August 5, 2009

MEMORANDUM

SUBJECT: CASAC Review of Integrated Science Assessment for Partic ulate Matter: Second

External Review Draft

FROM: John Vandenberg, Ph.D.

Director

National Center for Environmental Assessment Research Triangle Park Division (B243-01)

TO: Holly Stallworth, Ph.D. Designated Federal Officer Clean Air Scientific Advisory Committee EPA Science Advisory Bo ard Staff Office (1400F)

The Integrated Science Assessment for Particul ate Matter: Second External Review Draft (ISA) prepared by the Environmental Protec tion Agency’s (EPA) National Center for Environmental Assessment – Research Triangle Park Division (NCEA –RTP) as part of EPA’s ongoing review of the National Ambient Air Qua lity Standards (NAAQS) for particulate matter (PM) was released on July 31, 2009. This second external draft ISA will be reviewed by the Clean Air Scientific Advisory Committee (C ASAC) PM NAAQS Review Panel (the CASAC PM Panel) at a public meeting to be held in Chapel Hill, NC on October 5–7, 2009. The purpose of the ISA is to identify, eval uate, and summarize scientific information on the health and

welfare effects associated with PM. The ISA is designed to “accurately reflect the latest scientific knowledge useful in indicating the kind and extent of identifiable effects on public health which may be expected from the presence of [a] pollutant in ambient air” (Clean Air Act, Section 108; 42 U.S.C. 7408). I am requesting that you forward the second external draft ISA to the CASAC PM Panel to prepare for that review.

This second external review draft ISA includes revisions based on the comments and advice provided by the CASAC PM Panel and the pub lic on the first external review draft ISA. In addition, we have incorporated informati on on policy-relevant stud ies published since the

release of the first external review dr aft ISA (December 2008) through May 15, 2009. Changes

to the content and structure of the draft are desc ribed on a broad scale in the list below together with the new charge questions for this CASA C PM Panel review. Specific revisions to the

second draft PM ISA are described in more detail in EPA’s recent response to the CASAC letter regarding the first draft PM ISA. We have carefully consid ered all of the comments provided by the CASAC PM Panel members and the public in creating this second draft ISA. The comments received on the first draft PM ISA, as well as recent CASAC comments on a first external review draft Carbon Monoxide ISA (March 2009), have been extremely useful as we continue to refine the development of the ISAs under EPA’s re vised process for review of the NAAQS.2 This second external review draf t ISA integrates the scientific evidence for review of the primary (health-based) and s econdary (welfare-based) NAAQS for PM and provides findings, conclusions and judgments on the strength, coheren ce and plausibility of the evidence. The draft ISA is supported by six Annexes that provide more comprehensive and detailed information on

the relevant evidence available fr om the disciplines of atmosphe ric sciences and human exposure (Annex A), dosimetry (Annex B), clinical studies (Annex C), toxicology (Annex D), epidemiology (Annex E) and source apportionment health studies (Annex F). These Annexes are provided with the ISA for the Panel’s information. The CASA C PM Panel is being asked to

review the draft ISA. NCEA-RTP will also address comments received on supporting material in

the Annexes to the extent that Panel member s wish to review and provide comments on the

Annexes.

Following the review of the second external review draft ISA, NCEA-RTP staff will produce a final PM ISA for release in December 2009 that addresses comments received from the CASAC PM Panel and the public. Additional steps in the NAAQS review process include the development of a draft risk and expos ure assessment (REA) and a policy assessment document. EPA’s Office of Air Quality Planning and Standards (OAQPS) will submit drafts of these documents for the CASAC PM Panel review and public comment.

