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Environment International Oct 2020Isofenphos-methyl (IFP), a chiral organophosphorus pesticide, is one of the main chemicals used to control underground insects and nematodes. Recently, the use of IFP on...
Isofenphos-methyl (IFP), a chiral organophosphorus pesticide, is one of the main chemicals used to control underground insects and nematodes. Recently, the use of IFP on vegetables and fruits has been prohibited due to its high toxicity. In this study, we investigated the enantioselective distribution and metabolism of IFP and its metabolites, namely, isofenphos-methyl oxon (IFPO) and isocarbophos oxon (ICPO), in male Sprague Dawley (SD) rats. Forty eight hours (48 h) after exposure, ICPO was the main detectable compound in blood (up to 75%) and urine (up to 77%), and we found that (S)-ICPO was significantly more stable than (R)-ICPO (p < 0.05). Therefore, (S)-ICPO was proposed as a suitable candidate biomarker for the biomonitoring of IFP in human urine and blood. After 48 h exposure, 21.2-41.0%, 4.1-15.1%, and 8.6-18.7% of dosed IFP was detected in the liver of racemic, R and S enantiomer-exposed rats, respectively, and R-IFP and R-IFPO showed a faster degradation (p < 0.05). Our results showed that after one week of consecutive exposure to IFP, ICPO was accumulated in the liver of rats in both racemic and enantiopure groups (no difference between the groups, p > 0.05). We found that cytochrome P450 (CYP) (i.e. CYP2C11, CYP2D2 and CYP3A2 enzymes and carboxylesterases) is responsible for the enantioselective metabolism of IFP in liver. In addition, rats exposed to (S)-IFP exhibited hepatic lipid peroxidation, liver inflammation and hepatic fibrosis. This study provides useful information and a reference for the biomonitoring and risk assessment of IFP and organophosphorus pesticide exposure.
Topics: Animals; Organothiophosphorus Compounds; Pesticides; Rats; Rats, Sprague-Dawley; Stereoisomerism
PubMed: 32663714
DOI: 10.1016/j.envint.2020.105940 -
Ecotoxicology and Environmental Safety Apr 2023Isofenphos-methyl (IFP) is widely used as an organophosphorus for controlling underground insects and nematodes. However, excessive use of IFP may pose potential risks...
Isofenphos-methyl (IFP) is widely used as an organophosphorus for controlling underground insects and nematodes. However, excessive use of IFP may pose potential risks to the environment and humans, but little information is available on its sublethal toxicity to aquatic organisms. To address this knowledge gap, the current study exposed zebrafish embryos to 2, 4, and 8 mg/L IFP within 6-96 h past fertilization (hpf) and measured mortality, hatching, developmental abnormalities, oxidative stress, gene expressions, and locomotor activity. The results showed that IFP exposure reduced the rates of heart and survival rate, hatchability, and body length of embryos and induced uninflated swim bladder and developmental malformations. Reduction in locomotive behavior and inhibition of AChE activity indicated that IFP exposure may induce behavioral defects and neurotoxicity in zebrafish larvae. IFP exposure also led to pericardial edema, longer venous sinus-arterial bulb (SV-BA) distance, and apoptosis of the heart cells. Moreover, IFP exposure increased the accumulation of reactive oxygen species (ROS) and the content of malonaldehyde (MDA), also elevated the levels of antioxidant enzymes of superoxide dismutase (SOD) and catalase (CAT), but decreased glutathione (GSH) levels in zebrafish embryos. The relative expressions of heart development-related genes (nkx2.5, nppa, gata4, and tbx2b), apoptosis-related genes (bcl2, p53, bax, and puma), and swim bladder development-related genes (foxA3, anxa5b, mnx1, and has2) were significantly altered by IFP exposure. Collectively, our results indicated that IFP induced developmental toxicity and neurotoxicity to zebrafish embryos and the mechanisms may be relevant to the activation of oxidative stress and reduction of acetylcholinesterase (AChE) content.
Topics: Animals; Humans; Zebrafish; Acetylcholinesterase; Oxidative Stress; Embryonic Development; Embryo, Nonmammalian; Water Pollutants, Chemical; Transcription Factors; Homeodomain Proteins
PubMed: 36871354
DOI: 10.1016/j.ecoenv.2023.114723 -
Environment International Jun 2019Isofenphos-methyl (IFP) is a very active and persistent chiral insecticide. However, IFP has lower activity against acetylcholinesterases (AChEs). Previously, it was...
