Transcriptomic profile of TiO2 particle overload in rat alveolar macrophages: examining responses between P25 and two pigment grade particles in vitro.

The industrial uses of titanium dioxide (TiO₂) are extensive, with pigment grades (particle size > 100 nm) being the most common forms produced. Nanoforms (particle size < 100 nm) of TiO₂ (e.g., P25) are also produced for specialist applications such as photocatalysts. P25 induced inflammatory and carcinogenic lung responses in rats at high exposure doses inducing lung overload. We previously identified an in vitro transcriptomic signature (18 genes) associated with overload of P25, in rat alveolar macrophages. The objective of the present study was to determine whether this signature also applies to other, more commonly used pigment grades of TiO₂. Using high-throughput sequencing, we examined the transcriptomic responses of three TiO₂ grades (the photocatalyst P25 and two pigment grades, G3-1 and Bayertitan T) in primary rat alveolar macrophages exposed in vitro at non-overload (4 µg/mL for P25; 2 µg/mL for G3-1 and Bayertitan T) or overload (40 µg/mL for P25; 20 µg/mL for G3-1 and Bayertitan T) doses. At an equivalent internalized volume of particles, the response to P25 overload was significantly higher than those to pigment particles. However, a consistent modulation of the 18-gene signature was observed across all three TiO₂ grades, albeit with a markedly lower magnitude of response for the pigment particles. Although the gene signature of particle overload in rat alveolar macrophages seems to apply across different TiO₂ particle grades, our results suggest that unrealistic and extreme exposure concentrations to the pigment TiO₂ particles would be required to induce in vivo toxicity similar to that observed with P25 particles.