RESUMEN
Commercially available insecticides present acute toxicity to the health of fish and other aquatic organisms, which may impair the local aquaculture. This study evaluated the gonadal morphology of freshwater fish exposed to pyriproxyfen and fenthion. Forty-five juvenile male Nile tilapias (Oreochromis niloticus) were divided into control, pyriproxyfen-exposed (0.01 g/L), and fenthion-exposed (0.001 g/L) groups. They were evaluated in three moments (30, 60, and 90 days). The variables analyzed were the gonadosomatic index (GSI), weight to length ratio, seminiferous tubules morphometry (diameter and height), tissue damage, and immunohistochemical analysis for caspase-3, tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF). Pyriproxyfen and fenthion injured the seminiferous tubule tissue, and the damage progressed according to the exposure time. In addition, the GSI gradually reduced over time in all groups compared with the first moment (30 days), while caspase-3, TNF-α, and VEGF values increased only in the fenthion-exposed group. Therefore, pyriproxyfen and fenthion changed the gonadal morphology of male Oreochromis niloticus, which may affect their reproduction in the wild or captivity.
Asunto(s)
Cíclidos , Piridinas , Masculino , Animales , Fentión/metabolismo , Fentión/toxicidad , Caspasa 3/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Organophosphates (OPs), pyrethrins and fipronil, are acaricides commonly used in cattle, mainly as pour on formulations. Scant information is available on their potential interactions with hepatic xenobiotic metabolizing enzymes. This work aimed to evaluate in vitro the potential inhibitory effects of widely employed acaricides on catalytic activities mediated by hepatic cytochrome P450 (CYP) and flavin-monooxygenase (FMO) enzymes in cattle. Bovine (n = 4) liver microsomes were incubated in the absence (control assays) and in presence of different OPs (fenthion, chlorpyrifos, ethion, diazinon and dichlorvos), fipronil and cypermethrin at 0.1-100 µm. Five oxidative enzyme activities were assayed by spectrofluorimetric or HPLC methods: 7-ethoxyresorufin O-deethylase (for CYP1A1), methoxyresorufin O-demethylase (for CYP1A2), benzyloxyresorufin O-debenzylase (for CYP2B), testosterone 6-beta hydroxylase (for CYP3A) and benzydamine N-oxidase (for FMO). All acaricides, particularly phosphorothionate-containing OPs, inhibited to some extent more than one enzyme activity. The most frequent inhibitor was fenthion, which inhibited (p < .05) all enzyme activities tested (from 22% at 1 µm to 72% at 100 µm). However, low inhibitory potencies (IC50s higher than 7 µm) of all acaricides studied were observed against the catalytic activities assayed. Therefore, the risk of in vivo metabolic interactions due to inhibition of monooxygenases would be low under common husbandry conditions.
Asunto(s)
Acaricidas , Microsomas Hepáticos , Bovinos , Animales , Microsomas Hepáticos/metabolismo , Acaricidas/metabolismo , Acaricidas/farmacología , Fentión/metabolismo , Fentión/farmacología , Hígado/metabolismo , Oxidación-ReducciónRESUMEN
Bioconcentration factors (BCFs) measured in the laboratory are important for characterizing the bioaccumulative properties of chemicals entering the environment, especially the potential persistent organic pollutants (POPs), which can pose serious adverse effects on ecosystem and human health. Traditional lethal analysis methods are time-consuming and sacrifice too many experimental animals. In the present study, in vivo solid-phase microextraction (SPME) was introduced to trace the uptake and elimination processes of pesticides in living fish. BCFs and elimination kinetic coefficients of the pesticides were recorded therein. Moreover, the metabolism of fenthion was also traced with in vivo SPME. The method was time-efficient and laborsaving. Much fewer experimental animals were sacrificed during the tracing. In general, this study opened up an opportunity to measure BCFs cheaply in laboratories for the registering of emerging POPs and inspecting of suspected POPs, as well as demonstrated the potential application of in vivo SPME in the study of toxicokinetics of pollutants.
