COMMENTS ON THE INTEGRATIVE SYNTHESIS IN CHAPTER 9 OF THE SECOND EXTERNAL REVIEW DRAFT OF AIR QUALITY CRITERIA FOR PARTICULATE MATTER,

Frederick H. Rueter, Ph.D.

CONSAD Research Corporation

July 11, 2001

In the Second External Review Draft of Air Quality Criteria for Particulate Matter, March 2001 [EPA, 2001], the Environmental Protection Agency (EPA) has updated the information provided in Air Quality Criteria for Particulate Matter, April 1996 [EPA, 1996] based on scientific information that has become available since publication of the 1996 criteria document. The "Integrative Synthesis" in Chapter 9 of EPA(2001) summarizes the EPA’s interpretation of all of the scientific information considered in both EPA(1996) and EPA(2001).

The overarching conclusion expressed by the EPA in its "Integrative Synthesis" appears on p. 9-36. It states:

Epidemiologic findings ... provide the strongest body of evidence directly relating ambient PM concentrations to biomedical outcomes. Numerous epidemiologic studies have shown statistically significant associations of ambient PM levels with a variety of human health endpoints, including mortality, hospital admissions, emergency department visits, other medical visits, respiratory illness and symptoms measured in community surveys, and physiologic changes in pulmonary function. Associations have been consistently observed between both short- and long-term PM exposure and these endpoints. The general internal consistency of the epidemiologic database and available findings demonstrate well that notable human health effects are associated with exposures to ambient PM at concentrations currently found in many geographic locations across the United States. [Emphasis added.]

Indeed, this conclusion is expressed even more strongly in Section 6.5 of EPA(2001) where, on p. 6-266, it is stated:

A very large and sufficiently convincing body of epidemiology evidence substantiates strong associations between short- and long-term ambient PM₁₀ exposures (inferred from stationary air monitor measures) and mortality/morbidity effects to conclude that PM₁₀ (or one or more PM₁₀ components) is a probable contributory cause of human health effects. [Emphasis added.]

The EPA interprets the statistical correlations found in the epidemiologic studies as evidence that exposure to ambient concentrations of PM causes morbidity and premature mortality. As explained below, EPA's interpretation is incomplete and, most likely, incorrect because it fails to take into account important evidence from other scientific disciplines, much of which is reported in EPA(1996) or EPA(2001). Those disciplines include especially meteorology, atmospheric chemistry and physics, the behavioral sciences, clinical medicine and toxicology. The pertinent evidence and its implications are discussed below.

EPA’s conclusions about the health effects of ambient PM concentrations are based on a variety of specific forms of epidemiologic studies. Detailed descriptions and discussions of the studies are contained in EPA(1996) and EPA(2001). Two distinct types of measurements of ambient PM concentrations are used in the various forms of studies.

The most prevalent forms of epidemiologic studies consist of longitudinal studies that have analyzed, for specific geographic areas, the statistical correlations between various measures of daily mortality or morbidity and daily measurements of PM concentrations in the outdoor air. The studies have been conducted for a number of geographic areas with notably different ambient PM levels. Most of the studies relate to individual areas. Several recent studies have applied identical data methods and model specifications to multiple geographic areas.

The studies generally have found statistically significant correlations between daily mortality or morbidity and ambient concentrations of PM. In some of the studies, similar correlations have also been found for one or two other air pollutants, separately or in conjunction with PM. The strongest correlations have been detected for elderly people (older than 65 years of age) with preexisting chronic cardiovascular and respiratory disease. The principal causes of death have included chronic obstructive pulmonary disease (COPD), pneumonia, cardiovascular disease, and stroke.

A small portion of the epidemiologic studies have consisted of cross-sectional studies that have analyzed, for specific population cohorts, the statistical correlation between long-term (typically annual) mortality rates and long-term (typically annual) average concentrations of airborne PM outdoors in different geographic areas. Many of those studies have found statistically significant correlations between long-term average PM levels and long-term mortality rates that have been adjusted for other pertinent risk factors, such as age, gender, body mass, education, smoking behavior, alcohol consumption, and occupational exposures to hazardous substances. The principal specific causes of death for which correlations have been detected in the studies are cardiovascular and pulmonary disease and, primarily for men who are current or former smokers, lung cancer.

As reported above, the EPA interprets the correlations found in the epidemiologic studies as evidence that exposure to current levels of ambient PM is "a probable contributory cause" of morbidity and premature mortality. When the entire body of relevant scientific evidence is considered, however, a markedly different inference is indicated by the epidemiologic studies.

