title: Deposition behavior of inhaled nanostructured TiO2 in rats: fractions of particle diameter below 100 nm (nanoscale) and the slicing bias of transmission electron microscopy.
abstract: BACKGROUND
  In experimental studies with nanomaterials where translocation to secondary organs was observed, the particle sizes were smaller than 20 nm and were mostly produced by spark generators. Engineered nanostructured materials form microsize aggregates/agglomerates. Thus, it is unclear whether primary nanoparticles or their small aggregates/agglomerates occur in non-negligible concentrations after exposure to real-world materials in the lung.
  
  
  OBJECTIVE
  We dedicated an inhalation study with nanostructured TiO(2) to the following research question: Does the particle size distribution in the lung contain a relevant subdistribution of nanoparticles?
  
  
  METHODS
  Six rats were exposed to 88 mg/m(3) TiO(2) over 5 days with 20% (count fraction) and <0.5% (mass fraction) of nanoscaled objects. Three animals were sacrificed after cessation of exposure (5 days), others after a recovery period of 14 days. Particle sizes were determined morphometrically by transmission electron microscopy (TEM) of ultra-thin lung slices. Since the particles visible are two-dimensional surrogates of three-dimensional structures we developed a model to estimate expected numbers of particle diameters below 100 nm due to the TEM slicing bias. Observed and expected numbers were contrasted in 2 × 2 tables by odds ratios.
  
  
  RESULTS
  Comparisons of observed and expected numbers did not present evidence in favor of the presence of nanoparticles in the rat lungs. In simultaneously exposed satellite animals agglomerates of nanostructured TiO(2) were observed in the mediastinal lymph nodes but not in secondary organs.
  
  
  CONCLUSIONS
  For nanostructured TiO(2), the deposition of nanoscaled particles in the lung seem to play a negligible role.
authors.affiliation: Institute and Policlinic for Occupational Medicine, Environmental Medicine and Preventive Research, School of Medicine and Dentistry, University of Cologne, Germany. peter.morfeld@evonik.com
authors.forename: Peter
authors.initials: P
authors.lastname: Morfeld
authors.forename: Silke
authors.initials: S
authors.lastname: Treumann
authors.forename: Lan
authors.initials: L
authors.lastname: Ma-Hock
authors.forename: Joachim
authors.initials: J
authors.lastname: Bruch
authors.forename: Robert
authors.initials: R
authors.lastname: Landsiedel
mesh_terms: D000336:Aerosols; D000818:Animals; D019570:Inhalation Exposure; D057230:Limit of Detection; D008168:Lung / Q000378:metabolism* / Q000648:ultrastructure; D008198:Lymph Nodes / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D015233:Models, Statistical; D053758:Nanoparticles; D016017:Odds Ratio; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014018:Tissue Distribution; D014025:Titanium / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000336:Aerosols; C009495:titanium dioxide; D014025:Titanium