Fluoroacetate poisoning and 'jamming' of the tricarboxylic acid cycle; mode of action of an 'active' fluoro compound synthesized via this cycle.
Explore the source record for details and available documents.
Citric Acid Cycle↗
SEARCH · PubMed Health
Results for “FLUORIDE POISONING”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Pharmacokinetics and neurotoxicity of dipterex in hens. A comparative study of administration methods.
We compared the tissue concentration of dipterex and the inhibition of the neuropathy target esterase (NTE) activity among groups of hens (n = 8 each) which were intravenously (i.v.), subcutaneously (s.c.) or orally (p.o.) administered the insecticide dipterex. The tissue concentrations of dipterex in the s.c. group were higher than those in the i.v. and p.o. groups. When dosed subcutaneously, the tissue concentration of dipterex was high in the brain, spinal cord and muscle at 3 hr after dosing and then concentrated in the spinal cord and muscle for the subsequent 3 hr. When dosed intravenously or orally, dipterex was evenly dispersed in various tissues. All hens treated with dipterex showed acute neurotoxic signs within 15 min after dosing. The hens dosed intravenously recovered from this acute poisoning within 3 hr, and the hens dosed orally recovered within 6 hr, while the hens dosed subcutaneously recovered within 24 hr after dosing. One hen in the s.c. group exhibited acute neurological sequelae following the acute poisoning. In addition, the loss of body weight was the largest in the s.c. group (157 +/- 49 g), moderate in the i.v. group (133 +/- 91 g), small in the p.o. group (96 +/- 54 g) and the smallest in the PMSF (phenylmethanesulfonyl fluoride, which was dosed to promote delayed neuropathy) group (80 +/- 49 g). In the untreated hens, the activity of NTE in both the cerebrum and cerebellum was higher than that in the midbrain (p < 0.01). There was no difference in NTE activity between the cerebrum and cerebellum. In both the cerebrum and midbrain, the inhibition of NTE activity in the p.o. group was less than that in the i.v. and s.c. groups, and no difference was found between the i.v. and s.c. groups. In the cerebellum, the inhibition of NTE activity in the s.c. group was larger than that in the i.v. and p.o. groups. These results indicate that the s.c. dosing of dipterex results in a stronger neurotoxicity compared to i.v. and p.o. dosing. However, it was difficult to induce the clinical signs of delayed neuropathy with any administration of dipterex in hens, even when the promotion of delayed neurotoxicity of dipterex was attempted with PMSF or double doses of dipterex itself.
Administration, Oral↗
Look what I found! Poison hunting on eBay.
BACKGROUND: Many substances deemed too dangerous for commercial use are still available to the general public. The purchase of these substances may potentially place members of the general public at risk for serious poisonings. This study was designed to document the large variety of dangerous poisons readily available on a popular online auction Web site. Methods. Over a 10-month period, the online auction Web site eBays was searched daily using the terms "poison" and "contents." Product name, active ingredients, what form the product is in, amount in container, and relative toxicity rating (Clinical Toxicology of Commercial Products, Gosselin, et al.) were recorded. If available, pictures of the products were saved. RESULTS: One hundred twenty-one individual products were identified. Fifty-five were in solid/tablet form, 37 were powders, and 29 were liquids. Product containers were full for 56 items and partially full for 65. Twenty-four products contained ingredients rated as "supertoxic" and included strychnine (10), arsenic trioxide (8), cyanide (2) and nicotine, pilocarpine, phosphorus, powdered conium maculatum (1 each). Sixty-three products contained "extremely toxic" ingredients including thallium, picrotoxin, soluble barium, antimony, mercury, arsenates, podophyllin, fluoride, zinc phosphide, atropine, scopolamine, and plant extracts of gelsemium, aconite, larkspur, and croton. Twenty-one products contained "very toxic" ingredients including lead, copper, camphor, caffeine, theobromine, creosote, pyrogallic acid, sparteine, quinine, lindane, warfarin, phenol, and digitalis. The remaining 13 were "moderately-slightly toxic." CONCLUSION: While the viability of the labeled ingredients could not be verified, the transportation, handling, and potential utilization of these dangerous poisons by the general public could result in serious poisonings.
Agrochemicals↗
Fatal poisoning from acute hydrofluoric acid ingestion.
A case of accidental oral poisoning with hydrofluoric acid in an adult is presented. The patient ingested the product from a drinking glass, mistaking it for water, and died approximately 90 minutes after the exposure. Severe acidemia and hypocalcemia were present, which resulted in refractory asystole. A plasma fluoride determination showed an extremely high fluoride level.
