Fig. 3

Short-term inhalation study: histopathologic effects and terminal bronchiolar epithelial cell proliferation 4 days after final exposure to AM or LA for 10 days. a–c, Representative images of normal terminal bronchiole and surrounding alveoli from air control (Con) group (a), mixed cell alveolar inflammation, predominantly macrophages and neutrophils (b), and bronchiolar epithelial hyperplasia (c). Slides were stained with hematoxylin and eosin. d–f, Immunostaining of cells with BrdU. Representative images of terminal bronchioles from Con (d) and high concentration LA (25 mg/m³ target) (e) groups. Positively labeled cells are indicated by brown nuclei; background staining used hematoxylin. f, Percentage of positive BrdU-labeled cells (labeling index, LI), shown as individual LI values (circles), mean values (horizontal bars), and standard error (vertical bars) for each group. *P < 0.05 and **P < 0.01 compared to air control (Con) group; ^ P < 0.01 by linear trend test among LA dose groups. Images were taken at 20x (a, c) or 40x (b, d, e) objective magnification