UNITED STATES ENVIRONMEN TAL PROTECTION AGENCY WASHINGTON, D.C. 20460

OFFICE OF THE ADMINISTRATOR

SCIENCE ADVISORY BOARD May 21, 2009

EPA-CASAC-09-008

The Honorable Lisa P. Jackson

Administrator U.S. Environmental Protection Agency 1200 Pennsylvania Ave., NW Washington, D.C. 20460

Subject: Review of EPA’s Integrated Science Assessment for Particulate Matter (First External Review Draft, December 2008)

Dear Administrator Jackson:

The Clean Air Scientific Advisory Comm ittee (CASAC) and members of the CASAC Particulate Matter (PM) Review Pane l met on April 1-2, 2009 to review the Integrated Science Assessment for Particulate Matter (First External Review Dr aft, December 2008, the PM ISA) and two planning documents related to this NAAQS review. The CASAC PM Review Panel also held a teleconference on May 7, 2009 to finalize this report. In this letter, we summarize the CASAC’s major recommendations on the ISA. Comments of individual panel members are

enclosed.

The CASAC commends the EPA Staff for the development of a generally excellent and comprehensive first-draft PM ISA. Most chapters were viewed as excellent, particularly for a

first-draft document. The document draws on a ma ssive base of evidence that is usefully summarized in tables and the appendices. Th e evidence is thoughtfu lly synthesized in a transparent fashion; the framework for classify ing the strength of evid ence has continued to evolve, and it provides transparen cy in documenting how determinations were made with regard to causation. The CASAC is particularly pl eased that the Agency has adopted a uniform descriptive language for various levels of confidence in making causality determinations. We support the five-level hierarchy developed for cau sal determinations, and recommend it as the model for future ISAs. Chapter 2 (“Integrativ e Health Effects Overview”), which summarizes and integrates across the chapters, was thought to be an invaluable component of the ISA. Below are CASAC’s major recommendations for improvement, followed by responses to the charge questions.

• The ISA should provide more context for the reader on the regulator y options considered in the last review, and on th e divergence between EPA’s most recent PM decisions andCASAC’s advice. This background would help CASAC and the public in identifying the key new information summarized in the ISA.

• In the summary chapter (Chapter 2, “Integra tive Health Effects Overview”), building on sufficient discussion in subsequent chapters , the ISA should more fully integrate the body of evidence related to PM size and compositi on for both health and welfare outcomes. Since Chapter 2 is intended as a summary, we recommend integrating conclusions about welfare effects into this chapte r, and, in fact, inserting the term “welfare” in the title of the chapter (“Integrative Health and Welf are Effects Overview”). In addition, we recommend bringing all important findings into this chapter, such as the Agency’s

determinations on the effects of PM 2.5 on cancer risk and on the health risks of various PM components.

• Welfare effects addressed in the ISA were too na rrowly restricted to visibility. There was little effort to apply the crit eria of causality laid out fo r health endpoints, even for visibility for which the evidence is stronge st among the various welfare outcomes. The implications of PM size and composition for cl imate effects need to be more thoroughly explored, both with regard to climate change and the associated health and welfare effects of climate change. The document’s restric tion of the range of welfare effects may perhaps reflect a priori conclusions on the “policy-relevan ce” of various outcomes. For example, rather than focusing exclusively on the most tolerant plants, a search for sensitive receptors for specific endpoints mi ght help to better focus the discussion of welfare effects and the search for a qu antifiable concentra tion-response (C-R) relationship for guiding development of a sepa rately determined secondary standard for PM. It would improve the ISA if the same causality framework were applied to PM and welfare effects, as for the health outcomes, emphasizing discrete endpoints and possible causal relationships. Visibil ity, it should be noted, is not fully separable from health outcomes since reduction of visibility may ha ve consequences for quality of life and well-being, which are arguably health outcome s. Additional discussion and emphasis on “sense of well being” studies is needed as they relate to urban visibility. The implications of these studies should be highlighted in th e summary section for Chapter 9 (“Ecosystem and Welfare Effects”) as well as in the full ISA summary in Chapter 2.

As an additional point, visibility effects in eastern and urban ar eas (non-Class 1 areas) deserve far greater attention, particularly in view of th e consideration of an urban visibility standard. EPA should also disc uss those data needed for developing an alternative optical standard for visibility.

• With respect to concentration -response functions, the ISA need s to set out as clearly as possible, the concentrations and their associat ed averaging times at which health effects

have been observed in relation to short-term and long-term exposures. This information is needed in anticipation of us e of these functions in the REA. This dimension of data display is currently lacki ng, but needs to be reflecte d in tables and figures.

• Other chronic health endpoints deserve more attention in the ISA. In particular, the coverage of lung cancer is limited as is that of chronic obstructiv e pulmonary disease.

2.

• The document should more fully address implications of particle size and composition for risk to health. At the least, the major ga ps in the evidence shoul d be identified.

• Revisions are needed to remove the impression that PM 10 is a separate pollutant from

PM 2.5 and PM 10-2.5. The ISA handles PM 10 , PM 2.5 , and PM 10-2.5 , as if they were separate entities, even though the latter two are components of PM 10 . The CASAC cautions against this approach and notes that PM 10 is a mixture that cont ains varying proportions of particles in the smaller and larger si ze ranges. The current approach leads to

inconsistencies in classification of evid ence, with for example the evidence for respiratory morbidity classified as sufficient for PM 2.5 , but likely for PM 10 , which includes

PM 2.5 . When possible, the partic le size distribution of the PM 10 mixture should be provided. To the extent possible, the documen t should take a more integrative approach in drawing inferences across th e range of PM sizes. Sim ilarly, a discussion of the relevance or importance of particle composition for the different particle size fractions is

warranted. The ISA can be useful in iden tifying gaps related to particle size and composition that should be addressed with new research.

Our specific responses to charge questions follow below:

1. The framework for causal determination and judging the overall weight of evidence is presented in Chapter 1. Is this fram ework appropriately applied for this PM ISA? How might the application of the framework be improved for PM effects?

The CASAC regards the framework for causal determination and judging the weight of evidence, as presented in Chapter 1, to be appr opriate. The two-step approach, using first a categorization of the evidence in support of causation and second an evaluation of exposureresponse is a reasonable, logical pr ocess. By characterizing the leve l of certainty with regard to the presence of causal effects, the ISA sets out a range of adverse health and welfare effects, along with an implied statement as to the like lihood of benefits following control. The categorization gives guidance to th e Administrator as to the potenti al for public health benefits from the PM (or other) National Ambient Air Qu ality Standards (NAAQS). The categorization reflects the strength of evidence and not the pote ntial magnitude of public health benefits; those

effects for which the evidence is less certain shou ld also receive consideration in the Risk and Exposure Analysis (REA) and in policy deliberations.

Because there is concern for susceptible and vulnerable populations, the concepts of confounding and effect modification need to be suffi ciently developed so th at readers of the ISA understand the relevance of the concept of effect modification when considering susceptibility. We suggest this topic be addressed in this chap ter and then more comprehensively in Chapter 8 with regard to susceptibility.

Publication bias is likely to be relevant in the assessment of causality, and perhaps even

more so in the assessment of the evidence char acterizing concentration-response relationships. Discussion is needed on the implications of pub lication bias; how it is detected and how its consequences should be taken into account.

32. Chapter 2 presents the integrative summary and conclusions from the health effects evidence at the beginning of the ISA with the evidence characterized in detail in subsequent chapters. (Environmental and public welfare effects evidence is evaluated and summarized in Chapter 9.) Is this a useful and effective summary presentation? How does the Panel view th e inclusion in Chapter 2 of only health categories with causal determinations of (a) li kely to be a causal relationship or (b) a causal relationship?

The ISA is comprehensive, lengthy, and co mplex. Chapters 3, 4, 5, 6, 7, and 8 are detailed and well documented, but are so extensive as to reduce the functionality of the document for readers. Consequently, the public and polic y makers need the high-level summary provided in the 26 pages of Chapter 2, which provides an excellent overview of the major acute and chronic health impacts of PM. CASAC commends the inclusion of Chapter 2 and recommends similar chapters for future ISAs. Inevitabl y, there are conclusions that require further documentation, but one can easily find the correspondi ng sections of subsequent chapters. In answer to the charge question posed, we are affi rmative and find it to be a “useful and effective summary presentation.”

As discussed above, the five-level hierarc hy developed for causal determination is appropriate. This is a reasonable approach to a central issue in the development of the ISAs (and previously the Criteria Documents). The EPA staff has critically re viewed the relevant literature on this topic and has made specific recommendations regarding their conclusions with regard to causality. We agree with the appr oach of starting with a list of the key health effects and a firm statement with regard to conclusi ons of causality and following th is by a brief description of the key findings supporting the conclusions. The di scussion in Chapter 2 should highlight the evidence leading to the assignments of classifica tion regarding the strengt h of evidence within the five-level hierarchy. This approach should become a model for future ISA documents.

In general, the CASAC concurs with focusing the summary on evidence with causal determinations of “(a) likely to be a causal relationship or (b) a causa l relationship.” But we make two recommendations. First, the summary s hould point the reader to appropriate sections of Chapter 1 where the definitions of the five-level hierarchy of causal determination are given. Second, CASAC further recommends that the fo cus on outcomes for which the strength of evidence for causation is at the higher levels shou ld not lead to exclusion of those outcomes for which the evidence is weaker. Third, emerging i ssues relevant to the PM NAAQS should also

receive consideration.

We also suggest that the findings of Chapter 9 for welfare effects be included in this summary and that the chapter title include welfare effect s. Without including this material, the summary is imbalanced and does not give sufficient weight to the ecosystem and welfare effects.

Additionally, CASAC recommends that the ISA should acknowledge and address the broader relationships between the ecosystem and welfare effects considered in Chapter 9 and human health. Climate change has diverse implic ations for human health and reduced visibility

4is a potential environmental stre ssor. We also suggest addition of a section entitled “Emerging

Issues.” This section could addr ess health effects for which the evidence has not reached the top two categories of strength of eviden ce and point to research needs. It could address topics of likely concern in the future, such as epigenetic changes or influences of PM on premature birth and low birth weight babies. It could also highlight other topics that have been identified through the extensive review process underlying the de velopment of the ISA.

3. To what extent are the atmospheric ch emistry and air quality characterizations clearly communicated, approp riately characterized, and relevant to the review of the PM NAAQS? Does the information on atmospheric sciences and exposure provide useful context and insights for the evaluation of human he alth effects of PM

in the ISA?

a. Is accurate and appropriate informat ion provided regarding PM source characteristics, techniques for measuring PM and its components, policyrelevant background PM, and spatial and temporal patterns of PM concentration? Are the analyses and fi gures presented in Chapter 3 effective in depicting ambient PM characteristics?

Chapter 3 generally describes the rele vant atmospheric chemistry, air quality characterization and exposure assessments that are relevant to the NAAQS review. The chapter was well done and the length is ju stified, given the new data availa ble. There are changes to be made that will provide improvements in the presentation and completeness of the material that has been introduced. For example, although the ch apter indicates it will provide information on particle size, composition, and sh ape (line 23, page 3-3), there is no subsequent discussion of particle morphology or surface area with respect to the characteristics of the ambient aerosol.

The section on measurement methods needs to be improved. There needs to be a more complete discussion of PM mass measurements and the serious limitations of the current Federal Reference Method (FRM) for PM. The current FR M does not provide complete and adequately time-resolved concentration data, nor does it provid e an accurate indicator of mass concentration, given known losses of semivolatile constituents and retention of particle-bound water. There needs to be discussion of the quantification of PM 10-2.5 , and a justificatio n of the use of PM 10 as an indicator of coarse thor acic particle exposure.

There is a lack of information on the pres ence of chemically reactive species, e.g., reactive oxygen species, associated with partic les (particularly SOA and their formation by atmospheric chemistry) and of the chemical composition of coarse thoracic particles.

The emission inventory data needs to be be tter integrated with source apportionment results and the quantification of contributions from primary and secondary sources needs to be

better described.

Changes from previous reviews in the rationale and methodology for estimating the policy relevant background shoul d also be addressed.

5b. Is the evidence relating human exposure to ambient PM and errors associated with PM exposure assessm ent presented clearly, succinctly, and accurately? Are there PM exposure i ssues that should be expanded, shortened, added or removed?

The current exposure section should be reorgani zed to flow more logically and revised to

discuss additional PM issues. Correspondingly, the section on PM exposure and socioeconomic status (SES) should be better inte grated with the other exposure related issues. Presently, the section focuses primarily on 24 hr PM 2.5 exposures and corresponding ambi ent concentrations. It

should be modified to include discussions of shorter–term exposure (e.g., hourly) as well as exposures of longer duration (e.g., annual), and of PM 10 , PM 10-2.5. , and the components, in

addition to PM 2.5 . Further, the section should discuss how the relation between ambient PM and personal exposure varies under di fferent scenarios (e.g., populations measured at single points in time and intra- or inter-community comparisons).

c. To what extent does the Panel find Annex A appropriate, adequate and effective in supporting the ISA?

The balance of data between the Chapter and Annex is good, although the Annex needs a table of contents to make it more navigable. CASAC generally appreciated the completeness of the material presented in Appendix A. Usi ng the “search and find” approach, it does prove useful in supporting the material in Chapter 3. Annex A would be more useful if text references to the Annex were more specific (e.g. by referring to Table a-2, et c.) rather than just a generic

'see Annex A'.

4. The dosimetry of PM is discussed in Chapt er 4. The primary focus is on factors that might lead to differences in deposition a nd clearance between individuals, species, and as a function of the physicochemical properties of particles. Is the review of basic dosimetric principles presented in sufficient detail? A re the new particle translocation data adequately and accurate ly described? Recognizing an overall goal of producing a clear and concise chapter, are there topics that should added or receive additional discussion? Similarly, ar e there topics that should be shortened

or removed? To what extent does the Panel find Annex B appropriate, adequate and effective in supporting the ISA?

In general, the review of basic dosimetric principles is well written and presented in sufficient detail. It is a needed component of the ISA. Information about particle translocation is largely up to date.

There is one evident gap to be addressed. A section is needed under “4.2.4 Biologic Factors Modulating Deposition” that addresses ex ercise, increased ventilation, and route of breathing (nose vs. mouth). For both children and adults, exercise has a strong effect on deposition and retention and hence on dose. Fi rst, greater amounts of PM are inhaled with exercise, the amount inhaled being proportiona l to minute ventilation. Second, deposition

mechanisms are a function of linear velocity of the inhaled air, of residence time, and of other factors related to ventilation. Third, as vent ilation increases, most people switch from nose

6breathing to mouth breathing. The elimination of the nasal filter has a substantial impact on deposition, particularly the depositi on of larger particles in the ai rways. For example, coarse thoracic particles, filtered by the nose under sedentary conditi ons, have a greater probability of reaching the large airways and being de posited there under oral breathing.

The chapter also would be enriched by additional discussion of some specific PM components. For example, what are common l eachable components, and how do they differ in

their clearance mechanisms? What is the fate of metals coming from soluble particles? What organs do they reach and what are the implicatio ns of retention of PM components in the brain, heart, kidneys, liver, or other critical organs?

Annex B is appropriate, adequate, and eff ective in supporting the dosimetry chapter.

5. Chapter 5 is intended to support the evalua tion of health effe cts evidence for both short-term and long-term exposures to PM. Some potential modes of action may

underlie a number of health outcomes and ma y contribute to health effects of both short- and long-term exposures. Thus, the potential modes of action are described briefly in Chapter 5, and some specific study findings are discussed in more detail in the relevant sections of Chapters 6 or 7. What are views of the Panel on this approach and on the characterization of po tential modes of action for PM-related effects in Chapter 5?

Chapter 5 (“Possible Pathways/Modes of Action”) is essential to establishing a foundation for interpreting the evidence on the health risks of PM. It outlines basic mechanisms of action, and thus contributes to understanding the plausibility of the findings presented in subsequent chapters. The common fundamental t oxic mechanisms, limited in number, are well described, particularly the role of reactive oxygen species (ROS). The chapter is short, focused, and incorporates informative illustrations that de scribe the interplay of pathogenic mechanisms.

Each section provides a clear su mmary of biological effects. However, it is important to

establish whether these effects are similar across species a nd under what conditi ons. This could be true for paths of activation, species sensitivit y and/or tolerance, gende r-based differences in

response.

CASAC recommends expansion of section 5.1.3 on inflammation. Inflammation is an important pervasive mechanism, and additi onal highlights of neutrophil biology and the inflammatory process should be delineated. There should also be a discussion of acute

inflammation as well as chronic inflammation. This will undergir d sections on acute responses to air pollutants (e.g., bronchoconstriction, thrombosis and cardiova scular effects such as heartrate variability) versus responses influen ced by chronic inflammati on (e.g. proteolysis, emphysema, fibrosis, atherosclerosis, a nd other persistent anatomic changes).

CASAC notes the omission of one important mechanism—epigenetic effects of PM exposure. We recommend the addition of a ne w section after 5.1.10 on this topic. There is increasing evidence of PM-induced epigenetic changes in DNA, particularly DNA methylation and changes in histones. These epigenetic ch anges may be far more common and possibly more

7important than PM-induced changes in the primary structure of DNA. Such epigenetic changes, now readily measurable, can have a profound effe ct on gene expression an d cytokine levels. There are both animal studies as well as epidemiologic studies that demonstrate significant epigenetic changes in response to PM exposure.

We welcome the section entitled gaps in knowle dge. It is an excellent addition to the chapter. Other gaps could also be listed:

a. Changes in effects due to timing of exposure and timing post-exposure

b. The anatomic spatial distribution of retain ed particles and the implications of the distribution, e.g., airways vs. the deep lung and retention at carinal ridges

c. Deposition, uptake, translocation, and clearance of ultr afine particles

.

6. To what extent are the discussion and integr ation of evidence on the health effects of PM from the animal toxicological, hum an clinical, and epidemiologic studies, technically sound, appropriately balanced , and clearly communicated? Does the integration of health eviden ce focus on the most policy-relevant studies or health findings?

a. Are the tables and figures presented in Chapters 6 and 7 appropriate, adequate and effective in advancing the interpretation of these health studies? To what extent does the Panel find Annexes C, D and E appropriate, adequate and effective in supporting the ISA?

b. In Chapters 6 and 7, toxicological studies were included in the PM ISA text if they were conducted at PM concentrations <2 mg/m 3 . The toxicological focus in these chapters was on inha lation studies, with intratracheal

instillation studies and in vitro stud ies included only if they contributed significantly to the understanding of he alth effects from exposure to PM. The toxicological studies excluded from the text are presented in Annex D. What are the Panel members’ thoughts on this approach and the selection

criteria?

Chapter 6 does a reasonable job of integr ating toxicology, human clinical studies and epidemiological studies for each of the exposure scenarios discussed as well as for each of the outcomes of interest. However, the summary text sections need to be edited for consistency in approach and also to assure that the discussions are grounded and consistent with the antecedent sections that describe the evidence. Generally, the text relating to evidence characterization was satisfactory, but the review of details of the evidence was sometimes uneven. A discussion of the basis for assigning a level of causality need s to be presented for each of the pollutantoutcome causality statements. Further discussion is also required for both Chapters 6 and 7 on the level of causality for the PM components. Justification needs to be presented as to how

evidence related to PM 10 might have a lower leve l of certainty than PM 2.5 (or PM 10-2.5 ) when

PM 10 is comprised of both.

8There is an appropriate discus sion of the time-series studies , but this section needs to have an explicit finding that the evidence supports a relationship between PM and mortality that

is seen in these studies. Th is conclusion should be followed by the discussion of statistical methodology and the identif ication of any threshold that may exist.

In general the tables and figures of Chapte r 6 are used effectively to communicate the copious information in a succinct manner. Annexes C, D and E are thorough, appropriate, adequate and effective in supporting the goals of the PM ISA.

With regard to the judgment of consistency of results, significant effects that move in opposite directions (HRV effects) do not necessarily imply inconsistency, but rather the lack of understanding of potential underl ying mechanisms. Results pr esented need to incorporate specific issues of exposure, incl uding concentration and duration, variability of exposure and PM composition when possible. In reviewing the evidence, consideration also needs to be given to

the characteristics of th e population studied.

Inclusion of toxicological studies utilizing PM concentrations < 2 mg/m 3 serves to limit the inclusion of non-specific toxico logical effects. Yet, even at these concentrations non-specific or off-target effects can be obs erved. It is recommended to in clude high dose inhalation and instillation studies only when th e findings inform as to mechanisms leading to the biological

effects of PM. Effort should be made to di stinguish inhalation from instillation studies throughout the ISA.

7. What are the views of the Panel on the conclusions drawn in the draft ISA regarding the strength, consistency, coh erence and plausibility of the evidence for health effects of PM? In evaluating the evidence to draw preliminary judgments on causality, EPA carefully considered evidence from the various scientific disciplines for the PM indicators and general health or environmental effect categories. Examples of a few specific health categorie s are listed below that were particularly difficult in reaching a ca usal determination. We would appreciate CASAC

comments on all of the causal determinations presented in this first draft ISA.

• Short-term exposure to PM 2.5 and cardiovascular and respiratory morbidity.

• Short-term exposure to PM 2.5 and cardiovascular and respiratory mortality.

• Short-term exposure to PM 10-2.5 and respiratory and cardiovascular morbidity, and mortality.

• Long-term exposure to PM 2.5 and cardiovascular and respiratory mortality and lung cancer

.

This chapter provides a reasonably balanced presentation of most of the outcomes of interest. However, there are se veral aspects of the presentation of findings that need to be

addressed in the second draft. Fi rst, there needs to be specificity in interpreting associations that

come from cross-sectional studies as reflect ing exposure differences across regions and not increases in PM levels. Second, there needs to be greater balance in the presentation and discussion of study results, without undue we ight being given to positive findings or

characterization of estimates with confidence intervals that include the null as “positive”. This

9lack of balance is most evident for intermedia te outcomes related to cardiovascular disease (CVD). The summary statements at the end of the sections are more balanced, but the text needs to be more even. Further in the respiratory section there is a tendency to report primarily positive endpoints from studies with multiple en dpoints by drawing on the individual authors’ interpretations of their findings. In spite of this limitation, the overall conclusions regarding causality in the respiratory section are reasonable.

Studies support a link between long-term expos ure of airborne particle pollution to progression of intermediate cardiovascular endpoints such as su rrogate measures of atherosclerosis, including coronary artery calcium and carotid arte ry internal medial thickness. These studies must be interpreted in the context of their insensitivity to detect small changes in either IMT or coronary artery calcium. In a ddition, the relation of chr onic health impacts to acute health impacts should be discussed. In pa rticular, this discussion should examine whether chronic health impacts occu r through similar or diffe rent biological pathways.

Regarding the assessment of cancer mortalit y, particularly rela ted to lung cancer,

CASAC recommends that the c ohort study findings on mortality be incorporated in the cancer incidence section rather than pl acing that discussion in the foll owing section on mortality. For lung cancer, because of the poor survival, mortalit y and incidence are quite close. The literature search should be strengthened and better reflec t the most relevant, earl ier studies as well as relevant occupational studies. Th e section needs to better cons ider the plausibility of lung cancer, given the presence of known carcinogens in PM mixtures.

8. What are the views of the Panel on the defi nitions of susceptibility and vulnerability in Chapter 8? Are the characteristics incl uded within the broad susceptibility and vulnerability categories appropriate and cons istent with the definitions used?

CASAC generally supports the inclus ion of the material in this ch apter as part of the ISA. However, the title of the chapter is not descriptive of the content and should be revised, perhaps

to “Public Health and Welfare Considerations”. In general, there was strong support for having synthesis material such as that found in Chapter 8 to try to tie together in a succinct and policyrelevant way material presented in more detail in earlier sections. Th e introduction should more clearly motivate the need for and implications of characterizing susceptible and vulnerable subgroups. The policy-relevance of “vulnerable” subgroups that tend to have higher exposures suggests a need to better quantify inter-individua l variability, as well as spatial and temporal variability, in exposure, and to consider multip le PM sizes and components in the context of exposure. The policy-relevance of “susceptibl e” subgroups is that they may have different concentration-response functions th an the general population or that “effect modifiers” need to be considered. The concentration-response function material w ould have a better context if presented after the susceptibility material.

Furthermore, impaired visibility has generally been treated as an aes thetic effect without health-related consequences. In fact, most if not all visibility preference and valuation studies have emphasized in their partic ipant instructions, explicit guid ance to value only the aesthetic impact of impaired visibility and not to valu e any perceived health, psychological, or other effects. The committee questions this separation. It is well documented that impaired visibility

10or haziness can cause feelings of gloominess, confinement, loss of freedom, and in some cases depression. Conversely, good visib ility can cause one to have feelings of well-being and freedom and can be linked to positive health outcomes.

Several panelists expressed concern that the te rm “vulnerable” might not be the best term to use in capturing the range of popul ation characteristics th at affect the risks to health from air pollution exposure. CASAC recommends that key terms be carefully defined, such as “susceptible,” vulnerable,” and “characteristics,” and that a stronger conceptual framework be developed for understanding the implications of these factors fo r risks to health.

CASAC recommends that Table 8-1 be revised to be a more complete “road map” that not only lists the “characteristics” of sus ceptible and vulnerable groups, but provides an indication of the weight of evid ence and strength of a ssociation for each. These can be indicated qualitatively. EPA is encouraged to either furt her expand Table 8-1 or cr eate additional tables that would more clearly lay-out how the “characteristics” map to health effects endpoints with respect to time frame of the effect (l ong-term, short-term), PM size ranges (PM 2.5 , PM 10 , PM 10-

2.5 , and ultrafine), PM components of particular concern (e.g., black carbon, organic carbon, elemental carbon, sulfate, nitrate, and transition metals), and health effect(s) of particular concern (e.g., specific morbidity and mortality outcomes).

CASAC recommends greater cons istency in the content of Ta ble 8-1 and the explanatory text of the chapter, and for a consistent approach to defining and using terms and “characteristics.” For example, some “characteris tics” are evaluated using surrogates rather than direct measurements (e.g., for socioeconomic status). Furthermore, there may be some unavoidable overlap among characteristics and between susceptible and vulnerable subpopulations. For example, socioeconomic status may be associated with conditions that lead to higher exposures (e.g., because of locations or activity patterns of th e subpopulation) but also to higher susceptibility (e.g., because of health care history and pre-existing conditions). For purposes of transparency, EPA should identify and explain such overlap and the basis of a judgment to assign an issue to a pa rticular subgroup or category.

9. How useful and complete is the scientif ic evidence presented and summarized in Chapter 9 regarding the effects of atmos pheric PM on the environment, including (a) effects on visibility, (b) effects on individual organisms, (c) direct and indirect effects on ecosystems, (d) effects on materials, and (e) effects on climate? To what extent do the discussions and integration of evidence correctly represent and clearly

communicate the state of the science?

A summary of the Chapter 9 welfare effects should be added, and integrated with the

health effects summaries in th e Chapter 2 integrativ e overview. CASAC f ound that the Chapter 9 summary of welfare effects of PM (on visibilit y, individual organisms, ecosystems, materials, and climate) was complete, if uneven. The cl arity of the chapter could be improved by adding more detailed explanations of fundamental concep ts like urban vs. rural visibility and providing better definitions of acronyms a nd specialized technical jargon. Some of the conclusions on causality could be stated with more specificity, in ways that might provide a better indication of

11which effects might be most responsive to chan ges in PM concentrations and exposure durations, size fractions or chemical components.

The section on PM effects on climate needs si gnificant editing for clarity and focus and

there are some mistakes that need corrections . Potential benefits and harms of each PM component should be summarized along with the uncertainties.

This added specificity would be particularly useful for the section on climate effects,

which would benefit from more detail on differen tial effects of different PM components, the

relative contributions of PM com ponents originating in the US to global aerosol and radiation budgets, and discussion of potential health e ffects of PM-induced climate changes.

The Chapter 9 discussion of visibility effect s is substantially more detailed than the discussion of other public-welfare effects. To a large extent, this is ju stified by the strong and reasonably well-understood relationship between PM 2,5 concentration and visi bility impairment. However, the detail with which direct impact s on organisms and ecosystems are addressed is inadequate relative to the amount of informati on available and the potential importance of the issue. Important steps can be taken at this time toward causality determination, although it is recognized that quantitative findings of causality may not be possibl e from available data. In the well-defined process of causality determination, it is clear that the inte rmediate levels imply uncertainty that should drive future resear ch to inform the next review cycle.

Chapter 9’s focus on “recent” visibility information, available since the 2004 Criteria Document, relies heavily on information genera ted through the Regional Planning Organizations (RPO’s) to support State Implementation Plans (SIPs) under EPA’s Regional Haze Rule. One limitation of these data is that relatively litt le information is provide d on visibility in the suburban and urban areas, which are not protect ed by the Regional Haze Rule, and for which a possible secondary PM standard could provide benefits complementary to those provided by the Regional Haze Rule. Another limitation is that the PM/visibility association is described exclusively in terms of the chemical-species-s pecific reconstructed ex tinction approach that forms the basis of the Regional Haze Rule. While a similar approach could conceivably be used as an “indicator” for a secondary PM standard in urban areas, Chapter 9 could do a better job laying the groundwork for considering other pote ntial visibility indicators, such as the relationship with sub-daily PM 2.5 indicator recommended in the la st NAAQS review cycle, and the potential use of optical indicators. Ther e is strong support for using a nephelometer and

aethalometer combination fitted w ith size selective inle ts to routinely and continuously measure fine and coarse particle scatteri ng and absorption. In addition to measuring a variable directly related to visibility, the measurement also yields an estimate of fine and coarse particle mass on a

semi-continuous basis. Additional discussion of th e strengths and limitations of the different PM and optical measurement methods and their potentia l use as indicators for a secondary standard would be very helpful.

Panel members also suggest that additional discussion would be useful on the importance of (and ways to include measures of) coarse partic le contributions to visibility impairment which are especially important in urban areas in we stern states. Added discussion on the value of continuous particle size distribution measurements would be useful, as would some discussion of

12the importance of particle dens ities and differences between in ternally and externally mixed

aerosols.

Chapter 9 includes literature citations that relate to the effects of impaired visibility on psychological wellbeing, but it do es not summarize the findings of those studies, nor does it

discuss the relevance of these fi ndings to development of a more appropriate secondary standard that is different in form from the present id entical primary and secondary standards for PM.

With respect to the eventual formulation of proposal(s) in this review cycle for the secondary PM NAAQS, the scientific literature demonstrates visibi lity impairment from PM at mass concentration levels below those of the current PM primary and secondary NAAQS and at averaging times shorter than those of the cu rrent PM primary and secondary NAAQS. As the Clean Air Act requires review and advice to the Administrator on secondary NAAQS by the CASAC that specify a level of ai r quality requisite to protect the public welfare from any known or anticipated adverse effects, CASAC would expect to review policy-relevant summary results describing EPA analyses relating the proposal(s) for light extincti on indicator(s) for secondary PM NAAQS to the proposal(s) for the primary PM NAAQS. These analyses should also address the variation and ranges of PM mass concentrat ions, chemical composition, size distributions, and contributing sources across th e nation relevant to the sec ondary PM NAAQS in order to assist CASAC in providing a dvice to the Administrator.

10. This first external review draft PM ISA is of substantial length and reflects the copious amount of research recently conducted on PM. EPA has attempted to succinctly present and integrate the policy-rel evant scientific evidence for the review of the PM NAAQS. Does the Panel have opinions on how the document can be shortened without eliminating im portant and necessary content?

We recognize the length of the document reflect s the very extensive literature and data that were considered. Some shortening might be accomplished by removing descriptions of individual studies, unless highligh ting of strengths and weaknesses of particular studies is needed because of their importance. The document also need s a listing of the acronyms to assist readers.

We thank the Agency for the opportunity to provide advice early in the PM NAAQS review process, and look forward to the revi ew of the Second Draft ISA in October 2009.

Sincerely,

Dr. Jonathan M. Samet, Chair Clean Air Scientific Advisory Committee

Enclosures: CASAC Particulate Matter Review Panel Roster Compendium of Individual Comments

13NOTICE

This report has been written as part of the activities of the EPA's Clean Air Scientific Advisory Committee (CASAC), a federal advi sory committee independently chartered to provide extramural scientific information and ad vice to the Administrator and other officials of the EPA. CASAC provides balanced, expert assessmen t of scientific matters related to issues and problems facing the Agency. This report has not b een reviewed for approval by the Agency and, hence, the contents of this report do not necessa rily represent the views and policies of the EPA, nor of other agencies within the Executive Br anch of the federal government. In addition, any mention of trade names or commercial products does not constitute a recommendation for use. CASAC reports are posted on the EPA We b site at: http://www.epa.gov/casac.

14Enclosure A



### Clean Air Scientific Advisory Committee

Particulate Matter Review Panel

CHAIR

Dr. Jonathan M. Samet , Professor and Chair, Department of Preventive Medicine, University of Southern California, Los Angeles, CA

CASAC MEMBERS Dr. Joseph Brain , Philip Drinker Professor of Envir onmental Physiology, Department of Environmental Health, Harvard School of Public Health, Ha rvard University, Boston, MA

Dr. Ellis B. Cowling , University Distinguished Professo r At-Large Emeritus, Colleges of Natural Resources and Agricultur e and Life Sciences, North Caro lina State University, Raleigh,

NC

Dr. James Crapo , Professor of Medicine, Department of Medicine , National Jewish Medical and Research Center, Denver, CO

Dr. H. Christopher Frey , Professor, Department of Civ il, Construction and Environmental Engineering, College of Engineering, No rth Carolina State University, Raleigh, NC

Dr. Donna Kenski , Data Analysis Director, Lake Mi chigan Air Directors Consortium,
Rosemont, IL

Dr. Armistead (Ted) Russell , Professor, Department of Civ il and Environmental Engineering , Georgia Institute of Technology, Atlanta, GA

CONSULTANTS Dr. Lowell Ashbaugh , Associate Research Ecologist, Cr ocker Nuclear Lab, University of California, Davis, Davis, CA

Prof. Ed Avol , Professor, Preventive Medicine, Keck School of Medicine , University of Southern California, Los Angeles, CA

Dr. Wayne Cascio , Professor, Medicine, Cardiology, Brody School of Medicine at East Carolina University, Greenville, NC

Dr. Douglas Crawford-Brown , Professor Emeritus, Department of Environmental Sciences and Engineering, University of North Caro lina at Chapel Hill, Chapel Hill, NC

Dr. David Grantz , Director, Botany and Plant Sciences and Air Pollution Research Center, Riverside Campus and Kearney Ag ricultural Center, University of California, Parlier, CA

1516 Dr. Joseph Helble , Dean and Professor, Thayer School of Engineering, Dartmouth College,
Hanover, NH

Dr. Rogene Henderson , Senior Scientist Emeritus, Lovelace Respiratory Research Institute, Albuquerque, NM

Dr. Philip Hopke , Bayard D. Clarkson Distinguished Pr ofessor, Department of Chemical Engineering, Clarkson University, Potsdam, NY

Dr. Morton Lippmann , Professor, Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY

Dr. Helen Suh MacIntosh , Associate Professor, Environm ental Health, School of Public Health, Harvard University, Boston, MA

Dr. William Malm , Research Physicist, National Park Service Air Resources Division, Cooperative Institute for Research in the Atmosp here, Colorado State University, Fort Collins,

CO

Mr. Charles Thomas (Tom) Moore, Jr. , Air Quality Program Manager, Western Governors' Association, Cooperative Institute for Research in the Atmosphere, Colorado State University, Fort Collins, CO

Dr. Robert F. Phalen , Professor, Department of Comm unity & Environmental Medicine; Director, Air Pollution Health E ffects Laboratory; Professor of Occupational & Environmental Health, Center for Occupation & Environment H ealth, College of Medicine, University of California Irvine, Irvine, CA

Dr. Kent Pinkerton , Professor, Regents of the University of California, Center for Health and the Environment, University of California, Davis, CA

Mr. Richard L. Poirot , Environmental Analyst, Air Pollutio n Control Division, Department of Environmental Conservation, Vermont Agency of Natural Resources, Waterbury, VT

Dr. Frank Speizer , Edward Kass Professor of Medicine, Channing Laboratory, Harvard Medical School, Boston, MA

Dr. Sverre Vedal , Professor, Department of Environmen tal and Occupational Health Sciences, School of Public Health and Community Medici ne, University of Washington, Seattle, WA

SCIENCE ADVISORY BOARD STAFF Dr. Holly Stallworth , Designated Federal Officer, EPA Scie nce Advisory Board Staff Office, Washington, DCEnclosure B



### Compendium of Comments

CASAC Particulate Matter Review Panel on

PM Integrated Science Assessment (First External Review Draft, Dec. 2008)

Comments from Dr. Lowell Ashbaugh ____________________________________________ 2

Comments from Mr. Ed Avol ____________________________________________________ 4

Comments from Dr. Joseph Brain _______________________________________________ 9

Comments from Dr. Wayne Cascio ______________________________________________ 11

Comments from Dr. Ellis Cowling ______________________________________________ 35

Comments from Dr. James Crapo _______________________________________________ 39

Comments from Dr. Douglas Crawford-Brown ____________________________________ 41

Comments from Dr. David Grantz ______________________________________________ 45

Comments from Dr. Joseph Helble ______________________________________________ 49

Comments from Dr. Rogene Henderson __________________________________________ 51

Comments from Dr. Phil Hopke ________________________________________________ 52

Comments from Dr. Donna Kenski ______________________________________________ 55

Comments from Dr. Mort Lippmann ____________________________________________ 60

Comments from Dr. William Malm ______________________________________________ 65

Comments from Dr. Kent Pinkerton _____________________________________________ 69

Comments from Dr. Robert Phalen ______________________________________________ 73

Comments from Mr. Rich Poirot ________________________________________________ 76

Comments from Dr. Ted Russell ________________________________________________ 86

Comments from Dr. Frank Speizer ______________________________________________ 89

Comments from Dr. Helen Suh MacIntosh ______________________________________ 100

Comments from Dr. Sverre Vedal ______________________________________________ 104

1Comments from Dr. Lowell Ashbaugh

Review of Chapter 9 – Ecosystem and Welfare Effects

Charge questions

1. How useful and complete is the scientific evidence presented and summarized in Chapter 9 regarding the effects of atmospheric PM on the environment, including (a) effects on visibility, (b) effects on i ndividual organisms, (c) direct and indirect effects on ecosystems, (d) effects on materials, and (e ) effects on climate? To what extent do the discussions and integration of evidence corr ectly represent and clearly communicate the

state of the science?

