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<br />BIOLOGICAL REPORT 85(1.2$ )
<br />4-carboxylic acid or 2-aminothiazoline-4-carbox-
<br />ylic acid; combining with hydroxocobalamin (B~z)
<br />to form cyanocobalamin, which is excreted in urine
<br />and bile; and binding by methemoglobin in the
<br />blood (Towill et al. 1978; EPA 1980; Ballantyne
<br />1987a; Marrs and Ballantyne 1987).
<br />Absorption of hydrogen cyanide liquid or gas
<br />readily occurs through inhalation, ingestion, or
<br />skin contact (Towill et al. 1978; Egekeze and
<br />Oehme 1980; EPA 1980; Homan 1987). inhalation
<br />and skin absorption are the primary hazardous
<br />routes in cyanide toxicity in occupational expo-
<br />sure. Skin absorption is most rapid when the skin
<br />is cut, abraded, or moist. Inhalation of cyanide
<br />salts is also potentially hazardous because the cya-
<br />nidedissolves on contactwith moist mucous mem-
<br />branes. Regardless ofroute of exposure, cyanide is
<br />readily absorbed into the bloodstream and distrib-
<br />utedthroughoutthebody.Cyanide concentrates in
<br />ervthrocytes through binding to methemoglobin
<br />(Towill et al. 1978; EPA 1980), and free cyanide
<br />concentrations in plasma are now considered one
<br />of the better indicators of cytotoxicity (Ballantyne
<br />1967a). Because of the affinit}• of cyanide for the
<br />mammalian erythrocyte, the spleen may contain
<br />elevated cyanide concentrations when compared
<br />to blood; accordingly, spleen should always be
<br />taken for analysis in cases of suspected cyanide
<br />poisoning (Ballantyne 1975). Cyanide also accu-
<br />mulates in various body cells through binding to
<br />metalloproteins or enzymes such as catalase and
<br />cytochrome c oxidase (EPA 1980). The brain is
<br />probably the major target organ of cytotoxic
<br />hypoxia, and brain cytochrome oxidase may be the
<br />most active site of lethal cyanide action, as judged
<br />by distribution of cyanide, thiosulfate, and
<br />rhodanese (Solomonson 1981; Ballantyne 1987a).
<br />Significant positive correlations exi st between cya-
<br />nideconcentrationsin plasma,cerebrospinalfluid,
<br />and brain (Ballantyne 1987a); these correlations
<br />need further exploration.
<br />Hydrogen cyanide formation may contribute
<br />to the toxicity of snake venom, owing to the high
<br />levels of L-amino acid oxidase in some snake ven-
<br />oms (Vennesland et al. 1981b). This enzyme is
<br />harmless on injection, but the tissue destruction
<br />caused by other venom components probably pro-
<br />videsthe required substrate and cofactor for HCN
<br />production.
<br />Cyanide inhibits ion transport mechanisms in
<br />amphibian skin, gall bladder, and proximal renal
<br />tubules (Bello-Reuss et al. 19811. Measurable
<br />changes in cell membrane potentials of isolated
<br />gall bladder epithelium cells, for example, were in-
<br />duced by NaCN in a salamander (Necturus
<br />maculosus; Bello-Reuss et al. 1981). Cyanide-
<br />induced hyperpolarization was caused primarily
<br />by an increase in permeability of the cell mem-
<br />brane to potassium, which, in turn, was mediated
<br />by an elevation of intracellular calcium ion activ-
<br />ity, attributable to release from mitochondrial
<br />sources.
<br />The binding rate of CN to hemgproteins, spe•
<br />cifically hemoglobin components III and IV, is 370
<br />times to 2,300 times slower in a marjne polychaete
<br />annelid (Glycera dibranchiata), when compared to
<br />guinea pig (Cauia spp.), soybean (Glycinc max),
<br />and sperm whale (Phpseter macrogephalus); the
<br />significance of this observation is unclear but war-
<br />rants further exploration iMintorovitch et al.
<br />1969).
<br />Clinical Features
<br />Accidental exposure to cyanides or cyanogens
<br />through inhalation, skin exposure, and swallow-
<br />ingoccurs in agricultural fumigations laboratories,
<br />industrial operations, domestic abuge, and prod-
<br />ucts of combustion (Ballantyne and 1'yfarrs 1987b),
<br />Intentional exposure is reported from homicides,
<br />suicides (usually uncommon), judici8l executions,
<br />chemical warfare, and covert activities (Ba]]an-
<br />t}me and Marrs 1987b).
<br />Diagnosis of lethal cyanide poisoning is diffi-
<br />cult because of the absence of gross pathology or
<br />histology, nonspecific congestion of viscera, and
<br />cerebral or pulmonary edema. Sometimes the
<br />blood is bright red, and sometimes the odor of bit-
<br />teralmonds is detected, but neither it; sufficiently
<br />consistent for diagnostic purposes (Ba']lantyne and
<br />lviarrs 1987b).
<br />At low lethal doses of cyanide, the effects are
<br />principally on cytochrome oxidase in the central
<br />nervous system. At higher doses, cardiovascular
<br />signs and changes in electrical activity ofthe brain
<br />are among the most consistent changes measured
<br />(Way 1981, 19841. Acute and subacute toxic effects
<br />of poisoning with cyanide can vary $rom convul-
<br />sions, screaming, vomiting, and bloody frothing to
<br />less dramatic events, such as a slow, quiet onset to
<br />coma and subsequent death (Way 1881). In the
<br />first stage of cyanide poisoning, victims exhibit
<br />headache, vertigo, weak and rapid pulse, nausea,
<br />and vomiting. In the second stage, there are con-
<br />vulsions, falling, dilated pupils, clammy skin. and
<br />a weaker and more rapid pulse. In the final stage,
<br />heartbeat becomes irregular and slow; body tem-
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