Different Clinical Courses for Poisoning with WHO Hazard Class Ia Organophosphates EPN, Phosphamidon, and Terbufos in Humans

PURPOSE: Extremely hazardous pesticides are classified as World Health Organization (WHO) hazard class Ia. However, data describing the clinical course of WHO class Ia OP (organophosphate) poisonings in humans are very scarce. Here, we compare the clinical features of patients who ingested hazard class Ia OPs. METHODS: This retrospective observational case study included 75 patients with a history of ingesting ethyl p-nitrophenol thio-benzene phosphonate (EPN), phosphamidon, or terbufos. The patients were divided according to the chemical formulation of the ingested OP. Data regarding mortality and the development of complications were collected and compared among groups. RESULTS: There were no differences in the baseline characteristics and severity scores at presentation between the three groups. No fatalities were observed in the terbufos group. The fatality rates in the EPN and phosphamidon groups were 11.8% and 28.6%, respectively. Patients poisoned with EPN developed respiratory failure later than those poisoned with phosphamidon and also tended to require longer mechanical ventilatory support than phosphamidon patients. The main cause of death was pneumonia in the EPN group and hypotensive shock in the phosphamidon group. Death occurred later in the EPN group than in the phosphamidon group. CONCLUSION: Even though all three drugs are classified as WHO class Ia OPs (extremely hazardous pesticides), their clinical courses and the related causes of death in humans varied. Their treatment protocols and predicted outcomes should therefore also be different based on the chemical formulation of the OP.

New magnetic graphene-based inorganic-organic sol-gel hybrid nanocomposite for simultaneous analysis of polar and non-polar organophosphorus pesticides from water samples using solid-phase extraction.

A new graphene-based tetraethoxysilane-methyltrimethoxysilane sol-gel hybrid magnetic nanocomposite (Fe3O4@G-TEOS-MTMOS) was synthesised, characterized and successfully applied in magnetic solid-phase extraction (MSPE) for simultaneous analysis of polar and non-polar organophosphorus pesticides from several water samples. The Fe3O4@G-TEOS-MTMOS nanocomposite was characterized using Fourier transform-infrared spectroscopy, energy-dispersive X-ray spectroscopy, field emission scanning electron microscopy and X-ray diffraction. Separation, determination and quantification were achieved using gas chromatography coupled with micro electron capture detector. Adsorption capacity of the sorbent was calculated using Langmuir equation. MSPE was linear in the range 100-1000 pg mL-1 for phosphamidon and dimethoate, and 10-100 pg mL-1 for chlorpyrifos and diazinon, with limit of detection (S/N = 3) of 19.8, 23.7, 1.4 and 2.9 pg mL-1 for phosphamidon, dimethoate, diazinon and chlorpyrifos, respectively. The LODs obtained is well below the maximum residual level (100 pg mL-1) as set by European Union for pesticides in drinking water. Acceptable precision (%RSD) was achieved for intra-day (1.3-8.7%, n = 3) and inter-day (7.6-17.8%, n = 15) analyses. Fe3O4@G-TEOS-MTMOS showed high adsorption capacity (54.4-76.3 mg g-1) for the selected OPPs. No pesticide residues were detected in the water samples analysed. Excellent extraction recoveries (83-105%) were obtained for the spiked OPPs from tap, river, lake and sea water samples. The newly synthesised Fe3O4@G-TEOS-MTMOS showed high potential as adsorbent for OPPs analysis.

Ginger extract ameliorates phosphamidon induced hepatotoxicity.

Organophosphorus (OP) compounds commonly used as pesticides in agriculture cause serious health problems to living beings. The present study enumerates the ameliorating effect of ginger extract (GE) against phosphamidon (PHO, an organophosphorus insecticide) induced hepatotoxicity. GE was prepared from dried ginger and characterized for compound profile and antioxidant activity. Eight groups of albino rats (n = 6) were treated with 1/5th lethal dose of PHO for 5-20 days. Out of the treated 8 groups, 4 were simultaneously fed with GE (1 mg/kg body wt.) along with PHO. Alterations in the levels of hepatocellular oxidative stress (OS) markers in the treated groups indicated an enhanced generation of reactive oxygen species (ROS) and oxidative stress (OS). Upregulation of apoptotic markers, DNA fragmentation and appearance of apoptotic nuclei suggested induction of apoptosis in the liver cell that was found to be attenuated after GE treatment. Moreover, no toxicity and mortality was observed up to 100 mg/kg dose of GE for 30 days in the rat model studied. Thus, GE can be considered as an effective, economical and safe extract to circumvent PHO-induced hepatotoxicity.

