RESUMO
Humans are exposed to ethylenebisdithiocarbamates (EBDCs) from environmental sources. Exposure to EBDCs is chronic for workers in a variety of industries, where EBDCs are used for their properties as slimicides, vulcanization accelerators, antioxidants, and scavengers in waste-water treatment. EBDCs, and particularly the EBDC metabolite ethylenethiourea, have clearly defined, important toxic effects in various animal species, and there is reason to suspect they are carcinogenic in humans. In the absence of definitive information regarding human risk, further studies need to be done. In the interim, regular surveillance of workers with high levels of exposure to EBDCs, with specific attention to markers of thyroid and hepatic pathology, should be considered.
Assuntos
Antifúngicos/efeitos adversos , Saúde Ambiental , Etilenobis (ditiocarbamatos)/efeitos adversos , Etilenotioureia/efeitos adversos , Substâncias Perigosas/efeitos adversos , Animais , Antifúngicos/metabolismo , Etilenobis (ditiocarbamatos)/metabolismo , Etilenotioureia/metabolismo , Contaminação de Alimentos , Substâncias Perigosas/metabolismo , Humanos , CinéticaRESUMO
BACKGROUND: Hydroxocobalamin has been shown to be a rapid and powerful antidote in acute cyanide poisoning and to prevent cyanide poisoning during sodium nitroprusside administration. This cobalt-containing compound has been shown to be devoid of significant immediate side effects during acute administration. However, its potential delayed toxicity related to cobalt accumulation in tissue remains unknown. Therefore, we evaluated the toxicity of hydroxocobalamin as compared with that of cobalt salts on rat cardiac and diaphragmatic muscles. METHODS: For a 21-day period, rats were treated intraperitoneally with either hydroxocobalamin (70 mg kg-1 per day, n = 14), cobalt chloride hexahydrate (12 mg kg-1 per day, n = 14) or saline (n = 10). Hydroxocobalamin and cobalt chloride groups received equimolar doses of cobalt. We studied: (1) the mechanical properties of isolated left ventricular papillary muscles and diaphragmatic strips, (2) the cardiac and diaphragmatic cobalt tissue concentrations, and (3) the myocardial histological aspect. RESULTS: During the study period, no significant increase in body weight was noted in the cobalt-treated group (-4 +/- 1%), which was in contrast to the hydroxocobalamin-treated group (+21 +/- 2%) and the saline-treated group (22 +/- 2%). Compared with controls, the mechanical properties of cardiac and diaphragmatic muscles were unchanged after either hydroxocobalamin or cobalt salt treatments, and myocardial histological characteristics were similar in all groups. Conversely, large amounts of cobalt deposit were observed in the cobalt-treated group in both the diaphragm (41.90 +/- 16.30 vs 0.70 +/- 0.40 mu mol mu g-1 in the control group, P < 0.001) and the myocardium (16.90 +/- 6.40 vs 0.14 +/- 0.01 mu mol mu g-1 in the control group, P < 0.001). After hydroxocobalamin administration, cobalt concentrations were significantly lower in the diaphragm (25.10 +/- 16.50 mu mol mu g-1, P < 0.001 vs cobalt-treated group) and the myocardium (4.50 +/- 1.20 mu mol mu g, P < 0.001 vs cobalt-treated group). CONCLUSION: These results indicate that repeated administration of hydroxocobalamin was devoid of significant diaphragmatic and cardiac muscle toxicity and therefore remains a safe antidote for acute cyanide poisoning.
Assuntos
Antídotos/toxicidade , Cobalto/toxicidade , Diafragma/efeitos dos fármacos , Coração/efeitos dos fármacos , Hidroxocobalamina/toxicidade , Análise de Variância , Animais , Antídotos/administração & dosagem , Cobalto/administração & dosagem , Cianetos/intoxicação , Diafragma/patologia , Diafragma/fisiopatologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Coração/fisiopatologia , Hidroxocobalamina/administração & dosagem , Miocárdio/patologia , Intoxicação/tratamento farmacológico , Ratos , Ratos WistarRESUMO
Hydroxocobalamin is a powerful cyanide antidote that prevents sodium nitroprusside-induced cyanide toxicity. The pharmacokinetics of an i.v. bolus of hydroxocobalamin (70 and 140 mg/kg) were studied in conscious dogs (n = 6). Plasma hydroxocobalamin concentrations were measured using derivative spectrophotometry. The pharmacokinetics were compatible with a two-compartment model with a first-order distribution and elimination rate, and pharmacokinetic parameters were not different between the two doses, except for the elimination half-life. At 70 mg/kg, which is the recommended dose in acute cyanide poisoning, the elimination half-life was 7.36 +/- 0.79 h, the volume of distribution was 0.49 +/- 0.10 L/kg, and the total clearance 0.58 +/- 0.11 L/h. At high doses, hydroxocobalamin has a short elimination half-life and a limited volume of distribution that exceeds blood volume. These results could be useful in elaborating guidelines for the administration of hydroxocobalamin, when repetitive bolus and/or continuous infusion is required.