As discussed below, the most likely hypothesis that realistically accounts for all of the available pertinent evidence is that the principal cause of the excess mortality and morbidity detected in the epidemiologic studies is exposure to airborne biological and chemical substances (including, most notably, allergens) emitted indoors, rather than exposure to airborne PM or any other substances emitted from anthropogenic (human) sources into the outdoor air.

The Primal Role of Air Movement Caused by Meteorological Conditions

The main cause of differences in ambient concentrations of airborne substances at different times and in different locations is differences in air movement, caused by differences in meteorological conditions. Meteorology thus profoundly affects the air quality data used in both longitudinal and cross-sectional epidemiologic studies of the health effects of ambient air pollution.

When air movement increases, concentrations of airborne substances generally decline; when air movement decreases, concentrations generally increase. When air movement declines, airborne substances disperse from their sources of emission more slowly, and their concentrations near those sources rise. As explained below, meteorology exerts similar effects on substances emitted from anthropogenic and natural sources, and into outdoor and indoor air.

It is particularly important to realize that meteorological conditions directly affect the air exchange rate, the rate at which indoor air is replaced by outdoor air within structures. When a change in meteorological conditions (e.g., a decline in wind velocity or a thermal inversion) causes air movement to decrease, air exchange rates decrease; and conversely.

Specifically, as documented by the American Society of Heating, Refrigeration and Air-Conditioning Engineers (ASHRAE) in its Fundamentals Handbook [ASHRAE, 1981], a one percent increase (or decrease) in the average wind speed is associated with a one percent increase (or decrease) in a building’s air exchange rate, holding other pertinent conditions constant. In this regard, it should be noted that, on p. 9-24 of EPA(2001), the EPA correctly reports that:

For a home closed for heating or air-conditioning, the air exchange rate depends on the temperature difference between the indoor and outdoor air; the greater the difference, the greater the air exchange rate. If windows are opened for ventilation or doors are opened frequently, the air exchange rate will be higher.

The EPA never mentions, however, the direct relationship between wind speed and the air exchange rate documented by ASHRAE(1981). This serious deficiency should be rectified.

When air exchange rates decrease, the infiltration of airborne substances from outdoor to indoor air and the exfiltration of airborne substances from indoor to outdoor air both decrease. As anyone who has burned food in the kitchen knows, when windows and doors are opened to vent the room, the air clears rapidly when there is a nice breeze, but clears slowly when the air is calm. Similarly, substances in the outdoor air infiltrate indoors quickly when it is breezy, and slowly when it is not. This difference in air exchange rates under different wind conditions occurs regardless of whether windows or doors are open or closed (although obviously, for any wind conditions, the air exchange rate will be lower the more tightly a building is sealed).

Accordingly, when a decline in air movement causes the air exchange rate to decrease, diminished exfiltration causes the concentrations of substances emitted into indoor air from indoor sources to increase, and to become a larger portion of the total volume of airborne substances indoors. As a result, the aggregate concentration of substances in the indoor air contains an increased proportion of substances emitted from indoor sources and a decreased proportion of substances emitted initially into the outdoor air.

Thus, when a change in meteorological conditions decreases air movement and thereby causes the ambient concentrations of PM and other substances to increase in the outdoor air, the concentrations of airborne substances in the indoor air will tend to increase concurrently, and will generally contain an increased proportion of substances emitted from indoor sources. The ambient concentrations of substances in the outdoor and indoor air therefore will commonly be correlated over time due to their mutual dependence on air movement caused by meteorological conditions.

In fact, on at least two occasions in EPA(2001), the EPA explicitly acknowledges that covariation among airborne pollutant concentrations might arise from this source. On p. 6-4, the EPA states that such covariation might result from "correlated changes in response to wind and weather". Then, on p. 9-80, the EPA recognizes that the "concentrations of measured gaseous co-pollutants (and presumably unmeasured pollutants as well) ... are often correlated with concentrations of PM and its components because of ... wind speed and direction, atmospheric processes, ... and meteorological conditions." However, the important implications of this source of statistical correlations among airborne pollutant concentrations in relation to the correct interpretation of the results from the epidemiologic studies of the health effects of air pollution are never mentioned or explained in EPA(2001). This crucial defect should be remedied.

