Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 176
Filtrar
1.
J Pharmacol Toxicol Methods ; 100: 106610, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31302166

RESUMO

INTRODUCTION: Paraquat (PQ) is one of the most toxic herbicides to humans. However, it is still in use in many countries, including Japan, and many incidents, such as homicides, intentional ingestions, and occupational accidents, have been reported thus far. In PQ poisoning cases, it is possible to predict severity and prognosis using nomograms. Therefore, if the serum PQ level is determined immediately, a treatment plan can be rapidly established. However, most known analytical methods are time-consuming and therefore hardly ever contribute to patient treatment. METHODS: We developed a new method for PQ quantitation in serum by combining a probe electrospray ionization technique with mass spectrometry. This method requires virtually no serum pretreatment and can yield quantitation values in 18 s. RESULTS: We applied the proposed method to samples from real poisoning cases and compared the results with those obtained via liquid-chromatography-tandem mass spectrometry, revealing the absence of any significant differences at the 5% significance level (t(8) = 1.000, p > .05). The limits of detection and quantitation were 0.004 and 0.015 µg/L, respectively, and the calibration curve exhibited good linearity over the concentration range of 0.015-4.0 µg/mL (r2 = 0.998). DISCUSSION: As the proposed method is fast and easy to perform, it should be useful in emergency medical settings.


Assuntos
Herbicidas/sangue , Paraquat/sangue , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida , Herbicidas/envenenamento , Humanos , Limite de Detecção , Paraquat/envenenamento , Fatores de Tempo
2.
J Pharm Biomed Anal ; 174: 175-181, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31170631

RESUMO

Glufosinate and glyphosate, which are non-selective herbicides that include an amino acid moiety in their structures, are frequently used worldwide to control unwanted vegetation. Unfortunately, these readily available herbicides are also used by people to commit suicide, and thus represent important chemicals of interest in the fields of clinical medicine and forensics. Because of the high water solubility of these herbicides, most analytical methods for their detection require a derivatization step, which results in longer analysis times. Therefore, derivatization-based methods do not currently contribute to judgements on treatment decisions in emergency medicine. In this study, we addressed this limiting factor by developing an ultra-rapid and simple analytical technique using a combination of probe electrospray ionization (PESI) and tandem mass spectrometry (MS/MS), which gives quantitative results within 0.3 min. Herbicide standards were added to human serum that was then subjected to analysis (N = 5 per concentration). The analysis was repeated daily over eight consecutive days. The limit of detection (LOD) was 0.59 µg/mL for glufosinate and 0.20 µg/mL for glyphosate. The limit of quantitation (LOQ), i.e., the lowest point on the calibration curves, was 1.56 µg/mL for both the herbicides. The matrix effects were observed at three different concentrations (between 95.7%-104% for glufosinate, and between 90.7%-95.7% for glyphosate). When applied to samples taken from actual poisoning cases (six samples for each herbicide), the present method gave almost the same quantitative values as those obtained by conventional high-performance liquid chromatography with fluorescence detection. Thus, we believe that PESI-MS/MS could emerge as a rapid diagnosis method in the clinical emergency field.


Assuntos
Aminobutiratos/sangue , Glicina/análogos & derivados , Herbicidas/sangue , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Aminobutiratos/envenenamento , Calibragem , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Glicina/sangue , Glicina/envenenamento , Herbicidas/envenenamento , Humanos , Limite de Detecção , Padrões de Referência , Reprodutibilidade dos Testes , Extração em Fase Sólida
3.
Am J Emerg Med ; 37(8): 1600.e5-1600.e6, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31053371

RESUMO

INTRODUCTION: This report describes changes in blood and urine concentrations of glyphosate potassium over time and their correlations with clinical symptoms in a patient with acute glyphosate potassium poisoning. CASE REPORT: A 67-year-old man visited the emergency center after ingesting 250 mL of a glyphosate potassium-based herbicide 5 h before. He was alert but presented with nausea, vomiting, and bradyarrhythmia with atrial fibrillation (tall T waves). Laboratory findings revealed a serum potassium level of 6.52 mEq/L. After treatment with an injection of calcium gluconate, insulin with glucose, bicarbonate, and an enema with polystyrene sulfonate, the patient's serum potassium level normalized and the bradyarrhythmia converted to a normal sinus rhythm. During admission, the blood and urine concentration of glyphosate and urine aminomethylphosphonic acid (AMPA, a glyphosate metabolite) was measured at regular time intervals. The patient's glyphosate blood concentration on admission was 11.48 mg/L, and it had decreased rapidly by 16 h and maintained about 1mgl/L by 70 h after admission. Urine glyphosate and AMPA levels had also decreased rapidly by 6 h after admission. DISCUSSION: Glyphosate potassium poisoning causes hyperkalemia. Blood concentrations of glyphosate were decreased rapidly by 16 h after admission, and urine concentrations were also decreased by 6 h after admission.


