From: Lydia Wegman/RTP/USEPA/U S

To: nfrey@omb.eop.go v Cc: martin.karen@epa.gov, Beth Hassett - Sipple/RTP/USEPA/US@EPA, hannon.john@epa.gov, Scott Jenkins/RTP/USEPA/US@EPA, Joseph - J Dougherty/DC/USEPA/US@EP A Date: 06/13/2012 03: 17 P M Subject: Revisions to primary standard section of the PM preamble in response to interagency comments

Nathan, Please find attached revisions made to the primary fine particle standard section of the PM preamble. These changes address interagency comments 9 - 21 which we received last week. Please let me know if you have any questions. Thanks.***E.O. 12866 Review

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Page 2 of 133 EO12866_PM NAAQS_ 2060 - AO47

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Includes edits to Section III.E.4 as updated on 20120608 6560 - 50 - P III. Rationale for Proposed Decisions on the Primary PM 2.5 Standards This section presents the rationale for the Administrator’s proposed decision to revise the level and form of the existing primary annual PM 2.5 standard and to retain the existing primary 24 - hour PM 2.5 standard. As discussed more fully below, this rationale is based on a thorough review, in the Integrated Science Assessment, of the latest scientific information, published through mid - 2009, on human health effects associated with long - and short - term exp osures to fine particles in the ambient air. This proposal also takes into account: (1) staff assessments of the most policy - relevant information presented and assessed in the Integrated Science Assessment and staff analyses of air quality and human risks presented in the Risk Assessment and the Policy Assessment, upon which staff conclusions regarding appropriate considerations in this review are based; (2) CASAC advice and recommendations, as reflected in discussions of drafts of the Integrated Science As sessment, Risk Assessment, and Policy Assessment at public meetings, in separate written comments, and in CASAC’s letters to the Administrator; and (3) public comments received during the development of these documents, either in connection with CASAC meet ings or separately. In developing this proposal, the Administrator recognizes that the CAA requires her to reach a public health policy judgment as to what standards would be requisite to protect public health with an adequate margin of safety, based on sc ientific evidence and technical assessments that have inherent uncertainties and limitations. This judgment requires making reasoned decisions as to what weight to place on various types of evidence and assessments, and on the related uncertainties and lim itations. Thus, in selecting standards to propose, and subsequently in selecting the final standards, the Administrator is seeking not only to prevent fine particle concentrations that have been demonstrated to***E.O. 12866 Review

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Page 3 of 133 be harmful but also to prevent lower fine par ticle concentrations that may pose an unacceptable risk of harm, even if the risk is not precisely identified as to nature or degree. As discussed below, a substantial amount of new research has been conducted since the close of the science assessment in the last review of the PM 2.5 NAAQS (US EPA, 2004), with important new information coming from epidemiological studies, in particular. This body of evidence includes hundreds of new epidemiological studies conducted in many countries around the world. In it s assessment of the evidence judged to be most relevant to making decisions on elements of the primary PM 2.5 standards, the EPA has placed greater weight on U.S. and Canadian studies using PM 2.5 measurements, since studies conducted in other countries may well reflect different demographic and air pollution characteristics. 1 The newly available research studies as well as the earlier body of scientific evidence presented and assessed in the Integrated Science Assessment have undergone intensive scrutiny th rough multiple layers of peer review and opportunities for public review and comment . In developing this proposed rule, the EPA has drawn upon an integrative synthesis of the entire body of evidence between exposure to ambient fine particles and a broad ra nge of health endpoints (US EPA, 2009a, Chapters 2, 4, 5, 6, 7, and 8) focusing on those health endpoints for which the Integrated Science Assessment concludes that there is a causal or likely causal relationship with long - or short - term PM 2.5 exposures . T he EPA has also considered health endpoints for which the Integrated Science Assessment concludes there is evidence suggestive of a causal relationship with long - term PM 2.5 exposures in taking into account

1 Nonetheless, the Administrator recognizes the importance of all stud ies, including international studies, in the Integrated Science Assessment’s considerations of the weight of the evidence that informs causality determinations. Formatted: Font: Italic, No underline Formatted: Font: Italic, No underline Formatted: Font: Italic, No underline***E.O. 12866 Review

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Page 4 of 133 potential impacts on susceptible at - risk populations 2 and in considering alternative standard levels that provide protection with an appropriate margin of safety . The EPA has also drawn upon a quantitative risk assessment based upon the scientific evidence described and assessed in the Integrate d Science Assessment . These analyses, discussed in the Risk Assessment (US EPA, 2010a) and Policy Assessment (US EPA, 2011a, chapter 2), have also undergone intensive scrutiny through multiple layers of peer review and opportunities for public review and c omment. Although important uncertainties remain in the qualitative and quantitative characterizations of health effects attributable to ambient fine particles, the review of this information has been extensive and deliberate. This intensive evaluation of the scientific evidence and quantitative assessments has provided an adequate basis for regulatory decision making at this time. This section describes the integrative synthesis of the evidence and technical information contained in the Integrated Science Assessment , the Risk Assessment , and the Policy Assessment with regard to the current and potential alternative standards. The EPA notes that the final decision for retaining or revising the current primary PM 2.5 standards is a public health policy judgme nt made by the Administrator. The Administrator’s final decision will draw upon scientific information and analyses related to health effects and risks; judgments about uncertainties that are inherent in the scientific evidence and analyses; CASAC advice, and comments received in response to this proposal. In presenting the rationale for the proposed revisions of the primary PM 2.5 standards, this section begins with a summary of the approaches used in setting the initial primary PM 2.5 NAAQS in 1997 and in r eviewing those standards in 2006 (section III.A.1). The D.C. Circuit Court of Appeals remand of the primary annual PM 2.5 standard in 2009 is discussed in section III.A.2. Taking into consideration this

2 I n this proposal, the term “at - risk” is the broadly encompassing term used for groups with specific factors that increase the risk of PM - related health effects in a population. In the Integrated Science Assessment , as discussed in section III.B.3 below, the term “susceptibility” w as used broadly to recognize populations at greater risk.***E.O. 12866 Review

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Page 5 of 133 history, section II.A.3 describes EPA’s general approa ch used in the current review for considering the need to retain or revise the current suite of fine particle standards. Section III.B summarizes the body of scientific evidence supporting the rationale for the proposed decisions, including key health endp oints associated with long - and short - term exposures to ambient fine particles. This overview includes a discussion of susceptible at - risk populations and potential PM 2.5 - related impacts on public health. Section III.C outlines the approach taken by the EPA to assess health risks associated with exposure to ambient PM 2.5 , including a discussion of key uncertainties and limitations associated with these analyses. Section III.D discusses the scientific evidence, air quality, risk - based information; CASAC advic e; and the Administrator’s proposed decisions related to the adequacy of the current standards. Section III.E discusses the scientific evidence, air quality, and risk - based information; CASAC advice; and the Administrator’s proposed decisions related to al ternative standards. Section III.F summarizes the Administrator’s proposed decisions with regard to the primary PM 2.5 NAAQS. A. Background There are currently two primary PM 2.5 standards providing public health protection fr om effects associated with fine par ticle exposures . The annual standard is set at a level of 15.0 μg/m 3 , based on the 3 - year average of annual arithmetic mean PM 2.5 concentrations from single or multiple monitors sited to represent community - wide air quality. The 24 - hour standard is set at a level of 35 μg/m 3 , based on the 3 - year average of the 98 th percentile of 24 - hour PM 2.5 concentrations at each population - oriented monitor within an area. The past and current approaches for reviewing the primary PM 2.5 standards described below are all b ased most fundamentally on using information from epidemiological studies to inform the selection of PM standards that, in the Administrator’s judgment, protect public health with an adequate margin of safety. Such information can be in the form of air qua lity distributions over which health effect associations have been observed, or in the form of concentration - response functions that support quantitative risk assessment. However, evidence - and risk - based approaches using information from Formatted: Font: Italic, No underline***E.O. 12866 Review

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Page 6 of 133 epidemiological s tudies to inform decisions on PM 2.5 standards are complicated by the recognition that no population threshold, below which it can be concluded with confidence that PM 2.5 - related effects do not occur, can be discerned from the available evidence. As a result, any general approach to reaching decisions on what standards are appropriate necessarily requires judgments about how to translate the information available from the epidemiological studies into a basis for appropriate standards. This includes cons ideration of how to weigh the uncertainties in the reported associations across the distributions of PM 2.5 concentrations in the studies and the uncertainties in quantitative estimates of risk. Such approaches are consistent with setting standards that are neither more nor less stringent than necessary, recognizing that a zero - risk standard is not required by the CAA. 1. General Approach Used in Previous Reviews The general approach used to translate scientific information into standards used in the previous reviews focused on consideration of alternative standard levels that were somewhat below the long - term mean PM 2.5 concentrations reported in epidemiological studies (US EPA, 2011a, section 2.1.1). This approach recognized that the strongest evidence of PM 2 .5 - related associations occurs at concentrations near the long - term (i.e., annual) mean. In setting primary PM 2.5 annual and 24 - hour standards for the first time in 1997, the Agency relied primarily on an evidence - based approach that focused on epidemiolo gical evidence, especially from short - term exposure studies of fine particles judged to be the strongest evidence at that time (US EPA, 2011a, section 2.1.1.1). The EPA selected a level for the annual standard that was at or below the long - term mean PM 2.5 concentrations in studies providing evidence of associations with short - term PM 2.5 exposures, placing greatest weight on those short - term exposure studies that reported clearly statistically significant associations with mortality and morbidity effects. Fu rther consideration of long term mean PM 2.5 concentrations associated with mortality and respiratory effects in children did not provide a basis for establishing a lower annual standard level. The EPA did not place much weight on***E.O. 12866 Review

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Page 7 of 133 quantitative risk estimate s from the very limited risk assessment conducted, but did conclude that the risk assessment results confirmed the general conclusions drawn from the epidemiological evidence that a serious public health problem was associated with ambient PM levels allowe d under the then current PM 10 standards (62 FR 38665/1, July 18, 1997). The EPA considered the epidemiological evidence and data on air quality relationships to set an annual PM 2.5 standard that was intended to be the “generally controlling” standard; i.e. , the primary means of lowering both long - and short - term ambient concentrations of PM 2.5 . 3 In conjunction with the annual standard, the EPA also established a 24 - hour PM 2.5 standard to provide supplemental protection against days with high peak concentrat ions, localized “hotspots,” and risks arising from seasonal emissions that might not be well controlled by a national annual standard (62 FR 38669/3 ). In 2006, the EPA used a different evidence - based approach to assess the appropriateness of the levels of the 24 - hour and annual PM 2.5 standards (US EPA, 2011a, section 2.1.1.2). Based on an expanded body of epidemiological evidence that was stronger and more robust than that available in the 1997 review, including both short - and long - term exposure studies, the EPA decided that using evidence of effects associated with periods of exposure that were most closely matched to the averaging time of each standard was the most appropriate public health policy approach for evaluating the scientific evidence to inform selecting the level of each standard. Thus, the EPA relied upon evidence from the short - term exposure studies as the principal basis for revising the level of the 24 - hour PM 2.5 standard from 65 to 35 μg/m 3 to protect against effects associated with short - term exposures. The EPA relied upon evidence from long - term exposure studies as the principal basis for retaining the level of the 3 In so doing, the EPA noted that because an annual standard would focus control programs on annual average PM 2.5 concentrations, it would not only control long - term exposur e levels, but would also generally control the overall distribution of 24 - hour exposure levels, resulting in fewer and lower 24 - hour peak concentrations . Alternatively, a 24 - hour standard that focused controls on peak concentrations could also result in lo wer annual average concentrations . Thus, the EPA recognized that either standard could provide some degree of protection from both short - and long - term exposures, with the other standard serving to address situations where the daily peaks and annual averag es are not consistently correlated (62 FR 38669, July 18, 1997).***E.O. 12866 Review

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Page 8 of 133 annual PM 2.5 standard at 15 μg/m 3 to protect against effects associated with long - term exposures. This approach essentially t ook the view that short - term studies were not appropriate to inform decisions relating to the level of the annual standard, and long - term studies were not appropriate to inform decisions relating to the level of the 24 - hour standard. With respect to quanti tative risk - based considerations, the EPA determined that the estimates of risks likely to remain upon attainment of the 1997 suite of PM 2.5 standards were indicative of risks that could be reasonably judged important from a public health perspective, and, thus, supported revision of the standards. However, the EPA judged that the quantitative risk assessment had important limitations and did not provide an appropriate basis for selecting the levels of the revised standards in 2006 (71 FR 61174/1 - 2, October 17, 2006). 2. Remand of Primary Annual PM 2.5 Standard As noted above in section II.B.2, several parties filed petitions for review in the US Court of Appeals for the District of Columbia Circuit following promulgation of the revised PM NAAQS in 2006. These petitions challenged several aspects of the final rule including the level of the primary PM 2.5 annual standard. The primary 24 - hour PM 2.5 standard was not challenged by any of the litigants and, thus, not considered in the court’s review and decision. On judicial review, the D.C. Circuit remanded the primary annual PM 2.5 NAAQS to the EPA on grounds that the Agency failed to adequately explain why the annual standard provided the requisite protection from both short - and long - term exposures to fine particl es including protection for susceptible at - risk populations. American Farm Bureau Federation v. EPA , 559 F. 3d 512 (D.C. Cir. 2009) . With respect to human health protection from short - term PM 2.5 exposures, the court considered the different approaches used by the EPA in the 1997 and 2006 PM NAAQS decisions, as summarized in section III.A.1. The court found that the EPA failed to adequately explain why a primary 24 - hour PM 2.5 standard by itself wo uld provide the protection needed from short - term exposures and remanded the primary annual PM 2.5 standard to the EPA “for further consideration of whether it is set at a level Formatted: Font: Italic, No underline***E.O. 12866 Review

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Page 9 of 133 requisite to protect the public health while providing an adequate margin of sa fety from the risk of short term exposures to PM 2.5 .” American Farm Bureau Federation v. EPA , 559 F. 3d at 520 - 24 . With respect to protection from long - term exposure to fine particles, the court found that the EPA failed to adequately explain how the prim ary annual PM 2.5 standard provided an adequate margin of safety for children and other susceptible at - risk populations. The court found that the EPA did not provide a reasonable explanation of why certain morbidity studies, including a study of children in Southern California showing lung damage associated with long - term PM 2.5 exposure (Gauderman et.al, 2000) and a multi - city study (24 - Cities Study) evaluating decreased lung function in children associated with long - term PM 2.5 exposures (Raizenne et al., 199 6), did not warrant a more stringent annual PM 2.5 standard. Id. at 522 - 23. Specifically, the court found that: EPA was unreasonably confident that, even though it relied solely upon long - term mortality studies, the revised standard would provide an adequat e margin of safety with respect to morbidity among children. Notably absent from the final rule, moreover, is any indication of how the standard will adequately reduce risk to the elderly or to those with certain heart or lung diseases despite (a) the EPA’ s determination in its proposed rule that those subpopulations are at greater risk from exposure to fine particles and (b) the evidence in the record supporting that determination. Id. at 525. In addition, the court held that the EPA had not adequately exp lained its decision to base the level of the annual standard essentially exclusively on the results of long - term studies, and the 24 - hour standard level essentially exclusively on short - term studies. See 559 F. 3d at 522 (“[e]ven if the long term studies a vailable today are useful for setting an annual standard,..., it is not clear why the EPA no longer believes it useful to look as well to short - term studies in order to design the suite of standards that will most effectively reduce the risks associated with short - term exposure”); see also id. at 523 - 24 (holding that the EPA had not adequately explained why a standard based on levels in short - term exposure studies alone provided appropriate protection from health effects associated with short - term PM 2.5 expos ures given the stated need to lower the entire air quality distribution, and not just peak concentrations, in order to control against short - term effects). Formatted: Font: Italic, No underline Formatted: Font: Italic***E.O. 12866 Review

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Page 10 of 133 In remanding the primary annual PM 2.5 standard for reconsideration, the court did not vacate the st andard, id. at 530, so the standard remains in effect and is the standard considered by the EPA in this review. 3. General Approach Used in the Policy Assessment for the Current Review This review is based on an assessment of a much expanded body of scientific evidence, more extensive air quality data and analyses, and a more comprehensive quantitative risk assessment relative to the information available in past reviews, as presented an d assessed in the Integrated Science Assessment and Risk Assessment and discussed in the Policy Assessment . As a result, EPA’s general approach to reaching conclusions about the adequacy of the current suite of PM 2.5 standards and potential alternative sta ndards that are appropriate for consideration to consider is broader and more integrative than in past reviews. Our general approach also reflects consideration of the issues raised by the court in its remand of the primary annual PM 2.5 standard, since dec isions made in this review, and the rationales for those decisions, will comprise the Agency’s response to the remand. The EPA’s general approach takes into account both evidence - based and risk - based considerations, and the uncertainties related to both ty pes of information, as well as advice from CASAC (Samet, 2010c,d) and public comments on the first and second draft Policy Assessments (US EPA, 2010c,f). In so doing, EPA staff developed a final Policy Assessment (US EPA, 2011a) which provides as broad an array of policy options as is supportable by the available information, recognizing that the selection of a specific approach to reaching final decisions on the primary PM 2.5 standards will reflect the judgments of the Administrator as to what weight to pl ace on the various approaches and types of information presented in this document. The Policy Assessment concludes it is most appropriate to consider the protection against PM 2.5 - related mortality and morbidity effects, associated with both long - and short - term exposures, afforded by the annual and 24 - hour standards taken together, as was done in the 1997 review, rather than***E.O. 12866 Review

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Page 11 of 133 to consider each standard separately, as was done in the 2006 review (US EPA, 2011a, section 2.1.3). 4 As the EPA recognized in 1997, t here are various ways to combine two standards to achieve an appropriate degree of public health protection . The extent to which these two standards are interrelated in any given area depends in large part on the relative levels of the standards, the peak - to - mean ratios that characterize air quality patterns in an area, and whether changes in air quality designed to meet a given suite of standards are likely to be of a more regional or more localized nature . In considering the combined effect of annual and 24 - hour standards, the Policy Assessment recognizes that changes in PM 2.5 air quality designed to meet an annual standard would likely result not only in lower annual average PM 2.5 concentrations but also in fewer and lower peak 24 - hour PM 2.5 concentratio ns. The Policy Assessment also recognizes that changes designed to meet a 24 - hour standard would result not only in fewer and lower peak 24 - hour PM 2.5 concentrations but also in lower annual average PM 2.5 concentrations. Thus, either standard could be view ed as providing protection from effects associated with both short - and long - term exposures, with the other standard serving to address situations where the daily peak and annual average concentrations are not consistently correlated. In considering the c urrently available evidence, the Policy Assessment recognizes that the short term exposure studies are primarily drawn from epidemiological studies that associated variations in area - wide health effects with monitor(s) that measured the variation in daily PM 2.5 concentrations over the course of several years. The strength of the associations in these data is demonstrably in the numerous “typical” days within the air quality distribution, not in the peak days. See also 71 FR 61168, October 17, 2006 and Ameri can Farm Bureau Federation v EPA , 559 F. 3d at 523, 524 (making the 4 By utilizing this approach, the Agency would also be responsive to the remand of the 2006 standard . As noted in section II I .A.2, the D.C. Circuit, in remanding the 2006 primary annual PM 2.5 standard, concluded that the Administrator had failed to adequately explain why an annual standard was sufficiently protective in the absence of consideration of the long - term mean PM 2.5 concentrations in short - term exposure studies as well, and likewise had failed to explain why a 24 - hour standard was sufficiently protective in the absence of consideration of the effect of an annual standard on reducing the overall distribution of 24 - hour average PM 2.5 concentrations . 559 F. 3d at 520 - 24 . Formatted: Font: Italic, No underline***E.O. 12866 Review

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Page 12 of 133 same point) . The quantitative risk assessments conducted for this and previous reviews demonstrate the same point, that is, much, if not most of the aggregate risk associated with short - te rm exposures results from the large number of days during which the 24 - hour average concentrations are in the low - to mid range, below the peak 24 - hour concentrations (US EPA, 2011a, section 2.2.2; US EPA, 2010a, section 3.1.2.2) . In addition, there is no e vidence suggesting that risks associated with long - term exposures are likely to be disproportionately driven by peak 24 - hour concentrations. 5 For these reasons, strategies that focus primarily on reducing peak days are less likely to achieve reductions in the PM 2.5 concentrations that are most strongly associated with the observed health effects . Furthermore, a policy approach that focuses on reducing peak exposures would most likely result in more uneven public health protection across the U.S. by either providing inadequate protection in some areas or overprotecting in other areas (US EPA, 2010a, section 5.2.3). This is because reductions based on control of peak days are less likely to control the bulk of the air quality distribution, as discussed above. The Policy Assessment concludes that a policy goal of setting a “generally controlling” annual standard that will lower a wide range of ambient 24 - hour PM 2.5 concentrations, as opposed to focusing on control of peak 24 - hour PM 2.5 concentrations, is the most effective and efficient way to reduce total population risk and so provide appropriate protection. This approach, in contrast to one focusing on a generally controlling 24 - hour standard, would likely reduce aggregate risks associated with both long and short - term exposures with more consistency and would likely avoid setting national stand ards that could result in relatively uneven protection across the country, due to setting standards that are either more or less stringent than necessary in different geographical areas (US EPA, 2011a, p. 2 - 9). The Policy Assessment also concludes, however , that an annual standard intended to serve as the primary means for providing protection from effects associated with both long - and short - term PM 2.5 5 In confirmati on, a number of studies that have presented analyses excluding higher PM concentration days reported a limited effect on the magnitude of the effect estimates or statistical significance of the association (e.g., Dominici, 2006b; Schwartz et al, 1996; Pope and Dockery, 1992).***E.O. 12866 Review

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Page 13 of 133 exposures cannot be expected to offer an adequate margin of safety against the effects of all short - term PM 2.5 exposures. As a result, in conjunction with a generally controlling annual standard, the Policy Assessment concludes it is appropriate to consider setting a 24 - hour standard to provide supplemental protection, particularly for areas with high peak - to - mean ratios possibly associated with strong local or seasonal sources, or PM 2.5 - related effects that may be associated with shorter - than - daily exposure periods (US EPA, 2011a, p. 2 - 10). The Policy Assessment ’s consideration of the protection afforded by t he current and alternative suites of standards focuses on PM 2.5 - related health effects associated with long - term exposures , for which the magnitude of quantitative estimates of risks to public health generated in the risk assessment is appreciably larger i n terms of overall incidence and percent of total mortality or morbidity effects than for short - term PM 2.5 - related effects. Nonetheless, the EPA also considers effects and estimated risks associated with short - term exposures. In both cases, the Policy Asse ssment places greatest weight on health effects that have been judged in the Integrated Science Assessment to have a causal or likely causal relationship with PM 2.5 exposures, while also considering health effects judged to be suggestive of a causal relati onship or evidence that focuses on specific susceptible at - risk populations. The Policy Assessment places relatively greater weight on statistically significant associations that yield relatively more precise effect estimates and that are judged to be robus t to confounding by other air pollutants. In the case of short - term exposure studies, the Policy Assessment places greatest weight on evidence from large multi - city studies, while also considering associations in single - city studies. In translating inform ation from epidemiological studies into the basis for reaching staff conclusions on the adequacy of the current suite of standards, the Policy Assessment considers a number of factors (US EPA, 2011a, section 2.2). As an initial matter, the Policy Assessmen t considers the extent to which the currently available evidence and related uncertainties strengthens or calls into question conclusions from the last review regarding associations between fine particle exposures and health***E.O. 12866 Review

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Page 14 of 133 effects. The Policy Assessment also considers evidence on susceptible at - risk populations and potential impacts on such populations. Further, the Policy Assessment explores the extent to which PM 2.5 - related health effects have been observed in areas where air quality distributions extend to lower levels than previously reported or in areas that would likely have met the current suite of standards. In translating information from epidemiological studies into the basis for reaching staff conclusions on alternative standard levels for consi deration (US EPA, 2011a, sections 2.1.3 and 2.3.4), the Policy Assessment first recognizes the absence of discernible thresholds in the concentration response functions from long - and short - term PM 2.5 exposure studies (US EPA, 2011a, section 2.4.3). 6 In the absence of any discernible thresholds, the Agency’s general approach for identifying appropriate standard levels for consideration involves characterizing the range of PM 2.5 concentrations over which we have the most confidence in the associations repo rted in epidemiological studies . In so doing, the Policy Assessment recognizes that there is no single factor or criterion that comprises the “correct” approach, but rather there are various approaches that are reasonable to consider for characterizing the confidence in the associations and the limitations and uncertainties in the evidence. Identifying the implications of various approaches for reaching conclusions on the range of alternative standard levels that is appropriate to consider can help inform d ecisions to either retain or revise the standards. Final decisions will necessarily also take into account public health policy judgments as to the degree of health protection that is to be achieved. In reaching staff conclusions on the range of annual st andard levels that is appropriate to consider, the Policy Assessment focuses on identifying an annual standard that provides requisite 6 The epidemiological studies evaluated in the Integrated Science Assessment that examined the shape of concentration - response relationship s and the potential presence of a threshold focused on cardiovascular - related hospital admissions and emergency department visits associated with short - term PM 10 exposures and premature mortality associated with long - term PM 2.5 exposure (US EPA, 2009a, sect ions 6.5, 6.2.10.10 and 7.6). Overall, the Integrated Science Assessment concludes that the studies evaluated support the use of a no - threshold, log - linear model but recognizes that “additional issues such as the influence of heterogeneity in estimates bet ween cities, and the effect of seasonal and regional differences in PM on the concentration - response relationship still require further investigation” (US EPA, 2009a, section 2.4.3).***E.O. 12866 Review

