Titanium dioxide (TiO2) has for decades been approved for use in sunscreens as a physical sunblock. It is not known whether reducing the size of TiO2 particles in sunscreens creates new issues of safety and/or effectiveness. A study was therefore conducted to investigate the relative risk of skin penetration by TiO2 nanoparticles in healthy fair-skinned individuals.
The protocol for the study was approved by the Research Involving Human Subjects Committee of the US Food and Drug Administration, and informed written consent was obtained from each of the study participants. The participants were 6 fair-skinned individuals with phototypes II and III skin as defined by a UV-sensitivity questionnaire 1 and dermatological evaluation, who were recruited from the Washington, DC area. Daily applications of sunscreen with and without TiO2 nanoparticles at a concentration of 2 mg/cm2 were made to 2 test sites (5 x 5 cm) on the lower back of each participant, with a separate site as an untreated control. Except for the absence of tocopheryl acetate, the 2 custom-prepared sunscreen formulations used in the study (sunscreen with uncoated TiO2 nanoparticles [sunscreen plus TiO2] and [sunscreen only]) were identical to previously reported formulations.2 The sunscreens were applied once daily for 3 days to 2 of the participants. To further detect penetration of TiO2 nanoparticles, sunscreen was applied once-daily for 8 days to the 4 other participants. One day after the final sunscreen application, 5 shave biopsy specimens were acquired from each participant (2 from the sunscreen plus TiO2 site, 2 from the sunscreen-only site; and 1 from the control site). Details of the procedures for biopsy and tissue specimen processing, and of the biomarkers for immunohistochemistry, have been described,3 as have details of the biopsy-sample preparation for electron microscopy.2 Transmission electron microscopy was used to assess the penetration of TiO2 particles through epidermal-dermal skin layers. Confirmatory identification was done with scanning electron microscopy and energy dispersive X-ray spectroscopy (SEM-EDX) analysis as previously described.2
Coelho SG, Patri AK, Wokovich AM, McNeil SE, Howard PC, Miller SA. Repetitive Application of Sunscreen Containing Titanium Dioxide Nanoparticles on Human Skin. JAMA Dermatol. 2016;152(4):470-472. doi:10.1001/jamadermatol.2015.5944