Lack of Significant Dermal Penetration of Titanium Dioxide from Sunscreen Formulations Containing Nano- and Submicron-Size TiO2 Particles

Abstract

Titanium dioxide (TiO(2)) is included in some sunscreen formulations to physically block ultraviolet radiation. A dermal penetration study was conducted in minipigs with three TiO(2) particles (uncoated submicron sized, uncoated nano-sized, and dimethicone/methicone copolymer-coated nanosized) applied 5% by weight in a sunscreen. These and control formulations were topically applied to minipigs at 2 mg cream/cm(2) skin (4 applications/day, 5 days/week, 4 weeks). Skin (multiple sites), lymph nodes, liver, spleen, and kidneys were removed, and the TiO(2) content was determined (as titanium) using inductively coupled plasma mass spectroscopy. Titanium levels in lymph nodes and liver from treated animals were not increased over the values in control animals. The epidermis from minipigs treated with sunscreens containing TiO(2) showed elevated titanium. Increased titanium was detected in abdominal and neck dermis of minipigs treated with uncoated and coated nanoscale TiO(2). Using electron microscopy-energy dispersive x-ray analysis, all three types of TiO(2) particles were found in the stratum corneum and upper follicular lumens in all treated skin samples (more particles visible with coated nanoscale TiO(2)). Isolated titanium particles were also present at various locations in the dermis of animals treated with all three types of TiO(2)-containing sunscreens; however, there was no pattern of distribution or pathology suggesting the particles could be the result of contamination. At most, the few isolated particles represent a tiny fraction of the total amount of applied TiO(2). These findings indicate that there is no significant penetration of TiO(2) nanoparticles through the intact normal epidermis.

Perturbation of physiological systems by nanoparticles

“…For example, after four weeks of exposure of minipigs to TiO 2 nanoparticles in sunscreen, a small number of the TiO 2 nanoparticles migrated to the dermis, but they did not enter the circulatory system. 327 After exposure of hairless mice to TiO 2 with hydrophobic or hydrophilic surfaces of different sizes (10,25, and 60 nm) for 60 days, the nanoparticles penetrated the skin, entered the circulation, and accumulated in the spleen, heart, and liver. Pathological lesions caused by oxidative stress were found in the skin and liver.…”

Protección solar en el paciente pediátrico

“…1,2,7 Los protectores solares con filtros orgánicos pueden penetrar la piel en bajas cantidades (0.1 a 5%) mientras que los que poseen filtros inorgánicos no penetran la piel, incluso con su aplicación en nanopartículas pues su penetración se limita al estrato córneo. 8 Con el uso de filtros orgánicos se han descrito algunas reacciones adversas leves, fundamentalmente dermatitis por contacto o fotoalergia, principalmente con el uso de benzofenona y octilmetoxicinamato. 9 La posibilidad de deficiencia de vitamina D debida al uso adecuado de protectores solares aún es controvertida, aunque la mayoría de los autores ha demostrado que el uso de protectores solares a largo plazo tiene un efecto mínimo o ninguno en las concentraciones de vitamina D o en su función.los conocimientos sobre fotoprotección van aumentando con la edad, los comportamientos se van deteriorando y señalan la necesidad de cambiar las actitudes hacia la exposición solar y el bronceado.…”

Inorganic UV filters

“…TiO 2 is declared safe in concentrations up to 25% of the formulation by weight, both by ANVISA and the United States Pharmacopeia (USP) (Sadrieh et al, 2010).…”

“…TiO 2 has three crystalline forms, named anatase, rutile and brookite (Sadrieh et al, 2010), but only anatase and rutile are useful for sunscreen formulations (Serpone, Dondi, Albini, 2007). Anatase is the most photoactive polymorphic form of TiO 2 , having a higher photocatalytic activity than rutile.…”

“…This is due to two special properties of these materials: the first is the large size of the particles (above 200 nm), allowing reflection not only of UV radiation but also of visible light (wavelength between 400 -700 nm), and the second property, which is immutable, is their high refraction index (2.6 for TiO 2 and 1.9 for ZnO). Therefore, many manufacturers are producing micronized or sub-micronized inorganic UV filters (nanosized particles), because reducing the particle size improves the appearance of commercial sunscreens and enhances radiation absorption, enabling their utilization in cosmetic formulations such as lotions and emulsions for sunscreens (Kiss et al, 2008;Sadrieh et al, 2010;Serpone, Dondi, Albini, 2007;Wang, Balagula, Osterwalder, 2010). Particle sizes between 15 and 50 nm can display a less opaque appearance, due to their poor capacity to reflect UV-Vis radiation (Allen et al, 2002).…”