Neurotoxic impact of organophosphate pesticide phosphomedon on the albino rat.

Organophosphate pesticide phosphomedon was exposed to albino rat at a concentration of 35 ppm in the time interval of 30, 45 and 60 days. During the exposure period neurobehavioral symptoms such as reduce food intake, weight loss, increase water intake, low defecation frequency, increase locomotion frequency at high dose were observed. Locomotion frequency were less initially but higher in increasing dose concentration. The result was also different in both the sexes. A decrease social interaction and increase force swimming with increasing dose concentration, which was not significant as comparison to control. A significant histopathological changes observed in three dose concentrations. In 30 days phosphomedon exposure the nuclear shape changes to oval, pear shaped along with fibrosis, lipidosis, 45 days exposure showed the increase number of nucleus, Chromatolysis, inflammatory nucleus, pyknosis. In 60 days test group histopathological picture showed the swelling of cell body, lipidosis, demylination, necrosis in brain cells. Over all result indicated that due to impact of O. P pesticide phosphomedon a severe histopathological changes occurs which was distinctly observed in neurobehavioural changes.

Melatonin attenuates cognitive dysfunction and reduces neural oxidative stress induced by phosphamidon.

Melatonin is an important modulator of nervous system functioning and important neural antioxidant. Organophosphate pesticides like phosphamidon (PHOS) have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. This study was designed to explore the modulation of the effects of PHOS on cognitive function by melatonin (MEL). Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of malondialdehyde (MDA) and nonprotein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and prolongation of TL in the PHOS (1.74 mg/kg/day; p.o.)-treated group at weeks 6 and 8 as compared to the control group. Two-week treatment with MEL (5 mg/kg/day; i.p.) antagonized the effect of PHOS on SDL as well as TL. PHOS alone produced a significant increase in the brain MDA levels and decrease in the brain NP-SH levels. Treatment with MEL attenuated the effect of PHOS on oxidative stress. Together the results showed that MEL attenuated the cognitive dysfunction and decreased oxidative stress induced by PHOS in the brain.

Effect of piracetam and vitamin E on phosphamidon-induced impairment of memory and oxidative stress in rats.

Organophosphate pesticides, such as phosphamidon (PHOS), have been shown to adversely affect memory and induce oxidative stress after both acute and chronic exposure. The present study was therefore designed to investigate the effects of piracetam (PIR) and vitamin E on PHOS-induced modulation of cognitive function and oxidative stress in rats. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of malondialdehyde (MDA) and nonprotein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and a prolongation of TL in the PHOS (1.74 mg/kg/day per oral; p.o.)-treated group at weeks 6 and 8, as compared to the control group. Administration of PIR (600 mg/kg/day p.o.) or vitamin E (125 mg/kg/day p.o.) for 2 weeks antagonized the effect of PHOS on SDL as well as TL. PHOS per se produced a significant increase in brain MDA levels and a decrease in brain NP-SH levels, whereas administration of PIR (600 mg/kg/day p.o.) or vitamin E (125 mg/kg/day p.o.) attenuated these effects. Thus, the results of the study showed that both PIR and vitamin E attenuated the cognitive dysfunction and oxidative stress induced by PHOS in the rat brain.

Effect of phosphamidon on cognition and oxidative stress and its modulation by ascorbic acid and 4'-chlorodiazepam in rats.

