Paraquat Levels Research Articles

Percutaneous Permeability to Paraqut:In VitroExperiments with Human Skin

AbstractPercutaneous permeability to paraquat through intact and mechanically damaged human skin was measured in vitro from diluted solutions (1 mg/ ml). In intact human skin under occlusion, a permeability to paraquat of 3 × 10−5 cdhr was measured at steady state. The binding of paraquat to skin was determined and found to be negligible. The measured permeabilities were used in a pharmacokinetic model to predict paraquat levels in blood and lungs. The model predicts that for intact human skin and diluted paraquat solutions systemic toxicity is unlikely. However, the risk increased significantly when damaged skin or concentration paraquat solutions are involved.

Determination of paraquat in raw and formalin-fixed tissues by Electron Spin Resonance (ESR) spectroscopy

ESR method was applied to determine paraquat levels in fresh and formalin-fixed tissues. Paraquat was converted to paraquat radical by adding sodium dithionite to tissue homogenates and detected by ESR. Paraquat levels of more than 0.2 micrograms/ml homogenate could be quantified with 0.1 ml of the homogenate. The use of manganese ions for standardization of paraquat signal enabled much more accurate ESR measurements because this ion was quite stable and its signal did not overlap that of paraquat. Even with tissues fixed in formalin, tissues paraquat levels were measureable after removing formalin from the tissue extract. This fact was verified by studying two cases; the tissues were kept in formalin for 1.5 years in case 1 and for 6.5 years in case 2. In both cases, the paraquat contents in tissues were 0.02-0.08 micrograms/g. In this way ESR is one of the most suitable methods in determining low levels of paraquat in tissues even after they were preserved in formalin for a long time.

Immunotherapy for the treatment of acute paraquat poisoning.

For the purpose of sequestering paraquat in the plasma compartment and preventing it from accumulating in tissues the effects of intravenous administration of anti-paraquat antibodies to rats were studied. After an intravenous paraquat injection of 0.1 mg/kg, the plasma paraquat concentration from rats pretreated with anti-paraquat antibodies was significantly increased and the amount of paraquat excreted in urine was significantly decreased compared to the control group. The concentration of paraquat in bile and organs except liver, was not changed by the treatment, but the paraquat level in the liver was significantly increased. Although immunotherapy succeeded in sequestering paraquat in the plasma compartment, it could not prevent paraquat from accumulating in tissues.

Clinical studies on paraquat poisoning; prognosis and severity index of paraquat poisoning using the urine levels

The prognosis of paraquat poisoning has been assessed from serum paraquat levels using e.g. produfoot survival curve. The prognosis of paraquat poisoning has not been investigated from urinary paraquat levels. The purpose of this study is to clarify whether the prognosis of paraquat poisoning can be determined by urinary paraquat levels or not. Urinary severity index of paraquat poisoning (U-SIPP) was employed. U-SIPP is calculated as hours between ingestion of paraquat and start of intensive treatment multiplied by the paraquat level in the urine at the same time. Urinary excretion of paraquat is correlated with renal function. The prognosis of paraquat poisoning using U-SIPP was further discussed, based on creatinine clearance (Ccr) and the relation between serum and urine paraquat levels. The following results were obtained. 1) When creatinine clearance was greater than 20 ml/min, patients who died of circulatory failure were with U-SIPP level over 1250, patients who died of respiratory failure were with U-SIPP level between 1250 and 250, and survivors were with U-SIPP below 250. 2) Survival duration was closely correlative with U-SIPP in cases with Ccr greater than 20 ml/min (r = 0.8123, p less than 0.025). 3) When Ccr was greater than 20 ml/min, urinary paraquat levels were correlated very well with the serum levels at admission, even during direct hemoperfusion (DHP) treatment. 4) When diuretic agents such as furosemide was effective, the assessment of the prognosis of paraquat poisoning using urinary paraquat levels seemed to be possible. Urinary paraquat level was approximately measured by an applied qualitative analysis method with using a dilution method.

