Toxicokinetics of titanium dioxide (TiO2) nanoparticles after inhalation in rats

Pujalté, Igor; Dieme, Denis; Haddad, Sami; Serventi, A. M.; Bouchard, Michèle

doi:10.1016/j.toxlet.2016.11.014

Cited by 76 publications

(38 citation statements)

References 46 publications

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“…With the increasing production and applications of nano‐TiO 2 , human exposure to these NPs continues to increase. Moreover, it has been reported that after inhalation, ingestion, or skin application, nano‐TiO 2 could penetrate rapidly into the systemic circulation and reach various organs, including liver, spleen, heart, kidney, and brain . where they could possibly pose adverse effects to these second target organs.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, it has been reported that after inhalation, ingestion, or skin application, nano-TiO 2 could penetrate rapidly into the systemic circulation and reach various organs, including liver, spleen, heart, kidney, and brain. [15][16][17][18][19] where they could possibly pose adverse effects to these second target organs. After passage through the biological barriers, undoubtedly, nano-TiO 2 will inevitably end up in contact with the vascular endothelium and may induce cardiovascular damage before they reach other organs.…”

Section: Introductionmentioning

confidence: 99%

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The size‐dependent apoptotic effect of titanium dioxide nanoparticles on endothelial cells by the intracellular pathway

Zeng

Feng

Wu-xiang

et al. 2018

Environmental Toxicology

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Concerns over the health risk of the widely distributed, commonly used titanium dioxide nanoparticles (nano-TiO ) are increasing worldwide. Yet, up-to-now, our understanding in their potential effects on the cardiovascular system is very limited and the toxicological mechanisms are still unclear. In the present study, the CCK-8 assay was performed to determine the cytotoxicity of four sizes (10, 30, 50, and 100 nm) of anatase nano-TiO on human umbilical vein endothelial cells (HUVECs) in culture, and the flow cytometry was employed to investigate the potential of these nano-TiO to induce the apoptosis of HUVECs. The apoptotic pathway was also probed through the determination of the protein expression and activation of p53, Bax, Bcl-2, caspases-9, -7, -3, and PARP by western blot. The results showed that at the administrative levels (1, 5, 25 μg/mL), all the four sizes of nano-TiO could significantly inhibit the viability of HUVECs and elicit significant apoptosis in them, compared with the negative control (P < .05, P < .01). Moreover, the apoptotic rates of HUVECs were increased respectively with the elevating levels and decreasing sizes of the administrative nano-TiO , showing a clear dose- and size-dependent effect relationships. Interestingly, the increasing phosphorylation of p53, decreasing ratio of Bcl-2/Bax, and enhancing activation of the downstream proteins caspase-9, -7, -3, and PARP, were also observed with the decreasing sizes of the administrative nano-TiO in the western blot, indicating that the intracellular approach of apoptosis, the p53-caspase pathway, is the major way of the nano-TiO -mediated apoptosis in HUVECs in culture and that the size is an important parameter that may determine the potential of nano-TiO to induce cellular response. In conclusion, these results suggested that high levels of nano-TiO exposure may pose potential risks to human cardiovascular health by inducing cardiovascular EC apoptosis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The size‐dependent apoptotic effect of titanium dioxide nanoparticles on endothelial cells by the intracellular pathway

Zeng

Feng

Wu-xiang

et al. 2018

Environmental Toxicology

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“…In several studies, nanoparticles were detected in the liver, heart, kidneys, pancreas, spleen, brain or blood after inhalation and translocation through the lung barrier. 31,[35][36][37][38] Nevertheless, this phenomenon does not appear to be predominant as the translocation rate is slower than the lung clearance rate. 39 In conclusion, inhaled nanoparticles can be found in the lungs.…”

