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PubMed2000

Efficacy and safety of selamectin against fleas on dogs and cats presented as veterinary patients in Europe.

Two controlled and masked multi-centre studies were conducted to examine the efficacy of a novel topical avermectin, selamectin, against natural flea infestations on 418 dogs and 345 cats. Veterinary patients with viable flea infestations were enrolled in the studies, which were conducted in United Kingdom, France, Germany, and Italy. Animals were allocated randomly in a 2:1 ratio to one of two treatments: either selamectin alone at a minimum dosage of 6mgkg(-1) or fenthion at recommended dose rates. Concurrent use of an environmental spray (containing methoprene and either pyrethrins or permethrin) was permitted only for fenthion-treated animals. In-contact cats and dogs (animals living in the same home) received the same treatment as the first animal enrolled from the household, if recommended by the veterinarian. Study day 0 was defined as the day of first treatment. Animals were treated on days 0, 30, and 60, and flea comb counts and clinical evaluations were conducted on days 0, 14, 30, 60, and 90. Analysis of variance of ln(flea count+1) showed that values were significantly lower for selamectin alone compared with fenthion (with or without the concurrent use of an environmental spray) in dogs on days 30, 60, and 90 (P<0.05) and in cats on days 14, 30, 60, and 90 (P<0.01). For selamectin, the reductions in geometric mean flea counts on days 14, 30, 60, and 90, compared with day 0, were 92.5, 90.7, 98.1, and 99.1%, respectively, for dogs and 92.8, 92.7, 97.7, and 98.4%, respectively, for cats. Selamectin was shown to be safe and highly effective in the control of naturally acquired flea infestations on dogs and cats presented as veterinary patients in Europe.

Animals↗
PubMed2006

Exposure assessment of fruits contaminated with pesticide residues from Valencia, 2001- 03.

A total of 634 samples of oranges, tangerines, peaches, nectarines, khakis and watermelons were collected from an Agricultural Valencia Community Cooperative during the May 2001 to April 2003 campaigns and they were analysed for 15 pesticides among those recommended for pest treatment. A conventional multiresidue analytical procedure based on ethyl acetate extraction was used followed by gas chromatography coupled to a nitrogen phosphorus detector for routine analysis; and mass spectrometry was performed for confirmation. Recovery studies with spiked samples at 0.5 mg kg-1 for each pesticide ranged from 52% for acephate to 87% for fenthion with a standard deviation <20%. Limits of quantification ranged from 0.1 to 100 microg kg-1. A total of 43% of samples contained pesticide residues; and 5% exceeded the maximum residue levels (MRLs). Nine of the pesticides studied were found. Malathion, which was the most frequently detected, was found in 121 samples (19%) at 0.002-4.25 mg kg-1; followed by fenthion in 104 samples (16%) at 0.005-2.3 mg kg-1; and methidation in 68 samples (10%) at 0.008-1.3 mg kg-1. Khaki showed the highest contamination rates with 60% of contaminated samples that exceeded more often the MRLs; and fenthion was the pesticide more frequently detected in all the commodities studied at levels above the European MRLs. The estimated daily intakes of each pesticide calculated from the results obtained were much lower than the acceptable daily intakes.

Adult↗
PubMed2004

Extrahepatic metabolism of carbamate and organophosphate thioether compounds by the flavin-containing monooxygenase and cytochrome P450 systems.

The cytochrome P450 (P450) and flavin-containing monooxygenase (FMO) enzymes are the major oxidative enzymes in phase I metabolism. Many organophosphate and carbamate thioether compounds are excellent substrates for these enzymes. Stereoselective sulfoxidation of fenthion and methiocarb by human liver, kidney, and microsomes was investigated. A high level of stereoselectivity in the formation of fenthion +-sulfoxide was observed in kidney and intestinal microsomes. This activity was not inhibited by the P450 inhibitor 1-aminobenzotriazole but was dramatically reduced following mild heat treatment. In liver, fenthion was metabolized to its sulfoxide in a nonstereoselective manner, and the activity was sensitive to both 1-aminobenzotriazole and heat treatment. The carbamate pesticide methiocarb also was sulfoxidated with a high degree of stereoselectivity in human kidney microsomes. Human liver microsomes formed both stereoisomers in equal amounts. Sulfoxide formation in kidney was not inhibited by 1-aminobenzotriazole but was abolished in liver microsomes. Formation of methiocarb sulfoxides was not observed in intestinal microsomes. The relative contribution of FMO1 and FMO3 to the sulfoxidation of carbophenothion, demeton-O, ethiofencarb, fonofos, and methiocarb also was investigated by using baculovirus-expressed recombinant proteins. FMO1 showed the highest catalytic activity for all pesticides. This study indicates that FMO1 may have a bigger role in extrahepatic metabolism than previously thought.

