-
Journal of Chromatography. B,... Aug 2017A simultaneous analytical method was developed for the determination of methiocarb and its metabolites, methiocarb sulfoxide and methiocarb sulfone, in five livestock...
Simultaneous quantification of methiocarb and its metabolites, methiocarb sulfoxide and methiocarb sulfone, in five food products of animal origin using tandem mass spectrometry.
A simultaneous analytical method was developed for the determination of methiocarb and its metabolites, methiocarb sulfoxide and methiocarb sulfone, in five livestock products (chicken, pork, beef, table egg, and milk) using liquid chromatography-tandem mass spectrometry. Due to the rapid degradation of methiocarb and its metabolites, a quick sample preparation method was developed using acetonitrile and salts followed by purification via dispersive- solid phase extraction (d-SPE). Seven-point calibration curves were constructed separately in each matrix, and good linearity was observed in each matrix-matched calibration curve with a coefficient of determination (R) ≥ 0.991. The limits of detection and quantification were 0.0016 and 0.005mg/kg, respectively, for all tested analytes in various matrices. The method was validated in triplicate at three fortification levels (equivalent to 1, 2, and 10 times the limit of quantification) with a recovery rate ranging between 76.4-118.0% and a relative standard deviation≤10.0%. The developed method was successfully applied to market samples, and no residues of methiocarb and/or its metabolites were observed in the tested samples. In sum, this method can be applied for the routine analysis of methiocarb and its metabolites in foods of animal origins.
Topics: Animals; Cattle; Chickens; Chromatography, Liquid; Food Analysis; Limit of Detection; Linear Models; Meat; Methiocarb; Milk; Reproducibility of Results; Swine; Tandem Mass Spectrometry
PubMed: 28666230
DOI: 10.1016/j.jchromb.2017.06.025 -
Environmental Toxicology and... Jan 2016In this work, we examined the metabolism of the carbamate insecticides methiocarb and carbaryl by rat liver microsomes and plasma, and its effect on their...
In this work, we examined the metabolism of the carbamate insecticides methiocarb and carbaryl by rat liver microsomes and plasma, and its effect on their endocrine-disrupting activities. Methiocarb and carbaryl were not enzymatically hydrolyzed by rat liver microsomes, but were hydrolyzed by rat plasma, mainly to methylthio-3,5-xylenol (MX) and 1-naphthol, respectively. When methiocarb was incubated with rat liver microsomes in the presence of NADPH, methiocarb sulfoxide was formed. The hydrolysis product, MX, was also oxidized to the sulfoxide, 3,5-dimethyl-4-(methylsulfinyl)phenol (SP), by rat liver microsomes in the presence of NADPH. These oxidase activities were catalyzed by cytochrome P450 and flavin-containing monooxygenase. Methiocarb and carbaryl both exhibited estrogen receptor α (ERα) and ERβ agonistic activity. MX and 1-naphthol showed similar activities, but methiocarb sulfoxide and SP showed markedly decreased activities. On the other hand, methiocarb and carbaryl exhibited potent antiandrogenic activity in the concentration range of 1×10(-6)-3×10(-5) M. Their hydrolysis products, MX, and 1-naphthol also showed high activity, equivalent to that of flutamide. However, methiocarb sulfoxide and SP showed relatively low activity. Thus, hydrolysis of methiocarb and carbaryl and oxidation of methiocarb to the sulfoxide markedly modified the estrogenic and antiandrogenic activities of methiocarb and carbaryl.
Topics: Androgen Antagonists; Animals; CHO Cells; Carbaryl; Cell Line; Cricetulus; Cytochrome P-450 Enzyme System; Estrogens; Humans; Hydrolysis; In Vitro Techniques; Liver; MCF-7 Cells; Methiocarb; NADP; Oxygenases; Plasma; Rats
PubMed: 26774076
DOI: 10.1016/j.etap.2015.08.014 -
The Journal of Toxicological Sciences 2016The oxidative, reductive, and hydrolytic metabolism of methiocarb and the hydrolytic metabolism of carbaryl by liver microsomes and plasma of rats or humans were...
