Characterization of a Swine (Sus scrofa) Model of Oral Potassium Cyanide Intoxication

][4][5][7][8] The NIH Strategic Plan and Research Agenda for Medical Countermeasures specifies that ingested cyanide is a leading threatunique from inhaled and intravenous cyanide-because of the potentially higher cyanide dose, accessibility, delayed kinetics of absorption, and vulnerability of food and water suppl ies. 5,6,9,12,15,16,23,28,29When ingested, cyanide salts are exposed to the acidic environment of the stomach and form hydrogen cyanide, which gets absorbed and can cause systemic toxicity.19][20]23,[27][28][29] According to the Centers for Disease Control and Prevention, the potential LD 50 for oral KCN exposure is 1.8 to 7.3 mg/kg, but this figure is not well defined and is extrapolated from case report studies.Furthermore, the LD 50 for oral cyanide in swine is not well established, and dosing regimens must be based on previous studies performed mostly on small to moderate-sized animals.]21,22,24 Currently, no countermeasures are established for oral cyanide poisoning.Regulations of the US Food and Drug Association provide guidance on the new drug approval process when antidotes for chemical threats cannot be tested directly on human subjects for safety reasons. 10For scenarios where human studies are not feasible, the FDA (through application of the Animal Rule) can approve new therapeutics that have been studied in well-characterized animal models-preferably 2 species, one of which is a large mammal. 103][4] In these studies, pigs provided a reliable and reproducible model system.24][25][26] As a result, the toxicokinetic and pharmacodynamic principles of oral chemicals and antidotes observed in those species may not apply to humans.Studies of oral cyanide toxicity and treatment involving a large animal model that has similar physiology, size, and anatomy to humans would be useful in developing new antidotes.Previously, we studied acute intravenous cyanide toxicity in a swine model. 3,45][26] The use