Similar confounding factors affect cross-sectional studies of the statistical correlations between long-term mortality rates and long-term average PM concentrations in different geographic areas. As reported by Systems Applications International (SAI) in a report prepared under contract to the EPA, differences in annual volumes of pollutant emissions account for only a minor portion of measured variations in annual average pollutant concentrations among areas and over time. Specifically, for four pollutants [carbon monoxide (CO), nitrogen oxide (NO), nitrogen dioxide (NO₂), and sulfur dioxide (SO₂)], differences in their annual emission levels account for only 4 to 17 percent of the variance in their mean annual ambient air concentrations over space (among counties for CO, NO, and NO₂; among states for SO₂) and over time. SAI concludes:

These results indicate minimal correlation between the emissions estimates and air quality measurements. This is the result of uncertainties in the emissions estimates, the local scale of most of the air quality measurements, and the fact that a large part of the air quality variance is due to the variability of meteorological conditions and the effects of atmospheric chemistry. [SAI, 1994, p. 4-18. Emphasis added.]

Differences in air quality measurements are influenced more strongly by variations in meteorological conditions than by variations in pollutant emissions. Long-term average pollutant concentrations are relatively high in areas and time periods with comparatively high frequency and severity of meteorological conditions that cause poor air movement, and conversely.

Indeed, this association between the frequency and severity of poor air movement and the long-term average air pollutant concentrations in different urban areas has doubtless become stronger over time as urban areas have developed and implemented state implementation plans for criteria air pollutants that are expressly designed to assure compliance with the short-term national ambient air quality standards (NAAQS) for the pollutants. As areas adopt emissions control programs that assure that short-term pollutant concentrations do not exceed the corresponding NAAQS more frequently than once per year on average, the long-term average pollutant concentrations in any area will be determined primarily by the number of times per year that unfavorable meteorological conditions cause short-term pollutant concentrations to rise toward the short-term NAAQS, and how near they approach the NAAQS on those occasions. Areas with relatively high frequency and severity of such meteorological conditions will tend to have relatively high long-term average pollutant concentrations.

Moreover, as explained above, in circumstances where adverse meteorological conditions cause elevated pollutant concentrations outdoors, they will also tend to cause elevated levels of airborne substances indoors, and the indoor air will typically contain relatively high proportions of substances emitted from indoor sources. Thus, the long-term average concentrations of substances in the outdoor and indoor air also will commonly be correlated because of their mutual dependence on air movement caused by meteorological conditions.

Consequently, the mortality and morbidity that the epidemiologic studies have found to be correlated with daily and long-term average measurements of ambient concentrations of PM and other criteria pollutants in the outdoor air must also be correlated with the unmeasured ambient concentrations of numerous other airborne substances emitted from anthropogenic and natural sources into outdoor and indoor air. The mortality and morbidity therefore cannot validly be attributed solely to PM emitted into the outdoor air from anthropogenic sources. Rather, as Dr. George T. Wolff, the former chairperson of EPA’s Clean Air Scientific Advisory Committee, reports that several members of the committee that he chaired have already concluded, the studies actually reveal correlations between mortality or morbidity and air pollution in general. [Wolfe, 1996, p.30. Emphasis added.]

Thus, the premature mortality and elevated morbidity detected in the epidemiologic studies are doubtless caused by many airborne substances, operating individually or collectively. In marked contrast, the EPA chooses to interpret the results of the studies principally as evidence of the effects of a single pollutant, PM, and attributes to that pollutant most, if not all, of the elevated mortality and morbidity inferred from the results. That attribution is clearly unfounded and excessive.

In fact, EPA(2001) repeatedly acknowledges the uncertainties involved in interpreting the results from epidemiologic studies that involve covarying pollutant concentrations. The most explicit acknowledgment appears on p. 6-268, where the EPA states:

The inclusion of multiple pollutants often produces statistically unstable estimates. Omission of other pollutants may incorrectly attribute their independent effects to PM.

Similarly, on p. 9-39, the EPA says:

The ambient atmosphere contains numerous air pollutants, and it is important to continue to recognize that health effects associated statistically with any single pollutant may actually be mediated by multiple components of the complex ambient mix. Specific attribution of effects to any single pollutant may therefore be overly simplistic.

This discussion should be expanded to include an acknowledgment that covariation among pollutant concentrations also involves airborne substances in indoor air, including substances emitted into indoor air from indoor sources, and hence that health effects associated statistically with any pollutant in the outdoor air may actually be caused by indoor air pollutants emitted from indoor sources.