The oxidative, reductive, and hydrolytic metabolism of methiocarb and the hydrolytic metabolism of carbaryl by liver microsomes and plasma of rats or humans were examined. The effects of the metabolism of methiocarb and carbaryl on their nuclear receptor activities were also examined. When methiocarb was incubated with rat liver microsomes in the presence of NADPH, methiocarb sulfoxide, and a novel metabolite, methiocarb sulfone were detected. Methiocarb sulfoxide was oxidized to the sulfone by liver microsomes and reduced back to methiocarb by liver cytosol. Thus, the interconversion between methiocarb and the sulfoxide was found to be a new metabolic pathway for methiocarb by liver microsomes. The product of methiocarb hydrolysis, which is methylthio-3,5-xylenol (MX), was also oxidized to sulfoxide form by rat liver microsomes. The oxidations were catalyzed by human flavin-containing monooxygenase isoform (FMO1). CYP2C19, which is a human cytochrome P450 (CYP) isoform, catalyzed the sulfoxidations of methiocarb and MX, while CYP1A2 also exhibited oxidase activity toward MX. Methiocarb and carbaryl were not enzymatically hydrolyzed by the liver microsomes, but they were mainly hydrolyzed by plasma and albumin to MX and 1-naphthol, respectively. Both methiocarb and carbaryl exhibited PXR and PPARα agonistic activities; however, methiocarb sulfoxide and sulfone showed markedly reduced activities. In fact, when methiocarb was incubated with liver microsomes, the receptor activities were decreased. In contrast, MX and 1-naphthol showed nuclear receptor activities equivalent to those of their parent carbamates. Thus, the hydrolysis of methiocarb and carbaryl and the oxidation of methiocarb markedly modified their nuclear receptor activities.
Topics: Animals; Biotransformation; COS Cells; Carbaryl; Chlorocebus aethiops; Cholinesterase Inhibitors; Constitutive Androstane Receptor; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2C19; Humans; Hydrolysis; Liver; Male; Methiocarb; Microsomes, Liver; Oxidation-Reduction; PPAR alpha; Pregnane X Receptor; Rats, Sprague-Dawley; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid; Transfection
PubMed: 27665777
DOI: 10.2131/jts.41.677 -
Science (New York, N.Y.) Oct 2020
Topics: Animals; Endangered Species; Guinea-Bissau; Insecticides; Kenya; Methiocarb; Raptors
PubMed: 33060355
DOI: 10.1126/science.abd1862 -
Drug Metabolism Letters 2018The use of polypharmacy in the present day clinical therapy has made the identification of clinical drug-drug interaction risk an important aspect of drug development... (Comparative Study)
Comparative Study
BACKGROUND
The use of polypharmacy in the present day clinical therapy has made the identification of clinical drug-drug interaction risk an important aspect of drug development process. Although many drugs can be metabolized to sulfoxide and/or sulfone metabolites, seldom is known on the CYP inhibition potential and/or the metabolic fate for such metabolites.
OBJECTIVE
The key objectives were: a) to evaluate the in vitro CYP inhibition potential of selected parent drugs with sulfoxide/sulfone metabolites; b) to assess the in vitro metabolic fate of the same panel of parent drugs and metabolites.
METHODS
In vitro drug-drug interaction potential of test compounds was investigated in two stages; 1) assessment of CYP450 inhibition potential of test compounds using human liver microsomes (HLM); and 2) assessment of test compounds as substrate of Phase I enzymes; including CYP450, FMO, AO and MAO using HLM, recombinant human CYP enzymes (rhCYP), Human Liver Cytosol (HLC) and Human Liver Mitochondrial (HLMit). All samples were analysed by LC-MS-MS method.
RESULTS
CYP1A2 was inhibited by methiocarb, triclabendazole, triclabendazole sulfoxide, and ziprasidone sulfone with IC50 of 0.71 µM, 1.07 µM, 4.19 µM, and 17.14 µM, respectively. CYP2C8 was inhibited by montelukast, montelukast sulfoxide, montelukast sulfone, tribendazole, triclabendazole sulfoxide, and triclabendazole sulfone with IC50 of 0.08 µM, 0.05 µM, 0.02 µM, 3.31 µM, 8.95 µM, and 1.05 µM, respectively. CYP2C9 was inhibited by triclabendazole, triclabendazole sulfoxide, triclabendazole sulfone, montelukast, montelukast sulfoxide and montelukast sulfone with IC50 of 1.17 µM, 1.95 µM, 0.69 µM, 1.34 µM, 3.61 µM and 2.15 µM, respectively. CYP2C19 was inhibited by triclabendazole and triclabendazole sulfoxide with IC50 of 0.25 and 0.22, respectively. CYP3A4 was inhibited by montelukast sulfoxide and triclabendazole with IC50 of 9.33 and 15.11, respectively. Amongst the studied sulfoxide/sulfone substrates, the propensity of involvement of CY2C9 and CYP3A4 enzyme was high (approximately 56% of total) in the metabolic fate experiments.
