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Human Toxicology Jan 1988All reported cases of paraquat poisoning by absorption through the skin are briefly reviewed. It is concluded that, while paraquat cannot be absorbed significantly... (Review)
Review
All reported cases of paraquat poisoning by absorption through the skin are briefly reviewed. It is concluded that, while paraquat cannot be absorbed significantly through intact human skin, damage to the skin, either by paraquat itself or by other means, will permit greater systemic absorption and possibly poisoning. The lowest known concentration of paraquat to result in fatal poisoning through the skin is 5 g/l. Animal experiments with paraquat are also reviewed. The fact that the reported lethal dermal dose of paraquat in rats is slightly less than the oral dose is probably due to the lack of head restraint on the rats in the dermal dosing experiments. In vivo and in vitro tests on human skin at concentrations of 9 g/l and 5 g/l did not result in significant absorption of paraquat through the skin but in these experiments the skin was intact.
Topics: Animals; Diffusion; Female; Humans; Lethal Dose 50; Male; Paraquat; Rats; Skin; Skin Absorption
PubMed: 3278972
DOI: 10.1177/096032718800700103 -
The Journal of the Association of... Nov 2019
Topics: Paraquat; Poisoning
PubMed: 31793275
DOI: No ID Found -
Theriogenology Feb 2022Paraquat (PQ) is a heterocyclic pesticide that not only damages the testicular development and reduces the quality of semen, but also disturbs the secretion of hormones...
Paraquat (PQ) is a heterocyclic pesticide that not only damages the testicular development and reduces the quality of semen, but also disturbs the secretion of hormones in the reproductive system. However, the effects of PQ on oocyte maturation and its toxic mechanism have not been yet fully clarified. Here we showed that PQ exposure could have toxic effects on porcine oocyte maturation. PQ exposure with 100 μM inhibited cumulus cell expansion and significantly reduced the rate of first polar body extrusion during oocyte maturation. PQ-exposed oocytes could not develop to the 2-cell and blastocyst stage. PQ exposure with 100 μM significantly increased abnormal spindle rate (65.2% ± 1.0%) and misaligned chromosome rate (63.2% ± 3.4%) compared to the control group (38.3% ± 1.0% and 38.4% ± 1.0%, respectively; P < 0.05). F-actin also exhibited reduced distribution in PQ-exposed oocytes (10.3% ± 1.0%) compared to the control group (14.4% ± 1.0%, P < 0.05). In addition, PQ exposure reduced the active mitochondria levels, but apparently increased the reactive oxygen species (ROS), rH2AX, and LC3 (autophagy marker) levels. qPCR analyses showed that PQ exposure caused the aberrant expression of genes associated with cumulus cell expansion, but did not affect the expression of apoptosis-related genes. Taken together, these results indicate that PQ exposure impaired oocyte nuclear and cytoplasmic maturation probably through oxidative stress.
Topics: Animals; In Vitro Oocyte Maturation Techniques; Oocytes; Oogenesis; Oxidative Stress; Paraquat; Reactive Oxygen Species; Swine
PubMed: 34839230
DOI: 10.1016/j.theriogenology.2021.11.018 -
Toxicology and Applied Pharmacology Apr 2021By extending our Paraquat (PQ) work to include primates we have implemented a modelling and simulation strategy that has enabled PQ pharmacokinetic data to be integrated...
By extending our Paraquat (PQ) work to include primates we have implemented a modelling and simulation strategy that has enabled PQ pharmacokinetic data to be integrated into a single physiologically based pharmacokinetic (PBPK) model that enables more confident extrapolation to humans. Because available data suggested there might be differences in PQ kinetics between primates and non-primates, a radiolabelled study was conducted to characterize pharmacokinetics and excretion in Cynomolgus monkeys. Following single intravenous doses of 0.01 or 0.1 mg paraquat dichloride/kg bw, plasma PQ concentration-time profiles were dose-proportional. Excretion up to 48 h (predominantly urinary) was 82.9%, with ca. 10% remaining unexcreted. In vitro blood binding was similar across Cynomolgus monkeys, humans and rat. Our PBPK model for the rat, mouse and dog, employing a single set of PQ-specific parameters, was scaled to Cynomolgus monkeys and well represented the measured plasma concentration-time profiles over 14 days. Addition of a cartilage compartment to the model better captured the percent remaining in the monkeys at 48 h, whilst having negligible effect on model predictions for the other species. The PBPK model performed well for all four species, demonstrating there is little difference in PQ kinetics between non-primates and primates enabling a more confident extrapolation to humans. Scaling of the PBPK model to humans, with addition of a human-specific dermal submodel based on in vitro human dermal absorption data, provides a valuable tool that could be employed in defining internal dosimetry to complement human health risk assessments.