Adult↗
Carbonic anhydrase inhibitors. Inhibition of the beta-class enzyme from the methanoarchaeon Methanobacterium thermoautotrophicum (Cab) with anions.
The first inhibition study of the beta-class carbonic anhydrase (CA, EC 4.2.1.1) from the methanoarchaeon Methanobacterium thermoautotrophicum (Cab) with anions is reported here. Inhibition data of the alpha-class human isozymes hCA I and hCA II (cytosolic) as well as the membrane-bound isozyme hCA IV and the gamma-class enzyme from another archaeon, Methanosarcina thermophila (Cam) with a large number of anionic species such as halides, pseudohalides, bicarbonate, carbonate, nitrate, nitrite, hydrosulfide, bisulfite, sulfate, etc., are also provided for comparison. The best Cab anion inhibitors were thiocyanate and hydrogen sulfide, with inhibition constants in the range of 0.52-0.70 mM, whereas cyanate, iodide, carbonate, and nitrate were weaker inhibitors (Ki's in the range of 7.8-13.2 mM). Fluoride, chloride, and sulfate do not inhibit this enzyme appreciably, whereas the CA substrate bicarbonate, or other anions, such as bromide, nitrite, bisulfite, or sulfamate behave as weak inhibitors (Ki in the range of 40-45 mM). It is interesting to note that the metal poison, coordinating anions cyanide and azide are also rather weak Cab inhibitors (Ki in the range of 27-55 mM), whereas sulfamide is a very weak Cab inhibitor (Ki of 103 mM), although it strongly inhibits Cam (Ki of 70 microM). Surprisingly, phenylboronic and phenylarsonic acids, which have been investigated for the inhibition of all these CAs for the first time, showed very weak activity against the alpha-CA isozymes, but were effective Cab and Cam inhibitors. The best Cab inhibitors were just these two compounds (Ki's of 0.20-0.33 mM), whereas the best Cam inhibitor was sulfamic acid (Ki of 96 nM). These major differences of behavior between the diverse CAs investigated here toward anion inhibitors can be difficultly explained considering the convergent evolution of so diverse enzymes for the binding and turnover of small molecules such as carbon dioxide and anions.
Anions↗
[Poisoning caused by chronic exposure to volatile anesthetics. Molecular mechanisms and risk anesthetics].
The possible molecular mechanisms potentially inducing occupational disease among operating room personnel were examined; and the really dangerous anaesthetic agents were identified. As concerns the molecular mechanisms of parenchymatous injury, we surveyed: those connected with free radicals and biological reactive intermediates produced during halothane and nitrous oxide biotransformation; those coming from inorganic fluoride produced during biotransformation of any halogenated anaesthetic agent, and from inorganic bromide released during halothane metabolism; and, finally, those linked to vitamin B12 inactivation from nitrous oxide. Halothane and nitrous oxide can be considered as really dangerous anaesthetic agents for operating room personnel, and enflurane as an agent with marginal toxic power. On the contrary, isoflurane is a safe, useful compound, totally devoided of viscerotoxic effects. From data examined it is possible to conclude that an isoflurane-oxygen-air anaesthesia is safe for operating room personnel more than a balanced anaesthesia with intravenous drugs and nitrous oxide as maintenance.
Air Pollutants, Occupational↗
[Thermal degradation of dibutyltin fluoride (DBTF) and pulmonary toxicity of combustion products in the rat and guinea pig. 2. Acute and subacute toxicity of effluent gases issuing from the thermolysis of DBTF].
Explore the source record for details and available documents.
Animals↗
The in vivo effects of 3-deoxy-3-fluoro-D-glucose metabolism on respiration in Locusta migratoria.
The basis of the toxicity of 3-deoxy-fluoro-D-glucose (3FG) in adult Locusta migratoria is examined in vivo by a radiorespirometric analysis of 14CO2 from the locust after injections of 3FG prior to injections of D-[1-14C]glucose, D-[6-14C]glucose, or [1-14C]acetate. The results indicate that 3FG metabolism irreversibly inhibits glycolysis and not the hexose monophosphate pathway or the tricarboxylic acid cycle. It is also established that during metabolism of 3FG fluoride ion is released. Evidence for the metabolism of 3FG in the whole insect as far as triosephosphate isomerase is based on 3H2O release after injections of D-[3-3H]3FG. Further support for the metabolism of 3FG to fluorinated sugar phosphates is provided by chromatographic and 19F MNR analysis of 3FG poisoned locust tissue extracts. Based on these results a biochemical mode of toxicity of 3FG in locusts is discussed.
