Rat pulmonary responses to inhaled nano-TiO2: effect of primary particle size and agglomeration state

Abstract

BackgroundThe exact role of primary nanoparticle (NP) size and their degree of agglomeration in aerosols on the determination of pulmonary effects is still poorly understood. Smaller NP are thought to have greater biological reactivity, but their level of agglomeration in an aerosol may also have an impact on pulmonary response. The aim of this study was to investigate the role of primary NP size and the agglomeration state in aerosols, using well-characterized TiO2 NP, on their relative pulmonary toxicity, through inflammatory, cytotoxic and oxidative stress effects in Fisher 344 male rats.MethodsThree different sizes of TiO2 NP, i.e., 5, 10–30 or 50 nm, were inhaled as small (SA) (< 100 nm) or large agglomerates (LA) (> 100 nm) at 20 mg/m3 for 6 hours.ResultsCompared to the controls, bronchoalveolar lavage fluids (BALF) showed that LA aerosols induced an acute inflammatory response, characterized by a significant increase in the number of neutrophils, while SA aerosols produced significant oxidative stress damages and cytotoxicity. Data also demonstrate that for an agglomeration state smaller than 100 nm, the 5 nm particles caused a significant increase in cytotoxic effects compared to controls (assessed by an increase in LDH activity), while oxidative damage measured by 8-isoprostane concentration was less when compared to 10–30 and 50 nm particles. In both SA and LA aerosols, the 10–30 nm TiO2 NP size induced the most pronounced pro-inflammatory effects compared to controls.ConclusionsOverall, this study showed that initial NP size and agglomeration state are key determinants of nano-TiO2 lung inflammatory reaction, cytotoxic and oxidative stress induced effects.

Phagocytosis-dependent and independent mechanisms underlie the microglial cell damage caused by carbon nanotube agglomerates

“…This is consistent with previous studies reporting that nanoparticle agglomerates induced substantial biological responses after phagocytosis. For example, nano-aerosols that are composed of large agglomerates (> 100 nm) are more likely to promote pulmonary clearance via phagocytosis and the acute inflammatory responses of macrophages (Noël et al, 2013). It remains to be elucidated what factors determine whether the CNT agglomerates are phagocytosed, and how the extent of the CNT agglomerate toxicity is determined.…”

“…The length and fiber diameter of each CNT itself (#1: no information; #2: mean length of 3.5 μm, fiber diameter of 30 nm, #3: mean length of 4.51 μm, fiber diameter of 150 nm, #4: mean length of 3.0 μm, fiber diameter of 10-15 nm, #5: mean length of 3.3 μm, fiber diameter of 40-50 nm) seem not to correlate with the extent of toxicity of its agglomerates in this study. The biological responses to nanoparticles reportedly depend on the dimensions and concentrations of the nanoparticle agglomerates (Gosens et al, 2010;Noël et al, 2012Noël et al, , 2013. Furthermore, recent reports have suggested that it is not only the size but also the shape that determines the extent of the toxicity (Bhattacharjee et al, 2012).…”

Long‐term retention of pristine multi‐walled carbon nanotubes in rat lungs after intratracheal instillation

“…Smaller nanoparticles showed more widespread organ distribution (De Jong et al ., 2008). Exposure to small aggregates of TiO 2 nanoparticles produced increased oxidative stress effects and cytotoxicity than exposure to large aggregates of these nanoparticles (Noël et al ., 2013). Therefore, well‐dispersed MWCNTs might be more toxic and show more widespread organ distribution than aggregated MWCNTs, although published data have not indicated that dispersion affected the toxicity of TiO 2 nanoparticles (Kobayashi et al ., 2009).…”

Titanium Dioxide Nanoparticles: Occupational Exposure Limits

“…Zarówno aerozole SA, jak i LA nanocząstek TiO 2 z zakresu 10-30 nm indukują większe efekty prozapalne w porównaniu z kontrolą. Autorzy sugerują, że najdrobniejsze cząstki (5 nm) penetrują łatwiej do komórek, stąd większa cytotoksyczność, natomiast cząst-ki z zakresu 10-30 nm mają największą zdolność depozycji w rejonie pęcherzyków płucnych, co indukuje procesy zapalne (38).…”