Inhalation of poorly soluble particles. I. Differences in inflammatory response and clearance during exposure

Results from animal studies have indicated some uncertainties over the vali dity of a single general occupational control limit for all types of "parti culates (insoluble) not otherwise classified" (PNOC) (ACGIH, 2000). Therefo re, to examine the extent to which a given control limit may be valid for n ontoxic dusts with different physical characteristics, this study compared the pulmonary effects in rats of inhalation exposure to two poorly soluble dusts of similar density and with relatively low toxicity: titanium dioxide and barium sulfate. The objectives were to compare the dusts in (a) their buildup and clearance in the lungs during inhalation; (b) their transfer to lymph nodes; (c) the changes, with time, in the lavageable cell population ; and (d) the pathological change from histology. The exposure aerosol conc entrations were selected to achieve similar mass and volume lung burdens Fo r both dusts and to attain "overload" over the common exposure periods of a bout 4 mo and 7 mo. Despite obtaining similar lung burdens for both dusts, there was significantly more translocation of TiO2 to the hilar lymph nodes than with BaSO4. it was also found that clearance of TiO2 was retarded whe reas clearance of BaSO4 was not. Trends in these data were clarified by the use of a simple model of particle clearance. Retardation of particle clear ance and translocation to the lymph nodes are markers of the condition know n as "overload" in which the alveolar macrophage-based clearance of particl es from the deep lung is impaired. In addition, bronchoalveolar lavage show ed that TiO2 caused significantly more recruitment of inflammatory neutroph ils to lungs than BaSO4. These differences between the dusts were not due t o differences in toxicity, solubility, or lung deposition. The explanation that the different responses are dup to the different particle size distrib utions of the two dust types is examined in a companion paper (Tran et al., this issue).