Lack of significant dermal penetration of titanium dioxide from sunscreen formulations containing nano- and submicron-size TiO2 particles

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Topical
  • Animals
  • Chemistry, Pharmaceutical / methods
  • Electron Probe Microanalysis
  • Female
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Lymph Nodes / drug effects
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Mass Spectrometry
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Nanoparticles
  • Particle Size
  • Permeability
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / ultrastructure
  • Skin Absorption / drug effects*
  • Sunscreening Agents / pharmacokinetics*
  • Sunscreening Agents / pharmacology
  • Swine
  • Swine, Miniature / physiology
  • Titanium / pharmacokinetics*
  • Titanium / pharmacology


  • Sunscreening Agents
  • titanium dioxide
  • Titanium