Lack of significant dermal penetration of titanium dioxide from sunscreen formulations containing nano- and submicron-size TiO2 particles.

Titanium dioxide (TiO(2)) is included in some sunscreen formulations to physically block ultraviolet radiation. A dermal penetration study was conducted in minipigs with three TiO(2) particles (uncoated submicron sized, uncoated nano-sized, and dimethicone/methicone copolymer-coated nanosized) applied 5% by weight in a sunscreen. These and control formulations were topically applied to minipigs at 2 mg cream/cm(2) skin (4 applications/day, 5 days/week, 4 weeks). Skin (multiple sites), lymph nodes, liver, spleen, and kidneys were removed, and the TiO(2) content was determined (as titanium) using inductively coupled plasma mass spectroscopy. Titanium levels in lymph nodes and liver from treated animals were not increased over the values in control animals. The epidermis from minipigs treated with sunscreens containing TiO(2) showed elevated titanium. Increased titanium was detected in abdominal and neck dermis of minipigs treated with uncoated and coated nanoscale TiO(2). Using electron microscopy-energy dispersive x-ray analysis, all three types of TiO(2) particles were found in the stratum corneum and upper follicular lumens in all treated skin samples (more particles visible with coated nanoscale TiO(2)). Isolated titanium particles were also present at various locations in the dermis of animals treated with all three types of TiO(2)-containing sunscreens; however, there was no pattern of distribution or pathology suggesting the particles could be the result of contamination. At most, the few isolated particles represent a tiny fraction of the total amount of applied TiO(2). These findings indicate that there is no significant penetration of TiO(2) nanoparticles through the intact normal epidermis.

Quantitative determination of skin penetration of PEG-coated CdSe quantum dots in dermabraded but not intact SKH-1 hairless mouse skin.

Many cosmetics, sunscreens, and other consumer products are reported to contain nanoscale materials. The possible transdermal absorption of nanoscale materials and the long-term consequences of the absorption have not been determined. We used polyethylene glycol coated cadmium selenide (CdSe) core quantum dots (QD; 37 nm diameter) to evaluate the penetration of nanoscale material into intact, tape stripped, acetone treated, or dermabraded mouse skin. QD were suspended in an oil-in-water emulsion (approximately 9 microM) and the emulsion was applied at 2 mg/cm(2) to mouse dorsal skin pretreated as follows: intact; tape stripped to remove the stratum corneum; acetone pretreated; dermabraded to remove stratum corneum and epidermis. QD penetration into the skin was monitored in sentinel organs (liver and regional draining lymph nodes) using inductively coupled plasma mass spectrometry analysis of cadmium (from the CdSe QD). No consistent cadmium elevation was detected in the sentinel organs of mice with intact, acetone pretreated, or tape-stripped skin at 24- and 48-h post-QD application; however, in dermabraded mice, cadmium elevations were detected in the lymph nodes and liver. QD accumulation (as cadmium) in the liver was approximately 2.0% of the applied dose. The passing of QD through the dermabraded skin was confirmed using confocal fluorescence microscopy. These results suggest that transdermal absorption of nanoscale materials depends on skin barrier quality, and that the lack of an epidermis provided access to QD penetration. Future dermal risk assessments of nanoscale materials should consider key barrier aspects of skin and its overall physiologic integrity.

Migration of intradermally injected quantum dots to sentinel organs in mice.

Topical exposure to nanoscale materials is likely from a variety of sources including sunscreens and cosmetics. Because the in vivo disposition of nanoscale materials is not well understood, we have evaluated the distribution of quantum dots (QDs) following intradermal injection into female SKH-1 hairless mice as a model system for determining tissue localization following intradermal infiltration. The QD (CdSe core, CdS capped, poly[ethylene glycol] coated, 37 nm diameter, 621 nm fluorescence emission) were injected intradermally (ID) on the right dorsal flank. Within minutes following intradermal injection, the highly UV fluorescent QD could be observed moving from the injection sites apparently through the lymphatic duct system to regional lymph nodes. Residual fluorescent QD remained at the site of injection until necropsy at 24 h. Quantification of cadmium and selenium levels after 0, 4, 8, 12, or 24 h in multiple tissues, using inductively coupled plasma mass spectrometry (ICP-MS), showed a time-dependent loss of cadmium from the injection site, and accumulation in the liver, regional draining lymph nodes, kidney, spleen, and hepatic lymph node. Fluorescence microscopy corroborated the ICP-MS results regarding the tissue distribution of QD. The results indicated that (1) ID injected nanoscale QD remained as a deposit in skin and penetrated the surrounding viable subcutis, (2) QD were distributed to draining lymph nodes through the sc lymphatics and to the liver and other organs, and (3) sentinel organs are effective locations for monitoring transdermal penetration of nanoscale materials into animals.