Cyanide Release

1 i Cyanide Release. Considerable evidence suggests that the toxicity of organonitriles may occur as a result of the release of cyanide from the parent com- 

In general, substrate affinity and cyanide release increase with increasing size of the R group with benzylcyanide having a Km as low as 2.3 pM for rat nasal micro-somes. Metabolism of acrylonitrile may proceed via an epoxide, formed by CYP, which is then converted to the diol by epoxide hydrolase. The diol would then release cyanide by the same mechanism as other cyanohydrins. 

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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. 

As with the nitroxalkylcobalamins (119) and cobinamides, the co-binamides in which nitroxide is coordinated show electron spin resonance spectra very similar to the spectrum of free nitroxide. The high field line is not broadened as much as in the spectrum of a nitroxalkyl-cobinamide. No hyperfine splitting from methyl protons in the 2 or 6 positions can be observed for the bound nitroxide. However, treatment of the coordinate spin labeled compounds with cyanide releases the nitroxide. When this happens, the proton hyperfine can be observed (Fig. 25). Thus treatment with cyanide simply displaces the nitroxide and a spectrum for free nitroxide is observed. 

Grogan J, DeVito SC, Pearlman RS, et al. Modeling cyanide release from nitriles prediction of cytochrome P450 mediated acute nitrile toxicity. Chem Res Toxicol 1992 5(4) 548-552. 

Recent studies have shown that cyanide releases catecholamines from rat pheochromocytoma cells and brain slices (Kanthasamy et al. 1991b), from isolated bovine adrenal glands (Borowitz et al. 1988), and from the adrenals of mice following subcutaneous injection of high doses of potassium cyanide (Kanthasamy et al. 1991b). Thus, it was proposed that the cardiac and peripheral autonomic responses to cyanide are partially mediated by an elevation of plasma catecholamines (Kanthasamy et al. 1991b). 

There are numerous sources that release cyanide into water. Cyanide is released into water from both point and nonpoint sources. The major point sources of cyanide released to water are discharges from publicly owned treatment works (POTWs), iron and steel production, and organic chemical industries (Fiksel et al. 1981). Estimates based on data from the mid-to-late 1970s indicate that these sources account for 89% of the estimated 31 million pounds of total cyanide discharged annually to surface... 

Over 2,650 plant species can produce hydrogen cyanide (Seigler 1991 Swain et al. 1992). These include edible plants such as almonds, pits from stone fruits (e.g., apricots, peaches, plums, cherries), sorghum, cassava, soybeans, spinach, lima beans, sweet potatoes, maize, millet, sugarcane, and bamboo shoots (Fiksel et al. 1981). The cyanogenic glycoside content of a foodstuff is usually expressed as the amount of cyanide released by acid hydrolysis glycoside concentrations are rarely reported (WHO 1992). 

It is important to note that cytochrome P450-mediated hydroxylation can also occur at other carbon positions (i.e., positions other than that a to the cyano group) [8]. However, such hydroxylation does not result in cyanide release and represents a detoxication pathway. In fact, it is likely that most nitriles, even the toxic ones, are hydroxylated at multiple carbon positions [8]. The more toxic nitriles, however, are those in which metabolism at the a-carbon predominates. 

DeVito, S.C. and Pearlman, R.S. (1992) Physicochemical and structural factors influendng cyanide release from nitriles. Med. Chem. Res., 1, 461—465. 

Chadha, R.K., Lawrence, J.F., and Ratnayake, W.M.N. 1995. Ion chromatographic determination of cyanide released from flaxseed under autohydrolysis conditions. Food Add. Cont. 12, 527-533. 

A few weeks after the replastering of the church with a water-resistant cement mortar, the entire church had been fumigated with Zyklon B (hydrogen cyanide) to exterminate woodworm in the choir stalls. The hydrogen cyanide, released by the Zyklon B, did not just kill woodworm it... 

Toxic cyanide can be isolated in a special device called a Conway microdiffusion cell by treatment with acid, followed by collection of the weakly acidic F1CN gas that is evolved in a base solution. The cyanide released can be measured spectrophotometrically by formation of a colored species. 

ENGLER, S.H., SPENCER C.S., GILBERT L.E., Preventing cyanide release from leaves, Nature, 2000,406, 144-145. 

To prepare dynamic cyanohydrin systems under mild conditions, a range of aldehyde compounds and cyanide sources was evaluated. As a result, benzaldehydes 23A-E were selected due to their diverse substitution patterns and their inability to generate any side reactions. Even though there are many cyanide sources, acetone cyanohydrin 24 was chosen as cyanide source in presence of triethylamine base, resulting in smooth cyanide release. Dynamic cyanohydrin systems (CDS-3) were thus generated from one equivalent of each benzaldehyde 23A-E and acetone cyanohydrin 24 in chloroform- at room temperature (Scheme 10). One equivalent of triethylamine was added to accelerate the reversible cyanohydrin reactions and this amount was satisfactory to force the dynamic system to reach equilibrium even at low temperature. 

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