# j j j j j j j j j j j j j j 

# j j j j j j j j j j j

j j

j j

### mean level of21.7 IlgfmJ 

### measured at two urban-center monitors in 2003 (which is used as the basis for the risk assessment presented in Chapter4). This observation prompted sta:ffto further 3 explore the comparison between PM,0•2.5 

### levels monitored at Detroit and Windsor sites. This 4 explorationhas shown thatin recentyears, based on availableWindsor and Detroitdata from 5 1999 to 2003, the Windsormonitors used in this study typically have recorded PM,0•2.5 

### levels that 6 are generally less than halfthe levels recorded at urban-centerDetroitmonitors, though the 7 concentrations measured in Windsor are more similar to concentrations reported for suburban 8 areas well outside the city (Ross and Langstaff, 2005). These observations lead staffto conclude 9 that the statistically significant, generallyrobust association with hospital admissions in Detroit 10 reflects popUlation exposures that may be appreciablyhigherthan whatwould be estimated 11 using data from theWindsormonitors. Taking these observations into account, staffnonetheless 12 believes thatthese studies in general, and the Detroit study inparticular, do provide evidence of 13 associationsbetween short-term exposures to PM IO•2.S

### and hospital admissions. Staffdoes 14 conclude,however, thatthe association observed intheDetroit study, which staffjudgesto be 15 the strongest ofthese studies, likelyreflects exposure levels potentiallymuchhigher inthe central city area than thosereported in that study. Based onthis information, staffbelieves that alternative 24-hourPM IO•2.5 

### standards appropriate for consideration in this review need not 18 necessarily extend to levels down tll orbelow the ranges reported in these studies in orderto 19 provideprotection from the morbidity effectsrelated to short-term exposures to PM,0•2.S' 

### 20 Staffhas also looked at the evidencefrom U.S. and Canadian studies thatreport 21 statistically significant and generallyrobust associations with mortality and short-term exposures 22 to PM 10.2.5' 

### As discussed in section 9.2.3 ofthe CD, the evidence associatingmortality wirlr

. 23 short-term exposures to PM IO•2.5 

### is too uncertain to infer a likely causalrelationship, although-it 24 is suggestive ofapossible causal relationship. Staffidentifiedtwo such studies, conducted in 25 Phoenix (Mar et ai., 2000, 2003) and Coachella Valley, CA (Ostro etai., 2000, 2003), that report 26 981h percentilePM,0.2.S

### values ofapproximately 70 and 107 IlgfmJ, 

### and 99'h percentile values of 27 75 and 1341lgfmJ, 

### respectively. Staffnotes that these studies were conducted in areas with air 28 quality levels that would not have metthe currentPM 10 

### standards. A staffanalysis ofPM 10 

### and 29 estimated PMIO•2.5

### concentrations from the AQS database for 200I to 2003 suggests that 981h

January 2005 

### 5-68 Draft

-DoNot Quote or Cite

### particles at such a generally "equivalent" level, the evidence concerning air quality levels of thoracic coarse particles in the studies is not strong enough to provide a basis for revising the level ofprotection generally afforded by the current PM" standards. 5.4.4.2 Risk-based Considerations Beyond looking directly atthe relevant epidemiologic evidence and related air quality information, staffhas also considered the extent to which the PM".,., risk assessment results discussed in Chapter4 can help inform consideration ofalternative 24-hourPM1,.,., 

### standards. While one ofthe goals ofthe PM".,., risk assessmentwas to provide estimates ofthe risk reductions associated withjustmeeting alternative PM".,., standards, staffhas concluded thatthe nature and magnitude ofthe uncertainties and concerns associated with this portion ofthe risk assessmentweigh against use ofthese risk estimates as a basis for recommending specific standard levels. These uncertainties and concerns include, but are not limited to the following:

• as discussed above, concerns thatthe currentPM".,., levels measured at ambient monitoring sites in recent years may be quite differentfrom the levels used to characterize exposure in the original epidemiologic studies based on monitoring sites in different location, thus possibly over- orunderestimatingpopulation risk levels; greater uncertainty about the reasonableness ofthe use ofproportional rollback to simulate attainment ofalternative PM".,.,daily standards in any urban area due to the limited availability ofPM".,, air quality data overtime;

concerns that the locations used in the risk assessment are not representative of urban areas in the U.S. that experience the most significant 24-hour peak PM".,., concentrations, and thus, observations about relative risk reductions associated with alternative standards may not be relevant

### to the areas expected to have the greatest health risks associated with elevated ambient PM"." levels; and

concerns aboutthe much smaller health effects database that supplies the concentration-response relationships used in the risk assessment, compared to that available for PM", which limits our ability to evaluate the robustness ofthe risk estimates for the same health endpoints across different locations.
5.4.4.3 Summary [n considering the relevant dosimetric, toxicologic, and epidemiologic evidence, associated air quality information, and related limitations and uncertainties, staffconcludes that there is support for considering a 24-hour UPM".,., standard to replace the current PM" standards to provide protection against health effects associated with short-term exposures to thoracic coarse particles that are generally present in urban environments. [n looking at the evidenceofassociations between short-term exposure to PM".,., and morbidity and mortality,
5-69

## j j j j j j j j j j j j j j j j j j j j j j j j j j j j j j j j j j j j j j j j j j j I 

## j j j

# JONATHAN BORAK 

# & COMPANY, INC, Specialists in Occupational & Environmental Health

August 10, 2005

Rogene Henderson, Ph.D. Chair, Clean Air ScientificAdvisory Committee Lovelace Respiratory Research Institute 2425 Ridgecrest Drive, SE Albuquerque, NM 87108 Dear Dr. Henderson: I am writing at the request ofthe National Cattlemen's BeefAssociation ("NCBA") in orderto express my concerns regarding the scientific basis for the proposed NAAQS for coarse particulate rnatter (PM 10-2.5) that is currently under CASAC review. In an earlier letter (dated May 4,2005), I shared related concerns about the OAQPS Staff Paper (2nd draft) that was then under CASAC review. Since May, CASAC published its Reviewofthe NationalAmbientAirQuality Standards for. Particulate Matter(Second Draft PM StaffPaper, January2005) and thereafter EPA published a final PMSiaffPaper("SP") (EPA-452/R-05-005, June 2005). As a result, the coarse particulate focus has shifted, with attention now directed to the regulation of "urban coarse particles" as distinguished from "non-urban" and "rural coarse particles". This standard-setting process has continued despite repeated acknowledgement by EPA staffthat there is at best a "limited body ofevidence" to support a coarse particulate standard. There is inadequate evidence documenting adverse health effects ofcoarse particulate: "a growing, but still limited, body ofevidence on health effects associated with thoracic coarse particles from studies that use PM 1o•2
.5 as a measure ofthoracic coarse particles." (SP: 5-47) (emphasis added) Likewise, there are sig'nificant limitations to the epidemiologic support for such a standard:

234 Church Street, Suite 1100. New Haven, CT 06510/Telephone (203) 777-6611 I Fax (203) 777-1411Rogene Henderson, Ph.D August 10, 2005 Page 

### 2.

"staff recognizes thatthe substantial uncertainties associated with the limited available epidemiologic evidence present inherent difficulties in interpreting the evidence for setting appropriate standards

..." (SP: 5-52) (emphasis added) "The available epidemiologic evidence for effects of PM10.2.5 exposure is guite limited and is inherently characterized 

### by large uncertainties, reflective in part ofthe more heterogeneous nature ofthe spatial distribution and chemical composition ofthoracic coarse particles and the more limited and uncertain measurement methods that have generally been used to characterize their ambient concentrations." (SP: 5-53) (emphasis added) But even these cautionary notes and caveats are insufficient. As discussed below, the studies cited in the SP contain fewer relevant data and a less compelling "body ofevidence" about coarse particulate than is claimed in the SP. In the following discussion, I particularly address statements made in section 

