Artifacts in the definition of toxicity by cyanides and cyanogens

Misleading conclusions may be drawn in defining toxicity from administered cyanides or cyanogens if meticulous attention to detail is not given in the design, conduct and interpretation of experimental and analytical procedures. Problems may occur if specimens are not appropriately stored or if interfering factors, such as antidotal agents, are present. Measurement of whole blood cyanide concentrations is valuable for diagnostic purposes, but plasma concentrations may give a better functional index of blood cyanide providing that samples are immediately analyzed. The most appropriate tissues for cyanide and cytochrome oxidase determinations are brain and ventricular myocardium. Analyses should be carried out immediately on freshly sampled tissue. In addition to the use of biochemical techniques for determination of cytochrome oxidase activity, dynamic quantitative histochemical methods are useful for assessing effects of cyanide on regional parenchymal enzyme activity. In determining cyanide-related cyanogen toxicity, the signs are useful, but comparison of molar lethal toxicity data requires caution. Confirmatory antidotal studies should be carefully designed with respect to both the nature and timing of antidotal procedures. In vitro studies assist in confirming cyanide liberation and are of value for investigating mechanisms of cyanogenesis. Variations in toxicity between cyanides and cyanogens are due to both the influence of inherent toxicity of the cyanogen molecule and differences in the rate of accumulation of biologically active cyanide.