The potential risks of nanomaterials: a review carried out for ECETOC

Abstract

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.

Figure 1

Illustration of the different sources and applications of ultrafine and Nanoparticles (NP). Epidemiology and toxicology have demonstrated acute effects of anthropogenic NP (= UFP) in humans, as well chronic effects of existing, manufactured NP in animals. It remains an open issue whether the hazards and risks found with those types of NP can be extrapolated to newly developed engineered NP.

Figure 2

Dispersed Nanoparticles are needed in order to retain their specific properties for the technological applications.

Figure 3

Scheme of NP production and possible exposure.

Figure 4

Scheme of particle characterization for exposure assessment.

Figure 5

Diagram to illustrate the likely relationship between the three main characteristics of combustion derived NP and their ability to cause inflammation.

Figure 6

Regional deposition of inhaled NP with diameters between 1 nm and 1000 nm for nose and for mouth breathing in the extrathoracic airways (ET), the bronchial airways (Bb) and the alveolar region (AI) during breathing at rest, as predicted by ICRP 66 model (ICRP, 1994).

Figure 7

Penetration pathways of topically applied substances through the skin.

Figure 8

In vivo investigation of the distribution of a formulation containing ethanol (left picture) and Nanoparticles (right picture) on the surface of human skin.

Figure 9

Penetration of NP-size coated titanium dioxide into the horny layer 1 hour after long-term sunscreen application.

Figure 10

Superposition of the transmission and fluorescence image of a pilosebaceous orifice on a 25th removed tape strip stained with OsO₄ obtained by laser scanning microscopy, the distribution of titanium dioxide coating inside the mark of a pilosebaceous orifice is seen as red spots.

Figure 11

Schematic presentation of potential interactions between Nanoparticles and proteins. The first example shows the intended (covalent) binding of a protein to an NP as a drug-delivery-tool. The second example shows how proteins may absorb on the NP surface, thereby masking the particle properties and loosing functional protein. The third example shows how NP can bind and breakdown proteins, through their active surface area [15].