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<br />perature falls; there is cyanosis of lips, face, and
<br />extremities, coma, frothy bloody saliva flow from
<br />mouth, and death (Way 1981). If acute exposure is
<br />to a sublethal dose of cyanide, this may lead to
<br />signs of toxicity, but as detoxification proceeds
<br />theso signs will become less obvious and eventu-
<br />ally vanish, and cyanide will be excreted as
<br />thiocyanate without accumulating CBallantyne
<br />1987a).
<br />Chronic cyanide poisoning may develop in in•
<br />dividuais who ingest significant quantities of cya-
<br />nideorcyanide precursorsin theirdiets;effectsare
<br />exacerbated by dietary deficiencies in vitamin B,s,
<br />iodine, and sulfur amino acids, as well as by ]ow
<br />levels and insufficient distribution of detoxifying
<br />enzymes such as rhodanese (Solomonson 1981).
<br />Cyanide toxicity of dietary origin has been impli-
<br />cated in acute animal deaths and as a major etio-
<br />logicfactor in toxic ataxic neuropathY in humans,
<br />and as a cause of blindness in humans suffering
<br />from tobacco amblyopia and Leber's hereditary op-
<br />tic atrophy (Egekeze and Ochme 1980). An in•
<br />crease in blood plasma cyanide is observed in
<br />healthy individuals who smoke cigarettes (~ail-
<br />leux et al. 1988). An increase in blood plasma
<br />thiocyanate is also seen in smokers and in
<br />hemodial}•sis patients just before dial}•sis (~ail~
<br />Leux et al. 1988). Continuous intake of cyanide
<br />causes high levels of plasma thiocyanate and goi-
<br />ters in mammals: the antithyroid action (goiters)
<br />results from cyanide interference with iodine
<br />transport and thyroxine synthesis (Solomonson
<br />1981; Leduc 1981, ]9S4). Signs of chronic cyanide
<br />poisoning include demyelination, lesions ofthe op-
<br />tic nerve, decrease in sulfur-containing amino ac-
<br />ids, increase in thiocyanate, goiter, ataxia.
<br />hypertonia, and depressed thyroid function
<br />(Solomonson 1981). These ei'fects are common in
<br />areas that depend on cyanogenic plants-such as
<br />cassava-as a major dietary component (Solomon-
<br />son ] 981).
<br />Biochemically, cyanide affects the citric acid
<br />cycle: strongly inhibits catalases and proteinases;
<br />induces glycolysis in protozoans, [ish, and mam-
<br />mals; produces vitamin Bj_ deficient}•; and modi-
<br />fies the phosphorylation mechanism ofrespiratorv
<br />mitochondria] enzymes, causing arrested respire-
<br />lion due to inabilit}• to use oxygen (Leduc 19841.
<br />Cyanide biomagnification or cycling has not
<br />been reported, probably because of cyanide's high
<br />chemical reactivity and rapid biotransformation
<br />(Towill et al. 1975; Marrs and Ballantyne 1987).
<br />There is no evidence that chronic exposure to
<br />c}•anide results in teratogenic, mutagenic, or car-
<br />CYMIDE
<br />cinogenic effects (EPA 1980 ). Cyanide possibly has
<br />antineoplastic activit}•, as judged by a ]ow thera-
<br />peutic success against rat sarcomas (EPA 1980),
<br />but this requires additional documentation.
<br />Confirmatory evidence of cyanide poisoning
<br />includes elevated blood thiocyanate levels-ex-
<br />cept, perhaps, when death was rapid-and re-
<br />duced cytochrome oxidase activity in brain and
<br />myocardium, provided that all tLssues were taken
<br />within a day or so of death, frpzen quickly, and
<br />analyzed shortly thereafter (B~ehl 1984; Marrs
<br />and Ballantyne 1987). Evaluation of cyanide poi-
<br />soning and metabolism includes signs of toxicity,
<br />LD50 values, measurement pf cyanide and
<br />thiocyanate concentrations,cytochrome coxidase
<br />activity, metabolic modification oC in vivo cyano-
<br />genesis, rate of c-,yanide liberation Ln vitro, and in-
<br />fluence of modifying factors such as the animal
<br />species, dose, rate and frequency of administra-
<br />tion, route of exposure, differenti8l distribution of
<br />cyanide, detoxification rates, circ8dian rhythm in-
<br />teractions,age oftheorganism, and presence of an-
<br />tidotes (Ballantyne 1987a). For example, the
<br />concentration of cyanide measured in body fluids
<br />and tissues in humans and other animals follow-
<br />ing lethal administration of c}-anode depends on
<br />several factors: route of exposure, with oral route
<br />}•ieldinghighest residues and inhalation route the
<br />lowest; amount and duration of exposure; nature
<br />of the material, with HCN and C11~'' being most
<br />toxic; time to death; antidotes used; t,me to
<br />autopsy, with marked loss documented from sim-
<br />ple evaporation, thiocyanate form&tion, hydroly-
<br />sis, and polymerization; and time from autopsy to
<br />sample analysis, wherein cyanide concentrations
<br />may increase due to microbial action (Ballantyne
<br />and Marrs 19S7b/.
<br />Antidotes
<br />The antagonism of cyanide intoxication has
<br />been under investigation for at least 150 years. In
<br />1840, cyanide lethality was reported to be antago-
<br />nized b}-artificial respiration. In 188$, amyl nitrite
<br />was reported effective in antagonizing lethal ef-
<br />fects ofcyanide in dogs. In 1899, cobalt w•as shown
<br />to form a stable metal complex with cyanide and
<br />was used to antagonize cyanide. In 1933, the use of
<br />sodium thiosulfate as the sulfur donor was de-
<br />scribed (Wa~~ 1964). Many compounds are used to-
<br />day as cyanide antidotes including cobalt salts,
<br />rhodanese. sulfur donors, methemoglobin produc-
<br />ers, carbohydrates, drugs used to treat acidosis,
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