Topics: Animals; Computer Simulation; Herbicides; Humans; Infusions, Intravenous; Intestinal Elimination; Macaca fascicularis; Models, Biological; Paraquat; Rats; Renal Elimination; Risk Assessment; Skin Absorption; Species Specificity; Tissue Distribution; Toxicokinetics
PubMed: 33631232
DOI: 10.1016/j.taap.2021.115463 -
Cutis Jun 1993
Review
Topics: Adult; Female; Humans; Nail Diseases; Paraquat; Skin Diseases
PubMed: 8519183
DOI: No ID Found -
Human Toxicology Jan 1987The symptoms of paraquat poisoning depend largely on the amount of compound consumed, although in many cases the most characteristic feature of poisoning is lung damage,... (Review)
Review
The symptoms of paraquat poisoning depend largely on the amount of compound consumed, although in many cases the most characteristic feature of poisoning is lung damage, causing severe anoxia which leads to death. Studies in experimental animals have demonstrated that paraquat produces an acute damaging phase in the lung, followed by a reparative phase dominated by an extensive fibrosis. The latter is a major contributor to the lung lesion that causes anoxia. The specific toxicity in the lung can be explained in part by the selective accumulation of paraquat into this organ in comparison with other tissues. The accumulation is energy-dependent and probably specific to certain lung cells. It is now known that paraquat is accumulated into the lung by a recently described diamine transport process located in the alveolar epithelial cells and the Clara cells of the airways. When accumulated, paraquat undergoes a NADPH-dependent one-electron reduction to for its free radical which almost instantly reacts with molecular oxygen to reform the cation and concomitantly produce superoxide anion. This species of oxygen radical can contribute to the formation of more toxic species of radical which may directly damage vital cellular constituents. Paraquat has been shown to stimulate rapidly the pentose phosphate pathway and inhibit the synthesis of fatty acids in the lung in a dose-dependent manner. In addition there is a rapid increase in the pulmonary levels of mixed disulphides and the eventual reduction of NADPH levels in the lung. These results are consistent with the suggestion that paraquat causes a rapid and pronounced oxidation of NADPH which initiates compensatory biochemical responses in the lung.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Intestinal Absorption; Lung; NADP; Paraquat
PubMed: 3546084
DOI: 10.1177/096032718700600105 -
Human Toxicology Jan 1987In contrast to 10-15 years ago most cases of paraquat poisoning are now due to deliberate self-poisoning with parasuicidal or suicidal intent rather than to accidental... (Review)
Review
In contrast to 10-15 years ago most cases of paraquat poisoning are now due to deliberate self-poisoning with parasuicidal or suicidal intent rather than to accidental ingestion. Less commonly, poisoning may follow careless handling of paraquat during occupational use. Although paraquat can be absorbed through the skin if improperly handled, poisoning usually follows ingestion and has rarely been reported after subcutaneous, intravenous or intraperitoneal injection. Clinically, three degrees of intoxication may be distinguished. Mild poisoning occurs after the ingestion or injection of less than 20 mg of paraquat ion/kg body weight. In these cases patients are either asymptomatic or symptoms are confined to the gastrointestinal system. All patients recover fully. Moderate to severe poisoning usually follows the ingestion (rarely injection) of 20-40 mg of paraquat ion/kg body weight. Non-specific symptoms of ill health together with local gastrointestinal symptoms precede the development of renal failure (which may recover spontaneously) and pulmonary fibrosis which may not be manifest for days or weeks. Death occurs in the majority of cases but is usually delayed for 2-3 weeks. Acute fulminant poisoning follows the ingestion of substantial quantities of paraquat (greater than 40 mg of paraquat ion/kg body weight). In addition to local symptoms, multiple organ (cardiac, respiratory, hepatic, renal, adrenal, pancreatic, neurological) failure occurs. Death may supervene within hours and is never delayed for more than a few days. Initial general management has four priorities.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Humans; Paraquat; Prognosis; Referral and Consultation; Skin Absorption; Terminal Care
PubMed: 3546085
DOI: 10.1177/096032718700600107 -
Human Toxicology Jan 1987Over the past 20 years plus that paraquat has been used throughout the world, it has enjoyed an excellent safety record when used normally and for its intended purpose.... (Review)
Review
