Also, in a recent study of the interactions of ZnO nanoparticles with the tumor suppressor p53, Ng et al. found that the p53 pathway was activated in BJ cells (skin fibroblasts) upon treatment with ZnO nanoparticles, leading to a reduction in cell numbers. One implication of this response, the researchers concluded, was that in cells lacking robust p53, the protective response can be turned toward carcinogenesis due to exposure to DNA damage–inducing agents like ZnO nanoparticles (Biomaterials 2011;32:8218-25).
Weight of evidence
However, several researchers contend that current data strongly suggest that nanosized ZnO and TiO2 do not, in fact, pose such risks (Photodermatol. Photoimmunol. Photomed. 2011;27:58-67; Int. J. Dermatol. 2011;50:247-54; Sem. Cutan. Med. Surg. 2011;30:210-13).
In 2009, in response to increasing concerns about the potential adverse effects of ZnO- and TiO2-coated nanoparticles used in physical sunblocks, Filipe et al. evaluated the localization and possible skin penetration of these nanoparticles in three sunscreen formulations under realistic in vivo conditions in normal and altered skin. They tested a hydrophobic formulation containing coated 20-nm TiO2 nanoparticles and two commercially available formulations containing TiO2 alone or in combination with ZnO. The goal was to assess how consumers actually use sunscreens in comparison to the recommended standard condition for the sun protection factor test. Traces of the physical blockers could only be detected at the skin surface and uppermost area of the SC in normal human skin after a 2-hour exposure. No ZnO or TiO2 nanoparticles could be detected in layers deeper than the SC after 48 hours of exposure. The investigators concluded that significant penetration by ZnO or TiO2 nanoparticles into keratinocytes is unlikely (Skin Pharmacol. Physiol. 2009;22:266-75).
According to a safety review by Schilling et al., the current evidence implies that there are minimal risks to human health posed from the use of ZnO or TiO2 nanoparticles at concentrations of up to 25% in cosmetic preparations or sunscreens, regardless of coatings or crystalline structure. The researchers observed that these nanoparticles incorporated in topical products occur as aggregates of primary particles 30-150 nm in size that bond in a way that leaves them impervious to the force of product application. Consequently, their structure is unaffected, and no primary particles are released (Photochem. Photobiol. Sci. 2010;9:495-509).
Newman et al. reviewed studies and position statements from 1980 to 2008 in order to characterize the safety, use, and regulatory conditions related to nanosized ZnO and TiO2 in sunscreens. They reported that, while no data suggested significant penetration of the particles beyond the SC, there is a need for additional studies simulating real-world conditions, especially related to UV exposure and sunburned skin (J. Am. Acad. Dermatol. 2009;61:685-92).
In 2011, Monteiro-Riviere et al. performed in vitro and in vivo studies in which pigs received moderate sunburn from UVB exposure. The researchers found that UVB-damaged skin slightly mediated ZnO or TiO2 nanoparticle penetration in multiple tested sunscreen formulations, but they observed no transdermal absorption (Toxicol. Sci. 2011;123:264-80).
Conclusion
Zinc oxide has long been used as one of the two primary inorganic physical sunscreens. Its use in nanoparticle form has appeared effective, but the different physicochemical qualities of the metal oxide in nanosized form have prompted questions regarding safety. Current data suggest minimal risk to intact skin, but additional studies are needed.
Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in Miami Beach. She founded the cosmetic dermatology center at the University of Miami in 1997. Dr. Baumann wrote the textbook "Cosmetic Dermatology: Principles and Practice" (McGraw-Hill, April 2002), and a book for consumers, "The Skin Type Solution" (Bantam, 2006). She has contributed to the Cosmeceutical Critique column in Skin & Allergy News since January 2001 and joined the editorial advisory board in 2004. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Galderma, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Stiefel, Topix Pharmaceuticals, and Unilever.