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Page 15 of 133 protection from effects associated with both long - and short - term exposures. In so doing, the Policy Assessment explores different approaches for characterizing the range of PM 2.5 concentrations over which our confidence in the nature of the associations for both long - and short - term exposures is greatest, as well as the extent to which our confidence is reduced at lower PM 2 .5 concentrations. The approach that most directly addresses this issue considers studies that present confidence intervals around concentration - response relationships, and in particular, analyses that average across multiple concentration - response models rather than considering a single concentration - response model. 7 The Policy Assessment explores the extent to which such analyses have been published for studies of health effects associated with long - or short - term PM 2.5 exposures . Such analyses could pot entially be used to characterize a concentration below which uncertainty in a concentration - response relationship substantially increases or is judged to be indicative of an unacceptable degree of uncertainty about the existence of a continuing concentrati on - response relationship. The Policy Assessment concludes that identifying this area of uncertainty in the concentration - response relationship could be used to inform identification of alternative standard levels that are appropriate to consider. Further, the Policy Assessment explores other approaches that consider different statistical metrics from epidemiological studies. The Policy Assessment first takes into account the general approach used in previous PM reviews which focused on consideration of alt ernative standard levels that were somewhat below the long - term mean PM 2.5 concentrations reported in epidemiological studies. 8 This approach recognizes that the strongest evidence of PM 2.5 - related associations occurs at 7 This is distinct from confidence intervals around concentration - respons e relationships that are related to the magnitude of effect estimates generated at specific PM 2.5 concentrations (i.e., point - wise confidence intervals) and that are relevant to the precision of the effect estimate across the air quality distribution, rath er than to our confidence in the existence of a continuing concentration - response relationship across the entire air quality distribution on which a reported association was based . 8 Epidemiological studies typically report PM 2.5 concentrations averaged a cross the available ambient monitors . For multi - city studies, this metric reflects concentrations averaged across one or more ambient monitors within each area included in a given study and then averaged across study areas for an overall study mean PM 2.5 concentration . This is consistent with the epidemiological evidence considered in other NAAQS reviews.***E.O. 12866 Review

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Page 16 of 133 concentrations near the long - term (i.e., annual) mean . In using this approach, the Policy Assessment places greatest weight on those long - and short - term exposure studies that reported statistically significant associations with mortality and morbidity effects. In extending this approach, the Policy Assessment also considers information beyond a single statistical metric of PM 2.5 concentrations (i.e., the mean) to the extent such information is available. In so doing, the Policy Assessment employs distributional statistics (i.e., statistical characterization of an entire distribution of data) to identify the broader range of PM 2.5 concentrations that were most influential in generating health effect had the most influence on the calculation of relative risk estimat es in epidemiological studies. Thus, the Policy Assessment considers the range of PM 2.5 concentrations where the data analyzed in the study (i.e., air quality and population - level data, as discussed below) are most concentrated, specifically, the range of PM 2.5 concentrations around the long - term mean over which our confidence in the associations observed in the epidemiological studies is greatest. The Policy Assessment then focuses on the lower part of this range to characterize where in the distributions the data become appreciably more sparse and, thus, where our understanding of the associations correspondingly becomes more uncertain. The Policy Assessment recognizes there is no one percentile value within a given distribution that is the most appropriat e or “correct” way to characterize where our confidence in the associations becomes appreciably lower. The Policy Assessment concludes that the range from the 25 th to 10 th percentiles is a reasonable range to consider as a region where we have appreciably less confidence in the associations observed in epidemiological studies. 9 In considering distributional statistics from epidemiological studies, the final Policy Assessment 9 In the PM NAAQS review completed in 2006, the Staff Paper recognized that the evidence of an association in any epidemiological study is “strongest at and around the long - term average where the data in the study are most concentrated . For example, the int erquartile range of long - term average concentrations within a study [with a lower bound of the 25 th percentile] or a range within one standard deviation around the study mean, may reasonably be used to characterize the range over which the evidence of asso ciation is strongest” (US EPA, 2005, p. 5 - 22) . A range of one standard deviation around the mean represents approximately 68 percent of normally distributed data, and, below the mean falls between the 25 th and 10 th percentiles.***E.O. 12866 Review

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Page 17 of 133 recognizes that there are focused on two types of population - level metrics that CASAC advices are most useful to consider in identifying the PM 2.5 concentrations most influential in generating the health effect estimates reported in the epidemiological studies. The 10 Consistent with CASAC advice, t he most relevant information is the di stribution of health events (e.g., deaths, hospitalizations) occurring within a study population in relation to the distribution of PM 2.5 concentrations . However, in recognizing that access to health event data can be restric ted, as discussed in section III.E.4.b below, the Policy Assessment also considers the number of study participants within each study area as a reasonable an appropriate surrogate for health event data. 11 The Policy Assessment recognizes that an approach consid ering analyses of confidence intervals around concentration - response functions is intrinsically related to an approach that considers different distributional statistics . Both of these approaches could be employed to identify the range of PM 2.5 concentrati ons over which we have the most confidence in the associations reported in epidemiological 10 The second draft Policy As sessment focused on the distributions of PM 2.5 concentrations across areas included in several multi - city studies for which such data were available in seeking to identify the most influential range of concentrations (US EPA, 2010f, section 2.3.4.1). In it s review of the second draft Policy Assessment, CASAC advised that it “ would be preferable to have information on the concentrations that were most influential in generating the health effect estimates in individual studies ” (Samet, 2010d, p.2). Therefore, in the final Policy Assessment, EPA considered area - specific health event and area - specific population data along with corresponding PM 2.5 concentrations to generate a cumulative distribution of the population data relative to long - term mean PM 2.5 concent rations to determine the most influential range (US EPA, 2011a, Figure 2 - 7 and associated text). 11 In the absence of data on the number of health events or study participants, the distribution of PM 2.5 concentrations across study areas in multi - city studie s could also be considered to be representative of the PM 2.5 concentrations likely experienced by study participants, which are integral to the generation of effect estimates. This approach is particularly relevant for identifying the range of PM 2.5 concen trations most influential in generating the effect estimates in short - term exposure studies (e.g., time - series studies). In short - term exposure studies, a similar number of events are likely occurring on a daily basis and, thus, information on the PM 2.5 ai r quality distributions provides a better approximation of a study participant’s likely exposure in relation to the observed health effects as compared to long - term exposure studies where individual study participants’ exposures change over the course of t he study follow - up period (Samet, 2010d, p. 2). However, the EPA was unable to determine from the methodologies published for the epidemiological studies how the air quality data were statistically weighted to account for variations in the availability of daily PM 2.5 measurements by study area (Rajan et al., 2011, p. 7). Consequently, the EPA was unable to consider this type of information as part of its effort to identify the broader range of PM 2.5 concentrations that were most influential in generating th e health effect estimates in epidemiological studies (US EPA, 2011a, p. 2 - 71).***E.O. 12866 Review

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Page 18 of 133 studies. In applying these approaches, the Policy Assessment considers PM 2.5 concentrations from long and short - term PM 2.5 exposure studies using composite monitor distributions. 12 For multi - city studies, this distribution reflects concentrations averaged across one or more ambient monitors within each area included in a given study and then averaged across study areas for an overall study mean PM 2.5 concentration . Beyond considering air quality concentrations based on composite monitor distributions, the second draft Policy Assessment also considered PM 2.5 concentrations based on measurements at the monitor within each area that records the highest concentration ( i.e., maximum monitor) (US EPA, 2010f, sections 2.1.3 and 2.3.4.1). 13 Although the second draft P olicy A ssessment discussed whether consideration of alternative annual standard levels could should be based on either composite or maximum monitor distributions , the final Policy Assessment , consistent with CASAC advice (Samet, 2010d, p. 3), concluded that it is most reasonable to place more weight on an approach based on composite monitor distributions, which represent the PM 2.5 concentrations typically presented and used in epidemiological analyses and which provide a direct link between PM 2.5 concentrations and the observed health effects reported in both long - and short - term exposure studies (US EPA, 2011a, p. 2 - 13). In reach ing staff conclusions on alternative standard levels that are appropriate to consider, the Policy Assessment also includes a broader consideration of the uncertainties related to the concentration - response relationships from multi - city, long - and short - ter m exposure studies. Most 12 Using the term “composite monitor” does not imply that the EPA can identify one monitor that represents the air quality evaluated in a specific study area . Rather, as noted a bove, the composite monitor concentration represents the average concentration across one or more monitors within each area included in a given study and then averaged across study areas for an overall study mean PM 2.5 concentration . 13 The maximum monitor distribution is relevant because it is generally used to determine whether a given standard is met in an area and the extent to which ambient PM 2.5 concentrations need to be reduced in order to bring an area into attainment with the st andard . However, maximum monitor distributions represent a far less robust metric than composite monitor distributions for consideration of alternative annual standard levels in part because they are available for only a few epidemiological studies.***E.O. 12866 Review

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Page 19 of 133 notably, these uncertainties relate to our currently limited understanding of the heterogeneity of relative risk estimates in areas across the country. This heterogeneity may be attributed, in part, to the potential for different c omponents within the mix of ambient fine particles to differentially contribute to health effects observed in the studies and to exposure - related factors (US EPA, 2011a, pp. 2 - 25 to 2 - 26). The limitations and uncertainties associated with the currently ava ilable scientific evidence, including the availability of fewer studies toward the lower range of alternative annual standard levels being considered in this proposal, are further discussed in section III.B.2 below. The Policy Assessment recognizes that th e level of protection afforded by the NAAQS relies both on the level and the form of the standard. The Policy Assessment concludes that a policy approach that uses data based on composite monitor distributions to identify alternative standard levels, and t hen compares those levels to concentrations at maximum monitors to determine if an area meets a given standard, inherently has the potential to build in some margin of safety (US EPA, 2011a, p. 2 - 14). 14 This conclusion is consistent with CASAC’s comments on the second draft Policy Assessment , in which CASAC expressed its preference for focusing on an approach using composite monitor distributions “because of its stability, and for the additional margin of safety it provides” when “compared to the maximum mon itor perspective” (Samet, et al., 2010d, pp. 2 to 3) . In reaching staff conclusions on alternative 24 - hour standard levels that are appropriate to consider for setting a 24 - hour standard intended to supplement the protection afforded by a generally contro lling annual standard, the Policy Assessment considered currently available short - term PM 2.5 14 Sta tistical metrics (e.g., means) based on composite monitor distributions may be identical to or below the same statistical metrics based on maximum monitor distributions . For example, some areas may have only one monitor, in which case the composite and max imum monitor distributions will be identical in those areas . Other areas may have multiple monitors that may be very close to the monitor measuring the highest concentrations, in which case the composite and maximum monitor distributions could be similar i n those areas . As noted in Hassett - Sipple et al. ( 2010 ), for studies involving a large number of areas, the composite and maximum concentrations are generally within 5 percent of each other. Still other areas may have multiple monitors that may be separate ly impacted by local sources in which case the composite and maximum monitor distributions could be quite different and the composite monitor distributions may be well below the maximum monitor distributions (US EPA, 2011a, p. 2 - 14) .***E.O. 12866 Review

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Page 20 of 133 exposure studies. The evidence from these studies informs our understanding of the protection afforded by the suite of standards against effects associated with sh ort - term exposures. In considering the short term exposure studies, the Policy Assessment evaluates both the distributions of 24 - hour PM 2.5 concentrations, with a focus on the 98 th percentile concentrations to match the form of the current 24 - hour PM 2.5 st andard, to the extent such data were available, as well as the long - term mean PM 2.5 concentrations reported in these studies. In addition to considering the epidemiological evidence, the Policy Assessment also considers air quality information based on cou nty - level 24 - hour and annual design values 15 to understand the policy implications of the alternative standard levels supported by the underlying science . In particular, the Policy Assessment considers the extent to which different combinations of alternative annual and 24 - hour standards would support the policy goal of focusing on a generally controlling annual standard in conjunction with a 24 - hour standard that would provide supplemental pr otection . Based on the evidence - based considerations outlined above, the Policy Assessment develops integrated conclusions with regard to alternative suites of standards, including both annual and 24 - hour standards that are appropriate to consider in this review based on the currently available evidence and air quality information. In so doing, the Policy Assessment discusses the roles that each standard might be expected to play in the protection afforded by alternative suites of standards. Beyond these ev idence - based considerations, the Policy Assessment also considers the quantitative risk estimates and the key observations presented in the Risk Assessment. This assessment includes an evaluation of 15 urban case study areas and estimated risk associated w ith a number of health endpoints associated with long - and short - term PM 2.5 exposures (US EPA, 2010a). As part of the risk - based considerations, the Policy Assessment considers estimates of the magnitude of PM 2.5 - related risks associated with recent air qu ality levels and air quality simulated to just meet the current and alternative suites of standards using alternative simulation approaches. The Policy Assessment also 15 Design values are t he metrics (i.e., statistics) that are compared to the NAAQS levels to determine compliance.***E.O. 12866 Review

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Page 21 of 133 characterizes the risk reductions, relative to the risks remaining upon just meeting the current standards, associated with just meeting alternative suites of standards. In so doing, the Policy Assessment recognizes the uncertainties inherent in such risk estimates, and takes such uncertainties into account by considering the sensitivity of t he “core” risk estimates to alternative assumptions and methods likely to have substantial impact on the estimates. In addition, the Policy Assessment considers additional analyses characterizing the representativeness of the urban study areas within a bro ader national context to understand the roles that the annual and 24 - hour standards may play in affording protection against effects related to both long - and short - term PM 2.5 exposures. The Policy Assessment conclusions related to the primary PM 2.5 standa rds reflect an understanding of both evidence - based and risk - based considerations to inform two overarching questions related to: (1) the adequacy of the current suite of PM 2.5 standards and (2) potential alternative standards, if any, that are appropriate to consider in this review to protect against effects associated with both long - and short - term exposures to fine particles. In addressing these broad questions, the discussions included in the Policy Assessment were organized around a series of more spec ific questions reflecting different aspects of each overarching question (US EPA, 2011a, chapter 2, Figure 2 - 1). When evaluating the health protection afforded by the current or any alternative suites of standards considered, the Policy Assessment takes in to account the four basic elements of the NAAQS: the indicator, averaging time, form, and level. The general approach for reviewing the primary PM 2.5 standards described above provides a comprehensive basis to help inform the judgments required of the Admi nistrator in reaching decisions about the current and potential alternative primary fine particle standards and in responding to the remand of the 2006 primary annual PM 2.5 standard. B. Health Effects Related to Exposure to Fine Particles This section outline s key information contained in the Integrated Science Assessment (Chapters 2, 4, 5, 6, 7, and 8) and the Policy Assessment (Chapter 2) related to health effects associated with fine Formatted: Font: Italic, No underline***E.O. 12866 Review

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Page 22 of 133 particle exposures . As was true in the last review, evidence from epidemio logic studies plays a key role in the Integrated Science Assessment ’s evaluation of the scientific evidence. The following sections discuss available information on the health effects associated with exposures to PM 2.5 , including the nature of such health effects (section III.B.1) and associated limitations and uncertainties (section III.B.2), susceptible at - risk populations (section III.B.3), and potential PM 2.5 - related impacts on public health (section III.B.4). 1. Nature of Effects In considering the strength of the associations between long - and short - term exposures to PM 2.5 and health effects, the Policy Assessment notes that in the PM NAAQS review completed in 2006 the Agency concluded that there was “strong epidemiological evidence” for linking lon g - term PM 2.5 exposures with cardiovascular - related and lung cancer mortality and respiratory - related morbidity and for linking short - term PM 2.5 exposures with cardiovascular - related and respiratory - related mortality and morbidity (US EPA, 2004, p. 9 - 46; US EPA, 2005, p. 5 - 4). Overall, the epidemiological evidence supported “likely causal associations” between PM 2.5 and both mortality and morbidity from cardiovascular and respiratory diseases, based on “an assessment of strength, robustness, and consistency in results” (US EPA, 2004, p. 9 - 48). 16 In looking across the extensive new scientific evidence available in this review, our overall understanding of health effects associated with fine particle exposures has been greatly expanded (US EPA, 2009a, sections 2.3.1 and 2.3.2) . The currently available evidence is stronger in comparison to evidence available in the last review because of its breadth and the substantiation of previously observed health effects . A number of large multi - city epidemiological studies have been conducted throughout the U.S., including extended analyses of studies that were important to inform decision - making in the last 16 The term “likely causal association” was used in the 2004 Criteria Document to summarize the strength of the available epidemiological evidence available in the last review for PM 2.5 . However, this terminology was not based on a formal framework for evaluating evidence for inferring causation . Since the last review, the EPA has developed a more formal framework for reaching causal determinations with standardized language to express evaluation of the evidence (US EPA, 2009a, section 1.5) .***E.O. 12866 Review

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Page 23 of 133 review. These studies have reported consistent increases in morbidity and/or mortality related to ambient PM 2.5 concen trations, with the strongest evidence reported for cardiovascular - related effects. In addition, the findings of new toxicological and controlled human exposure studies greatly expand and provide stronger support for a number of potential biologic mechanism s or pathways for cardiovascular and respiratory effects associated with long - and short - term PM exposures (US EPA, 2009a, p 2 - 17; chapter 5; Figures 5 - 4 and 5 - 5). With regard to causal inferences described in the Integrated Science Assessment , the Policy Assessment notes that since the last review, the Agency has developed a more formal framework for reaching causal determinations that draws upon the assessment and integration of evidence from across epidemiological, controlled human exposure, and toxicol ogical studies, and the related uncertainties, that ultimately influence our understanding of the evidence (US EPA, 2011a, p. 2 - 18; US EPA, 2009a, section 1.5). This framework employs a five - level hierarchy that classifies the overall weight of evidence an d causality using the following categorizations: causal relationship, likely to be a causal relationship, suggestive of a causal relationship, inadequate to infer a causal relationship, and not likely to be a causal relationship (US EPA, 2009a, Table 1 - 3). 17 Using this causal framework, the Integrated Science Assessment concludes that the collective evidence is largely consistent with past studies and substantially strengthens what was known about fine particles in the last review to reach the conclusion th at a causal relationship exists between both long and short - term exposures to PM 2.5 and mortality and cardiovascular effects including cardiovascular related mortality. The Integrated Science Assessment also concludes that the collective evidence continue s to support a likely causal relationship between long - and short - term PM 2.5 exposures and respiratory effects, including respiratory - related mortality. Further, the Integrated Science Assessment 17 Causal inferences, as discussed in the Integrated Science Assessment, are based not only on the more expansive epidemiological evidence available in this review but also reflec t consideration of important progress that has been made to advance our understanding of a number of potential biologic modes of action or pathways for PM - related cardiovascular and respiratory effects (US EPA , 2009a, chapter 5) .***E.O. 12866 Review

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Page 24 of 133 concludes that the currently available evidence is suggestiv e of a causal relationship between long - term PM 2.5 exposures and other health effects, including developmental and reproductive effects (e.g., low birth weight, infant mortality) and carcinogenic, mutagenic, and genotoxic effects (e.g., lung cancer mortali ty) (US EPA, 2009a, sections 2.3.1 and 2.6; Table 2 - 6; US EPA, 2011a, Table 2 - 1). a. Health Effects Associated with Long - term PM 2.5 Exposures With regard to mortality, the Integrated Science Assessment concludes that newly available evidence significantly strengthens the link between long - term exposure to PM 2.5 and mortality, while providing indications that the magnitude of the PM 2.5 - mortality association may be larger than previously estimated (US EPA , 2009a, sections 7.2.10, 7.2.11, and 7.6.1; Figures 7 - 6 and 7 - 7). A number of large U.S. cohort studies have been published since the last review, including extended analyses of the American Cancer Society (ACS) and Harvard Six Cities studies (US EPA, 200 9a, pp 7 - 84 to 7 - 85; Figure 7 - 6; Krewski et al., 2009; Pope et al., 2004; Jerrett et al., 2005; Laden et al., 2006). In addition, new long - term PM 2.5 exposure studies evaluating mortality impacts in additional cohorts are now available (US EPA, 2009a, sect ion 7.6). For example, the Women’s Health Initiative (WHI) Observational Study reported effects of PM 2.5 on cardiovascular - related mortality in post - menopausal women with no previous history of cardiac disease (Miller et al., 2007 ), while ). The PM 2.5 effec t estimate in this study remained positive and statistically significant in a multi - pollutant model that included gaseous co - pollutants as well as coarse particles. In addition, multiple studies observed PM 2.5 - associated mortality among older adults using Medicare data (Eftim et al., 2008; Zeger et al., 2007, 2008). Collectively, these new studies, along with evidence available in the last review, provide consistent and stronger evidence of associations between long - term exposure to PM 2.5 and mortality (U.S . EPA, 2009a, sections 2.3.1 and 7.6). The strength of the causal relationship between long - term PM 2.5 exposure and mortality also builds upon new studies providing evidence of improvement in community health following reductions***E.O. 12866 Review

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Page 25 of 133 in ambient fine particles . Pope et al. (2009) documented the population health benefits of reducing ambient air pollution by correlating past reductions in ambient PM 2.5 concentrations with increased life expectancy. These investigators reported that reductions in ambient fine par ticles during the 1980s and 1990s account for as much as 15 percent of the overall improvement in life expectancy in 51 U.S. metropolitan areas, with the fine particle reductions reported to be associated with an estimated increase in mean life expectancy of approximately 5 to 9 months (US EPA, 2009a, p. 7 - 95; Pope et al., 2009). An extended analysis of the Harvard Six Cities study found that as cities cleaned up their air, locations with the largest reductions in PM 2.5 saw the largest improvements in reduc ed mortality rates, while those with the smallest decreases in PM 2.5 concentrations saw the smallest improvements (Laden et al., 2006). Another extended follow - up to the Harvard Six Cities study investigated the delay between changes in ambient PM 2.5 conce ntrations and changes in mortality (Schwartz et al., 2008) and reported that the effects of changes in PM 2.5 were seen within the 2 years prior to death (US EPA, 2009a, p. 7 - 92; Figure 7 - 9). With regard to cardiovascular effects, several new studies have examined the association between cardiovascular effects and long - term PM 2.5 exposures in multi - city studies conducted in the U.S. and Europe. The Integrated Science Assessment concludes that the strongest evidence comes from recent studies investigating ca rdiovascular - related mortality. This includes evidence from a number of large, multi - city U.S. long - term cohort studies including extended follow - up analyses of the ACS and Harvard Six Cities studies, as well as the WHI study (US EPA, 2009a, sections 7.2.1 0 and 7.6.1; Krewski et al., 2009; Pope et al., 2004; Laden et al., 2006; Miller et al., 2007). Pope et al. (2004) reported a positive association between mortality and long - term PM 2.5 exposure for a number of specific cardiovascular diseases, including is chemic heart disease, dysrhythmia, heart failure, and cardiac arrest (US EPA, 2009a, p. 7 - 84; Figure 7 - 7). Krewski et al. (2009) provides further evidence for mortality***E.O. 12866 Review

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Page 26 of 133 related to ischemic heart disease associated with long - term PM 2.5 exposure (US EPA, 200 9a, p. 7 - 84, Figure 7 - 7). With regard to cardiovascular - related morbidity associated with long - term PM 2.5 exposures, studies were not available in the last review. Recent studies, however, have provided new evidence linking long - term exposure to PM 2.5 wit h cardiovascular outcomes that has “expanded upon the continuum of effects ranging from the more subtle subclinical measures to cardiopulmonary mortality” (US EPA, 2009a, p. 2 - 17). In the current review, studies are now available that evaluated a number of endpoints ranging from subtle indicators of cardiovascular health to serious clinical events associated with coronary heart disease and cardiovascular and cerebrovascular disease. 18 The most important new evidence comes from the WH I study which provides evidence of nonfatal cardiovascular events including both coronary and cerebrovascular events (Miller et al., 2007; US EPA, 2009a, sections 7.2.9 and 7.6.1) . Toxicological studies provide supportive evidence that the cardiovascular morbidit y effects observed in long - term exposure epidemiological studies are biologically plausible and coherent with studies of cardiovascular - related mortality as well as with studies of cardiovascular - related effects associated with short - term exposures to PM 2. 5 , as described below (US EPA, 2009a, p 7 - 19). With regard to respiratory effects, the Integrated Science Assessment concludes that extended analyses of studies available in the last review as well as new epidemiological studies conducted in the U.S. and abroad provide stronger evidence of respiratory - related morbidity associated with long - term PM 2.5 exposure. The strongest evidence for respiratory - related effects available in this review is from studies that evaluated decrements in lung function growth, i ncreased respiratory symptoms, and asthma development (U.S. EPA, 2009a, sections 2.3.1.2, 7.3.1.1, and 7.3.2.1). 19 Specifically, extended analyses of the Southern California Children’s Health Study provide evidence that clinically important deficits in 18 Coronary and cerebrovasc ular events include myocardial infarction, coronary artery revascularization (e.g., bypass graft, angioplasty, stent, atherectomy), congestive heart failure and stroke . 19 Supporting evidence comes from studies “that observed associations between long - term exposure to PM 10 and an increase in respiratory symptoms and reductions in lung function growth in areas where PM 10 is dominated by PM 2.5 ” (US EPA, 2009a, p. 2 - 12) .***E.O. 12866 Review

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Page 27 of 133 lung function 20 associated with long - term exposure to PM 2.5 persist into early adulthood (U.S. EPA, 2009a, p. 7 - 27; Gauderman et al., 2004) . Additional analyses of the Southern California Children’s Health Study cohort reported an association between long - term PM 2.5 exposure and bronchitic symptoms (US EPA, 2009a, p. 7 - 23 to 24; McConnell et al., 2003) that remained positive in co - pollutant models, with the PM 2.5 effect estimates increasing in magnitude in some models and decreasing in others, and a strong modif ying effect of PM 2.5 on the association between lung function and asthma incidence (US EPA, 2009, 7 - 24; Islam et al., 2007). The outcomes observed in these more recent reports from the Southern California Children’s Health Study, including evaluation of a broader range of endpoints and longer follow - up periods, were larger in magnitude and more precise than previously reported. Supporting these results are new longitudinal cohort studies conducted by other researchers in varying locations using different me thods (US EPA, 2009a, section 7.3.9.1). New evidence from a U.S. cohort of cystic fibrosis patients provided evidence of association between long - term PM 2.5 exposures and exacerbations of respiratory symptoms resulting in hospital admissions or use of home intravenous antibiotics (US EPA, 2009a, p. 7 - 25; Goss et al., 2004). Toxicological studies provide coherence and biological plausibility for the respiratory effects observed in epidemiological studies (US EPA, 2009a, p. 7 - 42). For example, pre - and postna tal exposure to ambient levels of urban particles has been found to affect lung development in an animal model (US EPA, 2009a, section 7.3.2.2; p. 7 - 43). This finding is important because impaired lung development is one mechanism by which PM exposure may decrease lung function growth in children (US EPA, 2009a, p. 2 - 12; section 7.3). With regard to respiratory - related mortality associated with long - term PM 2.5 exposure, the Integrated Science Assessment concludes that “when deaths due to respiratory causes are separated from 20 Clinical significance was defined as an FEV 1 below 80 percent of the predicted value, a criterion commonly used in clinical settings to identify persons at increased risk for adverse respiratory conditions (US EPA, 2009a, p. 7 - 29 to 7 - 30) . The primary NAAQS for sulfur dioxide (SO 2 ) also includes thi s interpretation for FEV 1 (75 FR 35525, June 22, 2010).***E.O. 12866 Review