2. This first external review draft PM ISA is of substantial length a nd reflects the copious amount of research recently conducted on PM. EPA has attempted to succinctly present and integrate the policy-relevant scientific evidence for the review of the PM NAAQS. Does the Panel have opinions on how the doc ument can be shortened without eliminating important and necessary content?

The authors of this chapter have done an excellent synthesis of the releva nt science regarding the effects of atmospheric PM on the environment. Some sections require technical editing for grammar and spelling, but the technical evidence is complete and is presented well. The presentation could be made more useful in several ways.

The spatial distribution of aerosol extinction and contribution of sp ecies to extinction in Figures 9-7 through 9-23 would be more useful if the cont our intervals were sta ndardized for groups of related figures. As they are presented they s how the spatial patterns well but standardized intervals and ranges would also illustrate the tem poral changes. If it makes sense to standardize the different species it would also better illustrate the relative impact of the different species in different time periods. If the levels for each species are too different, it would still be helpful to standardize the scales for each time period of a gi ven species. It’s also not clear on these figures why the highest contour level has a different spacing than the others. That makes the red (highest) contour levels misleading.

The sentence on lines 3-5 of page 9-31 is not clea r. It’s either a run-on sentence or is missing a crucial piece that woul d tie it together.

Because Figures 9-12 and 9-13 (also 9-14 & 9-15 and 9-16 & 9-17), are compared in the text, it would be helpful to place each pair on the sa me page or on facing pages so the reader can visually compare them more easily.

In the discussion comparing IMPROVE and CSN data, there should be some mention of the different methods of handling bl ank subtraction. IMPROVE subtract s a blank from each sample for ions and carbon analyses, but CSN does not. This makes comparing the concentrations

between the networks a little more difficu lt; not impossible, but not straightforward.

The discussion of IMPROVE and CSN carbon data should comment on the different methods used to obtain the fractions. In fact, the disc ussion of carbon measurements in any network

should include the method used to make them a nd how that may affect the results. Comparison

2of total carbon between networks is less sensitive to the method used, but comparison of the fractions is highly de pendent on the method.

The statement on lines 7-8 of page 9-40 regarding fine soil and coarse mass is not entirely correct. The different ratio suggests a differe nt composition of coarse mass but does not necessarily suggest a difference in the size di stribution of suspendabl e soil materials. The statement is valid only if the assumption is true that fine soil is a good surrogate for coarse mass. In my experience that is just not true at all.

There is a mention on page 9-40 of the confounding effect of meteorologi cally driven interannual variability, but I would like to see an explicit statement calling for the investigation of the meteorological and climate-driven effects on particle concentrat ions and speciation. This is particularly relevant for th e comment on page 9-44 regarding the depression of wintertime particulate nitrate for several years measured by the IMPROVE network. This feature may be due to meteorological influences, but has not yet been investigated.

There are several mentions of “upwind sources” in the discussion on page 9-46. Presumably, this refers to the San Francisco Bay Area, but it should be more clearly stated.

I found a couple of references that were missi ng or misdirected. All references should be checked for accuracy. The reference to McDade (2006) is not in the list of references (see line 14 on page 9-44). The reference for the comment on lines 6-9 of page 9-48 (Pitchford, et al., 2007)

does not seem to be accurate. I coul d not find those statistics in that paper. I’m also skeptical of the statement on line 11 of page 9- 50 that over half the sulfate in remote areas of the Pacific

coastal sites is from outside the U.S. If this is a model result, it shoul d be labeled as suspect.

The discussion of fine particles on page 9-84 shou ld mention nanoparticle emissions as a direct source of fine particles. On page 9- 87, “occult deposition” should be defined.

On page 9-88, the discussion of dry deposition should include mention of the surrogate surface work and sampler developed by Dr. Cliff Davidson of Carnegie-Mellon University.

I believe there is some redundancy in section 9.5.1.2, and possibly elsewhere in the document. I suspect this may be due to the number of au thors required to produce such a comprehensive document. It may be possible to reduce its size by having a single person go through the entire document for consistency and to remove redundanc y. This task may be too time-consuming to actually carry it out, though.

I will list a few detailed comments:

• On page 9-2 is the statement that nitrate important in most of California. It would be accurate to say “much of California”, but not “most”.

• Equation 9-2 needs work. It looks like it was copied unsuccessfully from another document. For example, “Large” is printed as “ L arg e ”. Also, the text refers to bold text but there is none.

• There are grammatical errors throughout the chapte r, but most of them are before section 9.3.5. For example, there are several uses of the word “dominate” that should be “dominant”. There are cases of misplaced parentheses and some minor t ypographical spelling errors. The chapter needs to be reviewed carefully for grammatical accuracy.

3Comments from Mr. Ed Avol

General Comments:

The First Draft ISA is a remarkable overview of the breadth of recent PM research conducted primarily in the United States over the past seve ral years. EPA staff should collectively be congratulated and acknowledged for distilling an amazing array of data from multiple sources

into one central location for consideration. The authors and reviewers liste d as participating in the document’s preparation are among the acknowl edged experts in their respective fields, and EPA should be congratulated for assembling such a talented team to review this vast amount of material. There are, inevitably, differences of opinion in inferences, nuances, approaches, and conclusions, but the major accomplishment of assembling this material should not go unnoticed.

There are at least two comments/concerns I have w ith the stated approach. I was disappointed in

the decision to minimize or dismiss extended cons ideration of ultra-fine particles or trafficrelated pollution exhaust. The accumulating numbe r of carefully-performed and peer-reviewed research describing the observed associations be tween fresh combustion exhaust (primarily from motor vehicles) and a range of health outcomes (respiratory, cardiovascul ar, birth-related, and even developmental) suggest that there is a rapidly accumulating body of information on which to objectively and seriously consider the need for a criteria standa rd. If this consideration does not move forward within the context of the peri odic review of the current PM standards, I am

concerned about what and where the EPA believes the appropriate venue to be. Other countries, most notably in the European Union, have mo ved forward in quantif ying, monitoring, and regulating ultra-fine PM, while the United States has been slower to respond. In my opinion, this

decision should be re-considered and re-opened for discussion.

I was also disappointed to see the decision to effectively restrict doc ument consideration of health endpoints to primarily respiratory and cardiovascular results. Although the discussion “door” has arguably been left sli ghtly ajar to allow some natal or pre-natal health outcomes to possibly stand in the proverbial doorway, the deci sion to not endorse and include these and other developmental outcomes as important and critic al in our overall understanding of PM health effects seems outdated and short-sighted. Our re sponsibility to review the science and make recommendations that will lead to the developmen t of standards that protect the public health

extends to the full distribution of the population, and ought to in clude the widest breadth of

available credible scientific information in those deliberations. Our understanding of the mechanisms and pathways of exposure and effect have evolved beyond limiting our review to primary target organs of immedi ately present receptors, and our c onsideration of viable data for

deliberations in standard-s etting ought to, as well.

The document needs some clarifying comments rega rding health outcomes to be considered based on the strength of relationships. The cu rrent implication that only the two uppermost levels -- causal and likely causal – are being considered beyond this initial point is apparently mistaken, based on Staff comments, but the docum ent leaves the reader with that impression.

The Agency’s “official” perspective on Climat e Change is inconsistently presented and prioritized in the current document (mostly in Chapter 9). Given the importance of carbon

4aerosol in both air pollution and global climate matters, the ISA should raise the visibility and

discussion of such issues.

Finally, no other pollutant so readily lends itself to consideration of multi-pollutant mixtures and multi-pollutant exposures than PM. The chemical variability, as well as the size and source differences, make this an especially challenging exposure of interest, but the opportunity to view Pm as a multi-pollutant entity and develop a means of dealing with it in the context of the review process would be an invaluable step forward towards true consideration of multi-pollutant mixtures, compared to the current, and much le ss-realistic, approach of considering individual specific pollutants.

Specific Comments P1-14, lines 12-30 – Emphasis on cl inical studies, given both th e multi-pollutant nature of ambient exposures and the multi-compositional (and size) nature of PM, makes elucidation in

clinical studies even a higher threshold to surmount than for other pollutant reviews. Is there some way to take this into consideration?

Chapter 3: Source to Human Exposure P3-1, Introduction – There is a lo t of discussion here (in the In troduction?) about soluble organic aerosols (SOAs), without adequate justification as to why or wh at other other key constituents might be present. In my opinion, this should be moved or at least pref aced by some transitional justification.

P3-1, lines 20-29, P3-2 lines 1-10 – move th is to after SOA discussion in Section 3.3.

P3-2, lines20-22 – “Within a street canyon,...” seems to be tacked on to this paragraph and out of place (no real connection to the paragraph, except only in the broa dest possible sense).

P3-2, line 23 – “receptor modeling studies indicat e that the main source...” sounds odd – isn’t receptor modeling focused on receptors?

P3-2, line 27 – Is the observation that “vegetativ e burning and traffic-related emissions were less consistently identified...”, both which w ould presumably be in smaller-than-PM 2.5 size ranges close to the source, really a surprise? PM2.5 has a more regional spatial character.

P3-9, line 1 – It would be more accurate to begin this sentence “US national average...”

P3-23, line 10 – So what is the conclusi on one is to draw from all of this?

P3-26, line20 – There is LOTS of information pr esented on instrumentation and sampling; what to do with all of this to make it accessible? A summary table (such as the one in the Annex) would be helpful here, or reference to the annex table...

P3-26, line 21 – Why does this paragraph be gin with this comment about ”maximum concentration sites”? I would suggest that th e paragraph begin with the sentence “...The AQS

5contains measurements...” in line 23, and the pr evious two sentences be reversed in order and moved to P3-27, line 2.

P3-27, lines 8-9 – Isn’t this description a bout neighborhood scale monitoring? How do air pollution episodes relate to micro < 100m) or middle (100-500m) scales?

P3-27, line 15 – “Urban scale – This scale applies for assessment of air quality at an urban scale” is not much of an explanation...!

P3-27 – Reference is made to a number of di fferent monitoring networks (NAMS, SLAMS, CSN, IMPROVE, NCORE,...) without ever explaining what they are or how they overlap or differ. How about a summary table showing th e major networks, the frequency of sampling, typical monitoring array, sa mpling requirements, etc?

P3-28, line 4 – replace “ built” with “located”

P3-28, line 21 – “...local conditions...” comment should be clarified; it refers to atmospheric or meteorology (temperature, humidity, pressure).

P3-33, Tables 3-5 to 3-10, incl ude units in title (“...aged _ years ...”)

P3-38, line 12-13 – The comment is made here that there is a large amount of new information

about ultra-fines...but then the de cision is made to not consider it in the context of the PM

review...seems a bit inconsistent.

P3-38, lines 27-28. While I don’t disagree with the Watson et al comment about spatial scales of interest, from a health standpoint, micro or middl e scales (100s of meters ) may be a critically important consideration (for example, in the context of proximity to busy roads).

P3-44, Table 3-12 – where was the 828 ug/m3 1 hour average reading observ ed, and what was its explanation?

P3-85, Figure 3-41 – It seems surprising that na phthalene, which typi cally is pr esent in concentrations a magnitude higher than other PA Hs, is in the bottom half of these plots...?

P3-90 – The layout of figures and text through this section is confusing to the reader, in that the text under a given figure does not describe or relate to that figure...can this be adjusted?

P3-92 – What is the purpose and utility of this “EPA region office” presentation of data? It is arguably a bit deceptive, since Re gion 9 (for example) shows a nice downward or flat trend in Figure 3-47 that is below the NAAQS line, but within that region [Southern California/Riverside] large areas are out of compliance and will remain so for several years to come (according the AQMP estimates by the local agency).

6P3-94, Figure 3-49 – Here, too, the plots by EPA regi on office is deceptive. The trend lines look to be well under the NAAQS, but Southern California is still out of compliance. Are the most appropriate metrics being plotted and presented?

P3-132 – The discussion on this and the previous pages about temporal, spatial, and physical activity effects on exposure seems a little thin. There has been a LOT of work looking at personal exposures, time-activity, and spatial determ inations (diary-based, for the most part, until recently). None of it, as it relates to PM e xposure, is summarized or referenced here...?

P3-134, “New Developments in Microenvironm ental Exposure Monitoring Techniques – I expected to see something about the NIH Expos ure Biology Initiative samplers and innovations here (lab-on-a-chip, mini aturized samplers, etc) but no apparent mention...?

P3-135, line 4 – replace “guiet” with “quiet”

P3-135, lines 4-10 – “Personal clouds”, variab le locations, and other microenvironmental considerations may provide legitimate reasons for differences between personal measurements and fixed-site ambient measurements. The para graph in the text make s it sound like the personal

measurements are less credible or somehow fall s hort of being “equal” to a fixed-site monitor, when the true state of reality might very well be the reverse.

P3-138, lines 9-19 – Important points are raised in this section, but it should also be noted that one might infer from this discussion that zip codes are the appropriate unit for community assessment and assignment of exposure. This could be quite misleading in areas where the population is such that a given zi p code covers a wide geographic, or vari able topographic, or

variable trafficked/road-covera ge/vehicle-loaded, area. Acco rdingly, there should be some

caveats or considerations associ ated with the document text.

P3-138, lines 20 and 22 – replace “among” with “between”

P3-147, line 13 – Is “0.3%” a printing error? This doesn’t seem like much to be concerned

about...?

Miscellaneous Comments: Chapter 6 is important, but could be dramatical ly trimmed in size by m oving the “criteria-type” litany of study reports to the annex (e.g., page 6-112 discussion a bout asthmatic children and the page 6-116 discussion on asthmatic adults), a nd replacing these with a chapter-wide, more consistent summary of recent studies.

Chapter 8 was difficult to integrate. The title (Public Health Impacts) seems misleading, since what was presented were portions about concentration-response relations hips and susceptibility vs vulnerability. Table 8-1 is an evolutionary improvement, but the vuln erability portion of the

table is inconsistent and in n eed of revision. Some of the lis ted factors are subsets of other factors, while still others don’t qui te fit with the nomenclature as described. Alternatively, this sort of presentation and consider ation is a real improvement and should be continued (but this

7specific presentation needs some work). Arguably, Chapter 8 should appear as the executive summary, or as the concluding chapter, but its current location seems out-of-place.

8Comments from Dr. Joseph Brain

Chapter 1 : I presume that this document, the ISA-PM draft, sets the stage for recommendations regarding the confirmation or changes in the current NAAQS Standard for PM. I appreciate Table 1-1, which outlines the evolution of this standard, from 1971-2006. But the document is

less clear as to the future of the PM standar d. What options are being considered? Would changes be likely in regard to the size of the aerosol, the level of the aerosol, or the averaging time? As we consider the evidence, it would be helpful to know the options that are being

considered.

Section 1.2 delineates many of the issues which have been critical in the past. But some additional paragraphs at the end of this section should hi ghlight the most controversial aspects of the latest EPA final decision (September 21, 2006), and both the timing of future decisions and the possible scope. This would help CASAC and the public know what to look for. What are the critical issues, e.g. level, indicator size dist ribution, or averaging time? Are there other issues that need to be considered, e.g. the rela tionship between outdoor and indoor air?

Is this a topic that should be addressed? The ma jority of time for US citizens is spent in indoor environments. This may become an important dr iver of environmental considerations for human health. Don’t we need to do a better job in discussing the extent to which indoor air – although not regulated by the EPA – is in fluenced by outdoor PM sources?

Chapter 3 : The fields of nanotechnology and nanotoxico logy are expanding ra pidly. In addition to highly engineered novel par ticles, such as fullerenes and quantum dots, we are also recognizing that common polydisperse aerosols, such as diesel par ticles or road dust, have a nano component. Data in Chapter 3 show that there are significant numbers of particles that are

smaller than 0.1 μ m (100 nm). The presence of na noparticles should be explicitly acknowledged. In this and in other chapters, we need to acknowledge the possibility that these small particles have a significant role which is out of proportion to their contribution to mass. Even though their relative weight is small, their relative number and surface area may be large.

This is an area of active researc h, and this should be acknowledged. Some of this is included in Section 3.4.1.3, but the fact that ultrafines are comparable to nanoparticles should be acknowledged, and the growing body of research on nanoparticles should – in the future – be incorporated.

I’m also concerned about Section 3.4.1.2, PM Speci ation. There is a se ction on speciation, as well as on cations, but I believe that there shou ld be a section entitled “Metals.” There is increasing evidence that metal constituents of PM such as iron, manganese, vanadium, or manganese are responsible for many of the PM effects. For example, certainly on a mass basis, they are more toxic than elemental carbon. Some data on the variety of metals seen and their health effects should be noted in Chapter 3. PM metal content is an im portant determinant of toxicity.

Chapter 3 also is weighted down by a large amo unt of figures showing spatial and temporal variation of PM and PM components. Is this all necessary? It’s difficult for the reader to learn much from some of these data. For example, see Figure 3-22 or Table 3- 15. See also Figure 3-

929 and Table 3-17. Should some of these data be e liminated or put into an appendix? It’s heavygoing for much of this chapter, and it’s difficult to identify the most important conclusions. This point is underlined by the shear number of figures in Chapter 3. There are 81 figures. That may

be excessive.

10Comments from Dr. Wayne Cascio

Chapter 6

General comments: The authors, contributors, a nd reviewers of Chapter 6: Integrated Health Effects of Short-Term PM Exposure of the ISA for Particulate Matter have produced an comprehensive compendium of environmental health data that in large part achieves its goal of providing a thorough source of relevant human clin ical and epidemiological data, and animal toxicological data along with an integrated and balanced di scussion of its public health implications. This draft document appears to be unprecedented in scope and detail. In spite of the broad range of content and complexity the descriptions of the ci ted studies have an exceptional degree of accuracy and integration. The discussion is in general balanced, and the evidence supports the conclu sions. The style of the PM ISA for is consistent and the document is easy to read and the concepts are clearly communicated.

In general the Tables and Figures of Chapter 6 are used effectively to communicate the copious information in a succinct manner. Annexes C, D and E are appropriate, adequate and effective in supporting the goals of the PM ISA

.

The decision to include in Chapters 6 and 7 only toxicological inhala tion and intratracheal

instillation studies when conducted at PM concentrations <2 mg/m 3 , and in vitro studies when they contributed significantly to the understanding of health effect s is logical because it is under these conditions that such studies provide the most support of biological plausibility for the

health effects.

Specific Comments :

Figure 6-1. Excess risk estimates per 10μg/m3 increase in PM 10 , PM 2.5 , and PM 10 2.5 for studies of CVD ED visits and hospita lizations. Appropriate. The PM 10 2.5 should read PM 10-2.5 . The graphics of Figure 6-1 could be improved by placing the PM 10 , PM 2.5 , and PM 10-2.5 on the left hand side of Figure 6-1 in the same way as it is done in Table 6-6.

Figure 6-2; 6-3; 6-4. Th e graphics could be improved by placing the PM 10 , PM 2.5 , and PM 10-2.5 on the left hand side of Figure 6-2; 6-3; 6-4 in the same wa y as it is done in Table 6-6.

6-8, L. 3 . ApoE-/- mice. This genetic model of athero sclerosis in the mouse is primarily a model of peripheral vascular disease rath er than coronary artery disease. In the future other models should be incorporated into the atherosclero sis research, arrhythmia and cardiac dysfunction. Models that for example that modify the func tion of cells and proteins involved in the atherosclerotic process should be incorporated. Mouse models ava ilable today that might provide more relevant information for coronary heart disease include the ApoE/LDL receptor double KO, the macrophage uPA-transgenic/apoE KO, SR-BI/apoE dKO, and the SR-BI/ApoE-R61 h/h.

6-8. 6.2.1 . Heart Rate Variability. The m easures of heart rate variab ility (HRV) include time- and frequency-domain measures. The interpretation of HRV finding continues to be a challenge

11because studies judged to be well designed and with appropriate methods continue to show disparate findings. These unanticipated outcomes rather than explained by chance perhaps are indicating that the HRV result is reflecting a fundamental respons e of an individual that is determined in part by a number of factors including age and the presence of co-morbid conditions. It is also possible that time- and frequency-domain measure of HRV are inadequate to capture the true nature of PM ’s effect on heart rhythm. For ex ample, no data contained in the previous AQCD or the current ISA describes any studies utilizing non-linear measures of HRV. Non-linear functions capture the structure and comp lexity of RR intervals and have the potential to provide a more detail of randomness of the RR dynamics and possibly be more prognostic.

6-16, L. 4 . With respect to the paper by Gong et. al. 2003a, “This effect was observed immediately following the exposure and at 2-days post-exposure, ...” , it should read “.. and at 1 day post-exposure, ...”.

6-23, L. 13-25, The papers referenced regarding the assessment of arrhythmia by Dockery and colleagues (Dockery et al. 2005a, and 2005b were the first studies to inves tigate the association of air pollutants with arrhythmia utilizing an advanced internal cardiac defibrillator with the capability to store electrograms thereby allo wing a qualified cardiologist to distinguish arrhythmia from artifact, and supraventricular from ventricular arrh ythmia. This is an important point because such characterizati on was not present in the original paper by Peters et al. in 2000.

6-24, L. 11. “dame” should read “same”.

6-24, L. 12. “frome” should read “frame”.

6-27, L. 1-4. The following statement “Ectopic beats ar e defined as extra cardiac depolarizations

and are the most common disturba nce in heart rhythm. Ectopic be ats are usually benign, and may present with or without symptoms, such as palpita tions or dizziness. When three or more occur in succession, this is called a non-sustained vent ricular tachycardia.” shoul d be rewritten because of some inaccuracy. Consider the following, “E ctopic beats are defined as heart beats that originate at a location in the heart outside of the sinus node. They are the most common disturbance in heart rhythm. Ectopic beats are us ually benign, and may present with or without symptoms, such as palpitations or dizziness. Such beats can arise in the atria or ventricles. When the origin is in the atria the beat is called an atrial or supraventr icular ectopic beat. When such a beat occurs earlier than expected it is referred to as a premature supraventricular or atrial premature beat. Likewise, when the origin is in the ventricle the beat is defined as a ventricular ectopic beat, or when early a premature ventricular beat. When three or more occur ectopic beats occur in succession, this is called a non-sustained run of eith er supraventricular (atrial) or ventricular origin. When the rate of the run is greater than 100 beats per minute it is defined as a tachycardia.”

6-29. L. 15. For completeness the following sentence, “ .... likely owing to their rapid heart rates (~600 and ~350 bpm, respectively).” should be ame nded to, “... likely owing to their rapid heart rates (~600 and ~350 bpm, respectively) and repolarizing currents.”.

6-29, L. 18-19. For accuracy the following phrase, “...ve ntricular depolarization elicits the QRS

12complex, and the biopotential recove ry of the ventricles is refl ected by the T-wave. “ should be amended to, “...ventricular depolarization elicits the QRS complex, and the T-wave represents the repolarization of the ventricles.”

6-33. 6.2.3.2. Human Clinical Studies. L. 21-26. Mills et al. (2007) assume that increased ST depression during exercise represents an increased magnitude of ischemia. This is a reasonable conclusion particularly in view of canine studie s indicating that CAPS decr eases coronary artery blood flow (Bartoli et al. 2008). Yet, it is not proven that th e ST depression in man under conditions of PM exposure is caus ed by greater ischemia. An altern ative interpretation is that the greater ST depression could be secondary to he terogeneity of electrophys iological effects of particulate exposure on the myocardium that is enhance by the metabolic and ionic conditions

associated with ischemia or increased heart rate.

6-36. L. 4. “bronchia” should read “bronchial”.

6-40. L. 8-16 . Brauner et al. 2008 showed that eliminati ng particles with a HE PA filter in the homes of healthy aged adults improved microvasc ular function significan tly. The effect was attributed to the removal of PM as gases were not impacted by the HEPA filter. These findings

are similar to those observed in the Califor nia Freeway Study funded by the California Air

Resource Board under the direction of Dr. Willia m Hinds at UCLA School of Public Health where the filtering of PM from the passenger cab of a van containing rese arch subjects riding on the 405 and 710 freeways in Los Angeles, Califo rnia experienced fewer arrhythmias and a relative decrease in pro-NT BNP. These finding s (Cascio et. al. 2009) will be presented at American Thoracic Society in May 2009. Like Brauner et al. 2008 these outcomes were based on the elimination of PM rather than gases or th e stress associated with being a passenger while traveling on the freeway.

6-52. L 5-7 . For clarity the “QA interval” can be used interchangeably with the term “systolic time interval”. The term “QA interval” appears throughout the text. For th ose less familiar with the terminology using the “QA interval” might be confusing. A reference might be helpful as well. For example, Cambridge D and Whiting MV. Ev aluation of the QA interval as an index of cardiac contractility in anaesthe tized dogs: responses to changes in cardiac loading and heart

rate. Cardiovascular Res . 1986: 444-50, would provide the ba sis for this measurement.

6-49. L. 7-16 . Wellenius et al. 2007 reporte d that in a group of subject s with LV dysfunction that

PM did not affect measurements of BNP, failing to prove the hypot hesis that PM can worsen LV function. Yet, BNP the active peptide has a very short half-life and might not be the best biomarker for such a study. NT-pro BNP, the in active peptide also respons ive to LV ventricular pressure but with a substantially longer half-life might have b een a better biomarker to assess transient changes in LV function associated with PM and other air pollutant s. Thus the absence of a correlation between PM and BNP does not prove that PM does not have an impact on RV or

LV function in individuals with impaired cardiac mechanics.

6-59 . Section 6.2.8. “Blood Coagulation” is more a ppropriately named “Hemostasis, Thrombosis and Coagulation Factors”.

136-97. L. 15-7 . Just published in Environmental Health Perspectives are the findings of a CAPS coarse particle study. The reference is Graff DW, Cascio WE, Pappold A, Zhu H, Huang Y-C T, Devlin RB. Exposure to concentrated coarse ai r pollution particles causes mild cardiopulmonary effects in healthy young adults. EHP doi: 10.1289/ehp.0900558. Available 23 March 2009. In this study 14 healthy young volunteers were expose d to coarse concentrated ambient particles (CAPS) and filtered air. Coarse Pa rticle concentration averaged 89.0 μ g/m3 (range was 23.7 – 159.6). Volunteers were exposed to coarse CAPS a nd filtered air for two hours while undergoing intermittent exercise in a single-blind, cross- over study. Pulmonary, cardiac, and hematological endpoints were measured before exposure, immedi ately after exposure, an d again 24 hours after exposure. Compared to filtered air exposure, coarse CAPS exposure produced mild pulmonary inflammation as evidenced by a small increase in polymorphonuclear neutr ophils (PMNs) in the bronchoalveolar lavage (BAL) fluid 20 hours post-exposure. Ch anges in pulmonary function were not observed. Blood tissue plasminogen ac tivator (tPA) was decreased 20 hours after exposure. SDNN, a measure of overall HRV was decreased 20 hours after exposure to CAPS. Consequently it is concluded th at coarse CAPS exposure induces a mild physiologic response in healthy young volunteers approximately 20 hours af ter exposure. These changes are similar in type and magnitude to changes reported previous ly for healthy volunteers exposed to fine CAPS, suggesting that both size fractions are comparable at inducing acute cardiopulmonary changes.

6-99. L. 10 . “PM 2. ” Should read “PM 2.5 ”.

6-100. L. 21 and 23 . “H” should read either “HR” or “heart rate”.

6-101, L. 29 . “... organic and EC fraction..” should be written either as “...organic and elemental carbon....” , or “OC and EC”.

6-106, L. 22 . “H” should read “heart rate”.

6-107, L. 23-24 . “There is one study that used an indi rect measure of cardiac contractility (QAinterval) during ultrafine CAPs...” should be written as, “There is one study that used an indirect measure of cardiac contractility, the systolic time interval, as assessed by the QA-interval during

ultrafine CAPs...”.

6-125, L. 30-32 ., and 6-126, L.1. “Pietropaoli et al. (2004) observed a significant reduction in MMEF and DLCO in healthy adults 21 hours after a 2-h exposure to ultraf ine carbon particles (50 μ g/m3). This reduction in DLCO may reflect a PM-induced vasoconstrictive effect on the pulmonary vasculature.” This obs ervation might be important to the observation in the California Freeway Study (Cascio et al. accepted for pres entation at ATS May 2009) in which exposure to traffic related particles produced a relative incr ease in arrhythmia and NT-proBNP compared to filtered air. The release of NT-proBNP is cons istent with an acute increase in pulmonary pressures due to pulmonary vasocons triction with attendant RV stress.

6-134, L. 13. “Differenct” should be written “Differences”.

6-142, L. 25-26. Write out, “fine+ultrafine”.

146-6-150, L. 10 . “patter” should read “pattern”.

6-197, L. 22. “domaminergic” should be written as “dopaminergic”.

6-198, 6.4.3 . Summary and Causal Determination. It is agreed that the weight of the evidence is inadequate to assign a causal relationship between PM 10 , PM 2.5 , PM 10-2.5 , ultrafine particles, or specific PM components to CNS outcomes. Yet, this data is some of the most intriguing. These early findings should stimulate more comprehe nsive studies to elucid ate mechanism in the

animal models and man.

6-240, L. 16. “causes-specifici” should be written, “cause-specific”.

6-243, L.11. “HAs” should be written out as, “hospital admissions”.

Chapter 7.

The conclusions related to causation are c onservative and supporte d by the evidence.

7-2, L. 17-19. The statement, “The advanced lesi on that develops from this process can occlude perfusion to distal tissue, cau sing ischemia, and erode, degrade, or even rupture, revealing coagulant initiators (tissue facto r) that cause major clotting disord ers and infarction or stroke.” Should be clarified. Consider the following, “The advanced lesion that develops from this process can occlude perfusion to distal tissue, causing ischemia, and erode, degrade, or even rupture, revealing initiators of thrombosis (tissue factor) that cause major disorders caused by

arterial thrombosis and thromboembolism such as coronary artery syndrome or stroke.”

7-3, L. 8. The statement, “Agatston scores are freque ntly used to classify individuals into one of five groups (zero; mild; moderate ; severe; extensive) or accord ing to age- and sex-specific percentiles of the CAC distribution (Erbel et al., 2007).” Should be amended to read, “...the CAC distribution (Erbel et al., 2007 ) and as such the greatest util ity of the Agatson score is in ascribing a long-term clinical risk for cardiac ev ents. Yet, the Agatson score is not sensitive to

low levels of vascular calcium and as such this insensitivity might limit its utility in longitudinal epidemiological studies.”

7-3, L. 9-20 . Carotid artery internal medial thickne ss is an established measurement of large vessel atherosclerosis. Yet, recen t clinical trials have raised th e issue of its suitability as a measure of progression of atherosclerosis. As recent study puts this is sue into perspective. (Doggan S, Plantinga Y, Evans GW, Meijer R, Grobbee DE, Cots MS, Opal Investigators. Ultrasound protocols to measure carotid intima- media thickness: a post- hoc analysis of the OPAL study. Curr Med Res Opin 2009; 25(1):109- 22.). In their study they showed that in “healthy middle-aged subjects mean common CIMT protocols that include measurements at both near and far walls at multiple (> or = 2) angl es provide highest reprodu cibility combined with largest estimates of CIMT progression measur ed with high precision...” Such approaches are generally not taken this most likely limits the sensitivity of the assay.

157-4, L. 3-14 . As discussed previously the Agatston scal e is expected to be insensitive to small changes in vascular wall calcium.

7-84, L. 27 . The font of “infant mortality” s hould be changed to match the text.

7-86, L. 4 . The “n” should be written out as “numbers of subjects”.

Chapter 8.

Comment: The C-R relationship focuses on mortality effects with short- and long-term exposure to PM. The mortality endpoint is a hard endpoint but is also less sensitive indicator of health effects attendant to PM. Hospitalizations for clinical conditions are likely to provide greater sensitivity in determining the C-R relationship. From a public health perspective having a more sensitive indicator will be impor tant to fully understanding the pot ential health impact of PM, particularly at low concentrations. Yet, such da ta is limited and not sufficient to establish firm

conclusions. More data is needed in this area.

The definitions of susceptibility and vulnerability are logical and functional. Such definitions can be effectively used to categorize and summarize clinical studies with similar characteristics.

Pg. 8-6. L. 2. Spelling. “Medix are” should read “Medicare”.

References

R-3 . The full citation is now available: Anders en, Z. J., P. Wahlin, et al. (2008). "Size

distribution and total number concentration of ultrafine and accumulation mode particles and hospital admissions in children and the elderl y in Copenhagen, Denmark." Occup Environ Med 65(7): 458-66.

R-7 . Full reference now available. Bell, M. L., K. Ebisu, et al. (2008). "Seasonal and regional short-term effects of fine pa rticles on hospital admissions in 202 US counties, 1999-2005." Am J Epidemiol 168(11): 1301-10.

New References of Relevance not included in PM ISA and their Abstracts

Carder, M., R. McNamee, et al. (2008). "Intera cting effects of particulate pollution and cold temperature on cardiorespiratory mo rtality in Scotland." Occup Environ Med 65(3):

197-204. To determine whether the effect of black smoke on cardiorespiratory mortality is modified by cold temperatures. METHODS: Poisson regression mode ls were used to investigate the relationship between lagged bl ack smoke concentration and da ily mortality, and whether the

effect of black smoke on mortal ity was modified by cold temperature for three Scottish cities from January 1981 to December 2001. MAIN RE SULTS: For all-cause respiratory and noncardiorespiratory mortality, there was a signifi cant association between mortality and lagged black smoke concentration. Generally the maxi mum black smoke effect occurred at lag 0, although these estimates were not statistically si gnificant. A 10 mugm(-3 ) increase in the daily

16mean black smoke concentration on any given da y was associated with a 1.68% (95% CI 0.72 to 2.65) increase in all-cause mort ality and a 0.43% (95% CI -0. 97 to 1.86), 5.36% (95% CI 2.93 to 7.84) and 2.13% (95% CI 0.82 to 3.47) increas e in cardiovascular, respiratory and noncardiorespiratory mortality, respectively, over th e ensuing 30-day period. The effect of blacksmoke on mortality did not vary significantly between seasons (cool and warm periods). For allcause, cardiovascular and non-cardi orespiratory mortality the incl usion of interaction terms did not improve the models, although for all-cause an d non-cardiorespiratory mortality there was a suggestion for interaction between temperature a nd recent black smoke exposure. The results of this study suggested a greater effect of black smoke on mortality at lo w temperatures. Since extremes of cold and partic ulate pollution may coexist, for example during temperature inversion, these results may have im portant public health implications.

