Distribution and elimination of inhaled phenanthridone in fischer‐344 rats

Abstract

Aza‐arenes are widely distributed in the environment. Certain members of this chemical class are biologically active and therefore could pose health hazards to humans if inhaled or ingested. Since inhalation is the most likely route for significant exposure for aza‐arenes that are air pollutants, knowledge of the absorption, distribution, and excretion after inhalation is necessary to understand mechanisms of toxicity and predict health hazards associated with exposure to aza‐arenes. In this study, rats were exposed nose‐only to an aerosol of [ ¹⁴ C]phenanthridone, a mutagenic aza‐arene found in coal tar. Tissues, urine, feces, and expired air were collected at specified times and assayed for radioactivity. Radioactivity was rapidly absorbed from the respiratory tract and distributed to all tissues examined. It was rapidly eliminated from tissues (>80% in 12 h), being concentrated only in the large intestine at later timepoints. Excretion of radioactivity in both feces and urine was complete within 4 d. Virtually none of the dose was eliminated as [ ¹⁴ C]CO₂. [ ¹⁴ C]Phenanthridone was also administered orally to assess its absorption from the gastrointestinal tract. Absorption was nearly complete (83 ± 6%), indicating that phenanthridone ingested as a result of mucociliary clearance and swallowing, grooming, or coprophagy could also contribute to tissue exposure. These results are similar to those obtained from inhalation studies of other polycyclic aromatic hydrocarbons, indicating that as a class, inhaled polycyclic aromatic hydrocarbons may be rapidly absorbed from the respiratory tract, widely distributed throughout the body, and readily eliminated in both urine and feces.