Cyanide causes toxic effects by inhibiting
cytochrome c oxidase, resulting in cellular hypoxia and cytotoxic
anoxia, and can eventually lead to death.
Cyanide exposure can be verified by direct analysis of
cyanide concentrations or analyzing its metabolites, including
thiocyanate (SCN(-)) and 2-amino-2-thiazoline-4-carboxylic
acid (
ATCA) in blood. To determine the behavior of these markers following
cyanide exposure, a toxicokinetics study was performed in three animal models: (i) rats (250-300 g), (ii) rabbits (3.5-4.2 kg) and (iii) swine (47-54 kg).
Cyanide reached a maximum in blood and declined rapidly in each animal model as it was absorbed, distributed, metabolized and eliminated.
Thiocyanate concentrations rose more slowly as
cyanide was enzymatically converted to SCN(-). Concentrations of
ATCA did not rise significantly above the baseline in the rat model, but rose quickly in rabbits (up to a 40-fold increase) and swine (up to a 3-fold increase) and then fell rapidly, generally following the relative behavior of
cyanide. Rats were administered
cyanide subcutaneously and the apparent half-life (t1/2) was determined to be 1,510 min. Rabbits were administered
cyanide intravenously and the t1/2 was determined to be 177 min. Swine were administered
cyanide intravenously and the t1/2 was determined to be 26.9 min. The SCN(-) t1/2 in rats was 3,010 min, but was not calculated in rabbits and swine because SCN(-) concentrations did not reach a maximum. The t1/2 of
ATCA was 40.7 and 13.9 min in rabbits and swine, respectively, while it could not be determined in rats with confidence. The current study suggests that
cyanide exposure may be verified shortly after exposure by determining significantly elevated
cyanide and SCN(-) in each animal model and
ATCA may be used when the
ATCA detoxification pathway is significant.