Franco Suglia, S., A. Gryparis, et al. (2008) . "Association between traffic-related black carbon exposure and lung function amon g urban women." Environ Health Perspect 116(10): 1333-7. BACKGROUND: Although a number of studies have documented the relationship between lung function and traffi c-related pollution among children, few have focused on adult lung function or examined community-based populations. OBJECTIVE: We examined the relationship between black carbon (BC), a surrogate of traffic -related particles, and lung function among women in th e Maternal-Infant Smoking St udy of East Boston, an urban cohort in Boston, Massachusetts. METHODS: We estimated local BC levels using a validated spatiotemporal land-use regressi on model, derived using ambient and indoor monitor data. We examined associations between percent predic ted pulmonary function and predicted BC using linear regression, adjusting for sociodemographics (individual and neighborhood levels), smoking status, occupational exposure, type of cooking fuel, and a diagnosis of asthma or chronic bronchitis. RESULTS: The sample of 2 72 women 18-42 years of age included 57% who self-identified as Hispanic ve rsus 43% white, and 18% who were current smokers. Mean +/- SD predicted annual BC exposure level was 0.62 +/- 0.2 microg/m3. In adjusted analysis, BC (per interquartile range increase) was associated with a 1.1% decrease [95% confidence interval (CI), -2.5% to 0.3%] in forced expiratory volume in 1 sec, a 0.6% decrease (95% CI, -1.9% to 0.6%) in forced vital capacity, and a 3.0% decrease (95% CI, -5.8% to -0.2%) in forced mid-expiratory flow rate. We noted differential effects by smoking status in that former smokers were most affected by BC exposure, whereas current smoker s were not affected. CONCLUSION: In this cohort, exposure to traffic-related BC, a co mponent of particulate matter, independently predicted decreased lung function in urban wome n, when adjusting for tobacco smoke, asthma diagnosis, and socioeconomic status.

Goldberg, M. S., N. Giannetti, et al. (2008). "A panel study in congestive heart failure to

estimate the short-term effect s from personal factors and environmental conditions on oxygen saturation and pulse rate." Occup Environ Med 65(10): 659-66. This daily diary panel study in Montreal, Quebec, was carried out to determine whether oxygen saturation and pulse rate were associated with selected pers onal factors, weather c onditions and air pollution. Thirty-one subjects with CHF participated in this study in 2002 and 2003. Over a 2-month period, the investigators measured their oxygen sa turation, pulse rate, weight and temperature each morning and recorded these and other data in a daily diary. Air pollution and weather

conditions were obtained from fixed-site monitoring stations. The study made use of mixed regression models, adjusting for within-subject serial correlat ion and temporal trends, to

17determine the association be tween oxygen saturation and pu lse rate and personal and environmental variables. Depending on the model, we accounted for the effects of a variety of personal variables (e.g., body temperature, salt cons umption) as well as nitrogen dioxide (NO2), ozone, maximum temperature and change in barome tric pressure at 8:00 from the previous day. RESULTS: In multivariable analyses, the study found that oxygen saturation was reduced when subjects reported that they were ill, consumed salt, or drank li quids on the previous day and had higher body temperatures on the concurrent day ( only the latter was statistically significant). Relative humidity and decreased atmospheric pre ssure from the previous day were associated with oxygen saturation. In univariate analyses , there was negative associations with concentrations of fine particulates, ozone, and sulphur dioxide (SO2), but only SO2 was significant after adjustment for the effects of we ather. For pulse rate, no associations were found for the personal variables and in univariate an alyses the study found positi ve associations with NO(2), fine particulates (aer odynamic diameter of 2.5 microm or under, PM(2.5)), SO2, and maximum temperature, although only the latter two were significant after adjustment for environmental effects. The findings from the pr esent investigation sugge st that personal and environmental conditions affect intermediate physiological parameters that may affect the health of CHF patients.

Liao, D., E. A. Whitsel, et al. (2009). "Amb ient particulate air pollution and ectopy--the environmental epidemiology of arrhythmogene sis in Women's Health Initiative Study,

1999-2004." J Toxicol Environ Health A 72(1): 30-8. The relationships between ambient PM(2.5) and PM(10) and arrhyt hmia and the effect modificat ion by cigarette smoking were investigated. Data from U.S. Environmental Pr otection Agency (EPA) air quality monitors and an established national-scale, log-normal krigin g method were used to spatially estimate daily

mean concentrations of PM at addresses of 57,422 individuals from 59 examination sites in 24

U.S. states in 1999-2004. The acute and subacute exposures were estimated as mean, geocoded address-specific PM concentrations on the day of , 0-2 d before, and averaged over 30 d before the electrocardiogram (ECG) (Lag (0); Lag(1); Lag(2); Lag(1-30)). At the time of standard 12- lead resting ECG, the mean age (SD) of partic ipants was 67.5 (6.9) yr (84% non-Hispanic White; 6% current smoker; 15% with co ronary heart disease; 5% with ectopy). After the identification of significant effect modifiers, two-stage random -effects models were us ed to calculate centerpooled odds ratios and 95% confidence intervals (OR, 95% CI) of arrhythmia per 10 mug/m(3) increase in PM concentrations. Among current smokers, Lag(0) and Lag(1) PM concentrations were significantly associated ve ntricular ectopy (VE)-the OR ( 95% CI) for VE among current smokers was 2 (1.32-3.3) and 1.32 (1.07-1.65) at Lag( 1) PM(2.5) and PM(10), respectively. The interactions between current smoking and acute exposures (Lag(0); Lag(1); Lag(2)) were significant in relationship to VE. Acute exposur es were not significantly associated with supraventricular ectopy (SVE), or with VE am ong nonsmokers. Subacute (Lag(1-30)) exposures were not significantly associated with arrhyt hmia. Acute PM(2.5) and PM(10) exposure is directly associated with th e odds of VE among smokers, suggesting that they are more vulnerable to the arrhythmogenic effects of PM.

Ljungman, P. L., N. Berglind, et al. (2008). "Rap id effects of air pollution on ventricular arrhythmias." Eur Heart J 29(23): 2894-901. Air pollution has b een associated with ventricular arrhythmias in patients with implantable cardi overter defibrillators (IC Ds) for exposure periods of 24-48 h. Only two studies have investigated exposure periods <24 h. We aimed to explore

18such effects during the 2 and 24 pr eceding hours as well as in relati on to distance from the place of the event to the air pollution monitor. METHODS AND RESULTS: We used a case-crossover design to investigate the effect s of particulate matter <10 microm in diameter (PM10) and nitrogen dioxide (NO2) in 211 patients with ICD devices in Gothenburg and Stockholm, Sweden. Events interpreted as ventricular arrh ythmias were downloaded from the ICDs, and air pollution data were collected from urban b ackground monitors. We found an association between 2 h moving averages of PM10 and vent ricular arrhythmia [ odds ratio (OR) 1.31, 95% confidence interval (CI) 1.00-1.72], whereas the OR for 24 h moving averages was 1.24 (95% CI 0.87-1.76). Corresponding ORs for events occurring closest to the air pollution monitor were 1.76 (95% CI 1.18-2.61) and 1.74 (9 5% CI 1.07-2.84), respective ly. Events occurring in Gothenburg showed stronger associations th an in Stockholm. CONCLUSION: Moderate increases in air pollution appear to be associat ed with ventricular arrhythmias in ICD patients already after 2 h, although future studies including larger numbers of events ar e required to confirm these findings. Representative geographi cal exposure classification seems important in

studies of these effects.

Lucking, A. J., M. Lundback, et al. (2008). "D iesel exhaust inhalation increases thrombus

formation in man." Eur Heart J 29(24): 3043-51. Although the mechanism is unclear, exposure to traffic-derived air po llution is a trigger for acute myo cardial infarction (MI). The aim of this study is to investigate the effect of diesel exhaust inhalation on platelet activation and

thrombus formation in men. METHODS AND RESULTS: In a double-blind randomized crossover study, 20 healthy volunteers were exposed to dilute diesel exhaust (350 microg/m(3)) and filtered air. Thrombus formation, coagulatio n, platelet activation, and inflammatory markers were measured at 2 and 6 h following exposure. Thrombus formation was measured using the Badimon ex vivo perfusion chamber. Platelet activation was assessed by flow cytometry. Compared with filtered air, diesel exhaust in halation increased thrombus formation under lowand high-shear conditions by 24% [change in thrombus area 2229 microm(2), 95% confidence interval (CI) 1143-3315 microm(2), P = 0.0002] and 19% (change in thrombus area 2451 microm(2), 95% CI 1190-3712 microm(2), P = 0.0005), respectively. This increased thrombogenicity was seen at 2 and 6 h, using tw o different diesel engi nes and fuels. Diesel exhaust also increased platelet -neutrophil and platelet-monocyt e aggregates by 52% (absolute change 6%, 95% CI 2-10%, P = 0.01) and 30% (absolute change 3%, 95% CI 0.2-7%, P = 0.03), respectively, at 2 h following exposure compared with filtered air. CONCLUSION: Inhalation of

diesel exhaust increases ex vi vo thrombus formation and causes in vivo platelet activation in man. These findings provide a potential mechanis m linking exposure to combustion-derived air pollution with the triggering of acute MI.

Pereira Filho, M. A., L. A. Pereira, et al. (20 08). "Effect of air pollution on diabetes and cardiovascular diseases in Sao Paulo, Brazil." Braz J Med Biol Res 41(6): 526-32. Type 2

diabetes increases the risk of cardiovascular mort ality and these patients, even without previous myocardial infarction, run the risk of fatal coronary heart disease similar to non-diabetic patients surviving myocardial infarction. There is evidence showing that particulat e matter air pollution is associated with increases in cardiopulmonary morbidity and mortality. The present study was

carried out to evaluate the effect of diabetes mellitus on the association of air pollution with cardiovascular emergency room visits in a tertia ry referral hospital in the city of Sao Paulo. Using a time-series approach, and adopting gene ralized linear Poisson regression models, we

19assessed the effect of daily va riations in PM10, CO, NO2, SO2, a nd O3 on the daily number of emergency room visits for cardiovascular diseases in diabetic and non-diabetic patients from 2001 to 2003. A semi-parametric smoother (natural spline) was adopted to control long-term trends, linear term seasonal usage and weather variables. In this pe riod, 45,000 cardiovascular emergency room visits were registered. The observed increase in interquartile range within the 2- day moving average of 8.0 micr og/m(3) SO2 was associated with 7.0% (95%CI: 4.0-11.0) and 20.0% (95%CI: 5.0-44.0) increases in cardiovascu lar disease emergency room visits by nondiabetic and diabetic groups, re spectively. These data indicate that air pollution causes an increase of cardiovascular emergency room vis its, and that diabetic patients are extremely susceptible to the adverse effects of air pollution on their health conditions.

Pope, C. A., 3rd, D. G. Renlund, et al. (2008) . "Relation of heart failure hospitalization to exposure to fine particulate air pollution." Am J Cardiol 102(9): 1230-4. Cardiopulmonary disease has been associated with particulate ma tter (PM) air pollution. There is evidence that exposure to elevated PM concentrations increase s risk of acute ischemic heart disease events, alters cardiac autonomic function, an d increases risk of arrhythmias. It is plausible, therefore, that PM exposure may exacerbate heart failure (HF). A case-crossover study design was used to explore associations between fi ne PM (PM(2.5): particles with an aerodynamic diameter < or =2.5 microm) and 2,628 HF hospitalizations. Patie nts lived on Utah's Wasatch Front and were drawn from those hospitalized at Intermountain Healthcare facilities with a primary diagnosis of HF. A 14-day lagged cumulative moving average of 10 microg/m(3) PM(2.5) was associated with a 13.1% (95% confidence interval 1.3 to 26 .2) increase in HF admissions. The strongest PM(2.5)-HF associations were for elderly patients who had previously been admitted for HF and who required only a short period of hospitalizati on. HF hospitalizations are associated with lagged cumulative exposure to PM(2.5) of approxi mately 2 weeks. In conclusion, particulate airpollution may play a role in precipitating acute cardiac decompensation in otherwise wellmanaged patients with HF, perhaps through eff ects of PM on myocardial ischemia, cardiac autonomic function, and/or arrhythmic effects.

Rundell, K. W. and R. Caviston (2008). "Ultrafi ne and fine particulate matter inhalation decreases exercise performance in heal thy subjects." J Strength Cond Res 22(1): 2-5. The purpose of this study was to inve stigate effects of PM1 (particu late matter with aerodynamic diameter 0.02-2 microm) inhalation on exercise pe rformance in healthy su bjects. Inhalation of

internal combustion-derived PM is associated wi th adverse effects to th e pulmonary and muscle microcirculation. No data are available concerning air pollution and exercise performance. Fifteen healthy college-aged males performed 4 maximal effort 6-min cycle ergometer trials while breathing low or high PM1 to achieve maximal work accumulation (kJ). Low PM1

inhalation trials 1 and 2 were separated by 3 days; then after a 7 day washout, trials 3 and 4 (separated by 3 days) were done while breath ing high PM1 generated from a gasoline engine; CO was kept below 10 ppm. Lung function was done after trial 1 to verify nonasthmatic status. Lung function was normal before and after lo w PM1 exercise. PM1 number counts were not different between high PM1 trials (336,730 +/- 149,206 and 396,200 +/- 82,564 for trial 3 and 4, respectively) and were different from low PM 1 trial number counts (2,260 +/- 500) (P < 0.0001).

Mean heart rate was not different between trials (189 +/- 6.0, 188 +/- 7.6, 188 +/- 7.6, 187 +/- 7.4, for low and high PM1 trials; respectively). Wo rk accumulated was not different between low PM1 trials (96.1 +/- 9.38 versus 96.6 +/- 10.83 kJ) and the first high PM1 trial (trial 3, 96.8 +/-

2010.65 kJ). Work accumulated in the second high PM1 trial 4, 91.3 +/- 10.04 kJ) was less than in low PM1 trials 1 and 2, and high PM1 tria l 3 (P = 0.004, P = 0.003, P = 0.0008; respectively). Acute inhalation of high (PM1) typical of many urban environments could impair exercise performance.

Sint, T., J. F. Donohue, et al. (2008). "Ambient air pollution particles and the acute exacerbation of chronic obstructive pulmonary disease." Inhal Toxicol 20(1): 25-9. Investigation has repeatedly demonstrated an association between exposure to ambient air pollution particles and numerous indices of human morbidity and mortality. Individuals with chronic obstructive pulmonary disease (COPD) ar e among those with an increased sensitivity to air pollution particles. Current and ex-smokers account for 80 to 85% of all those with COPD. The human breathing in an urban site with a sign ificant level of particulate matter (PM) may be exposed to 720 microg daily. A single cigarette introduces 1 5,000 to 40,000 microg particle into the respiratory tract of the smoker. It is subs equently confounding why such a relatively small mass of airborne PM should have any biological effect in the patient with COPD, as these individuals are repeatedly exposed to particles (w ith a similar size and composition) at perhaps a thousandfold the mass of ambient PM. Regarding th is increased sensitivit y of COPD patients to air pollution particles, there are several possible explanati ons for this seeming contradiction, including correlations of PM levels with other components of air pollution, an accumulation of multiple independent risk factors in a patient, ch anges in individual activity patterns, disparities in dosimetry between healthy subjects and COPD patients, and some unique characteristic of an ambient air pollution PM. Regardless of the underl ying mechanism for the increased sensitivity of COPD patients, exposures of these indivi duals to elevated leve ls of PM should be discouraged. To provide a greater awareness of PM levels, the U.S. Environmental Protection Agency now includes levels of air pollu tion particles in an air quality index.

Rhoden, C. R., E. Ghelfi, et al. (2008). "Pul monary inflammation by ambient air particles is mediated by superoxide anion." Inhal Toxicol 20(1): 11-5 . Lung inflammation is a key response to increased levels of particulate air pollu tion (PM); however, the cellular mechanisms leading to this response remain poorly understoo d. We have previously shown that oxidants are critical mediators of the inflammatory response elicited by inhalation of ambient air particles. Here we tested the possible role of a specific oxidant, superoxide anion, by using the membranepermeable analog of superoxide dismutase, Mn( III) tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP). Adult Sprague-Dawley rats were instill ed with either urban air particles (UAP) or

saline. MnTBAP-treated rats r eceived 10 mg/kg (ip) MnTBAP 2 h prior to exposure to UAP. Recruitment of inflammatory cells into bronc hoalveolar lavage was evaluated 4 h after instillation. Rats exposed to UAP showed signifi cant increases in the total cell number (8.9 +/- 0.6 x 10(6); sham: 5.1 +/- 0.6 x 10(6), p < .02), th e numbers of polymorphonuclear leukocytes (26 +/- 4%; sham: 6 +/- 1%, p < .0001), protei n levels (1.2 +/- 0.5 mg/ml, sham: 0.4 +/- 0.1 mg/ml, p < .001), and a trend of increase in my eloperoxidase levels (5 +/- 1; sham: 2 +/- 1 mU/ml) in bronchoalveolar lavage (BAL). Pretreatment with Mn TBAP at a dose that prevented UAP-induced increases in oxidants effectively prevented increase in BAL cells (2.7 +/- 0.6 x 10(6), p < .0001 vs. UAP), PMN influx into th e lungs (4 +/- 3%, p < .0001 vs. UAP), and increase in myeloperoxidase (2 +/- 1 mU/ml) and protein leve ls in BAL (0.1 +/- 0.1 mg/ml). These data indicate that superoxi de anion is a critical mediator of the inflammatory response elicited by PM deposit ion in the lung.

21Yatera, K., J. Hsieh, et al. (2008). "Particulate matter air pollution exposure promotes recruitment of monocytes into atherosclerotic plaques." Am J Physiol Heart Circ Physiol 294(2): H944-53. Epidemiologic studies have shown an association between exposure to ambient particulate air pollution <10 microm in diameter (PM(10)) and increased cardiovascular morbidity and mortality. We previously show ed that PM(10) exposure causes progression of atherosclerosis in coronary arte ries. We postulate that the recr uitment of monocytes from the circulation into atherosclerotic lesions is a key step in this PM(10)-induced acceleration of atherosclerosis. The study object ive was to quantify the recruitm ent of circulating monocytes into vessel walls and the progres sion of atherosclerotic plaque s induced by exposure to PM(10). Female Watanabe heritable hyperlipidemic rabbits, which naturally develop systemic atherosclerosis, were exposed to PM(10) (EHC-93) or vehicle by intratracheal instillation twice a week for 4 wk. Monocytes, labeled with 5-br omo-2'-deoxyuridine (BrdU) in donors, were transfused to recipient rabbits as whole blood, and the recruitment of BrdU-labeled cells into vessel walls and plaques in recipients was measured by quantitative histological methodology. Exposure to PM(10) caused progres sion of atherosclerotic lesions in thoracic and abdominal

aorta. It also decreased circul ating monocyte counts, decreased circulating monocytes expressing high levels of CD31 (platele t endothelial cell adhesion molecule-1) and CD49d (very late antigen-4 alpha-chain), and increased expressi on of CD54 (ICAM-1) and CD106 (VCAM-1) in plaques. Exposure to PM(10) increased the numb er of BrdU-labeled m onocytes adherent to endothelium over plaques and increased the migra tion of BrdU-labeled monocytes into plaques and smooth muscle underneath plaques. We conc lude that exposure to ambient air pollution particles promotes the recruitment of circulat ing monocytes into athe rosclerotic plaques and speculate that this is a critically important step in the PM(10)-induced progression of

atherosclerosis.

Baccarelli, A., P. A. Cassano, et al. (2008). "Cardiac autono mic dysfunction: effects from particulate air pollution a nd protection by dietary methyl nutrients and metabolic polymorphisms." Circulation 117(14): 1802-9. Particulate air polluti on is associated with cardiovascular mortality and morbidity. To help identify mechanisms of action and protective/susceptibility factors, we evaluated whether the effect of particulate matter <2.5 mum in aerodynamic diameter (PM(2.5)) on heart rate variabil ity was modified by dietary intakes of methyl nutrients (folate, vitamins B(6) and B(12), methionine) and re lated gene polymorphisms (C677T methylenetetrahydrofolate reductase [MTHFR] and C1420T cytoplasmic serine hydroxymethyltransferase [cSHMT]). METHODS AN D RESULTS: Heart rate variability and dietary data were obt ained between 2000 and 2005 from 549 elderly men from the Normative Aging Study. In carriers of [CT/TT] MTHFR genot ypes, the SD of norma l-to-normal intervals was 17.1% (95% CI, 6.5 to 26.4; P=0.002) lower than in CC MTHFR subjects. In the same [CT/TT] MTHFR subjects, each 10-mug/m(3) in crease in PM(2.5) in the 48 hours before the

examination was associated with a further 8.8% (95% CI, 0.2 to 16.7; P=0.047) decrease in the SDNN. In [CC] cSHMT carriers, PM(2.5) was a ssociated with an 11.8% (95% CI, 1.8 to 20.8; P=0.02) decrease in SDNN. No PM(2.5)-SSDN asso ciation was found in s ubjects with either [CC] MTHFR or [CT/TT] cSHMT genotypes. The nega tive effects of PM(2.5) were abrogated in subjects with higher intakes (above median leve ls) of B(6), B(12), or methionine. PM(2.5) was negatively associated with heart rate variability in subjects w ith lower intakes, but no PM(2.5) effect was found in the higher intake gr oups. CONCLUSIONS: Genetic and nutritional

22variations in the methionine cy cle affect heart rate variabil ity either independently or by modifying the effects of PM2.5.

Gallus, S., E. Negri, et al. (2008). "Europea n studies on long-term exposure to ambient particulate matter and lung cancer." Eur J Cancer Prev 17(3): 191-4. European epidemiological studies on ambient air pollution and cancer published before December 2006 are reviewed, with focus on five analytic studies pr oviding data on the asso ciation between various measures of particulate matter (PM) and lung ca ncer. A case-control study of 755 men who died from lung cancer in Trieste, Italy, reported th at, compared with less than 0.18 g/m/day of deposition of particulate, the re lative risk (RR) was 1.1 [95% confidence interval (CI): 0.8-1.5] for 0.18-0.30 and 1.4 (95% CI: 1.1-1.8) for more th an 0.30 g/m/day. In the Netherlands Cohort Study on Diet and Cancer with 60 deaths fr om lung cancer, the RR was 1.06 (95% CI: 0.43-2.63) for an increase of 10 mug/m in black smoke. In the French Pollution Atmospherique et Affections Respiratoires Chr oniques study cohort based on 178 d eaths from lung cancer, the RR associated with an increase in exposure to 10 mug/m of total suspended particulate was 0.97 (95% CI: 0.94-1.01). A nested case-control study within the European Prosp ective Investigation

on Cancer and Nutrition included 113 nonsmokers or exsmokers diagnosed with lung cancer and 312 controls. The RRs were 0.91 (95% CI: 0.70-1.18) fo r an increase in PM with diameter </=10 mum (PM10) of 10 mug/m, and 0.98 (95% CI: 0. 66-1.45) for exposure over 27 mug/m compared with less than 27 mug/m. In a Norwegian re cord linkage study, based on 1453 lung cancer deaths, no significant excess risk was found for me n, and a modest association was observed for women. European studies of PM exposure and lung cancer do not show a clear association, but uncertainties remain for the measurement of exposure and latency.

Jerrett, M., R. T. Burnett, et al. (2009). "Lon g-term ozone exposure and mortality." N Engl

J Med 360(11): 1085-95. Although many studies have linked elev ations in tropospheric ozone to adverse health outcomes, the effect of long- term exposure to ozone on air pollution-related mortality remains uncertain. We examined the poten tial contribution of exposure to ozone to the risk of death from cardiopulmonary causes and specifically to death fr om respiratory causes. METHODS: Data from the study cohort of the American Cancer Society Cancer Prevention Study II were correlated with air-pollution data from 96 metropolitan sta tistical areas in the United States. Data were analyzed from 448,850 subjects, with 118,777 deaths in an 18-year follow-up period. Data on daily maximum ozone con centrations were obtained from April 1 to September 30 for the years 1977 through 2000. Data on concentrations of fine particulate matter (particles that are < or = 2.5 microm in aerodyn amic diameter [PM(2.5)]) were obtained for the years 1999 and 2000. Associations between ozone c oncentrations and the risk of death were

evaluated with the use of standard and multile vel Cox regression models. RESULTS: In singlepollutant models, increased concentrations of either PM(2.5) or ozone were significantly

associated with an increased risk of death from cardiopulmonary cause s. In two-pollutant models, PM(2.5) was associated with the risk of death from cardiovascular causes, whereas

ozone was associated with the risk of death from respiratory causes. The estimated relative risk of death from respiratory causes that was associat ed with an increment in ozone concentration of 10 ppb was 1.040 (95% confidence interval, 1.010 to 1.067). The association of ozone with the risk of death from respiratory causes was insensitive to adjustment for confounders and to the type of statistical model used. CONCLUSIONS: In this large study, we were not able to detect

an effect of ozone on the risk of death from cardiovascular causes when the concentration of

23PM(2.5) was taken into account. We did, however, de monstrate a significant increase in the risk of death from respiratory causes in associa tion with an increase in ozone concentration.

Pope, C. A., 3rd, M. Ezzati, et al. (2009). "Fin e-particulate air pollution and life expectancy in the United States." N Engl J Med 360(4): 376-86. Exposure to fine-particulate air pollution has been associated with increased morbidity a nd mortality, suggesting th at sustained reductions in pollution exposure shoul d result in improved life expectancy. This study directly evaluated the changes in life expectancy associated with diffe rential changes in fine particulate air pollution that occurred in the United States during th e 1980s and 1990s. METHODS: We compiled data on life expectancy, socioeconomic status, and demographic char acteristics for 211 county units in the 51 U.S. metropolitan areas with matching da ta on fine-particulate air pollution for the late 1970s and early 1980s and the late 1990s and ear ly 2000s. Regression models were used to

estimate the association between reductions in pollution and changes in life expectancy, with adjustment for changes in socioeconomic and de mographic variables and in proxy indicators for the prevalence of cigarette sm oking. RESULTS: A decrease of 10 microg per cubic meter in the concentration of fine particulate matter was asso ciated with an estimated increase in mean (+/- SE) life expectancy of 0.61+/-0.20 year (P=0.004). The estimated ef fect of reduced exposure to pollution on life expectancy was not highly se nsitive to adjustment for changes in socioeconomic, demographic, or proxy variab les for the prevalence of smoking or to the

restriction of observations to re latively large counties. Reducti ons in air pollution accounted for

as much as 15% of the overall increase in lif e expectancy in the study areas. CONCLUSIONS: A reduction in exposure to ambient fine-particulate air pollution contribut ed to significant and measurable improvements in life expectancy in the United States.

Kamdar, O., W. Le, et al. (2008). "Air pollution induces enhanced mitochondrial oxidative stress in cystic fibrosis airway epithelium." FEBS Lett 582(25-26): 3601-6. We studied the effects of airborne particulate ma tters (PM) on cystic fibrosis (CF) epithelium. We noted that PM

enhanced human CF bronchial epithelial apoptosis, activated caspase-9 and PARP-1; and reduced mitochondrial membrane potenti al. Mitochondrial inhibitors (4,4-diisothiocyanatostilbene-2,2'disulfonic acid, rotenone and thenoyltrifluoroacetone) blocked PMinduced generation of reactive oxygen species and apoptosis. PM upregulated pro-apoptotic Bad, Bax, p53 and p21; and enhanced mitochondrial lo calization of Bax. The anti-apoptotic Bcl-2, Bcl-xl, Mcl-1 and Xiap remained unchanged; ho wever, overexpression of Bcl-xl blocked PMinduced apoptosis. Accordingly, we provide the evidence that PM enhances oxidative stress and mitochondrial signaling mediated apoptosis via th e modulation of Bcl family proteins in CF.

Nadadur, S. S., N. Haykal-Coates, et al. (2009 ). "Endothelial effects of emission source particles: acute toxic response gene expression profiles." Toxicol In Vitro 23(1): 67-77. Air pollution epidemiology has established a str ong association between exposure to ambient particulate matter (PM) and cardi ovascular outcomes. Experimental studies in both humans and laboratory animals support varied biological me chanisms including endothelial dysfunction as potentially a central step to th e elicitation of cardiovascular events. We therefore hypothesized that relevant early molecular alterations on e ndothelial cells should be assessable in vitro upon acute exposure to PM components previously show n to be involved in health outcomes. Using a model emission PM, residual oil fly ash and one of its predominant cons tituents (vanadium-V), we focused on the development of gene expression profiles to fingerprint that particle and its

24constituents to explore potent ial biomarkers for PM-induced e ndothelial dysfunction. Here we present differential gene expressi on and transcription factor activa tion profiles in human vascular endothelial cells exposed to a non-cytotoxic dos e of fly ash or V following semi-global gene expression profiling of approximately 8000 genes. Both fly ash and it's prime constituent, V, induced alterations in genes involved in passi ve and active transport of solutes across the membrane; voltage-dependent ion pumps; induc tion of extracellular matrix proteins and adhesion molecules; and activation of numer ous kinases involved in signal transduction pathways. These preliminary data suggest that cardiovascular eff ects associated with exposure to PM may be mediated by perturbations in endot helial cell permeability, membrane integrity; and ultimately endothelial dysfunction.

Sun, Q., P. Yue, et al. (2008). "Air pollution exposure potentiates hypertension through reactive oxygen species-mediated activation of Rho/ROCK." Arterioscler Thromb Vasc

Biol 28(10): 1760-6. OBJECTIVE: Fine particulate matte r <2.5 microm (PM(2.5)) has been implicated in vasoconstriction and potentiation of hypertension in humans. We investigated the effects of short-term exposure to PM(2.5) in the angiotensin II (AII) infusion model. METHODS AND RESULTS: Sprague-Dawley rats were exposed to PM(2.5) or filtered air (FA) for 10 weeks. At week 9, minipumps containing AII we re implanted and the responses studied over a week. Mean concentration of PM(2.5) inside the chamber was 79.1+/-7.4 microg/m(3). After AII infusion, mean arterial pressure was significan tly higher in PM(2.5)-AII versus FA-AII group. Aortic vasoconstriction to phenylephrine was poten tiated with exaggerated relaxation to the Rhokinase (ROCK) inhibitor Y-27632 and increase in ROCK-1 mRNA levels in the PM(2.5)-AII group. Superoxide (O(2).(-)) produc tion in aorta was increased in the PM(2.5)-AII compared to the FA group, inhibitable by apocynin and L-NAM E with coordinate upregulation of NAD(P)H oxidase subunits p22(phox) and p47(phox) and de pletion of tetrahydrobiopterin. In vitro exposure to ultrafine particles (UFP) and PM(2.5) was associated with an increase in ROCK activity, phosphorylation of m yosin light chain, and myosin phosphatase target subunit (MYPT1). Pretreatment with the nonspecific anti oxidant N-acetylcysteine and the Rho kinase inhibitors (Fasudil and Y-27632) prevente d MLC and MYPT-1 phosphorylation by UFP suggesting a O(2)(.-)-mediated mechanism fo r PM(2.5) and UFP effects. CONCLUSIONS: Short-term air pollution exaggerates hypertension through O(2)(.-)-mediated upregulation of the Rho/ROCK pathway.

Min, K. B., J. Y. Min, et al. (2008). "The relationship between air pollutants and heart-rate variability among community resid ents in Korea." Inhal Toxicol 20(4): 435-44. Air pollution, both particulate and gaseous, is known to cause adverse health eff ects and is associated with increased cardiovascular mortality and morbidity. With a growing recognition in the importance of the autonomic nervous system in air pollution, we examined the effects of air pollutants, namely, particulate matter (PM10), sulf ur dioxide (SO2), and nitric dioxide (NO2), on cardiac autonomic function by measuring heart -rate variability (HRV) among community residents. This study was conducted at Taein Is land, located off the southern coast of South Korea; 1349 subjects (596 males and 753 females) were included in this analysis. Subjects responded to the interview about general ch aracteristics and an HRV examination was conducted. Exposure data were collected from the Environmental Management Corporation during the same period of HRV measurement. Lin ear regression analyses were carried out to

evaluate the association over 72 h, and the parameters of HRV i ndices were presented as the

25percentage change. The exposures to PM(10), SO(2), and NO2 were associated with reduced HRV indices, and significant decreases in the standa rd deviation of the normal to normal interval (SDNN) and low frequency (LF) domain effect, a nd the effect was largely continued until 12 h. Our results suggest that air pollutants stimulat e the autonomic nervous system and provoke an imbalance in cardiac autonomic control. Thus, thes e subclinical effects ma y lead to pathological consequences, particularly in high-ri sk patients and susceptible subjects.

Stafoggia, M., J. Schwartz, et al. (2008). "Does temperature modify the association between air pollution and mortality? A multicity case- crossover analysis in Italy." Am J Epidemiol 167(12): 1476-85. Adverse health effects of particulat e matter <10 microm in aerodynamic diameter (PM(10)) and high temperatures are we ll known, but the extent of their interaction on mortality is less clear. This pa per describes effect modification of temperature in the PM(10)- mortality association and tests the hypothesis that higher PM(10) effects in summer are due to enhanced exposure to particles. All deaths of residents of nine Italian cities between 1997 and 2004 were selected. The case-crossover approach wa s adopted to estimate the effect of PM(10) on mortality by season and temperat ure level. Three strata of te mperature corresponding to low, medium, and high "ventilation" were identifi ed, and the interaction between PM(10) and temperature within each stratu m was examined. Season and temper ature levels strongly modified the PM(10)-mortality association: for a 10-microg /m(3) variation in PM(1 0), a 2.54% increase in risk of death in summer (95% confidence interval: 1.31, 3.78) compared with 0.20% (95% confidence interval: -0.08, 0.49) in winter. Anal ysis of the interaction between PM(10) and temperature within temperature strata resulted in positive but, in most cases, nonstatistically significant coefficients. The au thors found much higher PM(10) effects on mortality during warmer days. The hypothesis that such an effect is attributable to enhanced exposure to particles in summer could not be rejected.

Tamagawa, E., N. Bai, et al. (2008). "Particu late matter exposure induc es persistent lung inflammation and endothelial dysfunction ." Am J Physiol Lung Cell Mol Physiol 295(1):

L79-85. Epidemiologic and animal studies have show n that exposure to particulate matter air pollution (PM) is a risk factor for the developm ent of atherosclerosis. Whether PM-induced lung and systemic inflammation is involved in this process is not clear. We hypothesized that PM exposure causes lung and systemic inflammation, wh ich in turn leads to vascular endothelial dysfunction, a key step in the initiation and progression of athe rosclerosis. New Zealand White rabbits were exposed for 5 days (acute, total dos e 8 mg) and 4 wk (chronic, total dose 16 mg) to either PM smaller than 10 mum (PM(10)) or saline intratracheally. Lung inflammation was quantified by morphometry; systemic inflammati on was assessed by white blood cell and platelet counts and serum interleukin (IL)-6, nitric oxide , and endothelin levels. Endothelial dysfunction was assessed by vascular response to acetylcho line (ACh) and sodium nitroprusside (SNP). PM(10) exposure increased lung macrophage s (P<0.02), macrophages containing particles (P<0.001), and activated macrophages (P<0.006). PM(10) increased serum IL-6 levels in the first 2 wk of exposure (P<0.05) but not in week s 3 or 4. PM(10) exposure reduced ACh-related relaxation of the carotid artery with both acu te and chronic exposure, with no effect on SNPinduced vasodilatation. Serum IL-6 levels corr elated with macrophage s containing particles (P=0.043) and ACh-induced vasodilatation (P=0.014 at week 1, P=0.021 at week 2). Exposure to PM(10) caused lung and systemic inflammation th at were both associ ated with vascular endothelial dysfunction. This suggests that PM-induced lung and systemic inflammatory

26responses contribute to the adve rse vascular events associated with exposure to air pollution.

Yatera, K., J. Hsieh, et al. (2008). "Particulate matter air pollution exposure promotes recruitment of monocytes into atherosclerotic plaques." Am J Physiol Heart Circ Physiol 294(2): H944-53. Epidemiologic studies have shown an association between exposure to ambient particulate air pollution <10 microm in diameter (PM(10)) and increased cardiovascular morbidity and mortality. We previously show ed that PM(10) exposure causes progression of atherosclerosis in coronary arte ries. We postulate that the recr uitment of monocytes from the circulation into atherosclerotic lesions is a key step in this PM(10)-induced acceleration of atherosclerosis. The study object ive was to quantify the recruitm ent of circulating monocytes into vessel walls and the progres sion of atherosclerotic plaque s induced by exposure to PM(10). Female Watanabe heritable hyperlipidemic rabbits, which naturally develop systemic atherosclerosis, were exposed to PM(10) (EHC-93) or vehicle by intratracheal instillation twice a week for 4 wk. Monocytes, labeled with 5-br omo-2'-deoxyuridine (BrdU) in donors, were transfused to recipient rabbits as whole blood, and the recruitment of BrdU-labeled cells into vessel walls and plaques in recipients was measured by quantitative histological methodology. Exposure to PM(10) caused progres sion of atherosclerotic lesions in thoracic and abdominal

aorta. It also decreased circul ating monocyte counts, decreased circulating monocytes expressing high levels of CD31 (platele t endothelial cell adhesion molecule-1) and CD49d (very late antigen-4 alpha-chain), and increased expressi on of CD54 (ICAM-1) and CD106 (VCAM-1) in plaques. Exposure to PM(10) increased the numb er of BrdU-labeled m onocytes adherent to endothelium over plaques and increased the migra tion of BrdU-labeled monocytes into plaques and smooth muscle underneath plaques. We conc lude that exposure to ambient air pollution particles promotes the recruitment of circulat ing monocytes into athe rosclerotic plaques and speculate that this is a critically important step in the PM(10)-induced progression of

atherosclerosis.

