# Titanium Dioxide in Chromogenic Devices: Synthesis, Toxicological Issues, and Fabrication Methods
## 3 Toxicity Assessment of TiO\({}_{2}\) NPs and Films
The ROS production caused the activation of a series of biochemical reactions that induced an unbalance of cell homeostasis, leading to DNA damage [128]. A recent work [129] demonstrated the reduction of the richness and evenness of gut microbiota, with the consequent disruption of gut microbial community compositions in adult mice exposed to TiO\({}_{2}\) NPs (50 mg/kg) by intragastric administration for 30 days. Mice presented a reduction in motor activity, even when the memory brain function was not damaged. [PERSON] et al. [130] studied the possible alteration of mice gut microbiota structure after oral administration of anatase and rutile TiO\({}_{2}\) NPs for 28 days. The concentrations used were the equivalent consumed by candy lovers. NPs were found to accumulate in the spleen, lung, and kidney; an alteration in terms of colon villi length and width were recorded in the intestine (Figure 5). Furthermore, oral administration of two different sizes of TiO\({}_{2}\) NPs (260 nm and 66 nm) for 10 days boosted susceptibility of the small intestine portions such as the duodenum, jejunum, and ileum of mice. The portions of organs extracted after the exposure to NPs reported high levels of TiO\({}_{2}\) accumulation with a consequent inflammation of several tissues by cytokines activation [131]. TiO\({}_{2}\) NPs are also used in the cosmetic and personal care industries, in particular in dermal consumer products such as sunscreens and UV radiation filters [132]. Four pathways of penetration across the skin have been identified depending on the physico-chemical properties of the compound: intercellular, transcellular, and two transappendageal pathways, through hair follicles and sweat glands [133]. The penetration of micro TiO\({}_{2}\) NPs in epidermis and dermis is considered highly improbable; microparticles tend to be retained on the outermost surface of the stratum corneum [134]. At the nanoscale level, the situation may be different [135; 136] because NPs can cross the derma, especially in the presence of irritations or lesions [137; 138]. Numerous in vitro and in vivo studies have been conducted to quantify the penetration rate of TiO\({}_{2}\) NPs on both undamaged and injured skin. According to works by [PERSON] et al. [7], a negligible amount of TiO\({}_{2}\) NPs penetrated healthy skin; this conclusion was corroborated by [PERSON] et al. [139]. Most of the studies reported so far in the literature deal with the direct exposure of living organisms and cells to TiO\({}_{2}\) NPs by different administration methods (oral, intravenous, intranasal, etc.) and incubation, respectively. These routes forecast the use of a NPs suspension, namely a physiological medium in which NPs are dispersed (such as saline buffers or culture medium). However, TiO\({}_{2}\) is widely used in the development of devices by the use of several techniques, for different fields, ranging from sensors to solar cells. Structure, concentration, and crystal and grain size are important properties that have to be understood in order to address their use in specific applications. In the case of devices, TiO\({}_{2}\) is used to form nanometric or microsized films with unique properties, often associated with other kinds of materials, to build multi layered devices. In this scenario, it is interesting to evaluate their toxicity, which is expected to differ from that observed in the studies reported above for NPs. Some works highlighted the compatibility of rutile and anatase TiO\({}_{2}\) surfaces as substrates for the cells grown. [PERSON] et al. [140] showed the good adherence and axonal growth of cultured rat cerebral cortex neurons on rutile surfaces. TiO\({}_{2}\) exhibited the highest degree of biocompatibility in terms of neurite extension observed in spiral ganglion (SG) neuritis, compared with other types of films made of gold or stainless steel [141].