Animals↗
Analytical toxicology: guidelines for sample collection postmortem.
The reliability and relevance of any analytical toxicology result is determined in the first instance by the nature and integrity of the specimen(s) submitted for analysis. This article provides guidelines for sample collection, labelling, transport and storage, especially regarding specimens obtained during a postmortem examination. Blood (5 mL) should be taken from two distinct peripheral sites, preferably left and right femoral veins, taking care not to draw blood from more central vessels. Urine (if available), vitreous humour (separate samples from each eye), a representative portion of stomach contents, and liver (10-20 g, right lobe) are amongst other important specimens. A preservative (sodium fluoride, 0.5-2% weight by volume (w/v) should be added to a portion of the blood sample/the sample from one vein, and to urine. Leave a small (10-20% headspace) in tubes containing liquids if they are likely to be frozen. Precautions to minimise the possibility of cross-contamination of biological specimens must be taken, especially if volatile poison(s) may be involved. If death occurred in hospital, any residual antemortem samples should be sought as a matter of urgency. Hair/nail collection should be considered if chronic exposure is suspected, for example, in deaths possibly related to drug abuse. A lock of hair the width of a pen tied at the root end is required for a comprehensive drug screen. The value of providing as full a clinical/occupational/circumstantial history as possible together with a copy of the postmortem report (when available) and of implementing chain-of-custody procedures when submitting samples for analysis cannot be over-emphasised.
Chemistry Techniques, Analytical↗
Protection of animals against soman (1,2,2-trimethylpropyl methylphosphono-fluoridate) by pretreatment with some other organophosphorus compounds, followed by oxime and atropine.
Explore the source record for details and available documents.
Amitriptyline↗
Inhibition of macrophage adenylate cyclase by the alpha-methylene-gamma-lactone moiety of sesquiterpene lactones from forage plants.
Inhibition of murine macrophage adenylate cyclase activity by sesquiterpene lactones isolated from toxic forage plants was highly correlated with the presence of the alpha-methylene-gamma-lactone moiety on the molecule (ie, hymenovin and helenalin). Tenulin, a sesquiterpene lactone which does not contain this reactive moiety, caused minimal inhibition of the enzyme. Reaction of the alpha-methylene-gamma-lactone moiety of hymenovin and helenalin with cysteine decreased the number of reactive moieties available to alkylate the enzyme, thus decreasing the inhibition of adenylate cyclase by these 2 sesquiterpene lactones. As the reaction time available for the reduction by cysteine of the alpha-methylene-gamma-lactone moiety decreases, the amount of adenylate cyclase inhibition increases. Stimulation of the hymenovin- or helenalin-inhibited adenylate cyclase by prostaglandin E1 or E2 or by sodium fluoride did not reverse the inhibition of the enzyme, but did stimulate the undamaged adenylate cyclase in the sesquiterpene lactone treatment groups to the same degree as in the nontreated control. These data indicate that sesquiterpene lactones containing an alpha-methylene-gamma-lactone moiety are potent inhibitors of macrophage adenylate cyclase activity. This moiety may have a significant role in the toxicity of some sesquiterpene lactones in poisonous plants when ingested by livestock.
Adenylyl Cyclase Inhibitors↗
[Illnesses caused by amalgam?].
BACKGROUND: As side effects of dental amalgam have been mentioned allergy, oral lichen, electro-galvanism, amalgam tattoos of gingiva or oral mucosa, and undesirable esthetics. Patients with amalgam restorations show increased mercury levels in different body fluids compared to amalgam-free controls. An intoxication due to dental amalgam fillings, however, is not to be expected-despite equivocal statements in the literature. SCIENTIFIC RESULTS: In contrast, recent studies revealed that dental amalgam contributes to mercury exposure less than assumed few years ago. Therefore, amalgam will stay an option as a restorative material in future. The removal of intact amalgam fillings in the intention of "detoxification" is not science-based. CONCLUSION: Successful caries prevention (e.g. due to the widespread use of fluoride) and the further development of esthetic restorative materials based on composite resins will limit the utilisation of amalgam. Thus, alternative materials have not been shown to have a lower rate of side effects (e.g. allergy) compared to amalgam.
Dental Amalgam↗
Intracellular transport and esterification of exchangeable cholesterol in cultured human lung fibroblasts.
