For Presentation at the Air & Waste Management Association’s 90" Annual Meeting & Exhibition, June 8-13, 1997, Toronto, Ontario, Canada
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Dose-Rate Dependent Health Risks Support Control of One-Hour Airborne Particle Levels !
Robert A. Michaels
RAM TRAC Corporation 3100 Rosendale Road Schenectady, NY 12309-1510
Michael T. Kleinman Professor, Community & Environmental Medicine
University of California/Irvine Irvine, CA 92717-1825
ABSTRACT
Twenty-four-hour airborne particle mass levels permissible under the National Ambient Air Quality Standard have been associated with mortality and morbidity in communities, motivating reconsideration of the standard. The effects, which are weak though statistically significant, remain unexplained. This study inquires whether 24-hour-average particle levels might encompass significant, undetected excursions.
Two monitoring technologies were used to quantify particle excursions. Data recorded in Birmingham, Alabama (16 April 1990), Penticton, British Columbia (30 July to 7 August 1994), and Zeebrugge,
Belgium (15 March 1993) revealed numerous excursions, one reaching 2,000 g/M3, twice that of the 1952 London fog. Toxicology experiments have demonstrated the harmfulness of brief exposure to particle levels in the range of observed excursions. This suggests that toxicological processes initiated by short-term inhalation of airborne particles may exert clinically important effects, and that weak associations of 24-hour-average particle mass with mortality and morbidity may represent artifacts of stronger, shorter-term associations whose full magnitude remains to be quantified. In one study, the area of lung surface developing lesions was elevated in rats breathing the same four-hour dose of aerosols, when the four-hour average rate of aerosol delivery included a short-term (five-minute) burst fifty percent above the average dose rate. Elevations were observed with each of two aerosols tested. The magnitude of the effect was higher with one of the two aerosols, whose dose rate included four excursions rather than just one excursion.
If particle excursions impair the ability of lungs, especially diseased lungs, to clear fine particles, then prolonged internal exposures may correlate with prolonged, potentially lethal, cardiopulmonary stress, especially for the frail elderly and infirm. Additional studies of short-term excursions are needed. Confirmation of the importance of dose rate may be derived from studies using an invariant total dose. Such studies could further support the recommendation that EPA control one-hour particle levels. INTRODUCTION
' This research was supported by Rupprecht & Patashnick, Inc.; Albany, New York.
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At Court direction, the U. S. Environmental Protection Agency (EPA) has been required to review the National Ambient Air Quality Standard (NAAQS) for airborne particles (1, 2, 54, 55). The present NAAQS limits particulate matter within a diameter of 10 microns (PMj0) to a time-weighted average
mass limit of 150 ug/M3 of air over 24 hours (and 50 ug/M3 annually). It is based primarily upon epidemiological associations of particle elevations during air pollution episodes with elevated mortality and morbidity in communities (for example, see 15, 44, 45). Particle levels during the 1952 London fog
have been estimated at 1,200 ug/M3 (53; PMyg < 1,200 ug/M2). Recent studies associate significant
elevations of morbidity and mortality with particle levels well within the NAAQS (reviewed most recently by EPA, 1995; 60), and below levels that can be explained by known toxicological mechanisms. However, one of us (Michaels) has reported that daily average particle mass levels within the NAAQS may be associated with excursions to the London fog range and higher (35). The present study inquires whether large increases in airborne particle mass lasting an hour or less might explain mortality and morbidity associated with small increases in particle mass over a one-day averaging time.
METHODS
The investigation included analyzing available bioassay, clinical, and epidemiological data. Two of the bioassays represent results obtained in an investigation published by Kleinman, ef al. (1989; 24), but excluded from that report. In both bioassays, rats were exposed for four hours to either of two aerosols as described (24). However, in the unpublished bioassays, the rates at which the aerosols were delivered included either one or four excursions. Excursions were defined as elevations of at least 50 percent above an otherwise constant steady state aerosol concentration, lasting for at least five minutes.
Literature analysis was used to resolve three technical issues. First, the study determined whether instrumentation is available to reliably and economically measure particle levels over short intervals. Second, it quantified short-term excursions of particle mass contributing to 24-hour averages well within the NAAQS. Third, it assessed the likely toxicological adequacy of such excursions, considering their relatively brief persistence, to cause mortality and/or morbidity.
The findings regarding the three issues elucidated above were evaluated relative to EPA policies and procedures for air pollutant standard setting under the Clean Air Act (3, 56) based upon the weight of evidence for the existence, nature, and magnitude of public health risks. Ultimately, the findings were evaluated relative to a major regulatory issue. That is, in view of currently available data and instrumentation, whether public health protection can be assured via the current airborne particle risk management approach, which limits particle levels over 24 hours and annually, but with negligible control of excursions, which only negligibly influence 24-hour and annual mass limits.
