Pulmonary retention of [14C]benzo[a]pyrene in rats as influenced by the amount instilled

Studies on the pulmonary retention of benzo[a]pyrene after inhalation have shown that clearance is biphasic, with one component clearing with a half-time greater than 1 day and another with a half-time less than 1 day. In the work reported here we demonstrated that the amount of benzo[a]pyrene instilled in the lungs can affect the rate at which the benzo[a]pyrene is cleared into the blood. Fischer-344 rats were given 16, 90 or 6400 ng of [14C]benzo[a]-pyrene/rat by intratracheal instillation. Rats were sacrificed at various times up to 7 days after instillation. Individual lung lobes and trachea were removed, digested, and analyzed by liquid scintillation spectrometry. At 24 h after instillation the amount of 14C covalently bound to lung macromolecules was determined in some rats. Benzo[a]pyrene equivalents remaining in the lungs was expressed as a percentage of the instilled dose as a function of time. A two-component negative exponential function was fit to the data. With increasing dose (16-6400 ng/rat), an increasing percent (89-99.76%) was cleared with a half-time less than 1 day and a decreasing percent (11.3-0.24%) was cleared with a half-time greater than 1 day, suggesting that the mechanism by which the slower clearances occurred had been saturated at higher doses. At 24 h after instillation, from 1 to 2 pmol of [14C]benzo[a]-pyrene equivalents/lung were covalently bound to lung macromolecules. There was no difference in the amount of covalently bound 14C over the range of instillation doses used, suggesting that a small amount of benzo[a]-pyrene equivalents was bound in the lungs regardless of the amount instilled. These results suggested that linear extrapolation from high dose studies to environmental concentrations might underestimate lung burdens of benzo[a]pyrene.