-
Clinical Toxicology (Philadelphia, Pa.) Jan 2022Cyanide (CN) is a metabolic poison that is capable of intoxicating individuals through accidental or intentional means. With high concentration exposures, death can...
BACKGROUND
Cyanide (CN) is a metabolic poison that is capable of intoxicating individuals through accidental or intentional means. With high concentration exposures, death can occur in minutes. In cases of mass casualty exposures, there is a need for a rapid-acting countermeasure capable of being administered in a short period of time in a pre-hospital setting to treat victims.
OBJECTIVE
These studies evaluate the safety and efficacy of a novel aqueous formulation of dimethyl trisulfide (DMTS) as an intramuscular (IM) CN countermeasure using non-anesthetized rodent models.
METHODS
Non-anesthetized rodents (mice and rats) were exposed to hydrogen cyanide (HCN) or potassium cyanide (KCN) along with immediate IM 10% DMTS treatment or vehicle treatment. Survival and other parameters, such as the time to recovery and assessment of clinical toxic signs (e.g., gasping, loss of righting reflex, convulsions, etc.), were quantified to determine the effectiveness of 10% DMTS treatment (12.5, 25, 75 mg/kg IM) compared to vehicle control treatment. A rat KCN delayed-treatment model with a 15-minute treatment delay was also utilized to simulate a real-life exposure/treatment scenario with 10% DMTS treatment. The stability of the 10% DMTS formulation was also assessed.
RESULTS
A 25 mg/kg IM dose of 10% DMTS exhibits potent efficacy against subcutaneous (SC) KCN challenge in both mice and rats and inhalational HCN exposure in mice. 10% DMTS treatment also shortens the time to recovery in rats using a delayed-treatment model.
CONCLUSION
IM treatment with 10% DMTS improves survival and clinical outcomes in non-anesthetized rodent models of acute CN toxicity. Additionally, the use of an SC KCN delayed-treatment model in rats is advised to assess the performance of a candidate CN countermeasure in a more realistic exposure/treatment scenario.
Topics: Animals; Antidotes; Cyanides; Humans; Mice; Potassium Cyanide; Rats; Sulfides
PubMed: 34219566
DOI: 10.1080/15563650.2021.1935991 -
Toxicology Sep 2002The effect of potassium cyanide on mitochondria DNA (mtDNA) in mouse brain was investigated in vivo and in vitro. When potassium cyanide (0, 0.1, 1.0 or 2.0 mM) was...
The effect of potassium cyanide on mitochondria DNA (mtDNA) in mouse brain was investigated in vivo and in vitro. When potassium cyanide (0, 0.1, 1.0 or 2.0 mM) was incubated with a crude mitochondria fraction prepared from mouse brain at 37 degrees C for 60 min, the damage of mtDNA was observed in a concentration-dependent manner. However, the mtDNA damage was prevented by a co-treatment with melatonin (1.5 mM), a scavenger of hydroxyl radicals (*OH). Furthermore, a subcutaneous injection of potassium cyanide (7mg/kg) caused both brain mtDNA damage and severe seizures in mouse. The damage of mtDNA and seizures induced by potassium cyanide were abolished by the pre-injection of melatonin (20 mg/kg). Hydrogen peroxide (1.5 mM) inflicted damage to brain mtDNA in the presence of Fe(2+) (3.0 microM). The damage was abolished by the co-treatment with melatonin. Furthermore, when cyanide (0, 0.1 or 1.0 mM) was incubated with the crude mitochondria fraction prepared from mouse brain, the lipid peroxidation was significantly increased in a concentration-dependent manner. The increased lipid peroxidation was completely inhibited by the co-treatment with melatonin (1.0 mM). These results suggest that reactive oxygen species including the *OH may play a cardinal role for mtDNA damage induced by potassium cyanide. Hence, the present study concluded that melatonin protects against DNA damage induced by the *OH produced by cyanide or hydrogen peroxide.
Topics: Animals; Brain Chemistry; DNA Damage; DNA, Mitochondrial; Electrophoresis, Agar Gel; Free Radical Scavengers; Hydrogen Peroxide; In Vitro Techniques; Iron; Lipid Peroxidation; Male; Melatonin; Mice; Potassium Cyanide; Seizures
PubMed: 12204540
DOI: 10.1016/s0300-483x(02)00244-5 -
Journal of Neurosurgery Jul 1993Glutamate has been shown to play an important role in delayed neuronal cell death occurring due to ischemia. Attenuation of synaptically released glutamate can be...
