This review is concerned with evaluating the toxicity associated with human exposure to silver and gold nanoparticles (NPs), due to the relative abundance of toxicity data available for these particles, when compared to other metal particulates. This has allowed knowledge on the current understanding of the field to be gained, and has demonstrated where gaps in knowledge are. It is anticipated that evaluating the hazards associated with silver and gold particles will ultimately enable risk assessments to be completed, by combining this information with knowledge on the level of human exposure. The quantity of available hazard information for metals is greatest for silver particulates, due to its widespread inclusion within a number of diverse products (including clothes and wound dressings), which primarily arises from its antibacterial behaviour. Gold has been used on numerous occasions to assess the biodistribution and cellular uptake of NPs following exposure. Inflammatory, oxidative, genotoxic, and cytotoxic consequences are associated with silver particulate exposure, and are inherently linked. The primary site of gold and silver particulate accumulation has been consistently demonstrated to be the liver, and it is therefore relevant that a number of in vitro investigations have focused on this potential target organ. However, in general there is a lack of in vivo and in vitro toxicity information that allows correlations between the findings to be made. Instead a focus on the tissue distribution of particles following exposure is evident within the available literature, which can be useful in directing appropriate in vitro experimentation by revealing potential target sites of toxicity. The experimental design has the potential to impact on the toxicological observations, and in particular the use of excessively high particle concentrations has been observed. As witnessed for other particle types, gold and silver particle sizes are influential in dictating the observed toxicity, with smaller particles exhibiting a greater response than their larger counterparts, and this is likely to be driven by differences in particle surface area, when administered at an equal-mass dose. A major obstacle, at present, is deciphering whether the responses related to silver nanoparticulate exposure derive from their small size, or particle dissolution contributes to the observed toxicity. Alternatively, a combination of both may be responsible, as the release of ions would be expected to be greater for smaller particles.

Due to the rapid development of a diverse array of nanoparticles, used in a wide variety of products, there are now many international activities to assess the potential toxicity of these materials. These particles are developed due to properties such as catalytic reactivity, high surface area, light emission properties, and others. Such properties have the potential to interfere in many well-established toxicity testing protocols. This article outlines some of the most frequently used assays to assess the cytotoxity and biological reactivity of nanoparticles in vitro. The article identifies key issues that need to be addressed in relation to inclusion of relevant controls, assessing particles for their ability to interfere in the assays, and using systematic approaches to prevent misinterpretation of data. The protocols discussed range from simple cytotoxicity assays, to measurement of reactive oxygen species and oxidative stress, activation of proinflammatory signaling, and finally genotoxicity. The aim of this review is to share knowledge relating to nanoparticle toxicity testing in order to provide advice and support for guidelines, regulatory bodies, and for scientists in general.

This critical review of the available human health safety data, relating to carbon nanotubes (CNTs), was conducted in order to assess the risks associated with CNT exposure. Determining the toxicity related to CNT exploitation is of great relevance and importance due to the increased potential for human exposure to CNTs within occupational, environmental and consumer settings. When this information is combined with knowledge on the likely exposure levels of humans to CNTs, it will enable risk assessments to be conducted to assess the risks posed to human health. CNTs are a diverse group of materials and vary with regards to their wall number (single and multi-walled CNTs are evident), length, composition, and surface chemistry. The attributes of CNTs that were identified as being most likely to drive the observed toxicity have been considered, and include CNT length, metal content, tendency to aggregate/agglomerate and surface chemistry. Of particular importance, is the contribution of the fibre paradigm to CNT toxicity, whereby the length of CNTs appears to be critical to their toxic potential. Mechanistic processes that are critical to CNT toxicity will also be discussed, with the findings insinuating that CNTs can exert an oxidative response that stimulates inflammatory, genotoxic and cytotoxic consequences. Consequently, it may transpire that a common mechanism is responsible for driving CNT toxicity, despite the fact that CNTs are a diverse population of materials. The similarity of the structure of CNTs to that of asbestos has prompted concern surrounding the exposure of humans, and so the applicability of the fibre paradigm to CNTs will be evaluated. It is also necessary to determine the systemic availability of CNTs following exposure, to determine where potential targets of toxicity are, and to thereby direct in vitro investigations within the most appropriate target cells. CNTs are therefore a group of materials whose useful exploitable properties prompts their increased production and utilization within diverse applications, so that ensuring their safety is of vital importance.

Nanotechnology is involved with the creation and/or manipulation of materials at the nanometer (nm) scale, and has arisen as a consequence of the novel properties that materials exhibit within the "nano" size range. The attraction of producing, and exploiting nanparticles (NPs; one dimension less than 100 nm) is a consequence of the fact that the properties are often strikingly different from bulk forms composed from the same material. As a consequence, the field of nanotechnology has generated substantial interest resulting in incorporation of NPs into a wide variety of products including electronics, food, clothing, medicines, cosmetics and sporting equipment. While there is general recognition that nanotechnology has the potential to advance science, quality of life and to generate substantial financial gains, a number of reports suggest that potential toxicity should be considered in order to allow the safe and sustainable development of such products. For example, substances which are ordinarily innocuous can elicit toxicity due to the altered chemical and physical properties that become evident within nano dimensions leading to potentially detrimental consequences for the producer, consumer or environment. Research into respirable air pollution particles (PM10) has focused on the role of ultrafine particle (diameter less than 100 nm) in inducing oxidative stress leading to inflammation and resulting in exacerbation of preexisting respiratory and cardiovascular disease. Epidemiological studies have repeatedly found a positive correlation between the level of particulate air pollution and increased morbidity and mortality rates in both adults and children. Such studies have also identified a link between respiratory ill health and the number of ambient ultrafine particles. In vivo and in vitro toxicology studies confirm that for low solubility, low toxicity materials such as TiO2, carbon black and polystyrene beads, ultrafine particles are more toxic and inflammogenic than fine particles. In many of these studies the term "ultrafine particle" can be directly exchanged for nanoparticle, as these particles are manufactured industrially. In such studies the NPs generate reactive oxygen species (ROS) to a greater extent than larger particles leading to increased transcription of pro-inflammatory mediators via intracellular signaling pathways including calcium and oxidative stress. To date, only limited NP compositions and structures have been tested, including materials such as carbon, polystyrene beads and TiO2 as surrogate particles that aimed to represent particulate air pollution. All of these materials are generally low toxicity and low solubility. Much work is required to identify whether the conclusions made for such materials can be extrapolated to engineered nanoparticles varying not only in size but also, shape, composition, structure, surface area, surface coating, and aggregation state. Therefore, it is necessary to reveal if the diversity of NPs available will confer to a varied extent and mechanisms...

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