The rapid alveolar absorption of diesel soot-adsorbed benzo[a]pyrene: bioavailability, metabolism and dosimetry of an inhaled particle-borne carcinogen

Exposure to diesel exhaust may contribute to lung cancer in humans. It rema ins unclear whether the carbonaceous core of the soot particle or its coat of adsorbed/condensed organics contributes most to cancer risk. Equally unc lear are the extent and rate at which organic procarcinogens desorb from so ot particles in the lungs following inhalation exposure and the extent of t heir metabolic activation in the lungs. To explore the basic relationship b etween a model polycyclic aromatic hydrocarbon (PAH) and a typical carrier particle, we investigated the rate and extent of release and metabolic fate of benzo[a]pyrene (BaP) adsorbed on the carbonaceous core of diesel soot. The native organic content of the soot had been denuded by toluene extracti on. Exogenous BaP was adsorbed onto the denuded soot as a surface coating c orresponding to 25% of a monomolecular layer. Dogs were exposed by inhalati on to an aerosol bolus of the soot-adsorbed BaP, Following deposition in th e alveolar region a fraction of BaP was rapidly desorbed from the soot and quickly absorbed into the circulation. Release rates then decreased drastic ally. When coatings reached similar to 16% of a monolayer the remaining BaP was not bioavailable and was retained on the particles after 5.6 months in the lung, However, the bioavailability of particles transported to the lym ph nodes was markedly higher; after 5.6 months the surface coating of BaP w as reduced to 10%, BaP that remained adsorbed on the soot surface after thi s period was similar to 30% parent compound. In contrast, the rapidly relea sed pulse of BaP, which was quickly absorbed through the alveolar epitheliu m after inhalation, appeared mostly unmetabolized in the circulation, along with low concentrations of phase I and phase II BaP metabolites. However, within similar to1 h this rapidly absorbed fraction of BaP was systemically metabolized into mostly conjugated phase II metabolites. The results indic ate that absorption through the alveolar epithelium is an important route o f entry to the circulation of unmetabolized PAHs.