Toxicokinetics of inhaled benzo[a] pyrene: Plasma and lung bioavailability

Bioavailability and toxicokinetic studies are essential in order to establi sh dose-response relationships of widely distributed environmental toxicant s such as benzo[a] pyrene (BaP), a polycyclic aromatic hydrocarbon. Fischer 344 rats were exposed for 4 h (via nose-only inhalation) to aerosol exposu re concentrations of 0.1, 1.0, and 2.5 mg/m(3) of BaP absorbed onto carbon black particles using a state-of-the-art model aerosol generation system. N ominal and chamber concentrations of the particulate aerosol were determine d gravimetrically with a seven-stage cascade impactor. The average aerosol for the 3 exposure concentrations used in this study exhibited a trimodal d istribution with 93% cumulative mass less than 15.85 mum, 89% cumulative ma ss less than 10 mum, 55.3% cumulative mass less than 2.5 mum, and 38% less than 1 mum. Fifty-five percent of the aerosol had a cumulative mass less th an PM2.5 and the mass median aerodynamic diameter (MMAD) +/- geometric stan dard deviation (GSD) for this mode was 1.7 +/- 0.085 mum. Plasma and lung s amples were collected at 30, 60, 120, and 240 min postexposure. The concent rations of BaP parent compound and metabolites were determined by highperfo rmance liquid chromatography. The toxicokinetic parameters were computed fr om the time course of plasma BaP concentration. The bioavailability of BaP increased as a function of exposure concentration, and toxicokinetic analys is indicates first-order pharmacokinetics for BaP. However, some toxicokine tic parameters such as clearance and volume of distribution remained consta nt throughout the duration of the postexposure period. BaP and its metaboli te concentrations in plasma peaked at 1 h postexposure. At 240 min postexpo sure, only trace levels of BaP remained in the plasma. The BaP metabolites in the lung showed an identical trend where no parent compound was detected . Among the metabolites detected, BaP 4, 5-, 7, 8-, and 9, 10-dihydrodiols, 3-OH-BaP, and 9-OH-BaP were predominant.