ABSTRACT
Organophosphate pesticides are widely used; however, their use is limited due to neurotoxicity and, to a lesser extent, cardiotoxicity in humans. Given the high energy demands of cardiac muscle, which is characterized by a dense population of mitochondria, any damage to these organelles can exacerbate cardiotoxicity. This study aims to elucidate whether the cardiotoxic effects of organophosphate pesticides originate from mitochondrial dysfunction. To investigate this, in silico toxicogenomic analyses were performed using various tools, such as the Comparative Toxicogenomic Database, GeneMANIA, STRING, and Cytoscape. Results revealed that 11 out of the 13 WHO-recommended Class Ia organophosphate pesticides target genes associated with cardiotoxicity. Notably, three of these genes were mitochondrial, with catalase (CAT) being the common differentially expressed gene among parathion, methyl parathion, and phorate. Furthermore, protein-protein interaction analysis indicated a strong association between CAT and superoxide dismutase 2, mitochondrial (SOD2). Subsequently, isolated heart mitochondria were utilized to assess CAT and superoxide dismutase (SOD) activities in vitro. The findings demonstrated that at a concentration of 7.5 ng/µL, both methyl parathion and phorate significantly decreased CAT activity by approximately 35%. Moreover, phorate reduced total SOD and SOD2 activities by 17% and 19%, respectively, at the same concentration. In contrast, none of the three organophosphate pesticides induced the opening of the mitochondrial permeability transition pore. These results suggest that the reduction in CAT and SOD2 activities, critical antioxidant enzymes, leads to the accumulation of reactive oxygen species within mitochondria, ultimately resulting in mitochondrial damage. This mechanism likely underlies the observed cardiotoxicity induced by these organophosphate pesticides.
ABSTRACT
Extensive use of pesticides in agricultural production has been causing serious health threats to humans and animals. Among them, phorate is a highly toxic organophosphorus insecticide that has been widely used in planting. Due to its harmful effects on human and animal health, it has been restricted for use in many countries. Analytical methods for the rapid and sensitive detection of phorate residues in agricultural products are urgently needed. In this study, a new method was developed by combining surface-enhanced Raman spectroscopy (SERS) and immunochromatography assay (ICA). Hybrid magnetic Fe3O4@Au@DTNB-Ab nanoprobes were prepared by modifying and growing Au nanoseeds on an Fe3O4 core. SERS activity of the nanoprobe was optimized by adjusting the concentration of the Au precursor. A rapid and sensitive assay was established by replacing the traditional colloidal gold-based ICA with hybrid SERS nanoprobes for SERS-ICA. After optimizing parameters including coating antibody concentrations and the composition and pH of the buffer solution, the limit of detection (LOD) for phorate could reach 1 ng/mL, with a linear range of 5~100 ng/mL. This LOD is remarkably lower than the maximum residue limit in vegetables and fruits set by the Chinese government. The feasibility of this method was further examined by conducting a spiking test with celery as the real sample. The result demonstrated that this method could serve as a promising platform for rapid and sensitive detection of phorate in agricultural products.
ABSTRACT
It is highly advantageous to devise an in vitro platform that can predict the complexity of an in vivo system. The first step of this process is the identification of a xenobiotic whose monooxygenation is carried out by two sequential enzymatic reactions. Pesticides are a good model for this type of tandem reactions since in specific cases they are initially metabolised by human flavin-containing monooxygenase 1 (hFMO1), followed by cytochrome P450 (CYP). To assess the feasibility of such an in vitro platform, hFMO1 is immobilised on glassy carbon electrodes modified with graphene oxide (GO) and cationic surfactant didecyldimethylammonium bromide (DDAB). UV-vis, contact angle and AFM measurements support the effective decoration of the GO sheets by DDAB which appear as 3 nm thick structures. hFMO1 activity on the bioelectrode versus three pesticides; fenthion, methiocarb and phorate, lead to the expected sulfoxide products with KM values of 29.5 ± 5.1, 38.4 ± 7.5, 29.6 ± 4.1 µM, respectively. Moreover, phorate is subsequently tested in a tandem system with hFMO1 and CYP3A4 resulting in both phorate sulfoxide as well as phoratoxon sulfoxide. The data demonstrate the feasibility of using bioelectrochemical platforms to mimic the complex metabolic reactions of xenobiotics within the human body.