Neurosteroids and micronutrient are known to possess neuromodulator and neuroprotective activities. The present study was designed to investigate the effect of 4'-chlorodiazepam (4CD) or ascorbic acid (Vit C) on phosphamidon (PM) induced modulation of cognitive function and oxidative stress in male Wistar rats. Cognitive function was measured by using step-down latency (SDL) on a continuous avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was estimated by measuring brain malondialdehyde (MDA) level, protein carbonyl (PC) and reduced glutathione (GSH) activity. A significant reduction in both acquisition and retention in SDL was found for the PM treated group at weeks 6 and 8 as compared to the control (p<0.001). PM caused a significant prolongation in both acquisition and retention in TL at 6 and 8 weeks as compared to the control (p<0.001). Two-week treatment of 4CD or Vit C antagonized the effect of PM on SDL and TL at 8th week. PM produced a statistically significant increase in the brain MDA and PC levels (p<0.001) and a significant decrease in the brain GSH activity (p<0.001). Treatment with 4CD or Vit C attenuated the effect of PM on MDA, PC and GSH activities. Results of this study suggest that Vit C and 4CD have potential in reversing cognitive dysfunction and oxidative stress induced by toxicants like PM in the brain.

Purification and characterization of carboxylesterase from the seeds of Jatropha curcas.

Carboxylesterases are hydrolases which catalyze the hydrolysis of various types of esters. Carboxylesterase from the seeds of Jatropha curcas has been purified to homogeneity using ammonium sulfate fractionation, CM-cellulose chromatography, Sephadex G-100 chromatography and preparative polyacrylamide gel electrophoresis (PAGE). The homogeneity of the purified enzyme was confirmed by PAGE, iso-electrofocusing and SDS-PAGE. The molecular weight of the purified enzyme was determined by both gel-permeation chromatography on Sephadex G-150 and SDS-PAGE. The molecular weight determined by Sephadex G-150 chromatography and SDS-PAGE both in the presence and absence of 2-mercaptoethanol was 31 kDa. The isoelectric point of the purified enzyme was found to be 8.9. JCSE-I (J. curcas seed esterase-I) was classified as carboxylesterase on the basis of substrate and inhibitor specificity. The K(m) of JCSE-I with 1-naphthyl acetate, 1-naphthyl propionate, 1-naphthyl butyrate and 2-naphthyl acetate as substrates were found to be 0.0,794, 0.0,658, 0.0,567 and 0.1 mM, respectively. The enzyme exhibited an optimum temperature of 45 °C and an optimum pH of 6.5. The enzyme was stable up to 15 min at 65 °C. The enzyme was resistant towards carbamates (carbaryl and eserine sulfate) and sulphydryl inhibitors (p-chloromercuricbenzoate, PCMB) and inhibited by organophosphates (dichlorvos, parathion and phosphamidon).

Age-related differences in acute neurotoxicity produced by mevinphos, monocrotophos, dicrotophos, and phosphamidon.

Age-related differences in the acute neurotoxicity of cholinesterase (ChE)-inhibiting pesticides have been well-studied for a few organophosphates, but not for many others. In this study, we directly compared dose-responses using brain and red blood cell (RBC) ChE measurements, along with motor activity, for mevinphos, monocrotophos, dicrotophos, and phosphamidon. Long-Evans hooded male rats were tested as adults and at postnatal day (PND) 17; PND11 pups were also tested with dicrotophos only. All chemicals were administered via oral gavage and tests were conducted at times intended to span peak behavioral and ChE effects. All OPs tested produced a rapid onset and recovery from the behavioral effects. There were age-related differences in the inhibition of brain, but not necessarily RBC, ChE. Mevinphos was clearly more toxic, up to 4-fold, to the young rat. On the other hand, monocrotophos, dicrotophos, and phosphamidon were somewhat more toxic to the young rat, but the magnitude of the differences was < 2-fold lower. Motor activity was consistently decreased in adults for all chemicals tested; however, there was more variability with the pups and clear age-related differences were only observed for mevinphos. These data show that three of these four OPs were only moderately more toxic in young rats, and further support findings that age-related differences in pesticide toxicity are chemical-specific.

Effect of progesterone on phosphamidon-induced impairment of memory and oxidative stress in rats.

