National Ambient Air Quality Objectives For Particulate Matter - Executive Summary

Risk Characterization

The data on the health effects of particulate matter have been examined in animal toxicity studies, controlled human exposure studies, and human epidemiological studies. By far the most compelling evidence for adverse health effects of airborne particulate matter at currently experienced levels in the atmosphere has come from the epidemiological studies. The epidemiological data appropriately identify the same susceptible sub-populations that would be expected clinically (the elderly, children and those with pre-existing disease), with responses dependent on the health endpoint. Acute effects, as noted in the epidemiological literature, and ordered according to severity, are as follows:

• increases in mortality due to cardio-respiratory diseases;
• increases in hospitalizations for cardio-respiratory diseases;
• decreases in lung function in children and in asthmatic adults;
• increases in respiratory symptoms which can lead to increases in respiratory-related activity restrictions and days lost from work or school.

This listing of effects does not accommodate the potential numbers of people impacted. If this were considered, then the description of effects would assume a pyramid shape, with relatively few people impacted by the more severe health outcomes (mortality and hospitalizations) while much greater numbers of people may be impacted with greater frequency by the less severe health consequences (respiratory symptoms, absenteeism, reduced lung function). In addition, long term or chronic effects have been found to be associated with exposure to particulate matter, including:

• reduced survival;
• reduced lung function and capacity in children;
• increases in the development of chronic bronchitis and asthma in some adults.

Overall, these findings from the epidemiological literature are not well supported by either the clinical or toxicological literature. Controlled human exposures to acidic and inert particles even at relatively high levels of PM compared to those generally experienced in the environment, have not been associated with significant alterations in respiratory functions in healthy individuals. Asthmatic individuals, especially asthmatic children and adolescents have, however, been identified as a susceptible subpopulation, responding to lower concentrations of acidic particles. The two major reasons for the lack of support by the clinical studies for the findings of the epidemiological studies are the extreme paucity of data on relevant exposures, and the ethical impossibility of investigating effects in precisely those persons most likely to be affected by air pollutants.

Animal toxicology studies have also demonstrated cardiorespiratory effects from acute, subchronic and chronic exposures to PM, but almost always at concentrations well above those occurring in the ambient environment. The toxicological evidence reviewed was able to demonstrate effects on the lung attributable to a particle effect, separate from effects related to the composition of the particle. The interpretation of results from experimental inhalation studies on animals and their significance for human exposures is fraught with uncertainty though. Therefore, the animal studies should be used to contribute primarily to an understanding of the mechanisms which lead to particle effects in humans.

Although the epidemiological studies are observational rather than experimental, they are nonetheless considered more relevant to a characterization of health risks associated with particulate air pollution than either animal toxicology or controlled human studies for several reasons:

they are the most direct way of assessing the adverse health outcomes of real world complex mixtures of pollutants to which people are exposed;

human populations, unlike laboratory animals, are highly heterogeneous, including individuals who encompass a large range of susceptibilities, disease status and exposures, and whose responses cannot be predicted from animal toxicology studies or are not available from controlled human exposure studies for ethical reasons;

population studies based on large administrative databases are able to demonstrate the impacts of pollution on public health, and even to enable some estimate of the costs of such impacts on society;

no extrapolation is necessary when assessing the effects on public health of a particular concentration of air pollutant as measured by the ambient monitoring network, despite our lack of knowledge about the exposures of each individual in the population (we need only know that the correlation is reasonable between the ambient monitor and the personal exposure).

These studies were conducted under a broad range of environmental conditions across many different geographical locales.

