Disposition and Metabolism of Free and Particle-Associated Nitropyrenes After Inhalation

Nitro-polynuclear aromatic hydrocarbons, including 1-nitropyrene, are constituents of diesel exhaust. Previous fractionation research has suggested that 1-nitropyrene and various dinitropyrenes may account for 20-50% of the total mutagenicity in the diesel particle extract (DPE). Dr. Bond and colleagues at the Inhalation Toxicology Research Institute examined the biological fate of inhaled 14C-1-nitropyrene (NP) in Fischer-344 rats. The investigators first determined the range over which the deposition, absorption, excretion, and metabolism of NP are linearly related to the inhaled NP dose. Next, they determined NP disposition (absorption, tissue distribution, metabolism, excretion). Finally they ran a simulation model to incorporate the disposition data and predict the tissue concentrations of NP and metabolites for other exposure scenarios.