Totlandsdal, A. I., M. Refsnes, et al. (2008). "Particle-induced cytokine responses in cardiac cell cultures--the effect of particles versus so luble mediators released by particle-exposed lung cells." Toxicol Sci 106(1): 233-41. Increased levels of particulate matter have been associated with adverse effects in the respir atory as well as the cardiovascular system. The biological mechanisms behind these associa tions are still unresol ved. Among potential mechanisms, particulate matter-associated cardiac effects may be initiated by inhaled small-sized particles, particle components and/or mediators related to infla mmation that translocate into the pulmonary circulation. In the present study cytoki ne responses (interleuki n [IL]-6, IL-1beta, and tumor necrosis factor [TNF]-alpha) of primary rat cardiomyocytes and cardiofibroblasts in mono- and cocultures induced by direct exposure to particles, were comp ared with cytokine responses induced by mediators released by part icle-exposed primary rat epithelial lung cells (conditioned media). Cells were exposed to a m odel ultrafine particle (ultrafine carbon black, Printex 90) and in selected experiments to an urban air particle sample (SRM 1648, St Louis, MO). In lung cell cultures both particle types induced release of IL-6 and IL-1beta, whereas TNF-alpha was only detected upon exposure to St L ouis particles. The release of IL-6 by cardiac cells was strongly enhanced upon exposure to conditioned media, and markedly exceeded the response to direct particle exposure. IL-1, but not TNF-alpha, seemed necessary, but not sufficient, for this enhanced IL-6 release. The ro le of IL-1 was demonstrated by use of an IL-1 receptor antagonist that partially reduced th e effect of the conditioned media, and by a

27stimulating effect on the cardiac cell release of IL-6 by exogenous addition of IL-1alpha and IL1beta. These in vitro findings lend support to the hypothesis that particle-induced cardiac inflammation and disease may i nvolve lung-derived mediators.

Totlandsdal, A. I., T. Skomedal, et al. ( 2008). "Pro-inflammatory po tential of ultrafine particles in mono- and co-cultures of primary cardiac cells." Toxicology 247(1): 23-32. Inhalation of particulate air pollu tion has been associated with increased risks for cardiovascular mortality and morbidity, but the underlying mech anisms are still under discussion. One possible pathway may be that inhaled particles cross th e air-blood barrier and in teract directly with cardiac tissue. The aim of the present study was to examine the pro-inflammatory potential of particles in cardiac cells. Mono- and co-cultures of primary adult male Wistar (Han) rat cardiomyocytes (CMs) and cardiofibroblasts (CFs) were exposed to increas ing concentrations of ultrafine (<100nm) carbon black particles (Printex 90). Expression and release of cytokines (IL6, IL-1beta and TNF-alpha) were measured by using quantitative real-time PCR and ELISA, respectively. Cytotoxicity was estimated by meas uring cellular release of lactate dehydrogenase (LDH). A particle concentration-de pendent increase in IL-6 release was observed in both CM mono- and co-cultures (EC(50) approximately 57mi crog/ml). Furthermore, IL-6 levels detected in both control and particle-exposed co-cultures were synergistically increased compared to mono-cultures (10-19-fold, dependent on the ex posure). Experiments with contact and noncontact co-cultures indicate that direct cellula r contact is of key importance for the enhanced release of IL-6 in co-cultures. An apparent part icle-induced release of IL -1beta was only detected in co-cultures. The release of TNF-alpha wa s low and did not seem notably influenced by particle exposure. Treatment with an IL-1 receptor antagonist appa rently eliminated the particleinduced release of IL-6. In conc lusion, ultrafine particles have a pro-inflammatory potential in primary cardiac cells. Furthermore, IL-1 seems cri tical in triggering part icle-induced release of IL-6. These pro-inflammatory responses may be e licited when particles are translocated into the pulmonary circulation upon inhalation or ad ministered intravascularly during medical procedures.

Lee, S. J., S. Hajat, et al. (2008). "A time-s eries analysis of any short-term effects of meteorological and air pollution factors on pr eterm births in Londo n, UK." Environ Res 106(2): 185-94. Although much is known about the incide nce and burden of preterm birth, its biological mechanisms are not well understood. Wh ile several studies have suggested that high levels of air pollution or exposur e to particular climatic factor s may be associated with an increased risk of preterm birt h, other studies do not support such an association. To determine whether exposure to various environmental factors place a large London-based population at higher risk for preterm birth, we analyzed 482,568 births that occurred between 1988 and 2000 from the St. Mary's Maternity Information Syst em database. Using an ecological study design, any short-term associations be tween preterm birth and variou s environmental factors were investigated using time-series regression techniques. Environm ental exposures included air pollution (ambient ozone and PM(10)) and clima tic factors (temperature , rainfall, sunshine, relative humidity, barometric pressure, and largest drop in barometric pressure). In addition to exposure on the day of birth, cumulative exposure up to 1 week before birth was investigated. The risk of preterm birth did not increase with e xposure to the levels of ambient air pollution or meteorological factors experienced by this population. Cumulative exposure from 0 to 6 days

before birth also did not show a ny significant effect on the risk of preterm birth. This large study,

28covering 13 years, suggests that there is no a ssociation between preter m births and recent exposure to ambient air pollution or recent changes in the weather.

Rankin, J., T. Chadwick, et al. (2009). "Mater nal exposure to ambient air pollutants and risk of congenital anomalies." Environ Res 109(2): 181-7. Studies have suggested an association between maternal exposure to ambient air pollution and risk of congenital anomaly. The aim of this study is to inve stigate the association between exposure to black smoke (BS; particulate matte r with aerodynamic diameter <4 microg/m(3)) and sulphur dioxide (SO(2)) duri ng the first trimester of preg nancy and risk of congenital anomalies. We used a case-control study design among deliveries to mothers resident in the UK Northern health region during 1985-1990. Case data were ascertained from the population-based Northern Congenital Abnormality Survey and contro l data from national data on all births. Data on BS and SO(2) from ambient air monitoring stati ons were used to average the total pollutant exposure during the first trimester of pregnancy ove r the daily readings from all monitors within 10 km of the mother's residence. Logistic regr ession models estimated the association via odds ratios. A significant but weak positive association wa s found between nervous system anomalies and BS (OR=1.10 per increase of 1000 microg/m(3) total BS; 95% CI: 1.03, 1.18), but not with other anomaly subtypes. For SO(2), a significan t negative association was found with congenital heart disease combined and patent ductus arterios us: OR significantly <1 for all quartiles relative to the first quartile. The relationship between SO(2) levels and other anomaly subtypes was less clear cut: there were either no significant associ ations or a suggestion of a U-shaped relationship (OR significantly <1 for moderate compared to lowest levels, but not w ith high SO(2) levels). Overall, maternal exposure to BS and SO(2) in the Northern region had limited impact on congenital anomaly risk. Studies with detailed exposure assessment are needed to further investigate this relationship.

Son, J. Y., Y. S. Cho, et al. (2008). "Effects of air pollution on postneon atal infant mortality among firstborn infants in Se oul, Korea: case-crossover and time-series analyses." Arch Environ Occup Health 63(3): 108-13. Infants are known to be susceptible to the adverse health effects of ambient air pollution. The authors examined the relati onship between air pollution and postneonatal mortality from a ll causes among firstborn infants in Seoul, Korea, during 1999- 2003, using both case-crossover and time-series anal yses. Using a bidirectional control-sampling approach, the authors compared the effects of various types of air pollution on postneonatal mortality. The relative risk of postneonatal mort ality from all causes was 1.000 (95% confidence interval [CI] = 0.998-1.002) for particulate matte r with a diameter < 10 mum, 1.002 (95% CI = 0.994-1.009) for nitrogen dioxide, 1.015 (95% CI = 0.973-1.058) for sulfur dioxide, 1.029 (95% CI = 0.833-1.271) for carbon monoxide, and 0.984 ( 95% CI = 0.977-0.992) for ozone for each 1- unit increase of air po llution level in the 1:6 control sel ection scheme. The authors observed a positive association between air pollution and in fant daily mortality except for the studied particulate matter and ozone, alt hough it was not statistically signi ficant. They obtained similar results in the time-series analysis. The risk of postneonatal infant death from all causes was positively associated with all studied air pollutants except ozone. The authors also confirmed that the bidirectional method with many controls will give a more efficient estimator than will a

method with fewer controls.

Epton, M. J., R. D. Dawson, et al. (2008). "The effect of ambient air pollution on

29respiratory health of school child ren: a panel study." Environ Health 7: 16. Adverse respiratory effects of particulat e air pollution have been identi fied by epidemiological studies.

We aimed to examine the health effects of am bient particulate air po llution from wood burning on school-age students in Christchurch, New Zeal and, and to explore the utility of urine and exhaled breath condensate biomarkers of exposure in this population. METHODS: A panel study of 93 male students (26 with as thma) living in the boarding h ouse of a metropolitan school was

undertaken in the winter of 2004. Indoor and outdoor pollution da ta was continuously monitored. Longitudinal assessment of lung function (FEV1 and peak flow) and symptoms were undertaken, with event studies of high pollution on biom arkers of exposure (urinary 1-hydroxypyrene) and effect (exhaled breath condensate (EBC) pH and hydrogen peroxide concentration). RESULTS: Peak levels of air pollu tion were associated with small but statistically signifi cant effects on lung function in the asthmatic students, but not hea lthy students. No signifi cant effect of pollution could be seen either on airway inflammation and oxidative stress either in healthy students or students with asthma. Minor increases in resp iratory symptoms were associated with high pollution exposure. Urinary 1-hydroxypyrene levels were raised in association with pollution events by comparison with low pollution contro l days. CONCLUSION: There is no significant effect of ambient wood-smoke particulate air pollution on lung function of healthy school-aged students, but a small effect on respiratory sympto ms. Asthmatic students show small effects of peak pollution levels on lung f unction. Urinary 1-hydroxypyrene show s potential as a biomarker of exposure to wood smoke in this population; however meas urement of EBC pH and hydrogen peroxide appears not to be usef ul for assessment of population h ealth effects of air pollution. Some of the data presented in this paper ha s previously been publis hed in Kingham and coworkers Atmospheric Environment, 2006 Jan; 40: 338-347 (details of pollution exposure), and Cavanagh and co-workers Sci Total Environ. 2007 Mar 1;374(1):51- 9 (urine hydroxypyrene data).

Ma, L., M. Shima, et al. (2008). "Effects of airborne particulate matter on respiratory morbidity in asthmatic children." J Epidemiol 18(3): 97-110. The effects of airborne particulate matter (PM) are a major human health concern. In this panel study, we evaluated the acute effects of exposure to PM on peak expiratory flow (PEF) and wheezing in children. METHODS: Daily PEF and wheezing were examined in 19 asthmatic children who were hospitalized in a suburban city in Japan for appr oximately 5 months. The concentrations of PM less than 2.5 mum in diameter (P M(2.5)) were monitored at a monitoring station proximal to the hospital. Moreover, PM(2.5) concen trations inside and outside th e hospital were measured using

the dust monitor with a laser di ode (PM(2.5(LD))). The changes in PEF and wheezing associated with PM concentration were analyzed. RESULT S: The changes in PEF in the morning and evening were significantly associated with in creases in the average concentration of indoor PM(2.5(LD)) 24 h prior to measurement (-2.86 L/min [95%CI: -4.12, -1.61] and -3.59 L/min [95%CI: -4.99, -2.20] respectively, for 10-mug/m(3) increases). The change in PEF was also significantly associated with out door PM(2.5(LD)) concentrations, but the changes were smaller than those observed for indoor PM(2.5(LD)). Ch anges in PEF and concentration of stationarysite PM(2.5) were not associated. The prevalen ce of wheezing in the morning and evening were also significantly asso ciated with indoor PM( 2.5(LD)) concentrations (odds ratios = 1.014 [95%CI: 1.006, 1.023] and 1.025 [95%CI: 1.013, 1.038] respectively, for 10-microg/m(3) increases). Wheezing in the evening was significa ntly associated with outdoor PM(2.5(LD))

concentration. The effects of indoor and outdoor PM(2.5(LD)) remained significant even after

30adjusting for ambient nitrogen dioxide con centrations. CONCLUSION: Indoor and outdoor PM(2.5(LD)) concentrations were associated with PEF and wheezing among asthmatic children. Indoor PM(2.5(LD)) had a more marked effect than outdoor PM(2.5(LD)) or stationary-site PM(2.5).

O'Connor, G. T., L. Neas, et al . (2008). "Acute respira tory health effects of air pollution on

children with asthma in US inner cities." J Allergy Clin Immunol 121(5): 1133-1139 e1. Children with asthma in inner-city communities ma y be particularly vulnerable to adverse effects of air pollution because of their airways disease and exposure to relatively high levels of motor

vehicle emissions. OBJECTIVE: To investigate the asso ciation between fluctuations in outdoor air pollution and asthma morbidity among inne r-city children with asthma. METHODS: We analyzed data from 861 children with persistent asthma in 7 US urban communities who performed 2-week periods of twi ce-daily pulmonary func tion testing every 6 months for 2 years. Asthma symptom data were collected every 2 months. Daily pollution measurements were

obtained from the Aerometric Information Retr ieval System. The relationship of lung function and symptoms to fluctuations in pollutant concentrations was examined by using mixed models. RESULTS: Almost all pollutant concentrations measured were below the National Ambient Air Quality Standards. In single-pollutant models , higher 5-day average concentrations of NO2, sulfur dioxide, and particles smaller than 2.5 mi crom were associated with significantly lower pulmonary function. Higher pollutant levels were independently associated with reduced lung function in a 3-pollutant model. Higher concentrations of NO2 and particles smaller than 2.5

microm were associated with asthma-related mi ssed school days, and higher NO2 concentrations were associated with asthma symptoms. CO NCLUSION: Among inner-city children with asthma, short-term increases in air pollutant concentrations below the National Ambient Air Quality Standards were associated with adverse re spiratory health effects. The associations with NO2 suggest that motor vehicle emissions may be causing excess morbidit y in this population.

Odajima, H., S. Yamazaki, et al. (2008). "Decline in peak expiratory flow according to hourly short-term concentration of particulate matter in asthmatic children." Inhal

Toxicol 20(14): 1263-72. The aim was to investigate the effect s of the 3-h mean concentration of suspended particulate matter (SPM) on peak e xpiratory flow (PEF) in asthmatic children. Subjects were 4- to 11-yea r-old boys and girls with asthma in Fukuoka, Japan. Daily

measurements of PEF were made between April 2002 and March 2003. PEF was measured morning and evening. To assess the association between 3-h mean concentrations of SPM and morning PEF and evening PEF separately, we used generalized estimating equations. All models

took into consideration seasonal effects: modified effects were examined using a two-level

indicator variable for the warm er months (April through Sept ember) and the colder months (October through March). Among the 70 asthmatic children, 44 were boys. In warmer months, declines in morning PEF for 10 microg/m(3) diffe rences in 3-h concentration of SPM measured at 2 a.m. to 5 a.m. of the same day and 11 p.m. to 2 a.m. and 8 p.m. to 11 p.m. of the previous day were -0.78 L/min (95% CI: -1.40, -0.16), -0.61 L/min (-1.18, -0.05) and -0.73 L/min (-1.32, - 0.15), respectively. Results were robust even after adjustment for other air pollutants. We also found that declines in evening PE F were weakly associated with increases in 3-h concentrations of SPM in warmer months, but the associations were not statistically si gnificant. In colder months we did not find any robust associati on between SPM and morning/evening PEF. In conclusion, an increased 3-h concen tration of SPM is associated w ith declines in PEF in warmer

31months.

Tecer, L. H., O. Alagha, et al. (2008). "P articulate matter (PM(2.5), PM(10-2.5), and PM(10)) and children's hospital admissions for asthma and respiratory diseases: a bidirectional case-crossover study ." J Toxicol Environ Health A 71(8): 512-20. Epidemiological studies reported ad verse effects of air pollution on the prevalence of respiratory diseases in children. The purpose of this study was to examine the association between air pollution and admissions for asthma and other respiratory diseases among children who were younger than 15 yr of age. The study used data on respiratory hospital admissions and air pollutant concentrations, includ ing thoracic particulate matter (P M(10)), fine (PM(2.5)), and coarse (PM(10-2.5)) particulate matter in Z onguldak, Turkey. A bidire ctional case-crossover design was used to calculate odd s ratios for the admissions adjusted for daily meteorological parameters. Significant increases were observed for hospital admissions in children for asthma, allergic rhinitis (AR), and upper (UPRD) and lower (LWRD) respir atory diseases. All fraction of PM in children showed significant positive associations with asthma admissions. The highest

association noted was 18% rise in asthma admissi ons correlated with a 10-microg/m(3) increase in PM(10-2.5) on the same day of admissions. Th e adjusted odds ratios for exposure to PM(2.5) with an increment of 10 microg/m(3) were 1.15 a nd 1.21 for asthma and allergic rhinitis with asthma, respectively. PM(10) exer ted significant effects on hospita l admissions for all outcomes, including asthma, AR, UPRD, a nd LWRD. Our study suggested a gr eater effect of fine and coarse PM on asthma hospital admissions compared with PM(10) in children.

Van Roosbroeck, S., R. Li, et al. (2008). "T raffic-related outdoor air pollution and respiratory symptoms in children: the impact of adjustment for exposure measurement error." Epidemiology 19(3): 409-16. Outdoor concentrations of soot and nitrogen dioxide (NO2) outside of schools have been associated with children's respiratory and eye symptoms. We assessed how adjustments for measurement error affect these associations. METHODS: Concentrations of air polluta nts outside children's school s were validated by personal measurements of exposure to tr affic-related air pollution. We estimated prevalence ratios of 4 health outcomes (current wheeze, conjunctivitis, phlegm, and elevated total serum immunoglobulin E) using school outdoor measurem ents, and then adjusted for measurement error using the personal exposure data and applying a regression calibration method. The analysis adjusting for measurement error was ca rried out using a main study/external validation design. RESULTS: Adjusting for measurement error produced effect estimates related to soot and NO2 that were 2 to 3 times higher than in the original study. The adjusted prevalence ratio for current phlegm was 5.3 (95% confidence inte rval = 1.2-23) for a 9.3 microg/m3 increase in soot, and 3.8 (1.0-14), for a 17.6 microg/m3 increase in NO2, compared with the original results of 2.2 (1.3-3.9) and 1.8 (1.1-2.8), respectively. Corre ctions were of similar magnitude for the prevalence of current wheeze, current conjunctiviti s, and total elevated total immunoglobulin E. CONCLUSIONS: The estimated effects of outdoor air pollution on respirat ory and other health effects in children may be substantially attenuated when based on exposure measurements outside schools instead of personal exposure.

Ballester, F., S. Medina, et al. (2008). "Reducin g ambient levels of fine particulates could substantially improve health: a mortality impa ct assessment for 26 European cities." J Epidemiol Community Health 62(2): 98-105. Recently new European policies on ambient air

32quality--namely, the adoption of new standards for fine particulate matter (PM(2.5)), have generated a broad debate about choosing the air quality standards that can best protect public health. The Apheis network estimated the number of potential premature deaths from all causes that could be prevented by re ducing PM(2.5) annual levels to 25 microg/m3, 20 microg/m3, 15 microg/m3 and 10 microg/m3 in 26 European citi es. The various PM(2.5) concentrations were

chosen as different reductions based on the limit values proposed by the new European Directive, the European Parliament, the US Environmental Protection Agency and the World Health Organization, respectively. The Apheis ne twork provided the health and exposure data used in this study. The concen tration-response func tion (CRF) was derived from the paper by Pope et al (2002). If no direct PM(2.5 )meas urements were availabl e, then the PM(10) measurements were converted to PM(2.5 )using a local or an assumed European conversion factor. We performed a sensitivity analysis us ing assumptions for two key factors--namely, CRF and the conversion factor for PM(2.5). Specifica lly, using the "at least" approach, in the 26 Apheis cities with more than 40 million inhabitants, reducing annual mean levels of PM(2.5) to 15 microg/m3 could lead to a reduction in the total burden of mortality among people aged 30 years and over that would be four times greater than the reduction in mortality that could be achieved by reducing PM(2.5) levels to 25 micr og/m3 (1.6% vs 0.4% reduction) and two times greater than a reduction to 20 microg/m3. The pe rcentage reduction could grow by more than seven times if PM(2.5) levels were reduced to 10 microg/m3 (3.0% vs 0.4%). This study shows that more stringent standards need to be adopted in Europe to protect public health, as proposed by the scientific community and the World Health Organization.

Lee, S. J., S. Hajat, et al. (2008). "A time-s eries analysis of any short-term effects of meteorological and air pollution factors on pr eterm births in Londo n, UK." Environ Res 106(2): 185-94.) In this case 482,568 births were anal yzed in a London based study. The births

occurred between 1988 and 2000 and data was ob tained from the St. Mary's Maternity Information System database. Short-term asso ciations between preterm birth and various

environmental factors were assess with time- series regression techniques. Environmental exposures included air pollution (ambient ozone and PM10) and climatic factors (temperature, rainfall, sunshine, relative humidity, barometric pressure, and largest drop in barometric pressure). In addition to exposur e on the day of birth, cumulative exposure up to 1 week before birth was investigated. The risk of preterm birth did not increase with exposure to the levels of ambient air pollution or meteor ological factors experienced by this population. Cumulative exposure from 0 to 6 days before birth also did not show any significant effect on the risk of preterm birth. This large study, covering 13 years, suggests that there is no association between preterm births and recent exposure to ambient ai r pollution or recent ch anges in the weather.

Rankin, J., T. Chadwick, et al. (2009). "Mater nal exposure to ambient air pollutants and risk of congenital anomalies." Environ Res 109(2): 181-7. Studies have suggested an association between maternal exposure to ambient air pollution and risk of congenital anomaly. The aim of this study is to inve stigate the association between exposure to black smoke (BS; particulate matte r with aerodynamic diameter <4 microg/m(3)) and sulphur dioxide (SO(2)) duri ng the first trimester of preg nancy and risk of congenital anomalies. We used a case-control study design among deliveries to mothers resident in the UK Northern health region during 1985-1990. Case data were ascertained from the population-based Northern Congenital Abnormality Survey and contro l data from national data on all births. Data

33on BS and SO(2) from ambient air monitoring stati ons were used to average the total pollutant exposure during the first trimester of pregnancy ove r the daily readings from all monitors within 10 km of the mother's residence. Logistic regr ession models estimated the association via odds ratios. A significant but weak positive association wa s found between nervous system anomalies and BS (OR=1.10 per increase of 1000 microg/m(3) total BS; 95% CI: 1.03, 1.18), but not with other anomaly subtypes. For SO(2), a significan t negative association was found with congenital heart disease combined and patent ductus arterios us: OR significantly <1 for all quartiles relative to the first quartile. The relationship between SO(2) levels and other anomaly subtypes was less clear cut: there were either no significant associ ations or a suggestion of a U-shaped relationship (OR significantly <1 for moderate compared to lowest levels, but not w ith high SO(2) levels). Overall, maternal exposure to BS and SO(2) in the Northern region had limited impact on congenital anomaly risk. Studies with detailed exposure assessment are needed to further investigate this relationship.

Son, J. Y., Y. S. Cho, et al. (2008). "Effect s of air pollution on post-neonatal infant mortality among firstborn infants in Seou l, Korea: case-crossover and time-series analyses." Arch Environ Occup Health 63(3): 108-13.) The relationship between air pollution and post-neonatal mortality from all causes am ong firstborn infants in Seoul, Korea, during

1999-2003 was studied. Both case-crossover and tim e-series analyses with a bidirectional control-sampling approach were used to compar e the effects of air po llutants on post-neonatal mortality. The relative risk of post-neonatal mortality from all causes was 1.000 (95% confidence interval [CI] = 0.998-1.002) fo r PM10, 1.002 (95% CI = 0.994-1.009) for NO2, 1.015 (95% CI = 0.973-1.058) for SO 2, 1.029 (95% CI = 0.833-1.271) for CO, and 0.984 (95% CI = 0.977-0.992) for O3 for each 1-unit increase of air pollution level in the 1:6 control selection scheme. The authors observed a positive associat ion between air pollution and infant daily mortality except for the studied particulate ma tter and ozone, although it was not statistically significant. They obtained similar results in the time-series analysis. Th e risk of post-neonatal infant death from all causes was positively asso ciated with all studied air pollutants except ozone. Therefore, while a posit ive association was observed between PM10 and post-neonatal mortality the findings were not statistically significant.

34Comments from Dr. Ellis Cowling

My specific assignment for review of the ISA for PM was Chapter 9 – Ecosystem and

Welfare Effects.

The set of 10 Charge Questions provided in John Vandenberg’s lette r of January 30, 2009 to Holly Stallworth included the following que stions with regard to Chapter 9:

How useful and complete is the scientific evidence presented in Chapter 9 regarding the effects of Atmospheric PM on the environmen t, including (a) effect s on visibility, (b) effects on individual organisms, (c) direct a nd indirect effects on ecosystems, (d) effects on materials, and (e) effects on climate? To what extent do the discussions and integration of evidence correctly represen t and clearly communicat e the state of the

science?

General Comments on the Presentation of Scie ntific Evidence Regarding Effects of PM on Visibility, Individual Organisms, Ecosyste ms, Materials, and Climate in the ISA

It is excellent that each of the “ Summary and Conclusion ” statements on pages 9-1, 9-5, 9-6, and 9-7 begins with a simple declarative sentence written in bold type indicating that “The

evidence is sufficient to infer a causal relationship between ambient PM and” [all five significant welfare effects of ambi ent PM covered in Chapter 9] visibility, individual organisms, ecosystems, materials, and climate . These statements set the stage for a throughgoing discussion about the body of scie ntific evidence that supports th ese very firm statements of causality. That is very good!

Also useful (but frequently lacking in precisi on of communication because of poor definitions of terms and the absence of a list of acronyms for the whole ISA) are the series of detailed presentations of scientific evidence regarding the effects of PM on all five of these same significant welfare effects including:

• visibility on pages 9-7 through 9-86; mechanisms of atmospheric deposition on pages 9-86 through 9-106 especially with regard to effects of airborne PM on

o individual organisms on pages 9-106 through 9-119

,

o ecosystems on pages 9-119 through 9-127

,

• materials on pages 9-127 through 9-132 ; and finally effects of PM on various aspects of

• climate on pages 9-132 through 9-156. Fortunately, some of these detaile d presentations fall more closely within the areas of special competence of some of my fellow PM CASAC Panel Members who also were assigned to review Chapter 9. For example, Bill Malm, regarding PM effects on visibility , and also David Grantz, Rich Poirot, and Lowell Ashbaugh regarding PM effects on materials and climate

. Thus, I am looking forward to liste ning very attentively to their Individual Comments on some of these special topics in contra st to the discussion about both mechanisms of atmospheric deposition and effects of PM constituents on individual organisms and ecosystems that are more close to my own areas of special competence.

35Detailed Comments on Some Limitations in the Clarity and Completeness of Chapter 9

.

First with regard to Clarity: Most of my difficulty in asse ssing the quality of the information provided in Chapter 9 is a result of a significant lack of precisi on in the terminology and lack of definitions of the acronyms used in this chapter.

On pages 9-1 through 9-7 for example, it is not clear what is meant by the acronym EC or the terms “crustal material,” “urban excess,” “urb an excess carbonaceous PM,” Midwest nitrate bulge,” “four light extinction components,” “hydrated sulfate pa rticles,” etc.

Clear definitions of terms and especially the acro nyms used in any ISA document are essential to understanding the science that is being assessed. Many more defini tions of terms and a complete list of all acronyms used in al l parts should be included in the Second External Review Draft of

this document.

Much confusion in many different parts of Chapter 9 (and in the other chapte rs of this ISA) are caused by sloppiness in the use (and many different meanings) of the word “level”). The word

“level” is sometimes used to mean “air concen tration,” other times to mean “amount,” other times to mean “consistency,” other times to mean “altitude” (distance above sea level),” other times to mean “unchanged,” other times to mean “d egrees” or “extent” or “types” of visibility impairment, species of organisms, or concepts of physiology or ecology, a nd still other times to mean “tolerance” or “acceptability” (for example in attitudes of citizens about haziness in the atmosphere). My advice is to use any or all of these other terms when they avoid the ambiguity that so often accompanies use of the word “level.”

An illustration of a biological c oncept that also is presented ve ry inadequately is found in the following paragraph near the bot tom of page 9-5 within the Summary of Effects on Individual Organisms and Ecosystems in the Summary and Conclusions section of Chapter 9:

“Many of the most important e ffects [of PM] occur in the soil. The soil environment is one of the most dynamic sites of biological diversity in nature. It is inhabited by microbial communities of bacteria, fungi, and actinomycetes. These organisms are essential participants in the nutrient cycles th at make nutrients available for plant uptake. Changes in the soil environment that influence the role of bacteria and fungi in nutrient cycling determine plant and ultimately ecosystem response.”

These five sentences (and especially the last sentence in this paragraph) give readers the unintended impression that scientific studies of “microbial communities” in soil have been shown to be affected by airborne PM [and, by implication, that th e many and diverse “nonmicrobial” organisms in soil -- such as rodents, insects, earth worms, nematodes, viruses, and roots of higher plants themselves – all have been studied but have NOT been shown to be affected by airborne PM].

Surprisingly, these very same ideas are presente d very much more adequately in the detailed discussions on pages 9-1 06 through 9-119 regarding Effects on Individual Organisms and on pages 9-119 through 9-127 regarding Effects on Ecosystems

.

36Second with regard to Completeness: During the recent efforts to streamline the NAAQS review processes, the following general policy question was recommended as a guide during the NAAQS review processes:

What scientific evidence and/or scientific insights have been developed since the last review to indicate if the cu rrent public-health based and/or the current public-welfare based NAAQS need to be revised or if alternat ive levels, indicators, statistical forms, or averaging times of these standards are need ed to protect public health with an adequate margin of safety and to protect public welfare?”

Since the Clean Air Act defines “public welfar e” to include the effect s of air pollution on “visibility, ... and personal comfort and wellbei ng.” and the present draft ISA for particulate

matter concludes that “ The evidence is sufficient to in fer a causal relationship between ambient PM and visibility impairment,” the most directly releva nt policy questions to be resolved by the current NAAQS-re view process for PM are:

1) “ Does the current public-welfare based NAAQS need to be revised?” and, if so 2) “What alternative levels, indicators, statis tical forms, or aver aging times of the secondary standard for PM should be consider ed in order to protect public welfare?”

The only parts of the present First External Review Draft of the ISA for PM that deal directly with the current secondary standard for PM are: 1) The very confusing paragraph on lines 8 through 16 on page 1-9 of Chapter 1, and 2) The section of Chapter 9 titled “ Urban Visibility Valuation and Preference ” on pages 9-74 through 9-83 where a preliminary attempt is made to: “separate out the aesthetic and wellbei ng components associated with the visibility condition produced by a given le vel of air pollution when assessing the need for additional regulation to protect [against] the public welfare effect[s] of visibility under the Seconda ry NAAQS.” This was attempted in the present ISA by analyzing results from the Urban Visi bility Preference Studies completed in recent years in Denver, Colorado, Phoeni x, Arizona, British Columbia, Canada, and Washington, DC (see pages 9-76 through 9-81 in the ISA).

Thus, I recommend that the Second External Review Draft of the ISA for PM and the First Draft Risk and Exposure Assessment for PM include s ections that deal exp licitly with the two questions printed in italic type in the above paragraph.

----------------------

My specific assignment for review of the February 2009 document titled: “ Particulate Matter National Ambient Air Quality Standards: Sc ope and Methods Plan for Urban Visibility Impact Assessment” was Chapter 3 – Quantitative Visual Air Quality Assessment.

Having carefully reviewed all th ree chapters in this documen t, I was generally satisfied with the approach outlined in this Scope and Methods Plan but recommend that earnest consideration also

37be given to including sections in the Second External Review Dr aft of the ISA for PM to be completed in July 2009 and the First Review Draf t of the Urban Visibility Impact Assessment (UVA) to be completed in September 2009 that d eal explicitly with th e following two specific policy questions:

1) “ Does the current public-welfare based NAAQS need to be revised?” and, if so

2) “What alternative levels, indicators, statis tical forms, and averaging times of the secondary standard for PM should be consider ed in order to protect public welfare?”

38Comments from Dr. James Crapo

The EPA Staff are to be congratulated on producing a comprehensive and well designed

overview of issues related to ambient particulate matter including the substantial amount of research on PM published since the last CASAC review of this topi c. In general, the integrative tables and figures are clear and presented in a form that allows consideration of the scope of the data with respect to potential adverse health effects for PM.

Chapter 2 – Integrative Health Effects This chapter provides an integrative summary a nd assesses the likelihood of causal relationships for specific health effects with respect to PM exposure. I like the genera l approach the EPA has used, including their five-level hierarchy for causa l determination. This is a rigorous approach to the central issue that has been requested on multiple previous ISA documents. The EPA staff has critically reviewed the relevant literature on this topic and has made concrete recommendations regarding their conclusions with regard to causalit y. I applaud the approach of starting with a list of the key health effects and a firm statement with regard to conclusions of causality and following this by a brief descrip tion of the key findings suppor ting the conclusions. Hopefully,

this will become a model for future ISA documents.

In general, I agree with the causality conclusions w ith regard to the key health effects and I agree with the selection of the health effects for emphasi s in this chapter. The focus of this chapter is on short- and long-te rm exposures to PM 10 and PM 2.5 . This implies that a firm decision has been made not to consider regulatory recommendations with regard to PM 10-2.5 . I believe we will ultimately need to evaluate epidemiologic and animal studies data with regard to PM 10-2.5 in

order to understand the cont ributory effects of coarse particulates. Data on PM 10-2.5 is incorporated in other chapters on Health Effects but not brought forward to the summary and conclusions in Chapter 2. From a regulatory pe rspective today this may be appropriate; however,

I would recommend that at le ast a summary section on PM 10-2.5 be included in Chapter 2.

I also liked section 2.2.3 on constituents or so urces linked to health outcomes. There are

insufficient data to derive concrete conclusi ons; however, there are suggestions that specific

constituents or sources will eventual ly be linked with specific health effects. This is likely to be an area that will expand in future reviews of PM.

Chapter 5 – Possible Pathways/Modes of Action This chapter provides a reasonable review of the possible pathways or modes of action of particulates in contributing to adverse health eff ects. The chapter is short, focused and provides a

number of alternative frameworks to consider th e mechanisms of actions of particulates. I found this chapter useful. Part of its strength is its brevity and its liberal use of illustrations. I would recommend keeping this approach for this section of the ISA.

Chapter 7 – Integrated Health Ef fects of Long-Term PM Exposure Chapter 7 is thorough and well writte n. It provides an excellent ove rview of the long-term health effects of PM exposure. An important strength of this chapter is the creation of Figures that clearly illustrate the combined primary findings with each of the topics (i.e., cardiovascular and systemic risks, respiratory risks, reproductive an d developmental risks, ca ncer risks and overall

39mortality. This is well done in Figure 7.8. Figur e 7.1 is also a very us eful summary figure. I would recommend that summary figures be create d for each of the sections – even where the data suggests no significant effect. The writte n summaries in each section are appropriate; however, I think there should be tables or figures that summarize and compare the primary data

for each section.

Chapter 7 would be strengthened by shortening it, achieving greater focus on the new findings, and a focus on the summary tables as suggested above.

40Comments from Dr. Douglas Crawford-Brown

I was not assigned to a specific char ge question, so I chose those that I felt are most in line with my area of expertise. A general comment is that the document is longer than I might have hoped to see. The other ISAs (for other NAAQS) produced recently have set a trend of significantly reducing the amount of material that would have been covered under the older Criteria Document system. This PM ISA reverses that tr end. I realize there is a LOT of PM material available in the literature, but I still would have liked to see a little more distillation of the literature down to the key studies an d points before production of the ISA.