Carbamates↗
PubMed1975

Changes in cross-resistance spectrum resulting from methyl parathion selection of Culex tarsalis Coq.

Larvae of a field strain of Culex tarsalis Coq. manifesting a broad spectrum of resistance to organophosphorus (OP) insecticides were selected further by methyl parathion pressure in the laboratory. There was a 6.9 times further increase in resistance to methyl parathion in larvae, i.e., from 13.4 times level of resistance in the parental strain to 93.5 times level in the F11 generation. With the exception of fenthion and malathion, cross resistance in larvae the parental strain. The F11 larval population exhibited high levels of cross-resistance to chlorpyrifos (29.6 times), fenitrothion (49.4 times), parathion (55.6 times), fenthion (76.8 times), and chlorpyrifos-methyl (253.8 times). The high levels and broad spectrum of resistance to diverse OP compounds suggest the involvement of more than one mechanism in resistance. Larval selection also affected the spectrum of OP resistance in adults. The F11 adult population exhibited high levels of resistance to dichlorvos (48 times) and chlorpyrifos-methyl (40.1 times) insecticides propoxur, Mobam, Landrin or carbaryl, or to the chrysanthemate insecticide cismethrin. Resistance to the OP insecticides methyl parathion, parathion, fentirothion, fenthion and chlorpyrifos-methyl was found to be fairly stable over nine generations in the absence of methyl parathion selection pressure.

Animals↗
PubMed1966

Development of resistance to various insecticides in Culex pipiens fatigans Wiedemann.

Since larvicidal treatment to reduce the numbers of Culex fatigans, the tropical house mosquito, offers a promising means of preventing the spread of filariasis, an assessment was made of the liability of C. fatigans to develop resistance to certain important insecticides. Strains of this mosquito from Burma, Cameroon, Sierra Leone and the USA (California) were submitted to larval selection for periods of seven to 23 generations. It was found that resistance to DDT or deutero-DDT rapidly developed to high levels and that to dieldrin or CP-47412 to moderate levels; dieldrin did not select for DDT-resistance.The organophosphorus compounds chosen developed only a modest tolerance-fivefold to sixfold with malathion or parathion, twofold to fourfold with fenthion or diazinon; the carbamate insecticide Hercules 5727 induced a threefold to fivefold tolerance. There was a general cross-tolerance from the selecting agent to all of the organophosphorus compounds tested and to the carbamate. A Rangoon strain that had already been made DDT-resistant subsequently developed a ninefold resistance to fenthion after 23 generations of selection with this organophosphorus compound, but this is still insufficient to annual the larvicidal effectiveness of fenthion.

Animals↗
PubMed1980

Gas-liquid chromatographic determination of organophosphorus insecticide residues in fruits and vegetables.

A method intended for regulatory purposes is described for the determination of organophosphorus insecticide residues in fruits and vegetables. Eighteen organophosphorus insecticides, azinphos-ethyl, chlorpyrifos, diazinon, dichlorvos, dimethoate, ethion, ethoate-methyl, fenitrothion, fenthion, formothion, malathion, methidathion, mevinphos, parathion, phosalone, phosphamidon, thiometon, and trichlorphon, and 7 metabolites, fenitrooxon, fenthion sulfoxide, fenthion sulfone, malaoxon, desethylphosphamidon, thiometon sulfoxide, and thiometon sulfone, were extracted from different crops with acetone and partitioned into hexane or ethyl acetate, according to their polarities. The hexane extract was cleaned up by eluting from a Florisil column with acetone-hexane (4+96). The ethyl acetate extract needs no cleanup. The concentrated extracts were analyzed by gas-liquid chromatography using thermionic detectors. Recoveries conducted at fortification levels ranging from 0.1 to 2 mg/kg were in most cases above 80%. The limit of sensitivity is less than 0.1 mg/kg.