FINDINGS
Identification of Monitoring Technologies
Two technologies were found capable of reliably measuring airborne particle levels in real time or over short intervals (12, 13, 33-38, 43, 46-51, 58). Inertial monitors can measure particles virtually continuously, whereas beta attenuation monitors can do so over intervals of an hour or less under
realistic field conditions. Both technologies represent alternatives to the reference gravimetric method for monitoring airborne particles. The technologies reflect evolution of the older technologies most
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notably in three directions: 1. toward greater sensitivity associated with utilizing non-gravimetric physical principles for measurement; 2. toward continuous monitoring and reduced sampling time; and 3. toward greater automation and reduced expense of operation. Indeed, inertial instruments are deployed in the U. K. Automatic Urban Network (AUN), gathering particle data with a 15-minute time resolution (50). Using this short time resolution, AUN posts on the Internet one-hour-average values, updated hourly, at monitors in approximately 30 cities (http://www.aeat.co.uk/products/centres/netcen/airqual/bulletins/ pm10.html), adding power to ongoing U. K. studies of particle health effects.
Airborne Particle Excursions
Data sets were screened to identify those which 1. were obtained using one or both of the identified technologies, 2. exhibited short time resolution, 3. encompassed at least one 24-hour period, and 4. revealed 24-hour airborne particle levels well within the current NAAQS. Screening identified three
locations, and 10 days, during which 24-hour average PM} < 150 mg/M3 . At all three locations, and
in six of the 10 identified cases meeting the screening criteria, excursions exceeding 150 ug/M3 were noted (Table 1; Figs. 1-3).
In Birmingham, Alabama on 16 April 1990 24-hour average PMjq was 70 ug/M3, but two one-hour-
average excursions exceeding 200 ug/M3 were recorded (Table 1; Fig. 1). In Penticton, British Columbia on approximately eight days between 30 July and 7 August 1994 24-hour average PMj9
varied from close to zero to close to 150 ug/M3 , but excursions exceeding 150 ug/M3 were recorded on four of the eight days (Table 1; Fig. 2). These included three one-hour-average excursions to 300 ug/M3 and two excursions to approximately 500 ug/M3. In Zeebrugge, Belgium on 15 March 1993 24hour average PMj¢ was 101 ug/M3, but several 15-minute-average excursions exceeding 200 ug/M3 were recorded (Table 1; Fig. 3). In one excursion, the 15-minute average reached 2,000 ug/M3, significantly exceeding the estimated magnitude, though not the persistence, of the 1952 London fog (<1,200-pg/M3; 53).
Bioassays
Elucidation of toxicological mechanisms by which fine particles induce adverse health effects observed clinically has been incomplete because of a dearth of animal models (53). However, animal studies have been conducted, and animal models are emerging. The previously unpublished Kleinman, et al. bioassays involved microscopic examination of rat lungs 48 hours after four-hour controlled exposures of groups of six rats to either of two sulfate aerosols, designated AMS and SAM, with the following compositions:
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component AMS SAM
varied components
ammonium 0.5 mg/M3 0.0 mg/M3 sulfuric acid 0.0 mg/M3 0.5 mg/M3
invariant components
iron sulfate 1.0 mg/M3 1.0 mg/M3 manganese sulfate 0.2 mg/M3 0.2 mg/M3 nitrogen dioxide 2.6 ppm 2.6 ppm ozone 0.6 ppm 0.6 ppm sulfur dioxide 5.0 ppm 5.0 ppm
The fraction of microscopically examined rat lung area exhibiting aerosol-induced lesions was evaluated in groups of rats exposed to excursions vs. no-excursion controls exposed to the same aerosol. Thus, except for the excursions, treated and control rats experienced identical exposures. Results are presented in Figure 4, which consists of two sets of paired columns. In both sets, the column to the right indicates greater lesion area in rats exposed to aerosol excursions. However, in the case of AMS, the increment over control rats was greater, reflecting the occurrence of four excursions, compared with only one in the case of rats exposed to the SAM aerosol.
Investigations into airborne particle-induced effects on rats and dogs, under way at Harvard University’s School of Public Health, are likewise closing the data gap between clinical and epidemiological studies vs. animal bioassays. The ongoing research has been published in abstract form (21, 41, 42), and more completely in oral and written reports by John Godleski to CASAC (20). The findings implicate shortterm, possibly electrophysiological mechanisms of fine-particle-induced cardiopulmonary malfunctioning, shown via electrocardiograms (EKGs).
Nearing, et al. (42) induced ST segment elevation and periods of apnea in dogs inhaling fly ash at 1,000 ug/M3 for 3 d, 4 h/d. Nearing, et al. (41) also demonstrated increased T-wave alternans amplitude,
indexing vulnerability to ventricular fibrillation, in dogs inhaling fly ash at 3,000 ug/M3 for 3 d, 3 h/d. ST segment elevation and T-wave alternans effects began soon after exposure and became most prominent by day three.