Effect of dimethylthiourea on plasma paraquat concentration

In a previous study, administration of the hydroxyl radical scavenger, dimethylthiourea (DMTU), and paraquat was associated with higher mortality in rats than was paraquat alone. In the present study, the possibility was evaluated that administration of DMTU increased plasma paraquat levels. Plasma paraquat concentrations were measured in Sprague-Dawley rats 1, 2, 4, 8 and 24 h after intraperitoneal (i.p.) injection of 29 mg paraquat cation/kg body wt. Another group of rats was treated identically except that they received i.p. injections of DMTU before injections of paraquat. Administration of DMTU was associated with increased plasma paraquat concentration ( P < 0.01). Pharmacokinetic analyses indicated that, compared to rats receiving paraquat alone, rats given paraquat and DMTU showed: (1) greater area under the paraquat concentration time-curve; (2) lower total body paraquat clearance; and (3) smaller apparent volume of distribution. Plasma biochemical studies indicated that paraquat caused hyperglycemia as well as an early reduction (compared to controls) in hepatic enzymes. We conclude that: (1) DMTU administration is associated with increased plasma paraquat concentrations; and (2) impaired synthesis or inhibition of release of hepatic proteins may be an early effect of paraquat.

Determination of paraquat in tissue using ion-pair chromatography in conjunction with spectrophotometry

Homogenized tissue was deproteinized with sulfuric acid. Paraquat in the superentatant was quantificated directly with the dithionite reagent (step 1) or concentrated by the XAD-2 column Chromatographic technique before paraquat determination (step 2). Tissue paraquat levels in the range of 0.01–75 mg/kg could be quantificated by second-derivative or zero-order spectroscopy using 2.5 g of tissues. The sensitivity could be increased tenfold by using 25 g of tissue samples. The coefficients of variation of withinrun and day-to-day precisions of spiked paraquat in tissue homogenates were below 5% at concentrations of 10.0, 1.0 and 0.1 mg/kg, respectively. The recoveries of the spiked paraquat in tissues ranging from 0.1–10 mg/kg were 91% by step 1 and 74% by step 2. Using these simple methods, steps 1 and 2, the paraquat concentrations in the psoas muscle, liver, lung and kidneys of a swine dosed with 0.16 g/kg of paraquat were investigated. The results were in close agreement with those of the TCA deproteinization method followed by cation-resin column chromatography. The proposed method offers the advantages of simplicity, rapidity, reasonable sensitivity and a wide range of concentrations.

Pharmacokinetic profile of paraquat following intravenous administration to the rabbit

Pharmacokinetic studies of paraquat in rabbits were performed using [ methyl- 14C]-paraquat. Plasma concentration of paraquat following i.v. administration to the rabbit was fitted to a 3-exponential function of pharmacokinetic analysis. Distribution and elimination were discussed on the basis of the 3-compartment open model system, which has a central and two peripheral compartments. Computer simulations of paraquat levels in each compartment indicated that the slow-uptake peripheral compartment contained a greater amount of paraquat than the central or the fast-uptake peripheral compartment. On the basis of the present results of the computer simulations in company with tissue distributions of paraquat reported by the other investigators, it is likely that the slow-uptake peripheral compartment contains the lung. In cases of paraquat-induced renal failures, the paraquat levels of the slow-uptake peripheral compartment were remarkably higher than in cases of normal renal functions. Histology of the rabbit tissues 7 days after i.v. administration of paraquat revealed that marked changes were observed only in the kidney, suggesting some renal failures induced by paraquat. In spite of the high concentration of paraquat, which was presumed with the computer simulations in this study, the rabbit lung showed a remarkable resistance to paraquat toxicity. The histology studies suggested the complexities of paraquat toxicity to the rabbit. The lung toxicity in the rabbit would be caused by not only the paraquat concentration in the lung but also some biochemical parameters in the tissue related to the mechanisms of paraquat toxicity.

The effects of paraquat dichloride on clinical chemistry measurements.

