Effects on experimental animals of long-term continuous inhalation of nitrogen dioxide

Abstract

One preliminary acute 8-hour study at a concentration of 123 mg/m 3 of nitrogen dioxide, and one 30-day repeated study at a level of 67 mg/m 3 were conducted. Both exposures produced marked lung irritation and high mortality in all species. The gross pathologic findings in the lungs of surviving animals indicated hemorrhagic pulmonary edema in the 123 mg/m 3 study, and vascular congestion and focal hemorrhage in the 67 mg/m 3 study. Five 90-day continuous studies were run at 0.9, 1.0, 9.2, 21.3, and 21.6 mg/m 3 of nitrogen dioxide. Except for a possible slight weight loss, there were no effects noted at 0.9 and 1.0 mg/m 3. At 9.2 mg/m 3 there was a significant increase of mortality in guinea pigs and rabbits, and at the 21.3 and 21.6 mg/m 3 levels there was a significant increase in mortality in all species except the dog. Minimal pathologic lung changes were seen at the highest concentrations. Cumulative 30−, 60−, and 90-day mortality data for the continuous exposure studies indicate that one cannot safely extrapolate from the 30-day results to anticipate the effects which may occur after 90 days. Care should also be taken in extrapolating continuous-exposure guidelines from data obtained in repeated-exposure studies. It is believed that the submarine guideline of 0.5 ppm (0.9 mg/m 3) will not cause any untoward effects in personnel exposed continuously for 60 days. The choice of analytical procedure is critical in measuring the concentration to which animals are exposed. Absorption of samples in 0.1 N NaOH is not satisfactory. Absorption directly into the nitriting reagent is the method of choice.