Glutamate has been shown to play an important role in delayed neuronal cell death occurring due to ischemia. Attenuation of synaptically released glutamate can be accomplished by modulators such as adenosine and baclofen. This study focused on the ability of adenosine to attenuate the excitotoxicity secondary to glutamate receptor activation in vitro after exposure to potassium cyanide (KCN) in hippocampal neuronal cell cultures. For this study, hippocampal cell cultures were obtained from 1-day-old rats and trypan blue staining was used for assessment of cell viability. It was found that the N-methyl-D-aspartate-specific antagonist MK801 (10 microM) attenuated neuronal cell death resulting from exposure to 1 mM KCN for 60 minutes. Adenosine (10 to 1000 microM) decreased neuronal cell death secondary to the same concentration of KCN in a dose-dependent manner. This same neuroprotective effect is mimicked by the adenosine A1-specific receptor agonist N6-cyclopentyladenosine (10 microM). The A1-specific receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (10 to 1000 nM) blocked the neuroprotective effect of adenosine in a dose-dependent manner. Therefore, neuronal cell death produced by KCN in the experimental model described was mediated at least in part by glutamate. This neuronal cell death was attenuated by adenosine via the A1-specific mechanism.
Topics: Adenosine; Animals; Cell Death; Cells, Cultured; Dizocilpine Maleate; Hippocampus; Neurons; Osmolar Concentration; Potassium Cyanide; Purinergic Antagonists; Theobromine; Theophylline
PubMed: 8315447
DOI: 10.3171/jns.1993.79.1.0111 -
Archives of Environmental Contamination... Aug 2005Vascular plants possess an enzyme system that detoxifies cyanide by converting it to the amino acid asparagine. This paper examines the potential of three woody plants...
Vascular plants possess an enzyme system that detoxifies cyanide by converting it to the amino acid asparagine. This paper examines the potential of three woody plants from the Salicaceae family to degrade cyanide. Pre-rooted trees were grown in carefully designed bioreactors with aqueous solution spiked with potassium cyanide at 23.0 +/- 1 degree C for a maximum of 144 h. Cyanide concentrations ranged from 0.95 to 1.15 CN mg/L. Cyanide in water and in plant tissues was analyzed spectrophotometrically. Results from the investigation indicated that significant reduction of aqueous cyanide was found during the presence of plants in all treatments. Little amounts of applied cyanide were detected in the tissues of plants, mainly in roots and bottom stem. Cyanide remaining in tissues varied with the species of plants, despite similar periods of exposure. The data also indicated that photolysis, hydrolysis, and microbial degradation were not occurring and that volatilization was minimal. In conclusion, transport and metabolism of cyanide in plants is most likely.
Topics: Biodegradation, Environmental; Biomass; Environmental Pollutants; Models, Biological; Populus; Potassium Cyanide; Salix; Species Specificity
PubMed: 15981035
DOI: 10.1007/s00244-004-0129-6 -
Journal of Hazardous Materials Feb 2003Standard soil samples contaminated with various standard cyanocompounds were prepared. Column elution experiments and analyses were conducted. Compounds with an easy...
Standard soil samples contaminated with various standard cyanocompounds were prepared. Column elution experiments and analyses were conducted. Compounds with an easy capacity for dissociation to ions, such as KCN and potassium hexacyanoferrate(III), were found to be eluted by forming free cyanide even in fresh water. Hexacyanoferrate(II) salts, such as potassium hexacyanoferrate(II) and iron(III) hexacyanoferrate(II), were found not to be dissociated in water, but were dissociated and diffused under alkaline conditions (pH >13). Hexacyanoferrate(II) ion was found to be more easily dissociated in water with a higher pH. Column tests as above were also conducted for soil samples taken from a former paint ink factory using iron(III) hexacyanoferrate(II), cyanogen chloride, potassium cyanate, copper cyanide, as well as potassium cyanide, as raw materials. It was demonstrate that iron(III) hexacyanoferrate(II) was dissociated and eluted under alkaline conditions. The elution rate was reduced when the contaminated soil was sandwiched with standard soil layers.Further, it was found that the Fe(CN)(6)(4-) ion eluted with NaOH from hexacyanoferrate acid in soil, were easily decomposed into cyanic acid or other byproducts by UV with the addition of ozone and H(2)O(2).
Topics: Ferrocyanides; Oxidation-Reduction; Pain; Poisons; Potassium Cyanide; Soil Pollutants; Ultraviolet Rays
PubMed: 12573832
DOI: 10.1016/s0304-3894(02)00248-0 -
Chemosphere Jul 2004Cyanide is a high-volume production chemical and the most commonly used leaching reagent for gold and silver extraction. Its environmental behavior and fate is of... (Comparative Study)
Comparative Study
Cyanide is a high-volume production chemical and the most commonly used leaching reagent for gold and silver extraction. Its environmental behavior and fate is of significant concern because it is a highly toxic compound. Vascular plants possess an enzyme system that detoxifies cyanide by converting it to the amino acid asparagine. This paper presents an investigation of the potential of Chinese vegetation to degrade cyanide. Detached leaves (1.5 g fresh weight) from 28 species of 23 families were kept in glass vessel with 100 ml of aqueous solution spiked with potassium cyanide at 23.5 degrees C for 28 h. Cyanide concentrations ranged from 0.83 to 1.0 CN mg l(-1). The disappearance of cyanide from the aqueous solution was analyzed spectrophotometrically. The fastest cyanide removal was by Chinese elder, Sambucus chinensis, with a removal capacity of 8.8 mg CN kg(-1) h(-1), followed by upright hedge-parsley (Torilis japonica) with a value of 7.5 mg CN kg(-1) h(-1). The lowest removal capacity had the snow-pine tree (Credrus deodara (Roxb.) Loud). Results from this investigation indicated that a wide range of plant species is able to efficiently metabolize cyanide. Therefore, cyanide elimination with plants seems to be a feasible option for cleaning soils and water contaminated by cyanide from gold and silver mines or from other sources.
