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14,000 ppm for 10-20 min (Sechzer et al. 1960). Tremor has not been reported at lower concentrations and, in fact, was specifically absent in many of the detailed neurobehavioral protocols discussed below.

Dyspnea is a commonly reported end point and can be induced by acute exposures to CO2 at >30,000 ppm (NRC 1996). Hyperventilation without dyspnea occurs at exposure concentrations as low as 10,000 ppm (NRC 1996). Dyspnea attributable to CO2 is aggravated by increasing the level of exertion. Studies at rest will be discussed, followed by discussion of those that included exercise protocols.

White et al. (1952) studied humans exposed to CO2 at 60,000 ppm for 16 min and reported that 19 of 24 subjects exhibited slight or moderate dyspnea and 5 of 24 exhibited severe dyspneic sensations. At 40,000-50,000 ppm for 17-32 min, 16 subjects reported dyspnea (Schneider and Truesdale 1922). In contrast, no dyspnea was reported in five subjects exposed at 32,000 ppm or at 25,000-28,000 ppm for several hours (Brown 1930).

In the most modern protocol to examine dyspnea, Menn et al. (1970) reported that eight subjects exposed to CO2 at 11,000 ppm exhibited no increase in dyspnea or intercostal pain during 30 min of maximal exercise. The same study reported that exposure to CO2 at 28,000 ppm during 30 min of maximal exercise produced increased dyspnea in three of eight subjects and intercostal pain in two of eight subjects, but subjects did not show increased dyspnea at one-half or two-thirds maximal exercise. Sinclair et al. (1971) reported that a 1-h exposure to CO2 at 28,000 ppm in four subjects caused no dyspnea or intercostal pain during steady strenuous exercise. Thus, the bulk of the data indicate a no-observed-adverse-effect level (NOAEL) for CO2 of about 28,000 ppm on the basis of the findings on dyspnea and intercostal pain.

Neither dyspnea nor intercostal pain occurred in four subjects exposed to CO2 at 28,000 ppm for 15-20 days and made to do 45 min of exercise twice daily at up to a heavy level, although the chronic portion of this protocol was not fully described (Sinclair et al. 1971). Similarly, there were no symptoms reported in six subjects exposed to CO2 at 20,000 ppm for 30 days or 29,000 ppm for 8 days and made to do 10 min of exercise twice a week at a workload of 150 watts (Guillerm and Radziszewski 1979; Radziszewski et al. 1988). Thus, 28,000 ppm is an appropriate chronic NOAEL for dyspnea and intercostal pain.

Headaches are commonly associated with increased CO2 concentrations in inspired air, but there is conflicting data on the concentrations reliably associated with that end point. There may also be an effect of exertion, because CO2 seems to cause more headaches at lower concentra-



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