### 5.4 ofthe SP. ToxicologiC evidence The evidence presented in the SP begins with consideration of"limited toxicologic studies" that evaluated adverse effects of urban road dust. Two specific studies are cited, Kleinman et al (1) and Steerenberg et al (2). In addition, the SP notes thatthe CD presented "some very limited in vitro toxicologic stUdies" suggesting that coarse particulate "may elicit proinflammatory effects." Kleinman study (1) 1) In this study, SO rats were exposed to resuspended "road dust" particles of undetermined composition with an MMAD of4

### tim: "only 4

### tim MMAD particles were tested" 

### (1). Neitherthe particle size distribution northe proportions of particles <2.5

### tim and >2.5

### tim was reported. Accordingly, it is not possible to know whether observed effects were due to fine particulate, coarse particulate, or both. The probable confounding ofthe coarse fraction by fine road dust particles was noted by the authors: "there are small but significant contributions of crustal elements from road dustto the submicrometer particle faction of PM1Q" (1).Rogene Henderson, Ph.D August 10, 2005 Page 3.

Because this study could not differentiate the putative effects of PM ,O•2 .5from those of PM2

.5, it is difficult to see its direct relevance to setting a PM1Q.2.5 standard. 2) Additional animals were exposed to submicrometer particles ofammonium sulfate or ammonium nitrate. Sulfate and nitrate were more consistent and more potent in their effects than was road dust: The "most consistent effects were observed in rats exposed to

...sulfate and nitrate"; their relative potencywas "SO.-2 

### > N03' 

### > road dust". (1) Thus, the authors concluded thatthe effects observed in the study were mainly due to submicrometer PM1Q components: "This study also supports the hypothesis that the fine fraction of PM1 0 is more toxic than the coarse fraction." (1). Because the findings attributed to resuspended road dustwere relatively weak and inconsistent, it is difficult to see the direct relevance ofthis study to setting a PM1Q.2.5 standard. Steerenberg study (2) 1) These authors evaluated the adjuvant activities offive "ambient" particulates (two samples ofdiesel exhaust, a residual oil fiy ash, and two actual ambient dusts) in two allergenicity models (ovalbumin in BALB/c mice and grass pollen in BN rats. Neither ofthe actual ambient dusts represented PM

## ,0

.2
.5
. The first (Ottawa dust, EHC-93) had been previously characterized (3); the count median diameterwas 0.5-0.6 Jim and the MMAD was 3-4 Jim. The second (road tunnel dust) was collected by a device that can classify particulate into three size classes: <0.1 Jim, 0.1-2.5Jim and 2.5-10 Jim (4), but there is no indication that the administered dustwas otherthan <PM1Q. We can reasonably expect that diesel and fly ash samples consisted of mainly submicrometer particles. In addition, a SUbstantial proportion ofat least one ofthe ambient dust particles was <2.5 Jim and there is no indication that the second ambient dust did not contain a substantial number of particles <2.5 Jim. Thus, it is not possible to attribute observed effects to PM

## ,0

.2
.5
. Because the study did not differentiate between fine and coarse particulate, it is difficultto see the direct relevance ofthis study to setting a PM ,0
.2.5 standard. 

### •Rogene Henderson, Ph.D August10,2005 Page 4. 2) All five particle types demonstrated adjuvant activity in the ovalbumin model, but only one (a sample ofdiesel exhaust) had such activity in the pollen model. The authors raise various concerns about the relevance ofthe ovalbumin model: "ovalbumin might not be the most relevant antigen for respiratory allergy in humans to studythe effects ofair pollution in an animal model

... more realistic antigens for studying the association between air pollution and allergy are pollen grains or house dust mite antigens." (2) Because the findings attributed to ambient (i.e., road) dustwere seen only in the model deemed less "relevant" and less "realistic", it seems inappropriate that staff so strongly embraced this study as directly relevant to setting a PM 10-2.s standard. Epidemiologic evidence The SP describes three groups ofepidemiologic stUdies. The first group focused mainly on the associations between PM exposure and morbidity. I expressed my concerns about those studies in my letter ofMay4, 2005 and rny concerns persist unchanged. The two other groups included studies that considered "mortality associations

