Pulmonary impact of titanium dioxide nanorods: examination of nanorod-exposed rat lungs and human alveolar cells (original) (raw)

Toxicological Effects of Titanium Dioxide Nanoparticles: A Review of In Vivo Studies

Journal of Nanomaterials, 2012

The essence of nanotechnology is the production of nanoparticles (NPs) with unique physicochemical properties allowing worldwide application in new structures, materials, and devices. The consequently increasing human exposure to NPs has raised concerns regarding their health and safety profiles. Titanium dioxide (TiO2) has been reported to induce adverse pulmonary responses in exposed animals. However, the potential more dangerous biological activities of TiO2NPs compared to their fine-sized counterparts are not fully understood. Therefore, this work is aimed to provide a comprehensive evaluation of the toxic effects induced by TiO2NPs inin vivoexperiments. It is intended to deeply understand the toxicological behaviour of TiO2NPs and to predict potential human health effects. Moreover, it may be an instrument to extrapolate relevant data for human risk evaluation and management and to identify those critical aspects that deserve great attention in future population and epidemiolog...

The effects of Nano titanium dioxide (TiO2NPs) on lung tissue

Bratislava Medical Journal, 2015

OBJECTIVES: The application of nanoparticles is widely spread in all aspects of modern life because of their unique features such as small size and high surface area. High surface area can be very reactive and produce reactive oxygen species (ROS). These nanoparticles can damage human and animal cells by increasing oxidative stress mechanism. Titanium dioxide nanoparticles (TiO 2 NPs) are among the top fi ve nanoparticles used in consumer products, paints, and pharmaceutical preparations.TiO 2 NPs have various capabilities such as robust oxidation, biocompatibility and photocatalytic properties. They are frequently used in a wide range of sciences, including pharmaceuticals, cosmetics, medicine and engineering. The ever increasing industrial and consumer applications of TiO 2 NPs raise concern over the possible risk association with their environmental exposure. METHODS: This study investigates the effects of TiO 2 NP on lung tissue by intraperitoneal injection to rats at different doses (15, 30, 60 and 70 mg/kg). RESULTS: Our results showed that intraperitoneal injection of TiO 2 NP creates capillary congestion and hemorrhage in alveolar wall, granulomas in lung parenchyma, and hemosiderin depositions in blood vessels adjacent to bronchioles without any infl ammation. The pulmonary side effects could be due to the production of ROS post TiO 2 NP exposure (Tab. 1, Fig. 5, Ref. 27).

The potential health challenges of TiO 2 nanomaterials

Titanium dioxide (TiO 2 ) nanomaterials (NMs) have found widespread applications owing to their attractive physical and chemical properties. As a result, the potential adverse impacts of nano-TiO 2 exposure on humans have become a matter of concern. This review presents the state-of-the-art advances on the investigations of the adverse effects of NMs, including the potential exposure routes of nano-TiO 2 (e.g. respiratory system, skin absorption and digestive system), the physico-chemical characterizations of nano-TiO 2 (e.g. crystal structure, shape,size, zeta potential, treatment media, aggregation and agglomeration tendency, surface characteristics and coatings), risk evaluation of nanotoxicity (e.g. cytotoxicity, ecotoxicity, phototoxicity, and phytotoxicity) and potential mechanisms of adverse effects (e.g. generation of reactive oxygen species, oxidative stress and organelle dysfunction). The review aims to facilitate scientific assessments of health risks to nano-TiO 2 , which would guide the safe applications of NMs in our daily life.

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

Toxicology Letters, 2017

The kinetics of TiO 2 nanoparticles was studied in rats after a 6-h inhalation. TiO 2 persisted in lungs, where highest tissue levels were found. TiO 2 in lungs reached peak values only at 48 h and levels decreased over 14 days. Fecal amounts suggest a mucociliary clearance of inhaled NPs and ingestion. A certain translocation to the olfactory bulb and the brain was also observed.

Toxicological Consequences of Titanium Dioxide Nanoparticles (TiO2NPs) and Their Jeopardy to Human Population

BioNanoScience

Titanium dioxide nanoparticles (TiO 2 NPs) are the most produced nanomaterial for food additives, pigments, photocatalysis, and personal care products. These nanomaterials are at the forefront of rapidly developing indispensable nanotechnology. In all these nanomaterials, titanium dioxide (TiO 2) is the most common nanomaterial which is being synthesized for many years. These nanoparticles of TiO 2 are widely used at the commercial level, especially in cosmetic industries. High usage in such a way has increased the toxicological consequences of the human population. Several studies have shown that TiO 2 NPs accumulated after oral exposure or inhalation in the alimentary canal, lungs, heart, liver, spleen, cardiac muscle, and kidneys. Additionally, in mice and rats, they disturb glucose and lipid homeostasis. Moreover, TiO 2 nanoparticles primarily cause adverse reactions by inducing oxidative stress that leads to cell damage, inflammation, genotoxicity, and adverse immune responses. The form and level of destruction are strongly based on the physical and chemical properties of TiO 2 nanoparticles, which administer their reactivity and bioavailability. Studies give indications that TiO 2 NPs cause both DNA strand breaks and chromosomal damages. The effects of genotoxicity do not depend only on particle surface changes, size, and exposure route, but also relies on the duration of exposure. Most of these effects may be because of a very high dose of TiO 2 NPs. Despite increased production and use, epidemiological data for TiO 2 NPs is still missing. This review discusses previous research regarding the impact of TiO 2 NP toxicity on human health and highlights areas that require further understanding in concern of jeopardy to the human population. This review is important to point out areas where extensive research is needed; thus, their possible impact on individual health should be investigated in more details.