Progesterone (a neurosteroid) is an important modulator of the nervous system functioning. Organophosphorus pesticides like phosphamidon have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. The present study was therefore designed to investigate the effects of progesterone (PROG) on phosphamidon-induced modulation of cognitive function and oxidative stress in rats. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of thiobarbituric acid reactive species (TBARS) and non-protein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and prolongation of TL in the phosphamidon (1.74 mg/kg/d; p.o.) treated group at weeks 6 and 8 as compared to the control group. Two weeks treatment with PROG (15 mg/kg/d; i.p.) antagonized the effect of phosphamidon on SDL as well as TL. Phosphamidon alone produced a significant increase in the brain TBARS levels and decrease in the brain NP-SH levels. Treatment with PROG (15 mg/kg/d; i.p.) attenuated the effect of phosphamidon on oxidative stress. Together, the results showed that progesterone attenuated the cognitive dysfunction and increased oxidative stress induced by phosphamidon in the brain.

Ameliorating effect of N-acetylcysteine and curcumin on pesticide-induced oxidative DNA damage in human peripheral blood mononuclear cells.

Endosulfan, malathion, and phosphamidon are widely used pesticides. Subchronic exposure to these contaminants commonly affects the central nervous system, immune, gastrointestinal, renal, and reproductive system. There effects have been attributed to increased oxidative stress. This study was conducted to examine the role of oxidative stress in genotoxicity following pesticide exposure using peripheral blood mononuclear cells (PBMC) in vitro. Further possible attenuation of genotoxicity was studied using N-acetylcysteine (NAC) and curcumin as known modulators of oxidative stress. Cultured mononuclear cells was isolated from peripheral blood of healthy volunteers, and exposed to varying concentrations of different pesticides: endosulfan, malathion, and phosphamidon for 6, 12, and 24 h. Lipid peroxidation was assessed by cellular malondialdehyde (MDA) level and DNA damage was quantified by measuring 8-hydroxy-2'-deoxyguanosine (8-OH-dG) using ELISA. Both MDA and 8-OH-dG were significantly increased in a dose-dependent manner following treatment with these pesticides. There was a significant decrease in MDA and 8-OH-dG levels in PBMC when co-treated with NAC or/and curcumin as compared to pesticide alone. These results indicate that pesticide-induced oxidative stress is probably responsible for the DNA damage, and NAC or curcumin attenuate this effect by counteracting the oxidative stress.

Assessment of phosphamidon-induced apoptosis in human peripheral blood mononuclear cells: protective effects of N-acetylcysteine and curcumin.

The molecular mechanism for noncholinergic toxicity of phosphamidon, an extensively used organophosphate pesticide, is still not clear. The aim of the present study is to find the possible molecular mechanism of this pesticide to induce apoptosis and the role of different drugs for attenuation of such effects. Human peripheral blood mononuclear cells (PBMC) were incubated with increasing concentrations of phosphamidon (0-20 µM) for 6-24 h. The MTT assay reveals that phosphamidon induces cytotoxicity in a dose-dependent manner. Cellular glutathione (GSH) is depleted in a dose-dependent manner from 55% to 70% at concentrations between 10 and 20 µM. The percentage of cells that bind to Annexin-V, which is a representative of cells either undergoing apoptosis or necrosis during 24 h incubation, increases in a dose-dependent manner. Above 5 µM, significant necrosis of cells was observed. DNA fragmentation assay revealed that at low concentration of phosphamidon (1 µM), no appreciable change in DNA fragmentation was seen; however, distinct fragmentation was observed beyond 2.5 µM. Phosphamidon was found to cause significant depletion of GSH, which correlates well with the percentage of cells undergoing apoptosis. An increasing trend in levels of cytochrome c was observed with increasing concentration of phosphamidon, indicating that the apoptotic effect of phosphamidon is mediated through cytochrome c release. Coadministration of the antioxidants N-acetylcysteine and curcumin attenuated phosphamidon-induced apoptosis. This further supports our hypothesis that oxidative stress, as indicated by GSH depletion, results in the induction of apoptosis by release of cytochrome c.

Effect of phosphamidon on convulsive behavior and biochemical parameters: modulation by progesterone and 4'-chlorodiazepam in rats.