Subject(s)
Pesticides , Phorate , Humans , Phorate/metabolism , Cytochrome P-450 CYP3A , Sulfoxides/metabolismABSTRACT
Phorate is a systemic, broad-spectrum organophosphorus insecticide. Although it is commonly used worldwide, phorate, like other pesticides, not only causes environmental pollution but also poses serious threats to human and animal health. Herein, we measured the blood glucose concentrations of high-fat-diet-fed mice exposed to various concentrations of phorate (0, 0.005, 0.05, or 0.5 mg/kg); we also assessed the blood glucose concentrations of high-fat-diet-fed mice exposed to phorate; we also assessed the distribution characteristics of the resistance genes in the intestinal microbiota of these mice. We found that 0.005 and 0.5 mg/kg of phorate induced obvious hyperglycaemia in the high-fat-diet-fed mice. Exposure to phorate markedly reduced the abundance of Akkermansia muciniphila in the mouse intestine. The resistance genes vanRG, tetW/N/W, acrD, and evgS were significantly upregulated in the test group compared with the control group. Efflux pumping was the primary mechanism of drug resistance in the Firmicutes, Proteobacteria, Bacteroidetes, Verrucomicrobia, Synergistetes, Spirochaetes, and Actinobacteria found in the mouse intestine. Our findings indicate that changes in the abundance of the intestinal microbiota are closely related to the presence of antibiotic-resistant bacteria in the intestinal tract and the metabolic health of the host.
ABSTRACT
It has been estimated that approximately one in seven of all global suicides is due to pesticide self-poisoning, mostly in rural areas of developing countries. Organophosphorus (OP) compounds are a group of pesticides exerting their toxicological effects through non-reversible inhibition of the enzyme acetylcholinesterase (AChE). Among these compounds, phorate (thimet) is one of the most dangerous compounds, the use of which is restricted in many countries. A case of intentional suicide after phorate ingestion in a 24-year-old Bengali male is described. This is the second case of suicidal ingestion of phorate reported in the forensic literature, and the first presenting complete toxicological findings.
ABSTRACT
Transmission Electron Microscopic (TEM) assessments were performed on the renal cells of common carp Cyprinus carpio to observe the deleterious effects of two organophosphate insecticides, Phorate and Dimethoate. Pesticides such as Phorate and Dimethoate often pollute aquatic systems where they may negatively impact fish, but so far, the ultrastructural toxicity of these pesticides remains poorly understood. Here, we use Transmission Electron Microscopy (TEM) to determine how acute exposure to sublethal concentrations of these two pesticides may affect the renal cells of common carp Cyprinus carpio. For each insecticide, the fish were divided in four experimental conditions: a control and three different exposure concentrations of the pesticide. The Phorate treated fish were exposed to three sublethal concentrations of 0.2 mg/L, 0.4 mg/L, 0.6 mg/L for a duration of 24, 48 & 72 h. The dimethoate treated fish were exposed to three sublethal concentrations of 0.005 mL/L, 0.01 mL/L, 0.015 mL/L for a duration of 24, 48 and 72 h. The two-dimensional transmission electron microscopy revealed ultrastructural abnormalities in the treated fish renal cells when exposed to two toxicants including deformation in the glomerulus, vacuolization of cytoplasm, degenerative nucleus and damaged mitochondria. Furthermore, the ultrastructural abnormalities were more prominent with the increase in the concentrations of both the insecticides and also with their exposure period. Overall, these results provide important baseline data on the ultrastructural toxicity of Phorate and Dimethoate and will allow important follow-up studies to further elucidate the underlying cellular mechanisms of pesticide toxicity in wildlife.