Toxicity of TiO2 Nanoparticles: Validation of Alternative Models

International Journal of Molecular Sciences

There are many studies concerning titanium dioxide (TiO2) nanoparticles (NP) toxicity. Nevertheless, there are few publications comparing in vitro and in vivo exposure, and even less comparing air–liquid interface exposure (ALI) with other in vitro and in vivo exposures. The identification and validation of common markers under different exposure conditions are relevant for the development of smart and quick nanotoxicity tests. In this work, cell viability was assessed in vitro by WST-1 and LDH assays after the exposure of NR8383 cells to TiO2 NP sample. To evaluate in vitro gene expression profile, NR8383 cells were exposed to TiO2 NP during 4 h at 3 cm2 of TiO2 NP/cm2 of cells or 19 μg/mL, in two settings—submerged cultures and ALI. For the in vivo study, Fischer 344 rats were exposed by inhalation to a nanostructured aerosol at a concentration of 10 mg/m3, 6 h/day, 5 days/week for 4 weeks. This was followed immediately by gene expression analysis. The results showed a low cytotox...

Presence of Titanium and Toxic Effects Observed in Rat Lungs, Kidneys, and Central Nervous System in vivo and in Cultured Astrocytes in vitro on Exposure by Titanium Dioxide Nanorods

International Journal of Nanomedicine

Background: Non-spherical titanium dioxide (TiO 2) nanoparticles have been increasingly applied in various biomedical and technological fields. Their toxicological characterization is, however, less complete than that of roundish nanoparticles. Materials and Methods: Anatase form TiO 2 nanorods, ca. 15x65 nm in size, were applied to cultured astrocytes in vitro and to the airways of young adult Wistar rats in vivo in 5, 10, and 8 mg/kg BW dose for altogether 28 days. Presence of nanorods and cellular damage was investigated in the astrocytes and in rat lungs and kidneys. Functional damage of the nervous system was studied by electrophysiological methods. Results: The treated astrocytes showed loss of viability without detectable apoptosis. In rats, TiO 2 nanorods applied to the airways reached the blood and various organs including the lungs, kidneys, and the central nervous system. In lung and kidney samples, nanorods were observed within (partly damaged) phagolysosomes and attached to organelles, and apoptotic cell death was also detected. In cortical and peripheral electrophysiological activity, alterations corresponding to energy shortage (resulting possibly from mitochondrial damage) and astrocytic dysfunction were detected. Local titanium levels and relative weight of the investigated organs, apoptotic cell death in the lungs and kidneys, and changes in the central and peripheral nervous activity were mostly proportional to the applied doses, and viability loss of the cultured astrocytes was also dose-dependent, suggesting causal relationship of treatments and effects. Conclusion: Based on localization of the visualized nanorods, on neuro-functional changes, and on literature data, the toxic mechanism involved mitochondrial damage, oxidative stress, and apoptotic cell death. These indicate potential human toxicity and occupational risk in case of exposure to rod-shaped TiO 2 nanoparticles.

Surface modification does not influence the genotoxic and inflammatory effects of TiO2 nanoparticles after pulmonary exposure by instillation in mice

Mutagenesis, 2017

The influence of surface charge of nanomaterials on toxicological effects is not yet fully understood. We investigated the inflammatory response, the acute phase response and the genotoxic effect of two different titanium dioxide nanoparticles (TiO2 NPs) following a single intratracheal instillation. NRCWE-001 was unmodified rutile TiO2 with endogenous negative surface charge, whereas NRCWE-002 was surface modified to be positively charged. C57BL/6J BomTac mice received 18, 54 and 162 µg/mouse and were humanely killed 1, 3 and 28 days post-exposure. Vehicle controls were tested alongside for comparison. The cellular composition and protein concentration were determined in bronchoalveolar lavage (BAL) fluid as markers for an inflammatory response. Pulmonary and systemic genotoxicity was analysed by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The pulmonary and hepatic acute phase response was analysed by Saa3 mRNA levels in lung tissue or Saa1 mR...

Titanium dioxide nanoparticles: some aspects of toxicity/focus on the development

Endocrine Regulations, 2015

Nanosized titanium dioxide (TiO2) particles belong to the most widely manufactured nanoparticles (NPs) on a global scale because of their photocatalytic properties and the related surface effects. TiO2 NPs are in the top five NPs used in consumer products. Ultrafine TiO2 is widely used in the number of applications, including white pigment in paint, ceramics, food additive, food packaging material, sunscreens, cosmetic creams, and, component of surgical implants. Data evidencing rapid distribution, slow or ineffective elimination, and potential long-time tissue accumulation are especially important for the human risk assessment of ultrafine TiO2 and represent new challenges to more responsibly investigate potential adverse effects by the action of TiO2 NPs considering their ubiquitous exposure in various doses. Transport of ultrafine TiO2 particles in systemic circulation and further transition through barriers, especially the placental and blood-brain ones, are well documented. Therefore, from the developmental point of view, there is a raising concern in the exposure to TiO2 NPs during critical windows, in the pregnancy or the lactation period, and the fact that human mothers, women and men in fertile age and last but not least children may be exposed to high cumulative doses. In this review, toxicokinetics and particularly toxicity of TiO2 NPs in relation to the developing processes, oriented mainly on the development of the central nervous system, are discussed Keywords: nanoparticles, nanotoxicity, nanomaterials, titanium dioxide, reproductive toxicity, developmental toxicity, blood brain barrier, placental barrier.