Although measurements in the clinical chemistry laboratory are routinely used to monitor renal and hepatic toxicity from paraquat, it is not known if paraquat, a strong oxidant, interferes with common laboratory tests. The authors analyzed the effects of paraquat (concentration range of 0 to 1000 mg/L) on the Beckman IDEAL and Technicon SMAC analyzers for 20 common analytes. Although 18 tests were unaffected by paraquat, creatinine values rose from 1.3 to 7.6 mg/dL on the SMAC and 1.3 to 3.0 mg/dL on the IDEAL. Also, LDH was unaffected, rising by 6 and 12% on the IDEAL and the SMAC, respectively. Values for these correlated positively with serum paraquat concentrations although little effect could be discerned at paraquat levels less than or equal to 10 mg/L. Thus, the magnitude of the effects were such that interference by paraquat with the measurements of creatinine and LDH can be considered insignificant in clinical circumstances.

Increased Plasma Paraquat Levels in Intoxicated Mice Following Antiparaquat F(ab′)2Treatment

Death most often results from human acute poisonings due to paraquat, a widely used herbicide. It causes a quick and insidious accumulation in lungs. It was proposed to study the effects of the administration of antiparaquat F(ab')2 fragments in mice intoxicated with paraquat. Antisera against a paraquat acid derivative coupled to bovine serum albumin were prepared in rabbits, then purified using immunoaffinity chromatography columns and fragmented by pepsin. Antiparaquat F(ab')2 antibodies obtained were preventively injected to mice. After intravenous paraquat injection of 8 mg/kg, plasma paraquat levels were measured from 0.25 to 48 hours. Plasma from antiparaquat F(ab')2 pretreated mice as compared with non-specific immunoglobulin pretreated control mice showed a significant increase (p less than 0.001) of the paraquat concentrations from the 4th (1.17 +/- 0.06 versus 0.20 +/- 0.01 microgram/ml) to the 48th hour (0.47 +/- 0.08 versus 0.02 +/- 0.01 microgram/ml). Although pulmonary paraquat concentrations presented no modification, it could be considered that these preliminary results would have to be studied thoroughly with a view to finding an efficient treatment in human acute poisoning with paraquat.

Protection from paraquat-induced lung damage and lethality in adult rats pretreated with clofibrate

Pretreatment of adult rats with the hypolipidemic agent clofibrate (60 mg/kg/day × 6 days) resulted in a marked degree of protection from paraquat-induced lung toxicity and lethality. The 10-day survival of treated rats was 39 56 (70%) compared to 21 76 (28%) (LT 50 = 2.8 days) for controls ( p < 0.001). Although clofibrate reportedly increases catalase activity in the liver, we found no increases in any of the antioxidant enzymes in the lung (catalase, superoxide dismutase, glutathione peroxidase, or G-6-PD) after clofibrate pretreatment. Lung lipid peroxidation at 24 and 48 hr post-paraquat was equivalent in both groups, although the clofibrate-pretreated rats showed significantly reduced lung edema and pathologic changes at these times. Blood paraquat levels were similar in both groups at 1, 3, and 24 hr postinjection. In two experiments, administration of clofibrate after paraquat injection afforded no protective effects. However, since pretreatment with clofibrate provided the best overall survival rate reported to date after a lethal dose of paraquat (35 mg/kg), further studies toward elucidating the mechanism(s) of action of this agent are warranted. Unraveling the protective mechanism(s) of the pretreatment regimen may still provide valuable clues to suggest effective post paraquat treatment approaches.

Paraquat poisoning in dogs and cats--differences between accidental and malicious poisoning.

ABSTRACTThe epidemiological, clinical, pathological and analytical findings in cases of accidental and malicious paraquat poisoning have been compared. These appear to indicate that in outbreaks which are probably malicious in origin, animals generally do not survive for long enough to develop specific pathological changes, but show appreciable tissue levels of paraquat on chemical analysis. In the sporadically occurring cases of accidental poisoning, tissue paraquat levels are low or undetectable and a presumptive diagnosis is more likely to be achieved on histopathological grounds.