1. The framework for causal determination and ju dging the overall weight of evidence is presented in Chapter 1. Is this framework appr opriately applied for this PM ISA? How might the application of the framework be improved for PM effects?

There is now emerging a consistent framework be ing applied across the va rious ISAs, so it is becoming easier to see the reasoni ng behind the causal conclusions drawn in this and other ISAs. There are quibbles I might have with the particular framework c hosen, but it is as good as any

other I have seen and at least serves to draw th e analyst’s attention to the key questions to be addressed. It appropriately separates a judgmen t of causality from one of there being a C-R function. The categories of strengt h of causality are sufficient a nd clearly defined, so I found it easy to understand why the analyst chose to place a given study a nd effect into a given category. Overall, I am satisfied with this system as a sufficient tool, and recommend no further tweaking, which allows everyone to now settle on examining the particular conclusions being drawn within

the framework.

The only point that continues to concern me is th at the judgments of causa lity still tend to be categorical: PM is or is not causally connected to e ffect X. I think a better system is one in which the degree of support for such a claim changes as the level of exposure changes. It would be useful to see how the support changes as one approaches low levels being considered for regulatory targets. There is some hint of this throughout the application of the framework, but it is never made explicit, especially in Chapter 1.

2. Chapter 2 presents the integrative summary and conclusions from the health effects evidence at the beginning of the ISA with the ev idence characterized in detail in subsequent chapters. (Environmental and public welfare effect s evidence is evaluated and summarized in Chapter 9.) Is this a useful and effective su mmary presentation? How does the Panel view the inclusion in Chapter 2 of only health categories w ith causal determinations of (a) likely to be a causal relationship or (b) a causal relationship?

I found Chapter 2 very useful, and it went a long way towards alleviating the general concern I mentioned above in regards to the length of the do cument. I feel it is appropriate to summarize only the findings from the studies that fall into these two causal categories, although mention can

be made of studies/effects that did not meet these criteria (without providing summaries of these). I found the discussion of the implications of exposure a nd dosimetry for the conduct and

41interpretation of epidemiologic studies useful, whic h was a real strength of this ISA, especially since this is one pollutant for whic h a lot can be said on these points.

The discussion in the chapter concerning comp osition of particles wa s adequate but not especially insightful. The summary table was good, but I would have expected a bit more of an assessment of, and justification for, a decision to either consider or not consider composition in any final risk assessments that might be conducted based on the ISA. I must admit that I read the REA first, and so was primed for this issue in turning to the ISA (the wrong order in which to read these), but still I expected more in the ISA on this point.

The chapter correctly summarizes th e susceptibility and vulnerability issues raised in subsequent chapters, and so serve th is issue well. I was less happy with th e discussion of C-R curves, feeling

it needed more of a mathematical treatment in this chapter. I always expect a discussion of such curves – whether in summary or in the comple te chapter being summarized – to include data plotted to visually indicate where there is a cl ear positive slope and where this disappears into then noise of studies, and some indication of the shape of the curve at all levels of exposure. Chapter 2 does not go very far down this road and so is less effective as a summary than I would

have wanted.

4. The dosimetry of PM is discussed in Chap ter 4. The primary focus is on factors that might lead to differences in deposition and clearance between individuals, species, and as a function of the physicochemical pr operties of particles. Is th e review of basic dosimetric principles presented in sufficient detail? Are th e new particle translocat ion data adequately and accurately described? Recognizing an overall goal of producing a clear an d concise chapter, are there topics that should added or receive additional discussion? Similarly, are there topics that

should be shortened or removed? To what extent does the Panel fi nd Annex B appropriate, adequate and effective in supporting the ISA?

I was comfortable with Chapter 4. It provided an overview of mechanisms of deposition and clearance at just enough detail to give the reader an understandi ng of the issues. It was perhaps

left to the reader to see th e implications for study interp retation, or for the drawing of

conclusions on causal connections in particular studies, but the informa tion is there to help in this regard. I found the level of techni cal detail also appropriate for a topic that can quickly become too mathematical for many readers.

The one area in which I would suggest a bit of improvement is in the inhomogeneity of deposition and clearance, especially in regards to carinal ridges. This is mentioned by never really explored.

I kept returning to Annex B for detail, and so I suppose this indicates the Annex served its purpose. I found it contain a lot of useful informa tion, even if it was a bit difficult to sort through it to find exactly the point being raised in the chapter itself.

428. What are the views of the Panel on the defini tions of susceptibility and vulnerability in Chapter 8? Are the characteristics included with in the broad susceptibility and vulnerability categories appropriate and consiste nt with the definitions used?

I am comfortable with these defi nitions. This is a topic that al ways gets a lively debate, and people tend to have some pretty entrenched positions on the issue (with good arguments to support their positions). But in the end, what ma tters is that the terms are well defined both verbally and operationally, and then applied consis tently. I feel the authors have satisfied these

criteria in the ISA and so the characteristics c onsidered serve the intended purpose as well as any other set of definitions might.

10. This first external review draft PM ISA is of substantial length a nd reflects the copious amount of research recently conducted on PM. EP A has attempted to succinctly present and integrate the policy-relevant scientific evidence for the review of the PM NAAQS. Does the Panel have opinions on how the document can be shortened without eliminating important and necessary content?

This is back to my original comment. The documen t was too long for me to read in its entirety. I instead read about 500 pages of it in enough deta il to determine whether the information was

sufficient. This leaves me with the uncomforta ble position of worrying about whether the other 500 or so pages might contain information or anal yses that would influence the interpretations and judgments I had formed in the sections I did read in detail.

Chapter 3 strikes me as a chapter that could usefu lly be pruned by half. It reads a bit like a data dump, with every bit of information to hand put into the document just in case someone might

find it of interest. In most of the cases of page after page of data, I had little sense that these data were telling a story that would be needed later in conducting an exposure assessment or interpreting epidemiologic studies. This doesn’t mean the data will not prove useful at some point – only that the authors didn’t focus my a ttention onto specific reas ons WHY the data might be important.

By way of contrast, there is about the same amount of data available in the literature on particle deposition and clearance, but Ch apter 4 is a third the size of Chapter 3. Chapter 4 also does a better job of focusing the reader’s attention onto the significance of the data being presented.

I saw little in Chapter 5 that could be deleted without loss of significant content, and so would not expect cuts to be made here.

Chapter 6 is the longest by far. I found myself focusing almost entirely on summary tables and figures, rather than the exhaustiv e page-after-page listings of char acteristics of specific studies. The chapter could easily be shortened by half with out loss of any content that the reader will care about. As it is written currently, it suffers from all of the pr oblems of the older criteria documents. This shortening would be accomplished by provision of even better summary tables and figures, perhaps with a Comments column to explain any special features of a study the author wants to highlight.

43In fact, Chapter 6 is even longer than the 200+ pages contained within it, because much of Chapter 7 is a similar presentation of study resu lts. The purpose of Chapter 7 is to provide an integrative approach, but I could find little of th at in the chapter. It became instead yet another place to serve as a repository of exhaustive study descriptions. There should be little need to describe studies by this chapter, and certainly no need to present even more data. The chapter

should instead focus on how the materials of earlier chapters, incl uding the dosimetry considerations, can be integrated into a consistent picture of whic h effects are causal, and at what levels of exposure, and under what conditions. There are places where Chapter 7 starts to approach this goal, but then the reader is plunged back again into listings of studies. This chapter is the one most in need of not shortening per se, bu t a better focus on the purpose of the chapter.

44Comments from Dr. David Grantz

The document as a whole makes a real contri bution and is well done, quite readable, and relatively complete. The following represent comments or suggesti ons for revision of the ISA, not in priority order.

1. It would be helpful to provide a list of acronyms. Further, it would be useful to describe briefly air monitoring programs such as AQS (page 2-2, line 11) to present the characteristics that make them particularly suitable for the specific analysis under

discussion.

2. The approach of Chapter 9, which deals with all welfare effects considered together, differs considerably from that of Chapte r 2 (and subsequent supporting chapters 3-8),

which deals with discrete health endpoints. There seems to have been little effort to apply the criteria of causality laid out earlier (e.g. Table 1-2), even for visibility which is the strongest welfare component in terms of ava ilable data. Indeed visibility is a nearly discrete endpoint which could be separated in to its own chapter. There is a sense that other components of welfare effects have been determined prior to preparation of this ISA to be non-“policy relevant”, and therefor e have received littl e critical attention.

Inconsistencies between the treat ment of health and welfare effects are numerous. It is interesting that (page 9-113, line 23-26) the most interesting plants are said to be the tolerant members of the population, whereas in th e health sections (and in the legislation)

it is the most sensitive and most vulnerable members of the population that are to receive greatest attention. A committed search for th e most sensitive receptors for specific endpoints (such as the sentinel species considered on page 9-116) might help to better

focus the discussion of welfare effects and aid the search for quantifiable C-R relationships that might guide development of a separately determined secondary

standard for PM.

A detailed chart of causality begins each subs ection in Section 2.3, and would be useful if added for each subsection of Chapter 9. Th e three non-visibility fi ndings of “inferred causality”--between PM and effects on orga nisms and ecosystems, on materials, and on climate are much too general, analogous to a finding of causality between PM and human health, rather than the various endpoints laid out in Chapters 2-8. Further, it is unclear whether the phrase (Section 9.2.2) of “suffici ent to infer a causal relationship” has exactly the same meaning as the phrase “suffi cient evidence to conclude that a causal relationship exists” that appears in Chapter 2. This should be clarified.

A consequence of this general approach to we lfare effects is that data that would have

been considered to contribute to a finding of “likely causal” or “contributing to biological plausibility” in the health context, receive little more than an uncritical listing in the welfare context. For example (page 9-108, line 1-12), the analysis of PM by Sheesley et al. (2004) might be used to infer likely causal ity or biological plausi bility, but is instead summarized as “does not provide the data needed to assess risk”. Similarly, data such as

45that presented by Oliveira and Pampulha ( 2006; page 9-118, line 28- 30) and other studies might be amenable to semi-quantitative analysis, yielding estimates of soil concentrations, inferred rates of depos ition, and potentially even atmospheric concentrations of PM. The challenges laid out for ecosystem data (page 9-120, line 26 through page 9-121, line 2) are not so different from the early stages of health effects investigations. These and other possible oppor tunities could be pursued throughout the welfare section, as a means to begin devel opment of the C-R relationships required to support a secondary PM standard. A more critic al reading of the available literature for quantitative relationships may l ead closer to C-R relationshi ps than seems possible from the current presentation. The discussion in S ection 9.2.2, for example, states generalities

but never discusses the directi on or magnitude of PM-induced changes. The text does not effectively support the finding of causality that begins the section.

3. The material in Chapter 9 could be reorgani zed to emphasize discrete endpoints, and possible causal relationships re lated to each. Visibility coul d be placed in its own, better focused chapter. Material presented in th e current chapter 9 on characterization of particles could be relocated to precede the health sections, and the material on deposition to extensive landscapes could be placed ear lier where it might inform discussion of resuspension and personal PM clouds in th e health context. This would isolate the material on effects on organisms and effects on ecosystems or communities, which could be considered together or separately, but in the context of discrete endpoints. This would

focus the discussion and remove the need fo r abrupt transitions, such as that into discussion of deposition in Section 9.4 (page 9-83).

The material on toxic metals should be assembled as needed for causality determinations within each endpoint. In the current draft, discussion of the nature and role of heavy metals is diffused throughout the chapter, bu t never brought to a focus or conclusion. As above, this would avoid the abrupt introduction of metals in Table 9- 3 (page 9-89) and in the text at top of page 9-90, where it appears out of place.

The discussion of organic pollutants is somewh at weak. These materials represent direct threats to organisms and ecosystems, and s ubstantial indirect th reats to food chains including human food supply. As such they may become central to the determination of a secondary PM standard. This discussion (pag e 9-114, line 27 to 9-116, line 10) is really a discussion of semivolatile compounds. These have unique transport properties, characterized by repeated distillation on su rfaces as a function of diel trends in temperature. This is not well captured by the text. The discussion of fugacity, which is defined at a constant temperature (page 9- 116, line 5-7), does not capture the well known leap-frog behavior of SVOCs across the surf ace of the earth. The discussion of POPs (page 9-103, line 30-31), is confusing with rega rds to the air plant re sponse route (really a contact route), and uptake by above ground plant ti ssue, (also a contact route) in contrast

to the distinction between th e two (top of page 9-104).

The discussion of bioaccumulation of organics (page 9-124 to 9-125) can be made quite a bit more quantitative, even if causality cannot be demonstrated at this stage.

464. There is some uncertainty about mercury resi dence times, and about the oxidation state of Hg (page 9-101-102, lines 31-6) under discussion at each point. It would be useful to state explicitly what combining forms Hg (II) is found in, and (e.g. page 9-103, top) whether gas or particle, and what oxidati on state, is under disc ussion at each point.

5. The use of visibility as a surrogate for welfare effects may have unintended consequences. This is considered more fully in comments regarding th e visibility plan. In order to keep regulatory environments si milar for day and night hours, a movement toward modeled or virtual visibility is to be encouraged. This avoids the application of dark viewing techniques (e.g. page 9-12, line 11), and allows explicit use of developed relationships between visibility and parameters such as RH, to be applied at all hours. In the limit, this could avoid use of dark pe riods to dump particul ates that exceed the secondary standard.

Visibility as a standard me tric is confounded by regionall y differing policy relevant backgrounds, and regionally differing popular pe rceptions of acceptable visibility. In the

ISA this is shown for residents of Chilliw ack and Abbotsford (Page 9-80). Buy-in of regulated communities may be compromised by regionally differing standards for PM mass, to achieve differing standards of visibility.

6. The treatment of urban visibility valuati on (Section 9.3.5 is written rather loosely, and never reaches a focus or conclusion. The acronym, VAQ, is used in several incompatible senses. The definition (page 9-74, line 24) improbably equates impairment with quality. VAQ is considered something to be s een (page 9-75, line 12), and then more appropriately as a quality that can be bette r or worse. The modifier, “low”, could be inserted prior to “VAQ” (line 25-26), since it is not likely that high VAQ would diminish a sense of well being.

7. The discussion of dry deposition (particularly page 9-86, lines 20-26 and page 9-90, lines 17-28) is somewhat vague and incomplete. Th e roles of sedimentation and resuspension are not considered adequately. The discussion is not entirely consistent with Figure 9-52. The consideration of eddy covariance techniques (page 9-88, line 34) might reconsider whether coarse particles are transporte d efficiently in high frequency eddies.

8. Page 9-47, line 8, in wintertime it may be that oxidizing potential to convert NOx to nitric acid is limiting. While this appears to be the implication of this sentence, this is an important point that requires further ela boration with respect to mechanisms and consequences for air quality.

9. The discussion regarding exchange of PM- borne materials across vegetated surfaces (page 9-95, line 1-3) is quite important and generally well done here. The concept of measured dry deposition exceeding bulk deposition requires further elaboration, particularly as to measurement technique fo r the two parameters. In the discussion of exchange of mercury (page 9-97, line 26-27) the two forms of deposition that are mentioned are both dry depositi on, in contrast to the text.

4710. The discussion of individual species near th e Harjavalta smelter (p age 9-126, line 21-24) is of interest, but should be placed in the context of th e section heading—Ecosystem

Function. The isolated consideration of a few in sect and spider specie s, without reference to their roles in the ecosystem, is analogous to a statement that influenza is good for buzzards. Misses the point a bit.

11. The discussion of direct impacts of coarse particles (page 9-108 to 9-109) is incomplete. Many consequences are mediated by disruption of leaf cuticle and waxes, from pathogen defense to control of water loss. Surface pH is important, particularly for colonization, but also for wax degradation. These need to be elaborated upon. It is not clear, and at least requires better referenc ing, that salt is generally take n up through abrasions in the shoot rather than through the ro ots, and that this leads to plants leaning away from the

ocean.

12. Minor comments: Page 9-2,line 5, there appears a discontinuity between discussion of pristine skies and polluted ones. Page 9-5, line 13, it is not correctly parallel to refer to PM deposition as a pollutant (PM is the pollutant). Page 9-6, line 2, N should be Ni. Page 9-7, line 11, BC is introduced here for possi bly the first time. Is this the same as EC, introduced earlier? Either way ther e needs to be a definition given. Figure 9-3 (page 9-14), it is uncle ar what 1.5 stands for in the internal labels for each line. Figure 9-31 (page 9-49) it is uncl ear what the three sizes of pi e charts in the legends, and the numbers 20, 60, and 100 represent. Page 9-22, line 10-14, better to provide a mathem atical equation. The form and intent of this verbally described transformation is unclear. Page 9-48, line 8, should be “east” end of gorge. Figures 9-38 to 9-43 (Pages 9-58 to 9-64) ar e quite difficult to interpret. The legend and caption can both be made more user friendly. Page 9-105, line 14, it is unclear whether pe trogenic refers to petroleum or geology. Page 9-113, line 12-22, a better di stinction should be made between tire dust and road

dust. Page 9-127, line 27-28, use of a bioluminescence a ssay is a type of bioa ssay that directly measures the toxicity of th e mixture of metals under c onsideration. This should be presented in the context of such direct effect measurements. Page 9-136, line 24, the ratio of diffuse to total solar radiati on is lowest at noon. Page 9-139, line 4-5, it is not clear what factor of 2 refers to. Page 9-140, line 26-28, the reduction in radiat ive forcing over the 80 year recover period requires further explanation here.

48Comments from Dr. Joseph Helble

1. Particle morphology may affect particle transpor t properties, depending u pon particle size. It will also affect particle surface area regardless of size. Because surface area and particle transport properties may both affect exposur e, discussion of current understanding of morphology or surface area distributions would be beneficial. This is acknowledged in the ISA in section 3.2 (line 23, page 3-3) where shape along with size and composition is listed as a variable characteristic of atmospheric PM.

2. This point is reinforced in Section 3.4.13. pa ge 3-24, where it is noted that “methods are being developed to measure the surface area of ultrafine particle s (line 23).” No additional discussion of surface area is provided. It arises again on p. 3-37 line 9, where “particle shape” is listed as one possi ble cause of differences noted among samples at supersites.

3. A listing of acronyms and abbreviations is needed at the start of the ISA. Some are not defined at all, others are not defined until they have been used many times in earlier sections. A listing is included in the Scope and Methods documents and is also warranted in the ISA.

4. Fly ash from combustion of coal, oil, and w ood can also produce particles in the PM1.0 size range and is therefore also a poten tial source of Fine particles (Tab le 3-1, page 3-6). It is in part a source of the metals that are listed in the table.

5. Similarly, primary PM (“minerals”) can be emitted as fly ash from fossil fuel and wood combustion, a source category listed in Table 3-1 but not in Tabl e 3-2. The tables are largely consistent, but review for full agreement would be helpful.

6. A brief narrative description of the sources co ntributing to the “miscellaneous” categories of PM 10 and PM 2.5 sources (Figur e 3-2) should be included.

7. Section 3.3.2.2 page 3-12 line 18 the senten ce beginning Robinson et al. (2007a) needs clarification. Presumably the statement indi cates that direct measurements of combustion source emissions do not accurately capture all of the semi-volatile organic content, leading to

an underestimation of the contribution of co mbustion sources to semi-volatile organics

observed in PM.

8. P. 3-37 line 20 discussed an arti fact when QBT filtering was us ed. Earlier in this section, page 3-21, only QBQ and TBQ are mentioned as commonly used methods. If QBT is not a typo, it should also be discussed on p. 3-21 wh en the other filter me thods are described.

9. Comments on the higher maxima noted in Ta ble 3-11 PM 10 distributions from AQ data would be helpful.

10. Page 3-104 notes that “compositi onal profiles used in receptor models can be extensive.” And variable? Worth addressing explicitly if the lite rature suggests differences would affect

conclusions drawn from CMB models.

4911. Page 3-146 line 2 the sentence begi nning “Particle chemis try” is confusing. It implies that chemical composition affects particle deposition behavior. While there is certainly a link between composition and size it is not a determinative relationshi p, and clearly it is size (and structure) that primarily affect deposition patterns.

12. The discussion relating exposure assessment and socioeconomic status makes points regarding neighborhood scale monito r distribution that do not app ear to be consistent with the data in the subsequent tables. Sp ecifically, lines 20-23 pa ge 3-161 argue that “neighborhood scale SES issues are not shown to be well represented.” The inference drawn

from the text as written is that monitors are not sufficiently well distributed, at the neighborhood level, in neighborhoods of lower SES status. A comparison of data in Tables 3-30 through 3-32 indicates, however, that a higher percentage of the less-educated population lives within 1 km of a monitor than is true for other educational attainment levels. It may be reasonable to argue that a higher concentration of monitors is needed in these neighborhoods, but the data as presented do not a ppear to suggest disparity in their siting.

13. Typographical Errors

a. Page 3-8 line 9 the word “exhaust” should be inserted after “vehicle”

b. Page 3-27 line 23 “from” should be inserted between “Except” and “some”

c. Page 3-66 the figures present correlation as fractional values, the text describes them in percentage terms. The discussion shoul d be made consistent with the figures.

d. Page 3-72 Figure 3-30 caption indicate s “Pittsburgh,” but the legend indicates “Philadelphia. This needs to be corrected.

e. Page 3-85 line 10 insert “are” be tween “than” and “ultrafine”

f. Page 3-103 line 24 insert appropriate table numbers

g. Page 3-114 line 12 delete “described”

h. Page 3-115 line 112 sentence beginning “In this section” unclear – comma needed after “average” - ?

i. Page 3-115 line 28 “have” should be changed to “has” j. Page 3-116 line 5 a colon needed after “components”

k. Figures 3-61 through 3-63 need to be made larger and sharper

l. Page 3-141 line 14 space needed between “be” and “evaluated”

m. Page 3-143 line 28 “suggests” should be “suggest”

n. Page 3-145 line 2 “utilities” should be “utility”

o. Page 3-148 Line 9 the “88” in conc entrations needs to be deleted

p. Page 3-149 line 1 Figure 3-71 shoul d be changed to Figure 3-74

q. Page 3-150 line 10 insert “and” before “indoor”

r. Page 3-152 line 2 insert ) after the first Zn

50Comments from Dr. Rogene Henderson

Chapter 1--Framework I thought the explanation of the EPA framework for causal determination was well done. It will provide the basis for future NAAQS documents for a ll criteria pollutants. In the future this standard approach might be placed in an appendix, but it is appropriate to include it in the PM

ISA text for discussion.

Chapter 2--Integrative H ealth Effects Overview I found this to be a useful chapter. I thought th e chapter needed a few more words about the

health effects of short and long term exposures to ultrafine PM and PM 10-2.5 particles, not just the

one sentence at the bottom of page 2-11 saying we have inade quate evidence to infer causal relationships. The chapter might also be expa nded to include the summary sections from Chapters 6 and 7 (see suggestion below) and serve as the health effects section of the ISA, with large parts of chapters 6 and 7 as appendices. That is not to say that Chapters 6 and 7 are not important. Those chapters contain the detailed information upon which Chapter 2 is based. But if one valued a shorter ISA, one could use an expanded Chapter 2 with a ppendices for the health effects. For my own benefit, I made a table that included each of the four particle sizes for rows and each of the major endpoints as columns, with the resultant cells showing the finding in terms of causality. I did this for both the short te rm and the long-term exposures. Such a simple summary table would be appropriate in Chapter 2.

Chapters 6 and 7: These are highly valuable summaries of the health effects of short and long term exposures to

PM conducted since the last revi ew. I found the sections labele d "Overall Summary and Causal

Determination" found at the end of each health e ffects section especially useful. I wonder if you might combine these sections with what is in Chapter 2, edit it to remove redundancies, put the details of the new studies described in Chapte rs 6 and 7 in Appendices, and use the expanded Chapter 2 as the Health Effects chapter.

51Comments from Dr. Phil Hopke

This Chapter is generally well written. Howeve r, there are a number of small additions and corrections that would improve its overall content and presentation. Xia and Hopke (2006) observed seasonal variat ion for the two major diastereoisomers coming from isoprene oxidation with the concentrations occurring during the summer and the lowest concentrations occurring during the winter. The variation of the ca rbon contribution of 2- methyltetrols to OC was found to follow the same pattern as the concen tration variation of 2- methyltetrols. During summer, the period of high photochemical activity, the maximum carbon contribution of 2-methyltetrols to OC was 2.8%. It should be noted that the byproducts of terpen e oxidation forming SOA ar e inherently oxidative in nature. Docherty et al. (2005) found that 47 % to 85% of SOA mass is composed of peroxide compounds. Organic peroxides represent an important class of reactiv e oxygen species (ROS) that have high oxidizing potenti al and could cause oxidative stress in cells on which such particles deposit. A major question is whether to persist in using a filter based method as the Federal Reference

Method where we know that the current FRM for PM 2.5 has good precision, totally undefined accuracy and when operating perfectly provides data with 66% of the days unmeasured. I suggest that such a measurement protocol is no longer acceptable. Itis critical to have essentially complete data capture, higher time reso lved data, and measurements that better reflect the actual concentration of particulate matter that exists in the atmosphere without the unknown

and unknowable losses of semivolatile materials th at come from a 24 “equilibration” period. The document is currently silent on these fundamental flaws of the FRM approach while putting in detail on studies of how people try and repli cate the inaccurate meas urements known to be provided by the FRM. It is time for a change in paradigm and move to continuous monitors that can remove some of the particle-bound water without as drastically disturbing the other semivolatile components. There should be some description of the Wagner and Leith passive monitors for PM 10 and PM 10-

2.5 . Since the short-term standard for PM 10 has been eliminated, it w ould be possible to provide long term monitoring for PM 10 or PM 10-2.5 for many more locations using passive samplers and thus, they are worth discussing. I find Figures 3-4 and 3-5 very hard to follow. They are described in a single sentence on page 3-29 and the point being made is left quite vague. Either clarify why the figures are there or

remove them. There is no discussion of trends in compositi on. We have data now from 2000 to 2008 at a

number of locations across the US. Is the composition changing relati ve to the overall mass

concentration?

There is no mention of the ultrafine measur ements in Rochester (Jeong et al., 2004, 2006) looking at the seasonal variability in the diurnal patterns of ultraf ines and distinguishing between vehicular, plume, and re gional nucleation events. Although not widely used, Unmix should also be mentioned on Page 3-105. It is mentioned on 3-107, but the methods should be introduced togeth er. Also it should be noted that PMF and Unmix have been applied to partic le size distributions to obtain source identification of ultrafine particles.

52An issue that is not presented is whether interconti nental dust events are rea lly contributors to the PRB or just constitute unusual events. For ex ample, there was a larg e Saharan dust storm in early July 2002 that contributed 25 μ g/m 3 on July 1 and 24 μ g/m 3 on July 2, 2002 (Lee et al., JGR 2006). It is logical to assign these well defined specifi c events to the PRB? There have been useful new approa ches to using satellite data to estimate fine particle exposure that are worth noting. Estimating fine particulate matter component concentrations and size distributions using

satellite-retrieved fractiona l aerosol optical depth: Part 1 - Method development Liu Y, Koutrakis P, Kahn R: JOUR NAL OF THE AIR & WASTE MANAGEMENT

ASSOCIATION Volume: 57 Issue: 11 Pages: 1351-1359 Published: NOV 2007 Estimating fine particulate matter component concentrations and size distributions using

satellite-retrieved fractio nal aerosol optical depth: Part 2 - A case study, Liu Y, Koutrakis P, Kahn R, et al. JOURNAL OF THE AIR & WASTE MANAGEMENT ASSOCIATION Volume: 57 Issue: 11 Pages: 1360-1369 Published: NOV 2007

It should be noted that one of the effects of ambi ent ozone when it infiltra tes into indoor air is that it can produce new particle formation by reacti on with the terpenes re leased by a variety of cleaning and personal care products . Weschler has published ex tensively on this subject.

53Comments on Chapter 4 There has been some useful recent work on the pene tration of fibrous partic les (high aspect ratio) through head and TB airways.

Record 1 of 6
Wang, Z; Hopke, PK; Ahmadi, G; Cheng, YS; Ba ron, PA. 2008. Fibrous particle deposition in human nasal passage: The influence of particle le ngth, flow rate, and geometry of nasal airway.

JOURNAL OF AEROSOL SCIENCE 39 (12): 1040-1054..

Author Full Name(s): Wang, Zuocheng; Hopke, Philip K. ; Ahmadi, Goodarz; Cheng, YungSung; Baron, Paul A.

DOI: 10.1016/j.jaerosci.2008.07.008

Record 2 of 6
Zhou, Y; Su, WC; Cheng, YS. 2008. Fiber Depo sition in the Tracheobronchial Region: Deposition Equations. INHALATION TOXICOLOGY 20 (13): 1191-1198..

Author Full Name(s): Zhou, Yue; Su, Wei-Chung; Cheng, Yung Sung

DOI: 10.1080/08958370802233082

Record 3 of 6
Zhou, Y; Su, WC; Cheng, YS. 2007. Fiber depos ition in the tracheobronchial region: Experimental measurements. INHALATION TOXICOLOGY 19 (13): 1071-1078..

Author Full Name(s): Zhou, Yue; Su, Wei-Chung; Cheng, Yung Sung

DOI: 10.1080/08958370701626634

Record 4 of 6
Su, WC; Cheng, YS. 2006. Deposition of fi ber in a human airway replica. JOURNAL OF

AEROSOL SCIENCE 37 (11): 1429-1441..

Author Full Name(s): Su, Wei-Chung; Cheng, Yung Sung

DOI: 10.1016/j.jaerosci.2006.01.015

Record 5 of 6
Su, WC; Cheng, YS. 2006. Fiber deposition pattern in two human respirat ory tract replicas.

INHALATION TOXICOLOGY 18 (10): 749-760..

Author Full Name(s): Su, Wei-Chung; Cheng, Yung Sung

DOI: 10.1080/08958370600748513

Record 6 of 6
Su, WC; Cheng, YS. 2005. Deposition of fi ber in the human nasal airway. AEROSOL SCIENCE

AND TECHNOLOGY 39 (9): 888-901..

DOI: 10.1080/02786820500295685

54Comments from Dr. Donna Kenski

General impressions (Chapters 1-3 and 9): Grea t job summarizing and or ganizing an enormous amount of data. Obviously it’s a very large docu ment, but in light of th e amount of new material available, I don’t think the length is excessive. Only Chapter 9 s eemed to overshoot the mark and need to be trimmed down some (see suggestions below). But overall, the document read well, used appropriate graphics to demonstrate and su mmarize data, and it was easy to follow the logic and organization. Chapter 1: 1-20, 23-25: This wording makes me a little unc omfortable; just what is meant by ‘an objective appraisal ... which includes weighing alternativ e views on controversial issues’? Must every comment be considered equally? Surely all comments are considered in light of the supporting

science? 1-25, Sec. 1.6: Well, it’s hardly concise, but gi ven the extensive new information available, the length is probably unavoidable. Wish there wa s an audio version we could download to our Ipods. 1-25, 13: edpolicy -> policy Chapter 2: I think this summary section really belongs at the end of the document, with perhaps a much briefer (3-4 pg) executive summary in the beginning of the report, like what was developed for the NOx/Sox 2ary ISA. This chapte r is just too long and de tailed to serve as an executive summary, although it is an admirable wrap-up of the whole report. It would just work

better at the end. Chapter 3: This chapter was really well done, and I think it had just the ri ght level of detail and focus. My comments are mostly minor. Sectio n 3.1 needs more work – it reads like it was cutand-pasted from other sections without any clear organization of its own. Once you get past the first 2 paragraphs, there’s no ‘flow’, and it meanders between PM, PM2.5, PMcoarse,, and PM10 in a somewhat confusing way. At the end of the 3 rd paragraph (p. 3-2, li nes 7-10) the text abruptly switches from discussing SOA to eval uating FRM monitors; it is not clear what the connection is between these subjects, if any. Para graph 4 (p. 3-2, lines 11-12) states that levels and spatial distributions of PM2.5 have remained relatively unchanged, but later sections go on to more accurately state that concentrations of PM2.5 have declined in most places around the country by about 10% since 1999. I think the balance of data presented in Chapte r 3 and supplementary data presented in Annex A is just about right. However, th e references to data in Annex A would be more helpful if they were more specific (i.e., refer to table A.11, not just Appendix A). And a table of contents for Appendix A would be helpful as well, just to make it easier to find the relevant information. Section 3.4.1.5 on Emerging methods was really too br ief to be useful. Beef up the description on satellite methods here or in the Annex,. On page 3.37, the short section on comparison of monitors at supe rsites seems out of place.

Artifacts etc. are better discussed in Sec. 3.4.1.2.

Section 3.5 on ambient concentratio ns is really well done and nicel y organized. Tables 3-11 and 3-12 are great, but please repeat the headings wh en a table has to be split between 2 pages as T3-11 is (p. 3-40, 3-41). The paragraph on p. 3-53 could be expanded to more comprehensively discuss what the FRM

measures vs. what the CSN monitors measure. Th ese issues impact subseque nt interpretations of

55the exposure and health data as well so they dese rve to be thoroughly vetted here. Also, please include a mention (probably obvious to all by now, but still...) th at the crustal component can have significant industri al or anthropogenic origins, despite the name. Figures 3-34 through 3-36 are particularly nice, with their corollary figur es 3-25 through 3-27. I appreciate the care that went into illustrating these basic relationshi ps between PM2.5 and PM10 with appropriate data analyses. 3-7, 14: of the microorganisms listed, 3 of the 4 are typically less than 2.5 um. Why are they presumed to be in the coarse mode? Are bacter ia and viruses necessarily associated only with larger particles? I don’t think this is the case . How much do these contribute to mass in the fine

and coarse fractions? 3-8, 9: motor vehicle exhaust 3-10, 9: replace the word nature with characterization 3-11, Fig 3-2 caption: add ‘anthrop ogenic’ to this capti on to clarify that na tural sources are not

included. 3-23, 25: the phrase ‘increas ed detection limits’ is ambiguous. ‘lowered detection limits’ would be preferable. 3-25, 17: reword: ‘electrical mobility diameter is often used to ...’ 3-28, 4: replace the word built with intended 3-28, 13: very -> every 3-32: Tables 3-3 and 3-4 are identical, despite the table titles. It l ooks like the PM10 data was mistakenly put in the PM2.5 table. 3-37, 7: What table is this referring to? 3-77, 9: change ‘visually’ to noticeably 3-41, 2: change ‘observations’ to sites. Most of the observations are 1 hr, but most of the sites

are 24-hr. 3-54, 11: the nitrate fraction in Chicago a nd Detroit is larger than in Denver. 3-55, 4: nitrate is elevated from fall thr ough spring, rather than spring through fall. 3-57, 8: the bacteria again – still unclear why they are expe cted in the coarse fraction. 3-66, 1-4: Should also mention that monitor placement plays a very large role in these

correlations – different states/ci ties have different priorities for monitoring (some focused more on particular sources or industries, some more on background or population oriented monitoring) so some of the variability will surely be due simply to monitor siting decisions. 3-72: This figure is Philadelphia, but it should be Pittsburgh. 3-77, 20: replace ‘sensible’ with expected 3-81, 7: delete ‘the’ at end of this line 3-82, 10: Population density seems what is m eant here, rather than neighborhood density 3-85, 9: Despite the declaration he re that ‘it is clear...’ , it really isn’t. Pe rhaps this is because the figure is supposed to be replaced? 3-50, 8-10: does the increase in PM number emissions necessar ily translate to equivalent

increases in mass emissions? 3-100, 3-101: Figures 3-54 and 3- 55 are difficult to read. Box plots would be less cluttered. 3-103, 24: At last a reference to specific tables in Annex A, but without the appropriate

numbers. 3-104: The discussion of profiles for recepto r models is a bit long-winded and could be shortened. The point to make is that no source pr ofile will perfectly represent emissions from a

56source category. This inherent variability in profiles is just a fact of life we need to live with, not usually a significant impediment to extrac ting useful information from a model. 3-105, 12: PMF is not only for time series data, but whatever data it is a pplied to must contain many observations. 3-106, 9-11: It’s not strictly true that all mass can’t be apportioned. CMB works fine as long as all the major sources are included. And there are ways to incorporate secondary sources as well. 3-107, 3-5: This sentence is murky; should be clarified. 3-110, 1: prime should be primary or principal 3-111, 1: categories as presente d above? Where, exactly? 3-112, 9: delete ‘transport from’

3-113: this discussion of em ission inventories (~lines 29- 34) should also mention the importance or advantages of using link-based netw orks for vehicle emissions (here or on the next page under subregional scale)

3-114: Its not clear whether this discussion of subregional scale models is referring to standalone models, or the incorporation of subregi onal models into CTMs. Might mention nested grids, Plume-in-grid, etc. 3-115, 24: mechanisms 3-116, 5: needs a colon after components 3-116, 23: MODIS got mangled – Moderate Resolution Imaging Spectroradiometer 3-119, 6: shouldn’t aroma tic be anthropogenic? 3-119, 9: particulari zed -> particulate 3-120, 4-5: reword : predicted also by CMAQ (otherwise it is ambiguous). Also, change pervasively to perversely or notoriously, and change CAST NET nodes to CASTNET sites. 3-122, 3: The figure numbers are wrong here – should be 3-64 through 3-66 and 3-67 through 3-

69. 3-122, 8: I don’t understand the conc lusion that the Voyageurs site was not affected by wild fires, since measured concentra tions increased. Please explain?

