Air pollution, ultrafine and nanoparticle toxicology: cellular and molecular interactions.

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 of toxicity.