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Page 28 of 133 all - cause (nonaccidental) and cardiopulmonary deaths, there is limited and inconclusive evidence for an effect of PM 2.5 on respiratory mortality, with one large cohort study finding a reduction in deaths due to respiratory causes associ ated with reduced PM 2.5 concentrations, and another large cohort study finding no PM 2.5 associations with respiratory mortality” (US EPA, 2009a, p. 7 - 41). The extended follow - up of the Harvard Six Cities study reported a positive but statistically non - significant association between long - term PM 2.5 exposure and respiratory - related mortality (Laden et al., 2006), whereas Pope et al. (2004) found no association in the ACS cohort (US EPA, 2009a, p. 7 - 84). There is emerging but limited evidence for an association between long - term PM 2.5 exposure and respiratory mortality in post - neonatal infants where long - term exposure was considered as approximately one month to one year (US EPA, 2009a, pp. 7 - 54 to 7 - 55). Emerging evidence of short - and long - term exposure to PM 2.5 and respiratory morbidity and infant mortality provide some support for the weak r espiratory - related mortality effects observed. Beyond effects considered to have causal or likely causal relationships with long - term PM 2.5 exposure as discussed above, the following health outcomes are classified in the Integrated Science Assessment as h aving evidence suggestive of a causal relationship with long - term PM 2.5 exposure: (1) reproductive and developmental effects and (2) cancer, mutagenicity, and genotoxicity effects (US EPA, 2009a, Table 2 - 6). With regard to reproductive and developmental ef fects, the Integrated Science Assessment notes, “[e]vidence is accumulating for PM 2.5 - related effects on low birth weight and infant mortality, especially due to respiratory causes during the post - neonatal period” (US EPA, 2009a, p. 2 - 13). New evidence ava ilable in this review reports significant associations between exposure to PM 2.5 during pregnancy and lower birth weight and infant mortality, with less consistent evidence for pre - term birth and intrauterine growth restriction. (US EPA, 2009a, section 7.4 ). The Integrated Science Assessment further notes that “[i]nfants and fetal development processes may be particularly vulnerable to PM exposure, and although the physical mechanisms are not fully understood, several hypotheses***E.O. 12866 Review

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Page 29 of 133 have been proposed involving direct effects on fetal health, altered placenta function, or indirect effects on the mother’s health” (US EPA, 2009a, section 7.4.1). Although toxicological studies provide some evidence that supports an association between long - term PM 2.5 exposure and a dverse reproductive and developmental outcomes, there is “little mechanistic information or biological plausibility for an association between long - term PM exposure and adverse birth outcomes (e.g., low birth weight, infant mortality)” (US EPA, 2009a, p. 2 - 13). With regard to cancer, mutagenic and genotoxic effects, “[m]ultiple epidemiologic studies have shown a consistent positive association between PM 2.5 and lung cancer mortality, but studies have generally not reported associations between PM 2.5 and lu ng cancer incidence” (US EPA, 2009a, p. 2 - 13 and sections 2.3.1.2 and 7.5; Table 7 - 7; Figures 7 - 6 and 7 - 7). The extended follow - up to the ACS study reported an association between long - term PM 2.5 exposure and lung cancer mortality (US EPA, 2009a, p. 7 - 71; Krewski et al., 2009) as did the extended follow - up to the Harvard Six Cities study when considering the entire 25 - year follow - up period (Laden et al., 2006). There is some evidence, primarily from in vitro studies, providing biological plausibility for th e PM - lung cancer relationships observed in epidemiological studies (US EPA, 2009a, p. 7 - 80), although in vivo toxicological studies of carcinogenicity generally reported mixed results (US EPA, 2009a, section 7.5). b. Health Effects Associated with Short - term PM 2.5 Exposures In considering effects associated with short - term PM 2.5 exposure, the body of currently available scientific evidence has been expanded greatly by the publication of a number of new multi - city, time series studies that have used uniform met hodologies to investigate the effects of short - term fine particle exposures on public health. This body of evidence provides a more expansive data base and considers multiple locations representing varying regions and seasons that provide evidence of the i nfluence of climate and air pollution mixes on PM 2.5 - associated health effects. These studies provide more precise***E.O. 12866 Review

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Page 30 of 133 estimates of the magnitude of effects associated with short - term PM 2.5 exposure than most smaller - scale single - city studies that were more co mmonly available in the last review (US EPA 2009a, chapter 6). With regard to mortality, new U.S. and Canadian multi - city and single - city PM 2.5 exposure studies have found generally consistent positive associations between short - term PM 2.5 exposures and cardiovascular - and respiratory - related mortality as well as all - cause (non - accidental) mortality (US EPA, 2009a, sections 2.3.1.1, 6.2.11 and 6.5.2.2; Figures 6 - 26, 6 - 27, and 6 - 28). In an analysis of the National Morbidity, Mortality, and A ir Pollution Study (NMMAPS) data, Dominici et al. (2007) reported associations between fine particle exposures and all - cause and cardiopulmonary - related mortality (US EPA, 2009a, p. 6 - 175, Figure 6 - 26). In a study of 112 U.S. cities, Zanobetti and Schwartz (2009) reported positive associations (in 99 percent of the cities) and frequently statistically significant associations (in 55 percent of the cities) between short - term PM 2.5 exposure and total (non - accidental) mortality (US EPA, 2009a, pp 6 - 176 to 6 - 17 9; Figures 6 - 23 and 6 - 24). 21 A Canadian 12 - city study (Burnett et al., 2004) is generally consistent with an earlier Canadian 8 - city study (Burnett and Goldberg, 2003) . Both studies reported a positive and statistically significant association between short term PM 2.5 exposure and mortality (US EPA, 2009a, p 6 - 182, Figure 2 - 1), although the influence of nitrogen dioxide (NO 2 ) and limited PM 2.5 data for several years during the study period somewhat diminished the findings reported in the 12 - city study. In ad dition to these multi - city studies, e vidence from available single - city studies suggests that gaseous copollutants do not confound the PM 2.5 - mortality association (US EPA, 2009a, section 2.3.1.1). Collectively, these studies provide generally consistent an d much stronger evidence for PM 2.5 - associated mortality than the evidence available in the last review . (US EPA, 2011a, p.2 - 24). With regard to cardiovascular effects, new multi - city as well as single - city short - term PM 2.5 exposure studies conducted since the last review support a largely positive and frequently statistically 21 Single - city Bayes - adjusted effect estimates for the 112 cities analyzed in Zanobetti and Schwartz (2009) were provided by the study author (personal communication with Dr. Antonella Zanobetti, 2009; see also US EPA, 2009a, Figure 6 - 24).***E.O. 12866 Review

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Page 31 of 133 significant association between short - term exposure to PM 2.5 and cardiovascular - related morbidity and mortality, substantiating prior findings. For example, among a multi - city cohort of older adults participating in the Medicare Air Pollution Study (MCAPS), investigators reported evidence of a positive association between short - term PM 2.5 exposures and hospital admissions related to cardiovascular outcomes (US EPA, 2009a, pp. 6 - 57 to 5 8; Dominici et al, 2006a; Bell et al, 2008). The strongest evidence for cardiovascular effects has been observed predominantly for hospital admissions and emergency department visits for ischemic heart disease and congestive heart failure, and cardiovascul ar - related mortality (US EPA, 2009a, Figure 2 - 1, p. 6 - 79, sections 6.2.10.3, 6.2.10.5, and 6.2.11; Bell et al., 2008; Dominici et al., 2006a; Tolbert et al., 2007; Zanobetti and Schwartz, 2009). In studies that evaluated the potential for confounding using co - pollutant models, PM 2.5 effect estimates for cardiovascular - related hospital admissions and emergency department visits generally remained positive, with the magnitude of PM 2.5 effect estimates increasing in some models and decreasing in others (US EPA, 2009a, Figure 6 - 5). Furthermore, these findings are supported by a recent study of a multi - city cohort of women participating in the WH I study that reported a positive but statistically nonsignificant association between short - term exposure to PM 2.5 and electrocardiogram measures of myocardial ischemia (Zhang et al., 2009). In focusing on respiratory effects, the strongest evidence from short - term PM 2.5 exposure studies has been observed for respiratory - related emergency department visits and hos pital admissions for chronic obstructive pulmonary disease (COPD) and respiratory infections (US EPA, 2009a, sections 2.3.1.1 and 6.3.8.3; Figures 2 - 1 and 6 - 13; Dominici et al., 2006a). In studies that employed co - pollutant models to evaluate the potential for confounding, PM 2.5 effect estimates for respiratory - related hospital admissions and emergency department visits generally remained positive, with the magnitude of PM 2.5 effect estimates increasing in some models and decreasing in others (US EPA, 2009a , Figure 6 - 15). Evidence for PM 2.5 - related respiratory effects has also been observed in panel studies, which indicate***E.O. 12866 Review

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Page 32 of 133 associations with respiratory symptoms, pulmonary function, and pulmonary inflammation among asthmatic children (US EPA, 2009a, p. 2 - 10) . Although not consistently observed, some controlled human exposure studies have reported small decrements in various measures of pulmonary function following controlled exposures to PM 2.5 (US EPA, 20009a, p. 2 - 10). Furthermore, the comparatively larger bo dy of toxicological evidence since the last review is coherent with the evidence from epidemiological and controlled human exposure studies that examined short - term exposures to PM 2.5 and respiratory effects (US EPA, 2009a, section 6.3.10.1). c. Summary In considering the extent to which newly available scientific evidence strengthens or calls into question evidence of associations identified in the last review between ambient fine particle exposures and health effects, the Policy Assessment recognizes th at much progress has been made in assessing some key uncertainties related to our understanding of health effects associated with long - and short term exposure to PM 2.5 . As briefly discussed above as well as in the more complete discussion of the evidence as presented and assessed in the Integrated Science Assessment , the Policy Assessment notes that the newly available information combined with information available in the last review provides substantially stronger confidence in a causal relationship betw een long - and short - term exposures to PM 2.5 and mortality and cardiovascular effects. In addition, the newly available evidence reinforces and expands the evidence supporting a likely causal relationship between long - and short - term exposure to PM 2.5 and r espiratory effects. The body of scientific evidence is somewhat expanded but is still limited with respect to associations between long - term PM 2.5 exposures and developmental and reproductive effects as well as cancer, mutagenic, and genotoxic effects. The Integrated Science Assessment concludes that these data provides evidence that is suggestive of a causal relationship for these effects. Thus, the Policy Assessment concludes there is stronger and more consistent and coherent support for associations betw een long - and short - term PM 2.5 exposure and a broader range of health outcomes than***E.O. 12866 Review

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Page 33 of 133 was available in the last review, providing the basis for fine particle standards at least as protective as the current PM 2.5 standards. 2. Limitations and Uncertainties Assoc iated with the Currently Available Evidence With respect to understanding the nature and magnitude of PM 2.5 - related risks, the Policy Assessment recognizes that important uncertainties remain in the current review (US EPA, 2011a, p. 2 - 25). Epidemiological studies evaluating health effects associated with long - and short - term PM 2.5 exposures have reported heterogeneity in responses both within and between cities and geographic regions within the U.S. In particular, the Policy Assessment notes that there are challenges with interpreting differences in health effects observed in the eastern versus western parts of the U.S., including evaluating effects stratified by seasons. 22 This heterogeneity may be attributed, in part, to differences in the fine particle com position or related to exposure measurement error. However, the currently available evidence and limited availability of city - specific PM 2.5 speciation data does not allow conclusions to be drawn regarding the relative toxicity of PM 2.5 components or group of components associated with any source categories of fine particles in different locations (US EPA, 2009a, p. 2 - 17) . Furthermore, important uncertainties remain in this review related to understanding the temporal and spatial variability in PM 2.5 concen trations, including PM 2.5 components, and associated health impacts across different geographic areas and seasons . I n considering the relationships between PM composition and health effects, the ISA notes that the scientific evidence continues to evolve and concludes that, while many constituents of PM can be linked with differing health effects, the evidence is not yet sufficient to allow differentiation of those constituents or sources that may be more closely related to specific health outcomes (US EPA, 2009a, p. 2 - 17) . In particular, based on assessing the body of available evidence, the ISA notes that (1) cardiovasc ular effects have been linked with elemental carbon as well as with PM 2.5 from crustal 22 Seasonal differences in effects may be related to PM 2.5 composition as well as regional differences in climate and infrastructure that may affect time spent outdoors or indoors, housing characteristics including ai r conditioning usage, and differences in baseline incidence rates (US EPA, 2009a, p. 3 - 182).***E.O. 12866 Review

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Page 34 of 133 sources, traffic, and wood smoke/vegetative burning; (2) respiratory effects have been linked with secondary sulfate PM 2.5 as well as with PM 2.5 from crustal/soil/road d ust and traffic sources; and (3) a few studies have reported associations between total mortality and secondary sulfate/long - range transport, traffic, and salt. While specific PM 2.5 constituents have been linked with various PM 2.5 - related health effects in a small number of studies, research continues to focus on the identification of specific constituents or sources that may be most closely related to specific PM 2.5 - related health outcomes. Exposure measurement error is also an important source of uncerta inty (US EPA, 2009a, section 3.8.6) . Variability in the associations observed across PM 2.5 epidemiological studies may be due in part to exposure error related to measurement - related issues, the use of central fixed - site monitors to represent population ex posure to PM 2.5 , models used in lieu of or to supplement ambient measurements, and our limited understanding of factors that may influence exposures (e.g., topography, the built environment, climate, source characteristics, ventilation usage, personal acti vity patterns, photochemistry). As noted in the Integrated Science Assessment, exposure measurement error can introduce bias and increased uncertainty in associated health effect estimates (US EPA, 2009a, p. 2 - 17). In addition, where PM 2.5 and other pollu tants (e.g., ozone, nitrogen dioxide, and carbon monoxide) are correlated, it can be difficult to distinguish the effects of the various pollutants in the ambient mixture (i.e., co - pollutant confounding). 23 Although many recent U . S . multi - city As noted above, although short - term studies did not analyze multipollutant of cardiovascular and respiratory hospital admissions and emergency department visits generally reported that PM 2.5 effect estimates remained positive, the magnitude of those effect estimates increased in some models , and decreased in others . In addition, a lthough evidence from single - city studies available in the last review suggest suggest s that gaseous copollutants do not confound the PM 2.5 - related mortality association (US 23 A copollutant meets the criteria for potential confounding in PM - health associations if: (1) it is a potential risk factor for the health effect under study; (2) it is correlated with PM; and (3) it does not act as an intermediate step in the pathway between PM exposure and the health effect under study (US EPA, 2004, p. 8 - 10) . Formatted: Font color: Black***E.O. 12866 Review

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Page 35 of 133 EPA, 2004, sectio n 8.4.3.3 ) which ), a conclusion that is further supported by studies that examined the PM 10 - mortality relationship (US EPA, 2009a, p. 6 - 182 and 6 - 201 ) . ), many recent U.S. multi - city studies have not analyzed multipollutant models. While uncertainties and limitations still remain in the available health effects evidence, the Administrator judges the currently available scientific data base to be stronger and more consistent than in previous reviews providing a strong basis for decision making in this revie w. 3. Susceptible At - Risk Populations In identifying population groups or lifestages at greatest risk for health risk from a specific pollutant, the terms susceptibility, vulnerability, sensitivity, and at - risk are commonly employed. The definition for these t erms sometimes varies, but in most instances “susceptibility” refers to biological or intrinsic factors (e.g., lifestage, gender , preexisting disease/conditions ) while “vulnerability” refers to nonbiological or extrinsic factors (e.g., socioeconomic factor s). Additionally, However, factors included in some cases, the terms “at - risk” and “sensitive” have been used to encompass both of these concepts . At times, however, factors of “susceptibility” and “vulnerability” are intertwined and are difficult to disti nguish. In the Integrated Science Assessment , the term “susceptibility” has been used broadly to recognize populations that have a greater likelihood of experiencing effects related to ambient PM exposure 24 , such that use of the term “susceptible population s” in the Integrated Science Assessment is defined as follows : Populations that have a greater likelihood of experiencing health effects related to exposure to an air pollutant (e.g., PM) due to a variety of factors including, but not limited to: genetic or developmental factors, race, gender, lifestage, lifestyle (e.g., smoking status and nutrition) or preexisting disease; as well as population - level factors that can increase an individual's exposure to an air pollutant (e.g., PM) such as socioeconomic st atus [SES], which encompasses reduced access to health care, low educational attainment, residential location, and other factors (US EPA, 2009a, p. 8 - 1) .

24 Although studies have primarily used exposures to PM 10 or PM 2.5 , the available evide nce suggests that the identified factors also increase risk from PM 10 - 2.5 (US EPA, 2009a, section 8.1.8) .***E.O. 12866 Review

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Page 36 of 133 Susceptible used as a term that encompasses factors related both to susceptibility and vulnerability. 25 In the development of a more recent Integrated Science Assessment, the Agency is using the term “at - risk” groups to more broadly define the populations with characteristics that increase the risk of pollutant - related health effects (US EPA, 201 1d , p. 8 - 1 ) . Therefore, in this proposal, the term “at risk” is the broadly encompassing term used for groups with specific factors that increase the risk of PM - related health effects in a population.At - risk populations could exhibit a greater risk of PM - related heal th effects than the general population for a number of reasons including , : being affected by lower concentrations of PM, experiencing a larger health impact at a given PM concentration or being exposed to higher PM concentrations than the general populatio n. Given the heterogeneity of individual responses to PM exposures, the severity of the health effects experienced by a susceptible an at - risk population may be much greater than that experienced by the population at large. As summarized below and presented in more detail in chapter 8 of the Integrated Science Assessment and section 2.2.1 of the Policy Assessment , the currently available epidemiological and controlled human exposure evidence expands our understanding of previously identified susceptible at risk populations (i.e., children, older adults, and individuals with pre - existing heart and lung disease) and supports the identification of additional susceptible at - risk populations (e.g., persons with lower socioeconomic status, genetic differences) ( US EPA, 2009a, section 2.4.1, Table 8 - 2). In addition, toxicological studies provide underlying support for the biological mechanisms that potentially lead to increased susceptibility to PM - related health effects (US EPA, 2009a, sections 2.4.1 and 8.1.8).

25 The term “susceptible population ” is defined in the Integrated Science Assessment as “ [ P ] opulations that have a greater likelihood of experiencing health effects related to exposure to an air pollutant (e.g., PM) due to a variety of factors including, but not limited to: genetic or developmental factors, race, gender, lifestage, lifestyle (e.g., smoking status and nutrition) or preexisting disease; a s well as population - level factors that can increase an individual's exposure to an air pol lutant (e.g., PM) such as socioeconomic status [SES], which encompasses reduced access to health care, low educational attainment, residential location, and other fa ctors (US EPA, 2009a, p. 8 - 1).***E.O. 12866 Review

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Page 37 of 133 Two different lifestages have been associated with increased susceptibility risk to PM - related health effects: childhood (i.e., less than 18 years of age) and older adulthood (i.e., 65 years of age and older). Childhood represents a lifestage where suscept ibility to PM exposures may be related to the following observations: children spend more time outdoors; children have greater activity levels than adults; children have exposures resulting in higher doses per body weight and lung surface area; and the dev eloping lung is prone to damage, including irreversible effects, from environmental pollutants as it continues to develop through adolescence (US EPA, 2009a, section 8.1.1.2). Older adults represent a lifestage where susceptibility to PM - associated health effects may be related to the higher prevalence of pre - existing cardiovascular and respiratory diseases found in this age group compared to younger age groups as well as the gradual decline in physiological processes that occur as part of the aging process (US EPA, 2009a, section 8.1.1.1). In addition, accumulating evidence suggests that the developing fetus may also represent an additional lifestage that is susceptible at greater risk to PM exposures (US EPA, 2009a, sections 2.3.1.2 and 7.4). With regard t o mortality, recent epidemiological studies have continued to find that older adults are at greater risk of all - cause (non - accidental) mortality associated with short - term exposure to both PM 2.5 and PM 10 , providing consistent and stronger evidence of effec ts in this susceptible at - risk population compared to the last review (US EPA, 2009a, Figure 7 - 7, section 8.1.1.1, Zeger et al., 2008). Evidence is accumulating for PM 2.5 - related infant mortality, especially due to respiratory causes during the post - neonata l period (US EPA, 2009a, sections 2.3.1.2 and 7.4). With regard to morbidity effects, currently available studies provide evidence that older adults have heightened responses, especially for cardiovascular - related effects, and children have heightened res ponses for respiratory - related effects (US EPA, 2009a, p. 2 - 23). In considering respiratory - related effects in children associated with long - term PM exposures, the Policy Assessment recognizes that our understanding of effects on lung development has been strengthened based on newly available evidence***E.O. 12866 Review

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Page 38 of 133 that is consistent and coherent across different study designs, locations, and research groups (US EPA, 2011a, p. 2 - 28). The strongest evidence comes from the extended follow - up for the Southern California Chi ldren’s Health Study which includes several new studies that report positive associations between long - term exposure to PM 2.5 and respiratory morbidity, particularly for such endpoints as lung function growth, respiratory symptoms (e.g., bronchitic symptom s), and respiratory disease incidence (US EPA, 2009a, section 7.3; McConnell et al, 2003; Gauderman et al., 2004; Islam et al., 2007). These analyses provide evidence that PM 2.5 - related effects persist into early adulthood and are more robust and larger in magnitude than previously reported. With regard to respiratory effects in children associated with short term exposures to PM 2.5 , currently available studies provide stronger evidence of respiratory - related hospitalizations with larger effect estimates ob served among children. In addition, reductions in lung function (i.e., FEV 1 ) and increases in respiratory symptoms and medication use associated with PM exposures have been reported among asthmatic children (US EPA, 2009a, sections 6.3.1, 6.3.2.1, and 8.4. 9). A number of health conditions have been found to put individuals at greater risk for adverse effects following exposure to PM. The currently available evidence confirms and strengthens evidence in the last review that individuals with underlying cardi ovascular and respiratory diseases are more susceptible to PM exposures (US EPA, 2009a, section 8.1.6; US EPA, 2011a, section 2.2.1). There is also emerging evidence that people with diabetes, who are at risk for cardiovascular disease, as well as obese in dividuals, may have increased susceptibility to PM exposures (US EPA, 2009a, section 8.1.6.4). As discussed in section 8.1.6 of the Integrated Science Assessment, this body of evidence includes findings from epidemiological and human clinical studies that associations with mortality or morbidity are greater in those with pre - existing conditions, and also includes evidence from toxicological studies using animal models of cardiopulmonary disease.***E.O. 12866 Review

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Page 39 of 133 Stronger evidence is available in this review than the last in dicating that people from lower socioeconomic strata are a susceptible an at - risk population relative to PM exposures (US EPA, 2009a, section 8.1.7; US EPA, 2011a, section 2.2.1). Persons with lower socioeconomic status (SES) 26 have been generally found to h ave a higher prevalence of pre - existing diseases; limited access to medical treatment; and increased nutritional deficiencies, which can increase this population’s risk to PM - related effects . Investigation of potential genetic susceptibility has provided evidence that individuals with specific genetic differences are more susceptible to PM - related effects (US EPA, 2009a, pp. 8 - 7 to 8 - 9) . More research is needed to better understand the relationship between genetic effects and potential susceptibility to PM - related effects (US EPA, 2011a, p. 2 - 109). In summary, there are several at - risk populations that may be especially susceptible or vulnerable to PM - related effects. These groups include those with preexisting heart and lung diseases, specific genetic dif

ferences, and lower socioeconomic status as well as the lifestages of childhood and older adulthood. Evidence for PM - related effects in these susceptible at - risk populations has expanded and is stronger than previously observed. There is emerging, though st ill limited, evidence for additional potentially susceptible at - risk populations, such as those with diabetes, people who are obese, pregnant women, and the developing fetus. The available evidence does not generally allow distinctions to be drawn between t he PM indicators in terms of whether populations are more susceptible at - risk to a particular size fraction (i.e., PM 2.5 and PM 10 - 2.5 ). 4. Potential PM 2.5 - Related Impacts on Public Health The population potentially affected by PM 2.5 is large. In addition, large subgroups of the U.S. population have been identified as susceptible at - risk populations as described in section III.B.3. While individual effect estimates from epidemiological studies may be small in size, the public health im pact 26 Socioeconomic status is a composite measure that usually consists of economic status, measured by income; social status measured by education; and work status measured by occupation (US EPA, 2009a, p. 8 - 14).***E.O. 12866 Review

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Page 40 of 133 of the mortality and morbidity associations can be quite large. In addition, it appears that mortality risks are not limited to the very frail. Taken together, these results suggest that exposure to ambient PM 2.5 concentrations can have substantial pu blic health impacts. With regard to susceptible at - risk populations in the United States, approximately 7 percent of adults (approximately 16 million adults) and 9 percent of children (approximately 7 million children) have asthma (US EPA 2009a, Table 8 - 3; CDC, 2008 27 ). In addition, approximately 4 percent of adults have been diagnosed with chronic bronchitis and approximately 2 percent with emphysema (US EPA, 2009a, Table 8 - 3). Approximately 11 percent of adults have been diagnosed with heart disease, 6 perc ent with coronary heart disease, 23 percent with hypertension, and 8 percent with diabetes (US EPA, 2009a, Table 8 - 3). In addition, approximately 3 percent of the U.S. adult population has suffered a stroke (US EPA, 2009a, Table 8 - 3). Therefore, large port ions of the United States population are in groups that may be susceptible at increased risk to health effects associated with exposures to ambient PM 2.5 . The size of the potentially at - risk population suggests that exposure to ambient PM 2.5 has significant impact on public health in the United States. C. Quantitative Characterization of Health Risks 1. Overview In this review, the quantitative risk assessment builds on the approach used and lessons learned in the last review and focuses on improving the character ization of the overall confidence in the risk estimates, including related uncertainties, by incorporating a number of enhancements, in terms of both the methods and data used in the analyses . The goals of this quantitative risk assessment are largely the same as those articulated in the risk assessment conducted for the last review . These goals include: (1) to provide estimates of the potential magnitude of premature mortality and/or selected morbidity effects in the population associated with recent ambie nt level of PM 2.5 and with simulating just meeting the 27 For percentag es, see http://www.cdc.gov/ASTHMA/nhis/06/table4 - 1.htm . For population estimates, see http://www.cdc.gov/ASTHMA/nhis/06/table3 - 1.htm . Formatted: Font: Italic, No underline***E.O. 12866 Review