Assuntos
Glicina/análogos & derivados , Herbicidas/sangue , Herbicidas/envenenamento , Hiperpotassemia/induzido quimicamente , Idoso , Arritmias Cardíacas/induzido quimicamente , Glicina/sangue , Glicina/envenenamento , Glicina/urina , Herbicidas/urina , Humanos , Hiperpotassemia/sangue , Hiperpotassemia/tratamento farmacológico , Masculino , Náusea/induzido quimicamente , Potássio/sangue , Tentativa de Suicídio , Resultado do Tratamento , Vômito/induzido quimicamente
4.
Carbohydr Polym ; 214: 317-327, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30926003

RESUMO

Development of novel biocompatible sensor material suitable for modest, cost-effective, and rapid practical application is a demanding research interest in the field of electroanalytical chemistry. In this context, for the first time, we utilized biocompatible chitosan-pectin biopolyelectrolyte (CS-PC BPE) complex for the simultaneous electroreduction of an important antibiotic drug (metronidazole-MNZ) and herbicide (metribuzin-MTZ). This sensor reveals an attractive welfares such as simplicity, biocompatibility, and low production cost. Under optimized experimental conditions, the electroanalytical investigation confirmed that CS-PC BPE modified glassy carbon electrode (CS-PC BPE/GCE) was found to sense MNZ and MTZ in the nanomolar range. Moreover, as-prepared CS-PC BPE/GCE exhibited prominent selectivity, stability, and reproducibility. Additionally, the possible MNZ and MTZ sensing mechanism of CS-PC BPE/GCE have been discussed in detail. Lastly, real sample analysis was also carried out and revealed from several investigations that the CS-PC BPE/GCE is a good electrochemical sensor system for the detection of targeted analytes.


Assuntos
Materiais Biocompatíveis/química , Quitosana/química , Metronidazol/sangue , Pectinas/química , Polieletrólitos/química , Triazinas/sangue , Antibacterianos/sangue , Antibacterianos/química , Carbono/química , Quitosana/síntese química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Química Verde/métodos , Herbicidas/sangue , Herbicidas/química , Humanos , Limite de Detecção , Metronidazol/química , Peso Molecular , Oxirredução , Pectinas/síntese química , Reprodutibilidade dos Testes , Triazinas/química , Viscosidade
5.
Clin Exp Nephrol ; 23(4): 474-483, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30859350

RESUMO

BACKGROUND: The herbicide paraquat (1, 1'-dimethyl-4, 4'-bipyridylium dichloride; PQ) is a poison well-known to cause delayed mortality due to acute kidney injuries (AKI). This study examines the changes in serum amino acids (AAs) metabolite profiles as surrogate markers of renal cell metabolism and function after paraquat poisoning. METHODS: To identify the metabolic profiling of free serum AAs and its metabolites, serum from 40 paraquat-poisoned patients with or without AKI is collected. LC-MS/GC-MS is performed to analyze AA molecules. A Cox proportional hazard model was used to assess for incidence of AKI. Receiver operating characteristic (ROC) curve is applied to evaluate AKI occurrence and prognosis. RESULTS: A total of 102 serum AAs and its metabolites were identified. Compared with non-AKI patients, 37 varied significantly in AKI patients. The univariate Cox proportional hazard model analysis revealed that the estimated PQ amount, plasma PQ concentration, urine PQ concentration, APACHE, SOFA scores and 16 amino acids correlated with the incidence of AKI. Further analyses revealed that 3-methylglutarylcarnitine, 1-methylimidazoleacetate, and urea showed higher cumulative hazard ratios for the occurrence of AKI during follow-up (P < 0.05). The area under the curve (AUC) of 3-methylglutarylcarnitine, 1-methylimidazoleacetate and urea were 0.917, 0.857, 0.872, respectively. CONCLUSION: 3-methylglutarylcarnitine, 1-methylimidazoleacetate and urea were associated with AKI in patients with paraquat intoxication.


