RESUMO
SCOPE: Different metabolic and excretion pathways of the benzyl glucosinolate breakdown products benzyl isothiocyanate and benzyl cyanide are investigated to obtain information about their multiple fate after ingestion. Detailed focus is on the so far underestimated transformation/excretion pathways-protein conjugation and exhalation. METHODS AND RESULTS: Metabolites, protein conjugates, and non-conjugated isothiocyanates are determined in plasma, urine, and breath of seven volunteers after consuming freeze-dried nasturtium or bread enriched with nasturtium. Samples are collected up to 48 h at selected time points. The metabolites of the mercapturic acid pathway are detectable in plasma up to 24 h after consumption. Additionally, mercapturic acid is the main metabolite in urine, but non-conjugated benzyl isothiocyanate is detectable as well. Protein conjugates show high amounts in plasma even 48 h after consumption. In breath, benzyl isothiocyanate and benzyl cyanide are detectable up to 48 h after consumption. CONCLUSION: Isothiocyanates are not only metabolized via the mercapturic acid pathway, but also form protein conjugates in blood and are exhaled. To balance intake and excretion, it is necessary to investigate all potential metabolites and excretion routes. This has important implications for the understanding of physiological and pharmacological effects of isothiocyanate-containing products.
Assuntos
Nasturtium , Tiocianatos/farmacocinética , Tioglucosídeos/farmacocinética , Acetonitrilas/sangue , Acetonitrilas/farmacocinética , Acetonitrilas/urina , Acetilcisteína/sangue , Acetilcisteína/urina , Adulto , Pão , Testes Respiratórios/métodos , Feminino , Alimentos Fortificados , Humanos , Pessoa de Meia-Idade , Folhas de Planta , Tiocianatos/sangue , Tiocianatos/metabolismo , Tiocianatos/urina , Tioglucosídeos/sangue , Tioglucosídeos/metabolismo , Tioglucosídeos/urinaRESUMO
OBJECTIVE: To establish the method for measurement of acetonitrile in blood and urine by head-space gas chromatography. METHODS: DB-ALC1 (30 m x 320 microm x 1.8 microm) and DB-ALC2 (30 m x 320 microm x 1.2 microm) capillary column were used to measure the acetonitrile in blood and urine with the isopropanol as internal standard reference. RESULTS: The limits of detection of acetonitrile in both blood and urine were 0.5 microg/mL, with a linear range of 5-1000 microg/mL (r = 0.999).The accuracy of this method was 93.2%-98.0%. The RSD for the intra-day and inter-day were less than 3.7%. CONCLUSION: The method is capable for measurement analysis of acetonitrile in blood and urine.
Assuntos
Acetonitrilas/sangue , Acetonitrilas/intoxicação , Acetonitrilas/urina , Cromatografia Gasosa/métodos , Cianetos/sangue , Cianetos/urina , Toxicologia Forense/métodos , Humanos , Reprodutibilidade dos Testes , Tentativa de SuicídioRESUMO
OBJECTIVE@#To establish the method for measurement of acetonitrile in blood and urine by head-space gas chromatography.@*METHODS@#DB-ALC1 (30 m x 320 microm x 1.8 microm) and DB-ALC2 (30 m x 320 microm x 1.2 microm) capillary column were used to measure the acetonitrile in blood and urine with the isopropanol as internal standard reference.@*RESULTS@#The limits of detection of acetonitrile in both blood and urine were 0.5 microg/mL, with a linear range of 5-1000 microg/mL (r = 0.999).The accuracy of this method was 93.2%-98.0%. The RSD for the intra-day and inter-day were less than 3.7%.@*CONCLUSION@#The method is capable for measurement analysis of acetonitrile in blood and urine.
