Cyanide acute

As a class of compounds, the two main toxicity concerns for nitriles are acute lethality and osteolathyrsm. A comprehensive review of the toxicity of nitriles, including detailed discussion of biochemical mechanisms of toxicity and stmcture-activity relationships, is available (12). Nitriles vary broadly in their abiUty to cause acute lethaUty and subde differences in stmcture can greatly affect toxic potency. The biochemical basis of their acute toxicity is related to their metaboHsm in the body. Following exposure and absorption, nitriles are metabolized by cytochrome p450 enzymes in the Hver. The metaboHsm involves initial hydrogen abstraction resulting in the formation of a carbon radical, followed by hydroxylation of the carbon radical. MetaboHsm at the carbon atom adjacent (alpha) to the cyano group would yield a cyanohydrin metaboHte, which decomposes readily in the body to produce cyanide. Hydroxylation at other carbon positions in the nitrile does not result in cyanide release. 

The propensity of nitriles to release cyanide subsequent to metaboHsm is the basis of their acute toxicity. Nitriles that form tertiary radicals at their alpha carbon atoms (eg, isobutyronitrile, 2-methylbutyronitrile) are substantially more acutely lethal than nitriles that form secondary radicals at their alpha carbons (eg, butyronitrile, propionitnle). Cyanohydrins are acutely toxic because they are unstable and release cyanide quickly. Alpha-aminonitriles are also acutely toxic, presumably by analogy with cyanohydrins. 

Manufacture, Shipment, and Analysis. In the United States, sodium and potassium thiocyanates are made by adding caustic soda or potash to ammonium thiocyanate, followed by evaporation of the ammonia and water. The products are sold either as 50—55 wt % aqueous solutions, in the case of sodium thiocyanate, or as the crystalline soHds with one grade containing 5 wt % water and a higher assay grade containing a maximum of 2 wt % water. In Europe, the thiocyanates may be made by direct sulfurization of the corresponding cyanide. The acute LD q (rat, oral) of sodium thiocyanate is 764 mg/kg, accompanied by convulsions and respiratory failure LD q (mouse, oral) is 362 mg/kg. The lowest pubhshed toxic dose for potassium thiocyanate is 80—428 mg/kg, with hallucinations, convulsions, or muscular weakness. The acute LD q (rat, oral) for potassium thiocyanate is 854 mg/kg, with convulsions and respiratory failure. 

Table 3. Example of the Influence of Route on the Acute Toxicity of Potassium Cyanide to the Rabbit (Female)...

Hydrogen cyanide (prussic acid) is a liquid with a boiling point of 26°C. Its vapour is flammable and extremely toxic. The effects of acute exposure are given in Table 5.34. This material is a basic building block for the manufacture of a range of chemical products such as sodium, iron or potassium cyanide, methyl methacrylate, adiponitrile, triazines, chelates. 

The nervous system is vulnerable to attack from several directions. Neurons do not divide, and, therefore, death of a neuron always causes a permanent loss of a cell. The brain has a high demand for oxy gen. Lack of oxygen (hypoxia) rapidly causes brain damage. This manifests itself both on neurons and oligodendroglial cells. Anoxic brain damage may result from acute carbon monoxide, cyanide, and hydrogen sulfide poisonings. Carbon monoxide may also be formed in situ in the metabolism of dichloromethylene. 

Clark Jr DR, HiU EF, Henry PF. 1991. Comparative sensitivity of little brown bats Myotis-lucifugus to acute dosages of sodium cyanide. Bat Res News 32 68. 

In humans, acute exposure to acrylonitrile results in characteristics of cyanide-type toxicity. Symptoms in humans associated with acrylonitrile poisoning include limb weakness, labored and irregular breathing, dizziness and impaired judgment, cyanosis, nausea, collapse, and convulsions (Baxter 1979). However, the doses that produce these effects were not clearly defined. Workers exposed to 16 to 100 ppm for 20 to 45 minutes complained of headaches and nausea, apprehension and nervous irritation (Wilson et al. 1948). The workers exposed to acrylonitrile vapors fully recovered. In a study with human volunteers exposed to acrylonitrile at doses of 2.3 and 4.6 ppm, no symptoms attributable to effects on the nervous system were observed (Jakubowski et al. 1987). 

Acute-Duration Exposure. Information is available regarding the effects of acute-duration inhalation exposure of humans to acrylonitrile and the effects are characteristic of cyanide-type toxicity. Quantitative data are limited but are sufficient to derive an acute inhalation MRL. Further studies of humans exposed to low levels of acrylonitrile in the workplace would increase the confidence of the acute MRL. Studies in animals support and confirm these findings. No studies are available on the effects of acute-duration oral exposure in humans however, exposure to acrylonitrile reveals neurological disturbances characteristic of cyanide-type toxicity and lethal effects in rats and mice. Rats also develop birth defects. Animal data are sufficient to derive an acute oral MRL. Additional studies employing other species and various dose levels would be useful in confirming target tissues and determining thresholds for these effects. In humans, acrylonitrile causes irritation of the skin and eyes. No data are available on acute dermal exposures in animals. 

Effects produced by exposure to acrylonitrile, particularly after acute exposures, are characteristic of cyanide toxicity. These effects can be detected in people exposed by evaluating signs and symptoms such as limb weakness, labored and irregular breathing, dizziness and impaired judgement, cyanosis and convulsions. While tests are not specific for acrylonitrile-induced toxicity, they do identify potential health impairment. Studies to develop more specific biomarkers of acrylonitrile-induced effects would be useful in assessing the potential health risk of acrylonitrile near hazardous waste sites. 

Studies using radioactivity-labeled acrylonitrile indicate that acrylonitrile or its metabolites form covalent adducts with cellular macromolecules in most tissues. Studies to develop chemical or immunological methods for measuring these adducts would be especially valuable in detecting and perhaps even quantifying human exposure to acrylonitrile. Adverse health effects demonstrated following exposure to acrylonitrile, particularly acute exposures, were characteristic of cyanide toxicity. Because these effects are also indicative of exposure to many other toxicants, additional methods are needed for more specific biomarkers of effects of acrylonitrile exposure. 

Dudley HC, Neal PA. 1942. Toxicology of acrylonitrile (vinyl cyanide) I. A study of the acute toxicity. Journal of Industrial Hygiene and Toxicology 24 27 - 36. 

Adverse effects of cyanide on aquatic plants are unlikely at concentrations that cause acute effects to most species of freshwater and marine fishes and invertebrates (USEPA 1980 Eisler 1991). Water hyacinth (Eichhorinia crassipes) can survive for at least 72 h in nutrient solution containing up to 300 mg CN/L and can accumulate up to 6.7 g/kg DW plant material. On this basis, 1 ha of water hyacinths has the potential to absorb 56.8 kg of cyanide in 72 h, and this property may be useful in reducing the level of cyanide in untreated wastewater from various... 

Despite the high lethality of large single doses or acute respiratory exposures to high vapor concentrations of cyanide, repeated sublethal doses seldom result in cumulative adverse effects. 

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