Assuntos
Lesão Renal Aguda/sangue , Aminoácidos/sangue , Carnitina/análogos & derivados , Glutaratos/sangue , Herbicidas/envenenamento , Imidazóis/sangue , Paraquat/envenenamento , Ureia/sangue , Lesão Renal Aguda/induzido quimicamente , Adulto , Área Sob a Curva , Biomarcadores/sangue , Carnitina/sangue , Estudos de Casos e Controles , Feminino , Herbicidas/sangue , Herbicidas/urina , Humanos , Masculino , Metaboloma , Pessoa de Meia-Idade , Paraquat/sangue , Paraquat/urina , Envenenamento/sangue , Envenenamento/urina , Modelos de Riscos Proporcionais , Curva ROC , Adulto Jovem
7.
Mol Cell Endocrinol ; 482: 45-56, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30550814

RESUMO

The aim of the present study was to compare the effect of oral and subcutaneous exposure to a glyphosate-based herbicide (GBH) on the female reproductive system, specifically in the ovaries and uterus of prepubertal lambs. To this end, ewe lambs were exposed to a s.c. (n: 5) or an oral (n: 5) environmentally relevant dose of GBH (2 mg/kg/day) or to vehicle (controls, n: 12), from postnatal day (PND) 1 to PND14. Serum glyphosate and aminomethylphosphonic acid (AMPA) concentrations were measured on PND15 and PND45. The ovaries and uterus were obtained and weighed on PND45. Ovarian follicular dynamics and uterine morphological features were determined by picrosirius-hematoxylin staining. The proliferation marker Ki67 was evaluated by immunohistochemistry in ovarian and uterine samples. Glyphosate but not AMPA was detected in serum of exposed lambs on PND15, whereas neither glyphosate nor AMPA were detected on PND45. Controls were negative for glyphosate and AMPA on PND15 and PND45. GBH exposure did not affect ovarian or uterine weight. However, on PND45, the ovary of GBH-exposed lambs showed altered follicular dynamics, increased proliferation of granulosa and theca cells, and decreased mRNA expression of FSHR and GDF9, whereas their uterus showed decreased cell proliferation but no alterations in the histomorphology or gene expression. In conclusion, GBH exposure altered the ovarian follicular dynamics and gene expression, and the proliferative activity of the ovaries and uterus of lambs. It is noteworthy that all the adverse effects found in the ovaries and uterus of both GBH-exposed groups were similar, independently of the administration route.


Assuntos
Glicina/análogos & derivados , Herbicidas/efeitos adversos , Ovário/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Útero/efeitos dos fármacos , Administração Oral , Animais , Animais Recém-Nascidos , Proliferação de Células , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Glicina/efeitos adversos , Glicina/sangue , Glicina/farmacologia , Fator 9 de Diferenciação de Crescimento/genética , Herbicidas/sangue , Herbicidas/farmacologia , Injeções Subcutâneas , Isoxazóis/sangue , Tamanho do Órgão/efeitos dos fármacos , Ovário/citologia , Ovário/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/genética , Receptores do FSH/genética , Carneiro Doméstico , Tetrazóis/sangue , Útero/citologia , Útero/metabolismo
8.
Wei Sheng Yan Jiu ; 47(6): 993-997, 2018 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-30593335

RESUMO

OBJECTIVE: To establish a simple and rapid ultra-performance liquid chromatography tandem mass spectrometry( UPLC-MS/MS) method for the determination of paraquat in serum, and to apply to the toxicokinetics of paraquat in rats. METHODS: The samples separated on ACQUITY UPLC BEH HILIC column( 2. 1 mm × 50 mm, 1. 7 µm)with acetonitrile-50 mmol/L ammonium formate( 0. 4% formic acid) as mobile phase. The analytes were analyzed using ESI operating in the positive multiple reaction monitoring( MRM) mode. The method was used in toxicokinetic study in poisoned rat. Toxicokinetic parameters were calculated by WinNonlin 7. 0 statistical software. RESULTS: Paraquat was linear in the range of 0. 3-1000. 0 µg/L, the recovery rate was 89. 0%-107. 7%, and the relative standard deviation( RSD) 1. 9%-13. 8%( n = 6). Toxicokinetic parameterswere as follows: C_(max), T_(max)and T_(1/2) were( 46. 50 ± 5. 11) mg/L, 0. 167 h, ( 63. 2 ±16. 2) h, respectively. CONCLUSION: This method is highly sensitive, high accuracy and is suitable for the analysis of paraquat in the toxicokinetic study in rats.