Asunto(s)
Monitoreo del Ambiente , Músculos/metabolismo , Compuestos Orgánicos/metabolismo , Plaguicidas/metabolismo , Tilapia/metabolismo , Animales , Fentión/metabolismo , Humanos , Hidrocarburos Clorados/metabolismo , Microextracción en Fase SólidaRESUMEN
Fenthion (MPP) is a popular organophosphorus pesticide that acts via inhibition of the enzyme cholinesterase. It is well known that fenthion is metabolized by plants, animals and soil microorganisms to sulfone and sulfoxide by oxidation of thioether and is further metabolized by conversion of P = S to P = O (oxon). Although human fenthion poisonings sometimes occur, details of the distribution of fenthion and its metabolites within the bodies of victims are unclear. In this study, we developed and validated an approach that uses liquid chromatography coupled with electrospray ionization-tandem mass spectrometry to quantify the concentrations of fenthion and its five metabolites (MPP-sulfoxide, MPP-sulfone, MPP-oxon, MPP-oxon sulfoxide and MPP-oxon sulfone) in the fluids [blood, cerebral spinal fluid (CSF) and urine] of a human cadaver. The calibration curves were linear in the concentration range 5-200 ng/mL. Our method allowed for repeatable and accurate quantification with intra- and inter-assay coefficients of variation smaller than 8.6% and 11.0%, respectively, for each target compound. We used the developed method to measure the fenthion concentration in the blood of a dead victim of fenthion poisoning and found the concentration to be in the comatose-fatal range. In addition, we detected for the first time fenthion and all five fenthion metabolites in the cadaveric blood and CSF. The concentrations of the oxidized forms of fenthion, including MPP-sulfone and MPP-sulfoxide, were higher in CSF than in the blood.
Asunto(s)
Fentión , Plaguicidas , Animales , Humanos , Fentión/análisis , Fentión/química , Fentión/metabolismo , Compuestos Organofosforados , Sulfóxidos/análisis , SulfonasRESUMEN
Out of the five isoforms of human flavin-containing monooxygenase (hFMO), FMO1 and FMO3 are the most relevant to Phase I drug metabolism. They are involved in the oxygenation of xenobiotics including drugs and pesticides using NADPH and FAD as cofactors. Majority of the characterization of these enzymes has involved hFMO3, where intermediates of its catalytic cycle have been described. On the other hand, research efforts have so far failed in capturing the same key intermediate that is responsible for the monooxygenation activity of hFMO1. In this work we demonstrate spectrophotometrically the formation of a highly stable C4a-hydroperoxyflavin intermediate of hFMO1 upon reduction by NADPH and in the presence of O2. The measured half-life of this flavin intermediate revealed it to be stable and not fully re-oxidized even after 30 min at 15 °C in the absence of substrate, the highest stability ever observed for a human FMO. In addition, the uncoupling reactions of hFMO1 show that this enzyme is <1% uncoupled in the presence of substrate, forming small amounts of H2O2 with no observable superoxide as confirmed by EPR spin trapping experiments. This behaviour is different from hFMO3, that is shown to form both H2O2 and superoxide anion radical as a result of â¼50% uncoupling. These data are consistent with the higher stability of the hFMO1 intermediate in comparison to hFMO3. Taken together, these data demonstrate the different behaviours of these two closely related enzymes with consequences for drug metabolism as well as possible toxicity due to reactive oxygen species.