3-128: I wish these tables could be converted to graphics and a fe w summary statements provided, for example, ‘PRB averages 5-10% of annual average mass at eastern sites and 15- 30% at western sites’...It’s difficult to extract regional differences and similarities from the

tables. 3-132: Table 3-27 is confusing; it ’s not clear what E and A and C are, and whether r is the same

as R 3-134, 22: is DE diesel exhaust? Spell out? 3-134, 28: have -> has

3-135: The discussion here of erro rs associated with monitor height was nice, especially in light of prior CASAC discussions on this issue. Good to have some quantification. 3-148, 9: concentrations 3-169, line 2: Chicago and Detroit both have larger % nitrate than Denver. Might also note that

the ‘crustal’ can include contributions from industr ial and construction activi ties (eg., in Detroit), so isn’t just ‘soil’, which implies some benign, nonanthropogenic origin. 3-171, sec. 3.8.1.5: These NEI inventory esti mates don’t really agree with the source apportionment information derived from the ambi ent data. The SA mode ls and studies show little or no impact from primary emissions of EGUs , but very large contri butions from secondary emissions. These paragraphs seem to overemphasize the role of primary pm25 and underplay

57the role of secondary formation. Could be more balanced, perhaps by giving a quantification of primary vs. secondary. Sec. 3.8.1.6 gi ves a more realistic picture.

Chapter 9: While I like starting a document with an executi ve summary, I think beginning this chapter with the summary and conclusions is pushing the concep t too far. Would prefer the chapter summary

and conclustions at the end of the chapter rather than the begi nning. ( for one thing, it is then

easier to determine whether the conclusions are appropriate based on the rest of the chapter’s contents). Nighttime visibility is obviously something that deserves more attention from EPA, perhaps through additional research effort s and financial support. The chapter in general overemphasizes visibility in rural areas, and especially western rural areas. I would have expected, given the plans for an urban visibility imp act assessment, that the authors might have chosen to add emphasis to urban visibility instead, especially given the wealth of particle data now available for urba n areas that can be easily analyzed for light extinction and visibility impacts. Likewise, because visibility impacts are driven primarily by PM2.5, and PM2.5 is highest in the eastern US, one would expect the chapter to reflect a more nationally balanced perspective. Some of the data presented seemed oddly out of date, or at least could have been easily updated, on par with the more current data in Chapter 3. Rather than discussi ng 10-year trends in IMPROVE data for 1995-2004 and 1988-1999 (Sec. 9.3.4.4), why don’t we have trends for

1988-2007? The differences in trends on best and worst haze days seems to merit much more discussion – why are best condi tions apparently improving, but worst days (at most western sites) are not? The explanation on p. 9-44 is t oo brief and the reference to trends varying depending on the length of the period selected is odd. Shouldn’t trends be come more stable as time increases? If they don’t, be cause of meteorological or other factors (emissions changes), it would be nice to see an example of that, suppor ted by some evidence of those influences. Figures 9-8 through 9-11 should be redrawn with consistent colo r scales within the group of maps being compared. The point of these is to make quantitative comparisons between seasons, and the lack of consistent scale makes this vastly more difficult. One might correctly infer from Fig. 9-9 that ammonium nitrate co ncentrations are lower in the third quarter, but the importance of how much lower they really are is completely lost. Likewise, figures 9-12 and 9-13 should have a consis tent color scale. Or more appropriately if you really want to show the urban-rural difference, calculate it and plot that, rather than expecting the reader to do it on the fly from these 2 plots. Section 9.3.4.3 in general did a poor job of presenting urban rural differences. Fi gure 9-24 is the only one worth keeping.

Section 9.3.4.5 should be shortened. Here again, there is way too much detail on western sites – most of this could be shortened drastically. The most useful of it was the urban-rural contrast discussed in the Schichtel study. The results fr om the weighted emissions tool don’t really belong in the ISA, especially not the projections to 2018. They don’t add significantly more to the discussion than the coverage of emissions in Chapter 3. The information on sensitivity to changes in precursors perhaps should be discussed in a separate section, or shortened/condensed to some statements (or even better, a map or two) that show which parts or the country are ammonia limited and which are nitrate limited. Even that might be better said in Chapter 3 since it is not strictly visi bility information.

58Section 9.3.5: Don’t forget the value that peop le place on views from and over water, and views of distant skylines (even in th e flat Midwest, we value our skyline, and the views of Chicago and Milwaukee from Lake Michigan are fantas tic). It’s not just about mountains. Chap 9 in general – lots of t ypos, subject-verb agreement problems, word use issues, inconsistent capitalization, especially of geographic areas. Needs careful proofing. Dominate ->dominant, predominate ->predominant Could we please discuss nitrate in the Midwest wit hout referring to it as a ‘ bulge’? Nitrate in the Midwest isn’t inherently any different from nitrate in California – they bo th arise as a result of

abundant ammonia and NOx emissions. Specific comments, given by Page, Line Number: 9-4, 17: were -> where 9-46, 6: there is no significant amount of nitrate in the Midwest in summer. And dominate should be dominant, here and almost everywhere el se it has been used (well, after about page . 9-69, 22: where -> were 9-75, 29: effecting -> affecting 9-83, 29: gas-phase 9-84, lines 9-11: is this statement really supporte d by the data shown in Chapter 8? It seems highly geographically variable, w ith many eastern sites having more mass in the fine fraction than coarse, and overall about e qual mass in each fraction. 9-157, 4: shouldn’t this be W/m2 /kg/yr? (missing first / )

59Comments from Dr. Mort Lippmann

The draft PM ISA provides a reasonably thorough and balanced presentation of a voluminous and complex literature on ambient air PM and its health and environmental effects. The summations and judgments made therein are, for the most part, reasonable and well focused on the needs of the Agency for its mandated task of periodic reconsideration of the suite of PM NAAQS.

The most serious failing is the decisi on to organize the discussion as though PM 10 was a separate pollutant from PM 2.5 and PM 10-2.5 . It should be obvious that PM 10 is a mongrel mixture of the other two, and was only retained because of the limited database for the exposures to, and effects of, PM 10-2.5 and the need to retain some control of the PM 10-2.5 concentrations in the name of public health protection. At this point, the only reasonable way to remedy this problem in the

next draft is to describe what is known about the makeup of PM 10 in the exposure atmosphere in any description of an association of measured PM 10 with a health-related effect. In some eastern US cities, where PM 2.5 is 90% of PM 10 , there will be little reason to implicate coarse particles in any association. By contrast, in some western US cities, where coarse PM accounts for 50% or

more of PM 10 , effects associated with PM 10 are more likely to be due to coarse PM. The reader

can then decide whether the effect associated with PM 10 is likely due to the fine or course

components.

Other unfortunate decisions in the organiza tion of the toxicology presentations were to include: 1) descriptions of the effects produced by exposures to diluted engine exhausts and other lab-generated mixtures in with the discussions of the effects of ambient air PM; and 2) descriptions of the effects produced by IT e xposures to high doses with those of inhalation exposures at more realistic exposures. These more artificial exposures should be described, but in separate sections, with some discussion of what useful information they can provide.

My comments specific to each chapter of the draft ISA follow.

Chapter 1:

Overall: Very well done.

Specific Comments: p. 1-14, line 23 change “coll ected” to “retained”. p. 1-25 , line 13 what is “edpolicy”?

Chapter 2:

Overall: Needs clarificati on and specific corrections.

Specific Comments: p. 2-5, lines 13,22 what is “diel”?

60p. 2-11, line 21,22 Change to “(i.e., cardiovasc ular morbidity and mortality, respiratory morbidity and mortality)”. It is exceedingly strange to omit cardiovascular mortality, especially for chronic exposure, where it is the biggest health impact of them all! pp. 2-12 – 2-14: Section 2.3.1 . As noted above in my first Overall Comment, it is very unfortunate and confusing to talk about effects of PM 10 without at least di scussing what is known

about the size distributio n of the particular PM 10 mixture in each case. It would also be helpful to include any information on PM composition whenever it is known. P. 2-20, lines 1-9 This brief summary of long- term exposure and excess mortality should be expanded to note that almost all of the excess is cardiovascular (Pope et al. 2004). P. 2-22, Table 2-1. The Oil Combustion section should include the epidemiological studies cited in Lippmann et al. (2006) and Hedley et al. (2002).

Chapter 3:

Overall: Provides a good summary review of important background material.

Specific Comment: p. 3-8, line 9 insert “emissions” after “vehicle”.

Chapter 4:

Overall: Provides a good summary review of important background material.

Specific Comments: p. 4-5, line 15 change “particulates” to “particles”. p. 4-7, line p. 4-27, line 26 change “filter” to “filtered”. p. 4-36, line 15 fix reference citation.

Chapter 5:

Overall: Provides a good summary review of important background material.

Specific Comments: None

Chapter 6:

Overall Comment: Provides a reasonably good summary review of importan t material, but needs some cleanup for careless errors.

Specific Comments: p. 6-3, line 13 change “affect” to “effect”. p. 6-3, line 31 change “is” to “are”. p. 6-4, line 23 change “linear” to “log-linear”. p. 6-5, line 2 change “the” to “ an enriched”. p. 6-5, line 23 change “cyclone” to “centrifuge”.

61p. 6-5, line 29 insert “and modi fied by” before “Maciejczyk”. p. 6-6, line 16 insert “particles” after “exhaust”. p. 6-6, line 24 change “particulates” to “particles”. p. 6-6, line 25 insert influence of the” before “co-pollutants”. p. 6-19, line 7 change “Tuxedo, NY” to “Manhattan”. p. 6-21, line 11 This discussion of short-term changes in HR and HRV needs to be expanded to include the short-term changes reported by Chen and Hwang et al. (2005), p. 6-197, line 30 the paper by Sama et al. (Sama, P., Long, T.C., Hester, S., Tajuba, J., Parker, J., Chen, L-C., Veronesi, B. (2007). The cellular and genomic response of an immortalized microglia cell line (BV2) to concentrated ambient particulate matter. Inhal.

Toxicol. 19:1079-1087). p. 6-247, Table 6-16 the Lippmann et al. refere nce at the beginning should be “2006”, not

“2000”.

Chapter 7:

Overall: Provides a less than adequate summary review of important material. Did the authors run out of time to get it right?

Specific Comments: p. 7-1, Heading for Section 7.2 change to “Cardiovascular and Systemic Morbidity

Effects” p. 7-2, line 24 define “CAC”. p. 7-3, line 9 define “CIMT”. p. 7-3, line 21 define “ABI”. p. 7-3, line 30 define “AAC”. p. 7-4, lines 3-14 Why start off this discussi on with a paper that shows essentially no response? p. 7-5, lines 23-29 Why give such prominence to an IT study? p. 7-6, line 1 the Sun et al. (2005) paper cited at the start of this section, and the Sun et al. (2008) paper are importan t reports on aspects of NYU’s second 6-month subchronic inhalation exposure study. The results of the first such study were summarized by Lippmann et al. (2005a), and refe rred to, in part, as ‘an other project’ on lines 24 and 25 of this page. The first study should be cited first, and reference to the Sun et al. (2005) paper should follow. p. 7-7, lines 23-24 “despite 85 % of the total particle number concentration for PM 2.5 being comprised of ultrafine PM” is a truly nonsense statement. What were the authors trying to say here? p. 7-7, line 30 How can anybody take seriously a study in which the “control” exposure

to PM 10 was 50% of that in the “exposed”? p. 7-8, lines 7-20 How can anybody take seriously a study in which such a high IT dose was

administered? p. 7-9, line 23 The Sun et al. (2008) and Reed et al. (2004; 2006; 2008) papers were not from the “same group”. The Sun et al. pape r was based on a study performed at NYU, while the Reed et al. papers descri bed work done at Lovelace (LRRI). p. 7-9, line 24 “HWS” was not defined. [hardwood smoke?]

62p. 7-10, line 9 “TAT” was not defined. p. 7-12, lines 4-8 I am mystified that the effect for the preceding 60 days of exposure were reported rather than those for the preceding 30 days of exposure. The most interesting finding was that the effect increased with time up to 30 days, and then decreased! p. 7-17, lines 14,15 Isn’t a -45% decrease a 45% increase? Please clarify! p. 7-17, line 21 Isn’t this saying that PM 10 exposure was protective? Please clarify! p. 7-23, line 6-8 The citation to Pe ters et al. (1999) is no longe r informative, and should be deleted. This cross-sectional preliminary an alysis does not, in a ny way, contradict the subsequent prospective cohort analyses of the same population by Gauderman et al. (2000, 2002, 2004). p. 7-24, lines 1-3 The Avol et al. (2001) paper is not adequa tely presented. Not only were the kids moving to cleaner PM areas havi ng greater lung development, but the kids moving to dirtier PM areas were having reduced lung development. p. 7-39, line 15 The Gunnison and Chen (2005) paper was not a preliminary study, but was based on the exact same exposures cited in line 11. p. 7-39, line 17-19 The Maciejczyk et al. (2005) study is a simultaneous (parallel) study of in

vitro exposures on the same days as the subchr onic inhalation expos ures, but is not a “second” parallel study. p. 7-104, Fig.7-8 Why weren’t the Pope et al . (2002) lung cancer da ta depicted here? p. 7-117, lines 4,5 Delete “likely to be”. The authors should have the courage to accept the overwhelming epidemiological evidence of excess annual mortality associated with annual average PM 2.5 , which is amply supported by the re sults of a series of subchronic

PM 2.5 exposure studies in animals showing progre ssive changes in atherosclerotic plaque development and progressive de terioration of cardiac function. p. 7-117, line 11 Change “short-term” to “short- and long-term”.

Chapter 8

Overview: Provides a less than adequate summar y review of extremely important material. Did the authors run out of time to get it right?

Specific Comments p. 8-2, lines 23-26 The authors list some valid r easons for heterogeneity in estimates between cities, but leave out the two mo st likely to account for the differences, i.e., differences in particle size distributions and in PM compositions. p. 8-7, line 16 Delete “f”. p. 8-8, line 26 The AHSMOG papers should be acknowledged here, w ith a notation that cigarette smoking is not a c onfounder for this population. p. 8-17, Section 8.2.4 The clearest cases for the in fluence of SES are in the annual mortality

cohort studies. WHY WERE N’T THEY CITED HERE? p. 8-19, lines 5,6 The Miller et al. (2007b) pape r does not fit the statement, and warrants

discussion here.

As EPA staff prepares to revise the ISA for PM, I’d like them to consider and, as appropriate, cite some additional peer reviewed papers that are highly relevant to PM NAAQS consideration. These are:

63• Chen, L.C. and Lippmann, M. Effects of metals within ambient air particulate matter on human

health. Inhal. Toxicol. 21:1-31 (2009).

• Peltier, R.E., Hsu, S.i., Lall, R., and Lippmann, M. Residual Oil Combustion: A major source of airborne nickel in New York City. J. Expos. Sci. Environ. Epidemiol. (in press).

• Peltier, R.E., and Lippmann, M. Residual Oil Com bustion: 2. Distribution of airborne nickel and vanadium within New York City. J. Expos. Sci. Environ. Epidemiol. (in press).

• Lippmann, M. Semi-Continuous Speciation Analyses for Ambient Air Particulate Matter: An Urgent Need for Health Effects Studies. J. Expos. Sci. Environ. Epidemiol. (in press).

64Comments from Dr. William Malm

Comments on the Visibility Section of Integr ated Science Assessment for Particulate Matter,

First External Review Draft

The purpose of the draft ISA is to id entify, evaluate, and summarize scientific

information on the health and welfare effects associated with PM. The ISA is intended to “accurately reflect the latest sc ientific knowledge useful in in dicating the kind and extent of identifiable effects on public hea lth which may be expected from the presence of [a] pollutant in

ambient air”

Charge to the CASAC PM Panel

We ask the Panel to focus on the fo llowing questions in their review:

• How useful and complete is the scientific evidence presented and summarized in Chapter 9 regarding the effects of atmospheric PM on the environment, including (a) effects on visibility, (b) effects on i ndividual organisms, (c) direct and indirect effects on ecosystems, (d) effects on materials, and (e ) effects on climate? To what extent do the discussions and integration of evidence corr ectly represent and clearly communicate the

state of the science?

The focus of this review is on Chapter 9, regard ing the effects of atmosp heric PM on visibility. To what extent do the discussions and integratio n of evidence correctly represent and clearly

communicate the state of the science?

In general, the section on visibility is well wr itten and by and large refl ects the state of the science. However, I have a few comments and corrections, which are summarized below.

Section 9.2.1 (Summary of effects on visibility):

Page 9.2: In the second paragraph it is stated that the visibility impairment from each of the major species can be estimated. I would use the word “approximated.” Moreover, the reader is left with the feeling that a cer tain amount of visibility impair ment “is” attributable to each chemical species, which, even if perfect measurem ents were made with zero uncertainty, is not true. The attribution of chemical species to ex tinction is an ill-defined problem and cannot in principle be done. However, with certain ap proximations and assumptions (internal versus external mixtures or assumptions concerning mi xing properties of internally mixed aerosols) meaningful apportionments of chemistry to exti nction can and are made. There should be some

discussion of these issues to demonstrate that EPA has a clear and in-depth understanding of all the issuable scientific questions.

Bottom of page 9.2: What is the Midwest nitrate bulge?

Page 9.3: Why do OC and EC have the highest extinction efficien cies – not because of size or index of refraction but largely because of density differences . Some discussion should be

65included. Biomass burning is referred to as wild and prescribed fire; there is no mention of agricultural fires.

What is urban excess carbonaceous material?

Comment on how much of the contemporar y carbon may be associated with SOA.

Page 9.4: Some additional discussion and emphasis on “sense of well being” studies as they relate to urban visibility. Topics are menti oned on page 9.75 but implications of these studies should be highlighted in the summary section and expanded upon in section 9.3.5.

Page 9.8: Again, agricultural bur ning is left out of the discus sion. It is a cl ear anthropogenic

source of carbonaceous material.

Page 9.10: Nice discussion of night sky visibility. The sentence, “...addition of a light into the sight path, the brightness of the night sky...,” seems to me to be a bit uncl ear. What is meant by adding a light to a sight path? A nd why would this be important?

The extinction of starlight is a resu lt of both scattering and absorption.

Page 9.13: Mie theory calculations do not addres s “particle shape”. Usually, spherical aerosols are assumed; however, more complicated shapes su ch as cylinders have been used. However, arbitrary shapes are not assumed because calcu lations are nearly impossible to carry out.

Page 9.15: Replace the reference of Sisler et al. (1996) with Malm et al. (1994).

Page 9.16: Particle size is the mo st influential property of aerosol with respect to their dry light extinction efficiency. This generally a true st atement; however, if one ha s particles within the accumulation mode, the biggest difference between s cattering by, say, sulfate and organics is not generally size but particle density. Ammonium nitrate has a density of 2.3, POM a density of 1.4; that is about a 60% difference in mass s cattering efficiency, just due to density!

Page 9.17: Add Malm et al. (2003) to the reference list.

Page 9.19: This figure and associated implica tions should be incorporated in the monitoring discussion in Chapter 2.

Page 9.20: At the top of page should be 3.9±1.5 m 2 /g.

Page 9.21: Here is the place where a discussion of internal versus external mixtures should be included. The improve algorithm is only an appr oximation of what is usually an internally mixed aerosol. Furthermore, the main difference between inorganic and or ganic dry efficiencies is due to assumptions of particle density.

66Pages 9.25-9.30: Great discus sion of spatial trends. However, the scales are all different, which leads to very misleading interpre tations. The scales for each species, at a minimum, between quarters for each species should be the same.

Pages 9.30-9.40: Same issue for comparisons between STN and IMPROVE.

Page 9.35: Differences between STN and IMPROVE samplers should be discussed. STN uses 5 different samplers (Met One, URG, two differe nt R&P instruments, and Anderson), all with

different filter sizes and face velocities. Th ese differences result in significantly different

monitored OC values for the same ambient OC leve ls because of volatiliza tion issues associated with SVOCs. Furthermore, STN values, as re ported by EPA, are not corrected for positive

artifacts effects. How were these issues addres sed in the presentations of POM data in Figures 9.19 and 9.20 and in any other figures where STN data are discussed?

Page 9.39: In Figure 9.24 where urban excess is discussed (comparison of IMPROVE to STN),

the above issues are critical. Ur ban excess is interpreted as ha ving its cause associated with emissions, whereas some of the difference may be due to sampling artifacts (blank issues, in particular).

Page 9.41: Trends in haze are ve ry dependent on POM, especia lly in the West. The episodic nature of wildfire makes it very hard to infer tren ds of haze. Some discussion of the role of POM in long-term trends especially as it relates to fire should be included here. It is especially critical in the northern Rocky Mountains and the southeas tern United States wh ere there are significant emissions associated with prescribed fire.

Page 9.47: Throughout all sections on attribution it would be help ful to have some estimate of uncertainties. I would guess that most of this discussion is semiquantitative at best (bottom of page); certainly, there isn’t any difference betw een 45% and 50%, as is implied in the write up.

Page 9.49: Some cumbersome wo rding: “However, the Gorge’s ...” Consider rewriting. What is the implication of this sentence? So what?

Figure 9.32: On this graph and all others like it, it would be helpful to have labels on each of the pies identifying the pertinent receptor site.

Page 9.51: “track various the or ganic...” Something is missing.

Page 9.52: It is recognized that current regional models underestimate SOA by significant amounts (see Robinson et al., 2007) for a variety of reasons. One is that source profiles (emission estimates) of SVOCs are severely und erestimated, and two, the chemistry in the chemical transport models is very much lacki ng. Some discussion of these potentially severe

model limitations should be presented before modeli ng results are discussed.

Page 9.57, second paragraph: It should be clearly stated that the estimate discussed here for SOA is clearly a lower bound.

67There is considerable discussion on the WRAP we ighted emissions potenti al. This technique needs to be clearly discussed as to what ex actly the calculation is and how it should be interpreted. What winds were used in the trajec tory calculations? From what heights were the trajectories started? All the assumptions can have significant effects on th e results. The reader should be made explicitly aware of the assumptions.

Page 9.71: The fact that sulfate explains 90% of the variance in scatte ring when sulfate only

contributes 64% of the extinction means what? I don’t think it means anything more than there

are collinearities between sulfate and other species. What is the point of Figure 9.50? The legend for Figure 9.50 is wrong or the graph legend is wrong. I think the legend should read “...particulate nitrate and organic mass...” instead of “...particulate nitrate...”

Page 9.72, bottom of page: “...sulfate concentr ations than to cha nges in nitric acid concentrations...” Not sure what the implications of this statement are. Nitric acid is a precursor to particle formation while sulfate is a secondary aerosol. Would it be more meaningful to talk about SO 2 and nitric acid where SO 2 is the precursor to sulfate aerosol.

Page 9.75: I think the whole discussion on th e bottom of page 9.75 should be expanded to present some conclusions of all the studied referenced here, maybe one more paragraph. I think these results are absolutely key to assessing the relevancy of a secondary visibility standard.

Pages 9.78 and 9.79: There are some conversions be tween variable issues here. For instance, the point is made that all three urban studies have about 20 dv as being acceptable visibility. Yet

it is stated that 0.76/km is the median extinction value for Denver’s acceptable visibility. Well, 0.76/km is something like 40 dv, not 20. Same issu e with the Phoenix st udy – certainly 45 km and 3.5 km do not correspond to 87 and 12 km visual ranges. The implication that about 20 dv impairment is acceptable at all three locations may not be true.

Page 9.83: $134 - $360/what? – day? year?

REFERENCES

Malm, W. C., Sisler, J. F., Hu ffman, D., Eldred, R. A., and Cahill, T. A. 1994. Spatial & seasonal trends in particle concentration & optical extinction in the United States. Journal of Geophysical Research, 99, 1347-1370.

Malm, W. C., Day, D. E., Kreidenw eis, S. M., Collett, J. L., and Lee, T. 5-10-2003. Humidity dependent optical properties of fine partic les during the Big Bend Regional Aerosol and Visibility Observational study (BRAVO). J ournal of Geophysical Research-Atmospheres, 108

, art. no. 4279.

Robinson, A. L., Donahue, N. M., Shrivastava, M. K., Weitkamp, E. A., Sage, A. M., Grieshop, A. P., Lane, T. E., Pierce, J. R., and Pandis, S. N. 2007. Rethinking organic aerosols: Semivolatile emissions and photochemical aging. Science, 315, 1259-1262.

68Comments from Dr. Kent Pinkerton

Charge Question #5:

Chapter 5 is intended to support th e evaluation of health effects ev idence for both short-term and long-term exposures to PM. So me potential modes of action may underlie a number of health outcomes and may contribute to health effects of both short- and long-term exposures. Thus, the potential modes of action are described briefly in Chapter 5, and some specific study findings are

discussed in more detail in the re levant sections of Chapters 6 or 7. What are views of the Panel on this approach and on the characterization of potential modes of action for PM-related effects in Chapter 5?

Overall impression:

The Integrated Science Assessment for Particulate Matter: First External Review Document is an excellent document. Chapter 5 provides to the reader a highly relevant summary of the plausible mechanisms by which inhaled part iculate matter could lead to a dverse health effects. The chapter is well-written and is presented in a highly succinct and clear fashion. I like the approach used by the authors to present further de tails in chapters 6 and 7 which summarize past

information available from the 2004 document and c over the latest literatu re for each topic under Chapter 5 in a clear and very complete fashion.

Additional Comments:

Possible pathways/modes of action, chapter 5 focuses on a myriad of pulmonary effects via a thorough coverage of critical cellular and biological parameters to encompass reactive oxygen species, cell signaling pathways, inflammation, epith elial barrier function, antioxidant defenses and adaptive responses. Measures of pulmonary function, allergic disorders, impaired lung defense mechanisms, resolution of inflammati on with progression of disease and pulmonary DNA damage are also included in plausible mechan isms that are outlined in a highly succinct fashion. Systemic effects of PM are summarize d to encompass endothelial dysfunction, altered vasoreactivity and activation of co agulation, as well as acute phase responses. The role of the autonomic nervous system by pulmonary reflexes is discussed. Translocation of ultrafine PM and soluble PM components is presented, along w ith new inhalation studies which contribute to

modes of action.

Chapter 6 presents the integrated health effects of short-term exposure.

Chapter 7 presents the integrated health effects of long-term exposure. Recent epidemiologic studies confirm and provide furt her support between long-term e xposure and increased risk of mortality in areas with mean c oncentrations from 14 to 29 μg/m 3

.

Specific Comments:

69Page 5-1. The potential pathways or modes of action describe d below do not appear to be specific to a particular size cl ass of PM. This statement is perhaps too strong and needs to be used with caution based on the growing evid ence the ultrafine PM effects. Yes, the mode of action could eventually be the same, but the degree to whic h these effects are manifested could be strikingly different.

Sections in the chapter are cl early and accurately prepared. In most instances, excellent references are provided. Howeve r, some sections lack references and/or assume similar pathways of action based on the presence of a pa rticular mediator that may not have been

documented with PM-based studies.

Page 5-4. PAH-induced changes suggested only documentation in mice. This has been documented in other species as well.

Each section provides a clear summary of pulmona ry effects. However, it is important to

establish whether these effects are similar across species a nd under what conditi ons. This could be true for paths of activation, species sensitivit y and/or tolerance, gende r-based differences in

response.

Page 5-7. Pulmonary function – has AHR be defined as airway hyper-reactivity?

Chapter diagrams are helpful. Some could be furt her clarified as to mean ing or association. In addition, summary or outcome of study would be clearly helpful.

Page 5-9. DNA damage. The final sentence of this section seems to be more speculative than confirmed by direct studies. DNA repair mech anisms may also influence genotoxic, mutagenic or carcinogenic potential of DNA damage. Is this statement true for particle-induced DNA damage?

Page 15-13. Have acute phase responses been shown to be PM-induced? The authors should cite or reference such studies. Cytokines such as il-6 stimulate the li ver to produce acute phase proteins including C-reactive protein and an tiproteases. (van Eden et al. 2001).

Page 5-15. Section 5.5 Disease of the cardiovascular and other or gan systems. This section

could benefit with further discus sion of those plausible mechanisms that could be attributed to particles. It is important to make clear whether particles lead to cardiovascular disease or are simply able to perturb existing cardiovascular disease.

Page 5-15. CAPs – de fined, BC – defined?

Page 5-15 to 5-17. New studies. The summary of new findings is extremely good. It might be nice to reference these new findings as well, even though it is unders tood that these are presented in detail in chapters 6 and 7.

Page 5-17. Gaps in knowledge. A nice addition to th e chapter. Other gaps not stated could also

be listed:

70a) measured effects due to timing of exposure and timing postexposure b) the spatial distribution of retained particles and its impact c) deposition, uptake and clearance of ultrafine particles.

Chapters 6 and 7:

Page 6-3: Nice presentation provi ded for the importance of lag times in the consideration of health impacts.

Pages 6-4 to 6-6: The history of concentrator systems used in experimental studies is critical in placing into perspective how we can use these find ings from both animal and human studies to

evaluate PM health effects. The description of advantages and limitations of concentrator systems is very helpful.

The use of tables throughout the chapter is very helpful. Howe ver, for Table 6-1 it would be

beneficial to add an additional column to list a summary or outcome for each study as done in

Table 6-2.

Page 6-19 to 6-21: The toxicology studies report ed are very reasonable, but are newer studies

also available?

Page 6-29, line 15: Is there a reference fo r heart beat frequency in mice and rats?

Page 6-35 to 6-36: The section on vasomotor fu nction clearly points out the importance of the endothelium and endothelial dysfunction.

Page 6-46 to 6-49: The sections on epidemiologi c studies and right vent ricular pressure would benefit to have simple summary statements at the end of each section. An example of such a summary statement is found on Page 6-66.

Page 6-95: Cardiac Contractility – Toxicological studies: Reference needed.

Page 6-96: Systemic Inflammation – Toxi cological studies: Reference needed.

Page 6-100: Section on Toxicolo gical studies is somewhat c onfusing and lacks references.

Page 6-103: Section on Toxicologi cal studies lacks references.

Page 6-108: Blood coagulation – Toxico logical studies: Reference needed.

Page 6-156 to 6-159: Allergic sensitizati on and methylation studies are fascinating.

Excellent summaries are provide d throughout chapters 6 and 7. Although the data is very complete and typically detailed, the organization of each chapter is easy to follow, especially in being able to seek out specific information on any given topic.

71One random consideration: I re ally like the strong, well-documented respiratory components of the Integrated Science Assessment document. However, I wonder if the autonomic control sections might be further expanded via the cons ideration of central ne ural control of the autonomic system through further discussi on of the mid-brain circuit connections?

72Comments from Dr. Robert Phalen

Chapter 1. Section 1.5 EPA Framew ork for Causal Determination.

This section presents “a consistent and transpar ent basis to evaluate the causal nature of air pollution-induced health or environmental effe cts” (p. 1-11). However, there are some weaknesses. My main concern is that causali ty might be accepted when it is not true.

1. In section 1.5.2 the statement “An associa tion is prima facie evidence for causation: alone, however...” does not recognize that the strength of an association is also a

factor that should be considered.

2. In section 1.5.3, page 1-16, lines 4 to 20 disc usses the difficulty in dealing with an

extraneous factor and in finding “the likely causal po llutant” in mixtures of pollutants. This issue may be a profound one for PM 2.5 , given that evidence for risks for mortality upon long term exposure are f ound in “eastern and central regions, but not in the western United States” (Zeger et al., Env. Health Persp. 116 (12): 1614- 1619, 2008). Thus, the likely causal pollutant is not PM 2.5 . Should section 1.5.3 include a requirement that th e indicator be valid at al l locations before accepting causality?

3. Based on comment #2, should Table 1-2 be modi fied? Specifically with respect to “Consistency of the observed associa tion”, should consistency among various geographical regions be added as an aspect for judging causality?

4. Also in Table 1-2 under “strength of the observed association” the entry concludes

with the statement that “wh ile large effects support causal ity, modest effects therefore do not preclude it”. It might be good to co mment on small effects also, or at least to

define how much of an effect is consider ed to be “large” and “modest”. Are any strengths too small to be used to support causality?

Chapter 3. Source to Human Exposure

The chapter adequately updates information related to human exposures to PM. There are several undefined acronyms.

1. pg. 3-2, lines 23 & 31: Two main sources of PM 2.5 in the East are initially presented, but the rest of the paragraph doesn’t smoothly follow. Perhaps an introductory sentence could explain what this paragraph is about.

2. Table 3.1: Under the column “Accumulation” , some new sources could be added, e.g. wind-blown dust and biological processes.

3. Figure 3.2: “EGUs” should be defined in the caption or on the figure.

4. Section 3.6: Policy Relevant Background might also incl ude excessive levels of resuspended dust on windy days. For example very strong dry wind periods in Southern California are probably capable of producing PM 2.5 exceedences. If any data on such conditions are available they should be menti oned. This natural problem could lead to excessive regulation of anthropogenic sources of PM2.5, which can have serious adverse economic consequences.

735. pg. 3-172, lines 5 to 7: Fugitive dust also contributes to PM 2.5 in the West. This should be added to the paragraph.

Chapter 4. Dosimetry

In general the chapter presents an excellent review of the current understanding of inhaled particle dosimetry. The suggestions for improvement are minor.

1. pg. 4-5, lines 16 & 17: Add “and individual gene tic variation”, as it is a significant factor in airway morphology.

2. Figures 4-3 and 4-4: In the caption, state whether or not an Inhalability correction was

used.

3. Figure 4-5 could be eliminated. The non-na tural breathing diminishes its utility, and section 4.2.4.2 treats gender more thoroughly (eg see pg. 4-16, lines 8 to 13. Also, see the admonition on pg. 4-17, lines 26-28.

4. pg. 4-11, line 21: Replace “lower respiratory tract”, which is not clearly defined, with “tracheobronchial and possibly al veolar regions”. This clarif ication is helpful in view of the predicted and measured increased TB efficiency in small children, which can

sometimes decrease alveolar doses.

5. Section 4.2.5: This summary could be eliminated. The preceding sections are sufficient, and the summary has some over simplified conclusions. There are several problems in the Summary, e.g. Inhalability in humans is 77% for a d

ae , not “near 100%” as stated, the carinal enhancements look wrong, etc.

6. Sections 4.3.1, 4.3.1.1 and 4.3.1.2: Two major im portant factors modifying particle clearance should be added; 1) respiratory tract infections and 2) cough. These factors are strong and widely occur in th e population at any given time.

7. pg. 4-23, lines 4 and 5: The last sentence s hould be dropped. It c onflicts with other studies, and the previously-m entioned dog data were for 2 μ m particles, while the rat data were for 15-20nm and 80nm particles given to intubated ventilated rats.

8. Section 4.3.4.3: The effect of respiratory tract in fection on particle clearance is very important and should be added to this section.

9. Section 4.3.5: This summary could be droppe d. It is not an ad equate summary and it is a bit misleading regarding diffe rences between rats and humans.

10. Section 4.4, pgs 4-32 to 4-36: The termi nology is poor. The section begins with “Soluble particles”, which s hould be replaced with some thing like “Particles that dissolve rapidly after deposition...”. Good terminology must be established and used for this section and also in Chapter 5. The concept of water-solubility doesn’t work in the respiratory tract. Ma ny substances that are very poorly soluble in pure water rapidly dissolve in the l ungs when finely divided.

11. pg. 4-33, lines 20 to 22: This sentence didn’t make logical se nse, it should be fixed or dropped.

12. Section 4.4.3: Again, the Summary is very poor. It should be dropped, as it detracts form the quality of the foregoing chapter. Many other chapters do not have summaries, so dropping this one should not be a problem.

74Chapter 5. Possible Pathways/Modes of Action

1. The word “soluble” is used th roughought, see comment 10. above.

2. Section 5.6: It would be he lpful to identify the study popul ations (e.g. human, rat etc.)

for each of the effects listed.