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Page 41 of 133 current and alternative suites of PM 2.5 standards in 15 selected urban study areas, including, where data were available, consideration of impacts on susceptible at - risk populations; (2) to develop a be tter understanding of the influence of various inputs and assumptions on the risk estimates to more clearly differentiate among alternative suites of standards; and (3) to gain insights into the distribution of risks and patterns of risk reductions and the variability and uncertainties in those risk estimates. In addition, the quantitative risk assessment included nationwide estimates of the potential magnitude of premature mortality associated with long - term exposure to recent ambient PM 2.5 concentrations to more broadly characterize this risk on a national scale and to support the interpretation of the more detailed risk estimates generated for selected urban study areas. The risk assessment conducted for this review is more fully described and presented in the Risk Assessment (US EPA, 2010a) and summarized in detail in the Policy Assessment (US EPA, 2011a, sections 2.2.2. and 2.3.4.2). The scope and methodology for this risk assessment were developed over the last few years with considerable input from CA SAC and the public as described in section I.B.3. 2. Summary of Design Aspects Based on a review of the evidence presented and assessed in the Integrated Science Assessment and criteria for selecting specific health effect endpoints discussed in the Risk Asse ssment (US EPA, 2010a, section 3.3.1), the following broad categories of health endpoints were included in the quantitative risk assessment: (1) all - cause, ischemic heart disease - related, cardiopulmonary - related, and lung cancer - related mortality associate d with long - term PM 2.5 exposure; (2) non - accidental, cardiovascular - related, and respiratory - related mortality associated with short - term PM 2.5 exposure; and (3) cardiovascular - related and respiratory - related hospital admissions and asthma - related emergency department visits associated with short - term PM 2.5 exposure. The evidence available for these selected health effect endpoints generally focu sed on the entire population, although some information was available to support analyses that considered differences in estimated risk for susceptible at - risk***E.O. 12866 Review

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Page 42 of 133 populations including older adults and persons with pre - existing cardiovascular and respiratory d iseases (US EPA, 2010a, p. 3 - 29). The quantitative risk assessment estimates risks for various health effects in 15 urban study areas. The selection of urban study areas was based on a number of criteria including: (1) consideration of urban study areas ev aluated in the last PM risk assessment; (2) consideration of locations evaluated in key epidemiological studies; (3) preference for locations with relatively elevated annual and/or 24 - hour PM 2.5 monitored concentrations; and (4) preference for including lo cations from different regions across the country, reflecting potential differences in PM 2.5 sources, composition, and potentially other factors which might impact PM 2.5 - related risk (US EPA, 2010a, section 3.3.2). Based on the results of several analyses examining the representativeness of these 15 urban study areas in the broader national context, the Risk Assessment concludes that these study areas are generally representative of urban areas in the U.S. likely to experience relatively elevated levels of risk related to ambient PM 2.5 exposure with the potential for better characterization at the higher end of that distribution (US EPA, 2011a, p. 2 - 42; US EPA, 2010a, section 4.4, Figure 4 - 17). 28 In order to estimate the incidence of a particular health effe ct associated with recent ambient conditions in a specific urban study area attributable to PM 2.5 exposures, as well as the change in incidence corresponding to a given change in PM 2.5 concentrations resulting from simulating just meeting current or altern ative PM 2.5 standards, three elements are required (US EPA, 2010a, section 3.1.1, Figures 3 - 2 and 3 - 3). These elements are: (1) air quality information (including recent air quality data for PM 2.5 from ambient monitors for the selected location, estimates of background PM 2.5 concentrations appropriate for that location, and a method for adjusting the recent data to reflect patterns of air quality estimated to occur when the area just meets a given set of PM 2.5 standards); (2) relative 28 The representativeness analysis also showed that the 15 urban study areas do not capture areas with the highest baseline morality risks or the oldest populations (both of which can result in higher PM 2.5 - related mortality estimates) . However, some of th e areas with the highest values for these attributes have relatively low PM 2.5 concentrations (e.g., urban areas in Florida) and, consequently, the Risk Assessment concludes failure to include these areas in the set of urban study areas is unlikely to excl ude high PM 2.5 - risk locations (US EPA, 2010a, section 4.4.1).***E.O. 12866 Review

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Page 43 of 133 risk - based concentrati on - response functions that provide an estimate of the relationship between the health endpoints of interest and ambient PM 2.5 concentrations; and (3) baseline health effects incidence rates and population data, which are needed to provide an estimate of th e incidence of health effects in an area before any changes in PM 2.5 air quality. 29 The Risk Assessment includes a core set of risk estimates supplemented by an alternative set of risk results generated using single - factor and multi - factor sensitivity anal yses . The core set of risk estimates was developed using the combination of modeling elements and input data sets identified in the Risk Assessment as having higher confidence relative to inputs used in the sensitivity analyses . The results of the sensitiv ity analyses provide information to evaluate and rank the potential impacts of key sources of uncertainty on the core risk estimates (US EPA, 2010a, sections 3.5 and 4.3, Table 4 - 3). In addition, the sensitivity analyses represent a set of reasonable alter natives to the core set of risk estimates that fall within an overall set of plausible risk estimates surrounding the core estimates (US EPA, 2010a, section 4.3.2). Recent air quality was characterized for the 15 urban study areas based on 24 - hour PM 2.5 c oncentrations measured for 3 years (i.e., 2005, 2006, and 2007) as described in section 3.2.1 of the Risk Assessment. Different methodologies were then used to simulate conditions for just meeting the current or alternative PM 2.5 standards (US EPA, 2010a, section 3.2.3). This included using the single rollback approach used in the risk assessment conducted for the last review which reflects a uniform regional pattern of reductions in ambient PM 2.5 concentrations across monitors (i.e., proportional rollback approach). The proportional rollback approach was used in generating the core risk estimates (US EPA, 29 Incidence rates express the occurrence of a disease or event (e.g., death, hospital admission) in a specific period of time, usually per year . Rates are expressed either as a value per population group (e.g., the number of cases in Philadelphia County) or a value per number of people (e.g., the number of cases per 10,000 residents in Philadelphia County), and may be age - and/or sex - specific . Incidence rates vary among geographic areas du e to differences in populations characteristics (e.g., age distribution) and factors promoting illness (e.g., smoking rates, air pollution concentrations) . The baseline incidence rate provides an estimate of the incidence rate (i.e., number of cases of the health effect per year, usually per 10,000 or 100,000 general population) in the assessment location unrelated to changes in ambient PM 2.5 concentrations in that location (US EPA , 2010a, section 3.4) .***E.O. 12866 Review

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Page 44 of 133 2010a, section 3.2.3.1). In sensitivity analyses, the Risk Assessment also applied two alternative rollback approaches (i.e., hybrid and locally - focused r ollback approaches) 30 to better characterize potential variability in the way air quality in urban areas responds to programs put in place to meet the current or alternative PM 2.5 standards . In considering the three rollback approaches collectively, the proportional and locally - focused methods are approaches that are more likely to represent “bounding” scenarios related to the spatial pattern of future redu ctions in ambient PM 2.5 concentrations. In contrast, the hybrid approach, in principle, reflects a m ore plausible or representative rollback strategy since it: (1) reflects consideration for site - specific information regarding larger PM 2.5 sources and their potential impact on source - oriented monitors and (2) combines elements of more locally - focused and regionally focused patterns of reductions (US EPA, 2010a, section 3.2.3). The peak - to - mean ratio of ambient PM 2.5 concentrations within a study area informs the type of rollback approach used to simulate just meeting the current or alternative suites of s tandards to determine the magnitude of the reduction in annual mean PM 2.5 concentrations for that study area and consequently the degree of risk reduction. 31 For example, study areas with relatively high peak - to - mean ratios are likely to have greater estima ted risk reductions for the current suite of standards (depending on the combination of 24 - hour and annual design values), and such locations can be especially sensitive to the type of rollback approach used, with the proportional rollback approach resulti ng in notably greater estimated risk reduction compared with the locally - focused rollback approach . In contrast, study areas with lower peak - to - mean ratios typically experience greater risk reductions when simulating just meeting the current or alternative annual - standard level than with simulating just meeting the current or 30 The hybrid rollback approach involves a combination of an initial step of a more localized reduction in ambient PM 2.5 concentrations at source - oriented monitors followed by a regional pattern of reduction across all monitors in a study area (US EPA, 2010a, section 3.2.3.2) . The locally - focused rollback app roach involves a focused reduction of concentrations only at those monitors exceeding the current or alternative 24 - hour standard levels (US EPA, 2010a, section 3.2.3.3). 31 The peak - to - mean ratio of ambient PM 2.5 concentrations also has a direct bearing on whether the 24 - hour or annual standard will be the generally controlling standard for a particular study area, with higher peak - to - mean ratios generally being associated with locations where the 24 - hour standard is likely the controlling standard.***E.O. 12866 Review

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Page 45 of 133 alternative 24 - hour standard level (again depending on the combination of 24 - hour and annual design values) . In addition, the type of rollback approach used will tend to have less of a n impact on the magnitude of risk reductions for study areas with lower peak - to - mean ratios. Consideration of these two factors helps to inform an understanding of the nature and pattern of estimated risk reductions and risk remaining upon simulation of ju st meeting the current and alternative suites of standards across the urban study areas (US EPA, 2010a, section 5.2.1). The concentration - response functions used in the risk assessment were based on findings from epidemiological studies that have relied o n fixed - site, population - oriented, ambient monitors as a surrogate for actual ambient PM 2.5 exposures. The risk assessment addresses risks attributable to anthropogenic sources and activities (i.e., risk associated with concentrations above policy - relevant background). 32 This approach of estimating risks in excess of background was judged to be more relevant to policy decisions regarding ambient air quality standards than risk estimates that include effects potentially attributable to PM 2.5 concentrations th at are not associated with North American anthropogenic emissions . In modeling risk associated with long - and short - term PM 2.5 exposures, the Risk Assessment initially focused on selecting concentration - response functions from multi - city studies. 33 Concentration response functions from two single - city studies provided coverage for additional health effect endpoints (i.e., emergency department visits for cardiovascular and/or respiratory effects) associated with short term PM 2.5 exposures (US EPA, 20 10a, p. 3 - 37). 32 Policy - relevant background estimates used in the risk assessment model were based on information presented in the Integrated Science Assessment (US EPA, 2009a, section 3.7, Table 3 - 23) and discussed in the Risk Assessment (US EPA, 2010a, section 3.2.2) . T hese values were generated based on a combination of Community Multiscale Air Quality model (CMAQ) and Goddard Earth Observing System (GEOS) - Chem modeling (US EPA, 2009a, section 3.7.1.2; US EPA, 2010a, section 3.2.2) . 33 As noted in section 3.3.3 of the R isk Assessment, multi - city studies have a number of advantages over single - city studies including: increased statistical power providing effect estimates with relatively greater precision and reduced problems with publication bias (i.e., in which studies w ith statistically insignificant or negative results are less likely to get published than those with positive and/or statistically significant results).***E.O. 12866 Review

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Page 46 of 133 With regard to modeling risks associated with long - term PM 2.5 exposure, concentration - response functions used in the risk model are all based on coho rt studies, in which a cohort of individuals is followed over time. In the core analysis, es timated premature mortality risk associated with long - term PM 2.5 concentrations used concentration - response functions from the extended ACS study (Krewski et al., 2009). This study had a number of advantages including: analyses that expanded upon previous publications presenting evaluations of the ACS long - term cohort study and extending the follow - up period to eighteen years; a rigorous examination of different model forms for estimating effect estimates; coverage for a range of ecological variables (e.g., social, economic, and demographic factors) which allowed for consideration of whether these factors confound or modify the relationship between PM 2.5 exposure and mortality; and updated and expanded data sets on incidence and exposure (US EPA, 2010a, p 2 - 9 and 3 - 38). As discussed in section III.B.3, persons of lower socioeconomic status have been identified as a susceptible an at - risk population. The ACS study cohort does not provide representative coverage for persons of lower - socioeconomic status and, th us, the Risk Assessment concludes that using the concentration - response functions from this study may result in risk estimates that are biased low (US EPA, 2010a, p. 5 - 7). Therefore, concentration - response functions from a reanalysis of the Harvard Six Cit ies study (Krewski et al., 2000) were used in a sensitivity analysis to better support generalizing the results of the risk assessment across the broader national population. 34 While being mindful that the use of concentration - response functions from Krews ki et al. (2009) introduces potential for low bias in the core risk estimates, the Policy Assessment also recognizes many strengths of this study and reasons for its continued use for generating the core risk estimates, including: 34 As noted in the last review, the ACS study population has persons generally representative of a highe r SES (e.g., higher educational status) relative to the Harvard Six Cities study population (12 percent versus 28 percent of the cohort had less than a high school education, respectively) (US EPA, 2004, p. 8 - 118) . The Policy Assessment concludes that the Harvard Six Cities study cohort may provide a more representative sample of the broader national population than the ACS study cohort (US EPA, 2011a, p. 2 - 40) .***E.O. 12866 Review

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Page 47 of 133 consideration of a large number of metropolitan statistical areas, inclusion of two time periods for the air quality data which allowed us to consider different exposure windows , and analysis of a wide range of concentration - response function models . Therefore, the Risk Assessment concludes that concentration response functions obtained from this study had the greatest overall support and were appropriate to incorporate in the core risk model (US EPA, 2010a, p. 3 - 38). In the core analysis, for modeling health endpoints associated w ith long - term exposure, the Risk Assessment concluded that modeling risks down to policy - relevant background would require substantial extrapolation of the estimated concentration - response functions below the range of the data on which they were estimated (i.e., the lowest measured levels reported in the epidemiological studies were substantially above policy - relevant background). Therefore, the Risk Assessment concluded it was most appropriate in the core analysis to estimate risk only down to the lowest m easured level to avoid introducing additional uncertainty into the analysis (US EPA, 2010a, 3 - 1 to 3 - 3). 35 A sensitivity analysis comparing the impact of estimated risks down to policy - relevant background rather than down to the lowest measured level (US EP A , 2010a, section 3.5.4.1) used annual estimates of policy - relevant background values for specific geographic regions (US EPA, 2010a, section 3.2.2, Table 3 - 2). With regard to modeling risks associated with short - term PM 2.5 exposure, concentration - response functions from two time - series studies were selected as the primary studies to support the core analysis. Concentration - response functions from Zanobetti and Schwartz (2009) were used in estimating premature non - accidental, cardiovascular - related, and res piratory - related mortality. Concentration response functions from Bell et al. (2008) were used in estimating cardiovascular - related and respiratory - related hospital admissions. In addition, concentration - response functions from two single city studies were used to estimate emergency department visits for cardiovascular and/or respiratory 35 To provide consistency for the different concentration - response functions selected from the l ong - term exposure studies, and, in particular, to avoid the choice of lowest measured levels unduly influencing the results of the risk assessment, the Risk Assessment concluded it was appropriate to select a single lowest measured level

– 5.8 μg/m 3 from t he later exposure period evaluated in Krewski et al. (2009) -- to use in estimating risks associated with long - term PM 2.5 exposures (US EPA, 2010a, p 3 - 3).***E.O. 12866 Review

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Page 4 8 of 133 illnesses associated with short - term PM 2.5 exposure (Tolbert et al., 2007; Ito et al., 2007; US EPA, 2010a, p. 3 - 37). For modeling health endpoints associated with short - t erm PM 2.5 exposure, the Risk Assessment estimates risk down to policy - relevant background exclusively using quarterly values to represent the appropriate block of days within a simulated year (US EPA, 2010a, section 3.2.2, Table 3 - 2). To estimate the chan ge in incidence of a health endpoint associated with a given change in PM 2.5 concentrations, information on the baseline incidence of that endpoint is needed (US EPA, 2010a, section 3.4). In calculating a baseline incidence rate to be used with a concentra tion - response function from a given epidemiological study, the Risk Assessment matched the counties, age grouping, and International Classification of Diseases (ICD) codes used in that study (US EPA, 2010a, section 3.4.2). An important component of a popul ation health risk assessment is the characterization of both uncertainty and variability. 36 The design of the risk assessment includes a number of elements to address these issues, including using guidance from the World Health Organization (WHO, 2008) as a framework for developing the approach used for characterizing uncertainty in the analyses (US EPA, 2010a, section 3.5). The Risk Assessment considers key sources of variability that can impact the nature and magnitude of risks associated with simulating j ust meeting current and alternative standard levels across the urban study areas (US EPA, 2010a, section 3.5.2) . These sources of variability include those that con tribute to differences in risk across urban study areas, but do not directly affect the degr ee of risk reduction associated with the simulation of just meeting current or alternative standard levels (e.g., differences in baseline incidence rates, demographics and population behavior). The Risk Assessment also focuses on factors that not only intr oduce variability into risk estimates across study areas, but also play an important role in determining the magnitude of risk reductions upon simulation of just meeting 36 Variability refers to the heterogeneity of a variable of interest within a population or across di fferent populations . Uncertainty refers to the lack of knowledge regarding the actual values of inputs to an analysis (US EPA, 2010a, p. 3 - 63) . Formatted: Font: Italic Formatted: Font: Italic, No underline***E.O. 12866 Review

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Page 49 of 133 current or alternative standard levels (e.g., peak - to - mean ratios of ambient PM 2.5 con centrations within individual urban study areas and the nature of the rollback approach used to simulate just meeting the current or alternative standards). Key sources of potential variability that are likely to affect population risks and the degree to w hich they were (or were not) fully captured in the design of the risk assessment are discussed in section 3.5.2 of the Risk Assessment. These sources include: PM 2.5 composition; intra urban variability in ambient PM 2.5 concentrations; variability in the pa tterns of reductions in PM 2.5 concentrations associated with different rollback approaches when simulating just meeting the current or alternative standards; co - pollutant exposures; factors related to demographic and socioeconomic status; behavioral differ ences across urban study areas (e.g., time spent outdoors); baseline incidence rates; and longer - term temporal variability in ambient PM 2.5 concentrations reflecting meteorological trends as well as future changes in the mix of PM 2.5 sources, including cha nges in air quality related to future regulatory actions (US EPA, 2010a, pp. 3 - 67 to 3 - 69). Single and multi - factor sensitivity analyses were combined with a qualitative analysis to assess the impact of potential sources of uncertainty on the core risk est imates (US EPA, 2010a, sections 3.5.3 and 3.5.4). The quantitative sensitivity analyses informed our understanding of sources of uncertainty that may have a moderate to large impact on the core risk estimates including: (1) characterizing intra urban popul ation exposure in the context of epidemiology studies linking PM 2.5 to specific health effects; (2) statistical fit of the concentration - response functions for short - term exposure - related health endpoints; (3) shape of the concentration - response functions; (4) specifying the appropriate lag structure for short - term exposure studies; (5) transferability of concentration - response functions from study locations to urban study area locations for long - term exposure - related health endpoints; (6) use of single - cit y versus multi - city studies in the derivation of concentration - response functions; (7) impact of historical air quality on estimates of health risk associate with long - term PM 2.5 exposures; and (8) potential variation in effect estimates reflecting composi tional differences in PM 2.5 (US EPA, 2011a,***E.O. 12866 Review

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Page 50 of 133 section 5.1.4). In addition to identifying sources of uncertainty with a moderate to large impact on the core risk estimates, the single and multi - element sensitivity analyses also produced a set of reasonable al ternative risk estimates that allowed us to place the results of the core analysis in context with regard to uncertainty and potential bias (US EPA, 2010a, section 5.1.4). The qualitative uncertainty analysis supplemented the quantitative sensitivity analy ses by allowing coverage for sources of uncertainty that could not be readily included in the sensitivity analysis (US EPA, 2010a, section 3.5.3). With respect to the long - term exposure - related mortality risk estimates 37 , the most important sources of uncer tainty identified in the quantitative sensitivity analyses included: selection of concentration - response functions; modeling risk down to policy - relevant background versus lowest measured level; and the choice of rollback approach used to simulate just mee ting current or alternative standards (US EPA, 2011a, p. 2 - 39) . With regard to the qualitative analysis of uncertainty, the following sources were identified as potentially having a large impact on the core risk estimates for the long - term exposure - related mortality: characterization of intra - urban population exposures; impact of historical air quality; and potential variation in effect estimates reflecting differences in PM 2.5 composition (US EPA, 2011a, p. 2 - 39). Beyond characterizing uncertainty and var iability, a number of design elements were included in the risk assessment to increase the overall confidence in the risk estimates generated for the 15 urban study areas (US EPA, 2011a, pp. 2 - 38 to 2 - 41). These elements included: (1) use of a deliberative process for specifying components of the risk model that reflects consideration of the latest research on PM 2.5 exposure and risk (US EPA, 2010a, section 5.1.1); (2) integration of key sources of variability into the design as well as the interpretation o f risk estimates (U.S.EPA, 2010a, section 5.1.2); (3) assessment of the degree to which the urban study areas are representative of areas in the U.S. experiencing higher 37 Given increased emphasis placed in this analysis on long - term exposure - related mortality, the uncertainty ana lyses completed for this health endpoint category were more comprehensive than those conducted for analyses of short - term exposure - related mortality and morbidity . This reflects, to some extent, limitations in the epidemiological data available for address ing uncertainty in the latter categories (U.S.EPA , 2010a, section 3.5.4.2).***E.O. 12866 Review

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Page 51 of 133 PM 2.5 - related risk (U.S.EPA, 2010a, section 5.1.3); and (4) identification and assessm ent of important sources of uncertainty and the impact of these uncertainties on the core risk estimates (U.S.EPA, 2010a, section 5.1.4). Two additional analyses examined potential bias and overall confidence in the risk estimates. The first analysis explo red potential bias in the core risk estimates by considering a set of alternative reasonable risk estimates generated as part of a sensitivity analysis. The second analysis compared the annual mean PM 2.5 concentrations associated with simulating just meeti ng the current and alternative suites of standards with the air quality distribution used in deriving the concentration response functions applied in modeling mortality risk. Greater confidence is associated with risk estimates based on simulated annual me an PM 2.5 concentrations that are within the region of the air quality distribution used in deriving the concentration - response functions where the bulk of the data reside (e.g., within one standard deviation around the long - term mean PM 2.5 concentration) (US EPA, 2011a, p. 2 - 38). 3. Risk Estimates and Key Observations As discussed below, three factors figure prominently in the interpretation of the risk estimates associated with simulating just meeting the current and alternative suites of st andards, including: (1) the importance of changes in annual mean PM 2.5 concentrations for a specific study area in estimating changes in risks related to both long - and short - term exposures associated with recent air quality conditions and air quality simu lated to just meet the current and alternative suites of PM 2.5 standards; (2) the ratio of peak - to - mean ambient PM 2.5 concentrations in a study area; and (3) the spatial pattern of ambient PM 2.5 reductions that result from using different approaches to si mulate just meeting the current standard levels (i.e., rollback approaches). The latter two factors are interrelated and influence the degree of risk reduction estimated under the current suite of standards. The magnitude of both long - and short - term expo sure - related risk estimated to remain upon just meeting the current suite of standards is strongly associated with the simulated change in annual mean***E.O. 12866 Review

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Page 52 of 133 PM 2.5 concentrations. The role of annual mean PM 2.5 concentrations in driving long - term exposure related risk estimates is intuitive given that risks are modeled using the annual mean air quality metric. 38 The fact that short - term exposure - related risk estimates are also driven by changes in long - term mean PM 2.5 concentrations is less intuitive, since changes in mean 24 - hour PM 2.5 concentrations are used to estimate changes in risk for this time period. 39 Analyses show that short - term exposure - related risks are not primarily driven by the small number of days with PM 2.5 concentrations in the upper tail of the ai r quality distribution, but rather by the large number of days with PM 2.5 concentrations at and around the mean of the distribution (US EPA, 2010a, section 3.1.2.2). Consequently, the largest part of the estimates of short - term exposure - related risk is rel ated to the changes in the portion of the distribution of short term PM 2.5 exposures that are well represented by changes in the annual mean. Therefore, the Policy Assessment focuses on changes in annual mean PM 2.5 concentrations to inform our understandin g of patterns of both long - and short - term exposure - related risk estimates across the set of urban study areas evaluated in the quantitative risk assessment (US EPA, 2011a, pp. 2 - 36 to 2 - 37). In estimating PM 2.5 - related risks likely to remain upon simulat ion of just meeting the current annual and 24 - hour standards in the 15 urban study areas, the Risk Assessment focuses on the 13 areas that would likely not have met the current suite of PM 2.5 standards based on recent air quality (2005 to 2007). These 13 a reas have annual and/or 24 - hour design values that are above the levels of the current 38 As noted in section 3.2.1 of the Risk Assessment (US EPA, 2010a), estimates of long - term exposure related mortality are actually based on an annual mean PM 2.5 concentration that is the average across monitors in a study area (i.e., based on the composite monitor distribution) . Therefore, in considering changes in long - term exposure - related mortality, it is most appropriate to compare composite monitor estimates generated for a stu dy area under each alternative suite of standards considered . The annual mean at the highest reporting monitor (i.e., based on the maximum monitor distribution) for a study area is the annual design value . The annual design value is used to determine the p ercent reduction in PM 2.5 concentrations required to meet a particular standard . Both types of air quality estimates are provided in Table 3 - 4 of the Risk Assessment (US EPA, 2010a, pp. 3 - 25 to 3 - 27). 39 Estimates of short - term PM 2.5 exposure - related mortality and morbidity are based on composite monitor 24 - hour PM 2.5 concentrations . However, similar to the case with long - term exposure - related mortality, under the current rules, it is the 98 th percentile 24 - hour concentration estimate d at the maximum monitor (the 24 - hour design value) that will determine the degree of reduction required to meet a given 24 - hour standard level (US EPA, 2011a, p. 2 - 37).***E.O. 12866 Review