Assuntos
Humanos , Acetonitrilas/urina , Cromatografia Gasosa/métodos , Cianetos/urina , Toxicologia Forense/métodos , Reprodutibilidade dos Testes , Tentativa de SuicídioRESUMO
1. Tissue distribution, metabolism, and disposition of oral (0.2-20 mg/kg) and intravenous (0.2 mg/kg) doses of [2-(14)C]dibromoacetonitrile (DBAN) were investigated in male rats and mice. 2. [(14)C]DBAN reacts rapidly with rat blood in vitro and binds covalently. Prior depletion of glutathione (GSH) markedly diminished loss of DBAN. Chemical reaction with GSH readily yielded glutathionylacetonitrile. 3. About 90% of the radioactivity from orally administered doses of [(14)C]DBAN was absorbed. After intravenous administration, 10% and 20% of the radioactivity was recovered in mouse and rat tissues, respectively, at 72 h. After oral dosing, three to four times less radioactivity was recovered, but radioactivity in stomach was mostly covalently bound. 4. Excretion of radioactivity into urine exceeded that in feces; 9-15% was exhaled as labeled carbon dioxide and 1-3% as volatiles in 72 h. 5. The major urinary metabolites were identified by liquid chromatography-mass spectrometry, and included acetonitrile mercaptoacetate (mouse), acetonitrile mercapturate, and cysteinylacetonitrile. 6.The primary mode of DBAN metabolism is via reaction with GSH, and covalent binding may be due to reaction with tissue sulphydryls.
Assuntos
Acetonitrilas/metabolismo , Acetonitrilas/farmacocinética , Radioisótopos de Carbono/metabolismo , Radioisótopos de Carbono/farmacocinética , Acetonitrilas/administração & dosagem , Acetonitrilas/química , Acetonitrilas/urina , Administração Oral , Animais , Radioisótopos de Carbono/administração & dosagem , Radioisótopos de Carbono/química , Cromatografia Líquida , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Injeções Intravenosas , Masculino , Espectrometria de Massas , Camundongos , Ratos , Especificidade da Espécie , Compostos de Sulfidrila/urina , Distribuição TecidualRESUMO
OBJECTIVES: To assess the concentration of acetonitrile (a saturated aliphatic nitrile) in the urine of habitual cigarette smokers and non-smokers, as exposure to smoke can be measured by monitoring ambient air or by in vivo tests, but acetonitrile measured in exhaled breath is reportedly a quantitative marker of recent smoking behaviour. SUBJECTS AND METHODS: The study included 101 volunteers (57 men and 44 women, mean age 49 years). An absence of urinary tract infection on urine analysis or clinical history was mandatory. The subjects were classified into five groups, i.e. a control group of non-smokers and four groups according to the number of cigarettes smoked daily. Urine samples were stored at 8 degrees C until acetonitrile was measured, within 24 h of collection, using proton-transfer reaction mass spectrometry (PTR-MS). Each measurement was repeated at least 10 times, and the mean used for statistical analysis. RESULTS: The mean (sd) acetonitrile level in the urine of 46 non-smokers was 3.74 (1.78) parts per billion volatile (ppbv). The concentration of acetonitrile increased with the number of cigarettes smoked daily, the highest concentration being in the subgroup of 13 very heavy smokers (>30 cigarettes/day) with means up to 28.04 (5.38) ppbv. CONCLUSION: PTR-MS is a quick, noninvasive online method for determining urinary acetonitrile levels, a marker for recent active and passive smoking behaviour, and thus for checking compliance. As smoking has been shown to affect the genesis of bladder cancer, further studies are required to determine the association of acetonitrile with bladder cancer.
Assuntos
Acetonitrilas/urina , Fumar/urina , Biomarcadores/urina , Feminino , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-IdadeRESUMO
Accurate diagnosis of acetonitrile ingestion is critical to management. Often this involves differentiating nail polish remover (acetone) from nail glue remover (acetonitrile). Initial symptoms of acetonitrile ingestion are indistinguishable from those of acetone and common alcohols. However, acetonitrile is metabolized to cyanide, producing severe delayed toxicity. Acetonitrile produced increased serum osmolality and osmolal gap, but these findings are non-specific and normal values cannot rule out potentially fatal exposure. Acetone, but not acetonitrile, was detectable in urine or serum with Acetest tablets; both were unreactive with a ketone dipstick. Acetone and acetonitrile could be detected with routine gas chromatography methods for alcohols. Both substances had identical retention times on the widely used stationary phase, 5% Carbowax 20M on graphitized carbon, and with GasChrom 254. Three other systems afforded unique retention times, but acetonitrile was easily mistaken for ethanol in two. Physicians and laboratories must take care to avoid misdiagnosis of acetonitrile ingestion as exposure to acetone, ethanol or another alcohol.
