Disposition and metabolism of [14C]dibenzo[c,g]carbazole aerosols in rats after inhalation.
Dibenzo[c,g]carbazole (DBC) is a nitrogen-containing polycyclic aromatic hydrocarbon that has been detected in tobacco tars, industrial oils, and diesel engine exhaust fumes. DBC is carcinogenic in respiratory tract tissue of hamsters and in lungs, kidneys, and livers of mice. The purpose of this research was to determine the respiratory tract deposition, distribution in tissues, metabolism, and excretion of DBC in rats after inhalation. Rats were exposed nose-only to 1.1 or 13 micrograms [14C]DBC/liter air for 60 min. Activity median aerodynamic diameters for the two concentrations of DBC ranged from 0.7 to 0.8 micron. Urine, feces, and selected tissues were collected for various times after exposure. The fractional deposition for the 1.1 and 13 micrograms/liter exposure concentrations was similar, 13 and 16%, respectively. The dominant route of excretion of 14C following exposure to either concentration of DBC was the feces, accounting for approximately 95% of the total 14C eliminated. Half-time for fecal excretion was 20 +/- 6 hr (means +/- SE). Gastrointestinal absorption of [14C]DBC was 43%. Radioactivity was widely distributed to all tissues examined, with the respiratory tract (lung, trachea, larynx, and nasal turbinates), upper gastrointestinal tract (stomach and small intestine), the liver, and the adrenals containing the highest concentrations of [14C]DBC equivalents within 1 hr after exposure. At both concentrations of DBC tested, clearance of 14C from tissues was rapid, with approximately 60 to 98% of the initial tissue burden being cleared with half-times ranging from 1 to 16 hr. The remaining 2 to 40% in the tissues was cleared with half-times that ranged from 1.5 to 14 days. Several metabolites were detected in the urine and feces, none of which appeared to be either glucuronide or sulfate conjugates. Small quantities of [14C]DBC were detected in the urine, although quantities were less than 1% of the initial respiratory tract burden of [14C]DBC. The results from this research indicate that DBC was rapidly absorbed from the lungs and translocated to many tissues. Prior to elimination, primarily in the feces, DBC was extensively metabolized. There appeared to be no effect of exposure concentration on the toxicokinetics of inhaled DBC.
D000336:Aerosols; D000818:Animals; D002227:Carbazoles / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000032:analysis; D006207:Half-Life; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects; D012137:Respiratory System / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D000336:Aerosols; D002227:Carbazoles; C013478:7H-dibenzo(c,g)carbazole