ABSTRACT
Organophosphorus pesticides (OPS) are widely used in the world, and many poisoning cases were caused by them. Phorate intoxication is especially common in China. However, there are currently few methods for discriminating phorate poisoning death from phorate exposure after death and interpretation of false-positive results due to the lack of effective biomarkers. In this study, we investigated the metabonomics of rat plasma at different dose levels of acute phorate intoxication using ultra-performance liquid chromatography quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS) analysis. A total of 11 endogenous metabolites were significantly changed in the groups exposed to phorate at LD50 level and three times of LD50 (3LD50) level compared with the control group, which could be potential biomarkers of acute phorate intoxication. Plasma metabonomics analysis showed that diethylthiophosphate (DETP) could be a useful biomarker of acute phorate intoxication. The levels of uric acid, acylcarnitine, succinate, gluconic acid, and phosphatidylcholine (PC) (36:2) were increased, while pyruvate level was decreased in all groups exposed to phorate. The levels of ceramides (Cer) (d 18:0/16:0), palmitic acid, and lysophosphatidylcholine (lysoPC) (18:1) were only changed after 3LD50 dosage. The results of this study indicate that the dose-dependent relationship exists between metabolomic profile change and toxicities associated with apoptosis, fatty acid metabolism disorder, energy metabolism disorder especially tricarboxylic acid (TCA) cycle, as well as liver, kidney, and nervous system functions after acute exposure of phorate. This study shows that metabonomics is a useful tool in identifying biomarkers for the forensic toxicology study of phorate poisoning.
Subject(s)
Metabolome , Metabolomics , Organophosphate Poisoning/blood , Organophosphate Poisoning/metabolism , Phorate/blood , Phorate/metabolism , Animals , Biomarkers/blood , Biomarkers/metabolism , Chromatography, High Pressure Liquid , Disease Models, Animal , Lethal Dose 50 , Mass Spectrometry , RatsABSTRACT
Phorate is a systemic organophosphorus pesticide (OP) that acts by inhibiting cholinesterases. Recent studies have reported that long-term low/moderate exposure to OP could be correlated with impaired cardiovascular and pulmonary function and other neurological effects. A 70-year-old farmer died after an intention ingestion of a granular powder mixed with water. He was employed on a farm for over 50 years producing fruit and vegetables, and for about 20 years, he had also applied pesticides. In the last 15 years, he used phorate predominantly. The Phorate concentration detected in gastric contents was 3.29 µg/mL. Chronic exposure to phorate is experimentally studied by histopathological changes observed in the kidney. In the light of current literature, our case confirms that there is an association between renal damage and chronic exposure to phorate in a subject exposed for years to the pesticide. Autopsies and toxicological analyses play a key role in the reconstruction of the dynamics, including the cause of the death.
ABSTRACT
BACKGROUND: Resistance to the dinitroaniline herbicide trifluralin in Lolium rigidum (annual ryegrass) often is mediated by the enhanced capacity to metabolize the herbicide to less toxic polar conjugates and/or by functionally recessive target-site mutations in α-tubulin. RESULTS: In two L. rigidum populations possessing enhanced trifluralin metabolism, resistance was largely reversed by recurrent selection with the thiocarbamate herbicide prosulfocarb (i.e. plant survival was two- to >20-fold lower). Their ability to metabolize trifluralin was significantly decreased (by ≈2.3-fold) following recurrent prosulfocarb selection, to levels comparable to those observed in susceptible plants or when trifluralin metabolism was inhibited by treatment with the insecticide phorate. CONCLUSIONS: This study provides evidence that trait(s) enabling efficient trifluralin metabolism in L. rigidum are purged from the population under prosulfocarb recurrent selection. The level of trifluralin metabolism in vitro and its inhibition caused by phorate action on trifluralin-metabolizing enzyme(s) is equivalent to the effect produced by prosulfocarb selection. The hypothetical link between the two phenomena is that the putative monooxygenase(s) conferring trifluralin metabolic resistance also mediate the activation of prosulfocarb to its toxic sulfoxide. Thus, we speculate that survival to prosulfocarb via a lack of metabolic herbicide activation, and survival to trifluralin conferred by enhanced herbicide metabolism, are mutually exclusive. These findings not only open up a new research direction in terms of the interaction between different herbicide resistance mechanisms in L. rigidum, but also offer strategies for immediate management of the population dynamics of metabolism-based resistance in the field. © 2020 Society of Chemical Industry.
