ReviewSize, source and chemical composition as determinants of toxicity attributable to ambient particulate matter
Highlights
► Identifying toxic component(s) of particulate matter is a major challenge. ► Evidence suggesting differential toxicity of components and sources are discussed. ► Targeted and contemporary studies are needed to further understand relative toxicity of particles. ► Goals of refined research are abatement policies, pollution control measures and improved health.
Introduction
Urban air pollution and particularly in the poorest regions of the world, indoor smoke from solid fuels, is recognised as a major contributor to the global burden of disease (Ezzati et al., 2002). Worldwide, it is estimated that PM2.5 (particulate matter less than 2.5 μm in diameter) ambient air pollution is responsible per annum, for approximately 0.8 million premature deaths and 6.4 million years of life lost (Cohen et al., 2005). The now well established evidence that particle exposures, experienced by populations in both developed and developing countries, causes a range of adverse health effects, primarily emerged from the findings of American epidemiological studies. The latter comprised both time-series and prospective cohort studies, reporting increased respiratory and cardiovascular mortality associated with acute and chronic exposures to particulate air pollution (Schwartz and Dockery, 1992a, 1992b; Dockery et al., 1993; Pope et al., 1995). These associations have subsequently proven to be robust in epidemiological studies conducted outside of the US, including rural areas in developing countries (Ostro et al., 1999; Katsouyanni et al., 2001; Hoek et al., 2002; Filleul et al., 2005). Further evidence to strengthen the association was uncovered when the benefits of US air quality regulations were evaluated. An analysis of the latter demonstrated an increase in life expectancy as a result of reductions in PM2.5 air pollution that occurred in the US during the 1980s and 1990s, suggesting at least partial reversibility of the mortality effect (Pope et al., 2009).
The impact of particulate air pollution on morbidity endpoints has also been subject to intense study, resulting in strong evidence of detrimental effects on respiratory conditions as well as negative impacts on cardiovascular diseases following both short-term and chronic exposures. Acute respiratory effects reported during short-term studies include heightened severity of symptoms in asthmatics and chronic obstructive pulmonary disease (COPD) sufferers, as well as increased hospital admissions for both patient populations (Pope and Kanner, 1993; Delfino et al., 1998; Zanobetti et al., 2000; Atkinson et al., 2001; Halonen et al., 2008). Chronic respiratory effects linked to ambient particulate pollution concentrations include reduced lung function and increased symptoms of bronchitis in both children and adults (Raizenne et al., 1996; Ackermann-Liebrich et al., 1997; Braun-Fahrlander et al., 1997; Zemp et al., 1999; Pierse et al., 2006), asthma symptoms and asthma-related emergency department visits and hospitalisations (Gehring et al., 2010; Meng et al., 2010) and childhood allergies (Morgenstern et al., 2008; Parker et al., 2009). Less conclusive, but potentially critical effects of ambient PM on respiratory outcomes include an impact on lung development in children as they reach adulthood (Gauderman et al., 2004) and the onset of COPD (Schikowski et al., 2005; Downs et al., 2007) and childhood asthma (Gehring et al., 2010). Other interesting epidemiological observations include a possible link between chronic PM exposure during childhood and vulnerability to COPD in adulthood (Grigg, 2009), and that infants subjected to higher prenatal levels of air pollution may be at greater risk of developing respiratory conditions (Hertz-Picciotto et al., 2005; Dominici et al., 2006; Mortimer et al., 2008). Evidence of cardiovascular effects, other than increased cardiac hospitalisations, associated with short and/or long-term elevations in particulate air pollution is strong for ischemic heart disease (Peters et al., 2001; Le Tertre et al., 2002; COMEAP, 2006; Dominici et al., 2006; Tonne et al., 2007; Zanobetti and Schwartz, 2007), increasing for heart failure (COMEAP, 2006; Pope et al., 2008) and cerebrovascular disease (Hong et al., 2002; Miller et al., 2007) and less conclusive for peripheral vascular (Dominici et al., 2006; Baccarelli et al., 2008) and cardiac arrhythmia/arrest (Peters et al., 2000). The promotion and vulnerability of atherosclerotic plaques is a potential mechanism by which PM air pollution could trigger cardiovascular mortality and morbidity and to support this, epidemiological studies have demonstrated that long-term exposure is indeed linked to the burden of atherosclerosis (Künzli et al., 2005), including progression of the disease during a prospective follow-up period (Künzli et al., 2010).
Other than the detrimental effects on cardiopulmonary heath, an increasing number of studies are investigating the potential for particulate air pollution to exert a wider threat, by for example, negatively influencing reproductive outcomes and neurological health. Effects have been reported on preterm delivery and/or preeclampsia (Darrow et al., 2009; Suh et al., 2009; Wu et al., 2009; Yi et al., 2010), cardiovascular malformations (Strickland et al., 2009) and foetal measurements (Hansen et al., 2008). Suggestions of negative neurological effects include reports of mild cognitive impairment (Ranft et al., 2009) and hospitalization for headache (Dales et al., 2009).
The capacity of inhaled PM to elicit oxidative stress in the lung, as well as systemically, has emerged as a unifying hypothesis to explain the acute and chronic health effects observed in populations exposed to elevated PM concentrations (Gilliland et al., 1999; Kelly, 2003; Borm et al., 2007). Several inter-related pathways exist by which inhaled particles can generate reactive oxygen species (ROS): direct introduction of oxidizing species into the lung, such as redox active transition metals as well as quinones or endotoxin on the particle surface; introduction of surface absorbed PAHs that can undergo bio-transformation in vivo; a lesser well defined ability of by the particle surface per se to elicit oxidative stress (Fig. 1).
