Disposition and metabolism of free and particle-associated nitropyrenes after inhalation

The objective of this project was to determine the biological fate of 1-nitropyrene (NP) aerosols in rats. The results from these studies indicate that, over the range of aerosol concentrations tested, pathways for excretion of 14C-NP equivalents in urine and feces were independent of the exposure concentration of NP, either in its pure form or associated with diesel exhaust particles. In all cases, fecal excretion was the major route of elimination of 14C-NP equivalents, with about 2 times more excreted by this route than by urine. Fractional respiratory tract deposition of 14C-NP did not appear to be dependent on exposure concentration. In most cases, half-times for elimination of 14C in urine and feces were about 15 to 20 hours. In all exposures, 14C was widely distributed in the tissues examined. Analysis of the tissues for NP and metabolites indicated that within 1 hour after exposure greater than 90% of the 14C was associated with NP metabolites. Lungs of rats exposed to 14C-NP coated on diesel exhaust particles contained nearly 5 times more 14C than lungs from rats exposed to pure aerosols of 14C-NP (148 vs 29 pmole g lung) within 1 hour after exposure. This difference was increased to 80-fold at 94 hours after exposure (80 vs 1 pmole g lung). Long-term clearance half-times of 14C from various tissues were similar, with values of about 30 to 50 hours measured. Pre-exposure to diesel exhaust prior to exposure to NP may result in increased retention of a small fraction of the NP. Equilibrium organ concentrations predicted for tissues following continuous exposure to NP suggest that both low inhaled concentrations of NP and association of NP with insoluble diesel particles can result in an increased retention of NP in the lungs above what might be predicted using data obtained from animal studies using high concentrations of pure NP