Effects of inhaled nano-TiO2 aerosols showing two distinct agglomeration states on rat lungs

Nano-aerosols composed of large agglomerates (LA) (>100 nm) are more likely to promote pulmonary clearance via macrophages phagocytosis. Small agglomerates (SA) (<100 nm) seem to escape this first defense mechanism and are more likely to interact directly with biological material. These different mechanisms can influence pulmonary toxicity. This hypothesis was evaluated by comparing the relative pulmonary toxicity induced by aerosolized nano-TiO2 showing two different agglomeration states: SA (<100 nm) and LA (>100 nm) at mass concentrations of 2 or 7 mg/m3. Groups of Fisher 344 male rats were nose-only exposed for 6 h. The median number aerodynamic diameters were 30 and 185 nm at 2 mg/m3, and 31 and 194 nm at 7 mg/m3. We found in rat's bronchoalveolar lavage fluids (BALF) a significant 2.1-fold increase in the number of neutrophils (p < 0.05) in the group exposed to the 7 mg/m3 LA nano-aerosol suggesting a mild inflammatory response. Rats exposed to the 7 mg/m3 SA nano-aerosol showed a 1.8-fold increase in LDH activity and 8-isoprostane concentration in BALF, providing evidence for cytotoxic and oxidative stress effects. Our results indicate that biological responses to nanoparticles (NP) might depend on the dimension and concentration of NP agglomerates.

► We compare the relative pulmonary toxicity induced by aerosolized nano-TiO2 (5 nm).
► Rats inhaled small (<100 nm) or large agglomerates (>100 nm) at 2 and 7 mg/m3.
► Exposure to large agglomerates at 7 mg/m3 shows a significant increase in neutrophil.
► Exposure to small agglomerates at 7 mg/m3 suggests cytotoxic and oxidative effects.
► Biological responses to nano-TiO2 might depend on the dimension of agglomerates.