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

1. Throughout this chapter and Ch apter 7, particle measurements are described as “increases”

rather than “levels”. Increases in levels are not the same as actual levels themselves. Yet, the epidemiology associations based on increases seem to be used by the EPA to set permissible levels of PM. A given increase can occur in dependently the level of PM. The issue of considering epidemiology associatio ns with “increases” rather than levels should be discussed and justified. I recall a pulmonary physician co mmenting on this issue during a proposal review session. He indicated that the resp iratory tract susceptibi lity to injury was very changeable and that a few days of exposure to clean air woul d make it more vulnerable. Perhaps regulating short-term “changes” or “increments” in PM measures (count, mass etc.) would be as good (or better) than regulating low levels . In any case EPA should address the PM “increases” issue. E.g. see pg. 6-10, lines 8 and 9; pg. 6-11, lines 24 and 27; and many places elsewhere. The possible importance of this issue might be seen in section 6.2.10.8 where the results of Villeneuve (2006) differed from the other study results. Also, conclusions based on increases

, such as that on pg. 6-94 (and other pages) should probably indicate that the conclusions may not apply to absolute levels.

Charge Question 4.

Detail in Chapter 4 is sufficient. Particle tran slocation is adequately described. The roles of cough and respiratory tract infections on particle clearance deserves greater emphasis. The

summaries should be made into true summaries of the foregoi ng material. Currently, they

introduce some new material. Annex B is ok.

75Comments from Mr. Rich Poirot

Comments on Chapter 9: Ecosystem and Welfare Effects

General Comments This chapter summarizes the policy-relevant scie nce that would support review of and possible revision to the secondary (welfare-based) PM N AAQS. It includes sections on PM effects on visibility, individual organisms, eco systems, materials, and climate. The section on visibility is substantially more detailed and informative than those on other welfare effects - about the length

of the other 4 effects sections combined. I th ink this emphasis is justified, since it seems unlikely that a secondary PM NAAQS could be an effective mechanism to ameliorate affects of PM on organisms, ecosystems, materials or clim ate. However the relationships between PM mass (especially PM 2.5 ) and/or PM species and visual air quality have been well known for many decades, and a secondary PM NAAQS to protect visi bility has been considered in every previous PM NAAQS review - including the original es tablishment of TSP standards in1971, when a secondary TSP standard of 150 ug/m 3 was based in part on (minimal) protection of aviation safety (maintaining visual flight rule conditions at airports).

The visibility section of this chap ter is clearly written and presents a substantial amount of recent information, much of which has been genera ted through the work of the Regional Planning Organizations (RPOs), and supporting groups at NPS, EPA, and th e IMPROVE program, to help develop the first round of State Implementation Pl an (SIP) revisions in response to the 1999 EPA Regional Haze Rule. Consequently, the focus is pr imarily on effects of i ndividual fine particle species (and coarse particle mass) at re mote National Parks and Wilderness Areas.

One general criticism then is that relatively little of the informa tion presented relates directly to causes and effects of visibility-impairing PM in the non-Class-1 rural, s uburban and urban areas to which a possible secondary PM NAAQS woul d apply (although conceiva bly a secondary PM NAAQS might be exceeded in some of the more polluted Class 1 areas, and could provide added mechanisms to assure improvements in those area s). We would also expect to see improvements in visibility outside Class I area s as an inevitable result of measures to reduce regional haze impacts within them. A secondary PM standa rd and the Regional Haze Rule need not be mutually exclusive from each othe r, although it seems useful to th ink of them as complementary

rather than as redundant mechanisms. So it woul d be useful to see more information focused on

the differences between urban/suburban and remo te area PM composition a nd visibility effects.

A second general criticism is th at the chapter is predominantly focused on the reconstructed aerosol extinction approach (chemical species measurements combined with generic dry extinction efficiencies and hygroscopic growth functions) which is the basis of the regional haze program. Conceivably, a similar approach might be employed for a secondary PM standard – employing for example the speciation data from the CSN network with a similar or modified “urban” haze equation. However, other approaches might also be considered and the chapter could do a better job supporting t hose alternate approaches. For example, in reviewing the PM

Criteria document in the last re view cycle, it was noted by CASAC (Warren White and others) that an early draft of the PM CD contained no information showing the simple but strong relationship that exists between fine particle mass and visibility (especially under conditions when effects of hygroscopic growth are minimized – such as by focusing on daytime only and/or

76constrained to hours of lower relative humidity). As a result, the following plot (with associated discussion) was added to the final 2004 PM CD.

Fi g ure 1. Illustration of Fine Mass / Visibilit y Relationshi p from 2004 PM CD

This graph had earlier been included by Warren White in a JAWMA critical discussion on visibility by Chow et al. (JAWMA 52:973-999, 2002), and attributed in turn to data collected in 1970-71 and published by Samuels et al. in 1973. One point Warren raised was that the strong, linear relationship between fine mass and visibi lity impairment was well known at the time of the original Clean Air Act. Another point emphasized in that di scussion, was that the information provided by detailed, costly, labor-intensive chemi cal speciation sampling (which currently requires use of intermittent filter samp ling over long averaging times) was of value primarily for estimating the effects of aerosol wate r. A more efficient regulatory approach might take better advantage of curre nt science and technology, by mini mizing the importance of water by constraining the averaging time to daytime-only and/or hours with RH < 70% - as has been done in establishing local visibility standa rds in Denver, Phoenix, Lake Tahoe, etc.

EPA staff and CASAC took a similar approach in recommending a secondary PM 2.5 standard in the last review, based on a daylight-only 4 to 8-hour averaging time (a lso corresponding more directly to periods when outdoor, sun-illuminated visibility is mo st important to most people). An alternative indicator might (if the lawyers allow it) be based more directly on optical measurements, such as by ASOS, transmissometer, nephelometer, or nephelometer + aethelometer (scattering + adsorpti on). To better support consider ation of a fine mass or optical indicators, it would be useful to include some additional attention in the ISA to discuss the characteristics, averaging times, strengths a nd limitations of various aerosol, optical and meteorological measurement methods; present some illustrative data from urban/suburban areas;

77and show how effects of water (currently avoide d as a component of PM mass), might best be quantified and/or minimized with alternative regulatory options.

Specific Comments

p. 9-2, line 7: Add “by part icles” after “scattering”.

p. 9-2, line 8: You might rephrase this to “While a large particle scatters more light than a similarly shaped smaller particle...” or “While a large particles scatter more light than a similar number of similarly shaped smaller particles...”

p. 9-2, line 19: Add “ed” to “call”.

p. 9-3, line 6: Change “and” to “or” or to “and/or”.

p. 9-3, line 16: “Western...”

p. 9-4, line 5: You could add “in rural areas” af ter “haze”. Note – here and elsewhere in this section, its not always clear whether you’re refe rring to urban areas or regional-scale (rural)

concentrations.

p. 9-4, lines 10-20: Need a reference for this study.

p. 9-4, line 21: You could insert “Perception of” or “The value of” before “urban visibility” to make it clear that you are not referring to urba n studies of optics, aer osols, sources, etc.

p. 9-4, line 34 and p. 9-5, line 1: You could delete “, the preferred measure of visibility impairment”, since I don’t think DVs are actual ly “preferred” by everyone , and also to make it clear that you don’t mean 19 to 25 DV was the preferred measure of impairment....

p. 9-6, line 2: While “N” is correc t, I suspect you mean “Ni”. It mi ght also be noted that Zn is an element typically most prevalent in the fi ne fraction, while V often has a relatively high

coarse fraction contribution.

p. 9-7, line 14: Change “is believed” to “is estimated to”.

p. 9-7, line 16 (or elsewhere): It might be useful to begin with some di scussion of EPA staff (& CASAC) recommendations (& policy decisions) from the last PM review. This would help lead

to a more “ a concise synthesis and evaluation of the most policy-relevant science used to help form the scientific foundation for review of the secondary (welfare-based) NAAQS”

p. 9-7, lines 16 to 18: Since the ”recent” inform ation presented here comes quite predominantly from regional haze-related analys es of rural IMPROVE data, I suggest modifying this sentence

to: In recent years, most visibility research involved ch aracterizing visibility levels and trends over broad regional scales, improving our understanding of the at mospheric processes and pollutants responsible for the regional impacts, and attributin g visibility-impairing pollutants at remote sites to emission sources, source types, and regions.

78p. 9-7, line 25 and first 2 lines on p. 9-8: Break th is into a few sentences or otherwise fix the grammar.

p. 9-12, line 14: Cha nge “are” to “is”. p. 9-12, lines 16-17: True, although NO 2 measurement data are often not available, are typically of questionable quality (include other oxidized N species), and ma y not represent the locations – such as in NOx plumes and in layered hazes – where NO 2 effects are most evident.

p. 9-14, line 11: You could change “theoretical” to “Mie theory”, as less sophisticated

“theoretical” calculations are ce rtainly possible – and are rout inely conducted for the regional haze program.

p. 9-16, line 3: Add “s” to e ither “term” or “inflate”

p. 9-16, line 21: Add “s” to “aerosol” or add “particles” or “effect s” after “aerosol”.

p. 9-18, lines 12-14: Can you provide some quantita tive estimates of the underestimation of total extinction due to coarse mode hygroscopic specie s at Brigantine or elsewhere (i.e. is this important?). Also, if we are concerned with e ffects of anthropogenic pollutants on extinction, is there any visibility consequen ce of replacing NaCl with NaNO 3 ?

p. 9-18, line 29: Cha nge “are” to “is”.

p. 9-20, line 18: Delete the first “components”.

p. 9-20, lines 19-22: Seems like either too much de tail or too little. You could just report the values they recommended, but if you also report the different values th ey “determined” from their review, then I think additi onal explanation is needed to ju stify why they felt compelled to

recommend numbers different fr om what they determined.

p. 9-21, lines 16-23 (or elsewhere ne arby): It might be informative to comment here on possible problems in applying this (remote site) equation to urban data – for example, organic mass might be < 1.8 * OC, and we might also not expect the higher OM concentrations to be well-aged.

p. 9-25, Figure 9-7 (and about the next 20 map figur es): The VIEWS system is an excellent tool and these color contour maps are very informa tive. However, a major limitation has been the

lack of user control in selecting the color contour levels. I think the system “auto-scales” these to display maximum information content for each map from the (10) colors employed. This is fine for seeing spatial pattern in an individual map, but makes it difficult to compare maps. I don’t think its critical for this ISA, but it would be useful for many future applications if options were provided for the VIEWS user to specify the contour levels and inte rvals (i.e. the maximum contour level, number of contour in tervals, and ranges of the bins).

p. 9-27, Figure 9-9, and in text discussion: The Agency has d ecided that effects of S and N deposition (including particle pha se) will be addressed in the re view of secondary SOx and NOx NAAQS and not in this PM NAAQS review, while the secondary aerosol effects of S and N compounds – such as on visibility – will be addr essed in the PM NAAQS review, but not in the secondary SOx and NOx NAAQS review. Since a mmonium sulfate and a mmonium nitrate have

79similar dry scattering efficienci es and hygroscopic growth functi ons and combined account for a majority of visibility impairment over much of th e country, it might have been interesting (& still would be) to break out a separate section on (for example include a map here of) the visibility

effects of combined S + N aerosols. Such a di scussion could be copy-past ed in both the PM and secondary SOx & NOx ISAs & REAs. A reason for this is that it might help support

consideration of SOx – NOx NAAQS metrics that might have been based on a combined sum of gaseous and aerosol S and N com pounds, that might have had (and been justified by) beneficial effects of S & N emissions reductions on both deposition-related and aerosol-related effects.

p. 9-35, lines 8-20 (and following figures): Line 9 indicates that Figures 9-22 and 9-23 show total carbon, but those figures actually show fi ne soil (the total carbon figures are missing).

There needs to be some discussion of the differences in the CS N TOT and IMPROVE TOR carbon methods – indicating that OC & EC don’t have the same meaning at urban & rural sites, although the missing total carbon comparison would be meaningf ul. Possibly the CSN OC & EC data could be adjusted to make it “IMPROVE- like” before combining it with the IMPROVE data in Figures 9-19 and 9-21 – otherwise I don’t thin k you should be combining the disparate data. As indicated before, using the same scales for paired IMPROVE and IMPROVE + CSN maps would be helpful. It would also be useful to delete the few urban IMPROVE sites (Washington, Phoenix, Puget Sound, etc.) from the otherwis e rural IMPROVE-only maps (if possible).

pp. 9-41, 9-43 (Figures 9-26, 9-27): A discomforting feature of the h aze trends in these figures is that the 10-year period 1995 – 2004 is the period of the Title IV Acid Rain SO2 emissions

reductions in the eastern US. Yet on the cleanest and haziest 20% days respectively, 6 of 14 and 8 of 14 eastern sites show no significant improve ment. This doesn’t inspire confidence in

successful outcomes of future contro ls. I suspect this may be partly related to the fact that a large portion of the acid rain SO 2 reductions occurred in the first (1 995) year of the Title IV program (and of this trend analysis) and due to spending of banked allowances etc., the actual emissions reductions over the 1995-2004 period have been relatively small. See figure below from EPA “Acid Rain Program 2007 Progress Report” http://www.epa.gov/airmarkets/progress/arp07.html

. Possibly some discussion of this “non-trend” could be added here.

80p. 9-45, Figure 9-29: Although there are cautionary remarks in the text on p. 9-44 describing this figure, as well as a warning that this “may be misleading” in the figure caption, I’m suspic this figure – generated from the “Causes of Haze” website – that shows increasing trends (significantly so at most sites) of ammonium nitrate extinction on the haziest days at all ious of

western IMPROVE sites over the period 1994-2003. Extraction of a simila r plot from the COH website for the cleanest 20% days shows an opposite tren d of decreasing ammonium nitrate extincti the cleanest 20% days at these sites – and I’m just finding this hard to believe, and suggest double-checking the calculations. If these opposite trends are correct, they would seem to warrant additional exploration (for example d on on

oing same for cen tral and eastern sites) and ffering some explanation(s) of causality).

st Days ys (right), 1994- 2003 from Causes of Haze Website ( http://www.coha.dri.edu o

Figure 3. Nitrate Extinction Trends at Western IMPROVE Sites on 20% Hazie (left) and 20% Clearest Da )

at

ent. An example of the data for the assen Volcanoes NP site is pasted in Figure 4 below. I notice that similar trend info rmation, including estimated extin ction calculations on worst 20% & best 20% days by species, site & year can be extracted from both the VIEWS and (for WRAP sites for 1994-2003) the Causes of Haze websites. Comparing the 2 separate sets of calculations (using the RHR1 equation on VIEWS), I note that the results are ge nerally very similar for most species at all sites, but there are substantial diffe rences – especially in the first few years – th seem likely to influence trend calculations, di rections and significan ce levels. I don’t know which one is right (if either are) , but note they are differ

L

81p. 9-45, lines 1-2: I don’t understand what “at any relative humidity” means here. Haze contributions are only proportional to species con centrations at very low humidity. At higher RH, the hygroscopic species contribute proportiona tely more, relative to their mass fractions.

Figure 4. Estimated Light Extinction on Worst 20% Days for sulfates and nitrates at Lassen Volcanoes IMPROVE site, 1994-2003, as extracted from the Causes of Haze (COH) and

V IE WS websites

0 1 2 3 4 5 6 7 8 9 10

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003Species Light Extinction on 20% Worst Days (Mm-1)

Sulfate_Ext (COH)
Sulfate_Ext (VIEWS)
Nitrate_Ext (COH)
Nitrate_Ext (VIEWS)

p. 9-46, lines 6,7: Nitrate does not “domin ate” in the summer in the Midwest.

p. 9-48, Figure 9-30 and several subsequent figures (9-32 through 9-36). You might add the time periods for which these plotted analysis results apply to the figure captions.

p. 9-57, line 24: Add “s” to “location”.

pp. 9-57 through 9-64: I have a hard time follo wing this discussion and interpreting these figures. A bit more explanation up front would be helpful. Are all these figures really necessary? Also, I note that a la rge majority (22 of 30 pages) of the discussion and illustrations in this “causes of haze” section 9.3.4.5 pertain to the WRAP RPO region (and to aerosol source apportionment in WRAP class 1 areas only), while only 7 pages are devoted to results from the other four RPO regions combined.

p. 9-74, lines 29-31: While I understand there are some good arguments and strong opinions to the contrary, I don’t concur that the existence of primary health sta ndards necessitates the separation (& removal) of “wellbeing” components (i.e. perceived health e ffects), from so-called

82“aesthetic” components when attempting to assess pe rceived levels of adversity or to evaluate

alternative levels at which seconda ry standards might be set. Fi rst, this requires an assumption that the primary standard has in fact been se t at a level below which all health effects are prevented. With the TSP primary standard of 260 ug/m 3 , or PM 10 of 150, or PM 2.5 of 65 or 35 ug/m 3 , any observers who perceived health effects at or just below the levels of the primary standard would have been correct, and any regul ators who argued that any perceived health

effects were irrational and should be discounted at those (health- protective) levels were wrong. Second, there’s a required assumpti on that its possible to separate a perceived health concern from the overall emotional response to the visual e ffects of polluted air. I’m not so sure this is really possible (or necessary), nor do I understand what a purely “aesthetic” response to impaired visibility would mean. Third, I’ll argue that th ere can be a perceived health effect which is

different from the actual health effect, but which is nonetheless an important source of stress, malaise, and/or emotional discomfort to the vi ewer. An analogy would be the strong perception

of “unhealthiness” associated with certain “ch emical” odors. This perception may occur at

ambient concentrations of such chemicals which ar e not (currently) demonstr ated to cause actual health effects. The perceived health effect una voidably contributes to th e perception of a foul, objectionable odor, which adversely affects the quality of life for those exposed to it.

pp. 9-76 - 9-98 (or in a subsequent section): In (or after) summarizing these various urban visibility valuation studies, it mi ght be useful to summarize the ur ban visibility standards that have resulted in part from some of these stud ies – or from other public policy decision-making processes (such as for California, statewide and fo r Lake Tahoe), as well as noting, the scientific and practical reasons for the details of the indicators, averaging times, levels and forms of these standards (such as constraints to day time-only, and to lower RH levels,...).

It can also be noted that almost all of the pr eceding discussion was based on results taken from remote, Class 1 areas (which are already “p rotected” by EPA’s Regional Haze Rule. Then there’s a jump to “urban” valuation and prefer ence studies, but no mention of such valuation studies in remote Class 1 areas, nor any discussion of visibility e ffects or valuation in the (nonClass 1, non-urban) suburban and rural areas which compose most (>95%) of the US land area.

p. 9-84, line 2: Since effects of PM (and its pr ecursors and transformati on products) on materials are also related to deposition, you might also add a mention of that to this intro on deposition. It might also be appropriate to mention here the PM species for which deposition is of concern for a materials damage or ecological perspective.

p. 9-84, line 25: you might insert “a s well as” after “soil,” and befo re “plant” to make it clear that your not talking about “bas e cations from soil, plant and insect fragments, ...” etc.

p. 9-85, lines 1-7: This discussi on of radiative effects doesn’t really belong in the “Forms of Deposition” section, unless you are referring to alteration of radi ative effects from reflective snow and ice surfaces as they are modified by deposition of light absorbing particles.

p. 9-89, lines 6-15: I’m surprised we need to go to Italy to find re ferences on primary vs. secondary PM components. Also, I doubt that Cl - is really an important secondary PM component in coastal or any ot her areas. Its predominantly a primary PM component, and often

83lost from particle phase, prior to deposition. Se condary organics are also important – especially in urban areas. Further, the deposition rates of fi ne particles are substantially less than for larger particles, such that the dry deposition of particulate matter components in urban areas is likely more heavily influenced by coarse particles, ga seous precursors (or former particle components that have disassociated from particle phase) than it is by fine partic les – even if the fine particle

fraction tends to incr ease during episodes.

p. 9-90, lines 15-16 and Table 9-3 on p. 9-89: W ould fit better in the “Mercury” section, 9.4.5.2.

p. 9-98, lines 21-22: Although anthropogenic V is t ypically heavily enriched in fine particles influenced by oil combustion sources, there can al so be substantial concentrations of V in soils, and deposition is likely often dominated by natural sources in some areas. p. 9-102, lines 1-6: There seem to be some inc onsistencies here. For example line 5 describes a global [Hg(0) I presume] reservoir “with a resi dence time of a couple of years”, while lines 31- 32 on p. 9-101 refer to an Hg(0) “residence time of about a year”. Also I doubt that Hg(II) in gas phase has a residence time of “months” or that Hg(II) associated with fine particles has a residence time “similar to Hg(0)” of 1 or 2 years.

p. 9-106, lines 17-18: Its not clear what “much of the burden” refers to. If it resides in the atmosphere, to what organisms is it a burden th ere? If you’re referring to the “atmospheric burden”, I think pretty much all of it resides either dissolved in fog or clouds or as liquids or

solid aerosols.

p. 9-106, line 27: You could add “and other mining activities” after “limestone quarries”.

p. 9-110, lines 1 &2, and generally throughout this section. Sometimes the terms “metals and “heavy metals” are not always used consistently here and sometimes just “trace elements” would

be a better term.

p. 9-111, line 3: should be “expos ures ...have” or “exposure has”.

p. 9-112, line 9: Change “of” to “to”.

p. 9-113, lines 12-22: I suggest re placing the term “tire dust” with “road dust” in lines 12 14 and 19, and using the term “tire wear” in line 16. For the most part, the dust you’re referring to is not predominantly composed of tire fragments, and its suspension to the ambient air is more driven by the aerodynamic action of moving vehicles rather than the direct action of tires on the road. p. 9-113, lines 19-22: What’s the meaning of “parti cles embedded in tire dust”? If Adachi and Tainosho used the term “tire dust”, explain what they meant by the term (how did they collect it?). Is there any explanation for the tw o different compositions of “brake dust”?

p. 9-132, lines 14-15: I don’t disagree with your assertion that fine mode particles generally have a larger effect on climate than la rge particles, but I th ink you need more explanation than “sizes close to the wavelengths of visible li ght” before proclaiming “therefore...”

84p. 9-136, lines 4, 5: This seems inconsistent w ith your citation to Fo rster et al., 2007 on p. 9-144 indicating a total direct aerosol RF of -0.04 + 0.04.

p. 9-138, Table 9-4 (or elsewhere in this chapter): It would be interesting to see the US subtotals or fractions of the global emissions in this tabl e – or otherwise provide some indications of the extent to which relatively small modulations in the relatively small US contributions to the global aerosol budget might be expected to influence climate.

p. 9-141, lines 1-3: You clai m 3 ways but only list 2.

p. 9-142, lines 5-12: The point is n’t clear to me here, but I assume any comparison of the effectiveness of reducing BC vs CO 2 or CH 4 , depends on the proportionate size of the reductions in the different pollutants.

p. 9-142, lines 27-30: Not sure what the point is in describing the different assumptions on (internal vs external) aerosol mixtures. Was the range of results -0.39 to -0.78 W/m 2 due to which mixture assumption was used, and if so, which assumption produced the largest result?

p. 9-144, lines 3-10: “These” in the second and thir d sentences doesn’t agree with “Progress” in the first sentence, and you only cite one inter-comparison. I al so don’t understand why “coarse aerosol fractions are largely re sponsible for variations in na tural emissions”. Do you mean

“coarse aerosol fractions are largely dependent on variati ons in natural emissions?”

p. 9-147, Figure 9-57: This is an in teresting graphic, but hard to read. I’d like to see it larger with a (much) shorter caption, which refers the reader to the text for a detailed explanation.

p. 9-155, lines 7, 8: Should be “role ... is” or “roles ...are”.

85Comments from Dr. Ted Russell

First, while I am sure I will note be the only one to comment on this, an 800 page document that

starts with “... a concise review , ...” might be open to some criticism for what is meant by “concise.” I recognize it could be longer, but I al so think it could be shorter without loosing much in terms of its support of the possible re vision of the NAAQS. EP A should resist making the ISA much larger in response to CASAC or other review. My ISA has travelled many thousands of miles to get read. On the other hand , it does pack a lot of information. As to where the document might be trimmed a bit, speaking as an air quality engineer type, there are parts of that section that might be put in an Annex. The main information s hould be to provide a foundation for understanding the health and welfare impact results later on.

Chapter 2

Chapter 2 on the Integrative Health Effects Over view is an important chapter, and reasonably well done. The integrative summary, along with th e conclusions, provide a solid and informative overview and highlight the key points. Inclusi on of just the causal and likely to be causal relationships make sense because those are what will drive the consider ation of revising the primary NAAQS. I would use exactly the same te rminology on page 2-11 and in the Tables (I would use causal and likely to be causal). While I like what ha s been laid out in terms of linkages between PM mass and the health endp oints, I think that the discussion of PM components and sources linkages to health outcomes is insufficient. I would have liked more of a summary similar to what was done for mass linka ges, or a statement as to why such is not there. Also, as the Chapter is now 25 pages long, and that this is the chap ter that will get read by those not wanting to read the other 800 pages, I think a wrap-up page or two would be called for. If you do decide to add more on impacts that do not make the t op two classes of causality, I would make that section short, focusing on what mi ght be important in the future, and if it is an area where there is a strong chance that as uncer tainties are reduced, that area might influence revision of the NAAQS.

While I like how they have laid out the health endpoints and linkages, I do not believe that the non-health effects endpoints should be left out of this chapter. The eco system/welfare endpoints need not get as much attention, but relegating all of that discussion to a single chapter at the end of the ISA sends the wrong impression and might l ead one to miss that we are extremely certain

about some of the welfare effects. There are some very important effects that are not included in the health assessment (that have possible health impacts via climate modification).

In Chapter 2 (page 2-4) an important point is glossed over: PM2.5 is a major fraction of PM10 in many urban areas. This likely drives much of the fi ndings reported here. This is also true at the top of page 2-6 (it is not surprising that PM 10 and PM2.5 are highly correlated much of the time and in many locations). On page 2-6 they note various methods to measure temporal variation in PM mass and components, but it does not include filter –based techniques anywhere in this section. For completeness, there should be a se ction just on measurem ents (one paragraph) before the discussion of spatial or temporal variability to discuss both integrated and continuous/semi-continuous methods, together. On page 2-7 they state factually that current inventories overestimate primary components etc... th e verdict is st ill out, and more goes in to

86this than just volatility issues. This comm ent can be removed from here, though should be discussed in Chapter 3. We are quite unsure of our emission estimates from the various sources, particularly for organic species.

Chapter 3

Like past ISA’s, I like the Sour ce-to-Human Exposure approach to cover that aspect of the review. It is potentially very efficient, though as indicated above , this chapter might be reduced a bit, keeping in mind what the key considera tions are later on (e.g., possible mechanisms and their linkage to specific compone nts; spatial and temporal variab ility and epidemiologic studies; components and epidemiologic results, etc.), and th at the chapter will be used for the exposure modeling as part of the risk assessment. I recognize that I might be asking for a bit of clairvoyance to see exactly where the risk assessment might go. The Scope and Methods Documents helped figuring out part of that (see below).

As noted above, one should tread a bit more cauti ously about stating that the volatility effects have led to specific under/overestimates in the in ventory. This process might be discussed, but there are many other factors that might lead to over/underestimates. (Also, 3-12, l18 is a bit

awkward in that the emissions do not estimate anything).

Section 3.7.2.3: This section needs to be expanded (o.k., forget one of my first comments above). Exposure modeling will be key to the Risk Assess ment, and either a thorough exposition of the models to be used should be contained here, or such will be required as part of the RA.

Like my comment above, Section 3.8.1.4 should be moved up to be inclusive of all measurement techniques that have been used extensively enoug h to be included in such a summary (e.g., filterbased techniques). Make a section 3.8.1.2

Section 3.8.2.3 is important and needs to make its points very strongly. It should answer the question (or lay the foundation for answering the question) as to whether confounding is a likely issue just based upon the correlations between pollutants and in the exposure studies. It actually only goes half way. It provides a strong statem ent about the indoor-outdoo r PM source exposure confounding, but not if a gaseous species may le ad to confounding. It ends on a negative note that may be of secondary importance (what it sa ys is important in terms of assessing the epi studies for the gaseous species impacts), but not if the gaseous species may confound the PM

results. .

Chapter 9.

This chapter suffers from not being as complete ly developed as it could/should be. There is no integrative summary. It is also very weak on assessing how anthropogenic emissions impact PM10-2.5 (and the resulting welfare effects) over natural emissions in urban areas, and how this relates to apportioning visi bility reduction. It should also be more specific about confidence, and probably more bold, and how uncertainties/certain ties should impact consideration of possible revisions to a secondary NAAQS. This is part icularly true for climate. While there are

87uncertainties in climate relationships, but there ar e topics for which we are relatively confident. This is particularly true for th e direct effects. Looking at the question as to what might drive revision of the NAAQS, climate change should be part of that, if not play a central role. I am concerned that this chapter in its current form l eads to a lack of consider ation of climate impacts (both ways). This section needs to make th e link between climate change and health impacts (which, I agree, are uncertain). It is not clear what the sectio n on POPs adds. (I would suggest focusing the climate section.)

A couple details:

What is meant by “warmed molecules can have long lifetimes and be transported large

distances...”

Given the issues that have come up in both Sc ope and Methods documents as to how to treat PM10-2.5, the PM ISA needs to do a more comprehensive job on that topic. The additional information and analysis includes how well it is treated in CMAQ, and the evaluation of CMAQ for simulating PM10-2.5. It also includes how well we can distinguish between the anthropogenic and natural PM10-2.5 fractions, and how the two correlate. Further, given that the SM-Welfare proposes to use scaling of th e source apportioned PM2.5 to estimate the corresponding PM10-2.5, the components of that pr ocess should be discussed here in greater

detail.

Another topic that I worry about fr om the point of insufficient cove rage is climate. While there are many uncertainties as to how aerosols impact climate, there is enough known that this topic should be influencing how we c onsider revising the secondary st andard, and possibly even the primary standard.

Specifics: Fig 3-1: In the caption, need to do a bit better job as to what the dashed lines versus solid lines

mean. Maps (e.g., Figs 3-19, 21 etc.) A bit more info than just the roads would be helpful (e.g., rivers). Fig. 3-30. I don’t think you mean P ittsburgh in the figure caption. I think it is Philadelphia. Did you mean to switch cities? Fig. 3-2: Should note anthropogenic. Page 3-18: Cations and Anions

. Page 3-122: Note sure why they think that th e Voyageurs site was not impacted by fires. Fig. 3-69... Why change colors from prior figures? Table 3-23: Be consistent in how you distingu ish between mod and obs (use mod; obs in the column headings).

88Comments from Dr. Frank Speizer

Chapter 1 General Comment: This chapter outlines both the hi storical Clean Air Act activities as related to Particles and provides a discussion by which criteria can be applied to establish causality. It

seems that after the several iterations that have ta ken place in trying to get this right, the Staff has put together a summary of the issues that are hard to fault, save one issue mentioned below. . One question might be whether th ere is a better way to summari ze the weight of evidence in terms of consensus building. A recent discussion at the Inte rgovernmental Panel on Climate Change adopted seven verbal expr ession of certainty. I list them here for purposes of discussion only to see if CASAC should consider them in our deliberations: Verbal Description Percent Certainty Virtually Certain Considered more than 99% likely Very Likely More than 90% Likely More than 66% More likely than not More than 50% Unlikely Less than 33% Very Unlikely Less than 10% Exceptionally unlikely Less than 5%

Intergovernmental Panel on Climate Change, 2007 The chapter reads well and needs only minor editing Added here are the factors in Chapter 1 fo r causation: (for purposes of discussion) Table 1-3. Weight of evide nce for causal determination.

Health Effects
Causal relationship Evidence is sufficient to conclude that there is a causal relationship between relevant pollutant exposures and the health outcome. That is, a positive association has be en observed between the pollutant and the outcome in studies in which chance, bias, and confounding could be ruled out with reasonable confidence. Evidence includes, for example, controlled human exposure st udies; or observational studies that cannot be explained by plausible alternatives or are supported by other lines of evidence (e.g. animal studies or mode of action information). Evidence includes replicated and consistent high-quality studies by multiple investigators. Likely to be a

causal relationship Evidence is sufficient to conclude that a causal relationship is likely to exist between relevant pollutant exposures and health outcome but important uncertainties remain. That is, a positive association has been observed between the pollutant and the outcome in studies in

which chance and bias can be ruled out with reasonable confidence but potential issues remain. For example: a) observational studies show positive associations but copollutant exposures are difficult to
address and/or other lines of ev idence (controlled human exposure, animal, or mode of action information) are limited or inconsistent; or b) animal evidence from multiple studies , sex, or species is positive but limited or no human data are available. Evidence generally includes

89replicated and high-quality studies by multiple investigators. Suggestive of

a causal relationship Evidence is suggestive of a causal relationship between relevant pollutant exposures and the health outcome, but is limited because chance, bias and confounding cannot be ruled out. For example, at least one high-quality study shows a positive association but the
results of other studies are inconsistent. Inadequate to

infer a causal relationship Evidence is inadequate to determine th at a causal relationship exists between relevant pollutant exposures and health outcome. The

available studies are of insufficient quantity, quality, consistency or statistical power to permit a conclusion regarding the presence or
absence of an association between relevant pollutant exposure and

the outcome. Suggestive of

no causal relationship Evidence is suggestive of no causal relationship between relevant pollutant exposures and health outcome. Several adequate studies, covering the full range of levels of exposure that human beings are known to encounter and considering susceptible or vulnerable subpopulations, are mutually consistent in not showing a positive association between exposure and the outcome at any level of

exposure.

. Specific Comments: Section 1.5, 1.11 Discussion of factors eval uated for causation’:, line 28: defines cause, in contrast to statistical association Not clear that this belo ngs here as part of the

discussion. Almost all of the fact ors entering causation with regard to population data are in fact

statistical.

Page 1.15-16: Confounding needs to be defined more clearly, just as effect modification is.

Chapter 2

General Comment: This is a useful summary if it indeed truly refl ects what is contained in subsequent chapters. There will need to be some cross checking to be sure that the major finding are all summarized here. I would likely take issue with the classification of cancer. I think it will need to be broken down to lung cancer and other canc ers as I think the ACS data w ould at least be “suggestive”.

Specific Comments Page 2-5, line 13: Assumption is that “diel” is short for diurnal but needs to be spelled out first

time.

Page 2-6, end of paragraph at line 23: Suggest a statement is needed here that the composition of PM10 changes by region and that th e distribution and ranking as sour ces of wild fires, road dust and EGUs would vary by region.

90Page 2-18, Paragraph on Cardiovascul ar Morbidity: There is an issue here in that using 1 year data for classifying exposure doe sn’t make biologic sense for a ch ronic effect. It needs to be made clearer that the 1 year figures are “ surrogate s” for long term exposure (over several years).

Page 2-23, Section 2.3.3.: This section coming afte r the Chronic effects s ection above needs to

be clarified that all the effects assessed in table 2.1 are in fact acute (or semi-acute) effects. Although the table indicates inadequa te data for a relationship to cancer there is no discussion in

the text. In addition the newer data from ACS would suggest that the classification might be moved up a notch to suggestive.

Chapter 3 General Comment: The authors of this chapte r have done an exceptional job in summarizing a large body of data and presenting in a readable fa shion that makes a very reasonable logical case for the factors that move particles from source to measuring sites, incl uding factors of size, chemistry and transport. Trends over time alt hough not large are impre ssive. Perhaps more

could have been included on the effects of wind direction, although I doubt that much useful data

is available that would alter conclusions reached. Th e last few sections of this chapter that relate to estimates for human exposure and population or community effects are logical and well summarized. I personally would have like to have seen a little more in interpretation of the directionality and factors affec ting the directionality of the su rrogates used to estimate population exposure. What factors lead to over or unde restimation, and perhaps how results might be adjusted for these factors. Perhaps this will come up in later chapters on Dosimetry or Health

Effects.

Specific Comments: Page 3-1, line 11: The use of the word “ uncontrollable” For desc ribing background pollution

level would it not be better to desc ribe this level as “natural occu rring”? Uncontrollable could be in the eyes of the beholder, since for some th e cost of controlling could predict what was uncontrollable (i.e. Too expensive to cont rol, or technologically difficult).

Page 3-2, last line 34: Some further explanati on of the range of values at National Parks is

indicated. If the natural occu rring background is < 1ug/m3 than what is being defined as background in the range of 3-63 is clearly being impacted by long ra nge transport. This makes for a confusing definition of background. Are we saying that background is natural plus long range transport and therefore varies regi onally depending on down wind sources or is background some thing consta nt, but not achievable?