Charge to the CASAC PM Panel

We are specifically asking that the CASAC PM Panel comment on the following topic areas that focus on more substantive chapte r revisions, but would also appreciate any other feedback in

their review of the second draft ISA:

1) Evaluation of the health evid ence in Chapters 6 and 7:

a) In response to the CASAC PM Panel comments about the determinations of causality for

PM 10 , we have refocused the evaluation of h ealth effects resulting from exposure to

PM 10 . PM 10 studies are now included where th ey provide insights into general relationships between PM and its effects, su ch as concentration-response relationships. Separate causality determinations are no longer presented for PM 10 ; however, PM 10 study results are considered in causality determinations for PM 2.5 and PM 10-2.5 where appropriate. Please comment on this approach to evaluation of eviden ce from studies of

PM 10

.

b) In the first draft ISA, causal judgments were made for cardiovascular morbidity, respiratory morbidity, and all- cause mortality. In the second draft PM ISA, causal judgments were made for cardiovascular effect s, and respiratory effects, using evidence from both morbidity and mortality. New sections were included within cardiovascular and respiratory effects for cause-specific mortality in Chapters 6 (Sections 6.2.11 and 6.3.9, respectively) and 7 (Sections 7.2.10 a nd 7.3.8, respectively) that draw upon the more complete discussions of this evidence in the later mortality sections (Sections 6.5 and 7.6). These latter sections continue to pr esent evidence of cause-specific mortality, as it informs the discussions and causality determinations for all-cause mortality. Furthermore, important results of analyses that examined potential effect modifiers,3 potential confounding by copollutants, PM -mortality concentration-response relationships, and the influence of different modeling approaches on the PM-mortality relationship remain in Chapter 6, Section 6.5. Considering both mortality and morbidity as part of a suite of effects, in addition to the other considerations underlying causality judgments, resulted in a change to the cau sal conclusion for long-term exposure to PM 2.5 and cardiovascular effects from “likely cau sal” to “causal.” The conclusion for cardiovascular effects with short-term exposure to PM 2.5 remained "causal." The conclusions for respiratory effects, for both short- and long-term exposure to PM 2.5 , remained "likely causal." Please comment on th e inclusion of cause-specific mortality, as part of a suite of cardiovascular and respirat ory effects, in the de velopment of causality judgments.

c) We reexamined the controlled human exposure and toxicological studi es of fresh diesel and gasoline exhaust and determined that while these exposure atmospheres contain relatively high mass concentrations of PM 2.5 , the particle number count distribution was predominantly in the ultraf ine size range. Therefore, fo r the second draft ISA, we considered the diesel and gasoline exhaust stud ies, in addition to the other considerations underlying causality judgments, when making our causal determinations for ultrafine PM exposure and cardiovascular and respiratory effects, resulting in a change from “inadequate” to “suggestive” for both categorie s. Diesel and gaso line exhaust studies also continued to be considered as part of the evidence for PM 2.5 health effects, as was

done for the first draft ISA. With considera tion of this rationale, please comment on the scope of evidence considered in the cau sal determinations for ultrafine PM.

d) The CASAC PM Panel recommended that we furt her consider the evidence related to PM exposure and cancer. Section 7.5 (Cancer) wa s revised to include evaluation of epidemiologic studies of both mortality and in cidence of cancer with exposure to PM, as well as a brief overview of the toxicologi cal evidence conducted using intratracheal instillation or dermal routes of exposure to better characterize the role of PM in mutagenicity, genotoxicity, and ca rcinogenicity. As a result of revisions to this section,

the causal determination for PM 2.5 and cancer was changed from "inadequate" to "suggestive"; the causal determination for PM 10-2.5 remained unchanged. Please comment on the expansion of this evaluation to include a summary of toxico logical studies using routes of exposure other than inhalation, as well as consideration of both mortality and

incidence studies.

2) Revisions to Chapters 1 (Introduction), 4 (Dos imetry), and 5 (Mode of Action): Changes to these chapters included expansion or clarification in a number of areas, as presented in more

detail in the recent letter from EPA’s Administra tor. These included expansion or addition of sections on the history of the previous PM NAAQS review in Chapter 1; deposition and clearance of particles in Chap ter 4; and epigenetics, lung de velopment, atherosclerosis and

consideration of acute and ch ronic responses in Chapter 5. Please comment on the revisions to these chapters.