Asunto(s)
Flavinas/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Oxigenasas/metabolismo , Dicroismo Circular , Escherichia coli , Antagonistas de Estrógenos/química , Antagonistas de Estrógenos/metabolismo , Fentión/química , Fentión/metabolismo , Flavina-Adenina Dinucleótido , Flavinas/química , Humanos , Insecticidas/química , Insecticidas/metabolismo , Cinética , NADP , Oxidación-Reducción , Oxígeno , Oxigenasas/genética , Tamoxifeno/química , Tamoxifeno/metabolismo , Taurina/análogos & derivados , Taurina/química , Taurina/metabolismoRESUMEN
Although fenthion (FEN) is widely used as a broad spectrum insecticide on various crops in many countries, very scant data are available on its biotransformation in humans. In this study the in vitro human hepatic FEN biotransformation was characterized, identifying the relative contributions of cytochrome P450 (CYPs) and/or flavin-containing monooxygenase (FMOs) by using single c-DNA expressed human enzymes, human liver microsomes and cytosol and CYP/FMO-specific inhibitors. Two major metabolites, FEN-sulfoxide and FEN-oxon (FOX), are formed by some CYPs although at very different levels, depending on the relative CYP hepatic content. Formation of further oxidation products and the reduction of FEN-sulfoxide back to FEN by the cytosolic aldehyde oxidase enzyme were ruled out. Comparing intrinsic clearance values, FOX formation seemed to be favored and at low FEN concentrations CYP2B6 and 1A2 are mainly involved in its formation. At higher levels, a more widespread CYP involvement was evident, as in the case of FEN-sulfoxide, although a higher efficiency of CYP2C family was suggested. Hepatic FMOs were able to catalyze only sulfoxide formation, but at low FEN concentrations hepatic FEN sulfoxidation is predominantly P450-driven. Indeed, the contribution of the hepatic isoforms FMO(3) and FMO(5) was generally negligible, although at high FEN concentrations FMO's showed activities comparable to the active CYPs, accounting for up to 30% of total sulfoxidation. Recombinant FMO(1) showed the highest efficiency with respect to CYPs and the other FMOs, but it is not expressed in the adult human liver. This suggests that FMO(1)-catalysed sulfoxidation may represent the major extra-hepatic pathway of FEN biotransformation.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Fentión/metabolismo , Insecticidas/metabolismo , Microsomas Hepáticos/metabolismo , Aldehído Oxidasa/metabolismo , Citosol/metabolismo , ADN Complementario/metabolismo , Relación Dosis-Respuesta a Droga , Fentión/administración & dosificación , Humanos , Insecticidas/administración & dosificación , Oxidación-Reducción , Oxigenasas/metabolismo , Isoformas de Proteínas , Sulfóxidos/metabolismoRESUMEN
We investigated the endocrine-disrupting actions of the organophosphorus pesticide fenthion and related compounds and the influence of metabolic transformation on the activities of these compounds. Fenthion acted as an antagonist of the androgenic activity of dihydrotestosterone (10(-7)M) in the concentration range of 10(-6)-10(-4)M in an androgen-responsive element-luciferase reporter-responsive assay using NIH3T3 cells. The antiandrogenic activity of fenthion was similar in magnitude to that of flutamide. Fenthion also tested positive in the Hershberger assay using castrated male rats. Marked estrogenic and antiestrogenic activities of fenthion and related compounds were not observed in MCF-7 cells. When fenthion was incubated with rat liver microsomes in the presence of NADPH, the antiandrogenic activity markedly decreased, and fenthion sulfoxide was detected as a major metabolite. The oxidase activity toward fenthion was exhibited by cytochrome P450 and flavin-containing monooxygenase. Fenthion sulfoxide was negative in the screening test for antiandrogens, as was fenthion sulfone. However, when fenthion sulfoxide was incubated with liver cytosol in the presence of 2-hydroxypyrimidine, an electron donor of aldehyde oxidase, the extract of the incubation mixture exhibited antiandrogenic activity. In this case, fenthion was detected as a major metabolite of the sulfoxide. Metabolic interconversion between fenthion and fenthion sulfoxide in the body seems to maintain the antiandrogenic activity.
Asunto(s)
Antagonistas de Andrógenos/farmacología , Sistema Endocrino/efectos de los fármacos , Fentión/efectos adversos , Fentión/metabolismo , Insecticidas/efectos adversos , Insecticidas/metabolismo , Receptores Androgénicos/efectos de los fármacos , Animales , Hígado/enzimología , Masculino , Microsomas Hepáticos , Ratas , Ratas Wistar , Sulfóxidos/análisisRESUMEN
The flavin-containing monooxygenase gene family (FMO1-6) in humans encodes five functional isoforms that catalyze the monooxygenation of numerous N-, P- and S-containing drugs and toxicants. A previous single nucleotide polymorphism (SNP) analysis of FMO1 in African-Americans identified seven novel SNPs. To determine the functional relevance of the coding FMO1 variants (H97Q, I303V, I303T, R502X), they were heterologously expressed using a baculovirus system. Catalytic efficiency and stereoselectivity of N- and S-oxygenation was determined in the FMO1 variants using several substrates. The I303V variant showed catalytic constants equal to wild-type FMO1 for methimazole and methyl p-tolyl sulfide. Catalytic efficiency (V(max)/K(m)) of methyl p-tolyl sulfide oxidation by R502X was unaltered. In contrast, methimazole oxidation by R502X was not detected. Both H97Q and I303T had elevated catalytic efficiency with regards to methyl p-tolyl sulfide (162% and 212%, respectively), but slightly reduced efficiency with regards to methimazole (81% and 78%). All the variants demonstrated the same stereoselectivity for methyl p-tolyl sulfide oxidation as wild-type FMO1. FMO1 also metabolized the commonly used insecticide fenthion to its (+)-sulfoxide, with relatively high catalytic efficiency. FMO3 metabolized fenthion to its sulfoxide at a lower catalytic efficiency than FMO1 (27%) and with less stereoselectivity (74% (+)-sulfoxide). Racemic fenthion sulfoxide was a weaker inhibitor of acetylcholinesterase than its parent compound (IC(50) 0.26 and 0.015 mM, respectively). The (+)- and (-)-sulfoxides were equally potent inhibitors of acetylcholinesterase. These data indicate that all the currently known FMO1 variants are catalytically active, but alterations in kinetic parameters were observed.
