RESUMO
Objective: To establish a method for determing the trichloroethylene(TCE)and trichloroethanol(TCOH)in blood samples by liquid-liquid extraction-gas chromatography with electron capture detector. Methods: With this method,ether was used as extraction solvent and trichloromethane was used as an internal standard. The whole blood sample was extracted with ether, and dehydrated by anhydrous sodium sulfate. Then the analytes were separated on HP-5 capillary column(30m×0.32mm×0.15µm)and detected byECD.The retention time was for qualitative analysis and the internal standard was for quantitation. Results: The standard curves of TCE and TCOH showed significant linearity between 95.5µg/L-7640.0µg/L(r=0.9997)and 19.0µg/L-1520.0µg/L(r=0.9992). The average recovery was 95.5%-103.6%.The intra-day and inter-day precisions(RSD)were 2.5%-6.8%(n=6)and 1.6%-4.3%(n=6) respectively. The detect limit of TCE and TCOH were 2.10 µg/L and 0.56µg/L(S/N=3)respectively.The blood can be kept 7 days at-20â refrigerator without significantly loss. Conclusion: This method is proved to be simple,practical and highly sensitive. It can satisfy the request for the determination of blood samples of humans exposed to TCE.
Assuntos
Cromatografia Gasosa/métodos , Etilenocloroidrina/análogos & derivados , Extração Líquido-Líquido/métodos , Tricloroetileno/sangue , Etilenocloroidrina/sangue , HumanosRESUMO
It was recently demonstrated that some drugs modulate in vitro metabolism of trichloroethylene (TCE) in humans and rats. The objective was to assess in vivo interactions between TCE and three drugs: naproxen (NA), valproic acid (VA), and salicylic acid (SA). Animals were exposed to TCE by inhalation (50 ppm for 6 h) and administered a bolus dose of drug by gavage, equivalent to 10-fold greater than the recommended daily dose. Samples of blood, urine, and collected tissues were analyzed by headspace gas chromatography coupled to an electron capture detector for TCE and metabolites (trichloroethanol [TCOH] and trichloroacetate [TCA]) levels. Coexposure to NA and TCE significantly increased (up to 50%) total and free TCOH (TCOHtotal and TCOHfree, respectively) in blood. This modulation may be explained by an inhibition of glucuronidation. VA significantly elevated TCE levels in blood (up to 50%) with a marked effect on TCOHtotal excretion in urine but not in blood. In contrast, SA produced an increase in TCOHtotal levels in blood at 30, 60, and 90 min and urine after coexposure. Data confirm in vitro observations that NA, VA, and SA affect in vivo TCE kinetics. Future efforts need to be directed to evaluate whether populations chronically medicated with the considered drugs display greater health risks related to TCE exposure.
Assuntos
Etilenocloroidrina/análogos & derivados , Naproxeno/metabolismo , Ácido Salicílico/metabolismo , Solventes/metabolismo , Ácido Tricloroacético/metabolismo , Tricloroetileno/metabolismo , Ácido Valproico/metabolismo , Analgésicos/metabolismo , Animais , Anti-Inflamatórios não Esteroides/metabolismo , Anticonvulsivantes/metabolismo , Etilenocloroidrina/sangue , Etilenocloroidrina/metabolismo , Etilenocloroidrina/farmacocinética , Etilenocloroidrina/urina , Masculino , Modelos Teóricos , Ratos , Ratos Sprague-Dawley , Medição de Risco , Solventes/farmacocinética , Ácido Tricloroacético/sangue , Ácido Tricloroacético/farmacocinética , Ácido Tricloroacético/urina , Tricloroetileno/sangue , Tricloroetileno/farmacocinética , Tricloroetileno/urinaRESUMO
There is considered the improvement of methodological approaches to the gas chromatographic methods- of the detection of vinyl chloride and 1,2-dichloroethane and their metabolites--chloroethanol and monochloroacetic acid in biological fluids. There were evaluated such metrological characteristics of methods, as repeatability, interlaboratoty precision, relevance and accuracy. The value of relative expanded uncertainty does not exceed 30%. There are reported optimal regimes of gas chromatographic analysis, conditions for sample preparation. The results of the contents ofthese chemical compounds and their metabolites in biological fluids from persons working in contact with chlorinated hydrocarbons are presented These techniques can be used for the detection ofthe fact of exposure to toxic substances, assessment of the level of exposure and biomonitoring.
