Change in agglomeration status and toxicokinetic fate of various nanoparticles in vivo following lung exposure in rats

The deposition characteristics in lungs following inhalation, the potential toxic effects induced and the toxicokinetic fate including a possible translocation to other sites of the body are predominantly determined by the agglomeration status of nanoscaled primary particles. Systemic particle effects, i.e. effects on remote organs besides the respiratory tract are considered to be of relevant impact only for de-agglomerated particles with a nanoscaled aspect. Rats were exposed to various types of nanoscaled particles, i.e. titanium dioxide, carbon black and constantan. These were dispersed in physiologically compatible media, e.g. phosphate buffer, sometimes including auxiliaries. Rats were treated with aqueous nanoparticle dispersions by intratracheal instillation or were exposed to well-characterized nanoparticle aerosols. Subsequently, alterations in the particle size distribution were studied using transmission electron microscopy (TEM) as well as the bronchoalveolar lavage (BAL) technique. Based on the results in various approaches, a tendency of nanoscaled particles to form larger size agglomerates following deposition and interaction with cells or the respiratory tract 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.

[1]  B. Asgharian,et al.  A multiple-path model of particle deposition in the rat lung. , 1995, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[2]  O. Creutzenberg,et al.  In vitro study revealed different size behavior of different nanoparticles , 2012, Journal of Nanoparticle Research.

[3]  Monika Maier,et al.  Does Lung Surfactant Promote Disaggregation of Nanostructured Titanium Dioxide? , 2006, Journal of occupational and environmental medicine.

[4]  F. Seiler,et al.  Investigations on the inflammatory and genotoxic lung effects of two types of titanium dioxide: untreated and surface treated. , 2003, Toxicology and applied pharmacology.

[5]  Jeffrey W Card,et al.  Pulmonary applications and toxicity of engineered nanoparticles. , 2008, American journal of physiology. Lung cellular and molecular physiology.

[6]  A. Churg,et al.  The uptake of mineral particles by pulmonary epithelial cells. , 1996, American journal of respiratory and critical care medicine.

[7]  R. Henderson,et al.  Comparative study of bronchoalveolar lavage fluid: effect of species, age, and method of lavage. , 1987, Experimental lung research.

[8]  Robert N Grass,et al.  Oxide nanoparticle uptake in human lung fibroblasts: effects of particle size, agglomeration, and diffusion at low concentrations. , 2005, Environmental science & technology.

[9]  Vincent Castranova,et al.  A biocompatible medium for nanoparticle dispersion , 2008 .

[10]  Christian Mühlfeld,et al.  Re-evaluation of pulmonary titanium dioxide nanoparticle distribution using the "relative deposition index": Evidence for clearance through microvasculature , 2007, Particle and Fibre Toxicology.

[11]  Robert Gelein,et al.  Effects of subchronically inhaled carbon black in three species. I. Retention kinetics, lung inflammation, and histopathology. , 2005, Toxicological sciences : an official journal of the Society of Toxicology.

[12]  J. Schnekenburger,et al.  Not ready to use – overcoming pitfalls when dispersing nanoparticles in physiological media , 2008 .

[13]  W. Koch Application of aerosols , 1998 .

[14]  Conrad Coester,et al.  Particle and Fibre Toxicology BioMed Central Methodology , 2008 .

[15]  Heinrich Ernst,et al.  Impacts after inhalation of nano- and fine-sized titanium dioxide particles: morphological changes, translocation within the rat lung, and evaluation of particle deposition using the relative deposition index , 2012, Inhalation toxicology.

[16]  Otto Creutzenberg Biological interactions and toxicity of nanomaterials in the respiratory tract and various approaches of aerosol generation for toxicity testing , 2012, Archives of Toxicology.

[17]  Claus-Michael Lehr,et al.  Interaction of metal oxide nanoparticles with lung surfactant protein A. , 2011, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[18]  Annegret Potthoff,et al.  Physico-chemical characterization in the light of toxicological effects , 2009, Inhalation toxicology.

[19]  Vincent Castranova,et al.  Improved method to disperse nanoparticles for in vitro and in vivo investigation of toxicity , 2007 .

[20]  H Salem,et al.  Intratracheal instillation as an exposure technique for the evaluation of respiratory tract toxicity: uses and limitations. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[21]  Icrp Human Respiratory Tract Model for Radiological Protection , 1994 .

[22]  Jeffrey I. Zink,et al.  Dispersion and stability optimization of TiO2 nanoparticles in cell culture media. , 2010, Environmental science & technology.

[23]  Jürgen Seitz,et al.  Efficient Elimination of Inhaled Nanoparticles from the Alveolar Region: Evidence for Interstitial Uptake and Subsequent Reentrainment onto Airways Epithelium , 2007, Environmental health perspectives.

[24]  O R Moss,et al.  Generation of nanoparticle agglomerates and their dispersion in lung serum simulant or water , 2009 .