Godleski, et al. (20, 21) used rats exhibiting either monocrotyline-induced pulmonary inflammation or SO>-induced chronic bronchitis. Rats with respiratory pathology then inhaled particles concentrated
from Boston air at 228 to 288 ug/M3 for 3 d, 6 h/d. Breathing rates declined from 17.1/min. in controls to 9/min. in exposed rats. Apnea for up to 22 seconds occurred. Bronchoconstriction occurred in 80 percent of rats exhibiting respiratory disease, compared with 25 percent of controls. Rats exhibited no
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signs of distress, but deaths occurred on all exposure days, possibly as a result of particle-induced arrhythmias or other EKG-related cardiopulmonary malfunction. Godleski (20) indicated that mortality might also be consistent with systemic effects following particle induction of proinflammatory mediators, such as the cytokines interleukin-1 and tumor necrosis factor-alpha.
Clinical Studies
Clinical literature was evaluated, confirming that high particle levels in the observed range of measured fine particle excursions can cause adverse respiratory effects. Numerous studies of short-term effects exerted by airborne particles during controlled acute human exposures were identified. Many of these reported positive results (4, 5-10, 14, 16-19, 22-30, 32, 40, 61, 62, 64). Table 2 exemplifies the positive studies, ranking the tabulated examples, along with findings of daily mortality studies (for example, see 15) and the current PM) standard (55), in order of increasing dose times exposure duration.
Table 2 indicates that adverse particle-associated health effects have been demonstrated beginning at
levels as low as 202 ug/M3 (64) and at exposure durations as short as 30 minutes (62, 64). These effects were documented in asthmatics at rest (64) or engaged in exercise (62). Participant ages in these studies varied from 19 to 50 (62) and 23 to 48 (64). Thus, no frail elderly, elderly, or infirm subjects were included in the studies. Other positive studies likewise involved asthmatic subjects exercising or at rest, of ages up to 57 years (10, 18, 22, 40). For obvious reasons, adverse effects, when observed, could not be allowed to progress to clinical significance. However, reported effects included increased airway resistance; reduced values of lung function parameters such as forced expiratory volume at one and three minutes (FEV, FEV3), forced vital capacity (FVC), and peak flow; as well as such symptoms as throat
irritation and coughing. Epidemiological Study
At least one epidemiological study points to short-term toxicological mechanisms for inducing morbidity and mortality which may persist for days after an air pollution episode. Lawther, et al. (1970; 31) used a diary method in which bronchitis patients recorded daily changes in the severity of their symptoms relative to their recollection of previous-day symptom severity. The diary method required participants to make an entry pertaining to a full day of symptom experience. Lawther, et al. reported a clear association of symptom severity with daily concentrations of smoke or sulfuric acid in London. They concluded, however, that this association could not be attributed to the measured 24-hour average concentrations, but more likely to “the effects of brief exposures to the maximum concentrations occurring during the day” (source document, page 538), which may be several times the 24-hour average (63) which served merely as a surrogate parameter for such excursions.
The studies described above demonstrate adverse health effects induced by short-term exposure to particles. However, the evaluation of the toxicological significance of responses which were precluded from progressing to clinical significance will also benefit from an inquiry into the possible mechanism(s) of toxicological action producing the demonstrated effects. Elucidation of plausible mechanisms might enable prediction of the clinical significance of similar exposures, or of exposures which are not terminated in a timely manner (as part of an experimental protocol), to more susceptible individuals.
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Only a single toxicological principle need be invoked to demonstrate that brief airborne exposures may be more toxicologically, and more clinically, significant for some individuals. Briefly intense airborne exposures may deposit an overwhelming number of particles per alveolar macrophage cell, inhibit particle clearance, and result in protracted internal pulmonary exposures. The duration of such exposures will be inversely proportional to the fine particle clearance rate. Individuals whose lung function is compromised may clear fine particles less efficiently and less rapidly than normal individuals under identical exposure conditions, increasing their effective exposure to fine particles, as indicated by Miller, et al. (1995; 39). They reported differentials favoring higher exposure of individuals having compromised respiratory systems, including approximately three-fold increases in the number of 1-y particles deposited per unit of respiratory surface area, per ventilatory unit, per alveolus, and per alveolar macrophage cell. They also reported similar findings with respect to 0.1-p particles.
Prolonged internal exposure to fine particles may correlate with irritation and prolonged, potentially lethal, reductions in the alveolar surface area available for gas exchange, and therefore in the efficiency and rate of gas exchange. These challenges may result in cardiopulmonary stress, possibly provoking episodes of apnea and cardiac arrhythmias, especially for the frail elderly, the infirm, and generally for individuals suffering from preexisting respiratory disease (especially if severe). These factors, and possibly increased susceptibility to airborne pathogens (52), suggest the likelihood that short-term adverse effects observed at subclinical intensities in young asthmatics whose cardiopulmonary health is otherwise robust may be exacerbated in older individuals suffering from preexisting health deficits.