Chromatography, Gas↗
PubMedDate not supplied

Effects of organophosphates on the visual system of rats.

The possibility that exposure to organophosphate insecticides can lead to ocular damage is suggested by Japanese studies from the 1960s and 1970s indicating that exposed humans developed chronic ocular degeneration, in addition to showing more commonly accepted effects of cholinesterase-inhibiting compounds. Other papers reported ocular lesions in laboratory animals treated with organophosphates. More recently, retinal degeneration following chronic organophosphate treatment has been reported to the Environmental Protection Agency by pesticide manufacturers in studies conducted in compliance with good laboratory practice regulations. Several factors, however, have prompted scepticism regarding organophosphate-induced ocular toxicity, including the widespread use of organophosphate compounds for both agricultural and ophthalmological practices without numerous additional reports of comparable ocular toxicity. We are developing a research program to address these issues involving electrophysiological, biochemical and histological investigations of rats treated with organophosphate insecticides. The research program is young, but early results are available. Notably, retinas from rats treated with a single subcutaneous injection of 100 mg kg-1 fenthion showed decreases in carbachol-stimulated release of inositol phosphate, an indicator of cholinergically-mediated intracellular second messenger systems. These effects persisted at least 56 days after fenthion administration. This could indicate several different toxicological actions, which are currently under investigation. It is concluded that the possible association between exposure to organophosphates and ocular toxicity cannot be dismissed, and that several important research issues need to be resolved.

Animals↗
PubMed1991

Postsynaptic neuromuscular dysfunction in organophosphate induced intermediate syndrome.

A 65-year-old Caucasian female developed an intermediate syndrome seven days after an acute cholinergic crisis, caused by the ingestion of fenthion. Cholinesterase activity in the blood, plasma and red cells was monitored daily by the method according to Nenner and serial serum fenthion levels were measured by capillary gas chromatography. Electromyographic studies showed fade on tetanic stimulation by means of surface electrodes at 20 Hz of the left M. abductor digiti quinti at day 7, which could no longer be observed at day 19. Fade on low-frequency stimulation and post-tetanic facilitation were both absent. A biopsy of the N. suralis was normal. A biopsy of the M. tibialis anterior revealed a limited rhabdomyolysis with a very weak staining for cholinesterase. It is hypothesized that the pathophysiologic process underlying the syndrome is the result of a time-confined phenomenon, which includes both changes in the postsynaptic structures by a desensitization process and a gradually restoring ratio of acetylcholine to acetylcholinesterase. This hypothesis is suggested by the similarity in the EMG-findings of this patient and those in myasthenia gravis, which is known to be characterized by a postsynaptic transmission defect.

Acetylcholinesterase↗
PubMed1996

In vitro and in vivo induction of heat shock (stress) protein (Hsp) gene expression by selected pesticides.

The chloroacetamide insecticide alachlor, polyhalogenated cyclic hydrocarbons endrin and chlordane and the organophosphate pesticides chlorpyrifos and fenthion induce oxidative tissue damaging effects including lipid peroxidation and nuclear DNA-single strand breaks. The mechanism involved in the induction of oxidative stress by these xenobiotics is unknown. No information is available regarding whether these pesticides can induce the expression of heat shock (stress) protein (Hsp) genes as a common protective mechanism against tissue damage. The pesticides were administered p.o. individually to female Sprague-Dawley rats in two 0.25 LD50 doses at 0 h and 21 h. The animals were killed at 24 h, and liver, brain, heart and lung tissues were removed to examine the induction of Hsps by Western and Northern blot analysis. In a separate series of experiments, cultured neuroactive PC-12 cells were treated 24 h with 50, 100 or 200 nM concentrations of these pesticides. Alachlor, endrin, chlorpyrifos and fenthion induced Hsp89 alpha and Hsp89 beta in hepatic and brain tissues, as well as in cultured PC-12 cells. Chlordane induced some expression of Hsp89 alpha but not Hsp89 beta in the hepatic and brain tissues of treated rats. Some expression of Hsp89 beta was observed in lung tissues of endrin and alachlor treated animals. These findings were substantiated by Western blot analysis using Hsp90 antibody. Except chlordane all these pesticides induced enhanced synthesis of Hsp90 in cultured PC-12 cells. The results indicate striking tissue differences in the patterns of the Hsps induced by the pesticides which were used, and demonstrate that these pesticides can induce the expression of Hsp89 alpha and Hsp89 beta genes in various target organs of rats. The results support the hypothesis that these genes may be mechanistically involved in protecting tissues against oxidative stress induced by structurally diverse pesticides.