Isofenphos-methyl (IFP) is a very active and persistent chiral insecticide. However, IFP has lower activity against acetylcholinesterases (AChEs). Previously, it was confirmed that phosphorothioate organophosphorus pesticides with N-alkyl (POPN) require activation by oxidative desulfuration and N-dealkylation. In this work, we demonstrated that IFP could be metabolized in human liver microsomes to isofenphos-methyl oxon (IFPO, 52.7%), isocarbophos (ICP, 14.2%) and isocarbophos oxon (ICPO, 11.2%). It was found that (R)-IFP was preferentially degraded compared to the (S)-enantiomer, and the enantiomeric fraction (EF) value reached 0.61 at 60 min. However, (S)-enantiomers of the three metabolites, were degraded preferentially, and the EF values ranged from 0.34 to 0.45. Cytochrome P450 (CYP) isoforms CYP3A4, CYP2E1, and CYP1A2 and carboxylesterase enzyme have an essential role in the enantioselective metabolism of IFP; but, the enzymes that participate in the degradation of IFP metabolites are different. The AChE inhibition bioassay indicated that ICPO is the only effective inhibitor of AChE. The covalent molecular docking has proposed that the metabolites of IFP and its analogs after N-dealkylation and oxidative desulfuration will possess the highest inhibitory activity against AChE. This study is the first to demonstrate that ICPO can be regarded as a potential biomarker for the biomonitoring of IFP and ICP exposure in humans.
Topics: Biomarkers; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2E1; Cytochrome P-450 CYP3A; Humans; Malathion; Microsomes, Liver; Molecular Docking Simulation; Organothiophosphorus Compounds; Stereoisomerism
PubMed: 30991225
DOI: 10.1016/j.envint.2019.04.018 -
Molecules (Basel, Switzerland) Jan 2022With the internationalization of traditional Chinese medicines (TCMs) and the increasing use of herbal medicines around the world, there are concerns over their safety....
With the internationalization of traditional Chinese medicines (TCMs) and the increasing use of herbal medicines around the world, there are concerns over their safety. In recent years, there have been some sporadic reports of pesticide residues in Chuanxiong Rhizoma (CX), although the lack of systematic and comprehensive analyses of pesticide residues and evaluations of toxicological risks in human health has increased the uncertainty of the potential effects of pesticides exposure in humans. This study aimed to clarify the status of pesticide residues and to determine the health risks of pesticide residues in CX. The findings of this study revealed that 99 batches of CX samples contained pesticide residues ranging from 0.05 to 3013.17 μg/kg. Here, 6-22 kinds of pesticides were detected in each sample. Prometryn, carbendazim, dimethomorph, chlorpyrifos, chlorantraniliprole, pyraclostrobin, and paclobutrazol were the most frequently detected pesticides, with detection rates of 68.69-100%. Insecticides and fungicides accounted for 43.23% and 37.84% of the total pesticides detected, respectively. Here, 86.87% of the pesticide content levels were lower than 50 μg/kg, and a small number of samples contained carbofuran, dimethoate, and isofenphos-methyl exceeding the maximum residue levels (MRLs). A risk assessment based on the hazard quotient/hazard index (HQ/HI) approach revealed that the short-term, long-term, and cumulative risks of pesticide residues in CX are well below the levels that may pose a health risk. Worryingly, six banned pesticides (carbofuran, phorate sulfone, phorate-sulfoxide, isofenphos-methyl, terbufos-sulfone, and terbufoxon sulfoxide) were detected. This study has improved our understanding of the potential exposure risk of pesticide multi-residues in CX. The results of the study will have a positive impact on improving the quality and safety of CX and the development of MRLs for pesticide residues.
Topics: Chromatography, Gas; Chromatography, Liquid; Drugs, Chinese Herbal; Food Contamination; Humans; Medicine, Chinese Traditional; Pesticide Residues; Risk Assessment; Tandem Mass Spectrometry
PubMed: 35163887
DOI: 10.3390/molecules27030622 -
European Journal of Cardio-thoracic... Oct 2022The Amaze trial showed that adding atrial fibrillation (AF) surgery to cardiac operations increased return to sinus rhythm (SR) without impact on quality of life or... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
The Amaze trial showed that adding atrial fibrillation (AF) surgery to cardiac operations increased return to sinus rhythm (SR) without impact on quality of life or survival at 2 years. We report outcomes to 5 years.
