Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 41
Filter
Add more filters










Publication year range
1.
Anal Bioanal Chem ; 386(6): 1717-26, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16953314

ABSTRACT

A new and simple procedure for the determination of parathion in human whole blood and urine using direct immersion (DI) solid-phase microextraction (SPME) and gas chromatography/mass spectrometry (GC/MS) is presented. This technique was developed using only 100 microL of sample, and ethion was used as internal standard (IS). A 65-microm Carbowax/divinylbenzene (CW/DVB) SPME fibre was selected for sampling, and the main parameters affecting the SPME process such as extraction temperature, adsorption and desorption time, salt addition, agitation and pH effect were optimized to enhance the sensitivity of the method. This optimization was also performed to allow the qualitative determination of parathion's main metabolite, paraoxon, in blood. The limits of detection and quantitation for parathion were 3 and 10 ng/mL for urine and 25 and 50 ng/mL for blood, respectively. For paraoxon, the limit of detection was 50 ng/mL in blood. The method showed linearity between the LOQ and 50 microg/mL for both matrices, with correlation coefficients ranging from 0.9954 to 0.9999. Precision and accuracy were in conformity with the criteria normally accepted in bioanalytical method validation. The mean absolute recoveries were 35.1% for urine and 6.7% for blood. Other parameters such as dilution of sample and stability were also validated. Its simplicity and the fact that only 100 microL of sample is required to accomplish the analysis make this method useful in forensic toxicology laboratories to determine this compound in intoxications, and it can be considered an alternative to other methods normally used for the determination of this compound in biological media.


Subject(s)
Parathion/blood , Parathion/urine , Solid Phase Microextraction/methods , Humans , Salts
2.
Biopharm Drug Dispos ; 21(5): 193-204, 2000 Jul.
Article in English | MEDLINE | ID: mdl-11180198

ABSTRACT

In order to find what form of hepatic cytochrome P450 (CYP) is involved in the metabolism of parathion to form paraoxon, rats were pretreated with the enzyme inhibitors, such as SKF 525-A and ketoconazole or enzyme inducers, such as dexamethasone, isoniazid, phenobarbital, and 3-methylcholanthrene. Parathion, 3 mg/kg, was infused in 1 min via the jugular vein. In rats pretreated with SKF 525-A or ketoconazole, nonspecific CYP inhibitors, the area under the plasma concentration-time curve from time zero to time infinity (AUC) and total body clearance (Cl) of parathion were significantly greater and slower, respectively, than those in respective control rats, suggesting that parathion was metabolized by CYPs. In rats pretreated with dexamethasone (CYP3A23 inducer), the AUC was significantly smaller (41.5 compared with 52.5 microg min/mL), Cl was significantly faster (72.2 compared with 57.1 mL/min/kg), and the amounts and/or tissue-to-plasma ratios of parathion was significantly (or tended to be) smaller than those in control rats. However, the pharmacokinetic parameters of parathion were not significantly different after pretreatment with other enzyme inducers compared with respective control rats. The above data suggested that parathion was metabolized to paraoxon by dexamethasone-inducible CYP3A23, the induction of which was confirmed by Western blot analysis. This was supported by in vitro intrinsic clearance (Cl(int)) of parathion to form paraoxon in hepatic microsomal fraction; the Cl(int) in rats pretreated with dexamethasone was significantly faster (0.0900 compared with 0.0290 mL/min/mg protein) than that in control rats.


Subject(s)
Aryl Hydrocarbon Hydroxylases , Cytochrome P-450 Enzyme System/metabolism , Enzyme Inhibitors/pharmacology , Insecticides/pharmacokinetics , Parathion/pharmacokinetics , Animals , Blotting, Western , Cytochrome P-450 CYP3A , Cytochrome P-450 Enzyme Inhibitors , Cytochrome P-450 Enzyme System/biosynthesis , Dexamethasone/pharmacology , Drug Interactions , Enzyme Induction/drug effects , Isoenzymes/antagonists & inhibitors , Isoenzymes/biosynthesis , Isoenzymes/metabolism , Isoniazid/pharmacology , Ketoconazole/pharmacology , Male , Methylcholanthrene/pharmacology , Microsomes, Liver/drug effects , Microsomes, Liver/enzymology , Microsomes, Liver/metabolism , Paraoxon/pharmacokinetics , Parathion/blood , Phenobarbital/pharmacology , Proadifen/pharmacology , Rats , Rats, Sprague-Dawley , Tissue Distribution
3.
Clin Chem Lab Med ; 37(6): 639-42, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10475071

