Technical report 122

GI tract may contribute to particle burden in organs

In addition to the interstitial clearance pathway from the alveolar region, clearance via the GI tract should be considered. Deposits of UFP in the tracheobronchial region cleared through the mucociliary escalator as well as particles deposited in the in the head region may contribute to particle translocation through the blood circulation via GI tract clearance. This second pathway was proposed based on the fact that the amount of UF 13C found in lung and liver at 24 h post-exposure was on average 63% greater than the amount predicted to be deposited in the whole respiratory tract, implying that additional to inhalation, uptake from the GI tract via the above mentioned mucociliary and head regions (with possible external contamination via oral uptake from the fur due to the fact that the study was done by whole-body inhalation), should be considered as adding to the lung-liver translocation process (Oberdörster et al, 2002). Hence, the translocated UFP that was measured in the liver should be regarded as blood-borne coming from two sources, lung-interstitial and GI-tract clearance. This is in contrast to other studies with UF radioactive metal particles which do not show significant translocation from the GI tract to other organs neither via the blood circulation, nor by these types of particles deposited in the lung to other extra-pulmonary organs (Kreyling et al, 2002; Kanapilly et al, 1980). These discrepancies were explained by differences in exposure conditions (nose-only by Kanapilly and intratracheal inhalation by Kreyling), chemical nature of UFP, rising questions on organ translocation differences between metals and carbon due to cellular-component interactions (e.g. protein binding). Although the translocated fraction in the Kreyling 2002, study was small (< 1%) and had no GI tract uptake, it did show a correlation to particle size and is probably also dependent of the intratracheal method of exposure.

Early studies by Ferin and Feldstein (1978) showed that rats exposed to Ti02, had fewer particles in the lymph node after inhalation than after intratracheal instillation, which gives an indication about differences in results because of exposure techniques.

The previous observations are supported by a 3 week inhalation study in Wistar rats exposed to fine and nano TI02 particles with recovery times of 3, 28 and 90 days. The results of this study using relative deposition index indicate that apart from particles found in AM and to some extent in type-1 pneoumocytes; capillary cells show limited particle accumulation either in the nano or fine-particle treated groups. This indicates that following exposure by inhalation translocation of fine and nano TiO2 particles from the lung to blood stream was minimal (Eydner et al, 2012).