Hepatic Aryl Hydrocarbon Hydroxylase and Cytochrome P450 Induction following the Transpulmonary Absorption of TCDD from Intratracheally Instilled Particles

Hepatic Aryl Hydrocarbon Hydroxylase and Cytochrome P450 Inductionfollowing the Transpulmonary Absorption of TCDD from IntratracheallyInstilled Particles. NESSEL, C. S., AMORUSO, M. A., UMBREIT,T. H., AND GALLO, M. A. (1990). Fundam. Appl. Toxicol. 15, 500-509.Inhalation of particles contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) will be an increasingly important route of human exposurein light of the increased utilization of municipal waste incinerationand the resultant emission of contaminated materials into theenvironment. The potential for pulmonary absorption of the compoundfrom respirable particles was assessed in the present studyfollowing the intratracheal instillation of TCDD (1) as a contaminantof gallium oxide particles and (2) in a corn oil vehicle. Groupsof five female Sprague-Dawley rats received 0, 0.005, 0.055,0.55, or 5.5 µg/kg TCDD in a single instillation and wereeuthanized 4 days later. Absorption was characterized by enzymeinduction aryl hydrocarbon hydroxylase (AHH) activity and totalcytochrome P450] and histopathological examination of the liver.Induction of hepatic enzymes was dose-dependent with both treatmentregimes. Up to an 18-fold increase in AHH and an 80% increasein cytochrome P450 were observed in treated animals. Inductionwas slightly higher when animals received TCDD in com oil thanwhen animals received TCDD-contaminated particles and was relativelycomparable to induction following oral exposure. Similar resultswere obtained when animals were treated with particles contaminatedup to 4 weeks prior to instillation. Characteristics of TCDD-inducedhepatotoxicity, including enlarged hepatocytes and fatty infiltration,were apparent in treated rats, but were not present in vehicle-instilledanimals. These results indicate that systemic effects occurfollowing pulmonary exposure to TCDD and that inhalation maybe an important route Of exposure for TCDD.