Correlation between particle size, in vivo particle persistence, and lung injury.

Abstract

Dosimetry parameters such as deposition, clearance, retention, and translocation and dissolution of inhaled particles in and to different lung compartments may be important for the persistence of particles in the lung and may correlate with adverse pulmonary effects. We investigated such correlations using a model involving TiO2 particles of two particle sizes (20 nm diameter, ultrafine; 250 nm diameter, fine) of the same crystalline structure (anatase). A 12-week inhalation experiment in rats resulted in a similar mass deposition of the two particle types in the lower respiratory tract. The ultrafine particles elicited a persistently high inflammatory reaction in the lungs of the animals compared to the larger-sized particles. In the postexposure period (up to 1 year) retention in the alveolar space per se was not different between fine and ultrafine TiO2. However, the following differences between the particle types were noted: a significantly different total pulmonary retention, both quantitatively (significantly prolonged retention of the ultrafine TiO2) and qualitatively (increased translocation to the pulmonary interstitium and persistence there of the ultrafine TiO2); greater epithelial effects (Type II cell proliferation; occlusion of pores of Kohn) and the beginning of interstitial fibrotic foci with ultrafine TiO2; significant sustained impairment of alveolar macrophage function after ultrafine TiO2 exposure as measured by the clearance of test particles. A correlation between particle surface area and effects was observed. A comparison of the adverse reactions with dosimetric parameters of TiO2 in different lung compartments in the postexposure period showed a correlation of the persistence of effects in both the alveolar and interstitial space with the persistence of particles in the respective compartment.

Efficient Elimination of Inhaled Nanoparticles from the Alveolar Region: Evidence for Interstitial Uptake and Subsequent Reentrainment onto Airways Epithelium

“…Furthermore, several publications have reported translocation into systemic circulation and accumulation in secondary target organs; these publications have been reviewed recently (Oberdörster et al 2005). This is different from epithelial surface retention observed for micron-sized poly-styrene and glass particles (Lehnert et al 1989; Oberdörster et al 1994). Our data do not provide any information about the interstitial localization of retained NPs.…”

“…Furthermore, Ferin and co-workers had shown the uptake of 20-nm ultrafine TiO 2 -particles in epithelial cells and in the interstitial spaces (Ferin et al 1992; Oberdörster et al 1994). Geiser et al (2005) showed that 1 hr after inhalation, 24% of inhaled 22-nm TiO 2 particles were within or beyond the epithelial barrier of the lungs in epithelial and endothelial cells, connective tissue, or capillaries.…”

Nanoparticles: Health Effects—Pros and Cons

“…Oberdörster et al (1994) observed that ultrafine TiO 2 instilled into rats and mice was more proinflammatory than fine TiO 2 , as TiO 2 induced a neutrophilic influx into the lungs. Oberdörster et al (1994) reported that particle surface chemistry is equally or more important in inflammation and acute toxicity.…”

“…Oberdörster et al (1994) observed that ultrafine TiO 2 instilled into rats and mice was more proinflammatory than fine TiO 2 , as TiO 2 induced a neutrophilic influx into the lungs. Oberdörster et al (1994) reported that particle surface chemistry is equally or more important in inflammation and acute toxicity. Freshly generated polytetrafluethylene (PTFE) fume containing UFPs < 26 nm induced hemorrhagic pulmonary inflammation and death after rats were exposed to 10–30 μg of dust, and aging of UFPs resulted in the loss of surface reactivity and toxicity (Oberdörster et al 1995).…”

The association of PM2.5 with full term low birth weight at different spatial scales

“…Both of these factors may explain some of the location differences in PM 2.5 effects on adverse birth outcomes. Particle size distribution will impact the ability of the particles to become biologically active as it affects lung deposition (Oberdörster et al, 1994; Carvalho et al, 2011). Chemical composition will in part determine the toxicological profile of the particulate matter.…”