Toxicity cyanides

The leaves, root and bark are considered safest for external use only. However, European elder has less toxicity than the western varieties. The bark, if used internally, should be only the European variety aged for at least one year to avoid cyanide toxicity. 

Neurotoxicity. Clinical signs indicative of disturbances of the nervous system in exposed humans have been well documented in short-term studies at high doses and appear to be reversible. These effects are characteristic of cyanide toxicity. Animal studies confirm findings in humans. In longer-term studies, effects on the nervous system have also been reported, but it is not certain if these effects are permanent or reversible following termination of acrylonitrile exposure. 

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. 

Ruby, S.M., P. Jaroslawski, and R. Hull. 1993. Lead and cyanide toxicity in sexually maturing rainbow trout, Oncorhynchus mykiss during spermatogenesis. Aquat. Toxicol. 26 225-238. 

Thiosulfate is usually low in the body, and higher levels can significantly protect against cyanide toxicity. 

Elzubeir, E.A. and R.H. Davis. 1988b. Sodium nitroprusside, a convenient source of dietary cyanide for the study of chronic cyanide toxicity. Brit. Poult. Sci. 29 779-783. 

Aitken, D., D.West, F.Smith, W.Poznanski, J.Cowan, J.Hurtig, E.Peterson, and B.Benoit. Cyanide toxicity following nitropmsside induced hypotension. Can. Anes. Soc. J. 24 651-660. Alarie, Y. 1997. Personal Communication to Sylvia Talmage, Oak Ridge National Laboratory, via e-mail, November 20, 1997. ... 

Schulz, V., R.Gross, T.Pasch, J.Busse, and G.Loeschcke. 1982. Cyanide toxicity of sodium nitroprusside in therapeutic use with and without sodium thiosulphate. Klin. Wochensch. 60 1393-1400. 

Cyanide toxicity was tested in rabbits by applying 1.69-5.28 mg CNVkg/day as sodium cyanide to the inferior conjunctival sac of one eye (Ballantyne 1983b, 1988). Irritation, lacrimation, and conjunctival hyperemia were present immediately after the treatment. Keratitis developed in some rabbits after a cyanide application of 0.9 mg CNTkg as hydrogen cyanide, 2.1 mg CNTkg as sodium cyanide, and 2.5 mg CN /kg as potassium cyanide. 

Increased duration of exposure to inhaled cyanide in mice resulted in lower LC50 values (Higgins et al. 1972 Matijak-Schaper and Alarie 1982). Additionally, cyanide toxicity was influenced by dilution of the gavage dose. Greater dilution resulted in higher mortality for the same total dose (Ferguson 1962). 

Ibrahim et al. 1963). Aiken and Braitman (1989) determined that cyanide has a direct effect on neurons not mediated by its inhibition of metabolism. Consistent with the view that cyanide toxicity is due to the inability of tissue to utilize oxygen is a report that in cyanide-intoxicated rats, arterial p02 levels rose, while carbon dioxide levels fell (Brierley et al. 1976). The authors suggested that the low levels of carbon dioxide may have led to vasoconstriction and reduction in brain blood flow therefore, brain damage may have been due to both histotoxic and anoxic effects. Partial remyelination after cessation of exposure has been reported, but it is apparent that this process, unlike that in the peripheral nervous system, is slow and incomplete (Hirano et al. 1968). The topographic selectivity of cyanide-induced encephalopathy may be related to the depth of acute intoxication and distribution of blood flow, which may result in selected regions of vascular insufficiency (Levine 1969). 

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). 

Several papers discuss the effects of oxygen alone or with other compounds on cyanide toxicity. Oxygen alone results in minimal antagonism in mice injected with potassium cyanide and only slightly enhances the antagonistic effects of sodium nitrite (Sheehy and Way 1968). The antidotal effect of sodium thiosulfate alone or in combination with sodium nitrite, was enhanced by oxygen. 

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. 

An increase in antidotal effect was noted when rhodanese was combined with thiosulfate (Frankenberg 1980). Similarly, other sulfane sulfur donors have protective effects against cyanide toxicity. 

In addition, other chemicals such as a-adrenergic blocking agents like chlorpromazine (O Flaherty and Thomas 1982 Way and Burrows 1976) or oxygen (Burrows et al. 1973 Sheehy and Way 1968) may be used to enhance the protective action of other antidotes. However, the mechanism of their action is not well understood. Further research for a potent and safe antidote, particularly among smoke inhalation victims who have carbon monoxide poisoning, to mitigate cyanide toxicity is desirable. 

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