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Clinical Toxicology (Philadelphia, Pa.) Feb 2022The clinical characteristics following self-poisoning with organophosphorus (OP) insecticides differs according to the insecticide ingested. Phenthoate is a dimethoxy...
BACKGROUND
The clinical characteristics following self-poisoning with organophosphorus (OP) insecticides differs according to the insecticide ingested. Phenthoate is a dimethoxy WHO Hazard Class II OP pesticide with limited literature on its clinical characteristics and outcome. We aimed to better understand its clinical characteristics by studying patients with phenthoate self-poisoning in Sri Lanka.
METHODS
We conducted a prospective cohort study of patients presenting with phenthoate self-poisoning to eight hospitals in Sri Lanka between 2002 and 2018. Clinical outcomes were recorded for each patient. Blood samples for measuring plasma phenthoate concentration, cholinesterase activity, and response to oximes were available for a very small number of patients recruited to a clinical trial.
RESULTS
Two hundred and ninety-two patients who ingested agricultural phenthoate formulations were included in the study. Median time to admission was 3.9 (IQR 2.4 - 6.8) h. Forty-two (14.4%) patients were intubated, mostly (30/37, 81%) within 24 h of ingestion (median time to intubation 7.2 [IQR 2.6-20.9] h). Median duration of intubation was 74.8 (IQR 26.8-232.5) h; the longest duration in a survivor was 592 h. Nineteen died (case fatality 6.5%, 95% CI 4.0-10.0); median time to death was 37 (IQR 16 - 101.7) h. Median plasma phenthoate concentration in patients with samples ( = 81) was 135 (IQR 62.7-356.5) ng/mL (0.42 µmol/mL [0.2 to 1.1 µmol/mL]). Five of six patients receiving pralidoxime chloride 2 g showed an initial increase in AChE and BuChE activity that was not sustained despite an infusion of pralidoxime.
CONCLUSION
Phenthoate self-poisoning has a 6.5% case fatality rate. Most patients who experience respiratory failure undergo early intubation; most deaths occurred among those patients who were intubated less than 24 h after ingestion. There was a non-sustained increase in cholinesterase activity with pralidoxime, but further studies are required to analyse the extent to which oximes are clinically effective in phenthoate self-poisoning.
Topics: Humans; Insecticides; Organophosphate Poisoning; Organothiophosphorus Compounds; Prospective Studies
PubMed: 33960866
DOI: 10.1080/15563650.2021.1917596 -
Journal of Hazardous Materials Jan 2024Extensive application of organophosphorus pesticides such as phenthoate results in its abundance in ecosystems, particularly in waterbodies, thereby providing the...
Extensive application of organophosphorus pesticides such as phenthoate results in its abundance in ecosystems, particularly in waterbodies, thereby providing the impetus to assess its role in aquatic organisms. However, the impact of phenthoate on marine algal physiological and proteomic response is yet to be explored despite its biological significance. In this study, we thus ought to investigate the impact of phenthoate in the marine dinoflagellate Prorocentrum lima, which is known for synthesizing okadaic acid (OA), the toxin responsible for diarrhetic shellfish poisoning (DSP). Our results showed that P. lima effectively absorbed phenthoate in seawater, with a reduction efficiency of 90.31% after 48 h. Surprisingly, the provision of phenthoate (100 and 1000 µg/L) substantially reduced the OA content of P. lima by 35.08% and 60.28% after 48 h, respectively. Meanwhile, phenthoate treatment significantly reduced the oxidative stress in P. lima. Proteomic analysis revealed that the expression level of seven crucial proteins involved in endocytosis was upregulated, suggesting that P. lima could absorb phenthoate via the endocytic signaling pathway. Importantly, phenthoate treatment resulted in the downregulation of proteins such as polyketide synthase (PKS)- 2, Cytochrome P450 (CYP450)- 1, and CYP450-2, involved in OA synthesis, thereby decreasing the OA biosynthesis by P. lima. Our results demonstrated the potential role of P. lima in the removal of phenthoate in water and exemplified the crucial proteins and their possible molecular mechanisms underpinning the phenthoate remediation by P. lima and also the regulatory role of phenthoate in restricting the OA metabolism. Collectively, these findings uncovered the synergistic mechanisms of phenthoate and P. lima in remediating phenthoate and reducing the toxic impact of P. lima.
Topics: Marine Toxins; Ecosystem; Organophosphorus Compounds; Proteomics; Pesticides; Okadaic Acid; Dinoflagellida
PubMed: 37801972
DOI: 10.1016/j.jhazmat.2023.132624 -
Journal of Forensic Sciences Nov 2018Organophosphates are widely used as pesticides. However, organophosphates are occasionally orally ingested to commit suicide. In this case, a man in his late 80s...