Assuntos
Herbicidas , Paraquat , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Herbicidas/sangue , Herbicidas/toxicidade , Paraquat/sangue , Paraquat/toxicidade , Ratos , Toxicocinética
9.
Chem Res Toxicol ; 31(10): 1080-1085, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30230318

RESUMO

We have documented that the herbicide propanil is immunotoxic in mice, and our in vitro tissue culture experiments largely recapitulate the in vivo studies. Laboratory studies on environmental contaminants are the most meaningful when these studies are conducted using concentrations that approximate levels in the environment. Many techniques to measure the distribution and pharmacokinetics (PK) on compounds rely on techniques, such as liquid scintillation counting (LSC) of radio-labeled starting compound, that require concentrations higher than environmental levels. The aim of this study was to compare tissue PK after exposure to propanil concentrations more relevant to levels of exposure to agricultural workers and the general population to concentrations previously reported for laboratory studies. To this end, we conducted a study to measure propanil distribution in three immune organs, using ultrasensitive accelerator mass spectrometry (AMS). We used two doses: the lower dose modeled levels expected in the environment or long-term occupational exposure to low doses, while the higher dose was to model the effects of an accidental exposure. Our results showed that the distribution and PK profiles from these two different concentrations was markedly different. The profile of the high dose (concentration) exposure was indicative of saturation of the detoxifying capability of the animal. In contrast, at the lower environmentally relevant concentration, in vivo concentrations of propanil in spleen, liver, and blood dropped to a very low level by 720 min. In conclusion, these studies highlight the differences in PK of propanil at these two doses, which suggests that the toxicity of this chemical should be re-investigated to obtain better data on toxic effects at doses relevant for humans.


Assuntos
Herbicidas/farmacocinética , Propanil/farmacocinética , Animais , Radioisótopos de Carbono/química , Relação Dose-Resposta a Droga , Feminino , Meia-Vida , Herbicidas/sangue , Herbicidas/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Propanil/sangue , Propanil/farmacologia , Baço/efeitos dos fármacos , Baço/metabolismo
10.
Toxicology ; 410: 171-181, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30118794

RESUMO

The objective of this study was to evaluate the potential for non-invasive biomonitoring of 2,4-Dichlorophenoxyacetic acid (2,4-D) in saliva. Using an in vitro rat salivary gland epithelial cell (SGEC) system, a collection of experiments investigating chemical protein binding, temporal and directional transport, as well as competitive transport with para-aminohippuric acid (PAH), a substrate for renal organic anion transporters, was conducted to identify cellular transport parameters required to computationally model salivary transport of 2,4-D. Additionally, a physiological protein gradient was implemented to mimic physiologically relevant concentrations of protein in rat plasma and saliva, and under these conditions the transfer of 2,4-D was markedly slower, driven by increased protein binding (i.e. reduced free 2,4-D species available to cross salivary barrier). The rate of transfer was directly proportional to the amount of unbound 2,4-D and demonstrated no indication of active transport. An in vivo assessment of 2,4-D exposure in rats revealed non-linear protein binding in plasma, indicating saturated protein binding and increased levels of unbound 2,4-D species at higher doses. A strong correlation between 2,4-D concentrations in saliva and unbound 2,4-D in plasma was observed (Pearson correlation coefficient = 0.95). Saliva:plasma 2,4-D ratios measured in vivo (0.0079) were consistent within the linear protein binding range and expected 2,4-D levels from occupational exposures but were significantly different than ratios measured in vitro (physiological conditions) (0.034), possibly due to 2,4-D concentrations in saliva not being at equilibrium with 2,4-D concentrations in blood, as well as physiological features absent in in vitro settings (e.g. blood flow). We demonstrated that 2,4-D is consistently transported into saliva using both in vitro and in vivo models, making 2,4-D a potential candidate for human non-invasive salivary biomonitoring. Further work is needed to understand whether current sensor limits of detection are sufficient to measure occupationally relevant exposures.