... reported

... in areas with relatively high PM 10-2.S" and studies that considered various outcomes (e.g., hospitalizations, medical visits, mortality) "in areas where PM 10 is typically dominated by coarse fraction particles". In the following discussion I present my concerns about those cited studies. Mortality Studies in Areas with Relatively High PM 10
-2
.S The SP cites three studies (six reports) in support oftheir statement that statistically significant mortality associations were reported in areas with "relatively high PM 1O•2.Sconcentrations". I note thatthe SP does notdefine or explain the term "relatively high

... concentrations." Phoenix study 1) The Phoenix study, published originally in 1997 (5) and after statistical reanalysis in 2000 (6), found "marginally significant (p<0.10)" associations between PM1o-2.s (referred to as PMCF) and total mortality, but there was no significant association between total mortality and PM2.S. PM measures were statistically associated with cardiovascular mortality, but that association wasRogene Henderson, Ph.D August 10, 2005 Page 5. weakest for PM10-2.5
. In the statistical reanalysis, the strength of marginally significant associations was reduced. A great number of statistical analyses were performed on a large numberof variables under a variety of lag conditions. The scope ofthese analyses (but not their actual number) is indicated by the authors in the following statement: "Summaries ofthe RR between the exposure variables and both total and cardiovascular mortality are presented in Table 6 and 7, respectively. Because ofspace limitations, we only present statistically significant (p<0.05) and marginally significant (p<0.10) results in thetables, although modelswere run using all ofthe pollutants listed in Table 5. We evaluated the associations

... using single-pollutant models." (5) Because Table 5 lists 17 pollutants and because there were at least 5 lag conditions and two mortality categories, I infer that at least 170 analyses were performed. The authors describe no adjustments and express no concerns about the statistical complexity caused by such multiple comparisons (7). In such a context, even when authors can justify not adjusting for multiple comparisons, it is difficultto supportthe assumption that "marginal" and "weak" associations (i.e., p<0.10) have much statistical meaning. Such concerns are heightened when "marginal" findings are internally inconsistent (i.e., sporadic findings within a data set) and externally inconsistent (i.e., not supported by most other studies and therefore unexpected). This is the case for the Phoenix coarse particulate data. 2) The lack ofsignificant association between PM2.5and total rnortality is surprising and difficultto reconcile with the robust associations documented in most studies (and described in the CD). Thatfinding does not seem adequately explained by merely observing that Phoenix PM2.5represented only a minority of total PMlO. In other cities where PM10.2.5 > PM2.5 (e.g., Topeka in the Harvard Six Cities study (8)), the expected positive association between PM2
.5and mortality was observed. Thus, the lack ofan association between PM2.5 and total mortality in Phoenix raises concerns aboutthe integrity ofthe database and whether it is appropriate as the basis for generalization. 3) A negative association was found between soil and total mortality, although soil was well correlated with PM10.2.5 (r=0.66). Similarfindings derive from the FactorAnalysis, which reported a significant negative association between "fineRogene Henderson, Ph.D August 10, 2005 Page 6.

soil" and total mortality; there was no significant association between "fine soil" and cardiovascular mortality. While it is unlikelythat exposure to crustal particulate is protective, these findings support the results ofother studies (e.g., (9)) that found few or no adverse health effects attributable to coarse crustal particulate. 4) It is unfortunatethatthis study used only single-pollutant models: "We evaluated the associations between total and cardiovascular mortality and the gaseous pollutants, PM mass metrics, and PM composition metrics using single-pollutant models." (5) In my earlier letter, I discussed (with respectto the Toronto (10) and Detroit (11) studies) the limitations that stem from use ofsuch models. Based on their study, which found that apparent associations with particulates disappeared after adjustment for co-pollutants, Burnett and colleagues recommended that: "all available air pollution measures be considered in assessing the effects ofany single pollutant on health". (10) Likewise, the HEI Health Research Committee echoed that recommendation in its comments on the Detroit study: "In orderto determine the relative effects of several risk factors on a health outcome, ideally all variables under considerations would be included in a single model." HEI Synopsis: 80 in (11) The use ofsingle-pollutant models limits the meaningfulness ofthe conclusions drawn fram the Phoenix study. Coachella 1) The SP cites three reports by Ostra and colleagues that evaluated mortality in the Coachella Valley (12-14). The first report considered only PM10, while the subsequent reports considered PM lO, PM2.5 and PM lO
.2
.5
. PM10data were available for a 10-year period, but PM2
.5data were available for only 2.5 years. Accordingly, the missing PM2
.5and PM10.2.5 were "estimated" using a predictive function that estimated PM10.2.5 as a cubic function of PM10· IRogene Henderson, Ph.D August 10, 2005 Page 7.

