Inhalation of 1-nitropyrene associated with ultrafine insoluble particles or as a pure aerosol: a comparison of deposition and biological fate.

A large number of the environmental particulate pollutants in the atmosphere, including diesel engine exhaust, have a complex mixture of organic compounds associated with them. Organic solvent extracts of many of these particulate pollutants have been shown to contain mutagenic activity which does not require metabolic activation in the Ames bioassay. Much of this direct-acting mutagenic activity has been attributed to nitroaromatic compounds present in these extracts. In the studies reported here, the direct-acting mutagen, [3H]nitropyrene (3H-NP), was used as a model nitroaromatic compound. Rats were exposed to this radiolabeled compound by nose-only inhalation either as a coating (approximately 6% by mass) on relatively inert, ultrafine 67Ga2O3 particles or as a homogeneous ultrafine aerosol. The tissue deposition, retention, and biological fate of each aerosol were investigated and compared. Respiratory tract clearance of 3H radioactivity from each exposure was very rapid with no apparent differences seen in the lung retention of this inhaled compound between each exposure over the course of these studies. Higher 3H-radioactivity levels were seen in stomach and large intestines of rats exposed to the 67Ga2O3-associated 3H-NP than in the same tissues from rats exposed to the pure 3H-NP aerosol. Rats exposed to the 3H-NP-67Ga2O3 aerosol excreted the majority of the deposited 3H radioactivity in the feces (75 +/- 18%), whereas pure 3H-NP exposed animals excreted a major portion of the radiolabeled in the urine (76 +/- 18%). It appeared that the major portion of the pure 3H-NP aerosol was cleared from the respiratory tract by direct absorption into blood, while the 67Ga2O3-associated 3H-NP was cleared by both blood absorption and mucociliary clearance followed by ingestion and fecal excretion. These differences in the deposition and biological fate between the particle-associated NP and the pure NP aerosol may have important implications in terms of the metabolic fate of inhaled nitroaromatic compounds and the health risks associated with human exposures to particulate environmental pollutants that contain this class of compounds.