METHODS
In a multicentre, phase III, pragmatic, double-blind, randomized controlled superiority trial, cardiac surgery patients with >3 months of AF were randomized 1:1 to adjunct AF surgery or control. Primary outcomes of 1-year SR restoration and 2-year quality-adjusted survival were already reported. This study reports on rhythm, survival, quality-adjusted survival, stroke, medication and safety to 5 years.
RESULTS
Between 2009 and 2014, 352 patients were randomized. By 5 years 79 died, 58 withdrew, 34 were lost to follow-up and the remaining 182 provided data. AF surgery significantly increased the odds of remaining in SR at 5 years {odds ratio = 2.98 [95% confidence interval (CI) 1.23, 7.17], P = 0.015}. There was a non-significant decrease in stroke incidence [odds ratio = 0.605 (95% CI 0.284, 1.287), P = 0.19], but no improved survival [5-year survival: AF surgery 77.3% (95% CI 71.1%, 83.5%), controls 77.8% (95% CI 71.7%, 84.0%), P = 0.85]. Quality-adjusted survival difference was negligible (-0.03; 95% CI -0.33, 0.27, P = 0.85). The composite of survival free of stroke and AF was better in the AF surgery group [odds ratio = 2.34 (95% CI 1.03, 5.31)]. There were no other differences.
CONCLUSIONS
Adjunct AF surgery confers a higher rate of SR to 5 years and a better composite outcome of survival free of stroke and AF but has no impact on overall or quality-adjusted survival or other clinical outcomes.
CLINICAL TRIAL REGISTRATION NUMBER
ISRCTN82731440.
Topics: Humans; Atrial Fibrillation; Catheter Ablation; Quality of Life; Treatment Outcome; Stroke
PubMed: 35348642
DOI: 10.1093/ejcts/ezac181 -
FEMS Microbiology Ecology Sep 2000An enrichment culture technique was used to isolate bacteria responsible for the enhanced biodegradation of ethoprophos in a soil from Northern Greece. Restriction...
An enrichment culture technique was used to isolate bacteria responsible for the enhanced biodegradation of ethoprophos in a soil from Northern Greece. Restriction fragment length polymorphism patterns of the 16S rRNA gene, partial 16S rRNA sequence analysis, and sodium dodecylsulfate-polyacrylamide gel electrophoresis total protein profile analysis were used to characterise the isolated bacteria. Two of the three ethoprophos-degrading cultures were pure and both isolates were classified as strains of Pseudomonas putida (epI and epII). The third culture comprised three distinct components, a strain identical to P. putida epI and two strains with 16S rRNA sequence similarity to Enterobacter strains. Isolate epI effectively removed a fresh ethoprophos addition from both fumigated and non-fumigated soil when introduced at high inoculum density, but removed it only from fumigated soil at low inoculum density. Isolates epI and epII degraded cadusafos, isazofos, isofenphos and fenamiphos, but only at a slow rate. This high substrate specificity was attributed to minor (cadusafos), or major (isazofos, isofenphos, fenamiphos) structural differences from ethoprophos. Studies with (14)C-labelled ethoprophos indicated that isolates epI and epII degraded the nematicide by removing the S-propyl moiety.
PubMed: 11098072
DOI: 10.1111/j.1574-6941.2000.tb00743.x -
Biophysical Journal Feb 2018
Topics: Bacteria; Escherichia coli; Fluorescence Polarization; Organothiophosphorus Compounds
PubMed: 29414695
DOI: 10.1016/j.bpj.2017.11.3786 -
RSC Advances Oct 2020In the present study, a modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) method was proposed for the simultaneous analysis of 75 pesticides in maca...
