Particulate Matter Physicochemistry and Toxicology: In Search of Causality-A Critical Perspective.

Results from epidemiology studies have shown statistical associations between ambient air particulate matter (PM) concentrations and mortality/morbidity, particularly among susceptible subpopulations. Although the epidemiology of ambient air PM is compelling, there remains considerable uncertainty in PM risk assessment, particularly with regard to identification of PM properties and mechanisms that are responsible for its observed adverse health effects. In addition, the biological mechanisms by which specific PM properties mediate their adverse health effects are currently not known. In vivo and in vitro toxicological studies have examined particles derived from a number of sources such as ambient air, combustion, and natural sources, as well as laboratory-derived surrogate particles, in order to identify the characteristics of particles that are responsible for their adverse health effects. These studies have identified a number of potential causal biogenic, physical, and chemical properties of PM. A number of PM physical and chemical properties have been found to elicit biological responses in animal models of disease, which has enhanced their plausibility as being properties responsible for PM-associated health effects. In vitro mechanistic studies have shown that PM derived from a variety of sources mediate their adverse biological effects by inducing an oxidative stress, which may alter intracellular signal transduction pathways that regulate a number of biological responses such as cell growth, stress response, apoptosis, and inflammation. The challenge of future PM toxicology research will be to demonstrate "biological plausibility and coherence" for potential causal PM properties.