Organophosphates are widely used as pesticides. However, organophosphates are occasionally orally ingested to commit suicide. In this case, a man in his late 80s committed suicide by ingesting both dichlorvos and phenthoate. Autopsy findings revealed a characteristic volatile odor from his mouth, stomach, lungs, liver, and kidneys. The esophageal mucosa was denatured and had lost elasticity. Serum cholinesterase activity was 9 IU/L. Toxicological analyses performed using high-performance liquid chromatography-tandem mass spectrometry revealed that dichlorvos concentrations in the left and right cardiac blood samples were 11.6 and 4.6 μg/mL, respectively. Phenthoate concentrations in the left and right cardiac blood samples were 5.8 and 0.51 μg/mL, respectively. The total amounts of dichlorvos and phenthoate in the stomach were 7.35 and 4.55 g, respectively. The case history, autopsy findings, and toxicological analyses indicated that the cause of death was acute fatal poisoning after oral ingestion of both dichlorvos and phenthoate.
Topics: Aged, 80 and over; Dichlorvos; Gastrointestinal Contents; Humans; Male; Organophosphate Poisoning; Organothiophosphorus Compounds; Suicide
PubMed: 29601635
DOI: 10.1111/1556-4029.13781 -
Biomedical Chromatography : BMC Jan 2022Phenthoate is a chiral organophosphate pesticide with a pair of enantiomers which differ in toxicity, behavior and insecticidal activity, and its acute toxicity on human...
Phenthoate is a chiral organophosphate pesticide with a pair of enantiomers which differ in toxicity, behavior and insecticidal activity, and its acute toxicity on human health owing to the inhibition of acetylcholinesterase highlights the need for enantioselective detection of enantiomers. Therefore, this study aimed to establish a simple rapid method for separation and detection of phenthoate enantiomers in fruits, vegetables and grains. The enantiomers were separated using reversed-phase high-performance liquid chromatography-tandem mass spectrometry for the first time. Rapid chiral separation (within 9 min) of the target compound was achieved on a chiral OJ-RH column with the mobile phase of methanol-water = 85:15(v/v), at a flow rate of 1 ml/min and a column temperature of 30°C. Acetonitrile and graphitized carbon black were used as the extractant and sorbent for pretreatment, respectively. This method provides excellent linearity (correlation coefficient ≥0.9986), high sensitivity (limit of quantification 5 μg/kg and limit of detection <0.25 μg/kg), satisfactory mean recoveries (76.2-91.0%) and relative standard deviation (intra-day RSDs ranged from 2.0 to 7.9% and inter-day RSDs ranged from 2.4 to 8.4%). In addition, a field trial to explore the stereoselective degradation of phenthoate enantiomers in citrus showed that (-)-phenthoate degraded faster than its antipode, resulting in the relative accumulation of (+)-phenthoate.
Topics: Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Fruit; Limit of Detection; Linear Models; Organothiophosphorus Compounds; Pesticide Residues; Plants, Edible; Reproducibility of Results; Stereoisomerism; Tandem Mass Spectrometry
PubMed: 34414593
DOI: 10.1002/bmc.5229 -
Chemosphere Sep 2020Chiral organophosphorus pollutants are existed ubiquitously in the ecological environment, but the enantioselective toxicities of these nerve agents to humans and their...
Chiral organophosphorus pollutants are existed ubiquitously in the ecological environment, but the enantioselective toxicities of these nerve agents to humans and their molecular bases have not been fully elucidated. Using experimental and computational approaches, this story was to explore the neurotoxic response process of the target acetylcholinesterase (AChE) to chiral phenthoate and further decipher the microscopic mechanism of such toxicological effect at the enantiomeric level. The results showed that the toxic reaction of AChE with chiral phenthoate exhibited significant enantioselectivity, and (R)-phenthoate (K=1.486 × 10 M) has a bioaffinity for the nerve enzyme nearly three times that of (S)-phenthoate (K=4.503 × 10 M). Dynamic research outcomes interpreted the wet experiments, and the inherent conformational flexibility of the target enzyme has a great influence on the enantioselective neurotoxicological action processes, especially reflected in the conformational changes of the three key loop regions (i.e. residues His-447, Gly-448, and Tyr-449; residues Gly-122, Phe-123, and Tyr-124; and residues Thr-75, Leu-76, and Tyr-77) around the reaction patch. This was supported by the quantitative results of conformational studies derived from circular dichroism spectroscopy (α-helix: 34.7%→30.2%/31.6%; β-sheet: 23.6%→19.5%/20.7%; turn: 19.2%→22.4%/21.9%; and random coil: 22.5%→27.9%/25.8%). Meanwhile, via analyzing the modes of toxic action and free energies, we can find that (R)-phenthoate has a strong inhibitory effect on the enzymatic activity of AChE, as compared with (S)-phenthoate, and electrostatic energy (-23.79/-17.77 kJ mol) played a critical role in toxicological reactions. These points were the underlying causes of chiral phenthoate displaying different degrees of enantioselective neurotoxicity.
