Long-term exposure to commercially available sunscreens containing nanoparticles of TiO2 and ZnO revealed no biological impact in a hairless mouse model.

BACKGROUND: The application of sunscreen is a critical component of a sun-safe strategy, however the possibility of unexpected, adverse outcomes resulting from long-term use of sunscreens containing nanoparticles of titanium dioxide (TiO2) and zinc oxide (ZnO) has not yet been examined. Here, immune-competent hairless mice were exposed over a 36-week period to weekly topical applications of sunscreens containing nanoparticles of ZnO or TiO2, or no metal oxide nanoparticles, with or without subsequent exposure to ultraviolet radiation (UVR). Control groups received no sunscreen applications, with or without UVR. RESULTS: Mice exposed to UVR in the absence of sunscreen developed statistically significant incidences of histologically-diagnosed malignant and benign skin neoplasms, whereas no statistically significant adverse biological outcomes were found in mice treated with the sunscreens containing ZnO or TiO2 nanoparticles. Elevated levels of Ti were detected in the livers of mice treated with sunscreen containing TiO2 nanoparticles compared to untreated control, but total Zn concentrations did not significantly alter in any major organs except for the skin of mice treated with ZnO sunscreen. Exposure to UVR did not have a significant impact on examined tissue concentrations of Zn or Ti. Few to no transcriptional changes were found in ZnO or TiO2-treated groups, but mice treated with the sunscreen containing only organic filters showed substantial gene disregulation. CONCLUSIONS: Taken together with previous work, this long-term study provided no basis to avoid the use of sunscreens containing metal oxide nanoparticles.

Comparison of dermal absorption of zinc from different sunscreen formulations and differing UV exposure based on stable isotope tracing.

In a pilot study to determine if zinc (Zn) from zinc oxide nanoparticles in sunscreen can penetrate human skin in vivo, nanoparticles (~30nm) of a stable isotope (52% (68)Zn enrichment) were incorporated into an essentially phytochemical-based formulation and applied to the backs of 3 human subjects twice daily for 5 days during the Southern Hemisphere winter. Blood and urine were collected prior to application and at regular intervals and up to 50 days. As observed in a larger outdoor trial following this pilot study but with a different formulation and with UV exposure: values of (68)Zn in blood continued to increase beyond the 5 day application phase with the highest measurement at 14 days after the first application; variable amounts of the (68)Zn tracer were observed in urine; and the amounts of extra Zn added to blood were small and indicate very low levels of absorption (minimal estimate <0.01% of the applied dose) through the skin. Reasons for differences in absorption detected in the stable isotope trials and previous investigations include: the sensitivity of the stable isotope method; the duration of the investigations; the number of applications of sunscreen formulation; in vitro methods with excised skin; lack of measurement of blood and urine; no skin flexing; and lack of UV exposure.

Small amounts of zinc from zinc oxide particles in sunscreens applied outdoors are absorbed through human skin.

Metal oxide nanoparticles are commonly used in personal-care formulations as protective agents against exposure to ultraviolet radiation. Although previous research has concluded that nanoparticles do not penetrate healthy skin, it remains contentious whether this conclusion holds under normal conditions of sunscreen use. Humans (n = 20) were exposed to sunscreens containing zinc oxide (ZnO) particles to determine if Zn from the particles was absorbed through skin over five consecutive days under outdoor conditions. Two sunscreens were tested-"nano sunscreen" containing 19-nm nanoparticles and "bulk sunscreen" containing > 100-nm particles. Venous blood and urine samples were collected 8 days before exposure, twice daily during the trial, and 6 days post-exposure. As the first application in nanotechnology studies, stable isotope tracing was used where the ZnO, enriched to > 99% with the stable isotope (68)Zn, allowed dermally absorbed zinc to be distinguished from naturally occurring zinc. The overwhelming majority of applied (68)Zn was not absorbed, although blood and urine samples from all subjects exhibited small increases in levels of tracer (68)Zn. The amount of tracer detected in blood after the 5-day application period was ∼1/1000 th that of total Zn in the blood compartment. Tracer levels in blood continued to increase beyond the 5-day application phase in contrast to those in urine. Levels of (68)Zn in blood and urine from females receiving the nano sunscreen appeared to be higher than males receiving the same treatment and higher than all subjects receiving the bulk sunscreen. It is not known whether (68)Zn has been absorbed as ZnO particles or soluble Zn or both.

UV light from 290 to 325 nm, but not broad-band UVA or visible light, augments the formation of melanocytic nevi in a guinea-pig model for human nevi.

We have previously described a guinea-pig model where pigmented nevi similar to human nevi can be produced by application of low-dose topical 7,12-dimethylbenzanthracene (DMBA) followed by solar-simulated light. Five groups of guinea-pigs were used to test the effect of various spectral bands of solar-simulated light on low-dose DMBA-induced melanocytic nevi. Animals were irradiated with either UVB to near UVA2 (290-325 nm), UVA, visible light, full solar spectrum or no irradiation three times per wk for 12 mo to determine the broad-band effect of nevi-inducing irradiation. There was a significant increase in nevi/animal in the UVB-treated group (mean 1.53) compared with all groups (versus UVA 0.3, p<0.001; versus visible light 0.24, p<0.001; versus full spectrum (UVB+UVA+visible) 0.68, p=0.02; versus control (nil irradiation) 0.37, p=0.01). No differences in skin thickness were found between any group (p=0.11). In conclusion, we present a report of the active waveband of melanocytic nevi induction; where UVB to near UVA2 is the likely responsible waveband. Furthermore, because there was a significant decrease in nevi/animal receiving the full solar spectrum compared with the UVB group, it is possible that broad-band UVA and or visible light may be inhibitory wavebands for nevi induction.