ABSTRACT

A simple and rapid method for the analysis of parathion in biological samples is presented. The method consists of the extraction of parathion from blood samples by headspace solid-phase micro-extraction (SPME), followed by capillary gas chromatography and mass spectrometry detection. The recoveries in the blood samples after addition of ammonium sulphate and sulphuric acid were between 85% and 89% compared to samples prepared in water. Linearity was established over a concentration range of 0.1-5 microg/g blood with acceptable coefficients of correlation and limits of detection reached 0.02-0.05 microg/g. The time for an analysis is 57 minutes for one sample, including the extraction step. In conclusion, HS-SPME in combination with GC/MS is an effective method for the determination and quantification of parathion-ethyl and parathion-methyl in biological material.


Subject(s)
Cholinesterase Inhibitors/blood , Insecticides/blood , Parathion/blood , Calibration , Gas Chromatography-Mass Spectrometry/methods , Hot Temperature , Humans , Regression Analysis , Sensitivity and Specificity
4.
Occup Environ Med ; 56(7): 449-53, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10472315

ABSTRACT

OBJECTIVES: This study presents criteria for assessing the individual pesticide burden of workers in the chemical industry. METHODS: A group of 1003 workers exposed to methylparathion or ethylparathion (alkyl phosphates), propoxur (carbamate), or cyfluthrin (pyrethroid) was investigated. After exposure to methylparathion or ethylparathion the methylparathion or ethylparathion and methylparaoxon or ethylparaoxon concentrations in plasma, the p-nitrophenol concentration in urine, and the activities of cholinesterase and acetylcholinesterase were measured. For exposure to propoxur the propoxur concentration in plasma, the 2-isopropoxyphenol concentration in urine, and the cholinesterase and acetylcholinesterase activities were measured. For exposure to cyfluthrin the cyfluthrin concentration in plasma was measured. RESULTS: At the same propoxur concentration only workers with a low individual acetylcholinesterase activity reported symptoms. Workers who metabolised cyfluthrin rapidly reported less symptoms than workers with a lower rate of metabolism. This tendency was also evident in cases of mixed exposure (cyfluthrin and methylparathion). CONCLUSIONS: In the assessment of exposure to pesticides susceptibility of the individual person has to be considered.


Subject(s)
Chemical Industry , Environmental Monitoring/methods , Occupational Exposure , Pesticides/blood , Acetylcholinesterase/blood , Adult , Cholinesterases/blood , Disease Susceptibility , Humans , Insecticides/blood , Insecticides/poisoning , Insecticides/urine , Middle Aged , Nitriles , Occupational Exposure/adverse effects , Parathion/blood , Parathion/poisoning , Parathion/urine , Pesticides/poisoning , Pesticides/urine , Propoxur/blood , Propoxur/poisoning , Propoxur/urine , Pyrethrins/blood , Pyrethrins/poisoning , Pyrethrins/urine , Risk Assessment
5.
J Anal Toxicol ; 20(7): 579-86, 1996.
Article in English | MEDLINE | ID: mdl-8934310

