This project aimed at studying the dispersion and retention behavior of dusts consisting of nanoscaled primary particles. Toxicological studies have demonstrated that the effects observed for nanoscaled particles are better correlated to the particle surface or particle number than to the administered mass doses. The toxicokinetic fate of nanoscaled particles and the potential effects induced after deposition in lungs are predominantly determined by the agglomeration status. Sytemic particle effects, i.e. effects on the remote organs, in addition to those on the target organ respiratory tract are conceivable only for particles with a nanoscaled aspect. In this study various types of nanoscaled particles, i.e titanium dioxide, carbon black, constantan and zinc oxide were dispersed in physiologically compatible media or generated as aerosols with well-defined characteristics. For aqueous nanoparticle suspensions, the hydrodynamic mean diameter and the ζ potential were determined, for aerosols the particle number or mass concentrations and the mass median aero-dynamic diameter (MMAD). For aqueous formulation of nanoparticles, phosphate buffer, sometimes including auxiliaries such as bovine serum albumin (BSA) or Tween® 80 (non-ionic surfactant), was used.

In an in vitro approach selected human bronchial and alveolar epithelial cell lines as well as fibroblasts grown on membranes were exposed from the apical side to the different particle types. After 1 hour the particles were detected by TEM technique in particular on the cellular surface whereas after 24 hours they were predominantly located in the cytoplasm.

In an in vivo approach rats were exposed to aqueous dispersions (administered by intratracheal instillation) or nanoparticle aerosols (inhalation) and alterations in the particle size distribution were studied using transmission electron microscopy (TEM) as well as the bronchoalveolar lavage (BAL) technique. Exemplarily, in BAL fluid after instillation, TiO₂ P25 increased in agglomerate size whereas TiO₂ T805 did not show a change as compared to the stock suspension.
As an additional endpoint, the chemical analysis of toxicokinetics was included to trace the fate of Eu₂O₃ particles following inhalative deposition in lungs. Only small Eu₂O₃ amounts were detected in remote organs.
Based on the results in various approaches, a tendency of nanoscaled particles to form larger size agglomerates following deposition and interaction with cells (in vitro) or the respiratory tract (in vivo) is predominant. The contrary trend, i.e. the increase of particle number due to a disintegration of agglomerates seems not to be of high relevance.

Due to the size of the document (PDF file, 20 MB) and to ensure a faster download, the document has been divided into the following files:

Contents and Abstract / Kurzreferat, pages 1 - 6 (PDF file, 672 KB)

Chapter 1 Introduction / Chapter 2 Literature Search / Chapter 3 Materials and Methods, p. 7 - 34 (PDF file, 377 KB)

Chapter 4 Results / 4.1 In vitro Experiments, p. 35 - 62 (PDF file, 12 MB)
Chapter 4 Results / 4.2 In vivo Experiments, p. 63 - 101 (PDF file, 6 MB)

Chapter 5 Discussion and conclusions / Appendices, p. 102 - 141 (PDF file, 1 MB)