Topics: Acetylcholinesterase; Circular Dichroism; Environmental Pollutants; Humans; Models, Theoretical; Molecular Dynamics Simulation; Neurotoxicity Syndromes; Organothiophosphorus Compounds; Physical Phenomena; Protein Structure, Secondary; Stereoisomerism
PubMed: 32416396
DOI: 10.1016/j.chemosphere.2020.127007 -
Lab on a Chip Oct 2020Presently, the use of several pesticides has been continuously rising owing to the increase in the production of food materials to meet the requirements of the growing...
Presently, the use of several pesticides has been continuously rising owing to the increase in the production of food materials to meet the requirements of the growing population of the world. The safety of food materials with regards to pesticides is an important health concern for people. With this aim, we have developed a smartphone-assisted paper-based sensor impregnated with citrate capped Cu@Ag core-shell nanoparticles (NPs) for selective determination of phenthoate pesticides in water and food samples. The mechanism for selective detection is based on the high affinity of phenthoate to interact with silver NPs present on the surface of CuNPs, which results in aggregation and a change in the color of the paper device. Furthermore, the proposed mechanism and interaction of phenthoate with Cu@Ag NPs was theoretically investigated by density functional theory (DFT) using Gaussian 16.0 software. The linear range for the determination of phenthoate was found in the range of 50-1500 μg L-1, with a limit of detection of 15 μg L-1, and a 92.6 to 97.4% recovery, and the interference studies demonstrated the selectivity for the determination of the target analyte from complex sample matrices. Finally, paper impregnated with Cu@Ag was exploited for the monitoring of the phenthoate pesticide in different water and food samples. The advantages of this paper-based sensor, coupled with a smartphone readout system, are that is it is user-friendly, easy-to-use, cost-effective, and can be applied at the sample source compared to sophisticated analytical instruments.
Topics: Food Safety; Humans; Limit of Detection; Metal Nanoparticles; Organothiophosphorus Compounds; Pesticides; Silver; Smartphone
PubMed: 32966488
DOI: 10.1039/d0lc00515k -
Environmental Science and Pollution... Oct 2020The risks of the health-associated problems of pesticide-exposed non-target organisms are ubiquitous, therefore an emerging concern to strike the balance between benefit...
The risks of the health-associated problems of pesticide-exposed non-target organisms are ubiquitous, therefore an emerging concern to strike the balance between benefit and risk factors. In the present study, by elucidating multiple biomarkers, the effects of Phenthoate 50 EC on the acute toxicity tests and different pathophysiological changes of common carp (Cyprinus carpio) fingerlings were studied in time- and concentration-dependent manners. The LC of Phenthoate 50 EC for the fish was 7.39 (6.716-8.076) ppm at 96 h. As an indicator of neurotoxicity, compared to the control group, significant (P < 0.01) reduction in brain acetylcholinesterase (AChE) activity was observed, whereas plasma glutamate-oxalacetate transaminase (PGOT) and plasma glutamate pyruvate transaminase (PGPT) activities were increased significantly (P < 0.01) at the doses of 2.22 and 3.69 ppm of Phenthoate 50 EC, respectively. Histopathological changes in the insecticide-treated fish liver suggested the hepatic tissue damages, while alteration of the blood, gills and kidney morphology; progressive decrease (P < 0.05) in the serum calcium levels; and significantly (P < 0.01) decreased blood glucose level at 2.22 and 3.69 or 5.17 ppm of Phenthoate 50 EC demonstrated the oxidative stress and requirement of the up-surging energy demands due to the exposure of this organophosphate chemical. These results advice the modulation caused by this widely used agrochemical on the physiology of aquatic fauna by changing the enzymatic and biochemical indices at cellular level.
Topics: Animals; Carps; Insecticides; Organothiophosphorus Compounds; Water Pollutants, Chemical
PubMed: 32607992
DOI: 10.1007/s11356-020-09697-x -
Toxicology Letters Oct 2019Organophosphates are chemical pollutants that are existed widely in the environment, but the reactions of these agents with blood proteins are still not fully clarified....
Organophosphates are chemical pollutants that are existed widely in the environment, but the reactions of these agents with blood proteins are still not fully clarified. The current story was to analyze the static and dynamic interactions between human serum albumin (HSA) and phenthoate and then uncover the impact of the conjugations on the acetylcholinesterase (AChE) activity at the microscopic scale. Experimental results revealed clearly that the bioconjugate of the HSA-phenthoate was yielded and the conformation of HSA can produce autoregulation during the reaction. Dynamic reaction processes suggested that the conformational flexibility of the specific protein domain was changed significantly in equilibrium, and the electrostatic interaction energy played a major role in total energy of the biosystems, which matches the results of wet experiment and molecular docking. We also found that the modes of homologous proteins-phenthoate have obvious distinctions, and this point is related closely to the local dynamic flexibility of biomolecular structures. Additionally, the degree of bioconjugation of the HSA-phenthoate is positively associated with the enzymatic activity of target AChE, which may be attributed to the competitive reactions between HSA and AChE. Evidently, this scenario could provide useful molecular information for the systematic exploration of the toxicokinetics of organophosphorus compounds.