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Page 53 of 133 standards (US EPA, 2010a, Table 3 - 3). 40 Based on the core risk estimates for these areas, using the proportional rollback approach, the Policy Assessment makes the follow ing key observations regarding the magnitude of risk remaining upon simulation of just meeting the current suite of standards: 1) Long - term exposure - related mortality risk estimated to remain upon just meeting the current standards are significant : Premature mortality related to ischemic heart disease attributable to long - term PM 2.5 exposure was estimated to range from less than 100 to approximately 2,000 cases per year across the urban study areas . The variability in these estimates reflects, to a great exte nt, differences in the size of study area populations . These estimates represent from 4 to 17% of all mortality related to ischemic heart disease in a given year for the urban study areas evaluated, representing a measure of risk that takes into account di fferences in population size and baseline mortality rates (US EPA, 2011a, p. 2 - 43, Table 2 - 2). These estimates of risk for mortality related to ischemic heart disease associated with long - term PM 2.5 exposure would likely be in a range of thousands of death s per year for the 15 urban study areas 41 (US EPA, 2011a, pp. 2 - 46 to 2 - 47). Based on these risk estimates for premature mortality related to ischemic heart disease alone, the Policy Assessment concludes that risks estimated to remain upon simulation of jus t meeting the current suite of standards are important from a public health standpoint (US EPA, 2011a, p. 2 - 47). The Risk Assessment also includes estimated risks for premature mortality related to cardiopulmonary effects and lung cancer, which increase th e total annual incidence of mortality attributable to long - term PM 2.5 exposure (see U.S. EPA, 2010a, section 4.2.1). 2) Short - term exposure - related mortality risk estimated to remain upon just meeting the current standards are much smaller than long - term exp osure - related mortality risks : Cardiovascular related mortality associated with short - term PM 2.5 exposure was estimated to range from less than 10 to 500 cases per year across the urban study areas . These estimates represent approximately 1 to 2 percent of total cardiovascular - related mortality in a given year for the urban study areas evaluated (US EPA, 2011a, p. 2 - 43, Table 2 - 3). Although long - and short - term exposure - related mortality rates have similar patterns in terms of the subset of urban study areas experiencing risk reductions for the current suite of standard levels, the magnitude of risk remaining is substantially lower, up to an order of magnitude smaller, for short - term exposure related mortality (US EPA, 2011a, p. 2 - 47). 3) Short - term exposure - related morbidity risk estimated to remain upon just meeting the current standards indicate hospitalizations are significantly larger for cardiovascular - related rather than respiratory - related events and emergency department visits for asthma - rel ated events are significant: Cardiovascular - related hospitalizations were estimated to range from approximately 10 to 800 cases per year across the study areas, which are less than 1 percent of total cardiovascular - related hospitalizations (US EPA, 2011a, p. 2 - 43, Table 2 - 3) . Respiratory - related hospital admissions attributable to short - term PM 2.5 exposure were significantly smaller than 40 Of the 15 urban study areas, only Dallas and Phoenix have both annual and 24 - hour de sign values below the levels of the current standards based on 2005 - 2007 air quality data (US EPA, 2010a, Table 3 - 3). 41 Premature mortality for all causes attributed to PM 2.5 exposure was estimated to be in a range of tens of thousands of deaths per year o n a national scale based on 2005 air quality data (US EPA, 2010a, Appendix G, Table G - 1). Formatted: Font: Italic, No underline

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Page 54 of 133 those related to cardiovascular events (US EPA, 2010a, Tables E - 102 and E - 111). Cardiovascular - and respiratory - related h ospital admissions together ranged up to approximately 1,000 admissions per year across the urban study areas. The estimated incidence of asthma related emergency department visits is several times larger than the estimates of cardiovascular and respirato ry - related hospital admissions (US EPA, 2011a, p. 2 - 47; US EPA, 2010a, Tables E 118 to E - 123 4) Substantial variability exists in the magnitude of risk remaining across urban study areas : Estimated risks remaining upon just meeting the current suite of stand ards vary substantially across study areas, even when considering risks normalized for differences in population size and baseline incidence rates . This variability is a consequence of the substantial differences in the annual mean PM 2.5 concentrations acr oss study areas that result from simulating just meeting the current standards. This is important because, as discussed above, annual mean concentrations are highly correlated with both long - and short - term exposure - related risk. The variability in annual mean PM 2.5 concentrations occurred primarily in those study areas in which the 24 - hour standard was the generally controlling standard. In such areas, the variability in estimated risks across study areas was largest when regional patterns of reductions in PM 2.5 concentrations were simulated, using the proportional rollback approach, as was done in the core analysis. Less variability was observed when more localized patterns of PM 2.5 reductions were simulated using the locally - focused rollback approach, as was done in a sensitivity analysis. When simulations were done using the locally - focused rollback approach, estimated risks remaining upon just meeting the current suite of standards were appreciably larger than those estimated in the core analysis (US EPA , 2011a, p. 2 - 46; US EPA, 2010a, section 4.3.1.1). 5) Simulation of just meeting the current suite of standards results in annual mean PM 2.5 concentrations well below the current standard for some study areas: In simulating just meeting the current suite of standards, the resulting composite monitor annual mean PM 2.5 concentrations ranged from about 15 μg/m 3 (for those study areas in which the annual standard was controlling) down to as low as abo ut 8 μg/m 3 (fo r those study areas in which the 24 - hour standard was the generally controlling standard or the annual mean concentration was well below 15 μg/m 3 based on recent air quality) (US EPA, 2011a, p. 2 - 46). Reductions in risk associated with simulating air qual ity to just meet alternative standard levels were also estimated in this review (US EPA, 2010a, sections 4.2.2, 5.2.2, and 5.2.3; US EPA, 2011a, section 2.3.4.2). The estimated percent of risk reductions are depicted graphically in the Policy Assessment (U S 2011a, Figures 2 - 11 and 2 - 12), showing patterns of estimated risk reductions associated with alternative suites of standards. 42 These figures also depict the level of confidence associated with
42 Patterns of risk reduction across alternative annual standard levels, in terms of percent change relative to risk estimates upon simulating just meeting the current standards, are similar for all health endpoints modeled (i.e., all - cause, ischemic heart disease - related, and cardiopulmonary - related mortality) . This similarity reflects the fact that the concentration - response functions used in the quantitative risk ass essment are close to linear across the range of ambient PM 2.5 concentrations evaluated . However, estimated incidence will vary by health endpoint (US EPA, 2011a, pp. 2 - 93 to 2 - 94, footnote 70). Formatted: Font: Italic, No underline

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Page 55 of 133 the risk estimates generated for simulating just meeting the current standards as well as alternative standard levels considered . As would be expected, patterns of increasing estimated risk reductions are generally observed as either the annual or 24 - hour standard, or both, are reduced over the ranges considered in the Risk Assessment . A number of the key observations regarding the magnitude of risk remaining upon simulation of just meeting the alternative suites of standards are analogous to the observations identified above for simulation of just meet ing the curren t standards (US EPA, 2011a, pp. 2 - 97 to 2 - 100). With regard to characterizing estimates of PM 2.5 - related risk associated with simulation of alternative standards, the Policy Assessment recognizes that greater overall confidence is associated with estimates of risk reduction than for estimates of absolute risk remaining (US EPA, 2011a, p. 2 - 94) . Furth ermore, the Policy Assessment recognizes that estimates of absolute risk remaining for each of the alternative standard levels considered, particularly in the context of long - term exposure - related mortality, may be underestimated (US EPA, 2011a, p. 2 - 97) . In addition, the Policy Assessment observes that in considering the overall confidence associated with the quantitative analyses, the Risk Assessment recognizes that: (1) substantial variability exists in the magnitude of risk remaining across urban study areas and (2) in general, higher confidence is associated with risk estimates based on PM 2.5 concentrations near the mean PM 2.5 concentrations in the underlying epidemiological studies providing the concentration - response functions. The variability in ris k is a consequence of the substantial differences in the annual mean PM 2.5 concentrations across urban study areas that result from simulating just meeting current or alternative standards. As PM 2.5 concentrations decrease from the mean PM 2.5 concentration s, the Risk Assessment concludes there is decreasing confidence in the risk estimates (US EPA, 2010a, p. 5 - 16). As lower long term mean PM 2.5 concentrations are simulated (i.e., ambient concentrations further from recent air quality conditions), the potent ial variability in such factors as the spatial pattern of ambient PM 2.5 Formatted: Font: Italic, No underline Formatted: Font: Italic, No underline***E.O. 12866 Review

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Page 56 of 133 reductions (i.e., rollback) increases, thereby introducing greater uncertainty into the simulation of composite monitor annual mean PM 2.5 concentrations, and, consequently, in the risk estimates (US EPA, 2010a, Appendix J). Based on consideration of the composite monitor annual mean PM 2.5 concentrations involved in estimating long - term exposure - related mortality, the Risk Assessment has higher confidence in using those concentrations t hat generally fall well within the range of ambient PM 2.5 concentrations considered in fitting the concentration - response functions used (i.e., within one standard deviation of the mean PM 2.5 concentration reported in Krewski et al. (2009) for 1999 - 2000) a s inputs to the risk model. For example, with the exception of one urban study area, those areas estimated to have risk reductions using alternative annual standard levels of 13 and 14 μg/m 3 had simulated composite monitor annual mean concentrations rangin g from approximately 10.6 to 13.3 μg/m 3 . With lower alternative annual standard levels of 12 μg/m 3 and 10 μg/m 3 , the composite monitor annual mean values ranged from approximately 9.0 to 11.4 μg/m 3 and 7.6 and 8.9 μg/m 3 , respectively. These concentrations are towards the lower end of the range of ACS data (in some cases approaching the lowest measured level) used in fitting the concentration - response functions, particularly for an annual standard level of 10 μg/m 3 , and, thus, the Policy Assessment concludes there is less confidence in the risk estimates associated with these levels compared with those for the higher alternative annual standard levels considered (US EPA, 2011a, p. 2 - 99). Thus, while simulation of risks for an alternative annual standard level of 10 μg/m 3 suggests that additional risk reductions could be expected with alternative annual standards below 12 μg/m 3 , the Policy Assessment recognizes that there is potentially greater uncertainty associated with these risk estimates compared with esti mates generated for the higher alternative annual standard levels considered in the quantitative risk assessment, since these estimates required simulation of relatively greater reductions in ambient PM 2.5 concentrations (US EPA, 2011a, p. 2 - 98). The results of simulating alternative suites of PM 2.5 standards including a combination of***E.O. 12866 Review

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Page 57 of 133 alternative annual and 24 - hour standard levels suggest that an alternative 24 - hour standard level can produce additional estimated risk reductions beyond that provided b y an alternative annual standard alone. However, the degree of estimated risk reduction provided by the alternative 24 - hour standard is highly variable (US EPA, 2010a, section 4.2.2). Thus, the Risk Assessment concludes more consistent reductions in estima ted risk and consequently degrees of public health protection are estimated to result from simulating just meeting the alternative annual standard levels considered (US EPA, 2010a, pp. 5 - 15 to 5 - 16). Furthermore, the Policy Assessment concludes that the ur ban study areas with the greatest degree of estimated reduction associated with simulating just meeting alternative 24 - hour standard levels of 30 and 25 μg/m 3 also had the lowest estimated annual mean PM 2.5 concentrations, and, therefore, there was substan tially lower confidence in these risk estimates (US EPA, 2011a, pp. 2 - 99 to 2 - 100). Based on the consideration of both the qualitative and quantitative assessments of uncertainty, the Risk Assessment concludes it is unlikely that the estimated risks are o ver - stated, particularly for premature mortality related to long - term PM 2.5 exposures. In fact, the Policy Assessment and Risk Assessment conclude that the core risk estimates for this category of health effects may well be biased low based on consideratio n of alternative model specifications evaluated in the sensitivity analyses 43 (US EPA, 2011a, p. 2 - 41; US EPA, 2010a, p. 5 - 16; Figures 4 - 7 and 4 - 8) . In addition, the Policy Assessment recognizes that the currently available scientific information includes e vidence for a broader range of health endpoints and susceptible at - risk populations beyond those included in the quantitative risk assessment, including lung function growth and respiratory symptoms in children and reproductive and developmental effects (US EPA, 2011a, section 2.2.1). In considering the set of quantitative risk estimates and related uncertainties and limitations related to long - and short - term PM 2.5 exposure discussed above together with consideration of the health endpoints which could not be quantified, the Policy Assessment concludes this information provides 43 Most of the alternative model specifications supported by t he currently available scientific information produced risk estimates that are higher (by up to a factor of 2 to 3) than the core risk estimates (US EPA, 2011a, pp. 2 - 40 and 2 - 41) .***E.O. 12866 Review

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Page 58 of 133 strong evidence that risks estimated to remain upon simulating just meeting the current suite of PM 2.5 standards are important from a public health perspective, both in terms of seve rity and magnitude (US EPA, 2011a, p. 2 - 47). Furthermore, while the alternative 24 - hour standard levels considered (when controlling) did result in additional estimated risk reductions beyond those estimated for alternative annual standards alone, these ad ditional estimated reductions are highly variable, in part due to different rollback approaches. Conversely, the Risk Assessment recognizes that alternative annual standard levels, when controlling, resulted in more consistent risk reductions across urban study areas, thereby potentially providing a more consistent degree of public health protection (US EPA, 2010a, p. 5 - 17). D. Conclusions on the Adequacy of the Current Primary PM 2.5 Standards The initial issue to be addressed in the current review of the prim ary PM 2.5 standards is whether, in view of the additional information now available, the existing standards should be retained or revised . In evaluating whether it is appropriate to retain or revise the current suite of standards, the Administrator conside red the scientific information from the last review and the broader body of evidence and information now available . The Administrator has taken into account both evidence - and risk - based considerations in developing conclusions on the adequacy of the curre nt primary PM 2.5 standards. Evidence - based considerations (section III.D.1) include the assessment of epidemiological, toxicological, and controlled human exposure studies evaluating long - or short - term exposures to PM 2.5 , with supporting evidence related to dosimetry and potential pathways/modes of action, as well as the integration of evidence across each of these disciplines, as assessed in the Integrated Science Assessment (US EPA, 2009a) and focus on the policy - relevant considerations as discussed in s ection III.B above and in the Policy Assessment (US EPA, 2011a, section 2.2.1). The risk - based considerations (section III.D.2) draw from the results of the quantitative analyses presented in the Risk Assessment (US EPA, 2010a) and focus on the policy - rele vant considerations as discussed in section III.C above and in the Policy Assessment (US EPA, 2011a, section 2.2.2). The advice received from CASAC is discussed Formatted: Font: Italic, No underline***E.O. 12866 Review

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Page 59 of 133 in section III.D.3. Finally, the Administrator's proposed conclusion on the adequacy of the cur rent PM 2.5 primary standards is provided in section III.D.4. 1. Evidence - based Considerations in the Policy Assessment In light of the health evidence described above, specifically with regard to factors contributing to greater susceptibility to health effects associated with ambient PM 2.5 exposures, the Policy Assessment considers the extent to which the currently available scientific evidence reports associations between fine particle exposures and health effects that extend to air quality concentratio ns that are lower than had previously been observed or that have been observed in areas that would likely meet the current suite of PM 2.5 standards (US EPA, 2011a, section 2.2.1). As noted above, the Integrated Science Assessment concludes there is no evid ence to support the existence of a discernible threshold below which effects would not occur (US EPA, 2009a, section 2.4.3). a. Associations with Long - term PM 2.5 Exposures With regard to associations observed in long - term PM 2.5 exposure studies, the Policy As sessment recognizes that extended follow - up analyses of the ACS and Harvard Six Cities studies provide consistent and stronger evidence of an association with mortality at lower air quality distributions than had previously been observed (US EPA, 2011a, pp . 2 - 31 to 2 - 32). The original and reanalysis of the ACS study reported positive and statistically significant effects associated with a long - term mean PM 2.5 concentration of 18.2 μg/m 3 across 50 metropolitan areas for 1979 - 1983 (Pope et al., 1995; Krewski et al., 2000). 44 In extended analyses, positive and statistically significant effects of approximately similar magnitude were associated with declining PM 2.5 concentrations, from an aggregate long - term mean in 58 metropolitan areas of 21.2 μg/m 3 in the orig inal monitoring period (1979 - 1983) to 14.0 μg/m 3 for 116 metropolitan areas in the most recent years evaluated (1999 - 2000), with an overall average across the 44 The study periods referred to in the Policy Assessment (US EPA, 2011a) a nd in this proposed rule reflect the years of air quality data that were included in the analyses, whereas the study periods identified in the Integrated Science Assessment (US EPA, 2009a) reflect the years of health status data that were included.***E.O. 12866 Review

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Page 60 of 133 two study periods in 51 metropolitan areas of 17.7 μg/m 3 (Pope et al., 2002; Krewski et al., 2009 ). With regard to the Harvard Six Cities Study, the original and reanalysis reported positive and statistically significant effects associated with a long - term mean PM 2.5 concentration of 18.0 μg/m 3 for 1980 - 1985 (Dockery et al., 1993; Krewski et al., 2000 ). In an extended follow - up of this study, the aggregate long term mean concentration across all years evaluated was 16.4 μg/m 3 for 1980 - 1988 45 (Laden et al., 2006). In an additional analysis of the extended follow - up of the Harvard Six Cities study, invest igators reported that the concentration - response relationship was linear and “clearly continuing below the level” of the current annual standard (US EPA, 2009a, p. 7 - 92; Schwartz et al., 2008). New cohort studies provide additional evidence of mortality a ssociated with air quality distributions that are generally lower than those reported in the ACS and Harvard Six Cities studies, with effect estimates that were similar or greater in magnitude (US EPA, 2011a, pp. 2 - 32 to 2 - 33). The WHI study reported posit ive and most often statistically significant associations between long - term PM 2.5 exposure and cardiovascular - related mortality, with much larger relative risk estimates than in the ACS and Harvard Six Cities studies, as well as morbidity effects at an agg regate long - term mean PM 2.5

45 Aggre gate mean concentration provided by study author (personal communication from Dr. Francine Laden, 2009).***E.O. 12866 Review

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Page 61 of 133 concentration of 12.9 μg/m 3 for 2000 (Miller et al., 2007). 46 Using the Medicare cohort, Eftim et al. (2008) reported somewhat higher effect estimates than in the ACS and Harvard Six Cities studies with aggregate long - term mean c oncentrations of 13.6 μg/m 3 and 14.1 μg/m 3 , respectively, for 2000 - 2002. The MCAPS reported associations between long - term PM 2.5 exposure and mortality for the eastern region of the U.S. at an aggregated long - term PM 2.5 median concentration of 14.0 μg/m 3 , although no association was reported for the western region with an aggregate long - term PM 2.5 median concentration of 13.1 μg/m 3 (US EPA, 2009a, p. 7 - 88; Zeger et al., 2008). 47 Premature mortality in children reported in a national infant mortality study as well as mortality in a cystic fibrosis cohort including both children and adults reported positive but statistically nonsignificant effects associated with long - term aggregate mean concentrations of 14.8 μg/m 3 and 13.7 μg/m 3 , respectively (Woodruff et al. , 2008; Goss et al., 2004). 46 Miller et al. (2007) studied postmenopausal women without previous cardiovascular disease in 36 study areas from 1994 to 1998, with a median follow - u p period of six years . The ambient PM 2.5 monitor nearest to a study subject’s residence (within 30 miles or 48 kilometers) was identified and used to assign long - term mean PM 2.5 concentrations to each subject . The annual average concentration in the year 2 000 was the primary exposure measure because of the substantially increased network of monitors in that year, as compared with previous years . Miller et al. (2007) reported a long - term mean PM 2.5 concentration across study areas of 13.5 μg/m 3
. This concent ration was presented in the Integrated Science Assessment (US EPA, 2009a, Figure 2 - 2, Table 7 - 8) and discussed in the second draft Policy Assessment (US EPA, 2010f, Figure 2 - 4) . In response to a request from the EPA for additional information on the air qu ality data used in selected epidemiological studies (Hassett - Sipple and Stanek, 2009), study investigators provided updated air quality data for the study period . The updated long - term mean PM 2.5 concentration provided by the study authors was 12.9 μg/m 3 ( personal communication from Cynthia Curl, 2009; Stanek et al., 2010) . The EPA notes that this updated long - term mean concentration matches the composite monitor approach annual mean calculated by staff for the year of air quality data (i.e., 2000) considered by the study investigators (Hassett - Sipple et al., 2010, Attachment A, p. 6) . The updated air quality data for the Women’s Health Initiative study was presented and considered in the final Policy Assessment (US EPA, 2011a, p. 2 - 32) . The Policy A ssessment notes that in comparison to other long - term exposure studies, the WHI study was more limited in that it was based on only one year of air quality data (US EPA, 2011a, p. 2 - 82). 47 Zeger et al. (2008) also reported positive and statistically signif icant effects for the central region, with an aggregate long - term mean PM 2.5 concentration of 10.7 μg/m 3
. However, in contrast to the eastern and western risk estimates, the central risk estimate increased with adjustment for COPD (used as a proxy for smok ing status) . Due to the potential for confounding bias influencing the risk estimate for the central region, the Policy Assessment did not focus on the results reported in the central region to inform the adequacy of the current suite of standards or alter native annual standard levels (US EPA, 2011a, p. 2 - 32).***E.O. 12866 Review

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Page 62 of 133 With respect to respiratory morbidity effects associated with long - term PM 2.5 exposure, the across - city mean of 2 - week average PM 2.5 concentrations reported in the initial Southern California Children’s Health Study was approxim ately 15.1 μg/m 3 (Peters et al., 1999). These results were found to be consistent with results of cross - sectional analyses of the 24 - Cities Study (Dockery et al., 1996; Raizenne et al., 1996), which reported a long - term cross - city mean PM 2.5 concentration of 14.5 μg/m 3
. In this review, extended analyses of the Southern California Children’s Health Study provide stronger evidence of PM 2.5 - related respiratory effects, at lower air quality concentrations than had previously been reported, with a four - year aggregate mean concentration of 13.8 μg/m 3 across the 12 study communities (McConnell et al., 2003; Gauderman et al., 2004, US EPA, 2009a, Figure 7 - 4). In also considering health effects for which the Integrated Science Assessment concludes evi dence is suggestive of a causal relationship, the Policy Assessment notes a limited number of birth outcome studies that reported positive and statistically significant effects related to aggregate long - term mean PM 2.5 concentrations down to approximately 12 μg/m 3 (US EPA, 2011a, p. 2 - 33). Collectively, the Policy Assessment concludes that currently available evidence provides support for associations between long - term PM 2.5 exposure and mortality and morbidity effects that extend to air quality concentrations that are lower than had previously been observed, with aggregate long - term mean PM 2.5 concentrations extending to well below the level of the current annual standard. T hese studies evaluated a broader range of health outcomes in the general population and in susceptible at - risk populations than were considered in the last review, and include extended follow - up for prospective epidemiological studies that were important in the last review as well as additional evidence in important new cohorts. b. Associations with Short - term PM 2.5 Exposures In light of the mixed findings reported in single - city, short - term exposure studies, the Policy Assessment places comparatively greater weight on the results from multi - city studies in considering the***E.O. 12866 Review

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Page 63 of 133 adequacy of the current suite of standards (US EPA, 2011a, pp. 2 - 34 to 2 - 35). With regard to associations reported in short - term PM 2.5 exposure studies, the Policy Assessment recognizes that long term mean concentrations reported in new multi - city U.S. and Canadian studies provide evidence of associations between short - term PM 2.5 exposure and mortality at similar air quality distributions than had previously been observed in an 8 - cities Canadi an study (Burnett and Goldberg, 2003; aggregate long - term mean PM 2.5 concentration of 13.3 μg/m 3 ). In a multi - city time - series analysis of 112 U.S. cities, Zanobetti and Schwartz (2009) reported a positive and statistically significant association with all cause, cardiovascular - related (e.g., heart attacks, stroke), and respiratory - related mortality and short term PM 2.5 exposure, in which the aggregate long - term mean PM 2.5 concentration was 13.2 μg/m 3 (US EPA, 2009a, Figure 6 - 24). Furthermore, city - specific effect estimates indicate the association between short - term exposure to PM 2.5 and total mortality and cardiovascular - and respiratory - related mortality is consistently positive for an overwhelming majority (99 percent) of the 112 cities across a wide ran ge of air quality concentrations (long - term mean concentrations ranging from 6.6 μg/m 3 to 24.7 μg/m 3 ; US EPA, 2009a, Figure 6 - 24, p. 6 - 178 to 179). The EPA staff notes that for all - cause mortality, city - specific effect estimates were statistically signific ant for 55 percent of the 112 cities, with long - term city - mean PM 2.5 concentrations ranging from 7.8 μg/m 3 to 18.7 μg/m 3 and 24 - hour PM 2.5 city - mean 98 th percentile concentrations ranging from 18.4 to 64.9 μg/m 3 (personal communication with Dr. Antonella Z anobetti, 2009). 48 With regard to cardiovascular and respiratory morbidity effects, in the first analysis of the MCAPS cohort conducted by Dominici et al. (2006a) across 204 U.S. counties, investigators reported a statistically significant association with hospitalizations for cardiovascular and respiratory diseases and short - term PM 2.5 exposure, in which the aggregate long - term mean PM 2.5 concentration was 13.4 μg/m 3
. Furthermore, a sub - analysis restricted to days with 24 - hour average concentrations of PM 2.5 at or below 48 Single - city Bayes - adjusted effect estimates for the 112 cities analyzed in Zanobetti and Schwartz (2009) were provided by the study authors (personal communication with Dr. Antonella Zanobetti, 2009 ; see also US EPA, 2009a, Figure 6 - 24).***E.O. 12866 Review

