Vicki Stone

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.

Carbon nanotubes (CNT) are an important new class of technological materials that have numerous novel and useful properties. The forecast increase in manufacture makes it likely that increasing human exposure will occur, and as a result, CNT are beginning to come under toxicological scrutiny. This review seeks to set out the toxicological paradigms applicable to the toxicity of inhaled CNT, building on the toxicological database on nanoparticles (NP) and fibers. Relevant workplace regulation regarding exposure is also considered in the light of our knowledge of CNT. CNT could have features of both NP and conventional fibers, and so the current paradigm for fiber toxicology, which is based on mineral fibers and synthetic vitreous fibers, is discussed. The NP toxicology paradigm is also discussed in relation to CNT. The available peer-reviewed literature suggests that CNT may have unusual toxicity properties. In particular, CNT seem to have a special ability to stimulate mesenchymal cell growth and to cause granuloma formation and fibrogenesis. In several studies, CNT have more adverse effects than the same mass of NP carbon and quartz, the latter a commonly used benchmark of particle toxicity. There is, however, no definitive inhalation study available that would avoid the potential for artifactual effects due to large mats and aggregates forming during instillation exposure procedures. Studies also show that CNT may exhibit some of their effects through oxidative stress and inflammation. CNT represent a group of particles that are growing in production and use, and therefore, research into their toxicology and safe use is warranted.

The rapid expansion of nanotechnology promises to have great benefits for society, yet there is increasing concern that human and environmental exposure to engineered nanomaterials may result in significant adverse effects. That is why the field of nanotoxicology – dealing with effects and potential risks of particulate structures <100 nm in size – has emerged, growing significantly over the past decade from long-standing foundations of well established knowledge on the toxicology of fibrous and non-fibrous particles and the interactions of viruses with cells. This review places nanoparticles in the context of conventional particle toxicology and so includes references to other types of particles, such as silica and asbestos, which have been extensively studied and can provide useful lessons relevant to newly engineered nanoparticles (NP). Discoveries of nanoparticle-specific concepts of toxicology related to their small size and large specific surface area go back to the early parts of the past century, although the distinctive biological effects and kinetics of NP were not recognized until the last decade of the past century. Today, the propensity of NP to cross cell barriers, enter cells and interact with subcellular structures is well established, as is the induction of oxidative stress as a major mechanism of nanoparticle effects. In addition to the significance of small size and surface area of NP, uncovering the impact of many other physico-chemical characteristics – in particular NP surface properties – for initiating effects in the mammalian organism and the environment is now an active area of research. The article aims to cover hazards relevant to humans, provides an introduction to some of the newly emerging literature on fate and behavior of NP in the environment, as well as describing their ecotoxicology in a variety of species. Major milestones in the research leading to our present understanding of nanotoxicology and the potential risks of NP to humans and the environment are summarized. These risks are likely to be different for different nanomaterials, ranging from perceived and very low for most, to real and very high for some. There are many questions that remain to be addressed, and we foresee for the future a continuing extended research in nanotoxicology. A full understanding of the hazard of NP will make a major contribution to the risk assessment that is so urgently needed to ensure that products that utilize NP are made safely, are exploited to their full potential and then disposed of safely.