by diazinon (n = 19), monocrotophos (n = 13) and methamidophos (n = 10).
Topics: Aldicarb; Animals; Animals, Wild; Carbofuran; Chromatography, Gas; Environmental Pollutants; Mass Spectrometry; Methomyl; Pesticides; Poisoning; South Africa
PubMed: 26824339
DOI: 10.4102/jsava.v86i1.1329 -
Journal of Zhejiang University.... Apr 2012The widespread use of organophosphorus pesticides (OPs) poses a great threat to human health and has made the detection of OP residues in food an important task,...
The widespread use of organophosphorus pesticides (OPs) poses a great threat to human health and has made the detection of OP residues in food an important task, especially in view of the fact that easy and rapid detection methods are needed. Because OPs have inhibitory effects on the activity of α-naphthyl acetate esterase (ANAE) in plants, in this work we evaluated the possibility of detecting OPs in vegetables with ANAE extracted from commercial flour. The limits of detection (LODs) obtained for methamidophos, dichlorvos, phoxim, dimethoate, and malathion in lettuce samples with crude ANAE were 0.17, 0.11, 0.11, 0.96, and 1.70 mg/kg, respectively. Based on the maximum residue limits (MRLs) for OPs in food stipulated by Chinese laws which are 0.05, 0.20, 0.05, 1.00, and 8.00 mg/kg for methamidophos, dichlorvos, phoxim, dimethoate, and malathion, respectively, the esterase inhibition method with crude ANAE had sufficient sensitivity to detect the residues of dichlorvos, dimethoate, and malathion in lettuce, but it could not be used to guarantee the safety of the same samples if methamidophos or phoxim residue was present. The sensitivity of the method was improved by the use of esterase purified by ammonium sulfate salting-out. The LODs obtained for methamidophos and phoxim with purified esterase were lower than the MRLs for these OPs in food. This is a very promising method for the detection of OP residues in vegetables using crude or purified esterase because of its cheapness, sensitivity, and convenience.
Topics: Flour; Food Analysis; Food Contamination; Naphthol AS D Esterase; Organophosphorus Compounds; Pesticides; Plant Extracts; Triticum; Vegetables
PubMed: 22467368
DOI: 10.1631/jzus.B11a0180