Acetamides↗
PubMed1982

Organophosphate inhibition of avian salt gland Na, K-ATPase activity.

1. Adult black ducks (Anas rubripes) were given freshwater or saltwater (1.5% NaCl) for 11 days and half of each group was also given an organophosphate (17 p.p.m. fenthion) in the diet on days 6-11. 2. After 11 days, ducks drinking saltwater had lost more weight and had higher plasma Na and uric acid concentrations and osmolalities than birds drinking freshwater. 3. Saltwater treatment stimulated the salt gland to increased weight and Na, K-ATPase activity. 4. Fenthion generally reduced plasma and brain cholinesterase activity and depressed cholinesterase and Na, K-ATPase activities in salt glands of birds drinking saltwater.

Animals↗
PubMedDate not supplied

Clinical and biochemical changes in chronically exposed organophosphate workers.

Health effects of occupational organophosphate exposure were investigated by subjecting 22 workers chronically exposed to an organophosphate pesticide, fenthion (O,O-dimethyl-O-(4-methylmercapto-3-methylphenyl)-phosphorothioate) to clinical evaluation, estimation of serum cholinesterase, serum alkaline phosphatase (SAP), serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT). The mean age of the workers was 31 years and the mean duration of fenthion exposure 8.2 years. Headache (59%), giddiness (50%), ocular symptoms (27%) and paresthesia (18%) were the commonest symptoms. Serum acetylcholinesterase and butyrylcholinesterase levels were significantly lower than in controls. After withdrawing the workers from organophosphate exposure for 3 weeks, the follow-up study revealed absence of transient symptoms. There was no change in their neurological status, and serum acetylcholinesterase and butyrylcholinesterase levels were raised significantly, whereas the other serum enzymes showed no significant change. For monitoring of occupational organophosphate exposure, the importance of both clinical and biochemical parameters is emphasised.

Adult↗
PubMed2006

Potential risk of pathogen transmission by acaricide-poisoned ticks.

Many aspects of tick poisoning with acaricides have yet to be elucidated. One of them is the influence of acaricide poisoning on tick infectivity to their hosts. To clarify this problem, we should know how tick poisoning develops after acaricide application. Data obtained during more than three decades of work with ticks of various species and with acaricides of different groups are presented in the paper. The first important phenomenon found was the gradual and progressive development of toxic symptoms after acaricide application, with death of the treated ticks delayed for days or even weeks ('slow-death syndrome'). The development of symptoms was much faster after the application of fenthion, an organophosphorous acaricide, when compared to DDT, a chlorinated hydrocarbon. The larger the adult ticks of a particular species, the more refractory they were to acaricide action. The duration of the development of toxic symptoms directly correlates with the degree of species-specific refractoriness. A special index T(LD(50)) (T(LC(50)) was introduced for comparing the duration of the poisoning development between different tick species, populations etc. The index determines the time when the final mortality is reached after using the LD(50) of a particular acaricide. Another index , T(LD(90)), was used for practical purposes. The values of these indices decreased with increasing age of tick populations. The prolonged duration of poisoning was also observed in nymphal ticks of species with a prolonged life-span and the ability to over-winter (Ixodes, Haemaphysalis) but not in ticks characterized by a short life-span (Dermacentor). During the entire period of poisoning, from acaricide application until tick death, the individual tick passes through six stages defined by its locomotor capabilities. The stages are the same for nymphs and adults of both hard and soft ticks after treatment with various acaricides. When ticks are at the initial stages of poisoning (1st to 3rd stage for DDT or 1st to 2nd for fenthion), they can attach to hosts and imbibe blood. The average body weight of such ticks after repletion corresponded to that of control ticks. Engorged nymphal ticks normally molted to adults, engorged females normally oviposited, and their progeny did not differ from the progeny of control females. This second important phenomenon, called 'overcoming the poisoning', was observed in all studied species of ticks from several genera. Thus, the slow development of tick poisoning creates a potential for ticks to attach to hosts and to gorge blood, and for infected ticks to transmit pathogens to those hosts, while the ability to overcome the poisoning allows the ticks to survive and makes possible the subsequent trans-stadial and transovarial passage of pathogens. These data can be considered as strong circumstantial evidence of the risk that ticks can present to humans and animals at the initial stages of poisoning after acaricide treatment.