In addition, EPA(2001) contains numerous discussions (e.g., on pp. 9-42, 9-45, 9-65, 9-70, 9-73, and 9-81) about epidemiologic studies in which the sizes of the health effects estimated for PM (and other individual pollutants) have decreased and become less statistically significant as the ambient concentrations of additional air pollutants are included in the statistical analysis. In fact, on p. 9-81 the EPA reports that: "Many recent studies demonstrate", for both mortality and hospital admissions, "that PM and co-pollutant effect size estimates will be highly unstable and often insignificant in multi-pollutant models when multicollinearity exists."

The EPA further states, on p. 9-42: "However, in many studies, PM indices showed the highest significance in both single- and multiple-pollutant models." This result quite likely occurs because, in contrast to other monitored air pollutants, PM is a mixture of substances with different sizes, shapes, chemical compositions, and physical behaviors. Accordingly, in statistical analyses, PM is doubtless a more effective analytic surrogate for all airborne substances (i.e., air pollution in general) than any individual chemical species, such as any of the other monitored air pollutants, could be.

It is also important to recognize the probable role of air movement in the anomalous results reported on pp. 9-58 and 9-60 of EPA(2001) in relation to the health effects of crustal material. The studies cited on those pages have either detected no association or a negative correlation between indices of crustal material and mortality. One study found a statistically significant "negative association between the crustal component of PM_2.5 and cardiovascular mortality." (p. 9-58)

It is not biologically plausible that exposure to elevated concentrations of crustal material is protective against mortality. This biologically implausible result can be reconciled, however, by recognizing that crustal material becomes airborne in response to air movement. In contrast, as discussed above, increases in air movement generally cause decreases in the concentrations of substances that are routinely emitted into outdoor or indoor air. Thus, the negative correlations estimated for crustal material are most likely actually attributable to decreased concentrations of other airborne substances that occur concurrently with increased concentrations of crustal material because of their mutual, but inverse dependence on air movement.

The Importance of Exposures to Airborne Substances Indoors

In the epidemiologic studies, the measured concentrations of PM are serving as markers (reliable analytic surrogates) for the concentrations of the other airborne substances that have been omitted from the statistical analyses. The omitted substances include, most importantly, substances emitted into indoor air from indoor sources. Those sources include anthropogenic activities such as cooking, heating and cleaning, as well as natural sources of bioaerosols such as common allergens, including spores from molds, fragments and feces of house-dust mites, and animal dander.

It is essential to consider substances in the indoor air as potential causative agents because behavioral studies of human activity patterns consistently find that people spend a substantial majority of their time indoors. On average, people spend 85 to 90 percent of the time indoors, and much of the remainder in transit within vehicles [Robinson and Nelson(1995), as cited in Chapter 7 of EPA(1996)]. The elderly people with chronic cardiovascular and respiratory disease for whom the strongest statistical correlations between mortality and ambient PM levels have been found in the epidemiologic studies doubtless spend even larger portions of their time indoors.

It is also important to realize that there is no scientific evidence that establishes a biological mechanism linking premature death with exposure to the ambient levels of PM experienced in the U.S. during the last 20 years. Rather, the EPA merely hypothesizes that increases in ambient concentrations of PM might cause respiratory or cardiovascular mortality through several potential biological mechanisms of toxicity.

The mechanisms that the EPA has posited in EPA(2001) include: inflammation of or injury to the lung, increased susceptibility to respiratory infections, increased airway reactivity and exacerbation of asthma, impairment of heart function by lowering the oxygen level in the blood and by increasing the work of breathing, systemic hemodynamic effects resulting from lung inflammation and cytokine production, increased risk of heart attacks or strokes due to increasing blood coagulability associated with lung inflammation, potential effects on hematopoiesis from interactions between PM and the lung, decreased heart rate variability, effects on autonomic control of the heart and the cardiovascular system, and the uptake of particles and the distribution of soluble substances into the systemic circulation. Direct physiological responses to PM are hypothesized to trigger sequences of events that culminate in respiratory or cardiovascular morbidity or mortality.

Based on its review of the extant scientific evidence relating to the posited biological mechanisms, the EPA expresses its general conclusion about the current state of scientific knowledge about the potential mechanisms by which PM might cause health effects. That conclusion, on p. 9-89 of EPA(2001), is:

Clearly, controlled exposure studies as yet have not been able to unequivocally determine the particle characteristics and the toxicological mechanisms by which ambient PM may affect biological systems.

This conclusion is particularly valid for concentrations of ambient PM that are not substantially higher than those occurring currently in the U.S. Accordingly, the qualifying adverb, "unequivocally", is unwarranted in the preceding conclusion and should be deleted.