Assuntos
Poluentes Ocupacionais do Ar/análise , Indústria Química , Cromatografia Gasosa/métodos , Dicloretos de Etileno/análise , Exposição Ocupacional/análise , Cloreto de Polivinila/química , Cloreto de Vinil/análise , Acetatos/sangue , Acetatos/urina , Poluentes Ocupacionais do Ar/sangue , Poluentes Ocupacionais do Ar/metabolismo , Poluentes Ocupacionais do Ar/urina , Etilenocloroidrina/sangue , Etilenocloroidrina/urina , Dicloretos de Etileno/sangue , Dicloretos de Etileno/metabolismo , Dicloretos de Etileno/urina , Humanos , Cloreto de Vinil/metabolismoRESUMO
Triclofos sodium (TCS) and chloral hydrate (CH) are widely used as sedatives for children, but no analytical method to simultaneously monitor concentrations of blood TCS, CH and their metabolites, trichloroacetic acid (TCA) and trichloroethanol (TCEOH), has been reported. The present study aimed to develop a simple analytical method for TCS and its metabolites (TCA, TCEOH and CH) in small-volume plasma from children. After acidification of specimens, TCS formic acid adduct or the metabolites derivatized using water/sulfuric acid/methanol (6:5:1, v/v) were measured by combined use of liquid chromatography tandem-mass spectrometry and gas chromatography mass-spectrometry. The limits of detection and quantification levels (µg/ml) were 0.10 and 0.29 for TCS, 0.24 and 0.72 for TCA, 0.10 and 0.31 for TCEOH, and 0.25 and 0.76 for CH, respectively. The mean recoveries were 82.8-107% for TCS, 85.4-101% for TCA, 91.6-107% for TCEOH, and 88.9-109% for CH. Within-run and between-run precision (percent of relative standard deviation, %RSD) using this method ranged from 1.1 to 15.7% and 3.6 to 13.5%, respectively, for TCS and all of its metabolites. The calibration curves were obtained with standard spiked plasma, and all of the coefficients of determination were more than 0.975. Subsequently, we applied the present method to plasma taken from five children after sedation induced by CH and TCS. In addition to TCS and CH, elevated TCA and TCEOH concentrations were detected. This new method can be applied for the pharmacokinetic analysis of TCS and its metabolites and the determination of the optimal TCS dosage in children.
Assuntos
Cromatografia Líquida/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Organofosfatos/sangue , Espectrometria de Massas em Tandem/métodos , Pré-Escolar , Hidrato de Cloral/sangue , Etilenocloroidrina/análogos & derivados , Etilenocloroidrina/sangue , Feminino , Humanos , Hidrólise , Hipnóticos e Sedativos/sangue , Lactente , Japão , Limite de Detecção , Masculino , Espectrometria de Massas , Reprodutibilidade dos Testes , Ácido Tricloroacético/sangueRESUMO
Chloral hydrate (CH) is a short-lived intermediate in the metabolism of trichloroethylene (TRI). TRI, CH, and two common metabolites, trichloroacetic acid (TCA) and dichloroacetic acid (DCA) have been shown to be hepatocarcinogenic in mice. To better understand the pharmacokinetics of these metabolites of TRI in humans, eight male volunteers, aged 24-39, were administered single doses of 500 or 1,500 mg or a series of three doses of 500 mg given at 48 h intervals, in three separate experiments. Blood and urine were collected over a 7-day period and CH, DCA, TCA, free trichloroethanol (f-TCE), and total trichloroethanol (T-TCE=trichloroethanol and trichloroethanol-glucuronide [TCE-G]) were measured. DCA was detected in blood and urine only in trace quantities (<2 microM). TCA, on the other hand, had the highest plasma concentration and the largest AUC of any metabolite. The TCA elimination curve displayed an unusual concentration-time profile that contained three distinct compartments within the 7-day follow-up period. Previous work in rats has shown that the complex elimination curve for TCA results largely from the enterohepatic circulation of TCE-G and its subsequent conversion to TCA. As a result TCA had a very long residence time and this, in turn, led to a substantial enhancement of peak concentrations following the third dose in the multiple dose experiment. Approximately 59% of the AUC of plasma TCA following CH administration is produced via the enterohepatic circulation of TCE-G. The AUC for f-TCE was found to be positively correlated with serum bilirubin concentrations. This effect was greatest in one subject that was found to have serum bilirubin concentrations at the upper limit of the normal range in all three experiments. The AUC of f-TCE in the plasma of this individual was consistently about twice that of the other seven subjects. The kinetics of the other metabolites of CH was not significantly modified in this individual. These data indicate that individuals with a more impaired capacity for glucuronidation may be very sensitive to the central nervous system depressant effects of high doses of CH, which are commonly attributed to plasma levels of f-TCE.