Aging↗
PubMed2005

Effect of interleukin-10 on pancreatic damage caused by organophosphate poisoning.

Organophosphate poisoning is a common cause of severe morbidity and mortality in emergency departments. Acute pancreatitis is a frequently reported consequence of organophosphate poisoning, but preventing this potentially severe complication has not been the subject of much research. We tested whether interleukin-10, a cytoprotective agent, could prevent or diminish pathological signs of acute pancreatitis caused by organophosphate poisoning. Thirty rats were divided into three equal groups. Group 1 did not receive any agent during the experiment. Group 2 received 0.8 g/kg fenthion intraperitoneally, followed by 6 ml/kg intraperitoneal normal saline 30 min and 3 h later. Group 3 received 0.8 g/kg fenthion intraperitoneally, followed by 2 microg/kg of interleukin-10 intraperitoneally 30 min and 3 h later. All rats underwent laparotomy and thoracotomy while still under anesthesia at 6 h, and tissue samples were obtained from the pancreas. After blood samples were taken by cardiac puncture, the animals were sacrificed. Organophosphate poisoning resulted in significant elevations of serum amylase and glucose. Interleukin-10 significantly reduced pancreatic damage as determined by pathologic scoring, but not by enzyme elevations. Interleukin-10 should be considered for larger studies in other animal models to confirm its ability to decrease pancreatic damage after organophosphate poisoning treatment with interleukin-10.

Acute Disease↗
PubMed2000

Rapid and cost-effective multiparameter toxicity tests for soil microorganisms.

Three biochemical parameters, DNA quantification in soil samples and two enzymatic activities, beta-galactosidase and dehydrogenase have been assessed as potential end-points for the use in cost-effective toxicity tests on soil microorganisms. The assessment included the development of a classical dose-response 24-h assay and the incorporation of measurements of the effects on microbial activities in soil column leaching studies and multispecies miniaturised terrestrial systems (MTS). Four different chemicals, copper, a new herbicide, thiabendazole and fenthion were studied. A rapid fluorescence DNA quantification technique did not produce adequate responses. The efforts to quantify DNA after extraction and clean-up procedures failed due to the presence of humic acids. From the protocol of the technique one could see that the technical procedure is time-consuming and expensive and, for this reason, not suitable for use as a parameter in rapid and cost-effective tests. However, the enzymatic activities showed their potential as toxicity end-points. Copper produced a concentration/response inhibition of beta-galactosidase and dehydrogenase with EC50 values of 78.39 and 24.77 mg Cu/kg soil, respectively. In the soil column study, these endpoints allowed the measurement of the microbial activities through the column. The effects of the new herbicide on beta-galactosidase and dehydrogenase activities were statistically significant for the highest application dose (40 g/ha). Thiabendazole affected the microbial activity when mixed within the soil, but no effects were observed when this fungicide was applied on the soil surface. Fenthion produced effects when applied either in the soil or on the soil surface. These results can be explained by the low mobility of thiabendazole. The results show the capabilities of these biochemical parameters to be included as endpoints in cost-effective bioassays.

Biological Assay↗
PubMed2005

A physiologically based pharmacokinetic model of organophosphate dermal absorption.

The rate and extent of dermal absorption are important in the analysis of risk from dermal exposure to toxic chemicals and for the development of topically applied drugs, barriers, insect repellents, and cosmetics. In vitro flow-through cells offer a convenient method for the study of dermal absorption that is relevant to the initial processes of dermal absorption. This study describes a physiologically based pharmacokinetic (PBPK) model developed to simulate the absorption of organophosphate pesticides, such as parathion, fenthion, and methyl parathion through porcine skin with flow-through cells. Parameters related to the structure of the stratum corneum and solvent evaporation rates were independently estimated. Three parameters were optimized based on experimental dermal absorption data, including solvent evaporation rate, diffusivity, and a mass transfer factor. Diffusion cell studies were conducted to validate the model under a variety of conditions, including different dose ranges (6.3-106.9 microg/cm2 for parathion; 0.8-23.6 microg/cm2 for fenthion; 1.6-39.3 microg/cm2 for methyl parathion), different solvents (ethanol, 2-propanol and acetone), different solvent volumes (5-120 microl for ethanol; 20-80 microl for 2-propanol and acetone), occlusion versus open to atmosphere dosing, and corneocyte removal by tape-stripping. The study demonstrated the utility of PBPK models for studying dermal absorption, which can be useful as explanatory and predictive tools that may be used for in silico hypotheses generation and limited hypotheses testing. The similarity between the overall shapes of the experimental and model-predicted flux/time curves and the successful simulation of altered system conditions for this series of small, lipophilic compounds indicated that the absorption processes that were described in the model successfully simulated important aspects of dermal absorption in flow-through cells. These data have direct relevance to topical organophosphate pesticide risk assessments.

