Abstract
This study investigated the acute and subchronic inflammatory effects of micrometer-size (micro-size) and nanometer-size (nano-size) particles after intratracheal (i.t.) installation in mice. The role of the type of compound, polymorphism, and size of the particles was investigated. Studied compounds were the two micro-size reference quartzes, SRM1878a and DQ12, a micro- and nano-size rutile titanium dioxide (TiO2), a nano-size anatase, and an amorphous TiO2. Particles were administered by a single i.t. instillation in mice at a fixed dose of 5, 50, and 500 μg, respectively. Inflammation was evaluated from the bronchoalveolar lavage fluid (BALF) content of inflammatory cells, the cytokines tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), as well as from lung histology. Evaluations were at 24 h (acute effects) and 3 months (subchronic effects) after instillations. Both types of quartz induced a dose-dependent acute increase of neutrophils, IL-6, and total protein in BALF. Limited subchronic inflammation was observed. All types of TiO2 induced a dose-dependent acute increase of neutrophils in BALF. In the acute phase, micro- and nano-size rutile and nano-size amorphous TiO2 induced elevated levels of IL-6 and total protein in BALF at the highest dose. At the nano-size rutile and amorphous TiO2, subchronic lung inflammation was apparent from a dose-dependent increase in BALF macrophages. Histology showed little inflammation overall. The two types of quartz showed virtually similar inflammatory effects. Nearly similar effects were observed for two sizes of rutile TiO2. Differences were seen between the different polymorphs of nano-size TiO2, with rutile being the most inflammogenic and amorphous being the most potent in regard to acute tissue damage.
Highlights
Inorganic particles can cause severe lung diseases and cancer, and can promote the development of allergies[1,2,3,4,5,6,7]
Due to low particle counts, suitable dynamic light scatter (DLS) size distribution spectra could not be obtained on the suspension filtered through a 0.8-μm filter, but the presence of 200- to 600-nm-size particles was indicated from light-scattering intensity data
When calculating the surface area from the dH obtained from the DLS data, the results indicate that the inflammatory effect of the two types of quartz and the two types of rutile TiO2 induced a comparable acute neutrophil inflammation at the highest dose, whereas the effect of the anatase and amorphous TiO2 was significantly lower (Fig. 10b)
Summary
Inorganic particles can cause severe lung diseases (such as pneumoconiosis and chronic obstructive pulmonary disease [COPD]) and cancer, and can promote the development of allergies[1,2,3,4,5,6,7]. Several new types of particulate chemicals have appeared, including a wide range of engineered nanoparticles. These nanoparticles may be more toxic than coarser particles due to their smaller size and increased specific surface area[8,9,10], but this need not always be the case[11,12,13,14,15]. Due to limitations of in vitro methods, animal studies are still necessary for the hazard evaluation and screening of new particles[16,17,18,19,20,21]. The gold standard for pulmonary toxicological evaluation of new substances is long-term inhalation studies, which best mimic real-life exposure conditions. As inhalation is a laborious and complicated method, alternative exposure methods, such as intranasal and intratracheal (i.t.) instillation, are often used to mimic inhalation exposure[22,23,24,25,26,27]
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