Asunto(s)
Oxigenasas/metabolismo , Xenobióticos/metabolismo , Acetilcolinesterasa/metabolismo , Animales , Baculoviridae/genética , Baculoviridae/metabolismo , Catálisis , Células Cultivadas , Inhibidores de la Colinesterasa/metabolismo , Fentión/metabolismo , Humanos , Isoenzimas/biosíntesis , Isoenzimas/genética , Microsomas/enzimología , Mutagénesis Sitio-Dirigida , NADP/metabolismo , Nitrógeno/metabolismo , Oxidación-Reducción , Oxigenasas/biosíntesis , Oxigenasas/genética , Sulfóxidos/metabolismo , Transformación BacterianaRESUMEN
The chloroacetamide insecticide alachlor, polyhalogenated cyclic hydrocarbons endrin and chlordane and the organophosphate pesticides chlorpyrifos and fenthion induce oxidative tissue damaging effects including lipid peroxidation and nuclear DNA-single strand breaks. The mechanism involved in the induction of oxidative stress by these xenobiotics is unknown. No information is available regarding whether these pesticides can induce the expression of heat shock (stress) protein (Hsp) genes as a common protective mechanism against tissue damage. The pesticides were administered p.o. individually to female Sprague-Dawley rats in two 0.25 LD50 doses at 0 h and 21 h. The animals were killed at 24 h, and liver, brain, heart and lung tissues were removed to examine the induction of Hsps by Western and Northern blot analysis. In a separate series of experiments, cultured neuroactive PC-12 cells were treated 24 h with 50, 100 or 200 nM concentrations of these pesticides. Alachlor, endrin, chlorpyrifos and fenthion induced Hsp89 alpha and Hsp89 beta in hepatic and brain tissues, as well as in cultured PC-12 cells. Chlordane induced some expression of Hsp89 alpha but not Hsp89 beta in the hepatic and brain tissues of treated rats. Some expression of Hsp89 beta was observed in lung tissues of endrin and alachlor treated animals. These findings were substantiated by Western blot analysis using Hsp90 antibody. Except chlordane all these pesticides induced enhanced synthesis of Hsp90 in cultured PC-12 cells. The results indicate striking tissue differences in the patterns of the Hsps induced by the pesticides which were used, and demonstrate that these pesticides can induce the expression of Hsp89 alpha and Hsp89 beta genes in various target organs of rats. The results support the hypothesis that these genes may be mechanistically involved in protecting tissues against oxidative stress induced by structurally diverse pesticides.
Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Proteínas de Choque Térmico/genética , Plaguicidas/toxicidad , Acetamidas/administración & dosificación , Acetamidas/metabolismo , Acetamidas/toxicidad , Animales , Northern Blotting , Western Blotting , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Células Cultivadas , Cloropirifos/administración & dosificación , Cloropirifos/metabolismo , Cloropirifos/toxicidad , Relación Dosis-Respuesta a Droga , Electroforesis en Gel de Poliacrilamida , Endrín/administración & dosificación , Endrín/metabolismo , Endrín/toxicidad , Femenino , Fentión/administración & dosificación , Fentión/metabolismo , Fentión/toxicidad , Regulación de la Expresión Génica/genética , Corazón/efectos de los fármacos , Proteínas de Choque Térmico/biosíntesis , Proteínas de Choque Térmico/efectos de los fármacos , Dosificación Letal Mediana , Hígado/efectos de los fármacos , Hígado/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Miocardio/metabolismo , Estrés Oxidativo/efectos de los fármacos , Células PC12/citología , Células PC12/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Distribución TisularRESUMEN
Fenthion (O,O-dimethyl-O-[3-methyl-4-(methylthio)-phenyl]-thiophos-phate ) is an organophosphate insecticide. A specific method to quantitate fenthion in postmortem matrices with solid-phase extraction combined with high-performance liquid chromatography-diode-array detection (HPLC-DAD) and gas chromatography-mass spectrometry (GC-MS) is presented. Fenitrothion (O,O-dimethyl-O-[3-methyl-4-nitrophenyl]-thiophosphate) is selected as the internal standard. For sample cleanup, a simple but selective solid-phase extraction is chosen after comparison with traditional liquid-liquid extraction procedures. Homogenized and appropriately diluted aqueous samples are applied, and the analytes are desorbed with 5 mL of dichloromethane. Aliquots of the extract are used for HPLC-DAD and GC-MS analysis, Liquid and GC conditions are as follows: gradient elution with a mixture of methanol and water (10:90 to 90:10, v/v) containing 0.0125M NaOH on an Aluspher RP-Select B column monitoring at 250 nm, and temperature programming from 60 to 300 degrees C on a dimethylpolysiloxane column in the SCAN mode, respectively. This method is applied to a suicidal case involving unsuspected acute intoxication with fenthion (concentration in blood, 3.8 micrograms/mL).
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Fentión/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Insecticidas/análisis , Anciano , Femenino , Fentión/metabolismo , Fentión/envenenamiento , Medicina Legal/métodos , Humanos , Insecticidas/metabolismo , Insecticidas/envenenamiento , SuicidioRESUMEN
Pesticides with N,N-dimethyl and thiomethyl moieties (aminocarb, methiocarb and fenthion) were irradiated under artificial light (lambda > 290 nm) in an amorphous wax phase from Persica laevis DC. The effect of the presence of the wax on the photolysis rate differed in the three pesticides, increasing it in aminocarb, having little effect in methiocarb and slowing it down in fenthion. The presence of the wax affected the qualitative photodegradation behaviour of all the pesticides. The data obtained were compared with those for pirimicarb, which had been studied earlier.
Asunto(s)
Carbamatos/efectos de la radiación , Citrus/química , Fentión/efectos de la radiación , Insecticidas/efectos de la radiación , Metiocarb/efectos de la radiación , Fenilcarbamatos , Fotólisis , Ceras/farmacología , Carbamatos/química , Carbamatos/metabolismo , Fentión/química , Fentión/metabolismo , Insecticidas/química , Insecticidas/metabolismo , Cinética , Luz , Metiocarb/química , Metiocarb/metabolismo , Modelos BiológicosRESUMEN
Identification of degradation products of the organophophorous pesticide fenthion formed in two orange varieties, Valencia Navel and Navel Late, under field conditions has been assessed using liquid chromatography quadrupole time-of-flight mass spectrometry and ion trap mass spectrometry. The structural elucidation of the metabolites was accomplished by the accurate mass measurements provided by the quadrupole time-of-flight mass spectrometer in MS and MS/MS modes. This instrument achieved elemental composition diagnosis for the precursor and product ions with absolute mass error of <5 ppm, which unambiguously establishes the identity of the metabolites even at low concentration. The presence of these compounds was also confirmed by electrospray ionization-ion trap mass spectrometry, performing successive fragmentation steps (MS(n)). Once identified, each molecule was confirmed by comparison with its analytical standard, also used to explore the quantitative capabilities of both mass analyzers. The extraction method was evaluated because it predetermines the metabolites that can be found (e.g., according to their polarity). Recoveries ranged from 70% for fenoxon sulfoxide (the most polar) to 101% for fenthion (the most apolar), which also indicates the method's facility to extract other more polar metabolites if present. Satisfactory linear range (r > 0.99) of more than 2 orders of magnitude was obtained with both analyzers for standards prepared in methanol and in untreated orange extracts. However, the matrix-matched standards showed suppression of the mass signal due to the matrix effect, especially for fenoxon sulfoxide and sulfone. The limits of quantification ranged from 0.005 to 0.015 mg/kg. The QqTOF-MS provided better quantification limits for fenthion and its sulfoxide and sulfone than the IT-MS. The resulting fenthion degration curves in oranges indicated that it was mainly degraded by sunlight photolysis to its sulfoxide and sulfone. However, hydrolysis was also observed by the appearance of fenoxon, fenoxon sulfoxide, and fenoxon sulfone, but always in low concentrations, which can be related to the rain events.