ABSTRACT

Gas chromatography-mass spectrometry (GC-MS), which combines the separation power of GC with the power of MS for the identification of unknown compounds, possesses high potential in systematic toxicological analysis (STA). Different factors, however, do not allow this potential to be fully exploited. Between them, the low selectivity of the mass spectrometer operating in continuous scan plays a critical role, in many cases precluding the possibility of selecting mass spectra in the total ion chromatogram (TIC) sufficiently clean for a positive identification by library search, even when using reverse search algorithms. Moreover, the large amount of information contained in GC-MS data file that results from the analysis of a biological extract makes the efforts of manual search almost useless and requires the availability of reliable methods for the automated detection and identification of peaks in a TIC. In this paper, a simple procedure that improves the performance of a bench-top GC-MS system in the purification of mass spectra of coeluting compounds and that can be easily combined with the automated processing of a GC-MS data file is described. It is based on the subtraction of the intensities of successive pairs of scans in the TIC, on the detection of positive and negative peaks in the transformed chromatograms, and on the search of the corresponding background-subtracted electron ionization mass spectra against reference libraries. In order to evaluate the proposed procedure, GC-MS data files obtained for the analysis of extracts of blank whole blood spiked with more than 100 drugs, poisons, and their metabolites at a concentration of 0.5 mg/L were used. Compared with the search of the raw TICs, the proposed procedure increased the number of identified substances and, in many cases, obtained higher match quality values for identification.


Subject(s)
Gas Chromatography-Mass Spectrometry/methods , Hazardous Substances/blood , Amitriptyline/blood , Chlorpromazine/blood , Humans , Maprotiline/blood , Morphine/blood , Parathion/blood
6.
J Anal Toxicol ; 20(3): 151-4, 1996.
Article in English | MEDLINE | ID: mdl-8735194

ABSTRACT

A sensitive capillary gas chromatographic (GC) method for the simultaneous determination of the organophosphate insecticide, parathion, and its active metabolite, paraoxon, in biological samples was developed. This method involved a simple liquid-liquid extraction of parathion and paraoxon from water, plasma, or tissues and capillary GC determination using electron-capture detection and splitless injection; malathion was used as the internal standard. A gradient oven temperature program was used; the injection port and detector temperatures were 200 and 300 degrees C, respectively. These techniques allowed quantitative determination of parathion and paraoxon at 9-210-ng/ml. concentrations;recoveries ranged from 79.4 to 110.3% for tissues and from 91.9 to 100.0% for plasma and water. The within-day and between-day coefficients of variation were less than 8.0%. The method was used to characterize the pharmacokinetics of parathion and paraoxon and the tissue distribution of paraoxon in rainbow trout.


Subject(s)
Insecticides/analysis , Paraoxon/analysis , Parathion/analysis , Animals , Brain Chemistry , Chromatography, Gas , Insecticides/blood , Kidney/chemistry , Malathion/blood , Malathion/metabolism , Muscles/chemistry , Myocardium/chemistry , Oncorhynchus mykiss , Paraoxon/blood , Parathion/blood , Reference Standards , Reproducibility of Results , Tissue Distribution
7.
Toxicol Lett ; 78(3): 245-52, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7542808

ABSTRACT

Paraoxon and chlorpyrifos-oxon, active metabolites of the organophosphorus insecticides parathion and chlorpyrifos, can be detoxified via A-esterases and aliesterases. These enzyme activities were measured in various tissues of Sprague-Dawley rats. High A-esterase activities were detected in liver, serum and liver mitochondrial/microsomal fractions. Low or no A-esterase activities were detected in other tissues and tissue fractions. A-Esterase substrate:substrate activity ratios suggest that the substrates are probably not degraded by the same enzyme. Highest aliesterase activities were observed in the small intestine and liver with moderate activity in kidney, serum and lungs. Low activities were noted in brain, spleen and skeletal muscle.


Subject(s)
Carboxylic Ester Hydrolases/metabolism , Chlorpyrifos/metabolism , Parathion/metabolism , Animals , Blood Proteins/metabolism , Brain/drug effects , Brain/enzymology , Carboxylesterase , Cell Fractionation , Chlorpyrifos/blood , Chlorpyrifos/toxicity , Intestine, Small/drug effects , Intestine, Small/enzymology , Kidney/drug effects , Kidney/enzymology , Liver/drug effects , Liver/enzymology , Lung/drug effects , Lung/enzymology , Male , Microsomes, Liver/drug effects , Microsomes, Liver/enzymology , Mitochondria, Liver/drug effects , Mitochondria, Liver/enzymology , Muscle, Skeletal/drug effects , Muscle, Skeletal/enzymology , Parathion/blood , Parathion/toxicity , Rats , Rats, Sprague-Dawley , Spleen/drug effects , Spleen/enzymology , Substrate Specificity , Tissue Distribution
8.
Arch Toxicol ; 67(2): 79-84, 1993.
Article in English | MEDLINE | ID: mdl-8481105

