Deposition, retention, and biological fate of inhaled benzo(a)pyrene adsorbed onto ultrafine particles and as a pure aerosol

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Abstract

The effect of ultrafine, airborne, carrier particles on the deposition, retention, and biological fate of inhaled polycyclic aromatic hydrocarbons (PAHs) was studied. Using a radiolabeled model PAH, [3H]benzo(a)pyrene ([3H]BaP), Fischer-344 rats were exposed by nose-only inhalation (30 min) to this compound, as a coating (15% by mass) on insoluble 67Ga2O3 particles or as a pure aerosol. These aerosols were produced by vapor condensation methods in a dynamic aerosol generation system. The concentrations of [3H]BaP in the coated and homogeneous aerosols were 0.6 and 1.0 μg/liter of air, respectively, while the mass median diameter of both these aerosols was approximately 0.1 μm. Pulmonary retention of 3H radioactivity was longer in animals exposed to the [3H]BaP coated on the 67Ga2O3 particles. The time required to clear 90% of the initial lung burden of 67Ga2O3-associated 3H radioactivity detected 30 min postexposure was approximately 1 day as compared to 4 hr for animals exposed to the pure [3H]BaP aerosol. Tracheal clearance of 90% of the 67Ga2O3-associated 3H radioactivity (as a fraction of the amount detected 30 min postexposure) required 1 day, while only 1.5 hr were required to clear the same percentage of 3H radioactivity from the tracheas of rats exposed to the pure [3H]BaP aerosol. The rates of clearance of this 3H material to other tissues suggested that a substantial amount of the [3H]BaP coated on 67Ga2O3 was cleared from lungs by mucociliary clearance and subsequent ingestion, whereas the majority of the pure [3H]BaP aerosol was cleared by direct absorption into blood. In both cases, the ultimate fate of the majority of the [3H]BaP and its metabolites was excretion in feces. However, clearance of the 67Ga2O3-associated [3H]BaP by ingestion may have been the cause for the higher levels and longer retention times of 3H radioactivity in stomach, liver, and kidneys when compared to the levels found in these same tissues from animals exposed to the pure [3H]BaP aerosol. Thus, particle association of BaP not only increased the respiratory tract retention of this PAH, but also increased the dose of this compound and its metabolites to stomach, liver, and kidneys.

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