Characterization of Bronchiolar Metaplasia of the Alveolar Epithelium in Female Sprague—Dawley Rats Exposed to 3,3',4,4',5-Pentachlorobiphenyl (PCB126)

Abstract

To test the dioxin toxic equivalency factor methodology, the National Toxicology Program conducted a series of 2-year rat bioassays of dioxin-like compounds. Following gavage exposure of female Harlan Sprague—Dawley rats to 2,3',4,4',5-pentachlorobiphenyl (PCB126), pulmonary alveolar epithelium at the junction of terminal bronchioles and along alveolar ducts was replaced by cuboidal to columnar ciliated cells. Scattered among these were cells exhibiting characteristics consistent with those of Clara cells; they lacked cilia and had a smooth apical surface that protruded into the alveolar space. This lesion was not typical of alveolar epithelial hyperplasia seen in rodent lungs; therefore, studies were done to characterize the lesion. Results of periodic acid-Schiff (PAS) staining, alcian blue (AB) staining, and GSTPi immunohistochemical staining of the lesions seen in treated rats were more similar to normal bronchiolar epithelium than normal alveolar epithelium or alveolar epithelial hyperplasia. These findings, along with the morphology of the cells, provide evidence that this lesion is closer in character to bronchiolar epithelium than alveolar type I or alveolar type II epithelium, and as a result, was called bronchiolar metaplasia.