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Cyanide Toxicokinetics: The Behavior of Cyanide, Thiocyanate and 2-Amino-2-Thiazoline-4-Carboxylic Acid in Multiple Animal Models
Journal of Analytical Toxicology
  • Raj K. Bhandari, South Dakota State University
  • Robert P. Oda, South Dakota State University
  • Ilona Petrikovics, Sam Houston State University
  • David E. Thompson, Sam Houston State University
  • Matthew Brenner, University of California, Irvine
  • Sari B. Mahon, University of California, Irvine
  • Vikhyat S. Bebarta, San Antonio Military Medical Center
  • Gary A. Rockwood, US Army Medical Research Institute of Chemical Defense
  • Brian A. Logue, South Dakota State University
Document Type
Article
Publication Date
5-1-2014
Disciplines
Abstract

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.

Format
application/pdf
DOI of Published Version
10.1093/jat/bku020
Publisher
Oxford Academic
Rights
Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S.
Citation Information
Raj K. Bhandari, Robert P. Oda, Ilona Petrikovics, David E. Thompson, et al.. "Cyanide Toxicokinetics: The Behavior of Cyanide, Thiocyanate and 2-Amino-2-Thiazoline-4-Carboxylic Acid in Multiple Animal Models" Journal of Analytical Toxicology Vol. 38 Iss. 4 (2014) p. 218 - 225
Available at: http://works.bepress.com/brian-logue/10/