CONCLUSION AND DISCUSSION
The findings of this study form the basis for drawing one principal conclusion about the airborne particle issue. Specifically, this study suggests that morbidity and mortality weakly associated with 24-hour elevations of airborne particle mass may be strongly associated with brief excursions of particle mass to levels known to have killed before (such as during the London fog). Several implications arise from this conclusion.
The U. S. EPA’s current NAAQS requires averaging PM) mass over 24 hours and one year, precluding
both detection and control of shorter-term exposures, which appear to be toxicologically significant. However, the Agency so far has declined to propose incorporating an airborne particle mass limit <24 hours (57), reflecting apparent confusion between the averaging time appropriate for health effect causation (and prevention) vs. manifestation:
“The current 24-hour averaging time is consistent with the majority of the results from community epidemiological studies, which have reported associations of 24-hour concentrations of PM 19, fine
particles, and TSP [total suspended particulates] with an array of health effects. Nevertheless, because some such studies have found a stronger association with a multiple day average..., the Staff considered whether a multiple day averaging time would be more appropriate... The 24-hour averaging time effectively protects against episodes lasting for several days while also protecting sensitive individuals who may experience effects after a single day of exposure. Thus, the staff concludes that a longer averaging time, such as 3 to 5 days, would not provide more effective protection than a 24-hour average” (source document, page VI-2; emphasis added).
The time frames over which adverse health effects are caused vs. manifested commonly bear little if any relation to one another. For example, a bullet wound may represent a nearly instantaneous cause of
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death, or a protracted cause. Likewise, diseases may result from instantaneous exposures to pathogens, but pathology typically develops after a significantly longer incubation period, and death (if it occurs) may occur over still longer time frames bearing no relation to the duration of the exposure event.
In the case of airborne particle associated health effects, exposure occurs at some background intensity over long periods, and episodically at sometimes lower and sometimes higher intensities. To illustrate,
Figure 5 depicts exposure to a 24-hour average PM 19 of 100 ug/M3 with a brief (15-minute) excursion
to 1,000 ug/M3, approximately equivalent to that attained during the 1952 London fog (53), and approximately half that actually observed in the present study (Fig. 3). Figure 5 also illustrates the ensuing process of particle accumulation in the lungs, and the slower rate of particle clearance. Finally, alternative time courses for the manifestation of adverse health effects are shown.
Three similar peaks represent possible one-day, two-day, or three-day delays in postexposure mortality, similar to delays reported in some epidemiological studies. Inasmuch as no prior knowledge may be assumed of the occurrence or length of any delay, a shallower curve is also depicted showing the statistical effect of averaging (‘curve smoothing’) over a three-day period. The curve illustrates that the longer-term averaging strategy offers a higher probability of encompassing a delayed mortality peak, if it occurs, whether it occurs after one, two, or three days after exposure. However, this benefit is offset by the reduced height of the curve, showing that each 24-hour mortality peak will be diluted over a 72hour period. This will reduce the probability of statistically identifying a 24-hour peak due to its dilution with (ideally) a 48-hour period of background mortality incidence.
The purpose of the airborne particle standard, as suggested by Figure 5 and the above analysis of multiple-day averaging, is not to assist epidemiologists to detect adverse health effects, but to prevent the effects from occurring. This should reduce attention to curve smoothing and the time frame for health effect detection, focusing it instead upon shorter time frames for health effect causation and prevention. EPA’s Criteria Document addresses the time frame issue for health effect causation (58). However, short-term health effects are excluded from consideration. Indeed, the document prefers the hypothesis of long-term causation:
“One of the best indications that there is a longer-term effect of PM is that the relative risks estimated in the long-term mortality studies are considerably larger than those in the acute mortality studies... This suggests that the long-term studies include the excess deaths inferred in acute studies, and also include some of the excess deaths attributable to air pollution that may occur during low-pollution baseline periods, and would not be inferred by the acute mortality studies” (source document, page 1-36).
The degree of risk posed by particles over any given exposure averaging time will be identical, whether the underlying processes causing pathology act constantly, sporadically, or both, within the selected averaging time. Further, particle-induced health effects clearly must be cumulative, so that exposures of longer duration will be associated with greater risks. This is widely accepted to be the case, for example, with respect to cigarette smoking. Thus, the issue of whether long-term or short-term risks are greater is irrelevant. The relevant issues are 1. whether excursion-associated relative risks to public health correlate with sufficiently high absolute risks to merit management via the NAAQS, and 2. whether observed mortality and morbidity can be plausibly explained without invoking short-term mechanisms of causation.