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Page 64 of 133 35 μg/m 3 indicated that, in spite of a reduced statistical power from a smaller number of study days, statistically significant associations were still observed between short - term exposure to PM 2.5 and hospital admissions for cardiovascular and respiratory diseases (Dominici, 2006b). 49 In an extended analysis of the MCAPS study, Bell et al (2008) reported a positive and statistically significant increase in cardiovascular hospitalizations associated with short - term PM 2.5 exposure, in which th e aggregate long - term mean PM 2.5 concentration was 12.9 μg/m 3 . These results, along with the observation that approximately 50 percent of the 204 county - specific mean 98 th percentile PM 2.5 concentrations in the study aggregated across all years were below the 24 - hour standard of 35 μg/m 3 , not only indicate that effects are occurring in areas that would meet the current standards but also suggest that the overall health effects observed across the U.S. are not primarily driven by the higher end of the PM 2.5 air quality distribution (Bell, 2009a, personal communication from Dr. Michelle Bell regarding air quality data for Bell et al., 2008 and Dominici et al., 2006a). Collectively, the Policy Assessment concludes that the findings from short - term PM 2.5 exposu re studies provide evidence of PM 2.5 - associated health effects occurring in areas that would likely have met the current suite of PM 2.5 standards (US EPA, 2011a, p. 2 - 35). These findings are further bolstered by evidence of statistically significant PM 2.5 - related health effects occurring in analyses restricted to days in which 24 - hour average PM 2.5 concentrations were below 35 μg/m 3 (Dominici, 2006b). In evaluating the currently available scientific evidence, as summarized in section III.B, the Policy Asse ssment first concludes that there is stronger and more consistent and coherent support for associations between long - and short - term PM 2.5 exposures and a broad range of health outcomes than was available in the last review, providing the basis for fine pa rticle standards at least as protective as 49 This sub - analysis was not included in the original publication (Dominici et al., 2006a) . Authors provided sub - analysis results for the Administrator’s consideration as a letter to the docket following publication of the proposed rule in January 2006 (personal communication with Dr. Francesca Dominici, 2006b) . As noted in section II I .A.3, this study is part of the basis for the conclusion that there is no evidence suggesting that risks associated with long - term expo sures are likely to be disproportionately driven by peak 24 - hour concentrations .***E.O. 12866 Review

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Page 65 of 133 the current PM 2.5 standards (US EPA, 2011a, p. 2 - 26). Having reached this initial conclusion, the Policy Assessment addresses the question of whether the available evidence supports consideration of standards that are more protective than the current standards. In so doing, the Policy Assessment considers whether there is now evidence that health effect associations have been observed in areas that likely met the current suite of PM 2.5 standards. As discussed above , long - and short - term PM 2.5 exposure studies provide evidence of associations with mortality and cardiovascular and respiratory effects both at lower ambient PM 2.5 concentrations than had been observed in the previous review and at concentrations allowed by the current standards (US EPA, 2011a, p. 2 - 35). In reviewing this information, the Policy Assessment recognizes that important limitations and uncertainties associated with this expanded body of scientific evidence, noted above in section III.B.2, need to be carefully considered in determining the weight to be placed on the body of studies available in this review. Taking these limitations and uncertainties into consideration, the Policy Assessment concludes that the currently available evidence clearly calls into question whether the current suite of primary PM 2.5 standards protects public health with an adequate margin of safety from effects associated with long - and short - term exposures. Furthermore, the Policy Assessment concludes this evidence provi des strong support for considering fine particle standards that would afford increased protection beyond that afforded by the current standards (US EPA, 2011a, p. 2 - 35). 2. Summary of Risk - based Considerations in the Policy Assessment In addition to evidence - based consideration, the Policy Assessment also considers the extent to which health risks estimated to occur upon simulating just meeting the current PM 2.5 standards may be judged to be important from a public health perspective, taking into account key u ncertainties associated with the quantitative health risk estimates. In so doing, the Policy Assessment first notes that the quantitative risk assessment addresses: (1) the core PM 2.5 - related risk estimates; (2) the related uncertainty and sensitivity anal yses, including additional sets of reasonable risk estimates generated to***E.O. 12866 Review

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Page 66 of 133 supplement the core analysis; (3) an assessment of the representativeness of the urban study areas within a national context; 50 and (4) consideration of patterns in design values and air quality monitoring data to inform interpretation of the risk estimates, as discussed in section III.C above. In considering the health risks estimated to remain upon simulation of just meeting the current suite of standards and considering both the qu alitative and quantitative assessment of uncertainty completed as part of the assessment, the Policy Assessment concludes these risks are important from a public health standpoint (US EPA, 2011a, p. 2 - 47). This conclusion reflects consideration of both the severity and the magnitude of the effects. For example, the risk assessment indicates the possibility that premature deaths related to ischemic heart disease associated with long - term PM 2.5 exposure alone would likely be on the order of thousands of death s per year in the 15 urban study areas upon simulating just meeting the current standards 51 (US EPA, 2011a, pp. 2 - 46 to 2 - 47). Moreover, additional risks are anticipated for premature mortality related to cardiopulmonary effects and lung cancer associated w ith long - term PM 2.5 exposure as well as mortality and cardiovascular - and respiratory - related morbidity effects (e.g., hospital admissions, emergency department visits) associated with short - term PM 2.5 exposures. Based on the consideration of both qualitat ive and quantitative assessments of uncertainty completed as part of the quantitative risk assessment, the Risk Assessment concludes that it is unlikely that the estimated risks are over - stated, particularly for mortality related to long - term PM 2.5 exposur e, and may well be biased low based on consideration of alternative model specifications evaluated in the sensitivity analyses (US EPA, 2010a, p. 5 - 16; US EPA, 2011a, p. 2 - 41). Furthermore, the currently available scientific information summarized in secti on III.B above provides evidence for a broader range of health endpoints and susceptible at - risk populations beyond those included in the quantitative risk 50 Based on analyses of the representativeness of the 15 urban study areas in the broader national context, the Policy Assessment concludes that these study areas are generall y representative of urban areas in the U.S. likely to experience relatively elevated levels of risk related to ambient PM 2.5 exposures (US EPA, 2011a, p. 2 - 42) . 51 Premature mortality for all causes attributed to PM 2.5 exposure was estimated to be on the o rder of tens of thousands of deaths per year on a national scale based on 2005 air quality data (US EPA, 2010a, Appendix G, Table G - 1).***E.O. 12866 Review

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Page 67 of 133 assessment (US EPA, 2011a, p. 2 - 47). In considering the risks estimated to occur upon simulating just meeting the current PM 2.5 standards, the Policy Assessment concludes that these estimated risks can reasonably be judged to be important from a public health perspective and provide strong support for consideration of alternative standards that would provide increased protection beyond that afforded by the current PM 2.5 standards (US EPA, 2011a, p. 2 - 48). 3. CASAC Advice CASAC, based on their review of drafts of the Integrated Science Assessment, the Risk Assessment, and the Policy Assessment, has provide d an array of advice both with regard to interpreting the scientific evidence and quantitative risk assessment, as well as with regard to consideration of the adequacy of the current PM 2.5 standards (Samet, 2009a b,c,d,e,f; Samet 2010a,b,c,d). With regard to the adequacy of the current standards, CASAC concluded that the “currently available information clearly calls into question the adequacy of the current standards” (Samet, 2010d, p. i) and that the current standards are “not protective” (Samet, 2010d, p . 1). Further, in commenting on the first draft Policy Assessment, CASAC noted: With regard to the integration of evidence - based and risk - based considerations, CASAC concurs with EPA’s conclusion that the new data strengthens the evidence available on asso ciations previously considered in the last round of the assessment of the PM 2.5 standard. CASAC also agrees that there are significant public health consequences at the current levels of the standard that justify consideration of lowering the PM 2.5 NAAQS f urther (Samet, 2010c, p.12). 4. Administrator’s Proposed Conclusions Concerning the Adequacy of the Current Primary PM 2.5 Standards In considering the adequacy of the current suite of PM 2.5 standards, the Administrator has considered the large body of eviden ce presented and assessed in the Integrated Science Assessment (US EPA, 2009a), the staff conclusions and associated rationales presented in the Policy Assessment , views expressed by CASAC, and public comments. In particular, the Administrator recognizes t hat the Integrated Science Assessment concludes that the results of epidemiological and experimental studies***E.O. 12866 Review

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Page 68 of 133 form a plausible and coherent data set that supports a causal relationship between long - and short - term PM 2.5 exposures and mortality and cardiovas cular effects, and a likely causal relationship between long and short - term PM 2.5 exposures and respiratory effects. Moreover, the Administrator reflects that these effects have been observed at lower ambient PM 2.5 concentrations than what had been observ ed in the last review, including at ambient PM 2.5 concentrations in areas that likely met the current PM 2.5 NAAQS. See American Trucking Associations v. EPA , 283 F. 3d at 369, 376 (revision of level of existing standards justified when effects are observed in areas that meet those standards) . With regard to the results of the quantitative risk assessment, the Administrator notes that the Risk Assessment concludes that the risks estimated to remain upon simulation of just meeting the current standards are im portant from a public health standpoint in terms of both the severity and magnitude of the effects . Based on her consideration of these conclusions, as well as consideration of CASAC’s conclusion that the evidence and risk assessment clearly call into que stion the adequacy of the public health protection provided by the current PM 2.5 NAAQS, the Administrator provisionally concludes that the current primary PM 2.5 standards, taken together, are not requisite to protect public health with an adequate margin o f safety and that revision is needed to provide increased public health protection. The Administrator provisionally concludes that the scientific evidence and information on risk provide strong support for consideration of alternative standards that would provide increased public health protection beyond that afforded by the current PM 2.5 standards. E. Conclusions on the Elements of the Primary Fine Particle Standards 1. Indicator In initially setting standards for fine particles in 1997, the EPA concluded it was appropriate to control fine particles as a group, rather than singling out any particular component or class of fine particles . The EPA noted that community health studies had found significant associations between various indicators of fine particles, an d that health effects in a large number of areas had significant Formatted: Font: Italic, No underline

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Page 69 of 133 mass contributions of differing components or sources of fine particles. In addition, a number of toxicological and controlled human exposure studies had reported health effects associations with high concentrations of numerous fine particle components. It was also not possible to rule out any component within the mix of fine particles as not contributing to the fine particle effects found in the epidemiologic studies (62 FR 38667, July 18, 19 77). In establishing a size - based indicator in 1977 to distinguish fine particles from particles in the coarse mode, the EPA noted that the available epidemiological studies of fine particles were based largely on PM 2.5 and also considered monitoring techn ology that was generally available. The selection of a 2.5 μm size cut reflected the regulatory importance of defining an indicator that would more completely capture fine particles under all conditions likely to be encountered across the U.S., especially when fine particle concentrations and humidity are likely to be high, while recognizing that some small coarse particles would also be captured by current methods to monitor PM 2.5 (62 FR 38666 to 38668, July 18, 1997). In the last review, based on the same considerations, the EPA again recognized that the available information supported retaining the PM 2.5 indicator and remained too limited to support a distinct standard for any specific PM 2.5 component or group of components associated with any source cate gories of fine particles (71 FR 61162 to 61164, October 17, 2006). In this current review, the same considerations continue to apply for selection of an appropriate indicator for fine particles. As an initial matter, the Policy Assessment recognizes that t he available epidemiological studies linking mortality and morbidity effects with long - and short - term exposures to fine particles continue to be largely indexed by PM 2.5 . For the same reasons discussed in the last two reviews, the Policy Assessment conclu des that it is appropriate to consider retaining a PM 2.5 indicator to provide protection from effects associated with long - and short - term fine particle exposures (US EPA, 2011, p. 2 - 50). The Policy Assessment also considers the expanded body of evidence a vailable in this review to***E.O. 12866 Review

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Page 70 of 133 consider whether there is sufficient evidence to support a separate standard for ultrafine particles 52 or whether there is sufficient evidence to establish distinct standards focused on regulating specific PM 2.5 components or a gr oup of components associated with any source categories of fine particles (US EPA, 2011a, section 2.3.1). A number of studies available in this review have evaluated potential health effects associated with short - term exposures to ultrafine particles. As n oted in the Integrated Science Assessment, the enormous number and larger, collective surface area of ultrafine particles are important considerations for focusing on this particle size fraction in assessing potential public health impacts (US EPA, 2009a, p. 6 - 83). Per unit mass, ultrafine particles may have more opportunity to interact with cell surfaces due to their greater surface area and their greater particle number compared with larger particles (US EPA, 2009a, p. 5 - 3). Greater surface area also incr eases the potential for soluble components (e.g., transition metals, organics) to adsorb to ultrafine particles and potentially cross cell membranes and epithelial barriers (US EPA, 2009a, p. 6 - 83). In addition, evidence available in this review suggests t hat the ability of particles to enhance allergic sensitization is associated more strongly with particle number and surface area than with particle mass (US EPA, 2009a, p. 6 - 127). New evidence, primarily from controlled human exposure and toxicological st udies, expands our understanding of cardiovascular and respiratory effects related to short - term ultrafine particle exposures. However, the Policy Assessment concludes this evidence is still very limited and largely focused on exposure to diesel exhaust, f or which the Integrated Science Assessment concludes it is unclear if the effects observed are due to ultrafine particles, larger particles within the PM 2.5 mixture, or the gaseous components of diesel exhaust (US EPA, 2009a, p. 2 - 22). In addition, the Int egrated Science Assessment notes uncertainties associated with the controlled human exposure studies using concentrated ambient particle systems which have been shown to modify the composition of ultrafine particles (US EPA, 52 Ultrafine particles, generally including particles with a mobility diameter less than or equal to 0.1 μm, are emitted directly to the atmosphere or are formed by nucleation of gaseous constituents in the atmosphere (US EPA, 2009a, p. 3 - 3).***E.O. 12866 Review

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Page 71 of 133 2009a, p. 2 - 22, see also sectio n 1.5.3). The Policy Assessment recognizes that there are relatively few epidemiological studies that have examined potential cardiovascular and respiratory effects associated with short - term exposures to ultrafine particles (US EPA, 2011a, p. 2 - 51). Thes e studies have reported inconsistent and mixed results (US EPA, 2009a, section 2.3.5). Collectively, in considering the body of scientific evidence available in this review, the Integrated Science Assessment concludes that the currently available evidence is suggestive of a causal relationship between short - term exposures to ultrafine particles and cardiovascular and respiratory effects. Furthermore, the Integrated Science Assessment concludes that evidence is inadequate to infer a causal relationship betwe en short - term exposure to ultrafine particles and mortality as well as long - term exposure to ultrafine particles and all outcomes evaluated (US EPA, 2009a, sections 2.3.5, 6.2.12.3, 6.3.10.3, 6.5.3.3, 7.2.11.3, 7.3.9, 7.4.3.3, 7.5.4.3, and 7.6.5.3; Table 2 - 6). With respect to our understanding of ambient ultrafine particle concentrations, at present, there is no national network of ultrafine particle samplers; thus, only episodic and/or site - specific data sets exist (US EPA, 2009a, p. 2 - 2). Therefore, the Policy Assessment recognizes a national characterization of concentrations, temporal and spatial patterns, and trends is not possible at this time, and the availability of ambient ultrafine measurements to support health studies is extremely limited (US EP A, 2011a, p. 2 - 51). In general, measurements of ultrafine particles are highly dependent on monitor location and, therefore, more subject to exposure error than accumulation mode particles (US EPA, 2009a, p. 2 - 22). Furthermore, the number of ultrafine part icles generally decreases sharply downwind from sources, as ultrafine particles may grow into the accumulation mode by coagulation or condensation (US EPA, 2009a, p. 3 - 89). Limited studies of ambient ultrafine particle measurements suggest these particles exhibit a high degree of spatial and temporal heterogeneity driven primarily by differences in nearby source characteristics (US EPA, 2009a, p. 3 - 84). Internal combustion engines and, therefore, roadways***E.O. 12866 Review

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Page 72 of 133 are a notable source of ultrafine particles, so conc entrations of these particles near roadways are generally expected to be elevated (US EPA, 2009a, p. 2 - 3). Concentrations of ultrafine particles have been reported to drop off much more quickly with distance from roadways than fine particles (US EPA, 2009a , p. 3 - 84). In considering both the currently available health effects evidence and the air quality data, the Policy Assessment concludes that this information is still too limited to provide support for consideration of a distinct PM standard for ultrafin e particles (US EPA, 2011a, p. 2 - 52). In addressing the issue of particle composition, the Integrated Science Assessment concludes that, “[f]rom a mechanistic perspective, it is highly plausible that the chemical composition of PM would be a better predict or of health effects than particle size” (US EPA, 2009a, p. 6 - 202). Heterogeneity of ambient concentrations of PM 2.5 constituents (e.g., elemental carbon, organic carbon, sulfates, nitrates) observed in different geographical regions as well as regional he terogeneity in PM 2.5 - related health effects reported in a number of epidemiological studies are consistent with this hypothesis (US EPA, 2009a, section 6.6). With respect to the availability of ambient measurement data for fine particle components in this review, there are now more extensive ambient PM 2.5 speciation measurement data available through the Chemical Speciation Network (CSN) than in previous reviews (US EPA, 2011a, section 1.3.2 and Appendix B, section B.1.3). Data from the CSN provide further evidence of spatial and seasonal variation in both PM 2.5 mass and composition among cities and geographic regions (US EPA, 2009a, pp. 3 - 50 to 3 - 60; Figures 3 - 12 to 3 - 18; Figure 3 - 47). Some of this variation may be related to regional differences in meteor ology, sources, and topography (US EPA, 2009a, p. 2 - 3). The currently available epidemiological, toxicological, and controlled human exposure studies evaluated in the Integrated Science Assessment on the health effects associated with ambient PM 2.5 consti tuents and categories of fine particle sources used a variety of quantitative methods applied to a***E.O. 12866 Review

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Page 73 of 133 broad set of PM 2.5 constituents, rather than selecting a few constituents a priori (US EPA, 2009a, p. 2 - 26). Epidemiological studies have used measured ambie nt PM 2.5 speciation data, including monitoring data from the CSN, while all of the controlled human exposure and most of the toxicological studies have used concentrated ambient particles and analyzed the constituents therein (US EPA, 2009a, p. 6 - 203). 53 The CSN provides PM 2.5 speciation measurements generally on a one - in - three or one - in - six day sampling schedule and, thus, do not capture data every day at most sites. 54 The Policy Assessment recognizes that several new multi - city studies evaluating short - term exposures to fine particle constituents are now available . These studies continue to show an association between mortality and cardiovascular and/or respiratory morbidity effects and short - term exposures to various PM 2.5 components including nickel, v anadium, elemental carbon, organic carbon, nitrates, and sulfates (US EPA, 2011a, section 2.3.1; US EPA, 2009a, sections 6.5.2.5 and 6.6). Limited evidence is available to evaluate the health effects associated with long - term exposures to PM 2.5 components (US EPA, 2009a, section 7.6.2). The Policy Assessment notes the most significant new evidence is provided by a study that evaluated multiple PM 2.5 components and an indicator of traffic density in an assessment of health effects related to long - term expos ure to PM 2.5 (Lipfert et al., 2006). Using health data from a cohort of U.S. military veterans and PM 2.5 measurement data from the CSN, Lipfert et al. (2006) reported positive associations between mortality and long - term exposures to nitrates, elemental ca rbon, nickel, and vanadium as well as traffic density and peak ozone concentrations (US EPA, 2011a, p. 2 - 54; US EPA, 2009a, pp. 7 - 89 to 7 - 90). 53 Most studies considered between 7 to 20 ambient PM 2.5 constituents, with elemental carbon, organic carbon, sulfates, nitrates, and m etals most commonly measured . Many of the studies grouped the constituents with various factorization or source apportionment techniques to examine the relationship between the grouped constituents and various health effects . However, not all studies label ed the constituent groupings according to their presumed source and a small number of controlled human exposure and toxicological studies did not use any constituent grouping . These differences across studies substantially limit any integrative interpretat ion of these studies (US EPA, 2009a, p. 6 - 203) . 54 To expand our understanding of the role of specific PM 2.5 components and sources with respect to the observed health effects, researchers have expressed a strong interest in having access to PM 2.5 speciation measurements collected more frequently (US EPA, 2011a, p. 2 - 53, including footnote 47) .***E.O. 12866 Review

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Page 74 of 133 With respect to source categories of fine particles associated with a range of health endpoints, the Integrated Science Assessment reports that the currently available evidence suggests associations between cardiovascular effects and a number of specific PM 2.5 – related source categories, specifically oil combustion, wood or biomass burning, motor vehicle emissions, a nd crustal or road dust sources (US EPA, 2009a, section 6.6; Table 6 - 18). In addition, a few studies have evaluated associations between PM 2.5 - related source categories and mortality. These studies include a study that reported an association between morta lity and a PM 2.5 coal combustion factor (Laden et al., 2000), while other studies linked mortality to a secondary sulfate long - range transport PM 2.5 source (Ito et al., 2006; Mar et al., 2006) (US EPA, 2009a, section 6.6.2.1). There is less consistency in associations observed between sources of fine particles and respiratory health effects, which may be partially due to the fact that fewer studies have evaluated respiratory - related outcomes and measures. However, there is some evidence for PM 2.5 - related as sociations with secondary sulfate and decrements in lung function in asthmatic and healthy adults (US EPA, 2009a, p. 6 - 211; Gong et al., 2005; Lanki et al., 2006). Respiratory effects relating to the crustal/soil/road dust and traffic sources of PM have be en observed in asthmatic children and adults (US EPA, 2009a, p. 6 - 205; Gent et al., 2009; Penttinen et al., 2006). Recent studies have shown that source apportionment methods have the potential to add useful insights into which sources and/or PM constitue nts may contribute to different health effects. Of particular interest are several epidemiological studies that compared source apportionment methods and reported consistent results across research groups (US EPA, 2009a, p. 6 - 211; Hopke et al., 2006; Ito e t al., 2006; Mar et al., 2006; Thurston et al., 2005). These studies reported associations between total mortality and secondary sulfate in two cities for two different lag times. The sulfate effect was stronger for total mortality in Washington D.C. and f or cardiovascular - related morality in Phoenix (US EPA, 2009a, p. 6 - 204). These studies also found some evidence for associations with mortality and a number of source categories (e.g., biomass/wood combustion, traffic, copper smelter, coal combustion, sea salt)***E.O. 12866 Review

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Page 75 of 133 at various lag times (US EPA, 2009a, p. 6 - 204). Sarnat et al. (2008) compared three different source apportionment methods and reported consistent associations between emergency department visits for cardiovascular diseases with mobile sources and bi omass combustion as well as increased respiratory related emergency department visits associated with secondary sulfate (US EPA, 2009a, pp. 6 - 204 and 6 - 211). Collectively, in considering the currently available evidence for health effects associated with s pecific PM 2.5 components or groups of components associated with any source categories of fine particles as presented in the Integrated Science Assessment, the Policy Assessment concludes that additional information available in this review continues to pr ovide evidence that many different constituents of the fine particle mixture as well as groups of components associated with specific source categories of fine particles are linked to adverse health effects (US EPA, 2011a, p. 2 - 55). However, as noted in th e Integrated Science Assessment, while “[t]here is some evidence for trends and patterns that link particular ambient PM constituents or sources with specific health outcomes...there is insufficient evidence to determine whether these patterns are consistent or robust” (US EPA, 2009a, p. 6 - 210). Assessing this information, the Integrated Science Assessment concludes that “the evidence is not yet sufficient to allow differentiation of those constituents or sources that are more closely related to specific heal th outcomes” (US EPA, 2009a, pp. 2 - 26 and 6 - 212). Therefore, the Policy Assessment concludes that the currently available evidence is not sufficient to support consideration of a separate indicator for a specific PM 2.5 component or group of components asso ciated with any source category of fine particles. Furthermore, the Policy Assessment concludes that the evidence is not sufficient to support eliminating any component or group of components associated with any source categories of fine particles from the mix of fine particles included in the PM 2.5 indicator (US EPA, 2011a, p. 2 - 56). The CASAC concluded that it is appropriate to consider retaining PM 2.5 as the indicator for fine particles and further asserted, “There [is] insufficient peer - reviewed litera ture to support any other***E.O. 12866 Review

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Page 76 of 133 indicator at this time” (Samet, 2010c, p. 12). CASAC expressed a strong desire for the EPA to “look ahead to future review cycles and reinvigorate support for the development of evidence that might lead to newer indicators that ma y correlate better with the health effects associated with ambient air concentrations of PM ...” (Samet, 2010c, p 2). Consistent with the staff conclusions presented in the Policy Assessment and CASAC advice, the Administrator proposes to retain PM 2.5 as th e indicator for fine particles. Further, the Administrator provisionally concludes that currently available scientific information does not provide a sufficient basis for supplementing mass - based, primary fine particle standards with standards using a sepa rate indicator for ultrafine particles or a separate indicator for a specific PM 2.5 component or group of components associated with any source categories of fine particles. Furthermore, the Administrator also provisionally concludes that the currently ava ilable scientific information does not provide a sufficient basis for eliminating any individual component or group of components associated with any source categories from the mix of fine particles included in the PM 2.5 mass - based indicator. 2. Averaging Ti me In 1997, the EPA initially set both an annual standard, to provide protection from health effects associated with both long - and short - term exposures to PM 2.5 , and a 24 - hour standard to supplement the protection afforded by the annual standard (62 FR 38667 to 38668, July, 18, 1997). In the last review, the EPA retained both annual and 24 - hour averaging times (71 FR 61164, October 17, 2006). These decisions were based, in part, on evidence of health effects related to both long - term (from a year to seve ral years) and short - term (from less than one day to up to several days) measures of PM 2.5 . The overwhelming majority of studies conducted since the last review continue to utilize annual (or multi - year) and 24 - hour averaging times, reflecting the averagin g times of the current PM 2.5 standards. These studies continue to provide evidence that health effects are associated with annual and 24 - hour averaging times. Therefore, the Policy Assessment concludes it is appropriate to retain the***E.O. 12866 Review