Assuntos
Hidrato de Cloral/metabolismo , Hidrato de Cloral/farmacocinética , Fígado/metabolismo , Adulto , Hidrato de Cloral/sangue , Hidrato de Cloral/urina , Ácido Dicloroacético/sangue , Ácido Dicloroacético/metabolismo , Ácido Dicloroacético/urina , Etilenocloroidrina/análogos & derivados , Etilenocloroidrina/sangue , Etilenocloroidrina/metabolismo , Etilenocloroidrina/urina , Glucuronatos/sangue , Glucuronatos/metabolismo , Glucuronatos/urina , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Ácido Tricloroacético/sangue , Ácido Tricloroacético/metabolismo , Ácido Tricloroacético/urinaRESUMO
A sensitive and reproducible method is described for the analysis of trichloroacetic acid in urine and 1,1,1-trichloroethane in blood using dynamic headspace GC/MS. Samples were analyzed using the soil module of a modified purge and trap autosampler to facilitate the use of disposable purging vessels. Coefficients of variation were below 3.5% for both analytes, and response was linear in the range of 0.01-7.0 microg/ml for trichloroacetic acid and 0.9 ng/ml-2.2 microg/ml for 1,1,1-trichloroethane. Attempts at using dynamic headspace for the analysis of trichloroethanol in urine were unsuccessful.
Assuntos
Etilenocloroidrina/análogos & derivados , Cromatografia Gasosa-Espectrometria de Massas/métodos , Ácido Tricloroacético/análise , Tricloroetanos/análise , Etilenocloroidrina/análise , Etilenocloroidrina/sangue , Etilenocloroidrina/urina , Humanos , Ácido Tricloroacético/sangue , Ácido Tricloroacético/urina , Tricloroetanos/sangue , Tricloroetanos/urinaRESUMO
The pharmacokinetics and metabolism of intravenously infused 14C-fotemustine (about 100 mg/m2) were examined in 2 cancer patients. Plasma levels of radioactivity increased to a maximum of 4.1 and 5.5 micrograms equivalents per g when the infusion stopped then declined triexponentially with mean half-lives of about 1/2, 10 and 80 h for the initial, mid and terminal phases, respectively. Plasma levels of intact drug were lower, with maximum levels of 1.1 and 2.8 micrograms/ml, and declined monophasically with a half-life of about 24 min. Plasma clearance was high (1426 and 764 ml/min) with the volume of distribution based on areas of 47.7 and 26.4 l. Most of the radioactivity was eliminated in urine (50.1 and 61.3%) over 7 days with smaller amounts in the feces (6.8 and 0.3%) and only minimal quantities (under 0.1%) as expired carbon dioxide. Metabolites of fotemustine were identified as chloroethanol and N-nitroso-1-imidazolone-ethyl-diethylphosphonate in plasma and as 1-hydantoin-ethyl-diethyl-phosphonate and acetic acid in urine.