Assuntos
Ácido 2,4-Diclorofenoxiacético/análise , Monitoramento Ambiental/métodos , Herbicidas/análise , Saliva/química , Ácido 2,4-Diclorofenoxiacético/sangue , Ácido 2,4-Diclorofenoxiacético/farmacocinética , Animais , Polaridade Celular/efeitos dos fármacos , Células Epiteliais , Herbicidas/sangue , Herbicidas/farmacocinética , Masculino , Exposição Ocupacional , Cultura Primária de Células , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Glândulas Salivares/citologia , Glândulas Salivares/metabolismo , Junções Íntimas/efeitos dos fármacos
11.
J Pharm Biomed Anal ; 159: 11-17, 2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-29960039

RESUMO

Paraquat is an effective herbicide chemical but a highly toxic compound for humans and animals. The measurement of paraquat concentration in blood is important to clinic or forensic practice. Herein, a method has been developed for the analysis of paraquat in human blood using dried blood spot (DBS) extraction and subsequent UHPLC-HRMS analysis. Three droplets (100 µL each) of blood were spotted on the Whatman® FTA classic card and then let dry by microwave irradiation (1200 W) for 5 min to prepare DBS. An 8 mm diameter punch was removed from the center of DBS and extracted with 190 µL of mobile phase (20 mM ammonium acetate with 0.1% formic acid and 5% acetonitrile in ultra-pure water) and 10 µL of internal standard (paraquat-d8, 100 ng/mL). After ultrasonic treatment for 10 min, the tube was centrifuged, and the supernatant was then filtered by 0.2 µm membrane and injected into the UHPLC-HRMS system. The method was validated considering the following parameters: selectivity, LOD and LLOQ, linearity, precision, accuracy. The method showed satisfactory linearity in the range of 1-1000 ng/mL, with high determination coefficient (0.9986). LOD was 0.5 ng/mL, and LLOQ was 1 ng/mL. Selectivity, intra and inter day precision and accuracy were acceptable. The validated method was then applied to authentic blood samples and has proved to be a simple, fast and reliable procedure for the determination of paraquat in blood.


Assuntos
Teste em Amostras de Sangue Seco/métodos , Herbicidas/sangue , Paraquat/sangue , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Humanos
12.
Toxicol Lett ; 295: 307-313, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30010034

RESUMO

Diuron is a broad-spectrum phenylurea derived herbicide which is commonly used across the globe. Diuron is toxic to the reproductive system of animals and carcinogenic to rat urothelium, and recently found to be genotoxic in human cells. In in vivo, it is metabolized predominately into 3-(3,4-dichlorophenyl)-1-methyl urea (DCPMU) in humans and 3-(3, 4-dichlorophenyl)urea (DCPU) in animals. Information on diuron toxicokinetics and related toxicity in human placenta is absent. We have investigated the toxicokinetics of diuron in ex vivo human placental perfusion and in in vitro human placental microsomes and human trophoblastic cancer cells (BeWo). Diuron crossed human placenta readily in placental perfusion. Furthermore, diuron was metabolized into DCPMU in perfused placenta and in in vitro incubations using microsomes from placentas of smokers. In incubations with placental microsomes from non-smokers, and in BeWo cells, metabolism to DCPMU was detected but only with the highest used diuron concentration (100 µM). Diuron metabolism was inhibited upon addition of α-naphthoflavone, a CYP1A1 inhibitor, underscoring the role of CYP1A1 in the metabolism. In conclusion, it is evident that diuron crosses human placenta and diuron can be metabolized in the placenta to a toxic metabolite via CYP1A1. This implicates in vivo fetal exposure to diuron if pregnant women are exposed to diuron, which may result in fetotoxicity.


