ATTACHMENT 


Overview of Revisions in Second Draft PM ISA in Response to 


CASAC Peer Review Comments dated May 21, 2009 


General ChanQes 

An acronym was added to the front of the ISA. 

When annexes or other sections were referenced in the text, they were specified (e.g ., Figures 


A.2 .1-1 through A.2 .1-6 in Annex A). 


New studies were added that were published on or before May.15, 2009. 


Chapter 1_-_Introduction 


Further detail was added on the history of the previous PM NAAQS review in Section 1 .2 . 


Section 1 .3 was expanded to include more information on the process ofISA development, 


including study selection criteria. Section 1 .5 was revised to include more specific 


considerations for causality determinations on PM. Additionally, consideration ofpublication 


bias was incorporated into Section 1 .5 . 


Chapter 2 - Intesrative Overview of Health and Welfare Effects 


Sections 2.1 and 2.2 : Concentrations and Sources of Atmospheric PM and Human 


Exposure ' 


The text was edited to reflect the larger edits made in Chapter 3 . 


Section 2.3: Health Effects 


This section was reorganized to focus on the health effects evidence from studies that examined 


associations between morbidity and mortality and PM2,s, PMIo-2 .s, and ultrafine PM. In addition, 


a discussion ofthe evidence for health outcomes that were suggestive of an association with PM 


was included . At the end of the discussion of the evidence for health effects associated with 


short-term and long-term exposure to a specific PM size fraction, a section was added that 


integrates the evidence across both exposure durations, including evidence from studies that 


examined the mode of action, dosimetry, atmospheric chemistry, and exposure assessment. 


When appropriate, figures were added that summarize the overall U.S. and Canadian 


epidemiologic evidence for specific size fractions and exposure durations, along with the 


concentrations reported in the studies. ' 


Section 2.4 : Policy-Relevant Considerations 


A new section was added that includes summaries for the evidence for susceptible 


subpopulations, lag structure ofassociations in epidemiologic studies, and the PM concentration-


response relationship . 

Section 2.5 : Welfare Effects 


A new section was added to summarize the findings of the welfare effects chapter (Chapter 9). 


Chapter 3 - Source to Human Exposure 


Section 3.2 : Overview of Basic Aerosol Properties 


Material was added on particle morphology. 


Section 3.3 : Sources, Emissions and Deposition of Primary and Secondary PM 


The sections on sources and emissions were expanded to include mobile sources (e.g ., gasoline 


and diesel fueled vehicles). Discussion ofdeposition processes was moved into this section from 


Chapter 9. 


Section 3.4 : Monitoring Issues 


The PM mass measurement section was reorganized with an emphasis on addressing PM,o-2.5 


measurement techniques and performance ofFRMs. The PM network and siting section was 


reorganized and annex tables were created to compare different monitoring networks and spatial 


scales for PM monitoring. Asection was added on satellite determinations of surface PM2.5 . 


The section on measurement methods relating to climate and welfare effects was substantially 


increased and harmonized with the measurement section in Chapter 9. 


Section 3.5 : Ambient PM Concentrations 


Abriefsynopsis of relevant findings from the 2004 Air Quality Criteria Document (AQCD) for 


PM was added to the beginning of Section 3 .5 . Most of the figures were updated for purposes of 


clarity and illustration; no additional data were incorporated into the tables or figures with the 


exception of PM constituent trends added to Section 3.5 .2 .1 . All PM size-specific discussions 


throughout this section were rearranged into the following order: PM2.5, PMIO-2 .s, PMto, ultrafine 


PM. This was done to matchthe order ofdiscussion in the rest of the document and to help 


clarify the fact that PM,o incorporates both PMZ.5 and PMlo-2 .5 . In addition, several other 


improvements were made to this section in response to CASAC comments including the 


following: 


added a summary ofthe findings from the PM concentration distribution tables (Tables 

3 .5-1 through 3 .5-3) 

expanded the ultrafine particle discussion to include information on nucleation, spatial 

" 

" 

variability and chemical composition ofultrafine particles 

" expanded the discussion on the statistical correlations between sites as shown in the figures 

and tables 

" added studies looking at neighborhood scale variability and near-roadway environments; 

" added a section on trends in constituents 

" added a discussion on diel variability in PM constituents 

Section 3.6 : Mathematical Modeling of PM (New Section) 


This section was added that incorporates receptor modeling and chemistry transport modeling 


(topics covered in Section 3.5 of the 1 S` External Review Draft) with expanded material 


requested by CASAC. 
Section 3.7 : Background PM (Section 3.6 in lst External Review Draft) 


More data and description were provided on current and previaus methods for estimating Policy 


Relevant Background. 


