During the last few years, research on toxicologically relevant properties of engineered nanoparticles has increased tremendously. A number of international research projects and additional activities are ongoing in the EU and the US, nourishing the expectation that more relevant technical and toxicological data will be published. Their widespread use allows for potential exposure to engineered nanoparticles during the whole lifecycle of a variety of products. When looking at possible exposure routes for manufactured Nanoparticles, inhalation, dermal and oral exposure are the most obvious, depending on the type of product in which Nanoparticles are used. This review shows that (1) Nanoparticles can deposit in the respiratory tract after inhalation. For a number of nanoparticles, oxidative stress-related inflammatory reactions have been observed. Tumour-related effects have only been observed in rats, and might be related to overload conditions. There are also a few reports that indicate uptake of nanoparticles in the brain via the olfactory epithelium. Nanoparticle translocation into the systemic circulation may occur after inhalation but conflicting evidence is present on the extent of translocation. These findings urge the need for additional studies to further elucidate these findings and to characterize the physiological impact. (2) There is currently little evidence from skin penetration studies that dermal applications of metal oxide nanoparticles used in sunscreens lead to systemic exposure. However, the question has been raised whether the usual testing with healthy, intact skin will be sufficient. (3) Uptake of nanoparticles in the gastrointestinal tract after oral uptake is a known phenomenon, of which use is intentionally made in the design of food and pharmacological components. Finally, this review indicates that only few specific nanoparticles have been investigated in a limited number of test systems and extrapolation of this data to other materials is not possible. Air pollution studies have generated indirect evidence for the role of combustion derived nanoparticles (CDNP) in driving adverse health effects in susceptible groups. Experimental studies with some bulk nanoparticles (carbon black, titanium dioxide, iron oxides) that have been used for decades suggest various adverse effects. However, engineered nanomaterials with new chemical and physical properties are being produced constantly and the toxicity of these is unknown. Therefore, despite the existing database on nanoparticles, no blanket statements about human toxicity can be given at this time. In addition, limited ecotoxicological data for nanomaterials precludes a systematic assessment of the impact of Nanoparticles on ecosystems.

Coated titanium dioxide (TiO₂) microparticles are commonly used as UV filter substances in commercial sunscreen products. The penetration of these microparticles into the horny layer and the orifice of the hair follicle was investigated. The distribution of the microparticles in the horny layer was analyzed using the method of tape stripping in combination with spectroscopic measurements. Deeper layers of the stratum corneum were devoid of TiO₂ even after repetitive application of sunscreen preparation when analyzing interfollicular areas. Only in the areas of the pilosebaceous orifices could microparticles be identified. The penetration of TiO₂ was investigated in histological skin sections. A biopsy was taken from a skin area from which the horny layer had been removed by tape stripping. In isolated areas, a penetration of coated TiO₂ into the open part of the follicle was observed. The amount of TiO₂ found in a given follicle was less than 1% of the applied total amount of sunscreens. A penetration of microparticles into viable skin tissue could not be detected.

Nanoparticles represent an important drug carrier system. Recently, we have reported on the penetration and storage behavior of particular and non-particular substances revealing the superiority of particular substances in the range of 300–400 nm. In this regard, it was assumed that the rigid hair shaft acts as a geared pump, moving the particles deeper into the hair follicle. In the present investigation, the storage reservoir capacity of the stratum corneum and the hair follicle infundibulum and canal are compared. Interestingly, we could demonstrate a 10 times longer storage within the hair follicles. These results underscore the importance of the hair follicle for drug delivery purposes, mainly highlighting new possibilities for the future concerning retarded delivery, application frequency, and galenic design.

In the past, it was assumed that the intercellular route was the only relevant penetration pathway for topically applied substances. Recent results on follicular penetration obtained at the Center for Experimental and Applied Cutaneous Physiology, Charité – Universitätsmedizin Berlin, Germany, emphasize that the hair follicles represent a highly relevant and efficient penetration pathway and reservoir for topically applied substances.