Phosphamidon (PHOS) has been shown to affect nervous system adversely. The present study was designed to explore the modulation of the effects of PHOS on convulsions by neurosteroids, progesterone (PROG), and 4'-chlorodiazepam (4'-CD), in both acute and chronic seizure models. In acute study, seizures were induced by either pentylenetetrazole (PTZ) injection or maximal electroshock seizures, while in the chronic study, kindling was induced by injecting PTZ (30 mg/kg, s.c.) on alternate days three times in a week. Oxidative stress was assessed in the brain by measuring the levels of malondialdehyde (MDA), acetylcholinesterase (AChE), and non-protein thiol (NP-SH). PROG and 4'-CD were able to modulate the PHOS-induced convulsions in acute PTZ convulsions as well as in chronic kindling model. However, they failed to reverse the derangements in oxidative stress parameters of MDA and NP-SH produced by PHOS in kindled animals. PROG significantly increased the AChE activity in untreated rats, while PROG and 4'-CD reversed the AChE activity inhibition induced by PHOS. The study indicates a possible anticonvulsive mechanism of neurosteroids, since both PROG and 4'-CD reversed PHOS-induced inhibition of AChE activity. The neurosteroids seem to play a protective role in PHOS-induced convulsions besides their antioxidant property.

Determination of organophosphorous pesticide phosphamidon in environmental water with luminol chemiluminescence detection.

A novel chemiluminescence method has been developed for the determination of the organophosphorous pesticide phosphamidon in environmental water samples, based on the reaction of phosphamidon with luminol-H2O2 in an alkaline medium using sodium dodecyl benzene sulfonate as the enhancer. Under optimum conditions, the increased chemiluminescence intensity was proportional to the concentration of phosphamidon in the range of 0.01-1.0 microg/mL and the detection limit was 0.0038 microg/mL (3 sigma). The relative standard deviation was <2% for 0.5 microg/mL phosphamidon (n = 11). The proposed method was applied to the determination of phosphamidon residue in an environmental water sample with satisfactory results. Further study was focused on the mechanism of phosphamidon, and a possible mechanism was proposed.

Determination of pesticides and toxic potency of rainwater samples in western Greece.

Rainwater samples from four municipalities located in Achaia Prefecture, Greece, were collected from March to September 2006. The toxic potency of pollutants present in 36 rainwater samples was tested using Daphnia pulex. The pesticide determination was conducted with GC-MS. Only phosphamidon was detected, which appeared in 52% and 13% of the rural and urban areas, respectively. The toxicity of rainwater was determined in 52% and 46.7% of the rural and urban area samples, respectively. Chemical analyses showed that in rural areas, the PO(4)(3-) ions had higher concentrations than in urban areas. On the other hand, the SO(4)(2-), NO(-)(3), and NO(-)(2) anions are more highly concentrated in urban areas. Correlation analysis proved that the toxicity of the rainwater samples is moderate, affected by the presence of the insecticide only in the rural areas. The results indicated that toxicity can be directly assessed via bioassays, even when unknown pollutants are present.

The Variations in Clinical Features According to Intoxicants in High Toxicity Organophosphorus Intoxication

PURPOSE: Organophosphorus (OP) pesticides are differentiated into 3 groups according to their toxicity. The differences in chemical composition of each OP pesticide determines its toxicokinetic characteristics. There are few human studies that address the clinical results of poisoning according to the OP pesticide. In this study, we aimed to examine the differences in clinical features among self-poisoning from 4 highly toxic OP pesticides. METHODS: The 4 kinds of OP poisonings included 17 cases of Dichlorvos, 17 cases of EPN, 17 cases of methidathion, and 13 cases of phosphamidon. We set primary outcomes as GCS, atropine dose required, duration of patient need for atropine, proportion who required ventilation, duration on ventilation, and the interval from ingestion to ventilation. Secondary outcomes were the proportion of OP-induced delayed neuropathy, duration of ICU stay, and proportion who required additional infusion of pralidoxime chloride (PAM). RESULTS: The EPN group required the largest amount of atropine, the longest duration of atropine use, the longest duration for support of mechanical ventilation, and the longest ICU stay. Furthermore the proportion who required additional PAM and neuropathy were in the EPN group. However, the EPN group had the longest interval from ingestion to ventilatory support. Meanwhile, the Dichlorvos group exhibited comparatively mild clinical features. CONCLUSION: Throughout this study, we found different clinical features to each OP pesticide poisoning. It can be explained by differences in chemical composition, which determined the speed of aging, the reactivation rate of OPenzyme, the metabolism, the fat solubility, and other characteristics of the pesticides.