We have studied the intracellular fate of exchangeable cholesterol in a model system with lipid vesicles (cholesterol/phospholipid mole ratio 1:1) and cultured human lung fibroblasts. Exchangeable [3H]cholesterol in lipid vesicles was readily incorporated into cellular plasma membranes and transported to intracellular esterification sites. The formation of [3H]cholesteryl esters was not affected by cytoskeleton-disrupting drugs. A reduction of cellular pinocytosis by 75% did not reduce the formation of tracer-labelled esters, suggesting that membrane flow due to the energy-dependent pinocytosis is no major contributor to the intracellular transport of molecular cholesterol between plasma membranes and esterification sites. The formation of [3H]cholesteryl esters was not significantly affected by energy poisons (NaF and KCN) but was inhibited (to 50%) by chloroquine at 50 microM. This may indicate that membrane-derived cholesterol passes through the lysosomal compartment on its way to intracellular esterification sites.
Cells, Cultured↗
Experimental and clinical toxicology of anticholinesterase agents.
Several organophosphorus compounds (OP) and carbamates (CA) are used as insecticides or warfare agents (OPs only). Their acute toxic effect in the central and peripheral nervous system is due to inhibition of acetylcholinesterase (AChE) at nerve endings which causes accumulation of acetylcholine and consequently overstimulation of the nicotinic and muscarinic receptors. The cholinergic syndrome appears at approximately 50% AChe inhibition whereas death is believed to occur at > 90%. Inhibition of AChE (phosphorylation) by most OPs is irreversible whereas CAs reversibly inhibit AChE (spontaneous reactivation with a t(1/2) of minutes); dimethylphosphorylated AChE partially and slowly (t(1/2) = 1-2 h) reactivates. Although long-term, mild neurobehavioural changes of questionable significance have been reported in some instances, recovery from the cholinergic syndrome appears to be complete, unless lesions develop in the central nervous system as a consequence of either convulsions or anoxia. Certain OPs and CAs have been reported to interact with cholinergic receptors in vitro. The toxicological relevance of these interactions is still not clear. Certain OPs cause OP-induced delayed polyneuropathy (OPIDP) which develops 2-5 weeks after an acute poisoning. The molecular target is believed to be neuropathy target esterase (NTE). OP insecticides are more potent AChE inhibitors rather than NTE inhibitors and therefore, the dose required to cause OPIDP is much higher than that causing the cholinergic syndrome. In the experimental animal, OPIDP is associated with > 70% NTE inhibition after single or repeated exposures. The threshold in man is not known, although there are indications that it is similar. Some non-neuropathic esterase inhibitors (OPs, CAs, sulfonyl fluorides) exacerbate the clinical outcome of OPIDP and other chemical axonopathies, and of nerve crush. The phenomenon has been called promotion and has so far been observed in experimental animals only.
Animals↗
Further studies on the mechanism of the late protective effects of phenylmethylsulfonyl fluoride on carbon tetrachloride-induced liver necrosis.
We previously reported that phenylmethylsulfonyl fluoride (PMSF) administration to rats (100 mg/kg, ip in olive oil) as late as 6 or 10 hr after CCl4 (1 ml/kg, ip as a 20% v/v solution in olive oil) can partially prevent the necrogenic response to the hepatotoxin at 24 hr. Here we confirm that observation by electron microscopy and provide further evidence that only in these circumstances were nuclear clumping of chromatin, slight dilatation of the endoplasmic reticulum, myelin figures and lipid droplets in the cytoplasm, large numbers of lysosomes and peroxisomes, glycogen, and slightly swollen mitochondria observable in the protected animals. A very minor part of the late protective effects of PMSF might be due to the effects of this drug on decreasing the intensity of covalent binding of CCl4-reactive metabolites or the intensity of CCl4-induced lipid peroxidation still occurring 6 or 10 hr after CCl4. PMSF administration did not prevent CCl4-induced decreases in cytochrome P450 content or glucose-6-phosphatase activity but partially prevented CCl4-induced calcium accumulation in liver. PMSF treatment increased glutathione and glycogen content in CCl4-poisoned animals, but did not markedly modify protein/phospholipid synthesis or degradation processes. Results suggest that the late protective effects of PMSF administration in CCl4-induced liver necrosis might be due to a favorable modulation of the calcium-calmodulin system similar to that previously described for other drugs.
Administration, Oral↗
[Kinetic properties of the fructose influx across the brush border of the rat jejunum. Effects of a diet rich in fructose].