Subject(s)
Herbicides , Lolium , Carbamates , Herbicide Resistance/genetics , Herbicides/pharmacology , Lolium/genetics , Trifluralin/pharmacologyABSTRACT
BACKGROUND: Multiple-herbicide resistance in Lolium rigidum and other weed species is increasingly exerting pressure on herbicide discovery research for solutions against resistance-prone weeds. In this study we investigate: (i) the responses of L. rigidum populations and wheat to the new herbicide cinmethylin in comparison with other pre-emergence herbicides, (ii) the effect of seed burial depths on cinmethylin efficacy and crop selectivity, and (iii) the basis of cinmethylin selectivity in wheat. RESULTS: Cinmethylin at 400 g ha-1 controls herbicide-susceptible and multiple-resistant L. rigidum, with a reduction of >85% in plant emergence and 90% in aboveground biomass. Cinmethylin provides effective control of a large number of field populations of L. rigidum with evident resistance to trifluralin. When the wheat seed is buried ≥1 cm below the cinmethylin-treated soil surface, the emergence of crop seedlings is not different from the untreated control. The organophosphate insecticide phorate synergizes cinmethylin toxicity in wheat, with an LD50 of 682 g ha-1 in the absence of phorate versus 109 g ha-1 in the presence of phorate (84% reduction). The synergistic effect of phorate with cinmethylin on herbicide-susceptible L. rigidum appears smaller (a 44% reduction in the LD50 of cinmethylin). CONCLUSIONS: Cinmethylin is effective in controlling multiple-resistant L. rigidum and appears safe for wheat when the seed is separated at depth from the herbicide applied to the soil surface. The basis of this metabolism-based selectivity is likely regulated by cytochrome P450 monooxygenases. © 2020 Society of Chemical Industry.
Subject(s)
Lolium , Herbicides , Trifluralin , TriticumABSTRACT
Herein, we studied phorate for its toxicological effects in human lymphocytes. Phorate treatment for 3â¯h has induced significant increase in the lymphocytic DNA damage. Compared to control, comet data from highest concentration of phorate (1000⯵M) showed 8.03-fold increase in the Olive tail moment (OTM). Cytokinesis blocked micronucleus (CBMN) assay revealed 6.4-fold increase in binucleated micronucleated (BNMN) cells following the exposure with phorate (200⯵M) for 24â¯h. The nuclear division index (NDI) in phorate (200⯵M) treated cells reduced to 1.8 vis-à-vis control cells showed NDI of 1.94. Comparative to untreated control, 60.43% greater DCF fluorescence was quantitated in lymphocytes treated with phorate (500⯵M), affirming reactive oxygen species (ROS) generation and oxidative stress. Flow cytometric data of phorate (200⯵M) treated lymphocytes showed 81.77% decline in the fluorescence of rhodamine 123 (Rh123) dye, confirming the perturbation of mitochondrial membrane potential (ΔΨm). Calf thymus DNA (ct-DNA) treated with phorate (1000⯵M) exhibited 2.3-fold higher 8-Hydroxy-2'-deoxyguanosine (8-oxodG) DNA adduct formation, signified the oxidative DNA damage. The alkaline unwinding assay revealed 4.0 and 6.5 ct-DNA strand breaks when treated to phorate and phorate-Cu (II) complex. Overall, the data unequivocally suggests the cyto- and genotoxic potential of phorate in human lymphocytes, which may induce comparable toxicological consequences in persons occupationally or non-occupationally exposed to insecticide phorate.
ABSTRACT
ABSTRACT: Objective To investigate the maximum allowable deviation of ion abundance ratios of characteristic fragment ions in common drugs ï¼poisonsï¼ in blood by gas chromatography-mass spectrometry ï¼GC-MSï¼ method. Methods Four common drugs ï¼poisonsï¼ ï¼dichlorvos, phorate, diazepam and estazolamï¼ were detected by GC-MS full scan mode after liquid-liquid extraction in two laboratories and under three chromatographic conditions. The deviations of ion abundance ratios of the four common drugs ï¼poisonsï¼ in marked blood samples with concentrations of 0.5, 1.0, 2.0, 5.0 and 10.0 µg/mL were analyzed. At the same time, the false negative rates of ion abundance ratios were analyzed when the mass concentration was limit of detection ï¼LODï¼, 2LOD, limit of quantitation ï¼LOQï¼ and 2LOQ, and the false positive rates of ion abundance ratios were analyzed with blank blood samples. Results Under the two laboratories, four common drugs ï¼poisonsï¼ and three kinds of chromatography conditions, the differences in deviations of the ion abundance ratios of marked blood samples were not statistically significant ï¼P>0.05ï¼. More than 95% of the absolute deviations of the ion abundance ratios of the marked blood samples were within the range of ±10%, and more than 95% of the relative deviations were within the range of ±25%. In cases of low concentration ï¼concentration less than 2LOQï¼ or low signal to noise ratio ï¼3-15ï¼, the false negative rate was less than 5% and the false positive rate was 0% when the relative deviation was greater than 50%. Conclusion The absolute deviations of ion abundance ratios of four common drugs ï¼poisonsï¼ in marked blood samples are advised to have a determination range within ±10%, and the determination range of relative deviations within ±25%.