Attenuation of phosphamidon-induced oxidative stress and immune dysfunction in rats treated with N-acetylcysteine.

The effect of N-acetylcysteine, a thiolic antioxidant, on attenuation of phosphamidon-induced oxidative stress and immune dysfunction was evaluated in adult male Wistar rats weighing 200-250 g. Rats were divided into four groups, 8 animals/group, and treated with phosphamidon, N-acetylcysteine or the combination of both for 28 days. Oral administration of phosphamidon (1.74 mg/kg), an organophosphate insecticide, increased serum malondialdehyde (3.83 +/- 0.18 vs 2.91 +/- 0.24 nmol/mL; P < 0.05) and decreased erythrocyte superoxide dismutase (567.8 +/- 24.36 vs 749.16 +/- 102.61 U/gHb; P < 0.05), catalase activity (1.86 +/- 0.18 vs 2.43 +/- 0.08 U/gHb; P < 0.05) and whole blood glutathione levels (1.25 +/- 0.21 vs 2.28 +/- 0.08 mg/gHb; P < 0.05) showing phosphamidon-induced oxidative stress. Phosphamidon exposure markedly suppressed humoral immune response as assessed by antibody titer to ovalbumin (4.71 +/- 0.51 vs 8.00 +/- 0.12 -log(2); P < 0.05), and cell-mediated immune response as assessed by leukocyte migration inhibition (25.24 +/- 1.04 vs 70.8 +/- 1.09%; P < 0.05) and macrophage migration inhibition (20.38 +/- 0.99 vs 67.16 +/- 5.30%; P < 0.05) response. Phosphamidon exposure decreased IFN-small u, Cyrillic levels (40.7 +/- 3.21 vs 55.84 +/- 3.02 pg/mL; P < 0.05) suggesting a profound effect of phosphamidon on cell-mediated immune response. A phosphamidon-induced increase in TNF-alpha level (64.19 +/- 6.0 vs 23.16 +/- 4.0 pg/mL; P < 0.05) suggests a contributory role of immunocytes in oxidative stress. Co-administration of N-acetylcysteine (3.5 mmol/kg, orally) with phosphamidon attenuated the adverse effects of phosphamidon. These findings suggest that oral N-acetylcysteine treatment exerts protective effect and attenuates free radical injury and immune dysfunction caused by subchronic phosphamidon exposure.

Attenuation of phosphamidon-induced oxidative stress and immune dysfunction in rats treated with N-acetylcysteine

The effect of N-acetylcysteine, a thiolic antioxidant, on attenuation of phosphamidon-induced oxidative stress and immune dysfunction was evaluated in adult male Wistar rats weighing 200-250 g. Rats were divided into four groups, 8 animals/group, and treated with phosphamidon, N-acetylcysteine or the combination of both for 28 days. Oral administration of phosphamidon (1.74 mg/kg), an organophosphate insecticide, increased serum malondialdehyde (3.83 ± 0.18 vs 2.91 ± 0.24 nmol/mL; P < 0.05) and decreased erythrocyte superoxide dismutase (567.8 ± 24.36 vs 749.16 ± 102.61 U/gHb; P < 0.05), catalase activity (1.86 ± 0.18 vs 2.43 ± 0.08 U/gHb; P < 0.05) and whole blood glutathione levels (1.25 ± 0.21 vs 2.28 ± 0.08 mg/gHb; P < 0.05) showing phosphamidon-induced oxidative stress. Phosphamidon exposure markedly suppressed humoral immune response as assessed by antibody titer to ovalbumin (4.71 ± 0.51 vs 8.00 ± 0.12 -log2; P < 0.05), and cell-mediated immune response as assessed by leukocyte migration inhibition (25.24 ± 1.04 vs 70.8 ± 1.09%; P < 0.05) and macrophage migration inhibition (20.38 ± 0.99 vs 67.16 ± 5.30%; P < 0.05) response. Phosphamidon exposure decreased IFN-у levels (40.7 ± 3.21 vs 55.84 ± 3.02 pg/mL; P < 0.05) suggesting a profound effect of phosphamidon on cell-mediated immune response. A phosphamidon-induced increase in TNF-α level (64.19 ± 6.0 vs 23.16 ± 4.0 pg/mL; P < 0.05) suggests a contributory role of immunocytes in oxidative stress. Co-administration of N-acetylcysteine (3.5 mmol/kg, orally) with phosphamidon attenuated the adverse effects of phosphamidon. These findings suggest that oral N-acetylcysteine treatment exerts protective effect and attenuates free radical injury and immune dysfunction caused by subchronic phosphamidon exposure.