ABSTRACT

We measured in nine patients, poisoned by organophosphorus agents (ethyl parathion, ethyl and methyl parathion, dimethoate, or bromophos), erythrocyte and serum cholinesterase activities, and plasma concentrations of the organophosphorus agent. These patients were treated with pralidoxime methylsulphate (Contrathion), administered as a bolus injection of 4.42 mg.kg-1 followed by a continuous infusion of 2.14 mg.kg-1/h, a dose regimen calculated to obtain the presumed "therapeutic" plasma level of 4 mg.l-1, or by a multiple of this infusion rate. Oxime plasma concentrations were also measured. The organophosphorus agent was still detectable in some patients after several days or weeks. In the patients with ethyl and methyl several days or weeks. In the patients with ethyl and methyl parathion poisoning, enzyme reactivation could be obtained in some at oxime concentrations as low as 2.88 mg.l-1; in others, however, oxime concentrations as high as 14.6 mg.l-1 remained without effect. The therapeutic effect of the oxime seemed to depend on the plasma concentrations of ethyl and methyl parathion, enzyme reactivation being absent as long as these concentrations remained above 30 micrograms.l-1. The bromophos poisoning was rather mild, cholinesterases were moderately inhibited and increased under oxime therapy. The omethoate inhibited enzyme could not be reactivated.


Subject(s)
Cholinesterase Reactivators/blood , Insecticides/poisoning , Organophosphate Poisoning , Pralidoxime Compounds/blood , Adult , Aged , Cholinesterase Inhibitors/blood , Cholinesterases/blood , Dimethoate/blood , Dimethoate/poisoning , Erythrocytes/enzymology , Female , Humans , Insecticides/blood , Male , Methyl Parathion/blood , Methyl Parathion/poisoning , Middle Aged , Organophosphorus Compounds/blood , Organothiophosphates/blood , Parathion/blood , Parathion/poisoning
9.
Pharmacol Toxicol ; 69(4): 233-7, 1991 Oct.
Article in English | MEDLINE | ID: mdl-1956875

ABSTRACT

Pharmacokinetics, metabolism (in vivo and in vitro), elimination and tissue distribution of 14C-parathion was studied after intravenous administration of 0.5 mg/kg to newborn, 1 week and 8 weeks old piglets. Body clearance increased from 7 ml/min./kg in newborn to 35 and 121 ml/min./kg in 1 and 8 weeks old piglets, respectively. Urinary excretion during the first 3 hr rose from 18 to 48 and 82% of the dose in newborn, 1 and 8 week old piglets. The main metabolite of parathion was p-nitrophenyl-glucuronide making up 85% of the urinary 14C excretion. About 6% was excreted as p-nitrophenyl-sulfate and only 1% as free (non-conjugated) p-nitrophenol. Unchanged parathion or paraoxon was not detectable in urine from any of the age groups. The in vitro experiments showed that biotransformation of parathion took place only when cofactors for oxidative reactions were present, indicating that oxidation is the first and necessary metabolic step and that hydrolysis does not contribute significantly to the elimination of parathion. The highest concentration of 14C 3 hr after administration was found in kidney and liver. In newborn piglets the 14C-concentration in tissues was higher than or equal to the plasma concentration. The 14C tissue/plasma ratio decreased with age for all tissues except kidney. Parathion was present in high concentrations in plasma, liver and kidney from newborn piglets, whereas the level just exceeded the detection limit in the 8 week old ones. Paraoxon was clearly detectable in plasma and liver from newborn piglets, while only traces were found in the older groups.


