Cyanide toxicokinetics

These experts collectively have knowledge of cyanide s physical and chemical properties, toxicokinetics, key health end points, mechanisms of action, human and animal exposure, and quantification of risk to humans. All reviewers were selected in conformity with the conditions for peer review specified in Section 104(i)(13) of the Comprehensive Environmental Response, Compensation, and Liability Act, as amended. 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective of the toxicology of cyanide. It contains descriptions and evaluations of toxicological studies and epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. 

In animal studies acetone has been found to potentiate the toxicity of other solvents by altering their metabolism through induction of microsomal enzymes, particularly cytochrome P-450. Reported effects include enhancement of the ethanol-induced loss of righting reflex in mice by reduction of the elimination rate of ethanol increased hepatotoxicity of compounds such as carbon tetrachloride and trichloroethylene in the rat potentiation of acrylonitrile toxicity by altering the rate at which it is metabolized to cyanide and potentiation of the neurotoxicity of -hexane by altering the toxicokinetics of its 2,4-hexane-dione metabolite.Because occupationally exposed workers are most often exposed to a mixmre of solvents, use of the rule of additivity may underestimate the effect of combined exposures. ... 

Leuschner, J., A.Winkler, and F.Leuschner. 1991. Toxicokinetic aspects of chronic cyanide exposure in the rat. Toxicol. Lett. 57(2) 195-201. 

Sousa, A.B., Manzano, H., Soto-Blanco, B., Gomiak, S.L. (2003). Toxicokinetics of cyanide in rats, pigs and goats after oral dosing with potassium cyanide. Arch. Toxicol. 77 330-4. 

Toxicokinetic data are available only for propionit-rile. When administered as a " C radioisotope, 92.5% of the compound was recovered. The majority was eliminated in air or urine within 24 h. About 27% was recovered as volatile organic material within 0.5 h of gavage exposure. By 3 h, either carbon dioxide or cyanide exhalation was estimated at 38 9% of the total. At 24 h, the total " C recovery in the urine was 0.76-5.83%. A small amount (<2%) was found in liver and kidneys at 72 h after dosing. It was concluded that propionitrile is rapidly absorbed from the gastrointestinal tract and eliminated through expired air as the parent compound, CO2, or cyanide. 

The U.K. Food Standards Agency suggested that a daily dose of 0.005 mg/kg of cyanide would be unlikely to cause acute effects (FSA 2006). A discussion paper from the FAO and WHO indicated that this estimate may be overly conservative and does not account for the different toxicokinetics for amygdalin (the cyanogenic glycoside present in apricot kernels) that involves bacterial enzymatic conversion to hydrocyanic acid once ingested (FAO/WHO 2009). Other organizations have indicated provisional tolerable... 

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