Since PM'O-2.5 was estimated from PM,o by means of a formula fitted to the existing data by ordinary least squares, it is not surprising that a high correlation was found between PM 10 and PM'O-2.5. But there was such poorfit for PM2.5 data thatthe authors concluded that "predictive models could not be successfully estimated" (14). It is disturbing that this study relied on estimated data that could notfitthe expected simple relationship: PM'O-2.5 

### = PM,o
- PM2
.5

. I presume thatthis reflects a decision to derive a bestfit equation for onlythe relationship between PM'O-2.5 and PM 1O, ratherthan finding the bestfit to simultaneously predict both PM'O-2.5 and PM2
.5

. Regardless ofthe correlation reported, it is difficultto acceptthat the predictive equation truthfully reflects the nature of PM in the Coachella Valley. In turn, inferences drawn from these estimated data should be viewed with skepticism. 

### 2) The above concerns aboutthe estimated coarse particulate data also raise concerns about the precision ofthe Coachella Valley effects data and their appropriateness for quantitative risk assessment. The SP established a criterion ("rough indicator of '" precision") for deciding whether studies effects data were sufficiently precise to be used in quantitative estimates ofexposure-response relationships:

. "The natural logarithm ofthe mortality-days (a product ofeach city's daily

mortality rate and the numberofdays forwhich PM data were available) can be used as a rough indicatorofthe degree of precision of effect estimates

... staff chose to consider only those urban areas in which studies with relatively greater precision were conducted, specifically including studies that have a natural log of mortality-days greaterthan or equal to 9.0 (i.e., approximately 8,000 deaths) fortotal non-accidental mortality." (SP, p. 4-6) Because the Coachella study contained only 2.5 years of PM2
.5data and deaths averaged 5.8 per day, the SP excluded this study from quantitative analyses. Likewise, because there were only 2.5 years of 'real' data for coarse particulate (i.e., measures of PM'O-2.5 determined literally as the difference between PM'0 and PM2 .5

), there were too few mortality-days to use the Coachella study for quantitative assessment ofexposure-response relationships for coarse particulate. IRogene Henderson, Ph.D August 10, 2005 Page 8.

Six Cities Study 1) The SP cites Steubenville, one ofthe cities included in the Harvard Six Cities study, as supporting the view that statistically significant mortality associations were reported in areas with "relatively high PM 1o-2 .5 concentrations". The study data were originally published in 1996 (8); a statistical reanalysis was published in 2003 (15). The staffview differs from the conclusions ofthe study authors: "The particle associations were specificallywith fine particle mass concentrations, with little additional contributions from the coarse particle mass fraction

... Forthe coarse particle mass fraction, the combined effect estimate was weaker, not statistically significant, and inconsistent in the city-specific associations."

. 