Assuntos
Antineoplásicos/farmacocinética , Compostos de Nitrosoureia/farmacocinética , Compostos Organofosforados/farmacocinética , Neoplasias Ovarianas/metabolismo , Neoplasias da Próstata/metabolismo , Idoso , Radioisótopos de Carbono , Etilenocloroidrina/sangue , Fezes/química , Feminino , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
Using an inhalation chamber, New Zealand albino rabbits were exposed to 350 ppm (n = 6) and 700 ppm (n = 8) of trichloroethylene (TRI) 4 hrs/day, 4 days/week for 12 weeks. Electroretinograms (ERG) and oscillatory potentials (OPs) were recorded weekly under mesopic conditions. Blood samples were also collected weekly to determine the concentration of TRI and its main metabolites. Recordings from the 350 and 700 ppm exposed groups showed a significant (p < 0.01) increase in the amplitude of the a- and b-waves (ERG), while the amplitude of the OPs was significantly (p < 0.01) decreased at 350 ppm and increased at 700 ppm. These electroretinal changes were reversed to the baseline value within six weeks after the inhalation stopped. The observed variations in a-wave and OP amplitudes were related to plasmatic level of trichloroethanol, while the effects on the b-wave were related to the blood level of TRI. These results confirm the neuro-ophthalmotoxicity of TRI and support the hypothesis that trichloroethanol is the major neurotoxic metabolite of TRI.
Assuntos
Retina/efeitos dos fármacos , Tricloroetileno/toxicidade , Animais , Eletrorretinografia , Etilenocloroidrina/análogos & derivados , Etilenocloroidrina/sangue , Masculino , Coelhos , Retina/fisiologia , Tricloroetileno/sangueRESUMO
Male Long-Evans rats were exposed to 0 (controls) or 500 ppm trichloroethylene (TRI) for 6 months, 6 h daily, and 5 days a week. The TRI metabolites trichloroethanol (TCE) in blood and trichloroacetic acid (TCA) in urine were measured. Specific parameters related to the renal damage were determined in urine [biomarker for glomerular damage: high molecular weight proteins (HMW), albumin (ALB); for proximal tubular damage: N-acetyl-beta-D-glucosaminidase (NAG), low-molecular-weight-proteins (LMW)]. Significantly increased concentrations of NAG and LMW in urine of exposed rats were detected. No DNA-strand breaks in kidney cells could be detected using the comet assay, and histological examinations were performed. Histological alterations were observed in glomeruli and tubuli of exposed rats. The release of biomarkers for nephrotoxicity suggested alterations preferably in the proximal tubules of the exposed rats.
Assuntos
Etilenocloroidrina/análogos & derivados , Nefropatias/induzido quimicamente , Tricloroetileno/toxicidade , Acetilglucosaminidase/urina , Albuminúria , Animais , Ensaio Cometa , Fragmentação do DNA/efeitos dos fármacos , Etilenocloroidrina/sangue , Histocitoquímica , Exposição por Inalação , Nefropatias/patologia , Masculino , Ratos , Ratos Long-Evans , Ácido Tricloroacético/urinaRESUMO
Rabbits treated with benzo(a)pyrene developed cardiac arrhythmias when exposed by inhalation to 8100 ppm trichloroethylene or 15000 ppm halothane to a greater extent and at lower doses of epinephrine challenge than did controls. Benzo(a)pyrene and 3-methylcholanthrene both increased the metabolism of trichloroethylene, but 3-methylcholanthrene did not increase its cardiotoxic effect. The basis of the arrythmogenic action of benzo(a)pyrene appears to be unrelated to its ability to induce xenobiotic metabolism.
Assuntos
Arritmias Cardíacas/induzido quimicamente , Benzopirenos/toxicidade , Animais , Benzo(a)pireno , Epinefrina/farmacologia , Etilenocloroidrina/análogos & derivados , Etilenocloroidrina/sangue , Halotano/sangue , Halotano/toxicidade , Masculino , Metilcolantreno/farmacologia , Fenobarbital/toxicidade , Coelhos , Fatores de Tempo , Ácido Tricloroacético/sangue , Tricloroetileno/metabolismoRESUMO
Control rabbits or those treated with the drug-metabolism inducer, phenobarbitol, or the inhibitors, 2-diethylaminoethyl-2,2-diphenylvalerate-HCI (SKF-525A) or 2,4-dichloro-6-phenylphenoxyethyldiethyl-amine-HBr (Lilly 18947) were exposed to 5600 ppm methylchloroform in an inhalation chamber under dynamic airflow conditions. Phenobarbital treatment slightly decreased blood levels of methylchloroform and the incidence of cardiac arrhythmias. The two inhibitors decreased the metabolism of methylchloroform and increased the incidence of arrhythmias. Methylchloroform rather than its metabolites appeared responsible for the arrhythmias. This arrhythmogenicity was altered by agents which affect the disposition and hence the blood levels of the compound.
