Office of Pharmaceutical Science, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland 20993, USA.
Toxicol Sci. 2010 May;115(1):156-66. doi: 10.1093/toxsci/kfq041. Epub 2010 Feb 15.
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.
二氧化钛（TiO(2)）被包含在一些防晒霜配方中，以物理方式阻挡紫外线辐射。在小型猪中进行了一项二氧化钛（TiO(2)）的经皮渗透研究，将三种 TiO(2)颗粒（未涂层亚微米级、未涂层纳米级和二甲硅油/硅酮共聚物涂层纳米级）以 5%的重量应用于防晒霜中。这些和对照配方以 2 mg 霜/cm(2)皮肤（每天 4 次，每周 5 天）的剂量局部应用于小型猪。去除皮肤（多个部位）、淋巴结、肝、脾和肾，并使用电感耦合等离子体质谱法（ICP-MS）测定 TiO(2)含量（以钛计）。处理动物的淋巴结和肝脏中的钛水平没有高于对照动物的值。用含有 TiO(2)的防晒霜处理的小型猪的表皮显示出升高的钛含量。用未涂层和涂层纳米级 TiO(2)处理的小型猪的腹部和颈部真皮中检测到钛含量增加。使用电子显微镜-能量色散 X 射线分析，在所有处理的皮肤样本的角质层和上毛囊腔中都发现了所有三种类型的 TiO(2)颗粒（用涂层纳米级 TiO(2)可观察到更多颗粒）。在所有三种类型的含 TiO(2)防晒霜处理的动物的真皮的不同部位也存在分离的钛颗粒；然而，没有分布模式或病理学表明这些颗粒可能是污染的结果。在大多数情况下，少数分离的颗粒仅代表应用的 TiO(2)总量的一小部分。这些发现表明，纳米级 TiO(2)颗粒没有通过完整的正常表皮显著渗透。