### 2) It is curious that staff put such emphasis on Steubenville, because in the context ofestimating exposure-response relationships for PM2.5, the SP had earlierdiscounted the Steubenville data as imprecise: "The natural logarithm of the mortality-days (a product of each city's daily mortality rate and the number ofdaysfor which PM data were available) can be used as a rough indicator ofthe degree of precision of effect estimates

... staff chose to consider only those urban areas in which studies with relatively greater precision were conducted, specifically including studies that have a natural log of mortality-days greaterthan or equal to 9.0 (i.e., approximately 8,000 deaths) for total non-accidental mortality." (SP, p. 4-6) On the basis ofthis criterion, Steubenville was excluded from the quantitative analysis. 3) Besides possible imprecision, it is likely thatthe Steubenville PM 1O-2
.5data were confounded by PM2
.5
. In five ofthe six study cities (but not Steubenville), correlations between PM2.5 and PM 1O-2 .5 were relatively low (0.23-0.45). In Steubenville, however, the correlation was "quite high (0.7)" (8). Furthermore, in ancillary analyses, it was shown that the estimated association with PM 1O-2 .5 was explained by PM2 .5 and that the estimated effect ofa given increase in PM 1o-2.5 increased "proportionately with the correlation between PM1Q.2.5 and PM2
.5

" (8). 

# ,Rogene Henderson, Ph.D August 10, 2005 Page 9.

Thus it seems very likely that the apparent association of mortality and coarse particulate in Steubenville was due to unresolved confounding. 4) It is also noteworthythat in one ofthe six cities (Topeka) there was a negative association between mortality and PM10-2.5 (but not PM2
.5

). Topeka was also the only city forwhich PM10.2.5 levels> PM2
.5levels. These findings suggest that in Topeka, a city "subject to windblown dust", coarse particulate was predominantly crustal and therefore associated with a negative exposure-effect relationship. This observation was noted above with reference to the negative mortality association between mortality and soil seen in Phoenix. Outcomes in Areas where PM 10 is Dominated by Coarse Particles The SP cites four studies (five reports) in support oftheir statement that statistically significant associations were reported for various other health outcomes "in areas where PM 10 is dominated by coarse particles". I notethat the SP does notdefine or explain theterm "dominated by coarse particles." Tucson study 1) The SP cites a 1997 study of cardiovascular hospitalizations (16) as evidence of adverse health outcomes "in areas where PM10 is dominated by coarse particles". However, the study contains no data on ambient levels of PM2
.5: "Unfortunately, no PM2
.5data are available in Tucson

..." (16). 2) The author notes that in western cities such as Tucson, PM2
.5represents a smaller proportion of PM10than in northeast cities: "in general, PM2.5 is about 50% of PM10 in such western locations, vs. about 62% in the northeast." (16) But in this studythe proportion of PM2.5 was probably greaterthan that otherwise expected because the source of PM data was a monitoring station, Garden Grove, that had been selected in part because it was less likely to measure wind blown crustal dust: "Several monitoring stations were available in Tucson

... most ofthem were more subject to windblown dust than the Garden Grove station." (17) 

# •Rogene Henderson, Ph.D August 10, 2005 Page 10.
3) In addition, the Garden Grove station was "located in a neighborhood site likelyto be representative of population exposure" (17). From that, I inferthat the station was located in a residential area where PM from domestic and vehicular sources was more likely and crustal coarse PM, as might be associated with arid western dust, less likely. The statement quoted above implies that such exposures are more representative ofthe sorts of "population exposures" that might be associated with the adverse health outcomes evaluated in the study. Accordingly, I am cautious to accept the SP conclusion thatthis study represents an area "where PMlO is dominated by coarse particles." Reno/Sparks study 1) The SP cites a study of hospital admissions for COPD in Reno/Sparks, Nevada (18). Butthere is no evidence in the study that PM,o was "dominated" by PM1O-2.5. To the contrary, the report contains the following relevant observations: a) During the time span ofthis study, data for PM2.5were notavailable in this area. Thus, one cannot determine objectivelythat PM,o was "dominated by coarse particles". b) Higher PM 10 peaks occurred during the winter season, an observation that the authors propose to be the result of "increased residential combustion due to cold weather in the study area" (18). c) A negative correlation was found between wind speed and levels of PMlO, which suggeststhatwind blown dust crustal dustwas not an important determinant of coarse particulate levels. d) Levels of PMlO were highest on weekdays and lowest on weekends. The authors attribute this difference to reduced weekend vehiculartraffic, but they did notdifferentiatethe relative contributions of reentrained road dustvs. vehicular exhaust. There is apparently no objective evidence in this study that PM 10was "dominated" by PMlO-2.5. Accordingly, it is difficultto see the direct relevance ofthis study to setting a PM 1O-2
.5standard. 2) It is also notable that this was a relatively small study. The study included 1814 days, but hospital admissions for COPD averaged only 1.72 per day. Applying the "rough indicator ofthe degree of precision of effect estimates" 