CONCLUSION
Based on the findings, a proper risk assessment strategy needs to be factored (i.e., perpetrator and/or victim drug) to overcome any imminent risk of potential clinical drug-drug interaction when sulfoxide/sulfone metabolite(s) generating drugs are coadministered in therapy.
Topics: Acetates; Albendazole; Aldicarb; Biotransformation; Cyclopropanes; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Drug Interactions; Humans; Isoenzymes; Methiocarb; Microsomes, Liver; Piperazines; Quinolines; Risk Assessment; Sulfides; Sulfones; Sulfoxides; Thiazoles; Triclabendazole
PubMed: 30117405
DOI: 10.2174/1872312812666180816164626 -
Molecules (Basel, Switzerland) Dec 2020This paper studies the degradation of methiocarb, a highly hazardous pesticide found in waters and wastewaters, through an electro-Fenton process, using a boron-doped...
This paper studies the degradation of methiocarb, a highly hazardous pesticide found in waters and wastewaters, through an electro-Fenton process, using a boron-doped diamond anode and a carbon felt cathode; and evaluates its potential to reduce toxicity towards the model organism . The influence of applied current density and type and concentration of added iron source, Fe(SO)·5HO or FeCl·6HO, is assessed in the degradation experiments of methiocarb aqueous solutions. The experimental results show that electro-Fenton can be successfully used to degrade methiocarb and to reduce its high toxicity towards . Total methiocarb removal is achieved at the applied electric charge of 90 C, and a 450× reduction in the acute toxicity towards , on average, from approximately 900 toxic units to 2 toxic units, is observed at the end of the experiments. No significant differences are found between the two iron sources studied. At the lowest applied anodic current density, 12.5 A m, an increase in iron concentration led to lower methiocarb removal rates, but the opposite is found at the highest applied current densities. The highest organic carbon removal is obtained at the lowest applied current density and added iron concentration.
Topics: Animals; Biodegradation, Environmental; Daphnia; Ecotoxicology; Electrochemistry; Electrodes; Insecticides; Methiocarb; Water Pollutants, Chemical
PubMed: 33322793
DOI: 10.3390/molecules25245893 -
EFSA Journal. European Food Safety... Oct 2018The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State the United... (Review)
Review
The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State the United Kingdom and co-rapporteur Member State Germany for the pesticide active substance methiocarb are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative use of methiocarb as an insecticide and a bird repellent on maize. The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.
PubMed: 32625712
DOI: 10.2903/j.efsa.2018.5429 -
Frontiers in Veterinary Science 2020Nowadays the intentional poisoning of domestic and wild animals is a crime in the European Union (EU), but as in the past the poison is still used in rural areas of a...
Nowadays the intentional poisoning of domestic and wild animals is a crime in the European Union (EU), but as in the past the poison is still used in rural areas of a number of European countries to kill animals that were considered harmful for human activities. From January 2014 up until October 2020, the Laboratory of Pharmacology and Toxicology of the Faculty of Veterinary Medicine (LFT-FMV) has done the analytical detection of poisoning substances in 503 samples of wildlife and domestic animals and pesticides residues were found in 239 of the samples analyzed. In this retrospective study, toxicology results from domestic species (dog, cat, sheep, cows, and horses), wildlife species (red foxes, birds of prey, lynx, and wild boar), and food baits, are presented. During this period the samples analyzed at the LFT-FMV, were received from all over the country. Analytical detections were performed via solvent extraction followed by thin layer chromatography. Molluscicides (47%, = 109) and Carbamates (24%, = 57) were found to be the first category of pesticides involved in intoxications, in both domestic and wild animals, followed by rodenticides (13%, = 30)-in this group second and third generation, were the most represented; Strychnine is the third (11%, = 26) even though this pesticide has been banned in Portugal since 1988 and in the European Union since 2006 and finally Organophosphates (5%, = 11) in the small number. This study allowed to realize that a great number of positive samples involved banned pesticides (i.e., Aldicarb and Strychnine) but, at the same time, many positives cases were due to the exposure to commercially available products (i.e., Methiocarb and Anticoagulant rodenticides). Also, it's possible to identify the areas where domestic species are the most affected (i.e., Setubal and Lisboa) and the areas where the wild animals are the mainly affected species (i.e., Faro, Castelo Branco, and Bragança).