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This report shows that available evidence supporting short-term causation of particle-associated health impacts in communities includes direct evidence of short-term particle-associated health impacts in clinical (31, 64) and laboratory (20, 21, 24, 41, 42) settings, and direct evidence of particle excursions in communities (35-38). However, directly linking particle excursions in communities with coincident or delayed adverse health impacts in the communities will require using simultaneous real-time and 24hour-average particle data in epidemiology studies. Limited particle excursion data presented in this report and elsewhere (35-38) are neither epidemiological nor adequate to infer a general relationship between daily and hourly airborne particle levels. Indeed, the absence of a general relationship can be inferred a priori, given the sporadic occurrence of various natural events (such as forest and grass fires) and technological events (such as fires in residences or commercial establishments, industrial process upsets, and blasting) which cause particle excursions. However, regulatory risk management need not be justified by direct epidemiological demonstrations when indirect evidence is persuasive (see EPA Airborne Pollutant Standard Setting, below). Indeed, if persuasive indirect evidence is available, the widely accepted philosophy of proactive regulation precludes requiring the most direct form of evidence, ‘body counting’, as a prerequisite for action. The present investigation, even if it falls short of directly associating particle excursions in communities with morbidity and/or mortality in the communities, nonetheless justifies Agency consideration of the short-term causation scenario for standard setting beyond the brief consideration reflected in the Staff Paper (57):
“The staff has also considered the evidence regarding effects associated with PM exposures of durations less than 24 hours. Some investigators prior to the 1987 review (Lawther, et al., 1970) speculated that the observed health effects might be largely due to short-term peaks on the order of an hour. Controlled human and animal exposures to specific components of fine particles, such as acid aerosols, also suggest that some effects, such as bronchoconstriction, can occur after exposures of minutes to hours. Some epidemiological studies of exposures to acid aerosols have also found changes in respiratory symptoms in children using averaging times less than a 24-hour period (e.g., 12 hours). However, it is not clear whether the majority of effects that have been associated with daily exposure to PM, including mortality and various measures of morbidity, would occur after only short duration exposures. Moreover, a 24-hour average can be expected to provide significant protection from potential effects associated with short-duration peaks in most urban atmospheres.” (pp. V1-2 to VI-3, emphasis added).
Thus, EPA rejects short-term causation and, concomitantly, a one-hour mass limit, based upon three incorrect premises: 1. that Lawther, et al. (31) merely “speculated” that peak exposure rather than 24hour exposure exacerbated bronchitis among the subjects of their investigation, 2. that standards for air pollutants must be based upon a “majority” of observed effects rather than just the one effect occurring at the lowest exposure level, and 3. that a 24-hour averaging time will protect against excursions, which is refuted by the present investigation. The Lawther, et al. study is further evaluated below.
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Lawther, et al. (1970; 31) did not merely “speculate” that exacerbation of bronchitis symptoms among their patients was caused by peak rather than 24-hour exposure. Rather, consistent with (later) EPA airborne pollutant standard setting under the Clean Air Act (see below), they drew the conclusion based upon clinical data on normal subjects. The relevant portion of the Lawther, et al. report follows:
“One further reservation is that the measurements quoted in the present paper relate only to 24-hour average concentrations of sulphur dioxide and other pollutants. The evidence that we have from experimental work on normal subjects suggests that the effects of inhaling prepared mixtures of pollutants are of rapid onset, and peak concentrations encountered during the day may therefore be more relevant than 24-hour averages. The effects that we have reported cannot be considered as the
result of 24-hour exposures to at least 500 ug/MB of sulphur dioxide together with 250 ug/M3 of smoke: they are more likely to reflect the effects of brief exposures to the maximum concentrations occurring during the day, and these may be several times the 24-hour averages” (source document, page 538; emphasis added).
Finally, the EPA Criteria Document (60) accepts as valid the Lawther, et al. findings:
“The analysis of the Lawther et al. (1970) study was made prior to the availability of current statistical methods such as Poisson regression using generalized estimating equations. The large differences seen by Lawther et al. (1970) at high levels would undoubtedly remain significant regardless of the analysis technique” (subject document, pp. 12-109 to 12-110).
EPA Airborne Pollutant Standard Setting
The findings reported in epidemiological and controlled human exposure studies must be evaluated relative to EPA policies and procedures for air pollutant standard setting (3, 56) based upon the weight of evidence for the existence, nature, and magnitude of public health risks. The Agency requested the American Thoracic Society to define toxicological effects, and degrees of effect, which might qualify as forming the basis for limiting air pollutants, and both the American Thoracic Society (1985; 3) and the U. S. EPA (1989; 56) have published these guidelines. Their implementation leaves much to the discretion of the implementer, but the guidelines are prescriptive and valuable nonetheless.
According to U. S. EPA policy (56), air pollution limits must be set based upon a clinically significant adverse effect, not any effect, as defined by American Thoracic Society (3):
"We define ‘adverse respiratory health effects' as medically significant physiologic or pathologic changes..." (source document, page 666).
