A proof of concept study for a structure activity model for the toxicity of nanoparticles

Nanoparticles are extremely small particles, each individual particlel being less than one ten millionth of a metre in size. We are exposed to nanoparticles in busy streets as they are present in traffic exhaust produced from combustion of fuel and such nanoparticles are considered to be important in causing the harmful effects associated with exposure to air pollution. There are other situations where nanoparticles are found in the air, such as the normal chemical reactions that occur in air, in plumes of volcanic ash and in dusty workplaces. However, a new source of novel types of nanoparticles has arisen with the rise of nanotechnology. Part of nanotechnology aims to design and develop new nanoparticles, because they have properties which make them attractive to industry for a range of purposes. This has caused alarm bells to ring since perhaps some of these new types of nanoparticles could be harmful. Experimental studies with nanoparticles have confirmed that nanoparticles of a material can be more toxic than larger particles of the same material and that they have the potential translocate from their site of deposition. In response to the ecognition that nanoparticles have properties that differ from larger particles, the sub-specialty of 'nanotoxicology' has developed. The special properties of nanoparticles and the proliferation in types that are becoming available means that there is a need for testing of these new nanoparticles and indeed there should be an effort to gain a more comprehensive understanding of all particles. The huge number of nanoparticles and their variants in size and coating means that there are a huge number of particles to be tested. However, there is substantial ethical pressure against animal testing and so short-term tests that use cells instead of animals are needed. Several groups addressing the agenda for research into nanoparticles and have suggested that a structure/activity paradigm could be developed that relates particle characteristics to toxicity and that this could eventually be predictive for toxicity of new nanoparticles. This project concerns a pilot study that aims to determine the physico-chemical characteristics of a panel of about 20 commercially available nanoparticles using state-of-the-science facilities at the Institute of Particle Science and Engineering and the newly-formed Free Radical Research Facility at UHI Millennium Institute. This structural data will be entered into the model. Activity data will be obtained in the University of Edinburgh by testing the panel of Nanoparticles in short/term cell toxicology tests that are based on epithelial cell toxicity and pro-inflammatory responses. This model is chosen because the epithelial cell response is well understood with respect to its role in pathological responses to particles and has been amply demonstrated to discriminate between pathogenic and non-pathogenic particle types and so has a degree of validation. This approach, using analysis of chemical structure to predict toxicological activity, has been used previously for chemicals but has never been attempted for particles and so this represents an important pilot study to test the feasibility of this approach. Oxidative stress is a type of chemical reactivity that has been put forward as an important mechanism for how particles cause toxic effects on cells so there is emphasis on the oxidative stress capacity of the particles in this study. The anticipated output is proof or disproof of the feasibility of a structure-activity relationship for nanoparticle toxicity.