Asunto(s)
Citrus sinensis , Fentión/metabolismo , Espectrometría de Masas/métodos , Inhibidores de la Colinesterasa/análisis , Inhibidores de la Colinesterasa/metabolismo , Fentión/análogos & derivados , Fentión/análisis , Análisis de los Alimentos , Hidrólisis , Insecticidas/análisis , Insecticidas/metabolismo , Espectrometría de Masas/normas , Plaguicidas , Sulfonas , SulfóxidosRESUMEN
The degrading regulations of combined pollutants of chlorfenvinfos and fenthion in red soil were studied, in which soil incubation, gas chromatography with nitrogen-phosphorus detection for analysis are utilized. The main conclusions drawn are as follows: under combined pollution condition, the degrading amount of fenthion was significantly higher than that of fenthion alone in soil; under saturated soil humidity, the degrading amount of fenthion was less changed, while that of chlorfenvinfos was increased by 33.3% - 1250%. Soil drought made degradation amount of fenthion decreased a little, while made chlorfenvinfos increased significantly prior to the 21st day after addition of pesticide; nitrogen fertilizer application stimulated both fenthion and chlorfenvinfos degraded; the chemical degrading amount of fenthion in soil with organic matter eliminated was decreased by 22.4% - 30.8%, while that of chlorfenvinfos was increased 42.1% - 2370% at the earlier stage, and was decreased 11% - 17.3% at the later stage. Therefore, there are differences of degrading regulation between single pesticide pollutant and combined pesticide pollutants in soil, and the degradation of organophosphorus pesticides in combined pollutants are influenced with each other.
Asunto(s)
Clorfenvinfos/metabolismo , Fentión/metabolismo , Insecticidas/metabolismo , Contaminantes del Suelo/metabolismo , Suelo/análisis , Biodegradación Ambiental , Compuestos Organofosforados/metabolismoRESUMEN
The purpose of this research was to determine if the route of administration influenced the biological half life of fenthion, an organophosphorous insecticide. Twenty mg/kg fenthion was given to groups of New Zealand White Rabbits via the oral, subcutaneous and intravenous routes respectively. The distribution of fenthion in the blood of New Zealand rabbits followed an open two compartment model. There were no significant differences in the kinetic parameters (2, beta, K12, K21, Kel) derived for the three different routes of administration. The biological half life of slightly over 11 hours, did not differ significantly with the route of administration.
Asunto(s)
Fentión/metabolismo , Administración Oral , Animales , Fentión/administración & dosificación , Fentión/sangre , Semivida , Inyecciones Intravenosas , Inyecciones Subcutáneas , Cinética , Conejos , Factores de TiempoRESUMEN
The in vivo metabolism of fenthion, an organophosphorus pesticide, and its sulfoxide (fenthion sulfoxide) was examined in goldfish (Carassius auratus). When goldfish were administered fenthion i.p. at a dose of 100 mg/kg, two metabolites were isolated from the tank water. They were identified as fenthion sulfoxide and fenthion oxon, in which > P = S of fenthion is transformed to > P = O, by comparing their mass and UV spectra, and their behavior in HPLC and TLC, with those of authentic standards. However, fenthion sulfone was not detected as a metabolite. The amounts of fenthion, fenthion sulfoxide and fenthion oxon excreted within 4 days were 2.7, 3.4 and 2.5%, of the initial dose of fenthion, respectively. Unchanged fenthion was detected in the body of the fish to the extent of 42-50% of the dose after 10 days, but fenthion sulfoxide and fenthion oxon showed very low concentrations. When fenthion sulfoxide was administered to the fish, about 70% of the dose was excreted unchanged into the tank water within 24 h, but little of the reduced compound, fenthion, was found. In contrast, fenthion was detected at 2.1% of dose in the body of goldfish as a metabolite of fenthion sulfoxide. The fact that fenthion is metabolized to the toxic oxon form in fish presumably has environmental and health implication for its use as a pesticide.
