Abstract
Despite a continuous increase of commercial products containing nanoparticles, only few materials are currently used in such large amounts, forms and sizes as titanium dioxide - TiO2. Besides its use in cosmetics, food industry and biomedicine, TiO2 nanoparticles (NPs) are also used as highly efficient photocatalysts due to their unique ability to convert complex organic materials to carbon dioxide, water and simple mineral acids via complex radical and electron transfer reactions. The main objective of the current project was to assess the potential dermal effect (phototoxicity and skin toxicity) of TiO2 nanosheets (TIG-800) synthesized from the lyophilized aqueous colloids of peroxo-titanic acid by high-temperature treatment. The effect was examined on reconstructed human skin model EpiDerm in the test pre-validated by ECVAM and adopted into the ICH S10 guidelines for the preclinical photo-safety assessment of drugs. In addition, two further commercial samples of nanocrystalline TiO2, namely Aeroxide P25 and Eusolex T-2000, and six benchmark materials from pre-validation studies were tested. None of the TiO2 NPs tested in the study caused acute phototoxicity or cytotoxicity in the reconstructed 3D tissues up to the highest concentration tested. The prediction of photo-irritation potency for the benchmark chemicals was comparable to previous studies. For some of the tested materials, we identified reasons for false negative results or variability in previously published datasets by improved dosing, conditions of irradiation, and choice of suitable solvents. The method proved its suitability for photo-irritation assessment of topically applied materials.
Highlights
Titanium dioxide (TiO2) has been widely used in a variety of industrial applications for decades and is considered an inert and safe material
In the current study, taking into account the occupational exposure scenario, we evaluated the dermal effects of TiO2 nanosheets (TIG-800) synthesized from lyophilized aqueous colloids of peroxo-polytitanic acid at a temperature of 800°C
Tissues were washed in Dulbecco’s phosphate-buffered saline solution (DPBS) and incubated at standard culture conditions (SCC) for 21 ±3 h
Summary
Titanium dioxide (TiO2) has been widely used in a variety of industrial applications for decades and is considered an inert and safe material. With the development of nanotechnologies and reported health risks caused by some nanoparticles (NPs), TiO2 in nano-form is under toxicological scrutiny. Mechanistic toxicological studies have shown that TiO2 nanoparticles predominantly cause adverse effects via induction of oxidative stress, resulting in cell damage, genotoxicity, inflammation and immune response. Studies on dermal exposure, conducted due to the wide use of TiO2 in cosmetics, as color additive and sunlight blocker, have shown repeatedly that TiO2, even in nano-form, has only minimal potential to penetrate healthy human skin and reach the bloodstream. It has been reported that TiO2 nanoparticles may be able to penetrate the skin surface through hair follicles or pores, but no details were given on the fate of such particles (Danish EPA, 2015)
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