PubMed: 33521089
DOI: 10.3389/fvets.2020.616293 -
Water Research May 2016Although there are no legal discharge limits for micropollutants into the environment, some regulations have been published in the last few years. Recently, a watch list... (Review)
Review
Although there are no legal discharge limits for micropollutants into the environment, some regulations have been published in the last few years. Recently, a watch list of substances for European Union-wide monitoring was reported in the Decision 2015/495/EU of 20 March 2015. Besides the substances previously recommended to be included by the Directive 39/2013/EU, namely two pharmaceuticals (diclofenac and the synthetic hormone 17-alpha-ethinylestradiol (EE2)) and a natural hormone (17-beta-estradiol (E2)), the first watch list of 10 substances/groups of substances also refers three macrolide antibiotics (azithromycin, clarithromycin and erythromycin), other natural hormone (estrone (E1)), some pesticides (methiocarb, oxadiazon, imidacloprid, thiacloprid, thiamethoxam, clothianidin, acetamiprid and triallate), a UV filter (2-ethylhexyl-4-methoxycinnamate) and an antioxidant (2,6-di-tert-butyl-4-methylphenol) commonly used as food additive. Since little is known about the removal of most of the substances included in the Decision 2015/495/EU, particularly regarding realistic concentrations in aqueous environmental samples, this review aims to: (i) overview the European policy in the water field; (ii) briefly describe the most commonly used conventional and advanced treatment processes to remove micropollutants; (iii) summarize the relevant data published in the last decade, regarding occurrence and removal in aqueous matrices of the 10 substances/groups of substances that were recently included in the first watch list for European Union monitoring (Decision 2015/495/EU); and (iv) highlight the lack of reports concerning some substances of the watch list, the study of un-spiked aquatic matrices and the assessment of transformation by-products.
Topics: Anti-Bacterial Agents; Butylated Hydroxytoluene; Cinnamates; Diclofenac; Environmental Monitoring; Environmental Policy; Estradiol; Estrone; Ethinyl Estradiol; European Union; Phenols; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical
PubMed: 26967909
DOI: 10.1016/j.watres.2016.02.047 -
Analytical Methods : Advancing Methods... Aug 2022High-temperature comprehensive two-dimensional gas chromatography (HTGC × GC) using a longitudinally modulated cryogenic system (LMCS) was developed for the analysis of...
High-temperature comprehensive two-dimensional gas chromatography (HTGC × GC) using a longitudinally modulated cryogenic system (LMCS) was developed for the analysis of low-volatility pesticides in cabbage. The method applied DB-17HT and DB-5HT as the first and second dimensional (D and D) columns, respectively. Twelve pesticides, namely 6 organochlorines (4,4'-DDT, β-endosulfan, endosulfan sulfate, endrin, heptachlor, and dicofol), 4 carbamates (metolcarb, isoprocarb, methiocarb, and carbofuran), 1 organophosphate (chlorpyrifos), and 1 pyrethroid (permethrin), were spiked into cabbage samples and prepared using QuEChERS. The applied oven temperature was up to 340 °C, enabling the elution of all the target pesticides and the matrix. The effects of initial oven temperature program, temperature ramp rate, LMCS trap temperature, and modulation period () on the separation results were investigated, leading to the suitable conditions of 80 °C, 15 °C min, 10 °C, and 12 s, respectively. The method detection limits, signal-to-noise ratio, and recoveries of the compounds were within the ranges of 0.01-0.09 mg kg, 4.26-32.7, and 78-104%, respectively. Good linearity ranges within the concentration range of 0.1-1 ppm with > 0.9134 were also obtained with the intra and interday precisions of the peak areas of 0.4-9.8% and 1.0-10.2%, respectively.
Topics: Brassica; Chromatography, Gas; Hydrocarbons, Chlorinated; Pesticides; Temperature
PubMed: 35929731
DOI: 10.1039/d2ay00998f