Focus on skin as a possible port of entry for solid nanoparticles and the toxicological impact.

Today, various anthropogenic sources account for an increasing atmospheric nanoparticle (NP) concentration and thus increase of human exposure to NPs. The situation may become problematic since commercial applications of nanotechnology expand more rapidly than the scientific knowledge on NP exposure. This review focuses on skin as a route of exposure for NPs and the toxicological impact in skin with special attention to physicochemical properties of NPs and skin. We will review data published on NP skin penetration, toxicological issues and on physicochemical NP characterisation. NPs are reported to be localised mainly in hair follicle openings and on the stratum corneum surface. Some studies report the localisation of NPs in the deeper layers of the stratum corneum, the viable epidermis and deeper hair follicle parts. Sporadically, penetration into the dermis is reported for 4 to 5 nm sized quantum dots. NP interactions with epidermal and dermal cells may cause cytotoxicity and undesired immune responses, especially in damaged skin. NP characteristics promoting skin penetration are still unclear. For sunscreen NP substances there are indications for cytotoxicity (TiO2) and genotoxicity (ZnO). Significant data gaps comprise skin penetration and toxicological areas of (metal) particles smaller than 10 nm. The importance of skin barrier function in NP exposure is underlined by NP's skin cell damaging potential. Although NP skin studies display, increasingly, a multidisciplinary character (penetration, toxicity studies) the results are often contradicting. Standardisation of available test systems for NPs and focusing on the correlating physicochemical NP properties to penetration potential is recommended.