Disposition and Metabolism of [14C]Dibenzo[c,g]carbazole Aerosols in Rats after Inhalation

Disposition and Metabolism of [^l4C]Dibenzo[c,g]carbazole Aerosolsin Rats after Inhalation. Bond, J. A. Ayres, P. H., Medinsky,M. A., Cheng, Y. S., Hirshfield, D., and McClellan, R. O. (1986).Fundam Appl Toxicol. 7, 76-85. Dibenzo[c.£]carbazole (DBC)is a nitrogen-containing polycyclic aromatic hydrocarbon thathas been detected in tobacco tars, industrial oils, and dieselengine exhaust fumes. DBC is carcinogenic in respiratory tracttissue of hamsters and in lungs, kidneys, and livers of mice.The purpose of this research was to determine the respiratorytract deposition, distribution in tissues, metabolism, and excretionof DBC in rats after inhalation. Rats were exposed nose-onlyto 1.1 or 13 Mg [¹⁴C]DBC/liter air for 60 min. Activity medianaerodynamic diameters for the two concentrations of DBC rangedfrom 0.7 to 0.8 pm. Unne. feces, and selected tissues were collectedfor various times after exposure. The fractional depositionfor the 1.1 and 13 ug/liter exposure concentrations was similar,13 and 16%, respectively. The dominant route of excretion of¹⁴C following exposure to either concentration of DBC was thefeces, accounting for approximately 95% of the total 14C eliminated.Half-time for fecal excretion was 20 ± 6 hr (x ±SE). Gastrointestinal absorption of [I4C]DBC was 43%. Radioactivitywas widely distributed to all tissues examined, with the respiratorytract (lung, trachea, larynx, and nasal turbinates), upper gastrointestinaltract (stomach and small intestine), the liver, and the adrenalscontaining the highest concentrations of [I4C]DBC equivalentswithin 1 hr after exposure. At both concentrations of DBC tested,clearance of I4C from tissues was rapid, with approximately60 to 98% of the initial tissue burden being cleared with half-timesranging from 1 to 16 hr. The remaining 2 to 40% in the tissueswas cleared with half-times that ranged from 1.5 to 14 days.Several metabolites were detected in the urine and feces, noneof which appeared to be either glucuronide or sulfate conjugates.Small quantities of [I4C]DBC were detected in the urine, althoughquantities were less than 1% of the initial respiratory tractburden of [I4C]DBC. The results from this research indicatethat DBC was rapidly absorbed from the lungs and translocatedto many tissues. Prior to elimination, primarily in the feces,DBC was extensively metabolized There appeared to be no effectof exposure concentration on the toxicokinetics of inhaled DBC.