Subject(s)
Gas Chromatography-Mass Spectrometry , Ions , Poisons , Humans , Ions/chemistry , Limit of Detection , Liquid-Liquid Extraction , Poisons/analysis , Poisons/bloodABSTRACT
Objective To investigate the maximum allowable deviation of ion abundance ratios of characteristic fragment ions in common drugs (poisons) in blood by gas chromatography-mass spectrometry (GC-MS) method. Methods Four common drugs (poisons) (dichlorvos, phorate, diazepam and estazolam) were detected by GC-MS full scan mode after liquid-liquid extraction in two laboratories and under three chromatographic conditions. The deviations of ion abundance ratios of the four common drugs (poisons) in marked blood samples with concentrations of 0.5, 1.0, 2.0, 5.0 and 10.0 μg/mL were analyzed. At the same time, the false negative rates of ion abundance ratios were analyzed when the mass concentration was limit of detection (LOD), 2LOD, limit of quantitation (LOQ) and 2LOQ, and the false positive rates of ion abundance ratios were analyzed with blank blood samples. Results Under the two laboratories, four common drugs (poisons) and three kinds of chromatography conditions, the differences in deviations of the ion abundance ratios of marked blood samples were not statistically significant (P>0.05). More than 95% of the absolute deviations of the ion abundance ratios of the marked blood samples were within the range of ±10%, and more than 95% of the relative deviations were within the range of ±25%. In cases of low concentration (concentration less than 2LOQ) or low signal to noise ratio (3-15), the false negative rate was less than 5% and the false positive rate was 0% when the relative deviation was greater than 50%. Conclusion The absolute deviations of ion abundance ratios of four common drugs (poisons) in marked blood samples are advised to have a determination range within ±10%, and the determination range of relative deviations within ±25%.
Subject(s)
Humans , Gas Chromatography-Mass Spectrometry , Ions/chemistry , Limit of Detection , Liquid-Liquid Extraction , Poisons/bloodABSTRACT
This work performed a large scale assessment for organophosphorus pesticides (OPPs) degradation activity of 121 Lactobacillus (L.) plantarum strains. Six L. plantarum strains (P9, IMAU80110, IMAU40100, IMAU10585, IMAU10209, and IMAU80070) were found to possess high capacity of degrading three commonly used OPPs, namely dimethoate, phorate, and omethoate; and they were selected for more detailed characterization. Moreover, the three OPPs were mainly detected in the culture supernatants but not in the cell extracts, further confirming that the OPPs were degraded rather than absorbed by the cells. Among the six selected strains, P9 was most tolerant to gastrointestinal juices and bile. We thus used ultra-high performance liquid chromatography electron spray ionization coupled with time-of-flight mass spectrometry (UPLC/ESI-Q-TOF/MS) to generate the metabolomic profiles of the strain P9 growing in MRS medium with and without containing phorate. By using orthogonal partial least squares discriminant analysis, we identified some potential phorate-derived degradative products. This work has identified novel lactic acid bacteria resources for application in pesticide degradation. Our results also shed light on the phorate degradation mechanism by L. plantarum P9.
ABSTRACT
Organophosphorus (OP) compounds, including pesticides and chemical warfare nerve agents (CWNA), are threats to the general population as possible weapons of terrorism or by accidental exposure whether through inadvertent release from manufacturing facilities or during transport. To mitigate the toxicities posed by these threats, a therapeutic regimen that is quick-acting and efficacious against a broad spectrum of OPs is highly desired. The work described herein sought to assess the protective ratio (PR), median effective doses (ED50), and therapeutic index (TI = oxime 24-h LD50/oxime ED50) of MMB4 DMS, HLö-7 DMS, and 2-PAM Cl against the OPs sarin (GB), VX, and phorate-oxon (PHO). All OPs are representative of the broader classes of G and V chemical warfare nerve agents and persistent pesticides. MMB4 DMS and HLö-7 DMS were previously identified as comparative efficacy leads warranting further evaluations. 2-PAM Cl is the U.S. FDA-approved standard-of-care oxime therapy for OP intoxication. Briefly, PRs were determined in male guinea pigs by varying the subcutaneously (SC) delivered OP dose followed then by therapy with fixed levels of the oxime and atropine (0.4 mg/kg; administered intramuscularly [IM]). ED50s were determined using a similar approach except the OP dose was held constant at twice the median lethal dose (2 × LD50) while the oxime treatment levels were varied. The ED50 information was then used to calculate the TI for each OP/oxime combination. Both MMB4 DMS and HLö-7 DMS provided significant protection, i.e., higher PR against GB, VX, and PHO when compared to atropine controls, but significance was not readily demonstrated across the board when compared against 2-PAM Cl. The ED50 values of MMB4 DMS was consistently lower than that of the other oximes against all three OPs. Furthermore, based on those ED50s, the TI trend of the various oximes against both GB and VX was MMB4 DMS > HLö-7 DMS > 2-PAM Cl, while against PHO, MMB4 DMS > 2-PAM Cl > HLö-7 DMS.