As documented in EPA(1996) and EPA(2001), numerous controlled toxicological studies have been conducted on the chemical and physical constituents of PM that are considered likely causative agents for the hypothesized biological mechanisms. The studies have variously examined healthy humans, asthmatics, healthy laboratory animals, and laboratory animals whose lungs have been compromised by respiratory disease. The suspect constituents include: acid aerosols; soluble transition metals such as iron, vanadium, nickel, manganese, zinc, and copper; residual oil fly ash (ROFA); ultrafine particles of Teflon, metal oxides, and carbon; diesel exhaust particulate matter; organic compounds; bioaerosols; and concentrated ambient PM. Those constituents have elicited detectable physiological responses in humans and animals only at concentrations that are much higher than the ambient concentrations that have been correlated with increased mortality in the epidemiologic studies. For example, clinical studies have consistently found that healthy people who are exposed for one hour to concentrations of sulfuric acid aerosol as great as 2,000 µg/m³ do not experience decreases in lung function, whereas the peak ambient levels of acid aerosols in the U.S. presently are less than 100 µg/m³ [EPA, 1996, p.13-69].

Based on the extant toxicological evidence, Dr. Mark J. Utell, chairperson of the Environmental Health Committee of EPA’s Science Advisory Board and chairperson of the Health Research Committee of the Health Effects Institute, and Dr. Mark W. Frampton conclude:

Available toxicological studies provide few clues in explaining acute mortality at low particle concentrations. Controlled clinical studies with acidic particles at concentrations greater than 20 times ambient fail to produce a pulmonary inflammatory response in healthy individuals; subjects with COPD, the group at presumably highest risk from the epidemiologic data, show no reduction of lung function with similar acute exposures. [Utell and Frampton, 1995, p. 645]

Moreover, on p. 9-95 of EPA(2001), the EPA acknowledges that this skepticism is shared by others. Specifically, the EPA states:

The plausibility of epidemiologically demonstrated associations between ambient PM and increases in morbidity and mortality has been questioned because associations with health effects have been observed at very low PM concentrations.

The extreme inconsistency between the epidemiologic results and the extant toxicological and mechanistic evidence strongly indicates that, in the epidemiologic studies, ambient PM is predominantly serving as a marker for other airborne substances that have been omitted from the analyses, including most notably substances emitted into indoor air from indoor sources.

In contrast, in sensitive population subgroups, such as asthmatics or people with sinus allergies, common allergens are proven causative agents for several of the hypothesized biological mechanisms (i.e., inflammation of pulmonary airways, increased airway reactivity and exacerbation of asthma, and aggravation of preexisting conditions) at current ambient concentrations. Asthmatics also have elevated risk of mortality from heart disease. For example, results presented on March 2, 2001 at the American Heart Association’s epidemiology meeting in San Antonio, Texas by Dr. Carlos Iribarren and colleagues from the Kaiser Permanente health plan in Oakland, California indicate that, among more than 22,000 nonsmokers, those who developed asthma symptoms over a 20-year period had a one-third higher risk of developing heart disease than the others.

Moreover, these sensitive subgroups include large numbers of people. Estimates based on data collected in the 1996 National Health Interview Survey (U.S. Bureau of the Census, 1999, Tables 14 and 232) indicate that 23.7 million citizens (8.9 percent of the total population) have hay fever (chronic allergic rhinitis without asthma), 14.6 million people (5.5 percent) have asthma, and 33.1 million people (12.5 percent) have chronic sinusitis. Among the elderly people (65 years of age or older) whom the epidemiologic studies have found to be most vulnerable, 2.3 million (6.8 percent of the elderly population) have hay fever, 1.5 million (4.6 percent) have asthma, and 4.0 million (11.7 percent) have chronic sinusitis.

Because people spend the bulk of their time indoors, and because sensitive people currently are frequently exposed indoors to airborne concentrations of bioaerosol and chemical allergens that trigger the hypothesized biological mechanisms, it is much more likely that the principal cause of the premature mortality and elevated morbidity detected in the epidemiologic studies is exposure to airborne substances indoors, than exposure to any substance emitted from anthropogenic sources outdoors. Exposure to airborne PM or any other substance emitted from anthropogenic sources into the outdoor air probably elicits the hypothesized biological responses in only a small number of hypersensitive individuals, and likely results in death or serious illness for at most a small portion of those people.

