exposure; however, welders exposed at 30 and 90 ppm for 40 min experienced varying degrees of dyspnea, cough, headache, chest tightness, nausea, and cyanosis, and hospitalization was required for pulmonary edema at the higher concentration (Norwood et al. 1966; Morley and Silk 1970). Similar symptoms and respiratory complaints were reported following release of a cloud of N2O4 from a railroad tank car (Bauer et al. 1996).

Epidemiologic studies on the long-term effects of elevated concentrations of NO2 are conflicting. It is likely that increases in respiratory illnesses are from NO2 in combination with other pollutants and that short-term peak concentrations are more detrimental than chronic, low-level exposures. Evidence suggests that children (5-12 years old) have a greater risk for developing respiratory disease from long-term exposure to higher concentrations, but infants do not.

Experimental studies with both healthy and asthmatic individuals exposed to NO2 are inconclusive. Negative results were obtained in many studies with exposures up to 4 ppm for 1 h; however, other studies report positive effects on pulmonary function at lower concentrations. In the studies that found statistically significant differences with NO2 exposure, the changes were within 10% of the measured value after air-only exposure and of questionable biologic significance even for asthmatic subjects. However, the available evidence also suggests that asthmatic subjects may experience an increase in airway responsiveness at 0.2-0.3 ppm.

NO has been used extensively in adults and children to lower pulmonary vascular resistance caused by acute respiratory distress syndrome, hypoxemic respiratory failure, persistent pulmonary hypertension, other heart or lung disease, and organ transplantation. The toxicity of NO is associated with methemoglobin formation and oxidation to NO2. Contamination of anesthesia gases has resulted in one fatality, but exposure concentrations were not measured. Therapeutic concentrations of 20-80 ppm for 24 h or 100 ppm for 20 min have not resulted in adverse effects among treated patients. However, an infant exposed at 80 ppm for 26 h developed clinically significant concentrations of methemoglobin, which were rapidly lowered with infusion of methylene blue and reduction of the NO concentration. Effects of NO on the airways are somewhat variable. It appears that NO might have either no effect or cause bronchoconstriction in normal subjects, but might result in bronchodilation in individuals with chemically-induced bronchoconstriction or asthma.

3. ANIMAL TOXICITY DATA

3.1. Acute Lethality

Acute lethality data from NO2 were found for several species. One group of investigators (Hine et al. 1970) studied the effects of varying concentration and duration of exposure in five different species of laboratory animal; these



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