Section 3.8 " Exposure Assessment (Section 3.7 in l" External Review Draft) 


This section was reorganized in response to CASAC comments to consolidate information 


related to general exposure assessment concepts, relevant studies, and the effect of exposure 


misclassification on epidemiologic study findings. Increased attention was given to PMIO-2 .s and 


ultrafine PM throughout the section. Descriptions oftime-weighted microenvironmental and 


GIS-based models were added to the modeling subsection. Findings from the relevant studies 


were organized by spatial scale in part to distinguish between issues related to near road 


variability and issues found at the urban scale. Exposure to PM components and PM as apart of 


a mixture were also presented in a separate subsection. A subsection on implications ofexposure 


assessment for epidemiologic studies was added. 


Chapter 4 - Dosimetry 


Section 4.2 .4 : Biological Factors Modulating Deposition 


Asubsection was added to describe the multiple influences ofphysical activity on particle 


deposition. Changes in breathing route and pattern with activity level were first presented. The 


discussion then shifted to the effect ofthese alterations in breathing on total deposition fractions 


and dose rates. Finally, effects on tracheobronchial and apical particle deposition with exercise 


were presented. In the subsection on age effects, additional discussion ofbreathing patterns and 


deposition differences between adults and children was added. 


Section 4.3.1 : Clearance Mechanisms and Kinetics (poorly soluble particles) 


Mucociliary clearance from the tracheobronchial airways is generally considered to be a rapid 


(days) process, but a portion ofthe particles deposited in these airways appear require 


considerably long periods (months) to clear. Discussion ofthis important phenomenon was 


expanded and updated. 


Section 4.3 .4 " Factors Modulating Clearance (poorly soluble particles) 


Anew discussion on the effects ofasthma, acute inflammation, and epithelial permeability on 


clearance was added to the subsection on respiratory disease. . 


Section 4.4.1 : Clearance Mechanisms and Kinetics (soluble constituents) 


The discussion ofparticle solubilization was expanded. Recent literature on leachable metals 


disposition following particle deposition was added. 


Chapter 5 - Mode of Action 


The following sections were added to the chapter: 


" Epigenetics (Section 5.1 .11) 

" Lung development (Section 5.1 .12) 

" Atherosclerosis (Section 5 .2 .3) 

" Acute and chronic responses (Section 5 .6) 
Discussions on the following topics were expanded: 

" Neutrophilic inflammation (Section 5.1 .3, Section 5.1 .9) 

" Epithelial permeability (Section 5.1 .4) 

Factors which affect resolution ofinflammation/progression or exacerbation ofdisease " 

(Section 5.1 .9) 

" Role of trigeminal nerve in CNS reflexes (Section 5.3) 


" CNS plasticity (Section 5 .3) 


" Translocation ofPM or soluble PM components (Section 5 .4) 


Effects on the CNS and other systems (Section 5 .5) 

Additional gaps in knowledge (Section 5.7) 

" Relevant information from new studies published since the first draft and crossreferencing of all items to the appropriate sections ofChapters 6 and 7 (Section 5.7) 

Paragraphs on ultrafine PM were added throughout chapter. 

whether health effects are similar across species, Where information was readily available on 

For example, it was noted that neurogenic inflammation may discussions were added to the text . 

However, in most cases new information was not be more important in rodents than humans. 


included because literature searches failed to identify publications that elucidate these topics . 


Chapter 6 - Integrated Health Effects of Short-Term PM Exposure 


For each section in Chapter 6, the causal determination for PMIO was removed, and evidence for 


health effects associated with PMIo was used to support the associations with PMZ,5 and/or PM,o_ 


2.5 where possible and appropriate. The discussion of cause-specific mortality has been 

incorporated in sections on cardiovascular and respiratory morbidity, as was done for lung cancer 

incidence and mortality and considered in drawing causal determinations for cardiovascular and 

respiratory effects. 

Section 6.1 : Introduction ~ The section on The introduction was updated to reflect the changes made throughout Chapter 6. 


methodological considerations was separated and moved to various sections ofChapter 1 . 


