Central nervous system cyanide toxicity

Respiratory Effects. Breathing irregularities including Cheyne-Stokes respiration developed in two persons who fell into cisterns containing copper cyanide or potassium cyanide (Dodds and McKnight 1985 Trapp 1970) or whose hands were exposed to hydrogen cyanide (Potter 1950). The effects reflect the central nervous system toxicity of cyanide. 

Effect of Dose and Duration of Exposure on Toxicity. The severity of neurological effects in humans and animals after acute oral exposure to cyanide is dose-related (Chen and Rose 1952 Lasch and El Shawa 1981). Central nervous system effects have been observed following acute-duration exposures (Levine and Stypulkowski 1959a) and chronic-duration exposures (Hertting et al. 1960), via the inhalation and oral routes. Necrosis is the most prevalent central nervous system effect following acute-duration exposure to high concentrations of cyanide, whereas demyelination is observed in animals that survive repeated exposure protocols (Bass 1968 Ibrahim et al. 1963). 

In addition to binding to cytochrome c oxidase, cyanide inhibits catalase, peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, and succinic dehydrogenase activities. These reactions may make contributions to the signs of cyanide toxicity (Ardelt et al. 1989 Rieders 1971). Signs of cyanide intoxication include an initial hyperpnea followed by dyspnea and then convulsions (Rieders 1971 Way 1984). These effects are due to initial stimulation of carotid and aortic bodies and effects on the central nervous system. Death is caused by respiratory collapse resulting from central nervous system toxicity. 

Neurological Effects. The central nervous system is the primary target for cyanide toxicity in humans and animals. Acute-duration inhalation of high concentrations of cyanide provokes a brief central nervous... 

The nervous system is the most sensitive target for cyanide toxicity, partly because of its high metabolic demands. High doses of cyanide can result in death via central nervous system effects, which can cause respiratory arrest. In humans, chronic low-level cyanide exposure through cassava consumption (and possibly through tobacco smoke inhalation) has been associated with tropical neuropathy, tobacco amblyopia, and Leber s hereditary optic atrophy. It has been suggested that defects in the metabolic conversion of cyanide to thiocyanate, as well as nutritional deficiencies of protein and vitamin B12 and other vitamins and minerals may play a role in the development of these disorders (Wilson 1965). 

The primary target for cyanide toxicity is the central nervous system following both acute and chronic exposure. Exposure to high doses of cyanide can rapidly lead to death (see Section 2.2). Cyanide is not stored in the organism and one available study indicates that >50% of the received dose can be eliminated within 24 hours (Okoh 1983). However, because of the rapid toxic action of cyanide, development of methods that would enhance metabolism and elimination of cyanide is warranted. 

Effect. No biomarkers were identified that are useful for characterizing effects induced by exposure to cyanide. The target organs of cyanide toxicity are the central nervous system and the cardiovascular... 

Adiponitrile s mechanism of toxicity is similar to cyanide because it can potentially liberate cyanide in the body spontaneously. It forms a stable complex with ferric iron in the cytochrome oxidase enzymes, thereby inhibiting cellular respiration. Cyanide affects primarily the central nervous system (CNS), producing early stimulation followed by depression. It initially stimulates the peripheral chemoreceptors (causing increased respiration) and the carotid bodies (thereby slowing the heart). Early CNS, respiratory, and myocardial depression result in decreased oxygenation of the blood and decreased cardiac output. These effects produce both stagnation and hypoxemic hypoxia in addition to cytotoxic hypoxia from inhibition of mitochondrial cytochrome oxidase. 

Toxic compounds which interfere with major pathways in intermediary metabolism can lead to depletion of energy-rich intermediates. For example, fluoroacetate blocks the tricarboxylic acid cycle, giving rise to cardiac and central nervous system effects which may be fatal (see Chapter 7). Another example is cyanide (see Chapter 7). 

Cyanide binds to the in the heme of the cytochrome aaj component of cytochrome c oxidase and prevents electron transport to Oj. Mitochondrial respiration and energy production cease, and cell death rapidly occurs. The central nervous system is the primary target for cyanide toxicity. Acute inhalation of high concentrations of cyanide (e.g., smoke inhalation during a fire) provokes a brief central nervous system stimulation rapidly followed by convulsion, coma, and death. Acute exposure to lower amounts can cause lightheadedness, breathlessness, dizziness, numbness, and headaches. 

HUMAN TOXICITY DATA (potassium cyanide) oral-human LDLo 2857 pg/kg oral-woman TDLo lOOmg/kg toxic effect central nervous system, pulmonary effects oral-man TDLo 13,699pg/kg. (sodium cyanide) oral-human LDLo 2857pg/kg oral-man TDLo 714 pg/kg toxic effect central nervous system oral-man LDLo 6557 pg/kg toxic effect central nervous system, gastrointestinal tract unreported-man LDLo 2206 pg/kg. 

Sodium cyanide, NaCN, is a cyanide salt that is a white, deliquescent, crystalline powder and is soluble in water. The specific gravity is 1.6, which is heavier than water. Sodium cyanide is toxic by inhalation and ingestion, with a TLV of 4.7 ppm and 5 mg/m of air. The target organs are the cardiovascular system, central nervous system, kidneys, liver, and skin. Reactions with acids can release flammable and toxic hydrogen cyanide gas. Cyanides are incompatible with all acids. The fourdigit UN identification number is 1689. The NFPA 704 designation is health 3,... 

Toxicity of hydrocyanic acid involves inactivation of the respiratory enzymes, leading to dizziness and high facial colour. In high doses the whole of the central nervous system ceases to function and death follows. However, large doses of raw plant material (> 3.5 mg/kg) are required for a toxic effect to occur. Our bodies are able to neutralise cyanides by converting them to thiocyanates, which are eliminated in the urine (Bruneton 1995), however, this capacity can be overloaded if doses of cyanide are sufficiently high. 

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