Assuntos
Hidroxocobalamina/farmacocinética , Animais , Cães , Feminino , Hidroxocobalamina/administração & dosagem , Injeções Intravenosas , MasculinoRESUMO
Hydroxocobalamin (OHCo) and cyanocobalamin (CNCo) are determined directly in biological media, without extraction, by using first derivative spectrophotometry. We diluted 200 mL of plasma, urine, or standards with 1.8 mL of pH 6 buffer (boric acid, potassium dihydrogen orthophosphate, and potassium hydroxide). The first derivative spectra of the dilutions were plotted between 320 and 400 nm. At the exact zero-crossing point for hydroxocobalamin, the derivative values of cyanocobalamin concentration were determined. The same procedure was followed for hydroxocobalamin at the zero-crossing point for cyanocobalamin. The derivative values of the concentration curves are linear in the range 5-100 microM. The minimum detection limit is approximately 5 microM for hydroxocobalamin of cyanocobalamin on the determination of hydroxocobalamin or vice versa, although the spectra strongly overlap. The method is fast and simple to use, thus making it easy to assess the in vivo transformation of hydroxocobalamin into cyanocobalamin after the administration of high doses of hydrocobalamin in cyanide poisoning.
Assuntos
Cianetos/intoxicação , Hidroxocobalamina/análise , Vitamina B 12/análise , Incêndios , Humanos , Concentração de Íons de Hidrogênio , Hidroxocobalamina/sangue , Hidroxocobalamina/urina , Indicadores e Reagentes , Espectrofotometria Ultravioleta , Vitamina B 12/sangue , Vitamina B 12/urinaRESUMO
Cyanide determination in whole blood can be performed by spectrophotometry after using diffusion coupled with coloration by hydroxocobalamin in a Conway dish. The technique may be accelerated by the use of a heating sheet at 45 degrees C. The method proved to be specific, sensitive, and fast, thus permitting measurements in emergency situations.
Assuntos
Cianetos/sangue , Emergências , Difusão , Humanos , Cianeto de Hidrogênio/sangue , Concentração de Íons de Hidrogênio , Indicadores e Reagentes , Lesão por Inalação de Fumaça/sangue , Fumar/sangue , Espectrofotometria Ultravioleta , Temperatura , Vitamina B 12/sangueRESUMO
1. We report two cases of acute mercury vapour intoxication in humans. The mercury vapour was released from smelting alloys (gold-mercury amalgam). The alloy was apparently contaminated with an unknown amount of mercury. 2. Within half an hour of the incident, the victims began having moderate headache, nausea, lumbar pain and shortness of breath at rest. The patients were treated with BAL (2,3 dimercaptopropanol), followed by DMSA (2,3 dimercaptosuccinic acid). 3. Serial measurements of mercury metal in plasma and in urine were made for ten days. 4. The results suggest that in spite of the treatment, relatively high concentrations of mercury remain in the plasma for a very long time, and this could be explained by the progressive release of mercury from red blood cells and tissues after oxidation. However, BAL and DMSA did not seem to be the most efficient antidotes. They reduce the plasma inorganic mercury uptake at concentrations of < 50 micrograms I-1.
Assuntos
Dimercaprol/uso terapêutico , Intoxicação por Mercúrio/tratamento farmacológico , Mercúrio/sangue , Doenças Profissionais/tratamento farmacológico , Succímero/uso terapêutico , Administração Oral , Adulto , Ligas , Dimercaprol/administração & dosagem , Quimioterapia Combinada , Eletrocardiografia , Eletroencefalografia , Eritrócitos/metabolismo , Humanos , Masculino , Mercúrio/urina , Intoxicação por Mercúrio/fisiopatologia , Metalurgia , Pessoa de Meia-Idade , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/fisiopatologia , Exposição Ocupacional , Oxirredução , Succímero/administração & dosagemRESUMO
Volatile nitriles are present in cigarette smoke. We tested the hypothesis that the presence of any of four nitriles in the blood can serve as a marker of recent cigarette smoking. We determined the sensitivity and specificity of these nitriles as indicators of daily cigarette smoking in 24 smokers (Group A) and 18 non-smokers (Group B), as well as the correlation between intensity of daily smoking and the blood concentration of acetonitrile. A new head space GLC assay method was used. Of the four nitriles, only acetonitrile was present in the blood of any study subject. Acetonitrile was moderately sensitive (67%) and entirely specific (100%) for self-reported daily smoking. There was fair correlation between blood acetonitrile concentration and the average daily number of cigarettes smoked (r2 = 0.39; P = 0.001), and the mean blood acetonitrile concentration was significantly higher (P = 0.03) among subjects with higher (> 10 cigarettes per day) current cigarette exposure (148.3 +/- 18.0 micrograms/l) than among smokers with low or minimal (1-10 cigarettes per day) exposure (43.3 +/- 6.0 micrograms/l). Thus, acetonitrile in blood appears to be highly specific and a moderately sensitive marker of cigarette smoking with a dose-effect relationship. As such, acetonitrile shows promise as a marker of current cigarette exposure.
