Comparison of the uptake of fine and ultrafine TiO2 in a tracheal explant system

To examine the relationship between particle uptake by pulmonary epithelial cells and particle size, we exposed rat tracheal explants to fine particles (FPs; 0.12 mu m) or ultrafine particles (UFPs; 0.021 mu m) of titanium dioxide for 3 or 7 days. By electron microscopy, particles were found in the epithelium at both time points, but in the subepithelial tissues, they were found only at 7 days. The volume proportion of both FPs and UFPs in the epithelium increased from 3 to 7 days; it was greater for UFPs at 3 days but was greater for FPs at 7 days. The volume proportion of particles in the subepithelium at 7 days was equal for both dusts, but the ratio of epithelial to subepithelial volume proportion was similar to 2:1 for FPs and 1:1 for UFPs. Mean volume of individual particle aggregates was similar for both dusts at 3 days but was markedly smaller for FPs at 7 days. These observations suggest that the behavior of particles of different size is complex: UFPs persist in the tissues as relatively large aggregates, whereas the size of FP aggregates becomes smaller over time. UFPs appear to enter the epithelium faster, and once in the epithelium, a greater proportion of them is translocated to the subepithelial space compared with FPs. However, if it is assumed that the volume proportion is representative of particle number, the number of particles reaching the interstitial space is directly proportional to the number applied; i.e., overall, there is no preferential transport from lumen to interstitium by size.