The unidirectional influx (i.e. initial rate of uptake) of D-fructose across the brush border of rat jejunum is a saturable function of concentration, with a Kt of 125 mM, which implicates a carrier mechanism. This mechanism appears to be very specific for fructose in view of the lack of influx inhibition observed in the presence of large concentrations of the sugars or polyols, D-glucose, D-galactose, D-mannose, D-xylose, L-sorbose, D-tagatose, sorbitol or mannitol. D-Fructose uptake is inhibited by incubation, preceded by a 30-min preincubation in the same inhibitory conditions, in the absence of Na, or in the presence of metabolic poisons, NaF, 2,4-dinitrophenol, monoiodoacetate. Phloridzin (10-3 M), with or without preincubation, has no effect on uptake. D-Fructose influx is stimulated by fructose feeding, mainly because the augmentation of the number of active sites of transfer: Jmax is increased two-fold, Kt is more weakly affected.
Animals↗
Animal health problems attributed to environmental contamination in lake Nakuru National Park, Kenya: a case study on heavy metal poisoning in the Waterbuck Kobus ellipsiprymnus defassa (Ruppel 1835).
A study was conducted in which samples of soil, forage, as well as serum, bone, kidney, and liver of waterbuck were collected from Lake Nakuru National Park. The objective was to determine the ecosystem health status in order to establish the causes of animal health problems previously recorded in some sections of the Park. Trace element analysis in serum indicated occurrence of copper (Cu) deficiency in the north and eastern sections of the Park where mean values were marginal (range: 0.36-0.81, mean: 0.62 mg/l) compared to concentrations recorded in the western part of the Park (range: 0.69-1.48, mean: 1.22 mg/l). Bone analysis on dry matter basis (DM) indicated higher (p < 0.01) levels of cadmium (Cd, 0.437 mg/kg), fluoride (F, 3178 mg/kg), and lead (Pb, 20.62 mg/kg) in animals from the east compared to those from the west (0.002, 1492, 4.87 mg/kg, respectively), suggesting heavy exposure. In addition, samples from the east had much lower than normal calcium (Ca)-to-phosphorus (P) ratios (mean: 1.9:1) compared to those recorded in the west (2.2:1), suggesting poor bone mineralization. There was a higher concentration of Cd in the kidney (16.24 mg/kg, p < 0.05) and Pb in the liver (58.3 mg/kg, p < 0.01) in animals from the east compared to those in the west (12.92 and 36.2 mg/kg, respectively), but the converse was true of Cu. The liver Cu status was better in animals from the west with, concentrations (mean: 21.7 mg/kg) being about twice those recorded in the east (11.9 mg/kg DM). Forage analysis revealed prospects of Ca, P, and Cu deficiencies in the entire Park. However, in the northeastern section of the Park (measuring 50 ha) where waterbuck residence times are high, forage concentrations of Cd (0.31 mg/kg DM), molybdenum (Mo, 7.20 mg/kg DM), Pb (2.88 mg/kg DM), and zinc (Zn, 126 mg/kg DM) were an order of magnitude greater (p < 0.01) than the levels recorded in the rest of the Park (ranges: 0.133-0.165, 3.69-5.61, 0.485-0.621, 11.6-17.4 mg/kg DM, respectively). These disparities were attributed to a higher soil concentration of Cd (2.77 mg/kg DM), Pb (85.1 mg/k DM) and Zn (1414 mg/kg DM) in this section compared to the rest of the Park (ranges: 0.10-0.15, 5.02-6.26, 1.49-5.44 mg/kg DM, respectively), and strongly suggest heavy metal contamination as the source of animal health problems in the Park.
Animals↗
Disruption of phosphatidylserine translocation to the mitochondria in baby hamster kidney cells.
Phosphatidylserine synthase is found predominantly in the microsomal fraction, and phosphatidylserine decarboxylase is found predominantly in the mitochondrial fraction of baby hamster kidney (BHK-21) cells. This segregation of enzymes of phosphatidylserine metabolism allows serine metabolism to phosphatidylserine and phosphatidylethanolamine to be used as an indicator of the intracellular movement of phosphatidylserine. After BHK-21 cells were pulse-labeled with [3H]serine, phosphatidylserine was efficiently labeled, and subsequently 40-50% of this radiolabeled lipid turned over to form phosphatidylethanolamine during a 7.5-h chase. Treatment of cells with NaN3 plus NaF or cycloheximide at the end of the pulse labeling period markedly inhibited the rate and extent of phosphatidylserine turnover during the chase period. The inhibition of phosphatidylserine turnover could not be attributed to inhibition of either phosphatidylserine decarboxylase or phosphatidylserine exchange protein activity. Subcellular fractionation of the BHK-21 cells demonstrated that cells poisoned with NaN3 plus NaF accumulated phosphatidylserine in the microsomal fraction relative to unpoisoned cells. The results indicate that metabolic energy is required for the transport of phosphatidylserine to the mitochondria.
Animals↗