Kinetics of paraquat elimination in the dog

The elimination and distribution kinetics of paraquat and the effect of paraquat-induced renal damage on these parameters have been studied in the dog. After intravenous administration, low doses (30–50 μg/kg) of paraquat were rapidly excreted in the urine at a clearance rate in excess of glomerular filtration rate, indicating that paraquat was eliminated by active secretion. This secretion could be inhibited by competition with N′-methylnicotinamide, a quaternary ammonium compound. Large doses (20 mg/kg) of paraquat induced renal failure, the extent of renal function impairment depending on the dose. The plasma concentration-time curve showed a triexponential decline, so that the elimination of paraquat could be described by a three-compartment open model. Simulation of paraquat levels in the peripheral compartments indicated that with early renal failure, fivefold higher levels would be achieved in the slow uptake compartment than under conditions of normal renal function. Since the energy-dependent accumulation of paraquat by the lung is a slow process, it was assumed that the slow uptake compartment included the lung. The implications of this are discussed in relation to the rational treatment of paraquat poisoning in man.

Paraquat poisoning: An analytical toxicologic study of three cases

Paraquat concentrations were measured in tissue, serum, urine and hemodialysate obtained from 3 patients who died 16.5 h, 22 days and 23 days after ingestion. In the patient who died 16.5 h post-ingestion, tissue paraquat levels were high. Kidney and liver had paraquat concentrations of 14 μg/g and 13.2 μg/g respectively, whereas lung tissue had a paraquat level of 3.8 μg/g. Low concentrations of paraquat were detectable in the tissues of the patients who died 22 and 23 days post-ingestion. Early in the poisoning, serum paraquat levels were high and large quantities of paraquat could be removed by both hemodialysis and forced diuresis. During an 8-h period, 713 mg of paraquat were removed by hemodialysis and 340 mg by forced diuresis. After the day of ingestion, little paraquat could be removed by hemodialysis or by forced diuresis; however, at all stages of the poisoning studied, hemodialysis was more effective than forced diuresis removing paraquat from the blood.

A Rapid and Sensitive Assay for the Determination of Paraquat in Plasma by Gas-Liquid Chromatography

A method for the determination of paraquat in plasma which involves a protein precipitation using trichloroacetic acid, followed by a reduction of the herbicide to ether extractable compounds and subsequent gas chromatographic quantitation is described. Ethyl viologen used as an internal standard has been demonstrated to behave similarly to paraquat during the entire course of sample preparation prior to gas chromatography. Paraquat levels as low as 0.030 mg per liter can be assayed.

The Interactions of Cu++and CN−with Paraquat Phytotoxicity to aChlorella

The interactions between copper (Cu++) and cyanide (CN−) with 1,1′-dimethyl-4,4′-bipyridinium ion (paraquat) on phytotoxicity toChlorella pyrenoidosaChick, IAC 251, were determined by measuring chlorophyll absorbance at 434 and 670 mμ. Cu++inhibited phytotoxicity and CN−accelerated paraquat activity with highly significant mutually antagonistic interactions occurring between Cu++(2 ppm) and CN−(16 ppm) at paraquat levels to 2 ppm.

Título en español.