Assuntos
Acetonitrilas/intoxicação , Cosméticos/intoxicação , Acetona/intoxicação , Acetonitrilas/sangue , Acetonitrilas/urina , Acidose/diagnóstico , Criança , Cromatografia Gasosa , Humanos , Corpos Cetônicos/sangue , Corpos Cetônicos/urina , Concentração Osmolar , Intoxicação/diagnósticoRESUMO
Chloroacetonitrile (CAN), a drinking water disinfectant by-product, possesses mutagenic and carcinogenic properties. The objective of this study was to investigate the biologic fate of CAN, using whole body autoradiographic (WBA) techniques. Male Sprague-Dawley rats were treated with a tracer dose of [2-14C]CAN (i.v., 88 muCi/kg, spec. act 4.07 mCi/mmol). At various time intervals (0.08, 1, 3, 6, 12, 24, and 48 h) after treatment, rats were processed for WBA. Over 12 h after administration, the radioactivity excreted in urine, feces, and exhaled as 14CO2 accounted for 51%, 2.7%, and 12% of the dose, respectively. Only 0.8% of the administered dose was exhaled as unchanged CAN. At an early time interval (5 min) extensive accumulation of radioactivity was observed in liver, kidney, and gastrointestinal (G.I.) walls. In addition, high levels of 14C were detected in the thyroid gland, lung bronchioles, adrenal cortex, salivary gland, and testes. At 1 h following administration, the olfactory bulb, olfactory receptor area of the brain and lumbar cistern showed high accumulations of radioactive CAN or its equivalents. At 3, 6, and 12 h after treatment, the radioactivity diffused homogeneously in all tissues and reconcentrated in several organs at later time periods (24 and 48 h). Our studies indicate extensive metabolic biotransformation of CAN in rats. The retention of radioactivity in the tissues of the thyroid gland, G.I., testes, brain and eye suggest that those organs are potential target sites of CAN toxicity.
Assuntos
Acetonitrilas/farmacocinética , Poluentes Químicos da Água/farmacocinética , Acetonitrilas/toxicidade , Acetonitrilas/urina , Córtex Suprarrenal/metabolismo , Animais , Autorradiografia , Fezes/química , Processamento de Imagem Assistida por Computador , Córtex Renal/metabolismo , Aparelho Lacrimal/metabolismo , Fígado/metabolismo , Masculino , Ratos , Ratos Endogâmicos , Distribuição Tecidual , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/urinaRESUMO
The excretion and tissue distribution of [1-14C]dichloroacetonitrile and [2-14C]dichloroacetonitrile were studied in male Fischer 344 rats and male B6C3F1 mice. Three dose levels of dichloroacetonitrile (DCAN) (0.2, 2, or 15 mg/kg) were administered to rats and two dose levels of DCAN (2 or 15 mg/kg) to mice. Daily excreta including exhaled volatiles and radiolabeled carbon dioxide (14CO2) were analyzed for radiolabeled carbon (14C) until greater than 70% of the radioactivity was excreted. At that time the animals were sacrificed and tissues were collected. Tissues and excreta were analyzed for 14C by combustion and liquid scintillation counting. Rats administered [1-14C]DCAN excreted 62 to 73% of the 14C in 6 days, with 42 to 45% in urine, 14 to 20% in feces, and 3 to 8% as CO2. Rats administered [2-14C]DCAN excreted 82 to 86% of the 14C in 48 hr, with 35 to 40% in urine, 33 to 34% as CO2, and 10 to 13% in feces. Mice administered [1-14C]DCAN excreted 83 to 85% of the 14C in 24 hr, with 64 to 70% in urine, 9 to 13% in feces, and 5 to 6% as CO2. Mice administered [2-14C]DCAN excreted 84 to 88% of the 14C in 24 hr with 42 to 43% in urine, 8 to 11% in feces, and 31 to 37% as CO2. Liver tissues retained the most 14C in all studies except the study of [1-14C]DCAN in rats, where blood contained the most 14C. These results indicate that DCAN was absorbed rapidly after oral administration in water. The differences in the route of excretion of [1-14C]DCAN compared to [2-14C]DCAN indicated that the molecule was being cleaved in the body and metabolized by different mechanisms.