# ,Rogene Henderson, Ph.D August 10, 2005 Page 11.

described in the SP (p. 4-6) and discussed above, we find that this study does not meetthe test. Thus, using staffcriteria this study should .be regarded as too imprecise to be used for quantitative analyses. Utah Valley study 1) The SP cites three reports by Pope and colleagues that evaluated respiratory disease and mortality in the Utah Valley (19-21). Butthere is no evidence in the study that PM 10 was "dominated" by PM10-2.5. Tothe contrary, the report contains the following relevant observations: a) Levels ofTSP and PM10, but not PM2
.5were measured and reported in this study. Thus, one cannot determine objectively that PM10 was "dominated by coarse particles". b) The major sources of PM 10 in the Utah Valleywere combustion-related. Those sources and their proportionate contributions were: steel mill (47- 

### 80%); wood burning 

### (-16%); road dust 

### (-11%); diesel fuel and oil combustion 

### (-7%) (19). Accordingly, one would expectthat PM2
.5

, not PM 10 would predominate in the area. Discussion The studies cited in the CD and SP raise important concerns about the public health risks of ambient coarse particulates and a number ofthem lend significant support to a weight-of-evidence assessment ofthe hazard. Unfortunately, they do not sustain quantitative risk assessment. For example, even if crustal coarse PM were shown to be inherently harmless, it would be reasonable to suppose that sufficiently high contamination levels could render that particulate toxic. Thus, it is not unreasonableto suggest that urban road dust could be more toxic than wind blown crustal PM. On the other hand, such weight-ot-evidence is not sufficient to establish and justify specific exposure standards. Important data deficiencies currently obstructthe setting ofsuch a standard. It is insufficient to argue on the basis offine PM studies (e.g., (22)) that significant levels oftoxic contaminants can be found in urban coarse PM. It is necessary instead to determine whether and when toxic contaminants achieve levels such thattheir hazards are more than theoretical. For example, the surface area ofa given particulate mass declines exponentially as particle size increases. Thus, for any given mass of PM:one can expect that the dose ofadsorbed toxicant 

# ,Rogene Henderson, Ph.D August 10,2005 Page 12.

received via inhalation from contaminated particulate will decline rapidly as particulate size increased. In otherwords, ifcrustal coarse particulate is essentially harmless but urban coarse proves harmful at relevant ambient concentrations, then any necessary coarse PM exposure standard developed in response should be focused on those components that.make the urban dust harmful (e.g., transition metals; PAHs; latex particles). Whether such standards are set specifically or categorically, they should be derived from toxicologic and epidemiologic studies that consider appropriately sized PM contaminated by well-characterized toxicants. One would also hope that future epidemiologic studies would be of sufficient size and rigor to be acceptable as the basis ofquantitative risk assessment. I urge CASAC to lend its full weight to ensure adequatefunding is available to support the gathering offurther data, and sound research and analysis ofthe potential health risks from coarse PM that are ofconcern to it. Such data and research are necessary to determine whetherthere is a need for a coarse PM to address public health risks at ambient concentrations, and to characterize the indicator and concentration.