Administration, Cutaneous↗
PubMed1979

Efficiency and safety of methidathion applied as a pour-on systemic insecticide for control of cattle lice.

Methidathion applied to cattle as a pour-on insecticide for control of lice (predominantly Linognathus vituli, but also Haematopinus eurysternus and Damalinia bovis) caused a reduction in the lice population of approximately 98% to 99% in laboratory trials at the minimum recommended dose of 4 mg/kg and a 98.8% to 100% efficiency was achieved in field trials. In a comparative efficiency trial in the laboratory methidathion at 3.5 to 5 mg/kg reduced the lice population by 98.8% to 99%, fenthion by 98.5% at 4.5 mg/kg and famphur by 99.7% at 16.5 mg/kg. Methidathion was tolerated by calves aged 15 to 20 weeks at dose rates up to 40 mg/kg indicating an approximate 7 fold safety margin, but 1 of 4 calves treated at 50 mg/kg died following treatment. Treatment with fenthion at 50 mg/kg, 7.4 times the average recommended rate, famphur at 75 mg/kg, 3 times the average rate and chlorpyrifos at 85 mg/kg, 5 times average rate, caused reductions in whole blood cholinesterase activity of 52%, 27% and 47% respectively which were similar to the reductions in cholinesterase activity found in calves treated with methidathion at similar levels above the recommended commercial dose rates. It was found that 2 day old calves were more sensitive to treatment with methidathion than calves 9 or 16 days old. A further 11,900 cattle of varying age, breed and sex were treated with methidathion under field conditions at the recommended rate of 4 to 8 mg/kg, and 534 cattle were treated at 24 mg/kg without any signs of toxicity.

Animals↗
PubMed1985

Some observations on the macula of pesticide workers.

To study the retinal changes in occupationally exposed pesticide workers, 79 subjects exposed to an organophosphate, fenthion, and 18 exposed to an organochlorine pesticide DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane], were subjected to a detailed study, including history taking, physical examination and ophthalmic evaluation. Fluorescein angiography was performed in selected cases. Serum cholinesterase level in 22 workers and serum DDT residue in 17 workers of the respective groups were also estimated. Fifteen workers (19%), who were exposed to fenthion had macular changes (P less than 0.01). The macular lesions were characterized by perifoveal irregularity of pigmentation and areas of hypopigmentation of 1/8-1/3 disc diameter. Mean age of the subjects having macular involvement was 30.6 years and mean duration of exposure 7.9 years. The symptoms reported by them were diminution of vision (8), dislike for bright light, flash of light, black dots in front of the eyes (2 each) and visual blurring (1). Paracentral scotoma and constriction of peripheral field were present in three workers each. Fluorescein angiography suggested pigment epithelium defect. Other causes of macular involvement in these workers were excluded; a possible role of pesticides in the genesis of these macular changes is suggested.

Adolescent↗
PubMed1995

Extrapyramidal manifestations complicating organophosphorus insecticide poisoning.

Six patients who developed extrapyramidal manifestations following poisoning with the organophosphorus (OP) insecticide fenthion are reported. The extrapyramidal features, in order of frequency, were dystonia, rest tremor, cog-wheel rigidity, and choreo-athetosis. The delay in onset of these signs, following poisoning, varied from 4 to 40 days, and they disappeared spontaneously in about 1 to 4 weeks in those who survived. The human extrapyramidal system is rich in cholinergic neurons and acetylcholinesterase (AChE). Inhibition of AChE by fenthion, which has ready access to central neurons on account of its lipid solubility, is postulated as the mechanism underlying the extrapyramidal manifestations.

Adult↗