In the crystalline silica-exposed group, the total BALF cell numbers, neutrophils, lymphocytes, eosinophils, and the percentage of neutrophils were significantly increased until 6-month post-exposure. For the MWCNT-exposed groups, LDH and TP levels in the BALF were significantly increased only in the group exposed to 1 mg/kg MWCNTs; however, the changes were transient and recovered GSK2118436 manufacturer after 1-week post-exposure (Fig. 5). BALF cytokine levels were not significantly changed at any

time point (data not shown). In contrast, LDH and TP levels in the BALF were significantly increased until 6-month post-exposure in the crystalline silica-exposed group (Fig. 5), and significant changes in IL-1β and IL-2 levels were observed in this group (data not shown). For all the groups, histopathological changes due to the instillation exposure of MWCNTs or crystalline silica were observed only in the lungs and lung-associated lymph nodes, and

not in the other tissues (i.e., the liver, kidney, spleen, and cerebrum). Table 1 summarizes the histopathological findings of the rats examined in this study and their severity scores at each time point. In the MWCNT-exposed groups, dose-dependent histopathological changes were observed. In the group exposed to 0.04 mg/kg MWCNTs, Selleckchem MDV3100 no significant changes were observed at any time points (Fig. 6 and Fig. 7Figs. 6a and 7a). In the group exposed to 0.2 mg/kg MWCNTs, minimal macrophage accumulation and phagocytosed MWCNTs were observed in the alveoli (Fig. 6 and Fig. 7). In the group exposed to 1 mg/kg MWCNTs, deposition of the MWCNTs and macrophage accumulation, part of which were granulomatous, was next observed in the alveoli and interstitium from 3-day to 1-month post-exposure (Fig. 6c and d). Most MWCNTs were phagocytosed

by alveolar macrophages. Further, hypertrophy of the bronchial epithelium and inflammatory cell infiltrations were observed. From 3- to 6-month post-exposure, histopathological findings were qualitatively similar to those at 1-month post-exposure; although the severity of the changes was gradually weaker. At 6-month post-exposure, deposition of the MWCNTs and macrophage accumulation, part of which were granulomatous, was observed in the alveoli and interstitium in the group exposed to 1 mg/kg MWCNTs; however, the severity of these changes was minimal (Fig. 7c). In the group exposed to 1 mg/kg MWCNTs, minimal MWCNT depositions were observed in the peribronchial lymph nodes at 6-month post-exposure (Fig. 7d). In the crystalline silica-exposed group, only minimal macrophage accumulation in the alveoli and interstitium was observed up to 1-week post-exposure. However, the severity of macrophage accumulation was increased after 1-month post-exposure, and, cytolysis of macrophages was observed, which was most severe at 6-month post-exposure.