Toxicity assessment of six titanium dioxide nanoparticles in human epidermal keratinocytes

Abstract Purpose The aim of this study was to evaluate and compare the toxicity of six different types of titanium dioxide (TiO2) nanoparticles (NP) on human epidermal keratinocytes (HEK). Materials and methods Six TiO2 NP (A (10 nm), A*(32 nm), B (27.5 nm), C (200 nm), C*(30–40 nm), and D*(200–400 nm)) were suspended in water or culture medium and characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). In addition, these NP were assayed with cell viability, cytokine release and cellular uptake in HEK. Results TiO2NP did not change in shape in the culture medium when visualized by TEM. There was an increase in agglomeration with all TiO2NP in the medium when measured by DLS. Since TiO2NP interfered with the CellTiter 96®AQueous One and MTT assays but had a minimal effect on alamar Blue (aB). The aB viability assay was selected to assess all six types of TiO2NP and sample B had a statistically significant decrease in viability at 0.4 mg/ml. A slight increase in TNF-α was noted in sample A*, C, and D* at as low as 0.05 mg/ml. Sample A* and B at certain concentrations showed an increase in Interleukin (IL)-6. IL-10 and IL-1β release for all TiO2NP were noted around the detection limit with no significant changes compared to control. A statistically significant decrease in IL-8 was noted for all TiO2NP at the highest concentrations due to the adsorption of IL-8 by TiO2. All TiO2NP were localized within cytoplasmic vacuoles of HEK and the element Ti was detected by energy-dispersive x-ray spectroscopy analysis. Conclusions Based on cell viability, only sample B was slightly cytotoxic to HEK and samples B and A* have the potential to cause inflammation indicated by an increase in IL-6.

[1]  Massimo Bovenzi,et al.  Titanium Dioxide Nanoparticle Penetration into the Skin and Effects on HaCaT Cells , 2015, International journal of environmental research and public health.

[2]  G. Adami,et al.  Nanoparticles skin absorption: New aspects for a safety profile evaluation. , 2015, Regulatory toxicology and pharmacology : RTP.

[3]  F. Rossi,et al.  Singlet oxygen plays a key role in the toxicity and DNA damage caused by nanometric TiO2 in human keratinocytes. , 2013, Nanoscale.

[4]  S. Hirakawa,et al.  Acicular, but not globular, titanium dioxide nanoparticles stimulate keratinocytes to produce pro‐inflammatory cytokines , 2013, The Journal of dermatology.

[5]  T. Egerton,et al.  UV absorption and scattering properties of inorganic‐based sunscreens , 2012, International journal of cosmetic science.

[6]  S. Schulte,et al.  Safety evaluation of sunscreen formulations containing titanium dioxide and zinc oxide nanoparticles in UVB sunburned skin: an in vitro and in vivo study. , 2011, Toxicological sciences : an official journal of the Society of Toxicology.

[7]  Wei Liu,et al.  Nano titanium dioxide induces the generation of ROS and potential damage in HaCaT cells under UVA irradiation. , 2010, Journal of nanoscience and nanotechnology.

[8]  Roberto Cingolani,et al.  Effects of cell culture media on the dynamic formation of protein-nanoparticle complexes and influence on the cellular response. , 2010, ACS nano.

[9]  S. Oldenburg,et al.  Interactions of aluminum nanoparticles with human epidermal keratinocytes , 2010, Journal of applied toxicology : JAT.

[10]  Tomas S Jonaitis,et al.  Concerns regarding nano-sized titanium dioxide dermal penetration and toxicity study. , 2010, Toxicology letters.

[11]  Wei Liu,et al.  Toxicity and penetration of TiO2 nanoparticles in hairless mice and porcine skin after subchronic dermal exposure. , 2009, Toxicology letters.

[12]  K. Amighi,et al.  In vitro evaluation of the cutaneous penetration of sprayable sunscreen emulsions with high concentrations of UV filters , 2009, International journal of cosmetic science.

[13]  N. Monteiro-Riviere,et al.  Limitations and relative utility of screening assays to assess engineered nanoparticle toxicity in a human cell line. , 2009, Toxicology and applied pharmacology.

[14]  Zita Szikszai,et al.  Investigation of micronized titanium dioxide penetration in human skin xenografts and its effect on cellular functions of human skin‐derived cells , 2008, Experimental dermatology.

[15]  N. Monteiro-Riviere,et al.  Assessment of Quantum Dot Penetration into Intact, Tape-Stripped, Abraded and Flexed Rat Skin , 2008, Skin Pharmacology and Physiology.

[16]  William W. Yu,et al.  Biological interactions of quantum dot nanoparticles in skin and in human epidermal keratinocytes. , 2008, Toxicology and applied pharmacology.

[17]  A. Barron,et al.  Biological Interactions of Functionalized Single-Wall Carbon Nanotubes in Human Epidermal Keratinocytes , 2007, International journal of toxicology.

[18]  Z. Chai,et al.  Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration. , 2007, Toxicology letters.

[19]  Nancy A. Monteiro-Riviere,et al.  Challenges for assessing carbon nanomaterial toxicity to the skin , 2006 .

[20]  R. Wepf,et al.  The Outermost Stratum Corneum Layer is an Effective Barrier Against Dermal Uptake of Topically Applied Micronized Titanium Dioxide , 1999, International journal of cosmetic science.