ZnO nanoparticles and organic chemical UV-filters are equally well tolerated by human immune cells

Nanotoxicology. 2016 Nov;10(9):1287-96. doi: 10.1080/17435390.2016.1206148. Epub 2016 Jul 19.


An important part of assessing the toxic potential of nanoparticles for specific applications should be the direct comparison of biological activities with those of alternative materials for the same application. Nanoparticulate inorganic ultraviolet (UV) filters, such as zinc oxide (ZnO), are commonly incorporated into transparent sunscreen and cosmetic formulations. However, concerns have been raised about potential unwanted effects, despite their negligible skin penetration and inherent advantages over organic chemical UV-filters. To provide useful application-relevant assessments of their potential hazard with/without UVA co-exposure, we directly compared cytotoxic and immune response profiles of human THP-1 monocytic cells to ZnO nanoparticles (30 nm) with bulk ZnO particulates (200 nm) and five conventional organic chemical UV-filters - butylmethoxydibenzoylmethane (avobenzone), octylmethoxycinnamate, octylsalicylate, homosalate and 4-methylbenzylidene camphor. High exposure concentrations of both organic and particulate UV-filters were required to cause cytotoxicity in monocyte and macrophage cultures after 24 h. Co-exposure with UVA (6.7 J/cm(2)) did not alter cytotoxicity profiles. Particle surface area-based dose responses showed that ZnO NPs were better tolerated than bulk ZnO. Organic and particulate UV-filters increased apoptosis at similar doses. Only particulates increased the generation of reactive oxygen species. Interleukin-8 (IL-8) release was increased by all particulates, avobenzone, homosalate and octylsalicylate. IL-1β release was only increased in macrophages by exposure to avobenzone and homosalate. In conclusion, direct effects were caused in monocytes and macrophages at similar concentrations of both organic UV-filters and ZnO nanoparticulates - indicating that their intrinsic cytotoxicity is similar. With their lower skin penetration, ZnO nanoparticles are expected to have lower bioactivity when used in sunscreens.

Keywords: Cytokine release; ROS; UVA; cytotoxicity; sunscreen.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Humans
  • Interleukin-8 / immunology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Nanoparticles / chemistry
  • Nanoparticles / toxicity*
  • Organic Chemicals / chemistry
  • Organic Chemicals / toxicity*
  • Reactive Oxygen Species / metabolism
  • Skin / drug effects
  • Skin / immunology
  • Sunscreening Agents / chemistry
  • Sunscreening Agents / toxicity*
  • Zinc Oxide / chemistry
  • Zinc Oxide / toxicity*


  • CXCL8 protein, human
  • Interleukin-8
  • Organic Chemicals
  • Reactive Oxygen Species
  • Sunscreening Agents
  • Zinc Oxide