Summary and Conclusions

In summary, the entire body of available scientific evidence strongly indicates that ambient PM is not a major causative agent for mortality and morbidity. In addition, the ambient concentrations of the airborne substances that most likely are the principal causative agents, such as bioaerosol and chemical allergens emitted from indoor sources into the indoor air, will not be reduced by the proposed NAAQS for PM_2.5. Accordingly, the sizable health improvements that the EPA estimates will be gained by reducing ambient PM concentrations are highly speculative. They probably will largely not occur, because the airborne concentrations of the principal causative agents will not be reduced.

In the epidemiologic studies, ambient PM is largely serving as a marker for other, omitted airborne substances. It is analogous to a thermometer, measuring the intensity of air pollution in general. Under those circumstances, promulgating standards that compel reductions in ambient PM concentrations will merely recalibrate the thermometer, but will not discernibly reduce the health effects revealed in the epidemiologic studies.

The true health benefits from reducing ambient PM levels are doubtless much smaller than the EPA’s estimates. Indeed, they are most likely negligible, and may in practice be zero.

American Society of Heating, Refrigeration, and Air-Conditioning Engineers (1981), Fundamentals Handbook, Atlanta, GA, ASHRAE.

Robinson, John and W.C. Nelson (1995), National Human Activity Pattern Survey Data Base, Research Triangle Park, NC, U.S. Environmental Protection Agency, 1995.

Systems Applications International (SAI, 1994), Retrospective Analysis of SO₂, NO_x, and CO Air Quality in the United States, Final Report prepared for U.S. EPA, Office of Policy Analysis and Review, Washington, DC by SAI, Research Triangle Park, NC, November 1994.

U.S. Bureau of the Census (1999), Statistical Abstract of the United States: 1999 (119th edition.) Washington, DC, 1999.

U.S. Environmental Protection Agency (EPA,1996), Air Quality Criteria for Particulate Matter, EPA 600/P-95/001aF-cF, U.S. EPA, Washington, DC, April 1996.

U.S. Environmental Protection Agency (EPA,2001), Air Quality Criteria for Particulate Matter, Second External Review Draft, EPA 600/P-99/002aB,bB, U.S. EPA, Washington, DC, March 2001.

Utell, Mark J. And Mark W. Frampton (1995), "Particles and Mortality: A Clinical Perspective", Inhalation Toxicology, 7:645-655, July 1995.

Wolff, George T. (1996), "Closure by the Clean Air Scientific Advisory Committee (CASAC) on the Staff Paper for Particulate Matter," EPA-SAB-CASAC-LTR-96-008, U.S. EPA, Washington, DC, June 13, 1996.

 

1.   EPA(2001) also indicates, on p. 9-80, that the correlations between ambient PM concentrations and the concentrations of measured and unmeasured co-pollutants might result from "commonality in source emissions", and identifies the large sources as: "motor vehicle emissions (gasoline combustion, diesel fuel combustion, evaporation, particles generated by tire wear, etc.), coal combustion, fuel oil combustion, industrial processes, residential wood burning, solid waste combustion, and so on." It is important to recognize that the prominence of those sources is a consequence of decisions made about the air pollutants that would be regulated and measured. The air pollutants for which measurements of ambient concentrations are generally available are the six criteria pollutants (PM, carbon monoxide, sulfur dioxide, nitrogen oxides, ozone, and lead) and selected chemical constituents (e.g., sulfates and nitrates), size categories (e.g., PM₁₀, PM_2.5), and precursors (e.g., volatile organic compounds) of those pollutants. The principal attribute that these pollutants have in common is that they predominantly are by-products of fossil fuel use, and hence are emitted from a small number of source categories. As explained in these comments, however, the health effects detected in the epidemiologic studies discussed in EPA(1996) and EPA(2001) are most likely actually attributable to other airborne substances that have been omitted from the studies, including most notably substances emitted into indoor air from indoor sources.

2.  It should be noted that the toxicological studies of the health effects of exposure to bioaerosols that are discussed in EPA(2001) have examined those effects in "healthy nonsensitized individuals". [Emphasis added.] Yet, there are large population groups (e.g., asthmatics and people with hay fever, or chronic allergic rhinitis without asthma) who are known to be highly sensitive to bioaerosols. Presumably, they are the people who will experience health effects from exposure to low concentrations of bioaerosols. Hence, they are the people who should be subjects in toxicological studies of bioaerosols, just as compromised animals are appropriate subjects for toxicological studies of other air pollutants.