Section: Inhalation Exposurementioning

confidence: 99%

Safety of titanium dioxide nanoparticles in cosmetics

Dréno¹,

Chuberre

et al. 2019

Acad Dermatol Venereol

156

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Titanium dioxide (TiO2) is widely used in a variety of products including cosmetics. TiO2 in its nanoparticle form (nano‐TiO2) is now the only form used as an ultraviolet (UV) filter in sunscreens, but also in some day creams, foundations and lip balms. While its efficacy as a UV filter is proven in the prevention of skin cancers and sunburns, some concerns have been raised about its safety. Indeed, considering its small size, nano‐TiO2 is suspected to penetrate dermal, respiratory or gastrointestinal barriers, disseminate in the body and therefore constitute a potential risk to the consumer. At the skin level, most studies performed in humans or animals showed that nano‐TiO2 did not penetrate beyond the outer layers of stratum corneum to viable cells and did not reach the general circulation, either in healthy or in compromised skin. The Scientific Committee on Consumer Safety (SCCS) considers nano‐TiO2 as a non‐sensitizer and as mild‐ or non‐irritant to skin and concludes in no evidence of carcinogenicity (supported by the European Chemicals Agency), mutagenicity or reproductive toxicity after dermal exposure to nano‐TiO2. According to the SCCS, nano‐TiO2 from sunscreens does not present any health risk when applied on the skin at a concentration up to 25%. However, the SCCS does not recommend the use of nano‐TiO2 in formulations that may lead to exposure of the consumer's lungs by inhalation (sprayable products and powders). Indeed, even if human data are sparse and inconsistent, lung inflammation was reported in animals. In 2016, the EU Cosmetic Regulation made nano‐TiO2 as an authorized UV filter, except in products that could lead to exposure of the lungs. After oral exposure, nano‐TiO2 absorption and toxicity are limited. The incidental oral exposure to nano‐TiO2 contained in lip balms is thus not expected to induce adverse health effects.

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“…The compound has numerous applications in industry, coating systems, medicine, everyday lives, and the environment. [1][2][3][4][5][6] Due to its widespread usage and specific physical and chemical properties, 7 nano-TiO 2 is transferred to the human body through various routes, including inhalation, environmental intake (food additives or packaging components), and biomedical applications (gastrointestinal absorption or skin exposure), 1,6,8 and subsequently travels through the blood circulation into the liver, brain, spleen, heart, kidneys, lungs, and ovaries. 3,[9][10][11][12] We have reported nano-TiO 2 deposition in various organs of mice after exposure for 14 consecutive days in the following order: liver .…”

Section: Introductionmentioning

confidence: 99%

Suppression of testosterone production by nanoparticulate TiO<sub>2</sub> is associated with ERK1/2-PKA-PKC signaling pathways in rat primary cultured Leydig cells

Li¹,

Mu²,

Ye³

et al. 2018

IJN

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BackgroundNanoparticulate titanium dioxide (nano-TiO2) enters the body through various routes and causes organ damage. Exposure to nano-TiO2 is reported to cause testicular injury in mice or rats and decrease testosterone synthesis, sperm number, and motility. Importantly, nano-TiO2 suppresses testosterone production by Leydig cells (LCs) and impairs the reproductive capacity of animals.MethodsIn an attempt to establish the molecular mechanisms underlying the inhibitory effect of nano-TiO2 on testosterone synthesis, primary cultured rat LCs were exposed to varying concentrations of nano-TiO2 (0, 10, 20, and 40 µg/mL) for 24 hours, and alterations in cell viability, cell injury, testosterone production, testosterone-related factors (StAR, 3βHSD, P450scc, SR-BI, and DAX1), and signaling molecules (ERK1/2, PKA, and PKC) were investigated.ResultsThe data show that nano-TiO2 crosses the membrane into the cytoplasm or nucleus, triggering cellular vacuolization and nuclear condensation. LC viability decreased in a time-dependent manner at the same nano-TiO2 concentration, nano-TiO2 treatment (10, 20, and 40 µg/mL) decreased MMP (36.13%, 45.26%, and 79.63%), testosterone levels (11.40% and 44.93%), StAR (14.7%, 44.11%, and 72.05%), 3βHSD (26.56%, 50%, and 79.69%), pERK1/2 (27.83%, 63.61%, and 78.89%), PKA (47.26%, 70.54%, and 85.61%), PKC (30%, 50%, and 71%), SR-BI (16.41%, 41.79%, and 67.16%), and P450scc (39.41%, 55.26%, and 86.84%), and upregulated DAX1 (1.31-, 1.63-, and 3.18-fold) in primary cultured rat LCs.ConclusionOur collective findings indicated that nano-TiO2-mediated suppression of testosterone in LCs was associated with regulation of ERK1/2–PKA–PKC signaling pathways.

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Toxicokinetics of titanium dioxide (TiO2) nanoparticles after inhalation in rats

Cited by 76 publications

References 46 publications

The size‐dependent apoptotic effect of titanium dioxide nanoparticles on endothelial cells by the intracellular pathway

The size‐dependent apoptotic effect of titanium dioxide nanoparticles on endothelial cells by the intracellular pathway

Safety of titanium dioxide nanoparticles in cosmetics

Suppression of testosterone production by nanoparticulate TiO<sub>2</sub> is associated with ERK1/2-PKA-PKC signaling pathways in rat primary cultured Leydig cells

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