The Pulmonary Toxicology of Ultrafine Particles

Abstract

Ultrafine particles are a component of air pollution, derived from primary combustion sources, and so we have undertaken a programme of study on the mechanisms of lung injury caused by ultrafine particles. Ultrafine particles made of low-solubility, low-toxicity materials are more inflammogenic in the rat lung than fine respirable, particles made from the same material. Ultrafine particles can cause inflammation via processes independent of the release of transition metals, as shown by the fact that soluble products from ultrafine carbon black have no ability to cause inflammation. The property that drives the greater inflammogenicity of ultrafines is unknown but very likely relates to particle surface area and involves oxidative stress. Increases in intracellular Ca(++) may underlie the cellular effects of ultrafines, although the mechanism whereby ultrafines have this effect is not understood. However, increased influx of Ca(++) into macrophages occurs via the membrane Ca(++) channels following contact with ultrafine particles, and involves oxidative stress. Increased Ca(++) in macrophages exposed to ultrafines can lead to the transcription of key pro-inflammatory genes such as TNFalpha. Ultrafine particles can also impair the ability of macrophages to phagocytose and clear other particles, and this may be pro-inflammogenic.

In vitro cellular responses to silicon carbide particles manufactured through the Acheson process: Impact of physico-chemical features on pro-inflammatory and pro-oxidative effects

“…A linear relationship is indeed detectable between H 2 O 2 production and the SSA parameter (y = 15.9x + 21.5, where y = H 2 O 2 production in nmol/10 6 cells and x = particle surface in cm²; R² = 0.9, supplementary Figure 1). This is in agreement with a previous study which has shown a significant impact of nanosized SiC specific surface area on in vitro cellular responses (Pourchez et al, 2012) and also with results previously published in the literature for other particles like TiO 2 and carbon black (Oberdörster et al, 1994;Oberdorster, 2000;Oberdörster et al, 2005;Brown et al, 2001;Höhr et al, 2002;Donaldson et al, 2002;Fubini, 2007).…”

In vitro cytotoxicity and genotoxicity studies of titanium dioxide (TiO2) nanoparticles in Chinese hamster lung fibroblast cells

“…The photocatalytic activity and cytotoxicity of the anatase nano-TiO 2 are higher than that of the rutile form (Kakinoki et al, 2004;Sayes et al, 2006). Similarly, several studies suggested that lung inflammation and consequently cancer in rats could be induced after inhalation and intratracheal instillation of TiO 2 nanoparticles, with stronger inflammogenic activity in comparison with its micron-sized counterpart (Donaldson et al, 2002;Falck et al, 2009;Renwick et al, 2004).…”

Nanoparticulate materials and regulatory policy in Europe: An analysis of stakeholder perspectives

“…These epidemiological studies suggest that an increase in ambient particle concentration is related to an increase in acute morbidity and mortality (von Klot et al, 2005). Studies indicate that the decrease of particle size and the corresponding increase in relative surface area correlates with an increase in defense reaction in the lung tissue (Oberdorster, 2001;Donaldson, et al, 2002;Zhang et al, 2003;Donaldson et al, 2004a) and the inhalation of nanoparticles may cause diseases like lung cancer, fibrosis and inflammation in the lung and further worsen cardiovascular or respiratory diseases like asthma or bronchitis (Borm, 2004;Donaldson, 2004b;Stone, 2004). However, it is important to note that this lung toxicity database has been limited to studies of three types of nanoparticles: titanium dioxide, carbon black and diesel particles (Warheit, 2004).…”