Topics: Acetylcholinesterase; Binding Sites; Binding, Competitive; Cholinesterase Inhibitors; Humans; Insecticides; Models, Biological; Molecular Docking Simulation; Organothiophosphorus Compounds; Protein Binding; Protein Conformation; Protein Domains; Serum Albumin, Human
PubMed: 31362050
DOI: 10.1016/j.toxlet.2019.07.025 -
The Science of the Total Environment Jun 2024Considering the widespread use of organophosphorus pesticides (OPs) and the global prevalence of hypertension (HTN), as well as studies indicating that different...
BACKGROUND AND OBJECTIVE
Considering the widespread use of organophosphorus pesticides (OPs) and the global prevalence of hypertension (HTN), as well as studies indicating that different glycemic statuses may respond differently to the biological effects of OPs. Therefore, this study, based on the Henan rural cohort, aims to investigate the association between OPs exposure and HTN, and further explores whether lipids mediate these associations.
METHODS
We measured the plasma levels of OPs in 2730 participants under different glycemic statuses using gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS). A generalized linear model, Quantile g-computation (QGC), adaptive elastic net (AENET), and Bayesian kernel machine regression (BKMR) models were used to assess the impact of OPs exposure on HTN, with least absolute shrinkage and selection operator (LASSO) penalty regression identifying main OPs. Mediation models were used to evaluate the intermediary role of blood lipids in the OPs-HTN relationship.
RESULTS
The detection rates for all OPs were high, ranging from 76.35 % to 99.17 %. In the normal glucose tolerance (NGT) population, single exposure models indicated that malathion and phenthoate were associated with an increased incidence of HTN (P-FDR < 0.05), with corresponding odds ratios (ORs) and 95 % confidence intervals (CIs) of 1.624 (1.167,2.260) and 1.290 (1.072,1.553), respectively. QGC demonstrated a positive association between OP mixtures and HTN, with malathion and phenthoate being the primary contributors. Additionally, the AENET model's Exposure Response Score (ERS) suggested that the risk of HTN increases with higher ERS (P < 0.001). Furthermore, BKMR revealed that co-exposure to OPs increases HTN risk, with phenthoate having a significant impact. Furthermore, triglycerides (TG) mediated 6.55 % of the association between phenthoate and HTN. However, no association was observed in the impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM) populations.
CONCLUSIONS
Our findings suggest that in the NGT population, OPs may significantly contribute to the development of HTN, proposing TG as a potential novel target for HTN prevention.
Topics: Humans; Hypertension; Environmental Exposure; China; Middle Aged; Organophosphorus Compounds; Male; Female; Lipids; Adult; Pesticides; Blood Glucose; Environmental Pollutants
PubMed: 38688361
DOI: 10.1016/j.scitotenv.2024.172711 -
Food Chemistry Mar 2022A simple, environmentally-friendly and reliable method was developed to simultaneously monitor the residue of methyl 1-naphthalene acetate, parathion-methyl,...
A simple, environmental-friendly and reliable d-SPE method using amino-containing metal-organic framework MIL-125-NH to determine pesticide residues in pomelo samples from different localities.
A simple, environmentally-friendly and reliable method was developed to simultaneously monitor the residue of methyl 1-naphthalene acetate, parathion-methyl, fenitrothion, bromophos and phenthoate in pomelo by using dispersive solid-phase extraction technique (d-SPE). In this method, these target analytes were captured by MIL-125-NH and detected by GC-MS/MS. The key parameters of d-SPE were optimized by the single factor experiment. Under the optimized conditions, a good determination coefficient (R > 0.9922) and extraction recoveries (64.7-116.8%) are obtained. The limit of detections (0.03-1.07 ng/g) is lower than the MRLs in citrus fruits established by EU (10-15000 ng/g) and China (10-10000 ng/g). The precisions of intra-day and inter-day are 1.3-8.9% and 3.8-14.9%, respectively. In addition, the sorbent MIL-125-NH is stable and can be reused at least eight times. These results prove the established method is efficient and reliable to detect the pesticide residues in pomelo.
Topics: Fruit; Metal-Organic Frameworks; Pesticide Residues; Solid Phase Extraction; Tandem Mass Spectrometry
PubMed: 34601418
DOI: 10.1016/j.foodchem.2021.131208