1. A Review on Ingested Cyanide: Risks, Clinical Presentation, Diagnostics, and Treatment Challenges
Tara B Hendry-Hofer, Patrick C Ng, Alyssa E Witeof, Sari B Mahon, Matthew Brenner, Gerry R Boss, Vikhyat S Bebarta J Med Toxicol. 2019 Apr;15(2):128-133. doi: 10.1007/s13181-018-0688-y. Epub 2018 Dec 11.
Cyanide, a metabolic poison, is a rising chemial threat and ingestion is the most common route of exposure. Terrorist organizations have threatened to attack the USA and international food and water supplies. The toxicokinetics and toxicodynamics of oral cyanide are unique, resulting in high-dose exposures, severe symptoms, and slower onset of symptoms. There are no FDA-approved therapies tested for oral cyanide ingestions and no approved intramuscular or oral therapies, which would be valuable in mass casualty settings. The aim of this review is to evaluate the risks of oral cyanide and its unique toxicokinetics, as well as address the lack of available rapid diagnostics and treatments for mass casualty events. We will also review current strategies for developing new therapies. A review of the literature using the PRISMA checklist detected 7284 articles, screened 1091, and included 59 articles or other reports. Articles referenced in this review were specific to risk, clinical presentation, diagnostics, current treatments, and developing therapies. Current diagnostics of cyanide exposure can take hours or days, which can delay treatment. Moreover, current therapies for cyanide poisoning are administered intravenously and are not specifically tested for oral exposures, which can result in higher cyanide doses and unique toxicodynamics. New therapies developed for oral cyanide exposures that are easily delivered, safe, and can be administered quickly by first responders in a mass casualty event are needed. Current research is aimed at identifying an antidote that is safe, effective, easy to administer, and has a rapid onset of action.
2. Cyanide toxicokinetics: the behavior of cyanide, thiocyanate and 2-amino-2-thiazoline-4-carboxylic acid in multiple animal models
Raj K Bhandari, Robert P Oda, Ilona Petrikovics, David E Thompson, Matthew Brenner, Sari B Mahon, Vikhyat S Bebarta, Gary A Rockwood, Brian A Logue J Anal Toxicol. 2014 May;38(4):218-25. doi: 10.1093/jat/bku020.
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.
3. Removal of cyanide adsorbed on pyrite by H2O2 oxidation under alkaline conditions
Yubo Tu, Peiwei Han, Lianqi Wei, Xiaomeng Zhang, Bo Yu, Peng Qian, Shufeng Ye J Environ Sci (China). 2019 Apr;78:287-292. doi: 10.1016/j.jes.2018.10.013. Epub 2018 Nov 14.
Large amounts of cyanide tailings are produced during the cyanidation process in gold extraction, which are hazardous solid wastes due to the toxic cyanide. Pyrite is one of the main minerals in cyanide tailings. The removal of cyanide adsorbed on pyrite by H2O2 oxidation under alkaline conditions was investigated in this study. It was found that the removal efficiency was positively correlated with pH from 5 to 12, but remained almost constant when pH was higher than 12. The highest cyanide removal efficiency of 91.10% was achieved by adding no less than 0.6 wt.% of H2O2. Cyanide removal was positively correlated with the CN- adsorption amount between 1.06 and 8.5 mg/g, and temperature between 25 and 85°C. The removal of cyanide adsorbed on pyrite by H2O2 oxidation under alkaline conditions was due to the oxidation of pyrite. Hexacyanoferrate, thiocyanate and sulfate were generated with mole ratios of about 2.03:1.12:3.17 during the cyanide removal.
