Fate and distribution of inhaled nitrogen dioxide in rhesus monkeys.

The intra- and extrapulmonary distributions of inspired nitrogen dioxide (NO2) were studied by exposing rhesus monkeys to air mixtures containing concentrations slightly greater than ambient (0.56 to 1.71 mg per m3, or 0.30 to 0.91 ppm) of NO2 labeled with tracer quantities of NO2 containing nitrogen-13 dioxide (13NO2). The 13NO2 (half-time, 10 min) was synthesized by the oxygen-16 (P, alpha)13N nuclear reaction in an isochronous cyclotron. The intrapulmonary location and concentration of the inspired 13NO2 was detected continuously by external monitoring of the annihilation radiation consequent to positron emissions from disintegrating 13N. The 13N concentration of arterial blood was also measured at intervals, and the blood values were correlated with those from the lung. Chemical measurements of NO2 concentration in inspired and expired air were performed by the Saltman method. Control studies were performed with xenon-125 (125Xe) (halftime, 17 hours). The results demonstrated that 50 to 60% of the inspired pollutant was retained by the primate during quiet respiration; the gas was distributed throughout the lungs. Once absorbed, NO2 or chemical intermediates remained within the lungs for prolonged periods after cessation of exposure, and dissemination of the pollutant or its derivatives to extrapulmonary sites occurred via the blood stream. Indirect evidence indicated the probable reaction of NO2 with water in the nasopharynx and lungs to form nitric and nitrous acids. The reaction of these acids with pulmonary and extrapulmonary tissues probably accounts for the biologic toxicity of NO2.