Assuntos
Arritmias Cardíacas/induzido quimicamente , Sistema Enzimático do Citocromo P-450 , Epinefrina/farmacologia , Hidrocarbonetos Clorados/toxicidade , Tricloroetanos/toxicidade , Animais , Antimetabólitos/farmacologia , Compostos de Bifenilo/farmacologia , Dietilaminas/farmacologia , Etilenocloroidrina/análogos & derivados , Etilenocloroidrina/sangue , Masculino , Fenobarbital/farmacologia , Proadifeno/farmacologia , Coelhos , Ácido Tricloroacético/sangue , Tricloroetanos/sangueRESUMO
Chloral hydrate (CH) is a widely used sedative. Its pharmacological and toxicological effects are directly related to its metabolism. Prior investigations of CH metabolism have been limited by the lack of analytical techniques sufficiently sensitive to identify and quantify metabolites of CH in biological fluids. In this study a gas chromatography mass spectrometry (GC/MS) method was developed and validated for determining CH and its metabolites, monochloroacetate (MCA), dichloroacetate (DCA), trichloroacetate (TCA) and total trichloroethanol (free and glucuronidated form, TCE and TCE-Glu) in human plasma. Of these, DCA and MCA are newly identified metabolites in humans. The drug, its plasma metabolites and an internal standard, 4-chlorobutyric acid (CBA), were derivatized to their methyl esters by reacting with 12% boron trifluoride-methanol complex (12% BF3-MeOH). The reaction mixture was extracted with methylene chloride and analyzed by GC/MS, using a selected ion monitoring (SIM) mode. The quantitation limits of MCA, DCA, TCA, and TCE were between 0.12 and 7.83 microM. The coefficients of variation were between 0.58 and 14.58% and the bias values ranged between -10.03 and 14.37%. The coefficients of linear regression were between 0.9970 and 0.9996.
Assuntos
Hidrato de Cloral/sangue , Ácidos Hidroxâmicos/sangue , Acetais/análise , Acetatos/sangue , Acidose Láctica/sangue , Acidose Láctica/tratamento farmacológico , Administração Oral , Criança , Hidrato de Cloral/administração & dosagem , Ácido Dicloroacético/sangue , Etilenocloroidrina/análogos & derivados , Etilenocloroidrina/sangue , Estudos de Avaliação como Assunto , Cromatografia Gasosa-Espectrometria de Massas/métodos , Glucuronatos/análise , Glucuronídeos/sangue , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ácido Tricloroacético/sangueRESUMO
We describe a simple, precise, and sensitive assay of tetrachloroethylene and trichloroethylene in tissues, suitable both for emergency cases and forensic medicine. The method employs headspace solid phase microextraction-capillary gas chromatography and electron capture detection. The case is relative to a 45-year-old woman discovered unconscious in a laundry area. The concentrations of the solvents in tissues were determined and compared to other previously published fatalities.