Many of the controlled human exposure studies focus upon asthmatics during exercise and at rest. These studies, described earlier in Table 2 and associated text, reveal symptoms of asthma exacerbation such as bronchoconstriction, increased airway resistance, reduced FEV; and FEV3, reduced FVC, and
reduced peak flow. The issue of whether these effects can form the basis for air pollutant standard setting under EPA’s Clean Air Act implementation policies and procedures is resolved by the American Thoracic Society:
"[I]t is important to consider differences between statistical significance and medical or biological
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significance... Not all [statistically significant] changes (e. g., physiologic) are necessarily adverse... [For example, according to the US EPA] the eye, nose, and throat irritation associated with ... urban ‘smog’ or photochemical oxidant air pollution is not medically important and is, therefore, not considered an ‘adverse health effect' in relation to the Clean Air Act. This irritation certainly is annoying or bothersome, which puts it in the category of an effect on human welfare. However, irritation that triggers an asthmatic attack is an adverse health effect. The EPA has portrayed this pollution burden (figure 1) by indicating the proportion of the population that might be affected... [and] an area of responses that might be considered adverse” (American Thoracic Society 1985, page 666; 3; emphasis added).
Clearly, the symptoms evoked by controlled clinical exposures as described and tabulated (Table 2) above do not include triggering an asthmatic attack. However, according to EPA and American Thoracic Society guidelines, this clinical endpoint need not be experimentally induced to be used in standard setting. Rather, the guidelines justify inferring greater severity of response with greater exposure. The American Thoracic Society, quoted above, continues as follows:
This spectrum of biologic responses would be evoked more strongly as the concentrations of pollutants are increased" (American Thoracic Society 1985, page 666; 3; emphasis added).
The U. S. EPA has proposed to regulate PM) 5 rather than PMjq (57). This proposal is irrelevant to the
present findings made or conclusions drawn. Effects exerted by particles are widely acknowledged to result predominantly from the most respirable (fine) fraction. PM 9 excursions undoubtedly encompass
excursions of PMj 5. Thus, the 24-hour PMjq standard of 150 ug/M3 can be expressed as an
equivalent one-hour standard of about 300 ug/M3, which may be in turn formulated as a one-hour PM) 5 mass equivalent if the NAAQS focus changes.
The present investigation has revealed that 1. significant airborne particle excursions occur over brief intervals of 15 minutes to one hour, 2. such excursions are potentially significant toxicologically, and 3. the effects caused by short-term exposure to particles constitute appropriate clinical bases for standard setting under the Clean Air Act. These findings add to the risk management options available to the EPA. The EPA must soon decide whether to risk further legal challenge by managing airborne particles to levels below those of demonstrated toxicological significance. The present investigation enables the Agency to reject standard setting in the absence of demonstrated statistical and clinical significance of the health risks being managed. Alternatively, the Agency can manage airborne particle risks based upon statistically and clinically significant public health endpoints, avoidance of which is consistent with EPA policies and procedures for airborne pollutant standard setting under the Clean Air Act.
The cost of NAAQS compliance is large, and will increase if the 24-hour airborne particle mass limit is revised downward. The cost to the Agency will be large if the proposed standard is legally challenged, and larger if it does not prevail. Compliance with a one-hour mass limit would be less burdensome because it would primarily affect equipment start-up and shutdown rather than constant facility operation. The present study suggests that a one-hour limit may eliminate the need to strengthen longerterm limits while being: 1. more effective at protecting health, 2. justified by available data, and 3. economically feasible.
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»
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American Lung Association. The Perils of Particulates. New York City, 24 pp., March 1994;
American Thoracic Society. Guidelines as to what constitutes an adverse respiratory health effect, with specific reference to epidemiologic studies of air pollution. American Reviews of Respiratory Disease, 131:666-8, 1985;
Anderson, K. R., et al. Controlled exposures of volunteers to respirable carbon and sulfuric acid aerosols. Journal of the Air & Waste Management Association, 42:770-6, 1992;
