HCN is a systemic poison; toxicity is due to inhibition of cytochrome oxidase, which prevents cellular utilization of oxygen. Inhibition of the terminal step of electron transport in cells of the brain results in loss of consciousness, respiratory arrest, and ultimately, death. Stimulation of the chemoreceptors of the carotid and aortic bodies produces a brief period of hyperpnea; cardiac irregularities may also occur. The biochemical mechanisms of cyanide action are the same for all mammalian species. HCN is metabolized by the enzyme rhodanese which catalyzes the transfer of sulfur from thiosulfate to cyanide to yield the relatively nontoxic thiocyanate.

Human exposures with measured concentrations were limited to occupational reports. Symptoms of exposed workers ranged from no adverse health effects to mild discomfort to frank central nervous system effects. Repeated or chronic exposures have resulted in hypothyroidism. Inhalation studies resulting in sublethal effects, such as incapacitation, and changes in respiratory and cardiac parameters were described for the monkey, dog, rat, and mouse; lethality studies were available for the rat, mouse, and rabbit. Exposure durations ranged from a few seconds to 24 hours (h). Regression analyses of the exposure duration-concentration relationships for both incapacitation and lethality for the monkey determined that the relationship is C2×t= k and that the relationship for lethality based on rat data is C2.6×t=k.

The AEGL-1 is based on human monitoring studies in which the preponderance of data as a weight-of-evidence consideration indicates that an 8-h exposure to HCN at 1 parts per million (ppm) would be without adverse health effects for the general population. Although the exposures were of chronic duration (generally 8 h/day (d) for extended work periods) and the data are lacking in various aspects of specific exposure concentrations and well-documented exposure-related symptoms, it is human data which are most relevant in determining the AEGL-1 threshold of notable discomfort.

Chronic exposures (5–15 years [y]) in three electroplating plants to mean concentrations of 6, 8, and 10 ppm produced exposure-related symptoms including headache, weakness, and objectionable changes in taste and smell (El Ghawabi et al. 1975), but the authors failed to relate symptoms to air concentrations. Over half of the workers presented with enlarged thyroids (characteristically observed in cases of chronic cyanide exposure), which may have been responsible for certain symptoms. In evaluating the El Ghawabi et al. (1975) study, a National Research Council (NRC) subcommittee concluded that a 1-h exposure at 8 ppm would cause no more than mild headache in healthy adults (NRC 2000). Mild headache meets the definition of the AEGL-1. Chronic exposures of 63 healthy adult cyanide-production workers to

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