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

Abstract

BackgroundNanotechnology offers great promise in many industrial applications. However, little is known about the health effects of manufactured nanoparticles, the building blocks of nanomaterials.ObjectivesTitanium dioxide (TiO2) 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.Materials and MethodsThe properties of TiO2 nanoparticles as well as the characteristics of aerosols of these particles were evaluated. Mice were exposed to TiO2 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 changesResultsMice exposed acutely to 0.77 or 7.22 mg/m3 nanoparticles demonstrated minimal lung toxicity or inflammation. Mice exposed subacutely (8.88 mg/m3) 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.ConclusionsMice subacutely exposed to 2–5 nm TiO2 nanoparticles showed a significant but moderate inflammatory response among animals at week 0, 1, or 2 after exposure that resolved by week 3 postexposure.

Effects of size and shape on filtration of TiO2 nanoparticles

“…Analysis of TEM photos of mobility-classified TiO 2 particles showed compact agglomerates of nanoscale primary particles. The physical shape obtained in this study is similar to TiO 2 particles observed in production facilities (Curwin and Bertke 2011;Koivisto et al 2012) as well as TiO 2 generated in the laboratory for inhalation exposure studies (Grassian et al 2007;Ma-Hock et al 2009;Noel et al 2013). The projected area diameter is close to the mobility diameter, where the length is about 30% larger than the mobility diameter.…”

“…Compact agglomerates consisting of primary particles were observed for mobility diameters between 50 and 500 nm, similar to those reported in the plants handling nanoscale TiO 2 materials (Curwin and Bertke 2011;Koivisto et al 2012). Also, several inhalation studies of rodents exposed to nanoscale TiO 2 particles showed that laboratory-generated particles have compact agglomerates in the 100 to 500 nm size range using either a Collison nebulizer (Grassian et al 2007) or dry powder generators including a brush dust generator (Ma-Hock et al 2009), a fluidized bed, and rotating brush generator (RBG; Noel et al 2013). These studies did not report measurements of TiO 2 physical dimensions.…”

The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles

“…These lesions correlate with the induction of 8-hydroxyguanosine (8-OHdG) as an oxidative stress marker in lung epithelial cells and activated macrophages [122]. Subacute exposure of C57B1/6 mice to 2-5 nm TiO 2 NPs in a whole-body exposure chamber caused a moderate but significant inflammatory response in the lung within the first two weeks of exposure, beyond which the inflammation resolved without permanent damage [123]. Inoue et al have demonstrated that intratracheal administration of 14 nm and 56 nm carbon black NPs induced slight lung inflammation and significant pulmonary edema compared with the vehicle [124].…”

Nanoparticles increase human bronchial epithelial cell susceptibility to respiratory syncytial virus infection via nerve growth factor-induced autophagy

“…2006), sunscreens and cosmetics, as well as their potential for causing inflammation and injury of the lower airways in a dose‐dependent manner (Oberdorster 2001; Chen and Schuster 2006; Grassian et al. 2007). …”