Having now firmly established associations between ambient PM and adverse health effects, the biggest gap in our knowledge of PM toxicity relates to which component(s) of ambient PM, and/or which of their physical and chemical characteristic(s), are responsible. It is only with this information that we can develop relevant PM management strategies that will be more effective in addressing public health. For example, whilst standards, guidelines and strategies aimed at reducing PM are based on ambient particle mass (which includes a mixture of particles from many sources), findings suggest this may be insufficient in representing causal pollutant components. Whilst a rodent toxicology study of Kodavanti et al. (2005) reported that exposure to high concentrations of concentrated ambient particles (CAPs) are not necessarily associated with biological effects, an epidemiological study of children with asthma reported relatively weak associations between exhaled nitric oxide (a marker of airway inflammation) and ambient particle mass when compared with specific PM components (namely elemental carbon [EC] and organic carbon [OC]) (Delfino et al., 2006).
Identification of the toxic components of PM is however a challenging task as particulate air pollution constitutes a complex mixture of particles, present in the atmosphere as solids or liquids that vary in mass, number, size, shape, surface area, chemical composition as well as reactivity, acidity, solubility and origin. Furthermore, chemical constituents can be internal or on the particulate surface, with a core and a shell having different compositions. Indeed, airborne PM presents a far greater complexity than most other common air pollutants. The identification of PM-specific effects is made even more difficult when one considers how PM can vary in space and time as a consequence of atmospheric chemistry and weather conditions, as well as the complex interactions that exists between it and gaseous air pollutants (such as ozone [O3]), especially since the latter has biologically plausible associations with various health endpoints that are also potentially related to PM. Indeed, some of the strongest epidemiological evidence on associations between PM and mortality and morbidity highlights the complexities of disentangling effects of specific components of these pollutant mixtures (Krewski et al., 2000; Gauderman et al., 2004).
The question of identifying the physical and chemical characteristics that determine PM toxicity is not a new one and there is no shortage of comprehensive reviews providing critical perspectives (Brunekreef and Forsberg, 2005; Grahame and Schlesinger, 2007; Schlesinger, 2007; Chen and Lippmann, 2009; Lippmann and Chen, 2009; Mauderly and Chow, 2008). As such, rather than duplicate previous work, this review adopts a different approach in an attempt to augment the existing literature. Following a summary of PM characteristics and research applications, we present a relatively brief and qualitative overview of the toxicity of what are believed to be the influential components and characteristics and sources. A main thrust of this review however is a discussion of the likely reasons this question continues to elude the scientific community, and the approaches that are necessary to further our appreciation as to what types and/or classes of PM, or their constituents, are harmful to human health.
Section snippets
What is particulate matter?
Particulate pollution encompasses emissions from both natural and man-made sources. The former includes wind-blown dust, sea salt, volcanic ash, pollens, fungal spores, soil particles, the products of forest fires and the oxidation of biogenic reactive gases. Man-made sources constitute fossil fuel combustion (especially in vehicles and power plants), industrial processes (producing metals, cement, lime and chemicals), construction work, quarrying and mining activities, cigarette smoking and
Epidemiological studies
The most direct evidence for linking health effects to air pollution exposure is provided by epidemiological studies, having the advantage of accurately representing conditions in a population. They also present an opportunity to study vulnerable populations, such as those with asthma or existing cardiovascular conditions. The results from these studies are however inherently complicated by uncertainties over exposure causality and confounding factors. In interpreting the results of
Chemical composition as a modulator of PM toxicity
A whole host of specific chemical components of PM have been targeted for study in terms of their potential to contribute to PM-induced health effects. The following sections discuss evidence for toxicity of the major constituents.
The role of particle size, surface area and solubility as determinants of PM toxicity
The wide array of species which can localise on the surface of PM, undoubtedly act as catalysts in the health effects associated with ambient PM. However surface reactivity is not the only aspect of particle toxicity. Evidence from in vivo exposures of model particles has indicated that particle size is also an important determinant of reactivity (Ferin et al., 1992; Brown et al., 2001; Zhang et al., 2003). PM-induced activity, independent of chemical composition, would imply the ability to
Source
As reiterated throughout this review, ambient PM is a chemically non-specific pollutant, originating from a variety of sources which, in line with chemical composition, size and solubility, appears to determine its toxicological characteristics. Sources will contain a mixture of pollutants and it is feasible that the mix is instrumental in health effects observed. Rather than focussing on the identification of chemical compounds therefore, an alternative rationale is to identify the source that
Research needs and challenges
Drawing conclusions from the studies discussed in this review is not an easy task, and as such demonstrates that, in spite of advancements in monitoring, epidemiology and toxicological methodologies, giving researchers more confidence in identifying which health risks may be causally related to ambient PM pollution, we cannot yet precisely quantify or rank the health effects of PM emissions from different sources or of individual PM components. This section focuses on the main reasons that
Discussion
An urgent need for progress in reducing the substantial impacts of ambient air PM on human health is to identify the sources and components thereof that have the greatest effects. However, that the number of chemical components, characteristics and sources linked to a wide range of health responses is so substantial underlies the size and complexity of this challenge. Indeed a belief by various commentators in the field is that the literature does not support the view that the impact of PM on
Acknowledgements
The authors would like to the Natural Environment Research Council and Medical Research Council for the funding received for this project through the Environmental Exposures & Health Initiative (EEHI). The research was also supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Tomas' NHS Foundation Trust and King's College London. The views expressed are those of the authors (s) and not necessarily those of the NHS, the NIHR or the
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