3) Evaluation of susceptible population groups in Chapter 8: In response to the CASAC PM Panel comments, we have now focused specifi cally on susceptible subpopulations (defined4 for this ISA as those subpopulat ions that have a greater like lihood of experiencing health effects related to PM exposure) in Chapter 8. Th e introduction of this chapter was revised to include this new definition of susceptible subpopulations, recognizing that the terms susceptible and vulnerable have sometimes been us ed interchangeably in the literature, and in other cases have been used to represent two di fferent categories (i.e ., biological factors [e.g., age gender, etc.] vs. non-biologic al factors [e.g., SES, differential exposure, etc.]), resulting

in the lack of a clear and consistent defin ition. The discussion was re organized to improve

the characterization of factors that may contribute to increased susceptibility to PM-induced

health effects. Each section was also revise d to include the differe nt exposure durations (short- and long-term) and PM size fractions ex amined in the studies discussed within each subsection of the chapter. Please comment on th e organization and presentation in Chapter 8 of evidence regarding su sceptible subpopulations.

4) Revisions to Chapter 3 on Source to Exposure: Consistent with revisions made to the health effects chapters, Chapter 3 wa s revised to clarify that PM 10 incorporates both PM 2.5 and

PM 10-2.5 and reorganized to begin with PM 2.5 and PM 10-2.5 , followed by PM 10 , where applicable. The discussion of measur ement techniques and chemistry of PM 10-2.5 has been expanded in Sections 3.4 and 3.5, in response to CASAC comments. In addition, Section 3.8 on human exposure to PM has been reorganized and expanded to better characterize the evidence and provide useful information for in terpretation of epidemiologic studies. We would appreciate comments from the CASAC PM Panel on these revisions.

5) Integrative Synthesis in Chapter 2: The CASAC PM Panel recommended expanding Chapter 2 to include all important findings of the PM ISA. The integration of health evidence in Chapter 2 was reorganized to focus on effects of PM 2.5 , PM 10-2.5 , and ultrafine particles, and was expanded to include discussions of e ffects for which a "suggestive" causality determination was drawn. New integration sections were added that combine the evidence

for health effects of PM 2.5 , PM 10-2.5 , and ultrafine PM across e xposure durations. In addition, these integration discussions incorporated ev idence related to mode of action, dosimetry, atmospheric chemistry, and exposure assessment to the extent possible. When appropriate, figures were added that summarize the overall U. S. and Canadian epidemiologic evidence for specific size fractions and expos ure durations, along with the c oncentrations reported in the studies or provided by study authors. A new s ection was also added to Chapter 2 that contains policy-relevant consid erations, including summaries for the evidence for susceptible subpopulations, lag structure of associations in epidemio logic studies, and the PM concentration-response relationship. Please comme nt on these revisions and additions to the integration of health effects evidence in Chapter 2

.

6) Welfare effects evaluation in Ch apter 9: Several revisions were made to the evaluation of the

welfare effects evidence in Chapter 9, in response to the CASAC PM Panel comment, to focus further on effects on climate and ecosyst ems and include further evaluation of urban visibility evidence, where possible. In a ddition, as recommended by the CASAC PM Panel, key findings and conclusions from this chap ter were incorporated in Chapter 2. The

discussion of PM effects on climate was increase d with substantially more detail from recent publications, including discussion of specific cl imate forcing effects from individual PM components and size fractions. The discussion of ecological effects was also reorganized to5 focus on the types of effects and effects of i ndividual components. For the effects of PM on visibility, new material was a dded including sections on direct optical measurements and the value of good visual air quality. Please commen t on the effectiveness of the reorganization and revisions regardi ng welfare effects.

We look forward to discussing these issues with the CASAC PM Panel at our upcoming meeting. Should you have any questions regarding th e second draft PM ISA, please feel free to contact Dr. Mary Ross (919-541-5170, ross.mary @epa.gov) or Dr. Lindsay Wichers Stanek (919-541-7792, stanek.lindsay@epa.gov).

cc: Karen Martin, OAR/OAQPS Peter Preuss, ORD/NCEA Mary Ross, ORD/NCEA Vanessa Vu, SAB/OA Debra Walsh, ORD/NCEA Lindsay Wichers Stanek, ORD/NCEA Lydia Wegman, OAR/OAQPS