Lung, liver, and kidney as potential target organs after exposure to 1-nitropyrene, as determined by the time course of covalently bound material.
Previous studies in which rats were exposed to [14C]-1-nitropyrene by inhalation indicated that lung, liver, and kidney consistently accumulated the highest concentrations of 14C after exposure. The purpose of the study described here was to determine the extent to which this 14C was covalently bound to macromolecules. Male F344/N rats were exposed to 360 ng [14C]-1-nitropyrene/l air for 1 h resulting in an average of 2.2 micrograms 1-nitropyrene deposited per rat. An additional group of rats was given 4.2 micrograms [14C]-1-nitropyrene by gavage. Total 14C in 23 tissues was determined for up to 96 h after inhalation exposure and up to 30 d after gavage. Lung, liver, and kidney contained the highest concentrations of 14C. Samples of these tissues were exhaustively extracted to determine the amount of radioactivity covalently bound to macromolecules. Regardless of the route of administration, the kidneys had the highest concentrations of covalently bound 14C. At 96 h after exposure kidneys had overall mean concentrations of 2.7 pmol bound/g tissue.micrograms nitropyrene administered. The overall mean concentration in liver was 0.18 pmol bound/g.microgram and the overall mean concentration in lung was 0.06 pmol/g.microgram at 96 h after exposure. Covalently bound material persisted in kidneys for the duration of the study (30 d postexposure). The calculated half-time for removal of bound 14C from kidneys was 150 d. These data suggest that kidney should be considered as one of the organs at risk after exposure to nitropyrene by inhalation or ingestion.
Medinsky
M A
MA
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
Bond
J A
JA
Hunsberger
S
S
Sun
J D
JD
D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D011721:Pyrenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D011721:Pyrenes; C032668:1-nitropyrene