Subject(s)
Cholinesterase Inhibitors/toxicity , Cholinesterase Reactivators/administration & dosage , Organophosphates/toxicity , Animals , Chemical Warfare Agents/toxicity , Guinea Pigs , Insecticides/toxicity , Male , Organothiophosphorus Compounds/toxicity , Oximes/administration & dosage , Phorate/toxicity , Pralidoxime Compounds/administration & dosage , Pyridinium Compounds/administration & dosage , Sarin/toxicityABSTRACT
Microbial consortia isolated from aged phorate contaminated soil were used to degrade phorate. The consortia of three microorganisms (Brevibacterium frigoritolerans, Bacillus aerophilus and Pseudomonas fulva) could degrade phorate, and the highest phorate removal (between 97.65 and 98.31%) was found in soils inoculated with mixed cultures of all the three bacterial species. However, the mixed activity of any of two of these bacteria was lower than mixed consortia of all the three bacterial species. The highest degradation by individual mixed consortia of (B. frigoritolerans+B.aerophilus, B. aerophilus+P. fulva and B. frigoritolerans+P. fulva) appeared in soil between (92.28-94.09%, 95.45-97.15% and 94.08-97.42%, respectively). Therefore, inoculation of highly potential microbial consortia isolated from in situ contaminated soil could result in most effective bioremediation consortia for significantly relieving soils from phorate residues. This much high phorate remediation from phorate contaminated soils have never been reported earlier by mixed culture of native soil bacterial isolates.
Subject(s)
Insecticides/metabolism , Microbial Consortia , Phorate/metabolism , Soil Microbiology , Soil Pollutants/metabolism , Bacillus/metabolism , Biodegradation, Environmental , Pseudomonas/metabolismABSTRACT
Phorate is a highly toxic agricultural pesticide currently in use throughout the world. Like many other organophosphorus (OP) pesticides, the primary mechanism of the acute toxicity of phorate is acetylcholinesterase (AChE) inhibition mediated by its bioactivated oxon metabolite. AChE reactivation is a critical aspect in the treatment of acute OP intoxication. Unfortunately, very little is currently known about the capacity of various oximes to rescue phorate oxon (PHO)-inhibited AChE. To help fill this knowledge gap, we evaluated the kinetics of inhibition, reactivation, and aging of PHO using recombinant AChE derived from three species (rat, guinea pig and human) commonly utilized to study the toxicity of OP compounds and five oximes that are currently fielded (or have been deemed extremely promising) as anti-OP therapies by various nations around the globe: 2-PAM Cl, HI-6 DMS, obidoxime Cl2, MMB4-DMS, and HLö7 DMS. The inhibition rate constants (ki) for PHO were calculated for AChE derived from each species and found to be low (i.e., 4.8×103 to 1.4×104M-1min-1) compared to many other OPs. Obidoxime Cl2 was the most effective reactivator tested. The aging rate of PHO-inhibited AChE was very slow (limited aging was observed out to 48h) for all three species. CONCLUSIONS: (1) Obidoxime Cl2 was the most effective reactivator tested. (2) 2-PAM Cl, showed limited effectiveness in reactivating PHO-inhibited AChE, suggesting that it may have limited usefulness in the clinical management of acute PHO intoxication. (3) The therapeutic window for oxime administration following exposure to phorate (or PHO) is not limited by aging.
