Cyanide lethality

Sprince, H., G.G. Smith, C.M. Parker, and D.A. Rinehimer. 1983. Protection against cyanide lethality in rats by L-ascorbic acid and dehydroascorbic acid. Nutr. Rep. Inter. 25 463-470. 

Rutkowski JV, Roebuck BD, Smith RP. 1985. Effects of protein-free diet and food deprivation on hepatic rhodanese activity, serum proteins and acute cyanide lethality in mice. J Nutr 115 132-137. 

Crystalline mass, mp 2V. Odor of soured fruit. bp7w 242° (dec) bp,j 132-134°. dj5 1.539. Vapor density 6.8 (air = l). Vapor pressure at 20° = 0.012 mm al 30° — 0.028 mm. Slightly sol in water. Freely sol in alcohol, ether, chloroform, acetone, and other common organic solvents also so] in phosgene, chloropicrin. benzyl cyanide. Lethal concn ... 

The antagonism of cyanide intoxication has been under investigation for at least 150 years. In 1840, cyanide lethality was reported to be antagonized by artificial respiration. 

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. 

Environmental. The toxicity of cyanide in the aquatic environment or natural waters is a result of free cyanide, ie, as HCN and CN . These forms, rather than complexed forms such as iron cyanides, determine the lethal toxicity to fish. Complexed cyanides may revert to free cyanide under uv radiation, but the rate is too slow to be a significant toxicity factor. Much work has been done to estabhsh stream and effluent limits for cyanide to avoid harmful effects on aquatic life. Fish are extremely sensitive to cyanide, and the many tests indicate that a free cyanide stream concentration of 0.05 mg/L is acceptable (46), but some species are sensitive to even lower concentrations. 

The use of black cyanide as a fumigant and rodenticide makes use of the atmospheric humidity action that Hberates hydrogen cyanide gas. It can only be used effectively ia confined spaces where hydrogen cyanide builds up to lethal concentrations for the particular appHcation. Black cyanide is also used ia limited quantities ia the production of pmssiates or ferrocyanides (see Iron compounds). 

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. 

Samples of smoke during fires have indicated that hydrogen cyanide is not of concern in fire deaths because the levels found were much below lethal levels. 

It is well known that hydrogen cyanide can be liberated during combustion of nitrogen containing polymers such as wool, silk, polyacrylonitrile, or nylons (1, 2). Several investigators have reported cyanide levels in smoke from a variety of fires (3, 4, 5). The levels reported are much below the lethal levels. Thus the role of cyanide in fire deaths would seem to be quite low. However, as early as 1966 the occurence of cyanide in the blood (above normal values) of fire victims was reported (6). Since then many investigators have reported elevated cyanide levels in fire victims (7-13). However, it has been difficult to arrive at a cyanide blood level which can be considered lethal in humans. In this report the results of cyanide analysis in blood of fire victims are reported as well as the possibility that cyanide may, in some cases, be more important than carbon monoxide as the principal toxicant in fire smoke. 

Establishing what the lethal level of blood cyanide is for humans is a difficult task. Based on extensive inhalation studies of HCN in mice a level of 1 mg/L of blood was suggested (12). In rats, a level of 2 mg/L of blood was found to be lethal (15). In limited experiments with cynomolgus monkeys, an exposure concentration of 150 ppm for 30 min would result in 3 mg/L of blood cyanide and would be lethal for these primates. Thus we have a range of 1 to 3 mg/L in experimental animals. The lethal level, however, has been found to be somewhat dependent upon exposure concentration and duration of exposure (12). 

Exposure to solid or liquid cyanogen halides can cause skin and eye irritation. Otherwise, casualties exposed to cyanides experience few effects at sublethal doses. Percutaneous absorption of a lethal dose may produce temporary rapid and deep breathing followed by convulsions and unconsciousness. Under these circumstances, the casualty will stop breathing within 2-4 minutes after exposure. Death will occur 4-8 minutes later. 

Lethal human toxicity values have not been established or have not been published. However, based on available information, this agent appears to be approximately half as toxic as Hydrogen cyanide (C07-A001). 

Summary of lethal and sublethal effects of free cyanide on freshwater fish... 

Figure 15.1 Summary of lethal and sublethal effects of free cyanide on freshwater fish. (Modified from Leduc, G., R.C. Pierce, and I.R. McCracken. 1982. The Effects of Cyanides on Aquatic Organisms with Emphasis upon Freshwater Fishes. Natl. Res. Coun. Canada, Publ. NRCC 19246. 139 pp. Avail, from Publications, NRCC/CNRC, Ottawa, Canada K1A OR6.)...

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