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Page 77 of 133 current annual and 24 - hour averaging times to provide protection from effects associated with both long and short - term PM 2.5 exposures (US EPA, 2011a, p. 2 - 57). In considering whether the information available in this review supports consideration of different averaging times for PM 2.5 standards specifically with regard to considering a standard with an averaging time less than 24 hours to address health effects associated with sub - daily PM 2.5 exposures, the Policy Assessment notes there continues to be a growing body of studie s that provide additional evidence of effects associated with exposure periods less than 24 - hours (US EPA, 2011a, p. 2 - 57). Relative to information available in the last review, recent studies provide additional evidence for cardiovascular effects associat ed with sub - daily (e.g., one to several hours) exposure to PM, especially effects related to cardiac ischemia, vasomotor function, and more subtle changes in markers of systemic inflammation, hemostasis, thrombosis and coagulation (US EPA, 2009a, section 6 .2). Because these studies have used different indicators (e.g., PM 2.5 , PM 10 , PM 10 - 2.5 , ultrafine particles), averaging times (e.g., 1, 2, and 4 hours), and health outcomes, it is difficult to draw conclusions about cardiovascular effects associated specif

ically with sub - daily exposures to PM 2.5 . With regard to respiratory effects associated with sub - daily PM 2.5 exposures, the currently available evidence is much sparser than for cardiovascular effects and continues to be very limited. The Integrated Scien ce Assessment concludes that for several studies of hospital admissions or medical visits for respiratory diseases, the strongest associations were observed with 24 - hour average or longer exposures, not with less than 24 - hour exposures (US EPA, 2009a, sect ion 6.3). Collectively, the Policy Assessment concludes that this information, when viewed as a whole, is too unclear, with respect to the indicator, averaging time and health outcome, to serve as a basis for consideration of establishing a primary PM 2.5 standard with an averaging time shorter than 24 - hours at this time (US EPA, 2011a, p. 2 - 57). With regard to health effects associated with PM 2.5 exposure across varying seasons in this***E.O. 12866 Review

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Page 78 of 133 review, Bell et al. (2008) reported higher PM 2.5 risk estimates for ho spitalization for cardiovascular and respiratory diseases in the winter compared to other seasons. In comparison to the winter season, smaller statistically significant associations were also reported between PM 2.5 and cardiovascular morbidity for spring a nd autumn, and a positive, but statistically non - significant association was observed for the summer months. In the case of mortality, Zanobetti and Schwartz (2009) reported a 4 - fold higher effect estimate for PM 2.5 associated mortality for the spring as c ompared to the winter. Taken together, these results provide emerging but limited evidence that individuals may be at greater risk of dying from higher exposures to PM 2.5 in the warmer months and may be at greater risk of PM 2.5 - associated hospitalization f

or cardiovascular and respiratory diseases during colder months of the year (US EPA, 2011a, p. 2 - 58). Overall, the Policy Assessment observes that there are few studies presently available to deduce a general pattern in PM 2.5 - related risk across seasons. In addition, these studies utilized 24 - hour exposure periods within each season to assess the PM 2.5 associated health effects, and do not provide information on health effects associated with a season - long exposure to PM 2.5 . Due to these limitations in the currently available evidence, the Policy Assessment concludes that there is no basis to consider a seasonal averaging time separate from a 24 - hour averaging time. Based on the above considerations, the Policy Assessment concludes that the currently availa ble information provides strong support for consideration of retaining current annual and 24 - hour averaging timers but does not provide support for considering alternative averaging times (US EPA, 2011a, p. 2 - 58). In addition, CASAC considers it appropriat e to retain the current annual and 24 - hour averaging times for the primary PM 2.5 standards (Samet, 2010c, pp. 2 to 3). The Administrator concurs with the staff conclusions and CASAC advice and proposes that the averaging times for the primary PM 2.5 standar ds should continue to include annual and 24 - hour averages to protect against health effects associated with long - and short - term exposures. Furthermore, the Administrator provisionally concludes,***E.O. 12866 Review

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Page 79 of 133 consistent with conclusions reached in the Policy Assessment and by CASAC, that the currently available information is too limited to support consideration of alternative averaging times to establish a national standard with a shorter - than 24 - hour averaging time or with a seasonal averaging time. 3. Form The “form” o f a standard defines the air quality statistic that is to be compared to the level of the standard in determining whether an area attains the standard. In this review, we consider whether currently available information supports consideration of alternativ e forms for the annual or 24 - hour PM 2.5 standards. a. Annual Standard In 1997, the EPA established the form of the annual PM 2.5 standard as an annual arithmetic mean, averaged over 3 years, from single or multiple community - oriented monitors. This form was i ntended to represent a relatively stable measure of air quality and to characterize longer - term area - wide PM 2.5 concentrations, in conjunction with a 24 - hour standard designed to provide adequate protection against localized peak or seasonal PM 2.5 concentr ations. The level of the standard was to be compared to measurements made at each community - oriented monitoring site, or, if specific criteria were met, measurements from multiple community - oriented monitoring sites could be averaged (62 FR 38671 to 38672, July 18, 1997). The constraints were intended to ensure that spatial averaging would not result in inequities in the level of protection provided by the standard (62 FR 38672, July 18, 1997). This approach was consistent with the epidemiological studies o n which the PM 2.5 standard was primarily based, in which air quality data were generally averaged across multiple monitors in an area or were taken from a single monitor that was selected to represent community - wide exposures. In the last review, the EPA tightened the criteria for use of spatial averaging to provide increased protection for vulnerable populations exposed to PM 2.5 . This change was based in part on an analysis of the potential for disproportionate impacts on potentially susceptible at - risk po pulations, which found that***E.O. 12866 Review

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Page 80 of 133 the highest concentrations in an area tend to be measured at monitors located in areas where the surrounding population is more likely to have lower education and income levels, and higher percentages of minority populations (71 FR 61166/2, October 17, 2006; US EPA, 2005, section 5.3.6.1). In this review, as discussed in section III.B.3, there now exist more health data such that the Integrated Science Assessment has identified persons from lower socioeconomic strata as a susceptible an at - risk population (US EPA, 2009a, section 8.1.7; US EPA, 2011a, section 2.2.1). Moreover, there now exist more years of PM 2.5 air quality data than were available in the last review. Consideration in the Policy Assessment of the spatial vari ability across urban areas that is revealed by this expanded data base has raised questions as to whether an annual standard that allows for spatial averaging, even within specified constraints as narrowed in 2006, would provide appropriate public health p rotection. In considering the potential for disproportionate impacts on susceptible at - risk populations, the Policy Assessment recognizes an update of an air quality analysis conducted for the last review (US EPA, 2011a, pp. 2 - 59 to 60; Schmidt, 2011a, Ana lysis A). This analysis focuses on determining if the spatial averaging provisions, as modified in 2006, could introduce inequities in protection for susceptible at - risk populations exposed to PM 2.5 . Specifically, the Policy Assessment considers whether per sons of lower socioeconomic status are more likely than the general population to live in areas in which the monitors recording the highest air quality values in an area are located. Data used in this analysis included demographic parameters measured at th e Census Block or Census Block Group level, including percent minority population, percent minority subgroup population, percent of persons living below the poverty level, percent of persons 18 years of age or older, and percent of persons 65 years of age and older. In each candidate geographic area, data from the Census Block(s) or Census Block Group(s) surrounding the location of the monitoring site (as delineated by radii buffers of 0.5, 1.0, 2.0, and 3.0 miles) in which the highest air quality value was monitored were compared to the average of***E.O. 12866 Review

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Page 81 of 133 monitored values in the area. This analysis looked beyond areas that would meet the current spatial averaging criteria and considered all urban areas (i.e., Core Based Statistical Areas or CBSAs) with at least two valid annual design value monitors (Schmidt, 2011a, Analysis A). Recognizing the limitations of such cross - sectional analyses, the Policy Assessment observes that the highest concentrations in an area tend to be measured at monitors located in areas where the surrounding populations are more likely to live below the poverty line and to have higher percentage of minorities (US EPA, 2011a, p. 2 - 60). Based upon the analysis described above, the Policy Assessment concludes that the existing constraints on spa tial averaging, as modified in 2006, may be inadequate to avoid substantially greater exposures in some areas, potentially resulting in disproportionate impacts on susceptible at - risk populations of persons with lower SES levels as well as minorities. There fore, the Policy Assessment concludes that it is appropriate to consider revising the form of the annual PM 2.5 standard such that it does not allow for the use of spatial averaging across monitors. In doing so, the level of the annual PM 2.5 standard would be compared to measurements made at the monitoring site that represents area - wide air quality recording the highest PM 2.5 concentrations 55 (US EPA, 2011a, p. 2 - 60). The CASAC agreed with staff conclusions that it is “reasonable” for the EPA to eliminate th e spatial averaging provisions (Samet, 2010d, p. 2). Further, in CASAC’s comments on the first draft Policy Assessment, they noted, “Given mounting evidence showing that persons with lower SES levels are a susceptible group for PM - related health risks, CAS AC recommends that the provisions that allow for spatial averaging across monitors be eliminated for the reasons cited in the (first draft) Policy Assessment” (Samet, 2010c, p. 13). In considering the Policy Assessment’s conclusions based on the results of the analysis discussed above and concern over the evidence of potential disproportionate impacts on susceptible at - risk populations as well as CASAC advice, the Administrator proposes to revise the form of the annual PM 2.5 55 As discussed in section VII I .B.1 below, the EPA is proposing to revise several terms associated with PM 2.5 monitor placement . Specifically, the EPA is proposing to revoke the term “community - oriented” and replace it with the term “area - wide” monitoring .***E.O. 12866 Review

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Page 82 of 133 standard to eliminate the use of spatial averaging. Thus, the Administrator proposes revising the form of the annual PM 2.5 standard to compare the level of the standard with measurements from each “appropriate” monitor in an area 56 with no allowance for spatial averaging. Thus, for an area with multiple monitors, the appropriate reporting monitor with the highest design value would determine the attainment status for that area. b. 24 - Hour Standard In 1997, the EPA established the form of the 24 - hour PM 2.5 standard as the 98 th percentile of 24 - hour concentrations at each population - oriented monitor within an area, averaged over three years (62 FR at 38671 to 38674, July 18, 1997). The Agency selected the 98 th percentile as an appropriate balance between adequately limiting the occurrence of peak concentrations and providing increased stability which, when averaged over 3 years, facilitated effective health protection through the development of more stable implementation programs. By basing the form of the standard on concentrations measured at po pulation - oriented monitoring sites, the EPA intended to provide protection for people residing in or near localized areas of elevated concentrations. In the last review, in conjunction with lowering the level of the 24 - hour standard, the EPA retained this form based in part on a comparison with the 99 th percentile form. 57 In revisiting the stability of a 98 th versus 99 th percentile form for a 24 - hour standard intended to provide supplemental protection for a generally controlling annual standard, an analysi s presented in the Policy Assessment considers air quality data reported in 2000 to 2008 to update our understanding of the ratio between peak - to - mean PM 2.5 concentrations. This analysis provides evidence that the 98 th 56 As discussed in section VII I .B.2.b below, the EPA propos es that PM 2.5 monitoring sites at micro - and middle - scale locations be comparable to t he annual standard unless the monitoring site has been approved by the Regional Administrator as a “relatively unique micro - scale , or localized hot - spot, or unique middle - scale site.” 57 In reaching this final decision, the EPA recognized a technical proble m associated with a potential bias in the method used to calculate the 98 th percentile concentration for this form . The EPA adjusted the sampling frequency requirement in order to reduce this bias . Accordingly, the Agency modified the final monitoring requ irements such that areas that are within 5 percent of the standards are required to increase the sampling frequency to every day (71 FR 61164 to 61165, October 17, 2006).***E.O. 12866 Review

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Page 83 of 133 percentile value is a more stable met ric than the 99 th percentile (US EPA, 2011a, Figure 2 - 2, p. 2 - 62). The Agency recognizes that the selection of the appropriate form of the 24 - hour standard includes maintaining adequate protection against peak 24 - hour concentrations while also providing a stable target for risk management programs, which serves to provide for the most effective public health protection in the long run. 58 As in previous reviews, the EPA recognizes that a concentration - based form, compared to an exceedance - based form, is more reflective of the health risks posed by elevated pollutant concentrations because such a form gives proportionally greater weight to days when concentrations are well above the level of the standard than to days when the concentrations are just above the level of the standard . Further, the Agency concludes that a concentration - based form, when averaged over three years, provides an appropriate balance between limiting peak pollutant concentrations and providing a stable regulatory target, thus facilitating the development of more stable im plementation programs. In considering the information provided in the Policy Assessment and recognizing that the degree of public health protection likely to be afforded by a standard is a result of the combination of the form and the level of the standard, the Administrator proposes to retain the 98 th percentile form of the 24 - hour standard. The Administrator provisionally concludes that the 98 th percentile form represents an appropriate balance between adequately limitin g the occurrence of peak concentrations and providing increased stability relative to an alternative 99 th percentile form. 4. Level In the last review, the EPA selected levels for the annual and the 24 - hour PM 2.5 standards using evidence of effects associate d with periods of exposure that were most closely matched to the averaging time of each standard. Thus, as discussed in section III.A.1, the EPA relied upon evidence from long - 58 See ATA III , 283 F.3d at 374 - 376 which concludes that it is legitimate for the EPA to consider overall stability of the standard and its resulting promotion of overall effectiveness of NAAQS control programs in setting a standard that is requisite to protect the public health . The context for the court’s discussion is identical to that h ere; whether to adopt a 98 th percentile form for a 24 - hour primary PM 2.5 standard intended to provide supplemental protection for a generally controlling annual standard. Formatted: Font: Italic, No underline***E.O. 12866 Review

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Page 84 of 133 term exposure studies as the principal basis for selecting the level of the annu al PM 2.5 standard that would protect against effects associated with long - term exposures. The EPA relied upon evidence from the short - term exposures studies as the principal basis for selecting the level of the 24 - hour PM 2.5 standard that would protect aga inst effects associated with short - term exposures. As summarized in section III.A.2 above, the 2006 decision to retain the level of the annual PM 2.5 standard at 15 μg/m 3 59 was challenged and on judicial review, the D.C. Circuit remanded the primary annual PM 2.5 standard to the EPA, finding that EPA’s explanation for its approach to setting the level of the annual standard was inadequate. a. Approach Used in the Policy Assessment Building upon the lessons learned in the previous PM NAAQS reviews, in considerin g alternative standard levels supp orted by the currently available scientific information, the Policy Assessment uses an approach that integrates evidence - based and risk - based considerations, takes into account CASAC advice, and considers the issues raised by the court in remanding the primary annual PM 2.5 standard. Following the general approach outlined in section III.A.3, for the reasons discussed below, the Policy Assessment concludes it is appropriate to consider the protection afforded by the annual a nd 24 - hour standards taken together against mortality and morbidity effects associated with both long - and short - term PM 2.5 exposures. This is consistent with the approach taken in the review completed in 1997 rather than considering each standard separate ly, as was done in the review completed in 2006. Beyond looking directly at the relevant epidemiologic evidence, the Policy Assessment considers the extent to which specific alternative PM 2.5 standard levels are likely to reduce the nature and magnitude o f both long - term exposure - related mortality risk and short - term exposure - related mortality 59 Throughout this section, the annual standard level is denoted as an integer value f or simplicity, although, as noted above in section I I .B .1 , Table 1, footnote 7, the standard level is defined to one decimal place, such that the current standard level is 15.0 μg/m 3
. Alternative standard levels discussed in this section are similarly defi ned to one decimal place.***E.O. 12866 Review

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Page 85 of 133 and morbidity risk (US EPA, 2011a, section 2.3.4.2; U.S.EPA, 2010a, section 4.2.2). As noted in section III.C.3 above, patterns of increasing estimated risk reductio ns are generally observed as either the annual or 24 - hour standard, or both, are reduced below the level of the current standards (US 2011a, Figures 2 - 11 and 2 - 12; US EPA, 2010a, sections 4.2.2, 5.2.2, and 5.2.3). Based on the quantitative risk assessment, the Policy Assessment observes, as discussed in section III.A.3, that analyses conducted for this and previous reviews demonstrate that much, if not most, of the aggregate risk associated with short - term exposures results from the large number of days during which the 24 - hour average concentrations are in the low - to mid - range, below the peak 24 - hour concentrations (US EPA, 2011a, p. 2 - 9). Furthermore, as discussed in section III.C.3, the Risk Assessment observes that alternative annual standard levels, when controlling, resulted in more consistent risk reductions across urban study areas, thereby potentially providing a more consistent degree of public health protection (US EPA, 2010a, pp. 5 - 15 to 5 - 16). In contrast, the Risk Assessment notes tha t while the results of simulating alternative suites of PM 2.5 standards including different combinations of alternative annual and 24 - hour standard levels suggest that an alternative 24 - hour standard level can produce additional estimated risk reductions b eyond that provided by an alternative annual standard alone. However, the degree of estimated risk reduction provided by alternative 24 - hour standard levels is highly variable, in part due to the choice of rollback approached used (US EPA, 2010a, p. 5 - 17). Therefore, the Policy Assessment concludes, consistent with CASAC advice (Samet 2010c, p. 1), that it is appropriate to set a “generally controlling” annual standard that will lower a wide range of ambient 24 - hour concentrations. The Policy Assessment co ncludes this approach would likely reduce aggregate risks associated with both long - and short - term exposures with more consistency than a generally controlling 24 - hour standard and would be the most effective and efficient way to reduce total PM 2 - 5 - relate d population risk and so provide appropriate protection. The staff believes this approach, in***E.O. 12866 Review

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Page 86 of 133 contrast to one focusing on a generally controlling 24 - hour standard, would likely reduce aggregate risks associated with both long - and short - term exposures with more consistency and would likely avoid setting national standards that could result in relatively uneven protection across the country due to setting standards that are either more or less stringent than necessary in different geographical areas. The Po licy Assessment recognizes that an annual standard intended to serve as the primary means for providing protection against effects associated with both long - and short - term PM 2.5 exposures cannot be expected to offer an adequate margin of safety against th e effects of all short - term PM 2.5 exposures. As a result, in conjunction with a generally controlling annual standard, the Policy Assessment concludes it is appropriate to consider setting a 24 - hour standard to provide supplemental protection, particularly for areas with high peak - to - mean ratios possibly associated with strong local or seasonal sources, or PM 2.5 - related effects that may be associated with shorter - than - daily exposure periods. Based on the above considerations, the approach used in the Policy Assessment to identify alternative standard levels that are appropriate for consideration focuses on translating information from epidemiological studies into the basis for staff conclusions on levels. This approach is broader and more integrative than th e general approach used by the EPA in previous reviews (see summary in section III.A.3 above; US EPA, 2011a, sections 2.1.3 and 2.3.4.1) and reflects the more extensive and stronger body of scientific evidence now available on health effects related to lon g - and short - term PM 2.5 exposures, a more comprehensive quantitative risk assessment, and more extensive PM 2.5 air quality data. In considering the currently available information, the Policy Assessment focuses on identifying levels for an annual standard and a 24 - hour standard that, in combination, provide protection against health effects associated with both long - and short - term PM 2.5 exposures. The Policy Assessment also considers the extent to which various combinations of annual and 24 - hour standards reflect setting a generally controlling annual standard with a 24 - hour standard providing supplemental protection (US***E.O. 12866 Review

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Page 87 of 133 EPA, 2011a, sections 2.1.3, 2.3.4.1). As discussed in the Policy Assessment, EPA staff recognizes that there is no single factor or crite rion that comprises the “correct” approach for reaching conclusions on alternative standard levels for consideration, but rather there are various approaches that are reasonable to consider (US EPA, 2011a, section 2.3.4.1). In reaching conclusions in the P olicy Assessment on the ranges of standard levels that are appropriate to consider, staff considered the relative weight to place on different evidence. The Policy Assessment initially focuses on long - and short - term PM 2.5 exposure studies conducted in the U.S. and Canada and places the greatest weight on health outcomes judged in the Integrated Science Assessment as having evidence to support a causal or likely causal relationship. The Policy Assessment also considers the evidence for a broader range of he alth outcomes judged in the Integrated Science Assessment to have evidence suggestive of a causal relationship, specifically studies that focus on effects in susceptible populations, to evaluate whether this evidence provides support for considering lower alternative standard levels. Several factors were taken into account in placing relative weight on the body of available epidemiological studies, for example, study characteristics, including study design (e.g., time period of air quality monitoring, cont rol for potential confounders); strength of the study (in terms of statistical significance and precision of results); and availability of population - level and air quality distribution data. As noted above in section III.A.3, the Policy Assessment places g reatest weight on information from multi - city epidemiological studies to inform staff conclusions regarding alternative annual standard levels. These studies have a number of advantages compared to single - city studies 60 that include providing representation of ambient PM 2.5 concentrations and potential health impacts across a range of 60 As discussed in section II I .B.1 above, the Policy Assessment recognizes that single - city studies provide ancillary evidence to multi - city studies in support of calling into question the adequacy of the current suite of standards . However, in light of the mixed findings reported in single - city short - term PM 2.5 exposure studies, and the likelihood that these results are influenced by localized events and not representative of air quality across the country, the Policy Assessment places comparatively greater weight on the results from multi - city studies in considering alternative annual and 24 - hour standard levels (US EPA, 2011a, p. 2 - 64) .***E.O. 12866 Review

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Page 88 of 133 diverse locations providing spatial coverage for different regions across the country, reflecting differences in PM 2.5 sources, composition, and potentially other exposure - rela ted factors which might impact PM 2.5 - related risks; lack of ‘publication bias’ (US EPA, 2004, p. 8 - 30); and consideration of larger study populations that afford the possibility of generalizing to the broader national population and provide higher statisti cal power than single - city studies to detect potentially statistically significant associations with relatively more precise effect estimates. In reaching conclusions in the Policy Assessment regarding alternative 24 - hour standard levels that are appropri ate to consider, staff also considers relevant information from single - city short - term PM 2.5 exposure studies. Although, as discussed above, multi - city studies have greater power to detect associations and provide broader geographic coverage in comparison to single - city studies, the extent to which effects reported in multi - city short - term PM 2.5 exposure studies are associated with the specific short - term air quality in any particular location is unclear, especially when considering short - term concentration s at the upper end of the air quality distribution (i.e., at the 98 th percentile value) for a given study area. In contrast, single - city studies are more limited in terms of power and geographic coverage but the link between reported health effects and the air quality in a given study area is more straightforward. Therefore, the Policy Assessment considers the results of both multi - city and single - city short - term exposure studies to inform staff conclusions regarding alternative levels that are appropriate to consider for a 24 - hour standard that is intended to provide supplemental protection in areas where the annual standard may not offer appropriate protection against the effects of all short - term exposures (US EPA, 2011a, pp. 2 - 62 to 2 - 65). b. Consideration of the Annual Standard in the Policy Assessment In recognizing the absence of a discernible population threshold below which effects would not occur, the Policy Assessment’s general approach for identifying alternative annual standard levels that are appr opriate to consider focuses on characterizing the range of PM 2.5 concentrations over which we***E.O. 12866 Review

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Page 89 of 133 have the most confidence in the associations reported in the epidemiological studies, and conversely where our confidence in the association becomes appreciably l ower. The most direct approach to address this issue, consistent with CASAC advise advice (Samet, 2010c, p.10), is to consider epidemiological studies reporting confidence intervals around concentration - response relationships (US EPA, 2011a, p. 2 - 63). Based on a thorough search of the available evidence, the Policy Assessment identified three long - term PM 2.5 exposure studies reporting confidence intervals around concentration response functions (i.e., Schwartz et al., 2008; Pope et al., 2002; Miller et al., 2007; US EPA, 2011a, pp. 2 - 65 to 2 - 70 and Figure 2 - 3). 61 In its assessment of these studies, the Policy Assessment places greater weight on analyses that averaged across multiple concentration - response models since this approach represents a more robust exa mination of the underlying concentration - response relationship than analyses considering a single concentration - response model. Although these analyses of long - term exposure to PM 2.5 provide information on the lack of any discernible population threshold, only Schwartz et al. (2008) conducted a multi - model analysis to characterize confidence intervals around the estimated concentration - response relationship that can help inform at what PM 2.5 concentrations we have appreciably less confidence in the nature of the underlying concentration - response relationship. Although analyses of confidence intervals associated with concentration - response relationships can help inform consideration of alterna tive standard levels, the Policy Assessment concludes that the single relevant analysis now available is too limited to serve as the principal basis for identifying alternative standard levels in this review (US EPA, 2011a, p. 2 - 70). The Policy Assessment explores other approaches that considered different statistical metrics to identify ranges of long - term mean PM 2.5 concentrations that were most influential in generating health effect estimates in long - and short - term epidemiological studies, placing grea test weight on those studies 61 The EPA carefully analyzed the published evidence, but was unable to identify any short - t erm PM 2.5 exposure studies that characterized confidence intervals around concentration - response relationships . Nor did CASAC or public comments on this issue, as addressed in their comments on the second draft Policy Assessment, identify any additional an alyses.***E.O. 12866 Review

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Page 90 of 133 that reported positive and statistically significant associations (US EPA, 2011a, p. 2 - 63). First, as discussed in section III.A.3 above, the Policy Assessment considered the statistical metric used in previous reviews. This ap proach recognizes that the strongest evidence of associations occurs at concentrations around the long - term mean concentration. Thus, in earlier reviews, the EPA focused on identifying standard levels that were somewhat below the long - term mean concentrati ons reported in PM 2.5 exposure studies. The long - term mean concentrations represent air quality data typically used in epidemiological analyses and provide a direct link between PM 2.5 concentrations and the observed health effects. Further, these data are available for all long - and short - term exposure studies analyzed and, therefore, represent the data set available for the broadest set of epidemiological studies. However, consistent with CASAC’s comments on the second draft Policy Assessment 62 (Samet, 201 0d, p. 2), in preparing the final Policy Assessment, EPA staff explored ways to take into account additional information from epidemiological studies, when available (Rajan et al., 2011). These analyses focused on evaluating different statistical metrics, beyond the long - term mean concentration, to characterize the range of PM 2.5 concentrations down through which staff continued to have confidence in the associations observed in epidemiological studies and below which there is a comparative lack of data suc h that the staff’s confidence in the relationship was appreciably less. This would also be the range of PM 2.5 concentrations which has the most influence on generating the health effect estimates reported in epidemiological studies. As discussed in section III.A.3 above, the Policy Assessment recognizes there is no one percentile value within a given distribution that is the most appropriate or “correct” way to characterize where our confidence in the associations becomes appreciably lower. The Policy Asses sment concludes that focusing on concentrations within the lower quartile of a distribution, such as the range from the 25 th to the 10 th percentile, is reasonable to consider as a region within which 62 While CASAC expressed the view that it would be most desirable to have information on concentration - response relationships, they recognized that it would also be “preferable to have information on the concentrations that were most influential in generating the health effect estimates in individual studies” (Samet, 2010d, p. 2).***E.O. 12866 Review