On Causality

In evaluating the epidemiological studies as a whole, a number of issues arise, key among them the issue of causality. Epidemiological studies do not themselves provide data on biological mechanisms that would explain the observed associations. Associations found in epidemiological studies between PM and health effects may reflect chance, bias or cause. A weight of evidence approach is used whereby multiple lines of evidence are brought together and duly considered in order to build a case for causality. On the basis of accepted criteria, the weight of evidence from the epidemiological literature that supports a causal link between particulate matter and adverse health effects is summarized as follows:

the probability of a relationship between PM and cardio-respiratory health has been ably established;

the strength of the association between exposure to PM and health outcomes can be considered relatively strong, since although the magnitude of the estimates of increased risk are generally small, they are remarkably stable among different studies and are often highly statistically significant;

a monotonically increasing (no threshold) concentration-response curve was observed from very low ambient levels up to much higher levels with remarkable consistency in many of the studies on acute and chronic mortality and hospitalizations;

the evidence is considered to be strong with respect to the specificity of the effect to respiratory and cardiac outcomes; non-respiratory effects are not associated with exposure to particulate pollution;

the specificity of cause is considered to be strong enough to conclude that particulate matter per se, rather than other pollutants or environmental variables, is associated with adverse health effects;

a logical temporal relationship exists, with exposure (e.g. daily peaks in PM), followed by effects (e.g. increased mortality and hospitalizations), although the rapidity with which mortality has been observed following incidents of high exposure remains a puzzle in terms of the mechanism of action of particles;

positive associations between particulate air pollution and cardio-respiratory related mortality and hospitalizations, and respiratory related health effects, have been consistently reported in numerous studies conducted under a broad range of environmental conditions in many cities on three continents, by a number of different investigators, providing a strongly coherent picture of the nature of particle-induced effects.

One of the most difficult questions has been, and continues to be, the role played by other gaseous pollutants (particularly SO₂, NO₂, CO and O³) in thetoxicity of particulate matter. Many of the available studies could not or did not consider several of these co-occurring gaseous pollutants. In analyses designed to help separate out the effects of one pollutant from another, the association of particulate matter with adverse health outcomes reported in the epidemiology literature was remarkably robust to inclusion (one at a time) of all four of the normally present gaseous air pollutants SO₂, NO₂, CO and ozone). Moreover, the magnitude of this association was often (but not always) greater than any of these other air pollutants individually or combined. The magnitude, robustness, and consistency of this association across so many locations with differing air pollutant mixtures supports the position that particulate matter of some kind is the best indicator for the effects of air pollution on adverse health outcomes. The question of which particle metric is the best indicator of toxicity remains unsettled, but current evidence suggests that some form of fine particle is the best measure of particle toxicity, although in some locations, and with respect to some endpoints, coarse particles remain important and cannot yet be entirely dismissed.

The second critical outstanding issue with respect to causality relates to the biological plausibility of the effects of particulate matter on human health. When evaluating the effects of low levels of ambient particulates, we need to clearly separate acute adverse effects from chronic effects that reflect long term levels of air pollution. The association of mortality with daily variations in particulate air pollution presents difficulties in establishing a plausible mechanism that could explain these associations, particularly the very short lag period, or in some cases no lag, between the recording of elevated particle concentrations and the occurrence of increased mortality. Several hypotheses have been put forth to explain acute particle related mortality, and although the puzzle is by no means resolved, neither is it beyond explanation. The answer may likely involve exacerbation of preexisting disease conditions and evidence is mounting for a critical role for ultrafine particles on the strength of some recent toxicological evidence that has shown that mortality in rats can be induced after exposure to relatively low concentrations of these tiny particles.

These suggested biological mechanisms still require much more research and confirmation. However, they help close a major gap in our understanding, thus providing some support for the idea of causality. Precise mechanisms of action have yet to be established. It should be noted, however, that biological plausibility is not an absolute requirement for a conclusion of causality. Epidemiological observations have often preceded the biologic knowledge of the day, as evidenced by the example of smoking and lung cancer. A fundamental purpose of epidemiology is to establish a cause with enough certainty that it will be justifiable and highly appropriate to take action to mitigate effects on public health. This point has clearly been reached with respect to particulate matter.