ours truly,

, DABT, FACP, FACOEMRogene Henderson, Ph.D August 10, 2005 Page 13. References 1. Kleinman MT, Bhalla OK, MautzWJ, et al: Cellular and immunological injury with PM-1 0 inhalation. Inhal Toxicol 7:589-602, 1995. 2. Steerenberg PA, Withagen CE, Dormans JAMA, et al: Adjuvant activity of various diesel exhaust and ambient particle in two allergic models. ,[ Toxicol Environ Health A 66:1421-1439,2003. 3. Bouthillier L, Vincent R, Goegan P, et al: Acute effects of inhaled urban particles and ozone. Lung morphology, macrophage activity, and plasma endothelin-1. Am J Pathol 153:1873-1884,1998. 4. Chang M, Sioutas C, Cassee FR, et al: Field evaluation ofa mobile highcapacity particle size classifier (HCPSC) for separate collection of coarse, fine and ultrafine particles. Aerosol Science 32:139-156,2001. 5. MarTF, Norris GA, Koenig JQ, et al: Association between air pollution and mortality in Phoenix, 1995-1997. Environ Health Perspect 108:347- 353,2000. 6. MarTF, Norris GA, Larson TV, et al. Air Pollution and Cardiovascular Mortality in Phoenix, 1995-1997. In: Revised Analyses oftime-series studies ofair pollution and health, Health Effects Institute (ed). Boston: Health Effects Istitute, pp. 177-182,2003. 7. Borak J, Bidulescu A: Some thoughts on multiple comparisons and their correction. OEM Rep 14:65-68, 2005. 8. Schwartz J, Dockery OW, Neas LM: Is daily mortality associated specifically with fine particles? JAirWaste Manage Assoc 46:927-939, 1996. 9. Schwartz J, Norris G, Larson T, et al: Episodes of high coarse particle concentrations are not associated with increased mortality. Environ Health Perspect 107:339-342,1999. 10. Burnett RT, Cakmak S, Brook JR, et al: The role of particulate size and chemistry in the association between summertime ambient air pollution and hospitalization for cardiorespiratory. Environ Health Perspect 105:614-620,1997. 11. Lipprnann M, Ito K, Nadas A, et al: Association of particulate matter components with daily rnortality and morbidity in Urban populations. In: Carnbridge: Health Effects Institute, 2000.Rogene Henderson, Ph.D August 10, 2005 Page 14.

12. Ostro BO, Hurley S, Lipsett MJ: Air pollution and daily mortality in the Coachella Valley, California: A study of PM1 0 dominated by coarse particles. Environ Res 81 :231-238, 1999. 13. Ostro BO, Broadwin R, Lipsett MJ: Coarse and fine particles and daily mortality in the Coachella Valley, California: A follow-up study. J Exp Analysis Environ Epidemiol 10:412-419,2000. 14. Ostro BO, Broadwin R, Lipsett MJ. Coarse particles and daily mortality in Coachella Valley, California. In: Revised analyses oftime-series studies of air pollution and health, Health Effects Institute (ed). Boston: Health Effects Institute, pp. 199-204,2003. 15. Klemm RJ, Mason R. Replication of reanalysis of Harvard Six-City Mortality Study. In: Revised analyses oftime-series studies ofair pollution and health, Health Effects Institute (ed). Boston: Health Effects Institute, 2003. 16. Schwartz

### J: Air pollution and hospital admissions for cardiovascular disease in Tucson. Epidemiol 8:371-377,1997. 17. ChoudburyAH, Gordian ME, Morris 88: Associations between respiratory illness and PM10 air pollution. Arch Environ Health 52:113-117,1997. 18. Chen L, Yang W, Jennison BL, et al: Air particulate pollution and hospital admissions for chronic obstructive pulmonary disease in Reno, Nevada. Inhal Toxicol 12:281-298,2000. 19. Pope CA, III: Respiratory disease associated with community air pollution and a steel mill, Utah Valley. Am J Public Health 79:623-628,1989. 20. Pope CA, III: Respiratory hospital admissions associated with PM10 pollution in Utah, Salt Lake, and Cache Valleys. Arch Environ Health 46:90-97, 1991. 21. Pope CA, Schwartz J, Ransom MR: Oaily mortality and PM10 pollution in Utah Valley. Arch Environ Health 47:211-217,1992. 22. Batalha JRF, 8aldiva PHN, Clarke RW, et al: Concentrated ambient air particles induce vasoconstriction of small pulmonary arteries in rats. Environ Health Perspect 110:1191-1197, 2002.