Topics: Biodegradation, Environmental; China; Kinetics; Plant Leaves; Plants; Potassium Cyanide; Spectrophotometry
PubMed: 15120557
DOI: 10.1016/j.chemosphere.2004.02.008 -
Environmental Science and Pollution... 2005Cyanide is found predominantly in industrial effluents generated by metallurgical operations. It is an extremely toxic compound, so that problems and catastrophic...
BACKGROUND
Cyanide is found predominantly in industrial effluents generated by metallurgical operations. It is an extremely toxic compound, so that problems and catastrophic accidents have recently occurred all around the globe. The goal of this study was to determine the toxicity of cyanide to a Chinese willow species, and to determine the removal capacity.
METHODS
The toxicity of potassium cyanide (KCN) to weeping willow trees (Salix babylonica L.) was tested. The normalized, relative transpiration of the plants was used to determine the phytotoxicity of cyanide. The cyanide removal capacity of weeping willows was also determined.
RESULTS AND DISCUSSION
In hydroponic solution, no chlorosis of leaves and only a small reduction in normalized relative transpiration was observed when weeping willows were exposed to low doses of cyanide (< or = 0.93 mg CN/L). Severe signs of toxicity were found for the treatment groups exposed to higher doses of cyanide (> or = 9.3 mg CN/L). Weeping willows grown in sandy soils survived the entire period (216 hours) without any toxic effect when irrigated with low doses of cyanide (3.72 mg CN/L). High doses of cyanide (> or = 18.6 mg CN/L) in irrigation water were fatal for the weeping willows within 216 hours. EC50 values for a 50% inhibition of the transpiration of the trees were estimated to be between 3.27 and 8.23 mg CN/L, depending on the duration of the exposure.
CONCLUSIONS
The results obtained for the Chinese willow species Salix babylonica were very similar to those obtained for the European species S. viminalis in earlier studies. Phytotoxic effects were only found at high doses of cyanide. A large proportion of applied cyanide was removed from the contaminated media in the presence of weeping willows. This gives rise to the conclusion that the metabolism of cyanide by weeping willows is possible.
RECOMMENDATIONS AND OUTLOOK
Cyanide elimination with trees seems to be a feasible option for cleaning soils and water contaminated with cyanide. A full-scale treatment has been installed in Denmark. For phytoremediation projects in China, weeping willow could be a suitable species. The tree can tolerate and remove cyanide, and it is a native Chinese species. Besides, the tree is of outstanding beauty and is planted as a common park tree in many parts of the world.
Topics: Biodegradation, Environmental; Industrial Waste; Metallurgy; Potassium Cyanide; Salix; Soil Pollutants; Water Pollutants
PubMed: 15859117
DOI: 10.1065/espr2005.02.237 -
Journal of Neurochemistry 1962
Topics: Amino Acids; Brain; Cyanides; Glutamates; Potassium; Potassium Cyanide; gamma-Aminobutyric Acid
PubMed: 13994947
DOI: 10.1111/j.1471-4159.1962.tb04205.x -
Chemico-biological Interactions Jan 1982The interaction of acrylonitrile (VCN) with rat blood has been investigated at the molecular level in an attempt to understand the possible mechanism of its toxicity....
The interaction of acrylonitrile (VCN) with rat blood has been investigated at the molecular level in an attempt to understand the possible mechanism of its toxicity. The results obtained were compared to those with potassium cyanide (KCN), a compound known to liberate cyanide (CN-) in biologic conditions. The radioactivity derived from K14CN was eliminated faster than that from [1-14C]VCN. Up to a maximum of 94% of 14C from VCN in erythrocytes was detected covalently bound to cytoplasmic and membrane proteins, whereas 90% of the radioactivity from KCN in erythrocytes was found in the heme fraction of hemoglobin. Determination of specific activity showed that binding occurred more in vivo than in vitro which indicated that the VCN molecule was bioactivated inside erythrocytes. These results indicate that KCN interacts mainly through CN- liberation and binding to heme, whereas VCN, which binds to cytoplasmic and membrane proteins, may cause damage to red cells by mechanisms other than release of CN-.
Topics: Acrylonitrile; Administration, Oral; Animals; Cyanides; Erythrocytes; Heme; Hemoglobins; Male; Membrane Proteins; Nitriles; Potassium Cyanide; Rats; Rats, Inbred Strains; Time Factors
PubMed: 7055848
DOI: 10.1016/0009-2797(82)90036-9 -
Journal of Neurocytology Oct 1972
Topics: Animals; Demyelinating Diseases; Lysophosphatidylcholines; Mice; Microinjections; Microscopy, Electron; Poisons; Potassium Cyanide; Sciatic Nerve
PubMed: 8530963
DOI: 10.1007/BF01099936