Assuntos
Cromatografia Gasosa/métodos , Tetracloroetileno/análise , Tetracloroetileno/intoxicação , Tricloroetileno/análise , Tricloroetileno/intoxicação , Eletroforese Capilar , Etilenocloroidrina/análogos & derivados , Etilenocloroidrina/análise , Etilenocloroidrina/sangue , Etilenocloroidrina/urina , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Tetracloroetileno/sangue , Tetracloroetileno/urina , Distribuição Tecidual , Ácido Tricloroacético/análise , Ácido Tricloroacético/sangue , Ácido Tricloroacético/urina , Tricloroetileno/sangue , Tricloroetileno/urinaRESUMO
A 58-year-old man fell into a trichloroethylene reservoir bath head first, during a maintenance degreasing bath and accidentally ingested the solvent. Although he showed deep coma, chemical burns and pneumonia on admission, these symptoms gradually subsided. The concentrations of trichloroethylene (TRI) and its metabolites, trichloroethanol (TCE) and trichloroacetic acid (TCA) in blood and urine were measured during hospitalization. Eight hours after the accident, the concentrations of TRI and its metabolites in serum were 31.4 micrograms/ml TRI, 16.5 micrograms/ml TCE and 79.5 micrograms/ml TCA. The serum TRI concentration decreased to 4.3 micrograms/ml on the following day. Elimination of TCE and TCA from serum occurred biphasically, the estimated half-lives of each metabolites being about 52.6 and 50.4 h in an initial fast phase and 268.3 and 277.2 h in a subsequent slow phase, respectively. Urinary TRI excretion persisted for the first 2 days. The urinary TCE and TCA excretions were longer than that of TRI with a biphasic decrease and the total amount of TCE excreted during the first 2 days was about two times that of TCA. The half-life of urinary TCE excretion (t1/2 25.7 h) was shorter than that of TCA (t1/2 52.1 h) in the fast phase but did no difference during the slow phase, with each half-time being about 166.3 h. The kinetics of TRI metabolites in blood and urine in this case were in slight agreement with the results following inhalation exposure previously reported in the literature.
Assuntos
Tricloroetileno/farmacocinética , Tricloroetileno/intoxicação , Acidentes Domésticos , Administração Oral , Etilenocloroidrina/análogos & derivados , Etilenocloroidrina/sangue , Etilenocloroidrina/intoxicação , Etilenocloroidrina/urina , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Tricloroacético/sangue , Ácido Tricloroacético/intoxicação , Ácido Tricloroacético/urina , Tricloroetileno/sangue , Tricloroetileno/urinaRESUMO
A young healthy female died after taking chloral hydrate syrup before surgery to extract third molars. Various aspects of the use of chloral hydrate are discussed, including the metabolism, active moiety, reported side effects, and effects on the heart. Recommendations are made concerning patient supervision, dosage limitations, and degree of sedation.
Assuntos
Anestesia Dentária , Hidrato de Cloral/intoxicação , Parada Cardíaca/induzido quimicamente , Medicação Pré-Anestésica/efeitos adversos , Adulto , Hidrato de Cloral/sangue , Etilenocloroidrina/análogos & derivados , Etilenocloroidrina/sangue , Feminino , Humanos , Bloqueio Nervoso , PrognósticoRESUMO
An alcoholic man, treated with chloral hydrate (CH) syrup to which he was dependent, was discovered comatose and in respiratory arrest. Death occurred on the ninth day of hospitalization following cerebral oedema. A woman, alcohol addicted, depressed, and epileptic was admitted in the Intensive Care Unit with heart and respiratory failure following CH absorption. She died three days later after a deep coma. In these two cases, CH intoxication was confirmed by toxicological analysis: CH and its major metabolite, trichloroethanol (TCE), were identified and determined in serum and urine using headspace-capillary gas chromatography-mass spectrometry. The concentrations measured were compared with those found in previously published fatalities. The analytical method used can be proposed for both clinical and forensic cases.