Aris, R., et al. The effects of sequential exposure to acid fog and ozone on pulmonary function in exercising subjects. American Reviews of Respiratory Disease, 143:85-91, 199 1a;
Aris, R., et al. Lack of bronchoconstrictor response to sulfuric acid aerosols and fogs. American Reviews of Respiratory Disease, 143:744-50, 1991b;
Avol, E. L., et al. Respiratory dose-response study of normal and asthmatic volunteers exposed to sulfuric acid aerosol in the sub-micrometer size range. Toxicology and Industrial Health, 4:173-84, 1988a;
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Balmes, J. R., et al. Acidity potentiates bronchoconstriction induced by hypoosmolar aerosols. American Reviews of Respiratory Disease, 138:35-9, 1988;
CASAC. Letter from George T. Wolff, CASAC Chairperson, to EPA Administrator Carol M. Browner transmitting CASAC comments on the April 1995 draft Air Quality Criteria for Particulate Matter. Washington, DC; Clean Air Science Advisory Committee (CASAC), EPA-SAB-CASAC-LTR-95-005, 4 pp., 31 August 1995;
Chow, J. C. Measurement methods to determine compliance with ambient air quality standards for suspended particles--summary of critical review. Environmental Manager, 1:12-5, May 1995;
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Culp, D. L., et al. Composition of human airway mucins and effects after inhalation of acid aerosols. American Journal of Physiology, in press, 1995;
Dockery, D. W., and C. A. Pope III. Acute respiratory effects of particulate air pollution. Annual Reviews of Public Health, 15:107-32, 1994;
Fine, J. M., et al. The role of titratable acidity in acid aerosol-induced bronchoconstriction. American Reviews of Respiratory Disease, 135:826-30, 1987a;
Fine, J. M., et al. The roles of pH and ionic species in sulfur dioxide- and sulfite-induced bronchoconstriction. American Reviews of Respiratory Disease, 136:1,122-6, 1987b;
Framptom, M. W., et al. Sulfuric acid aerosol exposure in humans assessed by bronchoalveolar lavage. American Reviews of Respiratory Disease, 146:626-32, 1992;
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Godleski, J. J. Oral and written report to the PM)9 Review Panel, U. S. EPA Clean Air Science
Advisory Committee (CASAC). Research Triangle Park, North Carolina; 14 December 1995;
Godleski, J. J., et al. Death from inhalation of concentrated ambient air particles in animal models of pulmonary disease. New Orleans, Louisiana; American Thoracic Society 1996 International Conference, 11-15 May, abstract in press, 1996;
Green, D. J., et al. Acute pulmonary response in healthy, non-smoking adults to inhalation of formaldehyde and carbon. Journal of Toxicology and Environmental Health, 28:261-75, 1989;
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Table 1. Short-Term Particle Excursions Without Exceedance of the 24-Hour PM-10 Standard
source 24-hour airborne excursion excursion- excursionaverage particle averaging _to-24-hour to-1952 particle mass time mass London-Fog mass excursion ratio ratio™* (ug /cu M) (ug/cu M) (minutes)
3/15/93 101 1,898 15
7/31/94 50 500 60
3/15/93 101 780 15
3/15/93 101 648, 15
3/15/93 101 553, 15
8/1/94 100 460 60
3/15/93 101 425 15
3/15/93 101 355, 15
s 8/1/94 100 320 60
Birmingham, Alabama 4/16/90 70 222 60 Birmingham, Alabama 4/16/90 70 208 60 Penticton, British Columbia 8/2/94 120 350 60 s 8/1/94 100 280 60
Zeebrugge, Belgium 3/15/93 101 283 15 Birmingham, Alabama 4/16/90 70 176 60 Penticton, British Columbia 8/3/94 120 290 60 Zeebrugge, Belgium 3/15/93 101 238 15 Zeebrugge, Belgium 3/15/93 101 230 15 Zeebrugge, Belgium 3/15/93 101 220 15 i 3/15/93 101 220 15
8/2/94 120 250 60
8/3/94 120 240 60
3/15/93 101 195 15
3/15/93 101 193 15
3/15/93 101 185 15
8/3/94 120 210 60
3/15/93 101 153 15
Birmingham, 3/1 day; Penticton, 9/9 days; Zeebrugge, 15/1 day Imean excursion (ug/cu M) we 99 373 we 3.9 0.3 standard deviation (ug /cu M) we 17 342 we 3.6 0.3 coefficient of variation a 17 91 os 92 91
locations examined
fraction exhibiting excursions days examined
fraction exhibiting excursions
“Sources: adapted from:
1. Institute of Hygiene and Epidemics, Belgium;
2. Meyer, M. B. Applications of continuous PM-10 measurements. Conference on the Role of Meteorology In Managing the Environment of the 90s. Scottsdale, Arizona; 26-28 January 1993;
3. Rupprecht, E.; M. B. Meyer, and H. Patashnick. Performance characteristics of a near real-time particulate mass monitor. Conference on Particulate Matter: Health and Regulatory Issues; Pittsburgh, Pennsylvania; 4-6 April 1995.
**Conservatively assumes London fog = 1,200 ug/cu M, but this estimate is probably total particulates rather than only PM-10. The deaths of approximately 4,000 people over 10 days in 1952 have been attributed to the London fog (see text for source).
