Inhaled Titanium Dioxide Nanoparticles: A Review of Their Pulmonary Responses with Particular Focus on the Agglomeration State

Nanotechnology represents major scientific and economic issues for the future. TiO2 is used as a reference nanoparticle (NP) for research and workplace exposure assessments due to its important industrial production. However, to date little consistent information exists about its human health effects. Approximately 50% of all TiO2in vivo studies targeting the respiratory tract have been by inhalation and these exposures are often in the form of agglomerates rather than as individual NPs. Therefore, the size of the NP agglomerates represents the effective size interacting with the biological material and could thereby influence the NP mechanisms of action. Thus, interpretation of nanotoxicological data without considering the agglomeration state could partly explain the heterogeneous results found in the scientific literature for TiO2 NPs. The objective of this review is to examine the literature concerning the importance of TiO2 aerosol characterization in the assessment of pulmonary toxicity in rodents. In this way, this review reveals that the pulmonary responses following inhalation of TiO2 NPs might not depend solely on the primary NP size, but also on the crystal phase, the NP agglomerate size, its structure and the mass concentration. It also shows that TiO2 NPs may exert their toxicity mechanisms specifically because of the size of their agglomerates in aerosols, thus supporting the concept that aerosols composed essentially of small (< 100 nm) or large (> 100 nm) NP agglomerates do not seem to follow the same pulmonary toxicity mechanisms.