Subject(s)
Animals, Newborn/metabolism , Parathion/pharmacokinetics , Swine/metabolism , Animals , Blood Proteins/metabolism , Liver/metabolism , Parathion/blood , Parathion/metabolism , Swine/growth & development , Tissue Distribution
11.
Food Chem Toxicol ; 23(1): 67-71, 1985 Jan.
Article in English | MEDLINE | ID: mdl-4038684

ABSTRACT

The effect of serum and serum fractions on the cutaneous penetration of [35S]parathion from surface deposits or adsorbed formulations was determined. The total quantity of [35S]parathion which penetrated pig skin was significantly greater when the receptor fluid was whole swine serum or the 500 or 10,000 MW retentate from ultrafiltration of the serum than when phosphate-buffered saline (PBSA), the 500 MW filtrate or distilled water, respectively, was used. The enhanced penetration was observed without any associated evidence of metabolic change and with both dosing methods. This result is consistent with the hypothesis that serum-parathion interactions are the cause of the enhanced penetration. The apparent solubility of parathion was 16 times greater in whole serum than in PBSA. Gel-filtration chromatography of the serum-parathion mixture revealed that approximately 11% of the 35S activity was associated with two protein fractions which had consistently different elution volumes. Most of the radioactivity, however, was not tightly bound and the equilibrium between bound and free parathion was rapidly reversible. The result of interaction between parathion and serum proteins was an increased apparent solubility, relative to PBSA, and increased cutaneous penetration. The significance of these findings is clear: when designing in vitro systems to model in vivo percutaneous absorption, investigators should consider that the affinity of the fluid interfacing with the dermis in vivo may influence the kinetics of penetration when subcutaneous blood flow is low.


Subject(s)
Parathion/metabolism , Skin Absorption , Animals , Chemical Phenomena , Chemistry , Chromatography, Gel , Chromatography, High Pressure Liquid , In Vitro Techniques , Molecular Weight , Parathion/blood , Skin/blood supply , Solubility , Swine
12.
Schweiz Med Wochenschr ; 113(23): 861-2, 1983 Jun 11.
Article in German | MEDLINE | ID: mdl-6879138

ABSTRACT

In a 41-year-old patient administration of 5 g parathion led to respiratory failure and unconsciousness. Ventilatory support and antidote therapy were initiated early. However, only extensive gastric lavage and lowering of the plasma concentration by hemoperfusion with activated carbon resulted in the crucial elimination of the poison. Antidote and supportive measures may overcome the hazards of cholinesterase-inhibition, but not the direct toxic effect on the cardiovascular system which is currently regarded as the predominant cause of death.


Subject(s)
Parathion/poisoning , Adult , Female , Gastric Lavage , Hemoperfusion , Humans , Parathion/blood , Suicide, Attempted
13.
J Invest Dermatol ; 80(4): 291-3, 1983 Apr.
Article in English | MEDLINE | ID: mdl-6403629

ABSTRACT

Percutaneous penetration of three insecticides was studied by two methods. The indirect (excretion analysis) and direct (skin patch removal) methods for determining penetration were compared in rats. Radiolabeled solutions of parathion, carbaryl, and DDT were applied to previously shaved rats at the rate of 4 micrograms/cm2. Recoveries of radioactivity in urine, feces, application site, and various tissues were measured at intervals over a 5-day period. Urinary excretion rates were corrected for incomplete excretion by intraperitoneal applications. In the 5 days following intraperitoneal administration, the urinary excretion of parathion and carbaryl was greater than 80% while less than 5% of DDT was excreted. A good correlation was found between the indirect and direct methods utilized to determine percutaneous absorption rates with the compounds tested at the later time intervals. All compounds showed more than 85% dermal penetration within 5 days. At the early time intervals (greater than 24 h), penetration by the direct method was significantly greater for parathion and carbaryl than by the indirect method.