Clinical Characteristics of Acute Dichlorvos Poisoning in Korea

Purpose: Dichlorvos has been in widespread use as an organophosphate (OP) insecticide compound. The purpose of this study was to access the epidemiology and clinical features of dichlorvos in Korea. Methods: This was a 38 multi-center prospective study of dichlorvos poisoning using surveys, a structural reporting system and review of hospital records from August 2005 to July 2006. A total of 54 patients with acute dichlorvos poisoning on a national basis were enrolled. We analyzed the epidemiologic characteristics and clinical manifestations of dichlorvos poisoning. In addition, the clinical features of dichlorvos poisoning were compared with others OP compounds. Results: During the study period, compounds involving pure OP poisoning were dichlorvos (22.7%), methidathion (8.4%), and phosphamidon (6.7%). In acute dichlorvos poisoning, all ingestion routes were oral. Intentional poisoning involved 74.1% of cases. The common initial complaints involved gastrointestinal (64.8%), systemic (61.1%), central or peripheral nervous system (53.7%), and respiratory symptoms (50.0%). The median arrival time to hospital after dichlorvos poisoning was 2.6 hours and mean hospitalization duration was 7.1 days. 2-PAM was administered in 35 patients in mean doses of 6.3 g/day intravenously. Atropine was administered in 30 patients with a mean dose of 62.8 mg/day (maximal 240 mg/day). Overall mortality rate for dichlorvos poisonings were 14.8% (8/54). Immediate causes for death included sudden cardiac arrest or ventricular dysrhythmias (50%), multi-organ failure (25%), acute renal failure (12.5%), and unknown causes (12.5%). Conclusion: When compared to previous reports, dichlorvos poisoning displayed relatively moderate severity. The presence of a lower GCS score, altered mental status, serious dysrhythmias, systemic shock, acute renal failure, and respiratory complications upon presentation were associated with a more serious and fatal poisoning.

Protective effect induced by atropine, carbamates, and 2-pyridine aldoxime methoiodide Artemia salina larvae exposed to fonofos and phosphamidon.

The acute toxicity of fonofos and phosphamidon on three age classes of Artemia salina was evaluated. An increase in toxicity of these organophosphorous (OP) insecticides was found following longer development of A. salina. The effects of pretreatment with the nonselective muscarinic antagonist atropine, the two reversible acetylcholinesterease inhibitors physostigmine and pyridostigmine, and the cholinesterase-reactivating oxime 2-pyridine aldoxime methoiodide (2-PAM), as individual and combined pretreatments, on OP-induced lethality in 24 h Artemia were also investigated. The lethal action of both OP insecticides was prevented by pretreatment of 24 h Artemia with atropine and 2-PAM, while physostigmine proved ineffective against intoxication with both OP insecticides and pyridostigmine exhibited a low synergic effect. In both cases, the inhibitory effects of combinations of atropine (10(-5)M) plus 2-PAM were greater than those elicited by either drug alone, with the maximum protection afforded being 100%. Combined pretreatment of atropine (10(-5)M) plus physostigmine practically abolished the lethal effects induced by both insecticides. Pretreatment with 2-PAM (10(-6)M) plus physostigmine afforded maximal protection of 100% and 76% on the lethality induced by fonofos and phosphamidon, respectively. The data obtained suggest that the combination of atropine plus 2-PAM or physostigmine and the combined pretreatment of 2-PAM plus physostigmine are effective in the prevention of the lethal effects induced by fonofos and phosphamidon in A. salina larvae.