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Ingested nanomaterials: effects of titanium dioxide in human cells

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Nowadays, the consumer products containing nanomaterials (NMs) are numerous. Among these, titanium dioxide nanomaterials (TiO2) are the most frequently applied, used as food additive, pharmaceuticals, toothpastes and many more. The wide commercialization of consumer products containing TiO2 contributes to a substantial increase of human exposure to this compound, which is worrying for public health, since the existent studies generated contradictory results about TiO2 safety. The fact that NMs are dependent of the context (surrounding matrix) can contribute to explain the contradictory results reported in the literature. Furthermore, it has been hypothesized that NMs physicochemical properties may define bio-nano interactions, which suggest that NMs with the same chemistry but with different shape, diameter, length, surface charge or functionalization may lead to different toxicities (Louro et al., 2019). This work aimed to assess whether the secondary physicochemical characteristics of three different TiO2, i.e., the characteristics after the digestion process, produce different biological effects in intestinal cells. The three NMs were obtained from the Joint Research Centre, Ispra, Italy (NM-102, NM-103 and NM-105), and display different charge, size and crystal structure, coated and uncoated, as characterized by the producer (Rasmussen et al., 2014). An in vitro digestion process was used to mimic human digestion (Brodkorb et al., 2019) and the resulting product was used for cytotoxicity assessment in a human intestinal cell line (Caco-2), in comparison to undigested NMs. In addition, cellular uptake was investigated using confocal microscopy. Preliminary results did not evidence a differential biological effect between the three NMs. Following 24h of exposure of Caco-2 cells, all the digested NMs behaved similarly at the concentrations tested (0.14 – 14.3 µg/ml) showing no cytotoxic effects. Likewise, no cytotoxic effects were observed upon exposure to undigested NMs. However, the results showed the nuclear localization of one NM, NM-102, suggesting that it may interact with the genome in cells exposed to this TiO2. Ongoing studies will confirm the subcellular localization of the NMs in exposed intestinal cells and will investigate their genotoxic effects in relation with the secondary properties.

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Nanomaterials Nanotoxicology Ingestion Genotoxicity Environmental Genotoxicity Genotoxicidade Ambiental

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