Assuntos
Acetonitrilas/sangue , Nicotiana , Plantas Tóxicas , Fumar/sangue , Biomarcadores/sangue , Cromatografia Gasosa/métodos , HumanosRESUMO
OBJECTIVE: Hydroxocobalamin has been proposed as a cyanide antidote. Little is known, however, about its pharmacokinetics in human cyanide poisoning. METHODS: We prospectively studied the pharmacokinetics of hydroxocobalamin in 11 smoke inhalation victims of whom all but one had objective evidence of cyanide exposure. Serum hydroxocobalamin levels were followed from just before drug administration to six days after a single 5 g dose of hydroxocobalamin. RESULTS: The results (mean +/- standard error) suggest a two compartment model. Distribution half-life is on the order of 1.86 +/- 0.34 h and the elimination half-life 26.2 +/- 2.7 h. The apparent volume of distribution is 0.45 +/- 0.03 L/kg. Renal and total body clearance are 0.31 +/- 0.06 and 0.83 +/- 0.07 L/h, respectively. CONCLUSION: The apparent volume of distribution suggests a predominantly extracellular partitioning of the antidote, even in the presence of cyanide, an important factor in terms of its antidotal effect. Hydroxocobalamin's elimination half-life in these cyanide-exposed patients far exceeds those found in previous studies of dogs and minimally-exposed humans. If confirmed, this half-life suggests that a single dose of hydroxocobalamin, sufficiently large enough to bind the cyanide present, should be adequate.
Assuntos
Antídotos/farmacocinética , Hidroxocobalamina/farmacocinética , Lesão por Inalação de Fumaça/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antídotos/uso terapêutico , Creatinina/sangue , Cianetos/antagonistas & inibidores , Cianetos/intoxicação , Feminino , Meia-Vida , Humanos , Hidroxocobalamina/uso terapêutico , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Lesão por Inalação de Fumaça/metabolismo , Fatores de TempoRESUMO
Hydroxocobalamin combines with cyanide to form cyanocobalamin. We hypothesised that the amount of cyanocobalamin formed after a fixed dose of hydroxocobalamin given for cyanide poisoning would correlate with initial blood cyanide concentration. We determined blood cyanide concentration in 12 patients exposed to residential fires, and compared this with markers of the amount of cyanocobalamin formed after treatment with 5 g intravenous hydroxocobalamin. All relationships were highly correlated (r2 0.79-0.95), for the whole group, and there appeared to be an almost linear relationship for the 9 patients with initial cyanide concentration below 40 mumol/L. Above this concentration, no further cyanocobalamin was formed from a single 5 g dose of hydroxocobalamin. In one patient with initial blood cyanide concentration of 96 mumol/L, however, plasma cyanocobalamin concentration approximately doubled after a second 5 g dose of hydroxocobalamin. 5 g of hydroxocobalamin appears capable of binding all available cyanide ions for blood cyanide concentrations up to about 40 mumol/L. Beyond this, more hydroxocobalamin must be given for remaining cyanide ions to be bound. This information will allow clinicians to use rapidly measurable plasma cyanocobalamin concentrations to gauge severity of exposure and evaluate adequacy of treatment.
Assuntos
Cianetos/sangue , Cianetos/intoxicação , Hidroxocobalamina/uso terapêutico , Vitamina B 12/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Cianetos/metabolismo , Feminino , Humanos , Hidroxocobalamina/metabolismo , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Vitamina B 12/urinaRESUMO
BACKGROUND: The nature of the toxic gases that cause death from smoke inhalation is incompletely understood, and the mechanisms leading to incapacitation remain to be determined. Thermal degradation products of various compounds, including phosphorous-based fire retardants, are suspected capable of impairing human cholinesterase activity. The aim of this study was to measure the erythrocyte cholinesterase activity in victims of smoke inhalation. METHODS: We prospectively measured the erythrocyte cholinesterase activity in blood samples obtained at the scene of residential fires from 49 fire victims. We compared the results with those in an unmatched group of 45 persons with acute drug poisoning. RESULTS: The median (25th-75th percentiles) erythrocyte cholinesterase activity in the 49 fire victims, 1968 IU/L (1660-2276), was significantly lower than in the 45 control subjects 2460 IU/mL (1968-2890), (p = 0.0004). There was no significant difference of the red blood cell counts or plasma protein levels between the 2 groups, while the hematocrit was significantly greater in the fire victims than in the drug-poisoned patients. There was a significant correlation between blood cyanide and carbon monoxide concentrations in the fire victims (r = 0.494, p = 0.002). There was no correlation between erythrocyte cholinesterase activity and either blood cyanide (r = 0.11, p = 0.44) or blood carbon monoxide concentrations (r = 0.04, p = 0.78). CONCLUSIONS: We found a significantly lower level of erythrocyte cholinesterase activity in victims of residential fires, when compared with a convenience sample of hospitalized poisoned patients. Despite the limitations of the study, investigations of the toxic gases potentially responsible for impairment of cholinesterase activity and the clinical significance of this lower enzymatic activity merit further investigation.