Chronic inflammation, small airways disease and bronchiolar epithelial changes in silica-exposed rats. (A) Section of hematoxylin and eosin stained rat lung 150 d after exposure to 10 mg/kg bw silica dust. Areas of focal inflammation are present, and enlarged; inflamed lymph nodes are obvious (yellow box; 1×). (B) Close-up view of the enlarged peribronchial lymph nodes from (A). Pale granulomas are present within the lymph nodes (yellow arrows), and discrete granulomas are also seen in within the lung parenchyma (green arrow; 8×). (C) Higher magnification view of blue boxed area in (A). There is continuing inflammation with collections of foamy macrophages in the alveoli, foci of lipoproteinosis, and chronic and intra-alveolar inflammation. The terminal bronchiole (TB) is distorted and slightly constricted. Mild interstitial fibrosis is present (8×). (D) Close-up of boxed area in (C) showing atypical alveolar epithelial hyperplasia (blue arrows). The presence of degenerate foamy macrophages (FM) and acute inflammatory cells (neutrophils and eosinophils; yellow arrows) in the alveoli indicates continued toxicity (40×). (E) An example of atypical bronchiolar epithelial hyperplasia in the lung of a different rat 120 d after exposure to 10 mg/kg bw silica is shown. The bronchiolar epithelium extends into the alveoli with abnormal orientation of the epithelium, and cytological atypia are evident (blue arrow; 40×).