What Do We Need to Know about Airborne Particles to Make Effective Risk Management Decisions? A Toxicology Perspective

Epidemiologic studies have shown significant and consistent associations between ambient particulate matter (PM) and a variety of adverse cardiopulmonary health consequences. These associations are strongest in elderly sub-populations identified with preexistent cardiopulmonary diseases. While the consistency of the findings appears to warrant serious public health concern, the lack of clear mechanistic underpinnings ("biological plausibility") has prompted skepticism of the epidemiology. Toxicologists have embraced the challenge to address the issue of biologic plausibility in the context of the PM epidemiology and are vigorously investigating both causality and mechanisms by which effects might be mediated at the molecular, cellular, and organismic levels. Among the several hypotheses being touted, that involving constituent bioavailable transition metals appears most coherent with the epidemiologic observations. It provides a conceptual pathway that could have clinical implications. To date, the toxicology has involved relatively high doses of PM-metal to the lung of animal models and certainly more remains to be determined as to metal-specific biological roles at low environmental doses, especially in the context of host susceptibility. Nevertheless, the cumulative evidence is sufficiently cohesive to support our contention that metals are likely one important causal factor in the pathophysiological cascade leading to PM health effects. However, it would be premature at this point to consider metals in any risk management strategy for PM.