Assuntos
Hidrato de Cloral/intoxicação , Etilenocloroidrina/análogos & derivados , Hipnóticos e Sedativos/intoxicação , Adulto , Alcoolismo/tratamento farmacológico , Hidrato de Cloral/sangue , Hidrato de Cloral/urina , Overdose de Drogas , Etilenocloroidrina/sangue , Etilenocloroidrina/intoxicação , Etilenocloroidrina/urina , Evolução Fatal , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Hipnóticos e Sedativos/sangue , Hipnóticos e Sedativos/urina , Masculino , Transtornos Relacionados ao Uso de Substâncias/etiologiaRESUMO
BACKGROUND: Chloral hydrate is used worldwide as a first-line agent for procedural sedation in paediatric patients undergoing painless diagnostic investigations. Chloral hydrate overdoses in children and adults have been reported to cause various toxicities, including central nervous system, respiratory and cardiac depression with sometimes fatal outcome. PATIENT AND METHODS: A 3-month-old girl was admitted after an unintentional administration of a 10-fold dose of chloral hydrate (667 mg/kg). She showed respiratory insufficiency in need of intubation and ventilation. Gastric endoscopy revealed esophagitis and gastric ulcerations. To assess the need for hemodialysis, serum trichloroethanol (TCE) was determined using a mass spectrometric quantification after a methyl tertiary butyl ether extraction using an external standard method. The serum TCE level 6 h after administration was 89 mg/L and declined to 20 mg/L within 24 h. The child could be extubated the next day; her further course was uneventful. CONCLUSION: The repeated determination of serum TCE levels prevented a technically difficult and risky hemodialysis in this very young patient.
Assuntos
Hidrato de Cloral/intoxicação , Etilenocloroidrina/análogos & derivados , Hipnóticos e Sedativos/intoxicação , Diálise Renal , Adulto , Hidrato de Cloral/metabolismo , Etilenocloroidrina/sangue , Etilenocloroidrina/química , Humanos , Hipnóticos e Sedativos/metabolismo , Lactente , Espectrometria de MassasRESUMO
The present study was designed to examine the hypothesis that liver tissue repair induced after exposure to chloroform (CF) + trichloroethylene (TCE) + allyl alcohol (AA) ternary mixture (TM) is dose-dependent similar to that elicited by exposure to these compounds individually. Male Sprague Dawley (S-D) rats (250-300 g) were administered with fivefold dose range of CF (74-370 mg/kg, ip), and TCE (250-1250 mg/kg, ip) in corn oil and sevenfold dose range of AA (5-35 mg/kg, ip) in distilled water. Liver injury was assessed by plasma alanine amino transferase (ALT) activity and liver tissue repair was measured by (3) H-thymidine incorporation into hepatonuclear DNA. Blood and liver levels of parent compounds and two major metabolites of TCE [trichloroacetic acid (TCA) and trichloroethanol (TCOH)] were quantified by gas chromatography. Blood and liver CF and AA levels after TM were similar to CF alone or AA alone, respectively. However, the TCE levels in blood and liver were substantially decreased after TM in a dose-dependent fashion compared to TCE alone. Decreased plasma and liver TCE levels were consistent with decreased production of metabolites and elevated urinary excretion of TCE. The antagonistic interaction resulted in lower liver injury than the summation of injury caused by the individual components at all three-dose levels. On the other hand, tissue repair showed a dose-response leading to regression of injury. Although the liver injury was lower and progression was contained by timely tissue repair, 50% mortality occurred only with the high dose combination, which is several fold higher than environmental levels. The mortality could be due to the central nervous system toxicity. These findings suggest that exposure to TM results in lower initial liver injury owing to higher elimination of TCE, and the compensatory liver tissue repair stimulated in a dose-dependent manner mitigates progression of injury after exposure to TM.
Assuntos
Clorofórmio/toxicidade , Regeneração Hepática , Fígado/efeitos dos fármacos , Propanóis/toxicidade , Tricloroetileno/toxicidade , Administração Oral , Animais , Clorofórmio/sangue , Clorofórmio/farmacocinética , D-Alanina Transaminase/sangue , Interações Medicamentosas , Etilenocloroidrina/análogos & derivados , Etilenocloroidrina/sangue , Injeções Intraperitoneais , Fígado/química , Fígado/enzimologia , Masculino , Propanóis/sangue , Propanóis/farmacocinética , Ratos , Ratos Sprague-Dawley , Ácido Tricloroacético/sangue , Tricloroetileno/sangue , Tricloroetileno/farmacocinética , Tricloroetileno/urinaRESUMO
Chlorate hydrate is commonly used for neonatal sedation, but blood levels are infrequently monitored, reflecting an underemphasis of acute toxic effects. This report describes a case of chloral hydrate toxicity in a term infant with cardiac, renal, neurologic, bladder and gastrointestinal dysfunction. The effects of exchange transfusion are described as well as pharmacokinetics.