Asunto(s)
Fentión/metabolismo , Carpa Dorada/metabolismo , Insecticidas/metabolismo , Animales , Fentión/toxicidad , Insecticidas/toxicidad , Sulfóxidos/metabolismoRESUMEN
Organophosphorus pesticides are generally transformed by the reactions including oxidation, reduction, hydrolysis, hydroxylation, dehydrochlorination, dealkylation, methylation, isomerization, and conjugate formation. Although the degradation process of pesticides in soils is complicated, main factors may be soil constituents, soil microflora, and chemical structures of pesticides. Chemical structures are especially important for soil metabolism of organophosphorus pesticides, because the priority of the reactions mentioned above is decided. Although organophosphorus pesticides are generally hydrolyzable, the order of hydrolysis varies with chemical structures. It might be said that the slower the hydrolysis rate of the molecule, the more the possibility to be attacked by reactions other than hydrolysis. In such cases, oxidation and reduction are primarily important for the degradation of organophosphorus pesticides. Flooded soils in paddy fields give a favourable environment for the reduction of organophosphorus pesticides having labile substituents such as nitro groups. The threshold of reduction in-flooded soil is expressed as redox potential. Eh, the Eh of paddy soil fluctuates to a great extent, depending on seasons and soil types, especially organic matter content. The result of laboratory experiments with fenthion, disulfoton, Kitazin P (0,0-diisopropyl S-benzyl phosphorothiolate), edifenphos (0-ethyl S,S-diphenyl phosphorodithiolate) and amiprophos (0-ethyl 0-(2-nitro-p-tolyl) N-isopropyl phosphoramidothionate) suggested the participation of several factors mentioned above in the degradation of organophosphorus pesticides.
Asunto(s)
Insecticidas/metabolismo , Suelo , Anaerobiosis , Biodegradación Ambiental , Disulfotón/metabolismo , Fentión/metabolismo , Fungicidas Industriales/metabolismo , Japón , Compuestos Organotiofosforados , Oxidación-Reducción , Factores de TiempoRESUMEN
A case of poisoning with a new organophosphate (fenthion) is reported in which the initial cholinergic crisis was delayed 5 days and recurred 24 days after ingestion. Psychosis was a persistent and sometimes singular manifestation. Because of the high lipid solubility of this pesticide, toxin analysis of repeated fat biopsies was an essential component of the management of this patient.
Asunto(s)
Fentión/envenenamiento , Intento de Suicidio , Tejido Adiposo/metabolismo , Adulto , Encéfalo/metabolismo , Femenino , Fentión/metabolismo , Humanos , Psicosis Inducidas por Sustancias/etiología , Factores de TiempoRESUMEN
The in vitro metabolism of fenthion and its sulfoxide (fenthion sulfoxide) in sea bream (Pagrus major) and goldfish (Carassius auratus) was investigated and compared with that in rats. Fenthion was oxidized to fenthion sulfoxide and the oxon derivative, but not to its sulfone, in the presence of NADPH by liver microsomes of sea bream, goldfish, and rats. These liver microsomal activities of the fish were lower than those of rats but were of the same order of magnitude. The NADPH-linked oxon- and sulfoxide-forming activities of liver microsomes of the fish and rats were inhibited by SKF 525-A, metyrapone, alpha-naphthoflavone, and carbon monoxide. The oxidizing activity to fenthion sulfoxide was also inhibited by alpha-naphthylthiourea. Several cytochrome P450 isoforms and flavin-containing monooxygenase 1 exhibited these oxidase activities. Fenthion sulfoxide was reduced to fenthion with liver cytosol of the fish and rats upon addition of 2-hydroxypyrimidine, N(1)-methylnicotinamide, or butyraldehyde, each of which is an electron donor of aldehyde oxidase, under anaerobic conditions. The activity was inhibited by menadione, beta-estradiol, and chlorpromazine, which are inhibitors of aldehyde oxidase. The activities in the fish livers were similar to those of rat liver. Aldehyde oxidase purified from the livers of sea bream and rats exhibited the reducing activity. Thus, fenthion and fenthion sulfoxide are interconvertible in fish and rats through the activities of cytochrome P450, flavin-containing monooxygenase, and aldehyde oxidase.