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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 -
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 -
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 -
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 -
Toxicology Letters Jul 1984This study was designed to provide information on the cumulative effects of phenthoate, an organophosphorus insecticide. Male rats were given the test compound orally 6...
This study was designed to provide information on the cumulative effects of phenthoate, an organophosphorus insecticide. Male rats were given the test compound orally 6 days/week for a minimum of 10 weeks and until the cumulative LD50 (CLD50) remained constant for 3 consecutive weeks. The oral LD50 value for phenthoate in rats was highest (116 mg/kg) in groundnut oil followed by dimethylsulfoxide (DMSO) and alcohol. The animals with lesser weight were more susceptible than the heavier animals. Rats receiving 2.5 to 10 mg/kg phenthoate for 13 weeks showed varying decreases in weights of liver, heart, spleen, brain, testes and adrenals. At 40 mg/kg, none of the animals survived. The CDL50 for 13 weeks was 12 mg/kg with a cumulative toxicity factor of 6.3. The compound has been rated as a moderately hazardous one.
Topics: Administration, Oral; Animals; Body Weight; Lethal Dose 50; Male; Organ Size; Organothiophosphorus Compounds; Rats
PubMed: 6464035
DOI: 10.1016/0378-4274(84)90047-x -
Toxicology Letters Mar 1983A concomitant decrease in acetylcholinesterase (AChE) activity and increase in acetylcholine (ACh) concentration was observed in the brain of Anabas testudineus (Bloch)...
A concomitant decrease in acetylcholinesterase (AChE) activity and increase in acetylcholine (ACh) concentration was observed in the brain of Anabas testudineus (Bloch) during a 48-h phenthoate treatment. On return to phenthoate-free fresh water, the decline in enzyme activity and rise in ACh concentration was found to persist for up to 20 days following exposure. Normal values for brain AChE activity and ACh concentration were restored only after 60 days following transfer to phenthoate-free fresh water. It is concluded that inhibition of AChE results in ACh accumulation which, in turn, initiates a faster rate of recovery of the enzyme in fish exposed to the highest concentration of phenthoate.
Topics: Acetylcholine; Acetylcholinesterase; Animals; Brain; Fishes; Organothiophosphorus Compounds; Water Pollutants, Chemical
PubMed: 6836603
DOI: 10.1016/0378-4274(83)90155-8 -
Journal of Toxicology. Clinical... 1994Five metabolites were detected in the plasma and urine of a patient following ingestion of the organophosphate insecticide, phenthoate. Intact phenthoate was detected...
Five metabolites were detected in the plasma and urine of a patient following ingestion of the organophosphate insecticide, phenthoate. Intact phenthoate was detected only in gastric lavage fluid. After methylation of acidic extracts of plasma and urine, phenthoate acid, demethyl phenthoate, demethyl phenthoate oxon acid, demethyl phenthoate S-isomer, and demethyl phenthoate acid S-isomer were identified with synthesized phenthoate analogues by gas chromatography and gas chromatograph-mass spectrometry. The main metabolites were phenthoate acid and demethyl phenthoate oxon acid. Although demethyl phenthoate oxon acid was a significant metabolite, no phenthoate oxon, phenthoate oxon acid or demethyl phenthoate oxon were detected. If the oxon was formed in the patient, it may have been rapidly degraded by carboxylesterase or glutathione transferase to demethyl phenthoate oxon acid.
Topics: Chromatography, Gas; Humans; Insecticides; Male; Middle Aged; Organothiophosphorus Compounds; Poisoning
PubMed: 8308949
DOI: 10.3109/15563659409000430 -
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 -
Toxicology and Applied Pharmacology Aug 1983Malathion and phenthoate carboxylesterase activities were investigated in pulmonary alveolar macrophages (PAM) in Sprague-Dawley rats. PAM was found to be capable of...
Malathion and phenthoate carboxylesterase activities were investigated in pulmonary alveolar macrophages (PAM) in Sprague-Dawley rats. PAM was found to be capable of hydrolyzing phenthoate at a faster rate than malathion. Oral administration to rats with O,O,S-trimethyl phosphorothioate (OOS-Me), a pneumotoxic impurity present in technical grades of malathion and phenthoate, increased the activities of these esterases in PAM without affecting an activity in lung microsomal carboxylesterase. The time course study indicated that this increase was maximal on Day 1 following treatment with OOS-Me at 20 and 40 mg/kg of doses. To assess the usefulness of measuring these esterases in PAM as an indicator of lung damage, paraquat and bromobenzene were administered to rats with treatment regimens which have been shown previously to result in histopathologically demonstrable pneumotoxicity. Malathion and phenthoate carboxylesterase activities in PAM were increased by two- to threefold following treatment with paraquat or bromobenzene. These treatments also increased lung microsomal malathion carboxylesterase activity by threefold. Furthermore, infection of rats with Pseudomonas aeruginosa by intratracheal inoculation increased malathion and phenthoate carboxylesterase activities in PAM by two- to threefold without increasing these activities in lung microsomes. These results indicate that PAM may play a significant role in detoxifying airborne malathion and phenthoate when inhaled. Furthermore, the activities of malathion and phenthoate carboxylesterases may be useful for detecting lung injury produced by pneumotoxic chemicals as well as bacterial infection.
Topics: Animals; Carboxylesterase; Carboxylic Ester Hydrolases; Insecticides; Lung; Macrophages; Male; Microsomes; Organothiophosphates; Organothiophosphorus Compounds; Paraquat; Pulmonary Alveoli; Rats; Rats, Inbred Strains
PubMed: 6612731
DOI: 10.1016/0041-008x(83)90187-4