Assuntos
Citocromo P-450 CYP1A1/metabolismo , Diurona/sangue , Herbicidas/sangue , Troca Materno-Fetal , Placenta/irrigação sanguínea , Placenta/enzimologia , Circulação Placentária , Ativação Metabólica , Linhagem Celular Tumoral , Diurona/efeitos adversos , Feminino , Herbicidas/efeitos adversos , Humanos , Cinética , Microssomos/enzimologia , Gravidez , Medição de Risco , Fumar/efeitos adversos , Fumar/sangue , Toxicocinética
13.
Basic Clin Pharmacol Toxicol ; 123(3): 356-359, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29569337

RESUMO

The correlation between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication and the parameters of metabolic impairment was examined in the last eight male survivors of 80 workers exposed to TCDD during the production of herbicides in a chemical factory in 1965-1967. Their median TCDD blood level was 112 (46-390) pg/g lipids, and the median TCDD body deposit was 3.9 (0.8-11.7) µg. This puts these patients into the most severely intoxicated group of subjects, according to back-calculated levels of TCDD. The median TCDD blood level in eight controls was 12 pg/g (<0.10 to 22.2 pg/g). Markers of metabolic impairment - diabetes, dyslipidaemia, arterial hypertension, carotid artery plaque, skin microvascular reactivity, eye fundus hypertensive angiopathy and history of coronary heart disease - were assessed and compared to a general male population of comparable age. Measured parameters compared with a population of comparable age were as follows: prevalence of diabetes (62.5% versus 17.6%), arterial hypertension (87.5% versus 71.8%), dyslipidaemia (87.5% versus 88.8%), history of coronary heart disease (62.5% versus 26.0%) and eye fundus hypertension angiopathy (50% versus 14%). All eight patients (100% versus 43%) developed plaques in carotid arteries, six had stenosis >50% and two had a carotid intervention (stenting or endarterectomy). Total cholesterol levels decreased compared to the earlier study this patient group in 2008, most likely due to a more intensive use of lipid-lowering drugs. Several metabolic parameters were higher (diabetes as much as 3.5-fold) in the group of severely TCDD-intoxicated subjects than in a general population of comparable age. This suggests that TCDD plays a role in the development of metabolic impairment and vascular changes.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Exposição Ocupacional/efeitos adversos , Dibenzodioxinas Policloradas/toxicidade , Idoso , Carga Corporal (Radioterapia) , Doenças Cardiovasculares/etiologia , República Tcheca/epidemiologia , Diabetes Mellitus/etiologia , Poluentes Ambientais/sangue , Poluentes Ambientais/toxicidade , Seguimentos , Herbicidas/sangue , Herbicidas/toxicidade , Humanos , Masculino , Dibenzodioxinas Policloradas/sangue , Prevalência
14.
PLoS One ; 13(1): e0191149, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29342170

RESUMO

2,4-Dichlorophenoxyacetic acid (2,4-D) is a chlorophenoxy herbicide used worldwide. We describe a high-performance liquid chromatography (HPLC) method with UV detection for the determination of 2,4-D in female and male rat serum. This allows to observe the change of serum 2,4-D concentration in rats with time and its pharmacokinetics characteristics with a simple, rapid, optimized and validated method. The serum samples are pretreated and introduced into the HPLC system. The analytes are separated in a XDB-C18 column with a mobile phase of acetonitrile (solvent A) and 0.02 M ammonium acetate (containing 0.1% formic acid) (solvent B) using a gradient elution at a flow rate of 1.0 mL/min. The wavelength for UV detection was set at 230 nm. Calibration curve for 2,4-D was constructed over a range of 0.1-400 mg/L. The method was successfully applied to study the pharmacokinetics of 2,4-D in rats in this study. After oral administration of 300 mg/kg and 60 mg/kg 2,4-D, the mean Cmax values were 601.9 and 218.4 mg/L, the AUC0→∞ values were 23,722 and 4,127 mg×h/L and the clearance (Cl) were 1.10 and 0.02 L/(h×kg), respectively. The developed method was found to be specific, precise, reproducible and rapid.


Assuntos
Ácido 2,4-Diclorofenoxiacético/sangue , Cromatografia Líquida de Alta Pressão/métodos , Herbicidas/sangue , Ácido 2,4-Diclorofenoxiacético/farmacocinética , Animais , Calibragem , Feminino , Herbicidas/farmacocinética , Ratos , Ratos Sprague-Dawley , Espectrofotometria Ultravioleta
15.
Fa Yi Xue Za Zhi ; 34(6): 590-594, 2018 Jun.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-30896094

RESUMO

OBJECTIVES: To develop a method to screen and quantify 10 common herbicides (paraquat, diquat, glyphosate, glufosinate, cyanazine, atrazine, metazachlor, acetochlor, chlorsulfuron, and metsulfuron) in blood. METHODS: With acetonitrile-water solution [V(acetonitrile)∶V(water)=3∶1] as protein precipitant, 10 common herbicides in blood were detected using ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). RESULTS: All the 10 herbicides had good linearity in their linear range (coefficient of determination R2≥0.993), with the recovery rates 67.4%-111.9%, the relative standard deviations 1.5%-10.8%, the accuracies 85.1%-106.1%, intra-day precisions 2.7%-13.5%, and inter-day precisions 3.3%-13.3%. CONCLUSIONS: This method is easy to operate with high recovery rates. It enables rapid and accurate qualitative screening and quantitative analysis of various herbicides in blood simultaneously.


