Influence of Adsorption to Carbon Black Particles on the Retention and Metabolic Activation of Benzo[a]Pyrene in Rat Lungs Following Inhalation Exposure or Intratracheal Instillation

Abstract

There is a need to define the influence of adsorption of organic compounds onto particles on the biological fate of these compounds when inhaled. In this study, rats were exposed by nose-only inhalation (2 h) to 2 mg/m³ or 20 mg/m³ of pure [¹⁴C]BaP or [¹⁴C]BaP adsorbed onto carbon black particles at 0.2 mg/m³, 2.0 mg/m³, or 20 mg/m³ (total mass concentration ≃ 100 mg/m³). In separate studies, rats were intratracheally instilled with amounts of pure [14C]BaP and [¹⁴C]BaP on carbon black that were similar to those deposited in lungs by inhalation. In all cases, clearance of ¹⁴C from lungs had a rapid short-term component and a slower long-term component of clearance. As a percentage of the calculated initial lung deposition after inhalation or instillation, the long-term retention of ¹⁴C was similar for all amounts of pure [¹⁴C]BaP used and also similar for both methods of administration. The long-term lung retention of ¹⁴C as a percentage of the initial lung deposition was increased 16–60 times as a result of adsorption onto carbon black. This increased retention was higher for the smaller mass coatings of [¹⁴C]BaP on carbon black. Also, long-term retention of ¹⁴C in lungs was 3–5 times higher after instillation as compared to inhalation for the same corresponding mass coating percentage of [¹⁴C]BaP on carbon black. Covalent interactions of the BaP-associated ¹⁴C with lung macromolecules were also measured. Levels of covalently bound ¹⁴C were proportional to the long-term retention levels of ¹⁴C in lungs. These results indicate that adsorption onto carbon black increases the long-term retention of inhaled BaP in lungs and that this increased retention facilitates the lung metabolism of BaP to reactive metabolites that can covalently bind to lung macromolecules. These results also indicate that instillation studies can provide useful qualitative data, but cannot be compared quantitatively with data derived from inhalation studies.