Cyanide following exposure

As a class of compounds, the two main toxicity concerns for nitriles are acute lethality and osteolathyrsm. A comprehensive review of the toxicity of nitriles, including detailed discussion of biochemical mechanisms of toxicity and stmcture-activity relationships, is available (12). Nitriles vary broadly in their abiUty to cause acute lethaUty and subde differences in stmcture can greatly affect toxic potency. The biochemical basis of their acute toxicity is related to their metaboHsm in the body. Following exposure and absorption, nitriles are metabolized by cytochrome p450 enzymes in the Hver. The metaboHsm involves initial hydrogen abstraction resulting in the formation of a carbon radical, followed by hydroxylation of the carbon radical. MetaboHsm at the carbon atom adjacent (alpha) to the cyano group would yield a cyanohydrin metaboHte, which decomposes readily in the body to produce cyanide. Hydroxylation at other carbon positions in the nitrile does not result in cyanide release. 

In a case study of a human male accidentally sprayed with acrylonitrile, recurring signs of cyanide poisoning were seen over a 3 day period (Vogel and Kirkendall 1984). This indicates that acrylonitrile is also metabolized to cyanide following predominantly dermal exposure. 

Studies using radioactivity-labeled acrylonitrile indicate that acrylonitrile or its metabolites form covalent adducts with cellular macromolecules in most tissues. Studies to develop chemical or immunological methods for measuring these adducts would be especially valuable in detecting and perhaps even quantifying human exposure to acrylonitrile. Adverse health effects demonstrated following exposure to acrylonitrile, particularly acute exposures, were characteristic of cyanide toxicity. Because these effects are also indicative of exposure to many other toxicants, additional methods are needed for more specific biomarkers of effects of acrylonitrile exposure. 

Ruby, S.M., D.R. Idler, and Y.P. So. 1987. Changes in plasma, liver, and ovary vitellogenin in landlocked Atlantic salmon following exposure to sublethal cyanide. Arch. Environ. Contam. Toxicol. 16 507-510. 

Report No. MSL-2985, Monsanto Company. U.S. EPA OTS Submission 88-920007543. Bonsall, J.L. 1984. Survival without sequelae following exposure to 500 mg/m3 of hydrogen cyanide. Human Toxicol. 3 57-60. 

Cyanide has not been shown to accumulate in the blood and tissues following chronic oral exposure to inorganic cyanides. Following the treatment of groups of 10 male and 10 female rats with hydrogen cyanide in the diet at < 10.4 mg CN /kg/day for 2 years, virtually no cyanide was found in plasma or kidneys (Howard and Hanzal 1955). Low levels were found in erythrocytes (mean of 1.9 pg/100 g). 

This section will describe clinical practice and research concerning methods for reducing toxic effects of exposure to cyanide. However, because some of the treatments discussed may be experimental and unproven, this section should not be used as a guide for treatment of exposures to cyanide. When specific exposures have occurred, poison control centers and medical toxicologists should be consulted for medical advice. The following texts provide specific information about treatment following exposures to cyanide ... 

Bonsall JL. 1984. Survival without sequelae following exposure to 500 mg/m3 of hydrogen cyanide. Hum Toxicol 3 57-60. 

Toxicity follows exposure to chemical agents dispersed as solids, liquids, aerosols, or vapor (Table 23.1). CW agents have characteristics that make them uniquely suited to warfare. In addition to their extreme toxicity, their chemical structures are simple, and the manufacturing processes for most are relatively uncomplicated and inexpensive. Cyanide and phosgene are manufactured in large quantities for use in industry and are shipped in bulk by truck or train. 

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