Repeated Inhalation Exposures to 1-Nitropyrene (NP) or Benzo[a]Pyrene (BaP) in Association with Ca2O3Particles and SO2: Tissue Distribution, Binding, and Metabolism of [14C]NP and [14C]BaP

Abstract

It has been suggested that association of polycyclic aromatic hydrocarbons (PAH) with particles or coexposure to (SO2) may alter the biological fate of PAH. Croups of F344 rats inhaled 1-nitropyrene (NP) or benzolalpyrene (BaP) aerosol, with and without coexposures to SO2, and NP or BaP adsorbed on Ga2O3, particles with and without coexposures to SO2 or filtered air for 4 wk. On the last day of the 4-wk exposures, [14C]NP and [14C]BaP were used in the exposure atmospheres of groups that had been previously exposed to unlabeled NP and Baf: and those that had been sham-exposed. Tissue distributions of 14C were measured at times up to 4 wk after cessation of inhalation exposures. Levels in lung of 14C bound to total macromolecules and specifically bound to DNA were measured to assess interaction of reactive metabolites with macromolecules. Metabolizing capacity was also measured in lung and nasal tissue. Distribution of 14C in tissues was largely unaffected by association of [14C]BaP or [14C]NP with Ga2O3 particles or coexposure to SO2, or prior to exposure to BaP or NP except for minor differences in gastrointestinal tract levels and a significant effect of SO2 exposure on lung and liver clearance of [14C]BaP. Capacities of lung and nasal tissue to metabolize [14C]NP and [14C]BaP were also largely unaffected by exposure atmospheres of prior exposure. Covalent binding of 14C to macromolecules was low and, in the case of DNA binding, below limits of detection for all exposure groups. These data indicate that repeated inhalation exposures to NP and BaP, association with CA2O3 particles, and coexposure to SO2 do not markedly alter the biological fate of inhaled NP or BaP and their metabolites.