Assuntos
Herbicidas , Cromatografia Líquida de Alta Pressão , Herbicidas/sangue , Espectrometria de Massas , Espectrometria de Massas em Tandem
17.
Basic Clin Pharmacol Toxicol ; 122(2): 271-277, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28862800

RESUMO

The last eight survivors of 80 workers accidentally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during production of herbicides based on trichlorophenoxyacetic acid in 1965-1967 in a chemical factory were followed. All were men, mean age 72.4 ± 1.3 years. Their current median TCDD blood level was 112 (46-390) pg/g lipids. Neurological examination revealed central nervous system impairment in all individuals and signs of polyneuropathy in 87.5%, which was confirmed by a nerve conduction study (NCS) in 75%. A Lanthony test demonstrated acquired dyschromatopsia in 87.5% of the patients, with deterioration of mean colour confusion index (CCI) from 1.52 ± 0.39 in 2010 to 1.73 ± 0.41 in 2016. Single-photon emission computer tomography (SPECT) of the brain showed focal reduction of perfusion in various brain locations in all patients and worsening in six patients. Visual-evoked potentials (VEP) was abnormal in 62.6% of individuals. Most patients complained of psychological problems. The neuropsychological test battery showed most positive impairments in the Trail Making Test evaluating processing speed (average level in the range of mild neurocognitive impairment), which correlated with mean CCI (p < 0.05). CONCLUSION: Fifty years after exposure, blood levels of TCDD are still 10 times higher than the general population. NCS, VEP, Lanthony test and SPECT findings deteriorated from examination of these patients in 2004 and in 2010. The total of abnormal tests per patient in 2016 is very high. Minor differences among patients and their reduced count may explain why the number of impairments in 2016 does not correlate with TCDD blood level.


Assuntos
Acidentes de Trabalho , Encéfalo/efeitos dos fármacos , Indústria Química , Herbicidas/efeitos adversos , Síndromes Neurotóxicas/etiologia , Exposição Ocupacional/efeitos adversos , Saúde do Trabalhador , Dibenzodioxinas Policloradas/efeitos adversos , Polineuropatias/induzido quimicamente , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Circulação Cerebrovascular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Visão de Cores/efeitos dos fármacos , Potenciais Evocados Visuais/efeitos dos fármacos , Herbicidas/sangue , Herbicidas/síntese química , Humanos , Masculino , Condução Nervosa/efeitos dos fármacos , Exame Neurológico , Testes Neuropsicológicos , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/fisiopatologia , Síndromes Neurotóxicas/psicologia , Imagem de Perfusão/métodos , Dibenzodioxinas Policloradas/sangue , Dibenzodioxinas Policloradas/síntese química , Polineuropatias/diagnóstico , Polineuropatias/fisiopatologia , Fatores de Tempo , Tomografia Computadorizada de Emissão de Fóton Único
18.
Artigo em Chinês | MEDLINE | ID: mdl-29081105

RESUMO

Objective: To determine the scavenging effect and the change of metabolism of paraquat (PQ) using hemoperfusion (HP) once and twice within 12 hours after intoxication and explore the better scheme of HP. Methods: 18 beagles were randomly divided into 3 groups. Single HP group, Double HP group and Control group. Peripheral veins blood was collected at different times within 48 hours after exposure in each group. Toxin concentration was measured, analyzed and compared among 3 groups. Results: 6 hours after exposure, Single HP group and Double HP group has finished the first HP treatment, and the concentration of PQ was lower than that of the control group, the difference was statistically significant (P<0.05) . 10 hours after exposure, there was no statistical difference of toxin concentration among 3 groups (P>0.05) . 12 hours after exposure, Double HP group has finished the second HP treatment, the concentration of PQ was significantly lower than that of Single HP group and Control group (P<0.05) . 24 hours and 48 hours after exposure, there was no statistical difference of toxin concentration among 3 groups (P>0.05) . Statistical difference were not observed in toxicokinetical parameters among 3 groups (P>0.05) . Conclusion: HP treatment once and twice within 12 hours after intoxication could effectively reduce the toxin concentration in the peripheral veins blood after HP for about 4 hours, then the toxin concentration would return to the same level as Control group quickly. It was suggested that at the beginning of poisoning, HP treatment once or twice could not significantly change the metabolism of paraquat.


