## 4 Discussion
Exposure to 50 g mL\({}^{-1}\) TiO\({}_{2}\) NPs (anatase) increased the production of IL-1 in THP-1 macrophages as well as the expression of IL-8 in Caco-2 cells. This suggested an inflammatory response induced by TiO\({}_{2}\) NPs [25]. [PERSON] et al. [11] \begin{table}
\begin{tabular}{c c c c c} \hline
**Sample** & **K** & **E** & **BMD** & **72h-IC50 (ug mL\({}^{-1}\))** \\ \hline S1 & 12.2 \(\times\) 10\({}^{4}\) & 1.63 & 306.9 & 1088.6 \\ S2 & 1494.4 & 1.57 & 97.3 & 343.7 \\ S3 & 16 \(\times\) 10\({}^{3}\) & 1.56 & 99.4 & 353.6 \\ S4 & 16,978 & 1.71 & 62.8 & 194.7 \\ \hline \end{tabular} \(K\)—the dissociation constant, E—the Hill exponent, BMD—the benchmark dose and the 50% inhibitory concentration.  
\end{table} 
Table 1: Hill model parameters for Caco-2 cells after 72 h incubation. reported that during acute exposure to TiO\({}_{2}\) (6 or 48 h) as well as repeated exposure twice a week (for 21 days after inoculation (10 or 50 \(\upmu\)g mL\({}^{-1}\))), no effect was observed in terms of enterocyte differentiation; however, an inflammatory response with increased mucus secretion was induced. [PERSON] et al. [30] studied the impact of E171 and TiO\({}_{2}\) NPs on intestinal cells (Caco-2 and Caco-2 with HT29-MTX mucus excretion) at the following exposure times and concentrations: 6, 24, and 48 h (1-200 \(\upmu\)g mL\({}^{-1}\)) or three times a week for 3 weeks (1-100 \(\upmu\)g mL\({}^{-1}\)). They reported that the substance's toxicity was due to the effect of oxidation, with oxidative stress causing DNA damage and accumulation of ROS inside cells. Additionally, an increased cellular response was observed after 21 days of exposure to E171. Other factors can also influence the toxicity of nanoparticles. [PERSON] et al. [16] demonstrated that TiO\({}_{2}\) nanoparticles in various crystalline forms showed general cytotoxicity towards Caco-2 cells, while oxidative damage to DNA depended on the surface area of the TiO\({}_{2}\) NPs. At the same time, however, contradictory results have also been reported in studies on TiO\({}_{2}\) toxicity. While some authors pointed to its potential toxicity [24; 31; 32], others observed little to no impact at all [25]. One of the main reasons behind such inconsistency may have been, apart from the different properties of the nanoparticles themselves, the diversity of food matrices with which the particles were provided. [PERSON] et al. [33] demonstrated that after a 24 h exposure to TiO\({}_{2}\) NPs concentrated below 200 \(\upmu\)g mL\({}^{-1}\), the nanoparticles did not induce any toxicity in Caco-2 cells. However, when the TiO\({}_{2}\) nanoparticles were pretreated with liquids simulating digestion (200 \(\upmu\)g mL\({}^{-1}\)), they inhibited the growth of undifferentiated Caco-2 cells [33]. [PERSON] et al. [34] did not observe cytotoxicity in Caco-2 cells after a 24 h exposure to TiO\({}_{2}\) NPs concentrated between 1.2 and 80 \(\upmu\)g cm\({}^{-3}\). In their subsequent study the authors also did not report cytotoxic effects on Caco-2 cells, nor did they observe a significant impact on IL-8 expression (over 2 weeks at concentrations up to 80 \(\upmu\)g cm\({}^{-3}\)) [35].