Page 3-3, line 20: Is it really seas onal differences in sources, or is it differences in photochemical activities by season. One suspects that latter, partly depending upon region where winter heating and summer cooling might result in match emissions from stationary sources and mobile sources between seasons not varying that much and dominate variable being amount of sunlight and

temperature.

Page 3-17. Paragraph ending line 15: This section provides well de scribe logic of what the FRM for PM10 is doing. However, in so doing it provides information that 50% of the particles

91greater than 10um are getti ng collected. I think some mention of an “upper limit” needs to be

indicated. Is it not the case that there is an abso lute cut off at 15 or 30um? And if so (or if not) a justification of what is getti ng through, particularly when focusing on mass, needs to be offered to deal with the mass not being dominated by these extra larg e particles.

Page 3-30, Figure 3-4. Need to change monitor indi cator from rectangle to circle, if I am reading figure correctly. Ditto figure 3-5.

Page 3-32, Tables 3-3 and 3-4: Need to provide footnote as to why data are “na” for New York City.

Pages 3-40 to 3-46. These pages contain a series of tables and figures that indicate the

distributions of PM measures across the 15 sites over the 3 year period. Although the reader can

look at these tables ad draw their own conclusi on, text contained that describes them does not indicate any particular finding. It simply describes what is in the tables. I would have thought that some summaries in text would be appropria te (like the 75%tiles are all above the annual standards or although some values exceed 1000 ug/m3 at the max, the 95%tile do not ever exceed 60ug/m3 for the 3 years 2005-2007 or Phoenix and Denver are the only cities with PM10-2.5 with annual means 20 or higher, etc). See text descriptions on pages 3-51-3-53 for Figures 3-9-3-13 which give a much better assessment of what is presented.

.Page 3-87, Figure 3-42. The text indicates that this figure is to be replaced. I look forward to seeing the replacement, particularly because this figure and the accompanying text to my mind is

critical to our understandi ng of the effects of distance from sour ce, particularly as related to road traffic for ultra-fine particles.

Page 3-109, Figure 3-58. T ypo in Vertical Axis.

Page 3-130, Figure 3-70. Should this be divided into two figures (i f data exist) since there is a real mixing of children, who contribute almost al l of the in school time, with adults who are more likely to be out and about or indoors in a different setting?

Page 3-132, after line 5: A furthe r conclusion here would be useful . If ambient concentration is better than personal exposure as a surrogate for ambient exposure is ambient exposure less likely to over or underestimate true exposure. Maybe th is will come up in the ne xt section, but with the relatively high correlations in table 3-27 some statement is necessary. ADDED note after page 3-160. This section is well written and summarizes well the issues needed to be considered. However, I would stil l like to see a more inte rpretive statement of the

bottom line. Do ambient measures over or unde restimate population human exposure and if so

in what direction and under what circumstances or what influences the direction of the over or

under estimation?

Page 3-168, line 7: Is this last sentence true for all regions? I would have thought that broadly in the Midwest or western plains we know more about PM10-2.5 as indicated in some of the

tables.

92Chapter 5

General Comment: This chapter presents a number of mechanisms of injury but does not appear to be presented in an even fashion. In some cases the mechanism is being discussed from a basic pathophysiologic perspective with no particular relation to PM expos ure, in others it is more focused on the effects of PM. I think this is ok, since in the next chapter it has been promised that the focus will be on PM. This might be help ed by some cross referencing on the last 2 pages where there are a number of bullets (some of whic h could be combined) with added references to places in Chapter 6 and 7 where they are discus sed. One issue that seems to be missing (and may be missing from the subsequent chapters) related to potential reproductive outcomes. Although there is not a lot of data there are severa l studies pointing in this direction so potential mechanisms probably should be considered.

Chapter 6

General Comments: Reasonably well done job of inte grating toxicology, human studies and epidemiology for each of the exposure scenarios discussed as well as for each of the outcomes of interest. However, the text gets overwhelming when it gets to the summari es. The initial parts of presenting the level of causal certainty is fine, but then the details prov ided on the various discip lines data (epi, human clinical, and tox) seem to get somewhat contradi ctory. For example, the discussion of short term respiratory morbidity general conclusion seems to be contradicted with di scussions of specific symptoms or pulmonary function, which does apply to all groups equally. Surely that is not the place to be bringing out the subgroup variation, unle ss the purpose is to confuse the reader. It is also quite redundant as all of the details are previously discussed in the chapter. I would have left more of the toxicological studies in the appendix only.

Specific Comments Page 6.3, paragraph beginning line 11: This is an appropriate discussi on of time-series, but somewhere in the paragraph it needs to be stated more explicitly that there is generally a relationship between PM and morta lity that is seen in these studi es. Then it becomes appropriate

to discuss the statistical issu es and issues of threshold

Page 6-4, line 23: Should this be “linear non- threshold”?

Page 6.7, line 11: Subtle, but would change “do” to “may”

Page 6-18, line 30: The reason one expects a dec line in HRV with exposure is because of the Framingham data that suggests lower HRV pred icts CVD. However, there are some who suggest that change in HRV in either direction represents a response. See top of page 6-21 on animal studies. It therefore may not be a ppropriate to call the response “inconsistent”.

Page 6.24, line 11: typo; ditto line 12

Page 6.28, line 5: “ discrepancy” is a value judgment that would appear unnecessary. I would suggest something like variability in the several studies.

93Page 6-54, lines 12 and 14: Please check whether 100ug/m3 is correct. (Would have thought it should be 10ug/m3.)

Page 6.85, line 19: Issue with the word “consiste nt” In fact looking at fi gure 6.2 the results is really quite consistent. All but one show a positive effect, albe it that not all are statistically significant. With the subsequent data on heart fa ilure admissions and ER visits it I suspect the summary could be a little more positive than as expressed.

Page 6.88, line 23: I would agree with the conclu sion as written but it begs the question of what is the summary of the ambulatory arrhythmia data. Will this come up later? If so probably

should indicate to be discussed in secti on 6? If not should be discussed here.

Page 6.90, line 27 end of summary. There is a part icular issue with rega rd to stroke. Some comment need to be made that the appropriate lag structure is simply not known. The 0-2 days may not be appropriate as the onset of symptoms may be much longer than is reflected in

administrative data bases on date of admission. Most of the studies ci ted do not include any specific query about symptom onset. This is pa rticularly true for the embolic disease which make up about 80+% of the events and in which th e events are likely to be acute than for the hemorrhagic strokes.

PAGE 6.94 SUMMARY: Logic well presented with discussion of toxicological data to support

mechanisms for the conclusion of likely causal

.

6.94, line 26 to end of 6.96: this section seems out of place. It is a summa ry of the details used in the second paragraph on page 6.94 and therefor e might all come before the last paragraph on page 6.94 (which is the conc lusion for the section on PM10.

Ditto next several sections.

Page 6.93, Section 6.2.11 Su mmary and Conclusions

Pollutant Chapt statement Reviewer position PM10 Likely causal agree PM2.5 Causal agret PM10-2.5 Inadequate evidence +/- agree Ultrafine Inadequate evidence agree Because PM2.5 is contained in PM10 and partic ularly because PM10-2.5 in inadequate some

discussion need to be here as to what th e evidence is that makes PM10 likely causal separate

from effects of PM2.5. Even is the argument is that for many of the studies it is the only data we

have. Further at least for Ultr afine, (and perhaps for PM10-2.5 it n eeds to be stressed that it is the lack of sufficient study rather than either in consistent studies or clea rly negative studies.

Respiratory effects Figure 6.5 and 6.6 and Table 6.7: Although all the info rmation is in these figures and table, (and is given in the text) it is somewh at frustrating in that I would like to see the odds ratios along side the pollution measures. How to do this? Maybe it is done in the Appendi x and I will check. If there however, a cross reference is necessar y. If not, it probably ought to be there.

94Page 6.117, lines 18-22: Potential problem in that the mass data for PM 2.5-.01 contains all of the

count data NC .01-.1 . Therefore the attenuation would be e xpected. This is hinted at in the

statement that the correla tions with the gasses is high but probably needs to be better spelled out.

Page 6.124, line 2: typo; ditto page 6.134, line 4

Page 6.152, line 5-6. The entire tox section (now th at it is written) probably could have been a

lot shorter. It reads too much like the old CD, and the writer coul d have been asked to shorten. As indicated here much of the tox material pres ented was done at high doses. And thus is less

relevant and therefore rele gated to the appendix. .

Figures 6.9-6.11. I find it useful in these figures to have provided the range of estimates from the 2004 CD. However, in presenting these indivi dual and multicity studies for the most part there is an overlap with 1 as presented? I assume there will be a combined risk assessment analysis presented in subsequent document but it would be useful to have it here as well.

Several of the figures: May want to put into the legend of these figures that they are expressed

as Excess Risk % (if that is what they are)!

Page 6.182, line 8. This sentence needs to be quali fied. It appears to apply only to asthmatics and the elderly. Summary and Conclusions

Pollutant Chapt statement Reviewer position

PM10 Short term Respiratory Morbidity likely causal agree PM10-2.5 Short term Respiratory Morb idity suggestive of causal agree PM2.5 Short term Respiratory Morbidity likely causal causal Ultrafine Short term Respiratory Morbidity inadequate evidence +/- agree PM CNS Symptoms or Disease inadequate evidence agree

PM10 Short term mortality likely causal agree PM2.5 Short term mortality likely causal causal PM10-2.5 Short term mortality suggestive of causal* +/- agree Utrafine Short term mortality inadequate evidence agree

* Might take issue with fact that although fewer studies, with regard to cardiovascular disease the measure of PM10-2.5 appear to be where PM2.5 were in 2004 and might move up to likely causal with a few more studies. (not likely to go the other way).

Page 6.247, Table 6.16 starting this page I do not find this a very useful table as a summary of Epidemiologic Studies for source apportionment. First many of the studies report ed are not epidemiology (e.g. the first one is mice). Second there is lots of NR or na reported in the table. I do not get the message from the table. Suggest redue more specifically or leave out.

95Chapter 7 General Comments: There are several difficulties with the way results are presented in this chapter. First of all most of the contrasts in exposure that are di scussed are presented as increases in pollution when in fact they are not increases but differences between regions. Secondly and perhaps more important results are reported as differences in hazard ratios or rates, albeit mostly with c.v.s given, that can only be described as null effect s. This is carried throughout the presentation of the in dividual outcomes. In particular this relates to intermediate outcomes related to CVDs. In fairness generally there is a summary statement at the end of the

section that indicates the author recognizes this but it needs to be part of the description of the results rather than what appears to be a pushing of the results. To anticipate what is coming it might also be discussed as to the role of th ese intermediate outcomes in the process of identifying health outcomes. If anything there is a prior that is menti oned early on that chronic inflammation is a major pathogenesis pathway. In fact since the markers used for estimating this effect are not related to air pol lution, it suggests that some othe r alternative mechanisms should

be invoked.

Specific Comments: Page 7.1, line 1: Minor point. S hould the order be changed in this sentence?. The chapter reviews, integrates, and summarizes rather than summarizes first.

Page 7.2, line 12: I am not sure that all would agree with this. Chroni c inflammation may be a component of Atherosclerosis but certainly is not the sole cause.

Page 7.2, line 24: Define CAC if first time used.

Page 7.2-7.3: Although useful to defi ne the clinical tools used to a ssess atherosclerosis, what is missing is the any quantitative assess ment of the coefficient of variat ion of theses tools. This is particularly important since the ne xt sections indicates small diffe rences resulting from deltas in PM of 10ug/m3..

Page 7.4, two paragraphs. There is something terribly wrong between these two paragraphs. The magnitudes of the deltas in the first paragraph are virtually zero and none are significant. To

discuss them as “increases” is l udicrous. On the other hand delta s in the second paragraph are 50 to 100 times higher and are signific ant, albeit the PM measures are different. Is there a decimal point error in one or the other?

All of the epidemiology section on Atherosclerosis: This entire section needs to be rewritten. Except for the one study from Germany all of the other data presented is definitely null. To describe any of the findings as showing “increases” “associations” etc. is misleading the reader. In addition, since these are cross sectional studies to describe differences in PM levels as

increases in also not correct.

Page 7.9, line 13: change “i ncrease” to “difference” Page7.15, line 13: again change increase to difference

96SAME PAGE, In line 15-16 in contrast to line s 13-14 is the reference to NON-FATAL CHD or MI? Otherwise these are two opposite statemen ts about PM10. Alternatively, one statement may be about PM10 and other PM2.5. Please check. Line 23, again change increase to difference Page 7.17, line 6: ditto Line 13-15: Two problems. What does it mean af ter adjusting for clinical characteristics to not find a prevalent difference in CHD? If one of the clinical characteristics is prevalence of disease this is what would be expected. Second the deltas reported with the c.v. give n are really null. To describe them as difference is misleading. Line 21: Again, these findings are null. (Alternativ ely to be consistent with the way others are being reported one would say that a 10ug //m3 difference in PM was protective! Lines 28-29: What does this mean given the previous sentences reflects a null?

Page 7.18, line 20: Don’t need OR and % di fference. (They are the same numbers) Page 7.21, line 4-5: This conclusion needs to re visited. Most the studie s reported are in fact null, albeit that they are in the direction that might lead to this conclusion. The important issue is

that the direction of the effects is supported by the toxicological work. This needs to be factored in, somehow, to the logic that allows th e author to reach this conclusion.

Page 7.32, Figure 7.4 As presented th is figure is more confusing th an enlightening. It mixes up both cross sectional effects with longitudinal change . It is not clear what arrows going in both

directions means. The text that describes some of the finding is much clearer. I would recommend leaving Figure out or expanding grea tly and perhaps even making it into multiple figures.

Page 7.33, sentence beginning line 1. Not clear what is meant by pulmonary function in first year of life, surely no t the measure reported. Paragraph beginning line 16. Not clear how exposure in 1 st and 2 nd trimester is separated from

3 rd trimester. Summary results

Pollutant Chapt statement Reviewer position PM10 Long term CVD morbidity suggestive of causal agree PM2.5 Long term CVD morbidity likely causal agree PM10-2.5 Long term CVD morbidity inadequate evidence for yes or no agree Utrafine Long term CVD morbidity inad equate evidence for yes or no agree

PM10 Long term Respir Morbidity likely causal agree PM10-2.5 Long term Respir Morbidity No da ta for conclusion on causality +/-agree PM2.5 Long term Respir Morb idity likely causal causal Ultrafine Long term Respir Morbidity inadequate evidence suggestive

Section 7.4.2 Toxicology of reproductive outcomes. Mu ch of this could have shortened or left to the appendix. As indicated before this section none of the mech anisms seem applicable to the epidemiologic findings. Therefore it seems the de tails of the toxicological data are not really helpful and just makes the chapter too long.

Pollutant Chapt statement Reviewer position

97PM10 Reproduct & Developmental suggestive of causal agree PM10-2.5 Reproduct.& Developmental inadequate evidence agree PM2.5 Reproduct & Developmental suggestive of causal agree Ultrafine Reproduct & Developmental No da ta for conclusion on causality agree

Section on Cancer: This section is extremely disappointing with re gard to the presentation of the epidemiologic data. The author seems much mo re comfortable presenti ng a discussion of the toxicology, carcinogenesis and mutagene sis even to the poin t of discussing in vitro studies. The epi is extremely naive. For example, on Page 7.87-88, Paragraph on Breast Ca and TSP: These data are presented in a crude fashion with out discussion of possible confounders. The ORs are in fact considerable higher than any reported with smoking, where the ex posures to potentially toxic agents are considerably higher than might be seen from environmental TSP. A more careful reporting therefore is wa rranted. Further there is no di scussion of any other studies. This appears to leave out the Pope analyses of the Amer Cancer Society study, which does

indicate a rather well co nfirmed risk about a 40% excess risk of total cancer with higher risks for lung cancer.

I would therefore disagree with the summary of inadequate data for an estimate of causality. I would suggest at l east suggestive.

Page 7.117, sentence beginning line 7: This needs to be reworded. The fact that the new studies

focused on CVD effects rather than respiratory effects doesn’t make the respiratory effects any less important (except there are le ss of them). I think the aut hors know this but the way they have said it reads as though a change in thinking has occurred. This will come up again in next chapter.

Pollutant Chapt statement Reviewer position PM10 Overall Chronic mortality suggestive of causal* likely PM2.5 Overall Chronic mortality likely causal agree PM10-2.5 Overall Chronic mortality inadequate evidence +/- agree

Ultrfine Overall Chronic mortalit y not considered suggestive *Might be argued that there are su fficient evidence to raise to likely

Chapter 8

General Comment: The authors have effectively laid out the poten tial susceptibility and vulnerability characteristics and then systematically discussed each. One might take issue with the conclusions that almost in every case because there is some inconsistency in the results reviewed th at the uncertainty that results leads to the position that more research is needed. Albeit it true that should not leave the document without indicating more or less to what degree the argument is made. In fact in most cases the reasons the particular characteristic is on the list is because there are some groups in which there is more than chance operating that a particular subgroup is more susceptible or more vulnerable. Chapter needs a c oncluding summary paragraph.

Specific Comments:

988.14, line 5: This statement may be true for “in a ssociation with exposure to PM” but is not true as stated in general. Clearly those with COPD are more suscep tible to exacerbations of COPD. Suggest qualify sentence more specifically.

99Comments from Dr. Helen Suh MacIntosh

Question 1: The framework for causal de termination and judging the overall weight of evidence is presented in Chapter 1. Is this framework appropriately applied for th is PM ISA? How might the application of the framework be improved for PM effects?

The two-step framework for causal determinatio n and weight of evidence is sound and is appropriately adapted to PM by allowing this fram ework to be applied separately for different sized particles (PM 10 , PM 10-2.5 , PM 2.5 , and ultra-fine particles), different adverse health/welfare outcomes, and short and long-term exposure periods. Although implicit to this framework, the explicit consideration of causal ity by major particle sources or components should also be considered, even though there is currently insufficient evidence to make any determinations. In addition, there should be some integration of evid ence across particle size s as well, especially given that PM 10 includes PM 2.5 , PM 10-2.5 , and ultrafine particles a nd that many recent health studies (especially of intermediate health markers) no longer examine PM 10 by itself. In this regard, it may be preferable to incl ude discussion and consideration of PM 10 after that for PM 2.5 and PM 10-2.5 , with findings used as evidence in s upport of or contrary to those for PM 2.5 and

PM 10-2.5 . Else, causal determinations for PM 10 should be made in part based on determinations

for PM 2.5 and PM 10-2.5 . This reorganization may help to explain apparent inconsistencies in causal determinations (as discussed further below).

Question 3 : To what extent are the atmospheric ch emistry and air quality characterizations clearly communicated, appropriately characterize d, and relevant to the review of the PM NAAQS? Does the information on atmospheric sciences and exposure pr ovide useful context and insights for the evaluation of human he alth effects of PM in the ISA?

a. Is accurate and appropriate information prov ided regarding PM source characteristics, techniques for measuring PM and its co mponents policy-relev ant background PM, and spatial and temporal patters of PM concentration? Are the a nalyses and figures presented in Chapter 3 effective in depicti ng ambient PM characteristics?

Chapter 3 presents PM composition, sources, an d spatial and temporal trends for PM, its associated size fractions and its major compone nts in a clear, concise, and well organized manner, with trends shown for different spa tial (neighborhood, urban, regional and global) and temporal (hourly, daily, and yearly). Specific comments are below:

• For clarity all figures and tables should explic itly state the averaging time of the measured

concentrations.

• As was done for PM 10 and PM 2.5 , maps illustrating the location of speciation monitors relative to population de nsity should be included, although perhaps just in Annex A.

• A table showing a summary of the exposure-relate d factors for each of th e selected 15 cities should be added. These factors may include pop ulation density, number of large stationary PM sources, some metric of traffic conges tion, percent of populati on living within 100 meters of a busy road (e.g., class A1 or A2), pe rcent of people living in apartments or single family homes, and central or room AC prevalence.

100• The Figures 3-14 through 3-18 were very informative and effectiv ely showed the variation in

PM 2.5 composition by region and by season; it woul d be helpful to have the sample sizes noted somehow as it would help determine the comparability and robustness of the city-tocity comparisons. The discussion of how co mposition may vary within a city and near sources should be expanded.

• Although noted, interpretation and discussion of Figure 3-43 should em phasize that even though neighborhood scale variability in PM 2.5 was rather low, it may not be the case for

PM 2.5 components, as concentrations of locally generated components, such as EC, have been shown to vary substantially over very s hort distances. The implications of spatial variability in the components to the interpretation of epid emiological studies should be explained.

• Diurnal variation in hourly EC, OC, SO 4 2- and other major particle components should also be presented and discussed, especially in rela tion to particle number concentrations.

• It would be interesting to include some discussion or gr aphic of sites that are in violation of the annual but not 24-h NAAQS for PM 10 and PM 2.5 , specifically related to whether these sites exhibit a seasonal or spatia l daily concentration pattern.

• Although introduced in Section 3.5.1.3 and discus sed later in 3.7.2.3, methods used in source proximity studies, such as land use regression models, should be mentioned in the section Estimating Source Contributions to PM (Section 3.5.4)

• The discussion regarding PM 10-2.5 measurement devices should be expanded, especially with regard to the precision of various methods (including difference, flow rates, etc.)

• Composition of PM 10-2.5 should be discussed.

b. Is the evidence relating human exposure to ambient PM and errors associated with PM exposure assessment presented cl early, succinctly, and accurate ly? Are there PM exposure issues that should be expande d, shortened, added or removed?

While relatively complete, this section is genera lly not as cohesive and clear as the previous section. It would benefit from an upfront sectio n that briefly introduces the concept of exposure, its relation to ambient levels, and its importance in the interpretation of ambient concentrations

and health risks. This introduction could then be followed by a brief description of the sections or discussions to follow. In addition, for consis tency it would be preferable for this section to follow the pattern established in other parts of the ISA, with each topic discussed for each PM size fraction (e.g., PM 2.5 , PM 10-2.5 , PM 10 , ultra-fine particles, and co mponents) and also for acute and chronic averaging periods. Alternatively, the exposure s ection could follow the general structure of the Human Exposure section in the Conclusions (Section 3.8.2) , which is very clear, well written, thoughtful and concis e. In addition, the section a ppears to focus primarily on PM 2.5 measured over 24-h periods (although the specific PM size fraction is often not mentioned). It would be preferable to include eviden ce or information of exposures for PM 10 and PM 10-2.5 as well and also for PM exposures (of all size ra nges) measured over shorter and longer time periods.

Specific comments are below:

101• Page 3-131, lines 7-3-132 is too complicated, long, and confusing. Its main points are important, making their clear and simple discussi on even more necessary. It is possible that this section is misplaced, adding to the confusion.

• Section 3.7.2.3 PM Exposure Modeling should include a discussion of time-weighed microenvironmental models and GIS-based spatial smoothing models.

• The section entitled “Outdoor Exposure to Loca l Sources” is misplaced and should be moved

to Section 3.5.4.

• Figures 3-74 and 3-75 should be clearly anno tated with regard to the location, study population, and time period of the study

• Section 3.7.4 Exposure Assessment and Socioeconomic Status is misplaced and should be

moved to the Section 3.4.2.2.

c. To what extent does the Panel find Annex A appropriate, adequate, and effective in supporting the ISA?

Annex A contains a voluminous amount of data, which takes away somewhat from its effectiveness. Further, several figures and tables are contained in both the ISA and in the Annex, probably mistakenly, but they should only appear in only one place. Regardless, the Annex adds important, supporting concentration and exposure information to the ISA. Figures that could be

condensed into tabular form include:

• city-specific maps of monitoring site by population density and SES, which while beautiful are numerous; data could be placed into a single table each for the PM 10 , PM 2.5 and speciation monitors.

• city-specific PM 2.5 composition pie charts, with data ex pressed in the table as a range if there are multiple pie charts for a given city

To help sort through the data, it may also be important to cate gorize findings further. For example, studies summarized in Section A.4.1 Exposure Assessment Study Findings should be grouped first by general topic area and then sorted al phabetically by last name of the first author.

Question 7: Strength, consistency, coheren ce, and plausibility of eviden ce for health effects of

PM?

The chapter on chronic health impacts should disc uss the relation of chro nic and acute impacts, for example whether they occur via similar or different biological pathways. The causal

determinations for the various PM measures are appropriate and s upported by the available scientific evidence. Some allowance may be necessary for determinations of causality for PM 10 either now or in the future, as an increasing number of health studies appear to no longer

examine the health risks associated with ambient PM 10 . As a result, additional evidence of

PM 10 -associated acute or chronic health impacts ma y be difficult to obtain or may have to be pieced together from PM 2.5 and PM 10-2.5

.

As mentioned above, causal determinations for PM 10 are not always the same as those for its size fraction groups, PM 2.5 and PM 10-2.5 , which can present seeming incons istencies. For example, if

short term effects of PM 2.5 are causal with relation to cardi ovascular morbidity, why isn’t the

102same determination made for PM 10 given that (1) PM 2.5 generally comprises a substantial

fraction of PM 10 and (2) correlations between 24-h ambient PM 10 and PM 2.5 tend to be strong. The practical implications of this and othe r seeming inconsistencies should be noted.

103Comments from Dr. Sverre Vedal

For each chapter, numbered points that are consider ed to be more major, general or substantial are followed by a subsection of more specific points.

Chapter 1. Introduction.

1. Organization . The flow of topics is generally good, but there are some places where consolidation and change in ordering might help. Examples: 1-15, line 21. This starts the discussion of conf ounding, but this is continued and completed only later (line 33 and p. 1-16) af ter it is interrupted by bri nging up the notion of effect modification. Line 25 starts a listing of th e “multiple ways” PM can be associated with outcomes, but only lists three ways . There are other ways of gett ing a spurious association: e.g., any number of non-pollutant factors that are associated either in space or time (depending on the study design) with PM. [By the way, I’m not sure effect modification has a place in a discussion of causation. Also, the definition of effect modification here is awkward and weird - effect modification simp ly means that exposure effects differ across some subgroups or strata of the population.] 1-16, line 32. The measurement error discussi on here should follow immediately after the multi-pollutant modeling discussion (line 11, et c.), rather than being interrupted by a discussion of stratified analysis.

2. Causality criteria and grades (Table 1-3). i. Although the Hill criteria probably need to be brought up, they have limited utility, as evidenced by all of the qualifie rs in the description of each cr iterion. The desire to avoid “criteria” is understandable, but replacement with “aspects” (1-18, line 8) is awkward – how

about “characteristics”? “corollaries”? ii. The weight of evidence grades (1-22) ar e problematic. Some suggestions: 1) drop “reasonable” as a qualifier to conf idence for the causal grade – “reasonable” to me is not strong enough to allow a categorization of causal; 2) I’m not sure I see much difference between “likely” and “suggestive” here; 3) why is there no “not causal” or “likely not causal” category vs. “suggestive” of not causal only? i.e., there is no symmetry here. In genera l, I don’t think there’s much to be gained by trying to make these grades parallel the 5-level categories of EPA Guidelines for Carcinogen Risk Assessment (footnote 1-21). iii. See 3.ii, below.

3. Things not discussed

. i. It is important in this ch apter to bring up publication bias : how it happens, the evidence for it, its impact on both the assessment of causality and the exposure-response relationship (slope and shape), and how it’s countered.

ii. There are also other soft criteria that have been floa ted recently (e.g., the Ioannidis series of papers) that highlight features influencing whether published findings turn out to be true; these could bear on our assessment of the published scie ntific literature (i.e., the literature being evaluated here) and the determination of causality . A few points that should increase suspicion and vigilance: small effects si zes, large number of potential comp arisons, flexibility in outcomes

104and modes of analysis, potential for conflict of in terest, a “hot” scientific field. I bring this up with some hesitation, but decided in favor of it when I again noted the many instances in the air pollution health effects literature where this perspective might have merit.

iii. What is the solution? Replication of specific findings is important and should be heavily weighted. To avoid selective re porting of positive findings, an attempt should be made to report and compare all findings (all exposure periods and lags, all endpoints, all subgroups, etc.), although this is admittedly a tall order.

Specific

. 1-12, line 17. It is not clear th at the type of important evid ence would vary by pollutant – it

would if this were based on the availability of evidence for di fferent pollutants, but I would think the important evidence shoul d be pretty much the same. 1-12, line 23. Sometimes there can be an inte rvention in observationa l studies: e.g., vitamin interventions with ozone, or fish oil with PM. 1-12, line 29. Toxicology studies are also useful in enhancing pl ausibility of exposure effects. 1-13, line 7. The definition of c ounterfactual is vague. We are concerned with exposure. We observe what happens with exposure; a counter factual is what we observe happens when there is no exposure, al l else being equal. 1-15, line 15. While this is true, clinical studies also have the pot ential of overestimating effects when exposures used (concentration or intensit y) are seldom experien ced in the real world. 1-16, line 15. “discongruities?” – the meaning is opaque here. 1-18, line 16. It’s not clear how analogy w ould not apply to the gaseous pollutants. 1-20, line 5. Coherence also refe rs to comparison of effects across study designs and across study endpoints. 1-20, line 27. I would argue that not meeting th e temporality criterion, when it can be assessed, rules out causality. 1-23, line 1. I don’t know what the authors are ge tting at here in comparing incidence and severity. 1-25, line 3. This discussion is unclear. If the point is that es timated mean population effects do

not reflect more extreme effects in individuals that would be more clin ically relevant, then please say that. If that is not the point, start again.

Chapter 5. Modes of action.

Figure 5.5. The emphasis here is on initial pulm onary oxidative stress and inflammation which “spills over” systemically. There should now al so be an arrow going directly from autonomic modulation to systemic oxidative stress and inflammation, based on the Gonzalez-Flecha work.

Chapter 6. Acute health effects

.

1. Selective highlighting of positive results (a perennial issue); see C h.1 comments (point 3.iii). In the review of individual study findings, as in previous CDs, there continues to be an obvious tendency to report the positive findi ngs, even though these might be one of among several endpoints. For example, in the review of controlled human exposure studies on HRV,

105findings from some generally negative studies (P eretz, Gong [6-18, line 23), etc) are summarized by highlighting the one or two positive findings selected from a host of the many possible findings from among the many time windows in which HRV was measured and the many HRV measures that were analyzed. One flagrant example of this tendency is the summary of the Diez-Roux MESA study of CRP (6-52, line 28) which found no PM effects for lags up to one week. When the averaging period was extended up to 30 or 60 days, a small effect on increased CRP was observed. Effects observed over those long averag ing periods are probably uninterp retable, however. This is reported as a “positive” study in the ISA. This finding is highlighted in the section summary (6- 103, line 8). Here the result was ch aracterized as being “stronger” at these long averaging times, when in fact it was only pres ent at these averaging times. Having said that, compared to earlier CDs, a better job is done in the ISA of summarizing effects on a comprehensive array of endpoints, re gardless of whether these were highlighted by the original authors.

2. In reviewing the toxicologica l findings, it might be better to distinguish instillation studies

from inhalation studies.

3. The assessments of causal determinati on (section 6.2.11; pp. 6.98-109) are not particularly transparent. For example, what specifically is the rationale for claiming a causal relationship for PM2.5, but only that such a relationship is li kely for PM10? And, why is PM10-2.5 merely

insufficient?

Specific

. 6-2, line 12. Differences in exposure measurement error may also contribute to between-city heterogeneity. 6-3, line 34. Transfer of effects is only a minor aspect of the measurement error issue in the 2004 CD, but is the only one touche d on here in this overview. 6-8, line 1. Might add how the ApoE -/- mouse model of atheroscle rosis differs from natural human atherosclerosis, eg, no co ronary atherosclerosis, etc. 6-8, line 19. There is no refe rence to the Rowan paper.

Section 6-2. I would consider including discussion of cardi ovascular mortality here, even though Section 6.5 summarizes mortality in general. 6-38, line 1. Need to include in th is summary the BAD vs. FMD finding. 6-55, line 24. Why is discussion on a study of oxygen saturation included in the section on systemic inflammation? 6-58, line 14, What is described here is not r eally hematopoiesis, simply changes in peripheral

blood cell counts. 6-59, line 18. I would say th e evidence here is limited a nd certainly inconsistent. 6-61, line 20. Although even for vWF, some epi st udies showed increases while others showed decreases. Also, only the Liao 2005 study is referred to, not the 2004b or 2007). 6-83, table 6-2. The PM2.5 MI Zanobetti a nd Schwartz reference should be 2006, not 2005. 6-88, line 13. How “more successful?” 6-106, line 3. It seems that the Mills (2008) study of DE that wa s almost entirely UFP should be included as a human clinical study here.

1066-109. I suggest that a section on PM chemical components (i.e., 6.2.11.5) be included here in addition to just sections on the PM size fract ions, although that is presented late in the chapter. 6-110, Table 6-5. I would not include the 1999 and 1998 studies of Boezen and Forsberg in this

table. This table is for more recent studies. 6-112, line 4. Should be Table 6.7, not 6.6. 6-215, line 19. PM10 findings were not robust to NO2 in the Canadian multi-city study (6-206, line 27). 6-225, line 26. Regarding Villeneuve 2003, this is not a cohort. Line 29 indicates a 5.4% increase in CV mortality for same day lag, but Fig 6-24 instead shows the lag 1 effect. Also, as opposed to what is stated, the PM2.5 effect is not quite significan t (see Table 4 of the Villeneuve 2003 paper). For Fig 6-23 regardi ng PM2.5, for total mortality at same day lag, the effect should be negative (Table 3 of V illeneuve 2003), for CV mortality for lag 1 the effect should be at least as negative as - 1.0%, and for respiratory mortality for lag 1 the graphed effect looks close to 3%, but this is not correct ei ther. I would recommend checking

the math that converts to the 10 μ g/m 3 increment and ensure that the graphed effects are

correct. 6-251 (section 6.6.2.4). Several of th e toxicological endpoints descri bed here are associated with long-term exposure and belong in Ch.7 only.

Chapter 7. Chronic health effects

.

1. This chapter presents a reasonably balanced presentation of findings, with exceptions. The

cardiovascular and birth outcomes sections ar e particularly good in this regard.

2. Regarding birth outcomes, specifically, one poin t that I did not see a discussion of was the potential for confounding by season. Air pollu tion and birth outcomes vary by season. Matching on time of the year of birth, for exam ple, does not adequately address this. In both

cohort studies and studies that us e birth certificate data, the proper controls for preterm births, for example, are not births occurring at the same time of the year as cases, but rather gestations of approximately the same duration. The influence of this potential source of confounding needs to

be considered for the relevant studies.

3. The Respiratory Effects section (7.3) is an exce ption to the generally ex cellent nature of this chapter. There is a tendency to report prim arily positive endpoints from studies with multiple endpoints, as well as a tendency to report as pos itive findings that are unquestionably negative; e.g., p.7-28, line 33 on asthma in the Kim 2004 st udy. The Pulmonary Function (7.3.2) section, especially, is poorly written and presents extr aneous information (e.g., Oftedal study description p.7-33). Unjustified claims are made; e.g., about l ack of reversibility a nd about the meaning of different lung function measures (p.7-34, lines 18-21). There is too much relaying of individual authors’ interpretation of their own findings. Unjustified summaries are made; e.g., Pulmonary Inflammation (p.7-50), especially regarding woodsmoke effect s (line 22). The overall conclusions regarding causality in this respiratory section, however, are reasonable.

107108 4. My preference would be to include discussion of cohort studies that include cancer mortality endpoints (eg, Pope 2002) in the se ction that is currently limite d to cancer incidence (section 7.5), rather than placing th at discussion in the foll owing section on mortality.

5. Regarding mortality, an exampl e of how further analyses modi fy initially-reported dramatic findings is provided by the Beelen 2008 study of tra ffic-associated mortality in the Netherlands. Effects were dramatically lower than those estimated based on an ear lier portion of the cohort (Hoek 2002). The Beelen study sugges ts that traffic-associated e ffects may not be greater than those due to PM itself, a finding at odds with that in the initial report. This perspective is not provided here, but is appropriate in a discussion of source- and co mponent-specific effects. On another issue relating to mort ality, section 7.6.7 on exposure ti me windows does not include the Krewski et al assessments on this question using the ACS cohort.

6. I would dispute that an expe rt elicitation provides much if any additional evidence or support (7-115, line 18).

Specific

. 7-4, line 11. It is not appropria te to report estimated increases in CAC here in the Diez-Roux study as if these were meaningful, in light of the wide CIs that esse ntially center on 0, or no effect. At the least, these s hould be reported as null findings. 7-16. It is not clear why Tabl e 7-1 shows only some selected endpoints, eg, for Puett et al. 7-21, line 9. “Modification” does not belong here. 7-32, Fig. 7-4. MMEF is synonymous with FEF25-75.