In the present study, a modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) method was proposed for the simultaneous analysis of 75 pesticides in maca and with ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). The developed method was validated in accordance with linearity, linear range, limit of detection, limit of quantification, accuracy, precision, and matrix effect. Each analyte had good linearity ( > 0.99) in the corresponding concentration range. The method LOD and LOQ values of all the analytes ranged from 0.01 μg kg to 303.35 μg kg and 0.03 μg kg to 1011.15 μg kg, respectively. The recoveries ( = 6) of the analyzed pesticides were in the range of 75.92-113.43%. The RSDs of precision were between 0.60% and 7.36%. All matrix effect values ranged from 81.79% to 118.71% and 80.36% to 119.64% in maca and , respectively. The analysis of 103 samples showed the presence of isofenphos-methyl in some of them. The method had a good application prospect and could be used as a general approach for the quantitative determination of pesticide residues in food.
PubMed: 35517969
DOI: 10.1039/d0ra06375d -
Talanta Dec 2016An effective method has been developed and validated for the determination of residues of 55 pesticides in tobacco. The proposed sample preparation method is based on...
An effective method for pesticide residues determination in tobacco by GC-MS/MS and UHPLC-MS/MS employing acetonitrile extraction with low-temperature precipitation and d-SPE clean-up.
An effective method has been developed and validated for the determination of residues of 55 pesticides in tobacco. The proposed sample preparation method is based on acetonitrile extraction, low-temperature precipitation (LTP) and dispersive solid phase extraction (d-SPE) clean-up. Gas chromatography and ultra-high performance liquid chromatography analysis, both coupled to tandem mass spectrometry (GC-MS/MS and UHPLC-MS/MS), were used for determination. LTP is easy to perform and was crucial to obtain a clean extract. Method quantification limit for the pesticides were between 25 and 75µgkg. Extraction recoveries obtained for blank samples spiked at 25, 75, 125 and 250µgkg levels ranged from 63 to 161% with relative standard deviations (RSD)≤20%. The method was successfully applied to the analysis of thirteen different tobacco samples, providing to be a robust procedure for routine analysis. The compounds pirimiphos methyl and isofenphos presented residues in the range of 35-51µgkg.
Topics: Acetonitriles; Chemical Precipitation; Chromatography, Liquid; Gas Chromatography-Mass Spectrometry; Pesticide Residues; Tandem Mass Spectrometry; Temperature; Nicotiana
PubMed: 27769424
DOI: 10.1016/j.talanta.2016.08.015 -
FEMS Microbiology Ecology Aug 2005An enrichment culture technique was used for the isolation of microorganisms responsible for the enhanced biodegradation of the nematicide cadusafos in soils from a...
An enrichment culture technique was used for the isolation of microorganisms responsible for the enhanced biodegradation of the nematicide cadusafos in soils from a potato monoculture area in Northern Greece. Mineral salts medium supplemented with nitrogen (MSMN), where cadusafos (10 mg l(-1)) was the sole carbon source, and soil extract medium (SEM) were used for the isolation of cadusafos-degrading bacteria. Two pure bacterial cultures, named CadI and CadII, were isolated and subsequently characterized by sequencing of 16S rRNA genes. Isolate CadI showed 97.4% similarity to the 16S rRNA gene of a Flavobacterium strain, unlike CadII which showed 99.7% similarity to the 16S rRNA gene of a Sphingomonas paucimobilis. Both isolates rapidly metabolized cadusafos in MSMN and SEM within 48 h with concurrent population growth. This is the first report for the isolation and characterization of soil bacteria with the ability to degrade rapidly cadusafos and use it as a carbon source. Degradation of cadusafos by both isolates was accelerated when MSMN was supplemented with glucose. In contrast, addition of succinate in MSMN marginally reduced the degradation of cadusafos. Both isolates were also able to degrade completely ethoprophos, a nematicide chemical analog of cadusafos, but did not degrade the other organophosphorus nematicides tested such as isazofos and isofenphos. Inoculation of a soil freshly treated with cadusafos or ethoprophos (10 mg l(-1)) with high inoculum densities (4.3 x 10(8) cells g(-1)) of Sphingomonas paucimobilis resulted in the rapid degradation of both nematicides. These results indicate the potential of this bacterium to be used in the clean-up of contaminated pesticide waste in the environment.
Topics: Antinematodal Agents; Biodegradation, Environmental; DNA, Bacterial; Flavobacterium; Organothiophosphorus Compounds; Pesticides; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Sphingomonas
PubMed: 16329956
DOI: 10.1016/j.femsec.2005.01.012