Subject(s)
Insecticides/toxicity , Skin/drug effects , Animals , Carbaryl/blood , Carbaryl/toxicity , Carbaryl/urine , DDT/blood , DDT/toxicity , DDT/urine , Humans , Insecticides/urine , Liver/analysis , Male , Methods , Parathion/blood , Parathion/toxicity , Parathion/urine , Rabbits , Rats , Rats, Inbred Strains , Saimiri , Skin/analysis , Swine
15.
Arch Toxicol ; 42(4): 311-5, 1979 Sep.
Article in German | MEDLINE | ID: mdl-518296

ABSTRACT

After ingestion of 200-300 ml E 605-forte (i.e., 100-150 g parathion) a maximal concentration of 10.2 mg/l could be measured in the plasma of a male patient. An extracorporeal hemoperfusion was carried out using XAD-4 resin. The clearance valued 83 ml/min at a blood flow of 100 ml/min, which is about 40% higher compared to perfusion on activated charcoal. The described method is possibly an improved technique which could raise the rate of survival following parathion intoxication. In our study, however, the fatal end could not be prevented due to the intake of a very high dose of the poison.


Subject(s)
Hemoperfusion , Parathion/poisoning , Charcoal , Humans , Ion Exchange Resins , Male , Middle Aged , Parathion/blood , Parathion/metabolism , Suicide , Tissue Distribution
16.
Arch Toxicol ; 41(1): 43-8, 1978 Oct 13.
Article in English | MEDLINE | ID: mdl-568924

ABSTRACT

Binding of parathion and paraoxon to bovine serum albumin (BSA) and human serum albumin (HSA) was studied by using equilibrium dialysis. The concentration of unbound organophosphate was determined from its anticholinesterase activity. Binding of parathion to BSA was shown to be reversible. The organophosphates interact with only one type of binding sites in BSA and HSA. The affinity constants at pH 7.2 and 4 degrees C for the interaction of BSA or HSA and parathion were found to be 2.7 X 10(6) and 1.5 X 10(6) M-1, respectively. The affinity constants for the interaction of the serum albumins and paraoxon were considerably lower, 6.0 X 10(3) and 1.6 X 10(4) M-1, respectively. Lowering the pH from 7.2 to 4.8 did not significantly affect the binding parameters. The great difference of affinity of the serum albumins to parathion and paraoxon is discussed with respect to the fate of parathion in the body.


Subject(s)
Paraoxon/blood , Parathion/blood , Serum Albumin, Bovine/metabolism , Serum Albumin/metabolism , Animals , Binding Sites , Cattle , Dialysis , Humans , Kinetics , Protein Binding
19.
Anaesthesist ; 25(12): 572-8, 1976 Dec.
Article in German | MEDLINE | ID: mdl-1008248

ABSTRACT

We examined the possibility that haemoperfusion with coated activated charcoal might be used in the therapy of alkyl phosphate intoxications. The criterion used was the effect of haemoperfusion on the elimination of alkyl phosphates from the blood. Clearance values for haemoperfusion of nitrostigmine, demeton-S-methyl sulfoxide and dimethoate were determined in vitro. Very good clearance values were ascertained at a blood flow rate of 100ml/min (mitrostigmine 59.20ml/min, demeton-S-methyl sulfoxide 83.70 ml/min, dimethoate 87.84 ml/min). Measurements of the nitrostigmine clearance as a function of various nitrostigmine concentrations in plasma showed that haemoperfusion is effective over a concentration range covering two powers of ten. A 7-h haemoperfusion with coated activated charcoal was performed on a suicide patient with severe nitrostigmine intoxication (Folidol-öl). Clearance values were obtained which were to be expected on the basis of the in vitro investigations. The nitrostigmine concentrations in the extracorporeal blood plasma fell as a result of haemoperfusion to a mid-value of 55 per cent of the initial level. In the patient the level of nitrostigmine in the blood rose showing that there had been a redistribution of nitrostigmine from the tissue or a subsequent absorption from the gastrointestinal tract into the vessels. The results support the use of haemoperfusion with coated activated charcoal in very severe cases of alkyl phosphate intoxication or where standard therapy fails.


Subject(s)
Parathion/poisoning , Perfusion/methods , Adult , Blood , Blood Flow Velocity , Charcoal , Dimethoate/blood , Filtration , Humans , Male , Parathion/blood , Parathion/metabolism , Sulfoxides/blood
SELECTION OF CITATIONS
SEARCH DETAIL
...