Table 2. Particle Effects Revealed In Controlled Acute Human Exposures
citation healthy | asthmatic | activity | subject {particle MMAD dose duration dose x effect(s) fl subjects | subjects level | age span |type(s) [*] duration (y) we (uM) (ug /cu M) (min.) —|(ug min/cu M)]... Yan and healthy: no effects; Vane 1994 30 25 at rest 23-48 |TSP we 202 30 6,060 asthmatic: reduced _lung| 8 function (FEV1)
beg et al., 0 15 exercise 19-50 |NaCl, H2SO4, NH3 0.80 700 30 21,000 reduced lung function (FEV1)
ann eto 17 exercise} 20-57 |NaCl, H2S04 i 190 120 22,800 | reduced lung function (FEV1)
Green, et . activated carbon + cough, reduced lung function|
al., 1989 24 0 exercise 18-35 formaldehyde 14 1,020 120 122,400 (FVC, FEV3, peak flow)
72,000 -|daily mortality and
we we we | ae we [ou 10 | 50-100) 1,440 ’ y_ mortality 144,000 _|morbidity begin
oe oe a oe wee wee 10 150 1,440 216,000 |NAAQS for PM-10
Framptom,) 19 0 exercise | 20-39 |NaCl +H2S04 0.9 2,000 120 240,000 _ [threat irritation; no effect on
et al., 1992 lung function
Balmes, et 5,900,000 to) increased specific airway]
al. 1988 0 12 at rest 25-41 |NaCl,30 mOsm 5.3 - 6.1 87,100,000 we 25,900,000 resistance
‘citations:
1. Balmes, J. R., et al. Acidity potentiates bronchoconstriction induced by hypoosmolar aerosols. American Reviews of Respiratory Disease, 138:35-9, 1988; 2. Framptom, M. W., et al. Sulfuric acid aerosol exposure in humans assessed by bronchoalveolar lavage. American Reviews of Respiratory Disease, 146:626-32, 1992; 3. Green, D. J., et al. Acute pulmonary response in healthy, non-smoking adults to inhalation of formaldehyde and carbon. Journal of Toxicology and Environmental Health, 28:261-75, 1989; 4. Morrow, P.E., et al. Effects of near ambient levels of sulphuric acid aerosol on lung function in exercising subjects with asthma and chronic obstructive pulmonary disease. Annals of Occupational Hygiene, 38(Supplement 1):933-8, 1994; 5. Utell, M. J., et al. Effect of inhaled acid aerosols on respiratory function: the role of endogenous ammonia. Journal of Aerosol Medicine, 2:141-7, 1989; 6. Yang, S.-C., and S.-P. Yang. Respiratory function changes from inhalation of polluted air. Archives of Environmental Health, 49:182-7, 1994.
**MMAD: mass median aerodynamic diameter
Fig. 1. Hourly PM-10 Fluctuations in Birmingham, Alabama on 16: April 1990 with a 24-Hour PM-10 Average of 70 Micrograms Per : Cubic Meter*
2 g :| 8B |= im 2 a
hour of the day
*Data provided by Rupprecht & Patashnick Co. (Albany, New York). Also see: Meyer, M. B. Applications of continuous PM10 measurements. Conf. on The Role of Meteorology in Managing the Environment of the 90s. Scottsdale, Arizona; 26-28 January 1993.
Fig. 2. Hourly and Daily PM, 9 Concentration In Penticton, British Columbia, 30 July to 7 August 1994*
500 7
1-Hour and 24-Hour PM-10 Cone [yg/m’]
100 24-Hour Average PM-10 ie} a —__——. —— 30-Jul-94 31-Jul-94 1-Aug-94 2-Aug-94 3-Aug-94 4-Aug-94. 5 Aug-94 — 6-Aug-94—7-Aug-94
Time
*source: Rupprecht, E., M. B. Meyer, and H. Patashnick. Performance characteristics of a near real-
time particulate mass monitor. Presentation at Conference on Particulate Matter: Health and Regulatory Issues. Pittsburgh, Pennsylvania 4-6 April 1995.
Fig. 3. Time Variation of 15-Minute Average PM-10; Zeebrugge, - Belgium; 15 March 1993 (24-Hour Average = 101 ug/cu Meter)* |
‘With permission from the source: Institute of Hygiene & Epidemics, Belgium.
Fig. 4. Pulmonary Effect of Five- To 10-Minute Sulfate Aerosol: Excursions During Four-Hour Controlled Exposures of Rats* :
A16.72+ |-2.25¢y
444.09+/-1.15| 2
rat lung lesion area at 48 hours| (percent of area examined)
excursions, n = 6 rats AMS, four
excursions, n = 6 rats SAM, zero excursions, n = 6 rats SAM, one excursion, n = 6 rats
AMS: ammonium, Fe + Mn sulfates (0.5, 1.0, 0.2 mg/cu M) SAM: sulfuric acid, Fe + Mn sulfates (0.5, 1.0, 0.2 mg/cu M)
ALL: ozone, NO2, SO2 (0.6, 2.6, 5.0 ppm)
*data source: Michael Kleinman, UC/Irvine, unpublished.
Time Course of Exposure To Airborne Particles Vs Time Course of Epidemiological Response
less)
imension
z Vv a} 3 5
magni
fine particle clearance
(124-h average exposure Mshort-term peak exposure
Bi three-day average mortality | Mone-day delayed mortality Eitwo-day delayed mortality |} U three-day delayed mortality j
J accumulation and clearance
time course (hours
Publication citation
Michaels, RA; and Michael T. Kleinman. Dose-dependent health risks support control of one-hour airborne particle levels. Proceedings, 90th Annual Meeting of the Air & Waste Management Association; Toronto, Ontario, Canada; 8-13 June 1997, 21 pp. 1997;