Inhalation Exposure Study of Titanium Dioxide Nanoparticles with a Primary Particle Size of 2 to 5 nm

TLDR

Nanotechnology offers promise across industries, yet the health effects of manufactured nanoparticles, particularly 2–5 nm TiO₂ particles, remain largely unknown. This study aimed to evaluate the pulmonary toxicity of 2–5 nm TiO₂ nanoparticles in a murine lung inflammation model, characterizing particle properties and aerosol characteristics. Mice were exposed in a whole‑body chamber acutely (4 h) or subacutely (4 h/day for 10 days) to TiO₂ aerosols, and toxicity was assessed by BAL cell counts, protein, LDH, cytokines, and histopathology. Acute exposure produced minimal lung toxicity, whereas subacute exposure increased BAL cells and macrophages, indicating a moderate inflammatory response that resolved by week 3 post‑exposure.

Abstract

Nanotechnology offers great promise in many industrial applications. However, little is known about the health effects of manufactured nanoparticles, the building blocks of nanomaterials.Titanium dioxide (TiO(2)) nanoparticles with a primary size of 2-5 nm have not been studied previously in inhalation exposure models and represent some of the smallest manufactured nanoparticles. The purpose of this study was to assess the toxicity of these nanoparticles using a murine model of lung inflammation and injury.The properties of TiO(2) nanoparticles as well as the characteristics of aerosols of these particles were evaluated. Mice were exposed to TiO(2) nanoparticles in a whole-body exposure chamber acutely (4 hr) or subacutely (4 hr/day for 10 days). Toxicity in exposed mice was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase (LDH) activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid. Lungs were also evaluated for histopathologic changesMice exposed acutely to 0.77 or 7.22 mg/m(3) nanoparticles demonstrated minimal lung toxicity or inflammation. Mice exposed subacutely (8.88 mg/m(3)) and necropsied immediately and at week 1 or 2 postexposure had higher counts of total cells and alveolar macrophages in the BAL fluid compared with sentinels. However, mice recovered by week 3 postexposure. Other indicators were negative.Mice subacutely exposed to 2-5 nm TiO(2) nanoparticles showed a significant but moderate inflammatory response among animals at week 0, 1, or 2 after exposure that resolved by week 3 postexposure.