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Food-grade titanium dioxide (E171) is a white additive widely used in solid and liquid food products. There is still debate about E171 toxic effects after oral consumption since this additive is deposited in colon, liver, spleen, testis and brain. The consumption of E171 commonly occurs with Western diets that are characterized by a high fat content. Thus, E171 could worsen adverse effects associated with a high fat diet (HFD) such as anxiety, colon diseases and testicular damage. We aimed to evaluate the effects of E171 on anxiety-like behavior, colon, liver and testis and to analyze if the administration of a HFD could exacerbate adverse effects. E171 was administered at ~5 mg/kg bw by drinking water for 16 weeks and mice were fed with a Regular Diet or a HFD. E171 promoted anxiety, induced adenomas in colon, goblet cells hypertrophy and hyperplasia and mucins overexpression, but had no toxic effects on testicular tissue or spermatozoa in regular diet fed-mice. Additionally, E171 promoted microvesicular steatosis in liver in HFD fed-mice and the only HFD administration decreased the spermatozoa concentration and motility. In conclusion, E171 administration increases the number of adenomas in colon, induces hypertrophy and hyperplasia in goblet cells and microvesicular steatosis. Image 1 • E171 promotes anxiety-like behavior in mice administered for 8 and 16 weeks. • E171 induces adenomas and goblet cells hypertrophy and hyperplasia in colon. • E171 promotes microvesicular and macrovesicular liver steatosis in HFD fed mice. • Colon tissue overexpress L1CAM and mucins after 16 weeks of E171 administration. • HFD injures testis tissue and decreases the spermatozoa concentration and motility. [ABSTRACT FROM AUTHOR]

Air Liquid Interface (ALI) system has emerged as a useful tool for toxicity evaluation of nanomaterials related to inhalation since the system mimics the aerosol exposure. We compared the biological responses of lung epithelial cells exposed to titanium dioxide (TiO 2) nanofibers and nanoparticles in ALI and submerged cell cultures systems. Cells were exposed to 2 and 10 μg/cm2 for 24 h, 48 h and 72 h and LDH release, TiO 2 internalization, DNA-double strand breaks (DSBs) and ROS production were assessed. LDH release was similar in both systems and particles had higher cytoplasmic uptake in submerged systems. Both TiO 2 types were located in the cytoplasm but nanofibers had nuclear uptake regardless to the system tested. Cells exposed to TiO 2 nanofibers had higher DSBs in the ALI system than in submerged cell cultures but cells exposed to TiO 2 nanoparticles had similar DSBs in both systems. ROS production was higher in cells exposed to TiO 2 nanofibers compared to cells exposed to TiO 2 nanoparticles. In conclusion, cytotoxicity of lung epithelial cells was similar in ALI or submerged cell cultures, however cells exposed to TiO 2 nanofibers displayed higher toxicity than cells exposed to TiO 2 nanoparticles. • Cytotoxicity and DNA damage are similar in ALI and submerged cell cultures. • Submerged cell cultures had greater TiO 2 deposition than ALI cell cultures. • TiO 2 nanofibers displayed higher cytotoxic than TiO 2 nanoparticles. • Both TiO 2 types have cytoplasmic location but nanofibers have also nuclear uptake. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the fourth worldwide cause of death and even if some dietary habits are consider risk factors, the contribution of food additives including foodgrade titanium dioxide (TiO2), designated as E171, has been poorly investigated. We hypothesized that oral E171 intake could have impact on the enhancement of colorectal tumor formation and we aimed to investigate if E171 administration could enhance tumor formation in a colitis associated cancer (CAC) model. BALB/c male mice were grouped as follows: a) control, b) E171, c) CAC and d) CAC + E171 group (n = 6). E171 used in this study formed agglomerates of 300 nm in water. E171 intragastric administration (5 mg/kg body weight/5 days/10 weeks) was unable to induce tumor formation but dysplastic alterations were observed in the distal colon but enhanced the tumor formation in distal colon (CAC + E171 group) measured by tumor progression markers. Some E171 particles were internalized in colonic cells of the E171 and CAC + E171 groups and both groups showed a decrease in goblet cells in the distal colon. However the CAC + E171 group showed a higher decrease of these cells that act as protection barrier in colon. These results suggest that E171 could worsen pre-existent intestinal diseases. [ABSTRACT FROM AUTHOR]

• Information required for nanomaterials registration is mainly based on tonnage. • Sub-nanometric nanomaterials and nanofibers could have different criteria for regulation. • For some nanomaterials, limits of exposure are based on the bulk material as a reference. • Metal oxides and carbon-based are the most regulated nanomaterials. • Measuring airborne nanomaterials concentrations in occupational settings is urgent. The increasing concern of possible adverse effects on human health derived from occupational engineered nanomaterials (ENMs) exposure is an issue addressed by entities related to provide guidelines and/or protocols for ENMs regulation. Here we analysed 17 entities from America, Europe and Asia, and some of these entities provide limits of exposure extrapolated from the non-nanosized counterparts of ENMs. The international landscape shows that recommendations are mostly made for metal oxide based ENMs and tonnage is one of the main criteria for ENMs registration, however, sub-nanometric ENMs are emerging and perhaps a novel category of ENMs will appear soon. We identify that besides the lack of epidemiological evidence of ENMs toxicity in humans and difficulties in analysing the toxicological data derived from experimental models, the lack of information on airborne concentrations of ENMs in occupational settings is an important limitation to improve the experimental designs. The development of regulations related to ENMs exposure would lead to provide safer work places for ENMs production without delaying the nanotechnology progress but will also help to protect the environment by taking opportune and correct measures for nanowaste, considering that this could be a great environmental problem in the coming future. [ABSTRACT FROM AUTHOR]