Se estudiaron los cambios en el azúcar y el comportamiento de las enzimas en caña de azúcar tratada con los desecantes Paraquat, Diquat y Dinitrobutilofenol (DNBP). Los agentes químicos se aplicaron en forma de aspersión foliar a caña inmadura, cultivada en arena, de las variedades P. R. 980 ó P. R. 1059. Fueron tres los objetivos: 1, Confirmar la reacción anormal de las enzimas y el azúcar durante la desecación de la caña; 2, explorar la sensibilidad de las enzimas con respecto a la concentración química y al tiempo; y 3, determinar si los tres diferentes agentes inician un patrón común de los cambios enzimáticos. El Paraquat se le aplicó a la variedad P. R. 980 a concentraciones de 0.0008 a 0.5 por ciento. Todos los tratamientos con Paraquat causaron la rápida marchitez del follaje, pero hubo poca relación entre la desecación de la hoja y el contenido de humedad de la yagua y el tallo, manteniéndose este último casi normal. La sacarosa foliar disminuyó marcadamente, confirmándose así un efecto similar observado previamente en la variedad P. R. 980. La aparición de ribosa en los extractos de la hoja indica que el Paraquat altera la fotosíntesis a concentraciones de 0.004 por ciento o más. Como la desecación ocurrió a una concentración más baja, parece ser que la fotosíntesis puede proseguir simultáneamente con una acción limitada del desecante. Se evidenció cierta interconversión entre la sacarosa y la rafinosa y otros azúcares no identificados, inducida por el Paraquat. El Paraquat al 0.5 por ciento aumentó la actividad de la amilasa foliar, y a todas las concentraciones, la de la enzima en el tejido reservante tierno. Se cree que la acción de la amilasa es la causa de la disminución de la sacarosa a pesar de una severa inhibición de la invertasa. La peroxidosa foliar fue grandemente suprimida por una concentración de hasta 0.0008 por ciento de Paraquat, y en el caso de la tirosinasa por concentraciones más elevadas, indicando la sensibilidad de las oxidasas de la caña al desecante. El Diquat, al 0.5 por ciento, se le aplicó a la variedad P.R. 980 de 6 meses de edad, tomándose muestras de los tejidos a intervalos durante el siguiente período de 144 horas. Los síntomas de las lesiones causadas eran idénticos a los del Paraquat. Una vez más la desecación inicial de las hojas no se reflejó en los valores de humedad de la yagua. El Diquat bajó marcadamente la sacarosa foliar dentro de las 24 horas, pero el tejido reservante tierno y el jugo del tallo no revelaron disminución en el contenido de sacarosa hasta 96 horas después. La ribosa fue identificada mediante la cromatografía de los extractos de las hojas. La invertasa fue severamente inhibida. La amilasa y la peroxidasa fueron estimuladas por el Diquat en el tejido reservante tierno. La fosfatasa de la hoja y la ATP-asa fueron evidentemente retardadas por el Diquat. La supresión de éstas fue acompañada por aumentos mayores y persistentes en el fósforo orgánico foliar. Al igual que el Diquat, se estudió por un tiempo prolongado la acción del DNBP al 1.0 por ciento. El desecante fue letal dentro de 8 horas, describiéndose los síntomas, y la desecación fue generalmente menos efectiva que la del Paraquat y el Diquat. El DNBP bajó significativamente la sacarosa foliar dentro de las 8 horas. La disminución de sacarosa continuó durante todo el estudio y fue acompañada por un aumento en el contenido de azúcares reductores. La cromatografía reveló acumulaciones de fructosa y glucosa, pero no de ribosa. La invertasa bajó a un nivel insignificante dentro de las 8 horas posteriores a la aplicación del DNBP. La actividad de la amilasa aumentó grandemente tanto en la hoja como en los tejidos reservantes tiernos, impidiendo así, aparentemente, que el tejido reservante acumulara sacarosa. El contenido de peroxidasa en la hoja y en los tejidos reservantes tiernos fue anormalmente elevado por efecto del DNBP. La fosfatasa y la ATP-asa no fueron afectadas por el DNBP; sin embargo, hubo acumulaciones definidas de fósforo orgánico en las hojas tratadas con DNBP. Se discute la importancia que tienen para la industria azucarera las relaciones entre los desecantes, las enzimas y el azúcar. Se propone que estos agentes químicos supresores de la invertasa tienen un potencial como agentes que afectan la madurez. Sin embargo, todavía no son lo suficientemente específicas las relaciones enzimáticas para percibir su potencial total como desecantes o como agentes que afecten la madurez. La amilasa y las oxidasas aparentemente deben controlarse para que puedan acumular o aún retener la sacarosa.

Factors in Paraquat‐Induced Chlorosis with Phaseolus Foliar Tissues1

AbstractBioassay procedures with leaf disks from Phaseolus vulgaris L., Indian bean, were used to determine factors influencing ( 1,1′‐dimethyl‐4,4'bipyridinium) paraquat activity. Relative phytotoxicity was determined by varying herbicide levels from 0 to 1.0 ppm ai with light intensity, temperature and reaction time. Reduction of extractable chlorophyll was closely related to increased paraquat concentrations. Increased time, temperature and light intensity accelerated rate and magnitude of leaf disk chlorosis induced with active paraquat levels.