Subject(s)
Acetylcholinesterase/metabolism , Cholinesterase Inhibitors/metabolism , Cholinesterase Reactivators/pharmacology , Obidoxime Chloride/pharmacology , Oximes/metabolism , Pesticides/toxicity , Phorate/toxicity , Animals , Antidotes/pharmacology , Cholinesterase Inhibitors/toxicity , Cholinesterase Reactivators/metabolism , Guinea Pigs , Humans , Kinetics , Obidoxime Chloride/metabolism , Oximes/pharmacology , RatsABSTRACT
The removal of five selected pesticide compounds in a brackish model groundwater solution was examined using a bench scale direct contact membrane distillation (DCMD) system. It was found that the rejection rate of the pesticides in DCMD is mainly influenced by its properties. Compounds with low hydrophobic characteristics and low vapour pressure showed a high rejection rate (70-99%), whereas compounds with a high vapour pressure or high hydrophobicity (LogD) showed a reduced rejection (30-50%) at a water recovery of 75%. The influence of groundwater feed solution contents such as the presence of organics (humic acid) and inorganic ions (Na+, Ca2+, Mg2+, Cl- and SO42-) as well as feed temperature (40, 55 and 70 °C) on the rejection of the pesticides in DCMD operation was also evaluated. The results showed that the presence of inorganic ions and organics in the feed solution influences the pesticides rejection in DCMD operation to a minor degree. In contrast, reduced rejection of pesticides with high vapour pressure was observed. A rapid small-scale column test (RSSCT) was carried out to study the removal of any remaining substances in the permeate by adsorption onto granular activated carbon (GAC). RSSCT showed promising performance of GAC as a post-treatment option.
Subject(s)
Distillation/methods , Groundwater/chemistry , Pesticides/chemistry , Water Pollutants, Chemical/chemistry , Water Purification/methods , Water/chemistry , Adsorption , Humic Substances , Hydrophobic and Hydrophilic Interactions , Ions , Membranes, Artificial , Temperature , Vapor PressureABSTRACT
OBJECTIVES: To investigate the maximum allowable deviation of retention time ï¼RTï¼ or relative retention time ï¼RRTï¼ between the common poisons ï¼drugsï¼ and standard solvent by gas chromatography-mass spectrometry ï¼GC-MSï¼. METHODS: After pretreatment with liquid-liquid extraction, four common poisons ï¼drugsï¼-dichlorvos, phorate, diazepam and estazolam-were detected by full scan mode GC-MS. RT and RRT were analyzed according to combined uncertainty and expanded uncertainty. RESULTS: The expanded uncertainty of RT and RRT were 6.0×10-4-14.1×10-3 and 2.5×10-6-5.9×10-5 ï¼k=3ï¼, respectively. The RT of poisons ï¼drugsï¼ was relatively stable in blood samples with different mass concentrations. Among dichlorvos, phorate, diazepam and estazolam, the absolute deviation and relative deviation of RT were ≤0.03 min and ≤0.4%, respectively, and those of RRT were ≤0.003 min and ≤0.3%, respectively. CONCLUSIONS: The maximum allowable deviations of RT and RRT for common poisons ï¼drugsï¼ in blood samples are recommended to be ±0.05 min and ±0.5%.
Subject(s)
Poisons , Gas Chromatography-Mass Spectrometry , Poisons/analysisABSTRACT
Objective To investigate the maximum allowable deviation of retention time (RT) or relative retention time (RRT) between the common poisons (drugs) and standard solvent by gas chromatography-mass spectrometry (GC-MS).Methods After pretreatment with liquid-liquid extraction, four common poisons (drugs) —dichlorvos, phorate, diazepam and estazolam—were detected by full scan mode GC-MS.RT and RRT were analyzed according to combined uncertainty and expanded uncertainty. Results The expanded uncertainty of RT and RRT were 6.0× lO-4-14.1×l0-3 and 2.5 ×l0-6-5.9× lO-5 (k=3), respectively.The RT of poisons (drugs) was relatively stable in blood samples with different mass concentrations.Among dichlorvos, phorate, diazepam and estazolam, the absolute deviation and relative deviation of RT were≤0.03 min and≤0.4%, respectively, and those of RRT were≤0.003 min and≤0.3%, respectively.Conclusion The maximum allowable deviations of RT and RRT for common poisons (drugs) in blood samples are recommended to be±0.05 min and±0.5%.