Fig. 2

Representative microscopic photographs of female rat lungs after inhalation exposure to TiO₂ NP (8 mg/m³). Loupe image (A, bar: 1000 mm) and magnified image (B–G, bar: 500 μm) of H&E-stained lung sections of the lungs shown in Figs. 1H and I. White–gray spots macroscopically detected were observed as nodular lesions with relatively clear boundaries (B and right side of C). Severe lesions tended to be scattered in the apex of the lung. The lesions were composed of cholesterol clefts, collagen bundles, and mast cells (enlarged in B). Lesions with mild changes were scattered below the apex of the lung (right side of C) in the subpleural area (D) and the hilum (E). The alveolar structure was well preserved, and the macrophages in the alveolar airspace were mostly destroyed (enlarged in C). The small pure white spots macroscopically detected were observed as clumps of black pigment (F) and were foci of aggregations of particle-phagocytosing macrophages. In the interstitium of the terminal bronchioles, also known as the broncho-vascular bundle, the deposition of particle-phagocytosing macrophages was mild (G)