ABSTRACT
I. Introduction and Background ........................................................................................... 314 II. Chemical Identities and Physicochemical Properties ....................................................... 314 III. Biological Mechanisms of Acute Toxicity ....................................................................... 314 IV. Metabolism and Detoxification of Cyanide ...................................................................... 315 V. Biochemical Sequelae of Cyanide Intoxication ................................................................ 316 VI. Determinants for Cyanide Toxicity .................................................................................. 317
A. Implications of Detoxification................................................................................... 317 B. Rate of Cyanide Absorption...................................................................................... 317 C. Biodistribution of Cyanide ........................................................................................ 319 D. Miscellaneous Factors ............................................................................................... 319
VII. Acute Toxicity of Cyanides .............................................................................................. 319 A. Toxicity to Laboratory Mammals ............................................................................. 319
1. Noninhalation Routes of Exposure..................................................................... 319 2. Inhalation Route of Exposure............................................................................. 321
B. Estimates of Acute Human Toxicity ......................................................................... 322 VIII. General Considerations on Repeated Exposue Toxicity................................................... 323 IX. Specific Organ, Tissue, and Functional End-Point Toxicity ............................................ 324
A. Neurotoxicity............................................................................................................. 324 B. Cardiotoxicity............................................................................................................ 326 C. Vascular Toxicity ...................................................................................................... 326 D. Respiratory Effects .................................................................................................... 327 E. Thyroid Gland Toxicity ............................................................................................ 327 F. Developmental and Reproductive Toxicity .............................................................. 327 G. Genotoxicity .............................................................................................................. 327 H. Oncogenicity ............................................................................................................. 328
X. Clinical Toxicology of Human Cyanide Poisoning.......................................................... 328 A. Clinical Presentation.................................................................................................. 328 B. Investigation and Confirmation of Poisoning ........................................................... 329 C. Management of Acute Cyanide Poisoning ............................................................... 329
1. First-Aid Measures ............................................................................................. 329 2. General Medical Management............................................................................ 330 3. Antidotes............................................................................................................. 330
XI. Cyanides in Military and Potential Terrorist Settings ......................................................... 331 A. Chemical Warfare Considerations ............................................................................... 331 B. Terrorist Implications ................................................................................................... 332
References ..................................................................................................................................... 334
The most commonly available cyanides are hydrogen cyanide (HCN), a highly volatile liquid, and sodium, potassium, and calcium cyanides, which are solids. They are widely used industrially and commercially; examples are in manufacturing processes (includes dyes, pigments, chelating agents, various nitrile, monomers, resins, and fibers), case hardening, electroplating, extraction of precious metals, and fumigation (Homan, 1987; Ballantyne, 1988; Ballantyne and Salem, 2005). In addition, due to their rapid lethal toxicity, they have been used for suicide, homicide, judicial execution, assassinations, and chemical warfare operations, and there exists a possibility for use by terrorists (Ballantyne, 1987a, 1987b; Gee, 1987; WHO, 2004; Ballantyne et al., 2006). Additionally, cyaniderelated toxicity and pathology may result from exposure to man-made and to naturally occurring cyanogens (Ballantyne, 1987b; Brimer, 1988). In addition, HCN is a product of combustion, and inhalation of smoke from fires may cause cyanide (CN) intoxication (Ballantyne, 1987c; Norris and Ballantyne, 1999; Ballantyne and Salem, 2005). As discussed later (Section XI.B), HCN has been employed by the military in chemical warfare operations because of its lethal and incapacitating effects. In addition, because of their known toxicity and comparatively ready availability, cyanides are possible candidates for use as psychological and lethal agents by terrorist organizations. This chapter discusses the experimental and human clinical toxicology of cyanides with particular reference to their potential for application as chemical warfare weapons and use by terrorists.