Section 6.2 " Cardiovascular Effects 

Controlled human exposure and toxicological studies were reorganized by particle type or source 

(e.g ., CAPs, diesel, gasoline, model particles, etc.) and subheadings were added. Intratracheal 

instillation studies were contained in their own subsection where applicable within the 

The summary sections were revised and condensed by removing specific toxicology sections. 

outcome headings and presenting the previous findings followed by new evidence in a more 

integrated fashion. The causal determinations for PMIO-2 .s and ultrafine particles were changed 

from inadequate to suggestive, whereas the causal determination for PM2.5 remained unchanged 

from the V ERD. 

Section 6.3 : Respiratory Effects 


The figures in Section 6.3 .1 were revised to include the results for all PM size fractions as 


Controlled human exposure and toxicological studies were reorganized opposed to PM2.s alone. 
by particle type or source (e.g ., CAPs, diesel, gasoline, model particles, etc.) and subheadings 

subsection where 

were added. Intratracheal instillation studies were contained in their own 

applicable within the toxicology sections. New epidemiology sections on allergic responses 

The summary (Section 6.3 .6 .1) and host defense (Section 6.3 .7 .1) were added for the 2"a ERD. 


sections were revised and condensed by removing specific outcome headings and presenting the 


previous findings followed by new evidence in a more integrated fashion. The causal 


determination for ultrafine particles was changed from inadequate to suggestive, whereas the 


causal determinations for PM2.5 and PMIo_Z .s remained unchanged from the l~` ERD. 


Section 6.4 " Central Nervous System Effects 


studies. Toxicological studies Anew epidemiology section was added that summarized new 


were reorganized by particle type or source (e.g ., CAPs, diesel, gasoline, model particles, etc.) 


and subheadings were added. 


Section 6.5: Mortality 


Along with incorporation of recent study findings, ancillary data (i.e., empirical Bayes-adjusted 


city-specific estimates and ambient PM concentrations) were included from Zanobetti and 


Schwartz (2009) for PMz.s and PMIO-2 .5 . ' 


Attribution of Health Effects to Specific Constituents or Sources Section 6.6: 


individual tables for epidemiologic, controlled human exposure, and toxicological studies were 


was moved to Annex F. The table that was formerly in Chapter 2 (Table 2-1 in the lst ERD) 

moved to this section, and includes studies from all three disciplines grouped by source category 

(e.g., crustal/soil/road dust, traffic, oil combustion, etc.) . A new summary was drafted that 

includes paragraphs by health outcome (i .e., cardiovascular effects, respiratory effects, and 

source categories and constituents . mortality) for the different PM 

Chanter 7 - Long Term Exposure and Health Effects 

For each section in Chapter 7, the causal determination for PM,o was removed, and evidence for 

health effects associated with PM,o was used to support the associations with PM2.5 and/or PMto_ 

2.5 where possible and appropriate. The discussion of cause-specific mortality has been 

incorporated in sections on cardiovascular and respiratory morbidity, as was done for lung cancer 

incidence and mortality and considered in drawing causal determinations for cardiovascular and 

respiratory effects. 

Section 7.2: Cardiovascular Effects 

The text was edited to balance the discussion of the intermediate cardiovascular outcomes so that 

this line ofevidence was consistent with the summary sections . Text was added to the 2°d ERD 

to relate chronic cardiovascular health impacts with acute cardiovascular health impacts. 

Toxicological studies were separated by exposure atmosphere (e.g., CAPS, ambient air, wood 

smoke, diesel, etc.) and intratracheal instillation studies were contained in their own subsection . 

Consideration ofevidence on cardiovascular mortality resulted in revision ofthe causal 

determination from "likely causal" to "causal." 
Section 7.3 : Respiratory Effects 

The text in this section was revised to more clearly differentiate between cross-sectional and 

cohort study designs. Additionally, the text was revised to ensure that the studies were 

The epidemiology sections on allergic characterized in a balanced and objective manner. 


response (Section 7.3 .6 .1) and host defense (Section 7.3 .7 .1) were expanded. 


Reproductive and Developmental Outcomes Section 7.4" 

Thetables and Several new epidemiologic studies were added to this section in the 2°d ERD. 

figures in this section were updated to include the newly identified studies. 