Assuntos
Hemoperfusão , Herbicidas/sangue , Herbicidas/envenenamento , Paraquat/sangue , Paraquat/metabolismo , Paraquat/envenenamento , Animais , Grupos Controle , Cães , Distribuição Aleatória , Resultado do Tratamento
19.
Forensic Sci Int ; 278: 304-312, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28800549

RESUMO

A liquid chromatography-tandem mass spectrometry method with solid-phase extraction (SPE) was developed and validated for the detection and quantitation of bentazone and its two hydroxylated metabolites, 6-hydroxybentazone and 8-hydroxybentazone, in postmortem blood. Sample cleanup was performed using a hydrophilic-lipophilic balanced (HLB) SPE cartridge and then separated on a C18 LC column using a gradient elution of 0.1% formic acid in distilled water and 0.1% formic acid in methanol. The identification of bentazone and its hydroxylated metabolites was performed using tandem mass spectrometry with electrospray ionization in negative ion mode with selective reaction monitoring. The retention times of bentazone, 6-hydroxybentazone, 8-hydroxybentazone, and 2-methyl-4-chlorophenoxyacetic acid (MCPA, internal standard) appeared separately in the chromatogram. The matrix effect, recovery, and process efficiency of bentazone were 75.3%, 103.6% and 77.9%, respectively. In addition, good accuracy (88.2-110.5%), precision (0.5-7.5%, bias), and linearity (5-500ng/mL) were obtained with this method. The limit of detection (LOD) of bentazone, 6-hydroxybentazone, and 8-hydroxybentazone were 0.05, 0.5, and 0.5ng/mL, respectively. The method developed herein was applied to authentic samples from three fatal cases from 2016 for the determination of the corresponding bentazone and its metabolites levels. The concentration ranges of bentazone, 6-hydroxybentazone, and 8-hydroxybentazone in the heart blood from the three victims were 46.0-91.8, 4.2-6.2, and 0.2-0.6µg/mL, respectively.


Assuntos
Benzotiadiazinas/sangue , Herbicidas/sangue , Idoso , Benzotiadiazinas/envenenamento , Cromatografia Líquida , Feminino , Toxicologia Forense , Herbicidas/envenenamento , Humanos , Limite de Detecção , Pessoa de Meia-Idade , Estrutura Molecular , Reprodutibilidade dos Testes , Extração em Fase Sólida , Suicídio , Espectrometria de Massas em Tandem
20.
Reprod Toxicol ; 73: 201-213, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28847621

RESUMO

Atrazine is an endocrine disruptor affecting testicular steroidogenesis, and promoting testicular atrophy and 3ß-HSD reduction. However, it remains unknown whether these effects are reversible or permanent. To address this issue was the aim of this study. Exposition of rats to 200mg/kg of atrazine resulted in transient increase in testicular weight, seminiferous tubules dilation and atrophy, and reduction in Leydig cell 3ß-HSD. Testicular atrophy and 3ß-HSD reduction were more pronounced after the recovery period of 75days. There was increase in aromatase expression after long-term exposure but it returned to control level after recovery. Moreover, there was increase in ED1-/ED2+, ED1+/ED2+ and ED1+/ED2- macrophages, in the recovery group. These macrophages were positive for 3ß-HSD, thereby raising possibility of their involvement in steroidogenesis. These findings further emphasize the adverse effects of atrazine on male reproduction, highlighting that testicular damages may be irreversible even after a recovery period longer than the spermatogenic cycle.


Assuntos
Atrazina/toxicidade , Herbicidas/toxicidade , Testículo/efeitos dos fármacos , 3-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Aromatase/metabolismo , Atrazina/sangue , Herbicidas/sangue , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Masculino , Ratos Wistar , Testículo/metabolismo , Testículo/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA