title: Deposition, metabolism, and excretion of 1-[14C]nitropyrene and 1-[14C]nitropyrene coated on diesel exhaust particles as influenced by exposure concentration.
abstract: Nitrated polycyclic aromatic hydrocarbons (nitro-PAH) have been detected in the environment, originating from sources such as diesel exhaust emissions and coal combustion fly ash. 1-Nitropyrene (NP) is a predominant mutagenic and carcinogenic nitro-PAH found in diesel exhaust emissions. Since inhalation of NP is a likely route of exposure in humans, it is important to determine the biological fate of inhaled NP both in its pure form and associated with particles. The purpose of this study was to determine the disposition of NP aerosols inhaled by rats. The studies described in this paper were designed to determine the deposition of [14C]NP over a range of exposure concentrations, identify the pathways and half-times for excretion of absorbed NP, and determine the distribution of inhaled NP and metabolites in tissues. Male F344 rats were exposed nose only to various concentrations of NP and NP coated on diesel exhaust particles (50-1100 ng/liter). The results indicate that, over the range of concentrations tested, pathways for excretion of [14C]NP equivalents in urine and feces were independent of the exposure concentration of NP, whether 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. The fractional deposition of [14C]NP in the respiratory tract did not appear to be dependent on exposure concentration. Half-times for elimination of 14C in urine and feces were about 15 to 20 hr. In all exposures, 14C was widely distributed in the tissues examined. Analysis of the tissues for NP and its metabolites indicated that within 1 hr after exposure, greater than 90% of the 14C was 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 pmol/g lung) within 1 hr after exposure. This difference was increased to 80-fold at 94 hr after exposure (80 vs 1 pmol/g lung). Long-term clearance half-times of 14C from various tissues were similar. The results demonstrate that particle association of NP significantly alters the biological fate of inhaled NP.
mesh_terms: D000336:Aerosols; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000032:analysis; D006207:Half-Life; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D011721:Pyrenes / Q000378:metabolism* / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D001335:Vehicle Emissions
chemical_list: D000336:Aerosols; D011721:Pyrenes; D001335:Vehicle Emissions; C032668:1-nitropyrene