Support for the Safe Use of Zinc Oxide Nanoparticle Sunscreens: Lack of Skin Penetration or Cellular Toxicity after Repeated Application in Volunteers

J Invest Dermatol. 2019 Feb;139(2):308-315. doi: 10.1016/j.jid.2018.08.024. Epub 2018 Nov 15.


Zinc oxide is a widely used broad-spectrum sunscreen, but concerns have been raised about the safety of its nanoparticle (NP) form. We studied the safety of repeated application of agglomerated zinc oxide (ZnO) NPs applied to human volunteers over 5 days by assessing the skin penetration of intact ZnO-NPs and zinc ions and measuring local skin toxicity. Multiphoton tomography with fluorescence lifetime imaging microscopy was used to directly visualize ZnO-NP skin penetration and viable epidermal metabolic changes in human volunteers. The fate of ZnO-NPs was also characterized in excised human skin in vitro. ZnO-NPs accumulated on the skin surface and within the skin furrows but did not enter or cause cellular toxicity in the viable epidermis. Zinc ion concentrations in the viable epidermis of excised human skin were slightly elevated. In conclusion, repeated application of ZnO-NPs to the skin, as used in global sunscreen products, appears to be safe, with no evidence of ZnO-NP penetration into the viable epidermis nor toxicity in the underlying viable epidermis. It was associated with the release and penetration of zinc ions into the skin, but this did not appear to cause local toxicity.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Fluoresceins / chemistry
  • Healthy Volunteers
  • Humans
  • Intravital Microscopy
  • Microscopy, Fluorescence, Multiphoton
  • Nanoparticles / administration & dosage*
  • Skin / diagnostic imaging
  • Skin / drug effects
  • Skin / metabolism*
  • Skin Absorption
  • Sunscreening Agents / administration & dosage
  • Sunscreening Agents / pharmacokinetics
  • Sunscreening Agents / toxicity*
  • Tissue Distribution
  • Tomography
  • Toxicity Tests, Subacute
  • Young Adult
  • Zinc Oxide / administration & dosage
  • Zinc Oxide / pharmacokinetics
  • Zinc Oxide / toxicity*


  • Fluoresceins
  • Sunscreening Agents
  • Zinc Oxide
  • zinpyr-1