Airway Exposure to Silica-Coated TiO2 Nanoparticles Induces Pulmonary Neutrophilia in Mice

Abstract

The importance of nanotechnologies and engineered nanoparticles has grown rapidly. It is therefore crucial to acquire up-to-date knowledge of the possible harmful health effects of these materials. Since a multitude of different types of nanosized titanium dioxide (TiO(2)) particles are used in industry, we explored their inflammatory potential using mouse and cell models. BALB/c mice were exposed by inhalation for 2 h, 2 h on 4 consecutive days, or 2 h on 4 consecutive days for 4 weeks to several commercial TiO(2) nanoparticles, SiO(2) nanoparticles, and to nanosized TiO(2) generated in a gas-to-particle conversion process at 10 mg/m(3). In addition, effects of in vitro exposure of human macrophages and fibroblasts (MRC-9) to the different particles were assessed. SiO(2)-coated rutile TiO(2) nanoparticles (cnTiO(2)) was the only sample tested that elicited clear-cut pulmonary neutrophilia. Uncoated rutile and anatase as well as nanosized SiO(2) did not induce significant inflammation. Pulmonary neutrophilia was accompanied by increased expression of tumor necrosis factor-alpha (TNF-alpha) and neutrophil-attracting chemokine CXCL1 in the lung tissue. TiO(2) particles accumulated almost exclusively in the alveolar macrophages. In vitro exposure of murine and human macrophages to cnTiO(2) elicited significant induction of TNF-alpha and neutrophil-attracting chemokines. Stimulation of human fibroblasts with cnTiO(2)-activated macrophage supernatant induced high expression of neutrophil-attracting chemokines, CXCL1 and CXCL8. Interestingly, the level of lung inflammation could not be explained by the surface area of the particles, their primary or agglomerate particle size, or radical formation capacity but is rather explained by the surface coating. Our findings emphasize that it is vitally important to take into account in the risk assessment that alterations of nanoparticles, e.g., by surface coating, may drastically change their toxicological potential.

The potential health risk of titania nanoparticles

“…Conflicting data showing that particle size is not related to inflammatory potential has also been reported [22,23,39,57,102]. It is likely that the factors involved in nanotoxicity are complex and interactive.…”

“…However, these changes were minimal when cells were R, rutile; A, anatase; B, brookite; it, intranasal instillation; INH, inhalation; NPs, nanoparticles; BW, body weight; "-", independent factor; "+", dependent factor. treated with uncoated rutile TNPs, anatase TNPs, and SiO 2 NPs [22]. UV Titan (rutile TiO2 modified with Al, Si, Zr and coated with polyalcohol) is reported to produce prolonged lung inflammation in dams and developmental neurotoxicity in pups [71].…”

“…TNP toxicity has been observed in diverse models, such as rodents [15][16][17][18], aquatic organisms [19][20][21], and human cells [22][23][24]. Female workers were reported to experience shortness of breath and pleural effusions after 5-13 months of exposure in a polyacrylic ester nanoparticle processing factory [25], raising significant doubt about the human safety of TNPs.…”

In-depth lab report: evaluation of a nanomaterial handling enclosure conducted at the Alice Hamilton Laboratories.

“…However, initial toxicological data indicate that there is reason for caution. Pulmonary inflammation has been observed in animals exposed to titanium dioxide (TiO 2 ) and carbon nanotubes (CNT) (Shvedova, Kisin et al 2005, Chou, Hsiao et al 2008, Rossi, Pylkkanen et al 2010. Other studies have shown that nanoparticles can translocate to the circulatory system and to the brain and cause oxidative stress (Elder, Gelein et al 2006, Wang, Liu et al 2008.…”

Genotoxicity and Cytotoxicity of Cadmium Sulfide Nanomaterials to Mice: Comparison Between Nanorods and Nanodots

“…Compared with their bulk counterparts, nanomaterials are often more toxic (Grassian et al, 2006;Pan et al, 2007). For example, a number of toxicological studies using rats have shown that exposure to nanodots induces greater inflammatory and cytotoxic effects than larger-sized particles at equivalent mass concentrations (Grassian et al, 2006;Gillespie et al, 2010;Rossi et al, 2010). Most nanomaterial toxicity studies have focused on nanodots (i.e., particles of various shapes with no predominant dimension, or 0D), and only a few studies have addressed the toxicity of elongated rod-like (1D) nanoparticles (Magrez et al, 2009;Song et al, 2010) or compared 1D nanomaterials with their 0D counterparts (Chithrani et al,2006;Pal et al, 2007;Ispas et al, 2009;Simon-Deckers et al, 2009).…”