Current hypotheses on the mechanisms of toxicity of ultrafine particles.

PM10 is a complex mixture of particles and we have focused here on the ultrafine component, i.e. particles with a diameter of less than 100 nm. In PM10 this fraction is mostly composed of combustion-derived, carbon-centred particles with associated hydrocarbons and metals. Progress in understanding the effects of ultrafine particles in the lungs has been achieved largely through the use of surrogate particles such as ultrafine carbon black and titanium dioxide. Using these types of particles, ultrafines have been shown to cause oxidative stress and pro-inflammatory effects in a number of in vivo and in vitro models. The mechanisms of the generation of the oxidative stress is not understood, but appears to be related to the large particle surface area in some way. Modulation of calcium signalling also appears to be involved in the stimulation of cytokine release by macrophages in response to ultrafines. Effects of PM10 are seen on cardiovascular mortality and morbidity, as well as on the lung. Although the role of ultrafine particles in these effects are not well understood there are plausible pathways that remain to be explored.