title: Safety evaluation of sunscreen formulations containing titanium dioxide and zinc oxide nanoparticles in UVB sunburned skin: an in vitro and in vivo study.
abstract: Sunscreens containing titanium dioxide (TiO(2)) and zinc oxide (ZnO) nanoparticles (NP) are effective barriers against ultraviolet B (UVB) damage to skin, although little is known about their disposition in UVB-damaged skin. Pigs were exposed to UVB that resulted in moderate sunburn. For in vitro studies, skin in flow-through diffusion cells were treated 24 h with four sunscreen formulations as follows: 10% coated TiO(2) in oil/water (o/w), 10% coated TiO(2) in water/oil (w/o), 5% coated ZnO in o/w, and 5% uncoated ZnO in o/w. TiO(2) (rutile, crystallite) primary particle size was 10 × 50 nm with mean agglomerates of 200 nm (range ca. 90 nm--460 nm); mean for ZnO was 140 nm (range ca. 60--200 nm). Skin was processed for light microscopy, scanning (SEM) and transmission electron microscopy (TEM), and time-of-flight secondary ion mass spectrometry (TOF-SIMS). UVB-exposed skin had typical sunburn histology. TEM showed TiO(2) NP 17 layers into stratum corneum (SC), whereas ZnO remained on the surface. TOF-SIMS showed TiO(2) and ZnO epidermal penetration in both treatments. Perfusate analyzed by TEM/energy dispersive x-ray spectroscopy or inductively coupled plasma mass spectrometry detected no Ti or Zn, indicating minimal transdermal absorption. In vivo, skin was dosed at 24 h occluded with formulations and at 48 h. TiO(2) NP in o/w formulation penetrated 13 layers into UVB-damaged SC, whereas only 7 layers in normal skin; TiO(2) in w/o penetrated deeper in UVB-damaged SC. Coated and uncoated Zn NP in o/w were localized to the upper one to two SC layers in all skin. By SEM, NP were localized as agglomerates in formulation on the skin surface and base of hair. TOF-SIMS showed Ti within epidermis and superficial dermis, whereas Zn was limited to SC and upper epidermis in both treatments. In summary, UVB-damaged skin slightly enhanced TiO(2) NP or ZnO NP penetration in sunscreen formulations but no transdermal absorption was detected.
authors.affiliation: Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, North Carolina 27606, USA. nancy_monteiro@ncsu.edu
authors.forename: N A
authors.initials: NA
authors.lastname: Monteiro-Riviere
authors.forename: K
authors.initials: K
authors.lastname: Wiench
authors.forename: R
authors.initials: R
authors.lastname: Landsiedel
authors.forename: S
authors.initials: S
authors.lastname: Schulte
authors.forename: A O
authors.initials: AO
authors.lastname: Inman
authors.forename: J E
authors.initials: JE
authors.lastname: Riviere
mesh_terms: D000818:Animals; D004890:Erythema / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D066298:In Vitro Techniques; D053768:Metal Nanoparticles / Q000528:radiation effects / Q000633:toxicity* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D012867:Skin / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects / Q000648:ultrastructure; D013471:Sunburn / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D013473:Sunscreening Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D013552:Swine / Q000502:physiology; D014025:Titanium / Q000493:pharmacokinetics / Q000528:radiation effects / Q000633:toxicity*; D014466:Ultraviolet Rays / Q000009:adverse effects; D015034:Zinc Oxide / Q000493:pharmacokinetics / Q000528:radiation effects / Q000633:toxicity*
chemical_list: D013473:Sunscreening Agents; C009495:titanium dioxide; D014025:Titanium; D015034:Zinc Oxide