million (ppm) and a range of 0-14 ppm, and data collected on 10 nuclear-powered attack submarines indicate an average CO concentration of 3 ppm and a range of 0-14 ppm (Hagar 2003).

The toxicology of CO in humans was reviewed by the World Health Organization (WHO) (1999), the U.S. Environmental Protection Agency (EPA) (2000), and the NRC (2002). Only human and animal data directly relevant to derivation of the EEGL and CEGL values are discussed in this chapter.

CO interferes with the oxygenation of blood and the delivery of oxygen to tissues because it has about 245 times more affinity for hemoglobin than does oxygen (Roughton 1970). The formation of carboxyhemoglobin (COHb) reduces the oxygen-carrying capacity of blood and shifts the oxygen dissociation curve, reducing the release of oxygen to tissues. Hypoxemia and subsequent tissue hypoxia comprise the best understood mechanism of CO toxicity. The cytotoxic effects of CO independent of oxygen are subjects of current research. CO also binds to muscle myoglobin, cytochrome c oxidase, and cytochrome P-450, and many of the adverse effects of CO might be associated with those reactions (WHO 1999;