Over the past 20 years plus that paraquat has been used throughout the world, it has enjoyed an excellent safety record when used normally and for its intended purpose. Its safety record is explained by the following reasons: inhalational exposure during normal use is not significant toxicologically; dermal exposure predominates during normal use; intact human skin provides a very good barrier against penetration by paraquat. Its safety record has been confirmed by several field studies, which have assessed exposure and health of workers, who have used paraquat for short and longer periods of time. The unanimous conclusions of the studies is that exposure to paraquat does not result in any acute or chronic adverse health effects. Minor and reversible injuries to the skin, eyes, nose and nails do occur and probably result from overexposure to the extremely irritant concentrated formulations. Most of these effects can be avoided using ordinary personal hygiene. There have been a few anecdotal cases reported in the literature when dermal absorption of paraquat has genuinely occurred and led to serious health effects. In all cases prolonged exposure to concentrated paraquat solutions has been involved resulting in severe and extensive skin damage, with removal of the barrier and absorption of lethal amounts of the chemical. Those cases involving exposure to concentrated paraquat solutions emphasise the need to handle such formulations, for example 'Gramoxone', with case and ensure that the spray solution is correctly made up--at a dilution of at least 1 part 'Gramoxone' to 40 parts water.
Topics: Agriculture; Environmental Exposure; Humans; Paraquat; Skin Absorption
PubMed: 3546082
DOI: 10.1177/096032718700600103 -
Developments in Toxicology and... 1986There is a striking discrepancy between: the efficacy of the kidneys, haemodialysis (HD) and Haemoperfusion (HP) in removing paraquat from the body and the poor... (Review)
Review
There is a striking discrepancy between: the efficacy of the kidneys, haemodialysis (HD) and Haemoperfusion (HP) in removing paraquat from the body and the poor prognosis of paraquat poisoning even when the blood and urine levels (which are good indices of concentrations in lung and other tissues) are very low. Extra-corporeal elimination techniques have been used worldwide in paraquat poisoning. Do they remove paraquat effectively? Certainly. Do they increase the survival rate? Probably not. The reason being that when these techniques of elimination are initiated, potentially lethal concentrations of paraquat have already been attained in the highly vascular tissues of vital organs and in pneumocytes. The data presented suggest that the successful treatment of paraquat poisoning does not depend on modification of toxicokinetics.
Topics: Adult; Animals; Diuresis; Hemoperfusion; Humans; Kinetics; Male; Paraquat; Peritoneal Dialysis; Renal Dialysis
PubMed: 3549236
DOI: No ID Found -
Human Toxicology Jan 1987Paraquat was discovered in 1955 and introduced to the market place in 1962. During the 23 years between introduction and the present day numerous successful practical... (Review)
Review
Paraquat was discovered in 1955 and introduced to the market place in 1962. During the 23 years between introduction and the present day numerous successful practical uses of the herbicide have been developed. In addition the characteristics of the chemical have allowed significant changes to be made in the ways that some crops are grown. Paraquat is a relatively non-selective foliage-applied contact herbicide. It is inactivated on contact with almost all naturally occurring soils and it was this property, perhaps above all others, that provided the greatest breakthrough in chemical weed control at the time of its discovery. Inactivation on contact with soil means that no biologically active residues remain in the soil, thus allowing planting or sowing to be carried out almost immediately after spraying. Although the non-systemic (contact) property of paraquat makes it less than ideal for the long-term control of perennial weeds, the same property is of real advantage when parts of crop plants are sprayed accidentally, for usually only the part receiving the spray is affected. Total annual usage of all herbicides in agriculture and horticulture in England and Wales, UK, over the period of 1980-1983 has been estimated at 26,360 tonnes used on 12402 X 10(3) ha (1 hectare = 1 X 10(4) m2). For paraquat (not including its mixtures with diquat and monolinuron) 270 tonnes were sprayed over 392,218 ha/year. It is estimated from sales records that in Europe 5 X 10(6) ha are sprayed annually with paraquat.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Agriculture; Paraquat
PubMed: 3546089
DOI: 10.1177/096032718700600102