Section 7.5 " Cancer 

This section was revised to include the results of epidemiologic studies examining lung cancer 

In the 1" ERD this section was limited to epidemiologic studies mortality and PM concentration. 


that focused on cancer incidence. Rates of lung cancer incidence and mortality are similar, and 


A new therefore the cancer section was expanded to include studies of lung cancer mortality. 

table (Table 7-7) was included that shows	the effect estimates from lung cancer incidence and 

as well as those reviewed in previous PM AQCDs. mortality studies reviewed in the 2°d ERD 

The inclusion of evidence for mortality due to lung cancer associated with PM2.5 concentrations 

strengthened the causal determination substantially. 

The section was also revised to include evidence from animal toxicological studies that has been 


the mutagenicity and carcinogenicity ofPM in the ambient
 accumulating for several decades on 

The majority of these toxicological studies were conducted using intratracheal instillation or air. 

dermal routes of exposure. Generally, the toxicological evidence reviewed in the rest of the ISA 

was limited to inhalation studies conducted at PM concentrations <2 mg/m3. For the 2nd ERD, 

toxicological studies conducted at higher concentrations and using various routes of exposure 

were cited in order to accurately characterize the role ofPM in mutagenicity, tumorogenicity, 


The toxicology section was reorganized such that mutagenicity and
 and carcinogenicity. 

genotoxicity studies are described first, followed by the carcinogenesis studies. Additionally, the 

toxicology section has new subheadings within each section for particle or source type, which is 

This evidence included brief consistent with toxicology sections for other health outcomes. 


summaries ofrelevant IARC and EPA documents on diesel exbaust, as well as reviews from the 


peer-reviewed literature . 


Also, a few recent studies examining the association between PM2.5 and epigenetic changes were 

As a result of revisions to this section, the causal determination added to the end of the section. 


for PM2.5 and cancer was changed from inadequate to suggestive . The causal determination for 


PM10-2 .5 and cancer remained unchanged (i .e., inadequate) from the l s` ERD. 


Section 7.6" Mortality 


Several new epidemiologic studies were added to this section in the 2"d ERD, most notably the 


The tables results ofthe HEI report of the reanalysis ofthe ACS cohort by Krewski et al. (2009). 


and figures in this section were updated to include the newly identified studies. 

Chapter 8 - Susceptible Subpoaulations 

Potentially Susceptible Subpopulations Section 8.1 " 

The definition of a susceptible subpopulation was clarified based on a workshop report from The 

Adiscussion on effect modification was included. The American Lung Association (2001) . 


table that was originally in this section was edited to reflect the susceptibility factors examined in 


The table was also 

the health effects literature that were subsequently discussed in this chapter. 


revised to include the different exposure durations (short- and long-term) and PM size fractions 


evaluated in the studies presented in the chapter. 


Sections 8.1 .1 through 8.1.7 


accurately reflect the exposure The remaining sections of this chapter were reorganized to more 

The susceptibility factors originally durations and size fractions where the evidence lies . 

were no longer characterized as included in the chapter were reconsidered and some 

susceptibility factors (e.g., air conditioning use and geographic location) and thus, were no 

longer discussed. 

Section 8.1 .8 

new section was included that summarizes the findings from all ofthe studies evaluated in this A 

chapter. 

Chapter 9 -Welfare Effects 

Visibility Section 9.2" Effects on 

section on Direct Optical Measurements (9.2 .2 .3 .) was

As recommended by CASAC, a new 

To enhance the discussion ofsense ofwell being as it relates to urban air quality, Section added. Key points ofthese new sections were 

9.2 .2 .4 . Value ofGood Visual Air Quality was added. 


also included in the summaries in both Chapter 9 and Chapter 2. Several figures were also 


revised for clarity and consistency. 

Section 9.3 : Effects on Climate 


climate was substantially, increased with more details from 


The section on aerosol effects on described in 

recent publications . Specific effects from PM components and size fractions were 

detail was added to the summary' section and carried through to 

more detail. In addition, more 

the summary in Chapter 2. 

Section 9.4" Ecological Effects 

types of effects (i .e ., direct and indirect effects) and This section was reorganized to focus on 

effects of individual PM components (i.e ., metals and organics). Deposition of PM specifically 

related to ecosystems was merged into this section while more detailed information on 

The causal determination was revised from causal 

deposition processes was moved to Chapter 3. 

to likely to be causal. Additionally, the introduction to the section was revised to include key 

conclusions from the recent NOX-SOX ISA (December 2008).