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Page 91 of 133 we begin to have appreciably less confidence in the asso ciations observed in epidemiological studies. 63 In staff’s view, considering lower PM 2.5 concentrations, down to the lowest concentration observed in a study, would be a highly uncertain basis for selecting alternative standard levels . (US EPA, 2009a, p. 2 - 71). As outlined in section III.A.3 above, the Policy Assessment recognizes that there are two types of population - level information to consider in identifying the range of PM 2.5 concentrations which have the most influence on generating the health effect estimates reported in epidemiological studies. The most relevant information to consider is the number of health events (e.g., deaths, hospitalizations) occurring within a study population in relation to the distribution of PM 2.5 concentrations likely expe rienced by study participants. Although not as directly relevant, However, in recognizing that access to health event data may be restricted, and consistent with advice from CASAC (Samet 2010d, p.2), EPA staff also considered the number of participants with in each study area can be used as a surrogate for health event data in relation to the distribution of PM 2.5 concentrations (i.e., study population data), as an appropriate surrogate for health event data . In applying this approach, the Policy Assessment focuses on identifying the broader range of PM 2.5 concentrations which had the most influence on generating health effect estimates in epidemiological studies . , as discussed in section III.A.3 above. As discussed below, in working with study investigators, EPA staff was able to obtain health event data for three large multi - city studies (Krewski et al., 2009; Zanobetti and Schwartz, 2009; Bell et al., 2008) and population data for the same 63 In the last review, staff believed it was appropriate to consider a level for an annual PM 2.5 standard that was somewhat below the averages of the long - term concentratio ns across the cities in each of the key long - term exposures studies, recognizing that the evidence of an association in any such study was strongest at and around the long - term average where the data in the study are most concentrated . For example, the int erquartile range of long - term average concentrations within a study and a range within one standard deviation around the study mean were considered reasonable approaches for characterizing the range over which the evidence of association is strongest (US E PA, 2005, pp. 5 - 22 to 5 - 23) . In this review, the Policy Assessment noted the interrelatedness of the distributional statistics and a range of one standard deviation around the mean which contains approximately 68 percent of normally distributed data, in th at one standard deviation below the mean falls between the 25 th and 10 th percentiles (US EPA, 2011a, p. 2 - 71) .***E.O. 12866 Review

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Page 92 of 133 three studies and one additional long - term exposure study (Miller et al., 2007); as documented in a staff memorandum (Rajan et al., 2011). For the three studies for which both health event and study population data were available, EPA staff analyzed the reliability of using study population data as a surrogate for health e vent data. Based on these analyses, EPA staff recognized that the 10 th and 25 th percentiles of the health event and study population distributions are nearly identical and concluded that the distribution of population data can be a useful surrogate for event data, providing support for consideration of the study population data for M iller et al. (2007), for which health event data were not available (Rajan et al., 2011, Analysis 1 and Analysis 2, in particular, Table 1 and Figures 1 and 2). With regard to the long - term mean PM 2.5 concentrations which are relevant to the first approach, Figures 1 through 3 (US EPA, 2011a, Figures 2 - 4, 2 - 5, 2 - 6, and 2 - 8) summarize data available for multi city, long - and short - term exposure studies that evaluated endpoints classified in the Integrat ed Science Assessment as having evidence of a causal or likely causal relationship or evidence suggestive of a causal relationship, showing the studies with long - term mean PM 2.5 concentrations below 17 μg/m 3
. 64 Figures 1 and 3 provide summaries of summari z e the health outcomes evaluated , relative risk estimates, air quality data, and geographic scope for long - and short - term exposure studies , respectively, that evaluated mortality (evidence of a causal relationship); cardiovascular effects (evidence of a caus al relationship); and respiratory effects (evidence of a likely causal relationship) in the general population, as well as in older adults (a susceptible , an at - risk population ). . Figure 2 provides a this same summary of information for long - term exposure studies that evaluated respiratory effects (evidence of a likely causal relationship) in children, a susceptible an at - risk population, as well as long - term exposure studies of children that evaluated developmental effects (evidence suggestive of a causal relationship). By following the general approach used in previous PM NAAQS reviews, one could consider identifying alternative standard levels that are somewhat below the long - term mean PM 2.5 concentrations reported in 64 Additional studies presented and assessed in the Integrated Science Assessment report effects at higher long - term mean PM 2.5 concentrations (e .g., US EP A, 2009a, Figures 2 - 1, 2 - 2, 7 - 6, and 7 - 7).***E.O. 12866 Review

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Page 93 of 133 these epidemiological studies. As ou tlined above in section III.A.3, With regard to consideration of additional information from epidemiological studies typically report which is relevant to the second approach, EPA has compiled a summary of the range of PM 2.5 concentrations based upon a compo site monitor corresponding with the 25 th to 10 th percentiles of health event or study population data from the four multi - city studies, for which distributional statistics are available 65 (US EPA, 2011a, Figure 2 - 7; Rajan et al., 2011, Table 1). By consideri ng this approach, one could focus on the range of PM 2.5 concentrations below the long - term mean ambient concentrations over which we continue to have confidence in the associations observed in epidemiological studies (e.g., above the 25 th percentile) where commensurate public health protection could be obtained for PM 2.5 - related effects and, conversely, identify the range in the distribution ; that is, below which our confidence in the associations is appreciably less, to identify alternati ve annual standard levels. The mean PM 2.5 concentrations associated with the studies summarized in Figures 1, 2, and 3 and with the distributional statistics analyses (Rajan et al., 2011) are based on concentrations averaged across ambient monitors within each area included in a given study are and then averaged across study areas to calculate an overall study mean concentration , as discussed above . As noted above in section III.A.3 and discussed in the Policy Assessment, a policy approach that uses data ba sed on composite monitor distributions to identify alternative standard levels, and then compares those levels to concentrations at appropriate maximum monitors to determine if an area meets a given standard, inherently has the potential to build in some m argin of safety (US EPA, 2011a, p. 2 - 14). In analyses conducted by EPA staff based on selected long - and short - term exposure studies, the Policy Assessment

65 Health event data (e.g., number of deaths, hospitalizations) occurring in a study population were obtained for three multi - city studies (Krewski et al., 2009; Zanobetti and Schwartz, 2009; Bell et al., 2008) and study population data were obtained for the same three studies and one additional study (Miller et al., 2007) (US EPA, 2011a, p.2 - 71). If health event or study population data were available for additional studies, the EPA could employ distribut ional statistics to identify the broader range of PM 2.5 concentrations that were most influential in generating health effect estimates in those studies.***E.O. 12866 Review

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Page 94 of 133 notes***E.O. 12866 Review

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Page 95 of 133 

### Figure 1. Summary of Effect Estimates (per 10 μg/m 3 

### ) and Air Quality Distributions for Multi - City, Long - term PM 2.5 

### Exposure Studies of the General Population and Older Adults

Source: US EPA, 2011a, Figure 2 - 4***E.O. 12866 Review

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Page 96 of 133 

### Figure 2. Summary of Effect Estimates (per 10 μg/m 3 

### ) and Air Quality Distributions for Multi - City, Long - term PM 2.5 

### Exposure Studies of Children

Source: US EPA, 2011a, Figure 2 - 5***E.O. 12866 Review

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Page 97 of 133 

### Figure 3. Summary of Effect Estimates (per 10 μg/m 3 

### ) and Air Quality Distrib utions for Multi - City, Short - term PM 2.5 

### Exposure Studies of the General Population and Older Adults

Source: US EPA, 2011a, Figure 2 - 6 Formatted: Font: 12 pt***E.O. 12866 Review

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Page 98 of 133 

### Figure 4. Translating Epidemiological Evidence from Multi - City Exposure Studies into an Annual PM 2.5 

### Standard

Source: US EPA, 2011a, Figure 2 - 8 Formatted: Font: 12 pt***E.O. 12866 Review

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Page 99 of 1 33 that the differences between the maximum and composite distributions were greater for studies with fewer years of air quality data (i.e., 1 to 3 years) and smaller numbers of study areas (i.e., 36 to 51 study areas). The differences in the maximum and comp osite monitor distribution were much smaller (i.e., generally within five percent) for studies with more years of air quality data (i.e., up to 6 years) and larger numbers of study areas (i.e., 112 to 204 study areas) (Hassett - Sipple et al., 2010; US EPA, 2010f, section 2.3.4.1). Therefore, any margin of safety that may be provided by a policy approach that uses data based on composite monitor distributions to identify alternative standard levels, and then compares those levels to concentrations at appropri ate maximum monitors to determine if an area meets a given standard, will vary depending upon the number of monitors and air quality distributions within a given area. See also, footnote 27 in section III.A.3 above and associated text . The Policy Assessment initially considers distributional statistics for both long - and short - term exposure studies that evaluated mortality (causal relationship), cardiovascular effects (causal relationship) or respiratory effects (likely causal relationship). In loo king first at the long - term mean concentrations in the long - term exposure studies Figure 4 summarizes statistical metrics for those studies included in Figures 1, 2, and 3 that provide evidence of statistically significant PM 2.5 - related effects, which are r elevant to the two approaches for translating epidemiological evidence into standard levels discussed above. The top of Figure 4 includes information for long - term exposure studies evaluating health outcomes classified as having evidence of a casual or lik ely casual relationship with PM 2.5 exposures (long - term mean PM 2.5 concentrations indicated by diamond symbols). The middle of Figure 4 includes information for short - term exposure studies evaluating health outcomes classified as having evidence of a casua l or likely casual relationship with PM 2.5 exposures (long - term mean PM 2.5 concentrations indicated by triangle symbols). The bottom of Figure 4 includes information for long term exposures studies evaluating health outcomes classified as having evidence s uggestive of a causal relationship (long - term mean PM 2.5 concentrations indicated by square symbols). Figure 4 also Formatted: Indent: First line: 0"***E.O. 12866 Review

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Page 100 of 133 summarizes the range of PM 2.5 concentrations corresponding with the 25 th (indicated by solid circles) to 10 th (indicated by open circles) pe rcentiles of the health event or study population data from the four multi - city studies (highlighted in bold text) for which distributional statistics are available In looking first at the long - term mean PM 2.5 concentrations reported in the multi - city lon g - term exposure studies, as summarized at the top of Figure 4 , the Policy Assessment observes positive and often statistically significant associations at long - term mean PM 2.5 concentrations ranging from 16.4 to 12.9 μg/m 3 66 (Laden et al., 2006; Lipfert et al., 2006; Krewski et al., 2009; Goss et al., 2004; Miller et al.; 2007; Zeger et al., 2008; Eftim et al., 2008; Dockery et al., 1996; McConnell et al., 2003 ; see Figures 1 and 2). ). In considering the one long - term PM 2.5 e xposure study for which health event data are available (Krewski et al., 2009), the Policy Assessment observes that the long - term mean PM 2.5 concentrations corresponding with study areas contributing to the 25 th and 10 th percentiles of the distribution of mortality data are 12.0 μg/m 3 and 10.2 μg/m 3 , respectively ( Figure 4; US EPA, 2011a, Figure 2 - 7; Rajan et al., 2011, Table 1). As identified above, although less directly relevant than event data, the number of participants within each study area can be us ed as a surrogate for health event data in relation to the distribution of PM 2.5 concentrations. The long - term mean PM 2.5 concentrations corresponding with study areas contributing to the 25 th and 10 th percentiles of the distribution of study participants for Miller et al. (2007) were 11.2 μg/m 3 and 9.7 μg/m 3 , respectively ( Figure 4; US EPA, 2011a, Figure 2 - 7; Rajan et al., 2011, Table 1). In then considering information from multi - city, short - term exposure studies reporting positive and statistically sign ificant associations with these same broad health effect categories, as summarized in the middle of Figure 4, the Policy Assessment observes positive and statistically significant associations at long - term mean PM 2.5 concentrations in a similar range of 15 .6 to 12.8 μg/m 3 (Franklin et al., 2007, 66 As discussed in footnote 58 section III.D.1.a above, the lowest long - term mean PM 2.5 concentration r eported in the long - term exposure studies was based on updated air quality data for Miller et al. (2007) . As noted in the Policy Assessment, these air quality data were based on only one year of ambient measurements (2000) and in comparison to other long - t erm exposure studies that considered multiple years of air quality data, were much more limited (US EPA, 2011a, pp. 2 - 81 to 2 - 82).***E.O. 12866 Review

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Page 101 of 133 2008; Klemm and Mason, 2003; Burnett and Goldberg, 2003; Zanobetti and Schwartz, 2009; Burnett et al., 2004; Bell et al., 2008; Dominici et al., 2006a; see Figure 3). In considering the two multi - city, short - term PM 2.5 exposure studies for which health event data are available, the Policy Assessment observes that the long - term mean PM 2.5 concentrations corresponding with study areas contributing to the 25 th and 10 th percentiles of the distribution of deaths and cardi ovascular - related hospitalizations are 12.5 μg/m 3 and 10.3 μg/m 3 , respectively, for Zanobetti and Schwartz (2009), and 11.5 μg/m 3 and 9.8 μg/m 3 , respectively, for Bell et al. (2008) ( Figure 4; US EPA, 2011a, Figure 2 - 7; Rajan et al., 2011, Table 1). Taking into consideration additional studies of specific susceptible lifestages at - risk populations (i.e., childhood children ), the Policy Assessment expands its evaluation of the long - term exposure studies to include a broader range of health outcomes judge d in the Integrated Science Assessment to have evidence suggestive of a causal relationship. This evidence was taken into account to evaluate whether it provides support for considering lower alternative levels than if weight were only placed on studies fo r which health effects have been judged in the Integrated Science Assessment to have evidence supporting a causal or likely causal relationship. The Policy Assessment makes note of a limited number of studies that provide emerging evidence for PM 2.5 - relate d low birth weight and infant mortality, especially related to respiratory causes during the post - neonatal period. This more limited body of evidence , as summarized at the bottom of Figure 4, indicates positive and often statistically significant effects a ssociated with long - term PM 2.5 mean concentrations in the range of 14.9 to 11.9 μg/m 3 (Woodruff et al., 2008; Liu et al., 2007; Bell et al., 2007; see Figure 2). As illustrated in Figure 2, although Parker and Woodruff (2008) did not observe an association between quarterly estimates of exposure to PM 2.5 and low birth weight in a multi - city U.S. study, other U.S. and Canadian studies did report positive and statistically significant associations between PM 2.5 and low birth weight at lower ambient concentrat ions***E.O. 12866 Review

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Page 102 of 133 (Bell et al., 2007; Liu et al., 2007). 67 There remain significant limitations (e.g., identifying the etiologically relevant time period) in the evaluation of evidence on the relationship between PM 2.5 exposures and birth outcomes (US EPA, 2009a, pp. 7 - 48 and 7 - 56) which should be taken into consideration in reaching judgments about how to weigh these studies of potential impacts on specific susceptible populations in considering alternative standard levels that provide protection with an appropriate mar gin of safety. With respect to carcinogenicity, mutagenicity, and genotoxicity (evidence suggestive of a causal relationship), the strongest evidence currently available is from long - term prospective cohort studies that report positive associations between PM 2.5 and lung cancer mortality. At this time, the PM 2.5 concentrations reported in studies evaluating these effects generally included ambient concentrations that are equal to or greater than ambient concentrations observed in studies that reported morta lity and cardiovascular and respiratory effects (US EPA, 2009a, section 7.5). Therefore, in selecting alternative standard levels appropriate to consider, the Policy Assessment noted that, in providing protection against mortality and cardiovascular and re spiratory effects it is reasonable to anticipate that protection will also be provided for carcinogenicity, mutagenicity, and genotoxicity effects (US EPA, 2011a, p. 2 - 78). In summarizing the currently available evidence and air quality information within the context of identifying potential alternative annual standard levels for consideration, the Policy Assessment first notes that the Integrated Science Assessment concludes there is no evidence of a discernible population threshold below which effects wo uld not occur. Thus, health effects may occur over the full range of concentrations observed in the epidemiological studies. In the absence of any discernible thresholds, the general approach used in the Policy Assessment for identifying alternative standa rd levels that would provide appropriate protection against effects observed in epidemiological studies has focused on the 67 As noted in section 7.4 of the Integrated Science Assessment, Parker et al. (2005) reported that over a 9 - month exposure pe riod (mean PM 2.5 concentration of 15.4 μg/m 3 ) a significant decrease in birth weight was associated with infants in the highest quartile of PM 2.5 exposure as compared to infants exposed in the lowest quartile.***E.O. 12866 Review

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Page 103 of 133 central question of identifying the range of PM 2.5 concentrations below the long - term mean concentrations where we continue to have c onfidence in the associations observed in epidemiological studies. In considering the evidence, the Policy Assessment recognizes that NAAQS are standards set so as to provide requisite protection, neither more nor less stringent than necessary to protect public health with an adequate margin of safety. This judgment, ultimately made by the Administrator, involves weighing the strength of the evidence and the inherent uncertainties and limitations of that evidence. Therefore, depending on the weight placed on different aspects of the evidence and inherent uncertainties, considerations of different alternative standard levels could be supported. As discussed in section III.A.3 above, the Policy Assessment recognizes that by applying the general policy approa ch used in previous reviews, one could focus on identifying alternative standard levels for the annual standard that are somewhat below the long - term mean PM 2.5 concentrations reported in the long - and short - term exposure studies. By expanding this approac h to consider additional population - level information from epidemiological studies, one could also focus on the range of PM 2.5 concentrations below the long - term mean concentrations over which we continue to have confidence in the associations observed in epidemiological studies, as well as the extent to which our confidence in the associations is appreciably less at lower concen trations, to identify alternative annual standard levels. Figure 4 provides a summary of the long - term mean PM 2.5 concentrations for the long - and short - term exposure studies presented in Figures 1 through 3 as well as the range of PM 2.5 concentrations cor responding with the 25 th to 10 th percentiles of health event or number of study participants data from the four multi - city studies, for which distributional statistics are available 68 (US EPA, 2011a, Figure 2 - 7; Rajan et al., 2011, Table 1). If health event or study population data were available for additional 68 Health event data (e.g., number of deaths, hospitalizations) occurring in a study population were obtained for three multi - city studies (Krewski et al., 2009; Zanobetti and Schwartz, 2009; Bell et al., 2008) and study population data were obtained for the same three studies and one additional study (Miller et al., 2007) (US EPA, 2011a, p.2 - 71).***E.O. 12866 Review

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Page 104 of 133 studies, the EPA could employ distributional statistics to identify the broader range of PM 2.5 concentrations that were most influential in generating effect estimates in those studies. The EPA antici pates that, in characterizing where the bulk of the data exist, patterns similar to those presented in Figure 4 would occur for the additional long - and short - term PM 2.5 exposure studies. Given the currently available evidence and considering the various a pproaches discussed above, the Policy Assessment concludes it is appropriate to focus on an annual standard level within a range of about 12 to 11 μg/m 3 (US EPA, 2011a, pp. 2 - 82, 2 - 101, and 2 - 106). As illustrated in Figure 4, a standard level of 12 μg/m 3 , at the upper end of this range, is somewhat below the long - term mean PM 2.5 concentrations reported in all the multi - city , long - and short - term exposure studies that provide evidence of positive and statistically significant associations with health effects classified as having evidence of a causal or likely causal relationship, including premature mortality and hospitalizations and emergency department visits for cardiovascular and respiratory effects as well as respiratory effects in children. Further, a l evel of 12 μg/m 3 would reflect consideration of additional population - level information from such epidemiological studies in that it generally corresponds with approximately the 25 th percentile of the available distributions of health events data in the st udies for which population - level information was available. 69 In addition, a level of 12 μg/m 3 would reflect some consideration of studies that provide more limited evidence of reproductive and developmental effects, which are suggestive of a causal relatio nship, in that it is about at the same level as the lowest long - term mean PM 2.5 concentrations reported in such studies (see Figure 4). Alternatively, an annual stan dard level of 11 μg/m 3 , at the lower end of this range, is well below the lowest long - term mean PM 2.5 concentrations reported in all multi - city long - and short - term exposure studies that provide evidence of positive and statistically significant associations with health effects 69 As outlined in section II I .A.3, the Policy Assessment considers the 25 th percentile to be the start of the range of PM 2.5 concentrations below the mean within whi ch the data become appreciably more sparse and, thus, where our confidence in the associations observed in epidemiological studies begins to become appreciably less . Formatted: Not Superscript/ Subscript***E.O. 12866 Review

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Page 105 of 133 classified as having evidence of a causal or likely causal relation ship. A level of 11 μg/m 3 would reflect placing more weight on the distributions of health event and population data, in that this level is within the range of PM 2.5 concentrations corresponding to the 25 th and 10 th percentiles of all the available distrib utions of such data. 70 In addition, a level of 11 μg/m 3 is somewhat below the lowest long - term mean PM 2.5 concentrations reported in reproductive and developmental effects studies that are suggestive of a causal relationship. Thus, a level of 11 μg/m 3 would reflect an approach to translating the available evidence that places relatively more emphasis on margin of safety considerations than would a standard set at a higher level. Such a policy approach would tend to weigh uncertainties in the evidence in such a way as to avoid potentially underestimating PM 2.5 - related risks to public health. Further, recognizing the uncertainties inherent in identifying any particular point at which our confidence in reported associations becomes appreciably less, the Policy A ssessment concludes that the available evidence does not provide a sufficient basis to consider alternative annual standard levels below 11 μg/m 3 (US EPA, 2011a, p. 2 - 81). The Policy Assessment also considers the extent to which the available evidence pro vides a basis for considering alternative annual standard levels above 12 μg/m 3 . As discussed below, the Policy Assessment concludes that it could be reasonable to consider a standard level up to 13 μg/m 3 based on a policy approach that tends to weigh unce rtainties in the evidence in such a way as to avoid potentially overestimating PM 2.5 - related risks to public health, especially to the extent that primary emphasis is placed on long - term exposure studies as a basis for an annual standard level. A level of 13 μg/m 3 is somewhat below the long - term mean PM 2.5 concentrations reported in all but one of the long - term exposure studies providing evidence of positive and statistically significant associations with PM 2.5 - related health effects classified as having a causal or likely causal relationship. As shown in Figure 4, the one long - term exposure study with a long - term mean PM 2.5 concentration just below 13 70 As discussed in section II I .A.3, the Policy Assessment identifies the range from the 25 th to the 10 th percentiles as a reasonable range to consider, in that it is a range where we have appreciably less confidence in the associations observed in epidemiological studies (US EPA, 2011a, p. 2 - 12) .***E.O. 12866 Review

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Page 106 of 133 μg/m 3 is the WHI study (Miller et al., 2007). As noted in section III.D.1.a above , including footnote 58 , t he Policy Assessment observes that in comparison to other long - term exposure studies, the WHI study was more limited in that it was based on only one year of air quality data (US EPA, 2011a, pp. 2 - 81 to 2 - 82). Thus, to the extent that less weight is placed on the WHI study than on other long - term exposure studies with more robust air quality data, a level of 13 μg/m 3 could be considered as being protective of long - term exposure related effects classified as having a causal or likely causal relationship. In also considering short - term exposure studies, the Policy Assessment notes that a level of 13 μg/m 3 is below the long - term mean PM 2.5 concentrations reported in most such studies, but is above the long - term means of 12.8 and 12.9 μg/m 3 reported in Burnett et al. (2004) and Bell et al. (2008), respectively. In considering these studies, the Policy Assessment finds no basis to conclude that these two studies are any more limited or uncertain than the other short - term exposure studies show n in Figures 3 and 4 (US EPA, 2011a, p. 2 - 82). On this basis, as discussed below, the Policy Assessment concludes that consideration of an annual standard level of 13 μg/m 3 would have implications for the degree of protection that would need to be provided by the 24 - hour standard, such that taken together the suite of PM 2.5 standards would provide appropriate protection from effects on public health related to short - term exposure to PM 2.5 (US EPA, 2011a, p. 2 - 82). The Policy Assessment also notes that a sta ndard level of 13 μg/m 3 would reflect a judgment that the uncertainties in the epidemiological evidence as summarized in section III.B.2 above, including uncertainties related to the heterogeneity observed in the epidemiological studies in the eastern vers us western parts of the U.S., the relative toxicity of PM 2.5 components, and the potential role of co - pollutants, are too great to warrant placing any weight on the distributions of health event and population data that extend down below the long - term mean concentrations into the lower quartile of the data. This level would also reflect a judgment that the evidence from reproductive and developmental effects studies that is suggestive of a causal relationship is too uncertain to support consideration of any***E.O. 12866 Review

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Page 107 of 133 lower level. Beyond evidence - based considerations, the Policy Assessment also considered the extent to which quantitative risk assessment supports consideration of these alternative standard levels or provides support for lower levels. In considering simu lations of just meeting alternative annual standard levels within the range of 13 to 11 μg/m 3 (in conjunction with the current 24 - hour standard level of 35 μg/m 3 ), the Policy Assessment concluded that important public health improvements are associated wit h risk reductions estimated for standard levels of 13 and 12 μg/m 3 , noting that the level of 11 μg/m 3 was not include in the quantitative risk assessment. The Policy Assessment noted that the overall confidence in the quantitative risk estimates varied for the different alternative standard levels evaluated and was stronge r for the highe r level s and substantially lower for the lowest level evaluated (i.e., 10 μg/m 3 ) . Based on the above considerations, the Policy Assessment concluded that the quantitative risk assessment provided support for considering alternative annual standard levels within a range of 13 to 11 μg/m 3 , but did not provide strong support for considering lower alternative standard levels (US EPA, 2011a, pp. 2 - 102 to 2 - 103). Taken together, the Policy Assessment concludes that consideration of alternative annual standard levels in the range of 13 to 11 μg/m 3 may be appropriate. Furthermore, the Policy Assessment concludes that the currently available evidence most strongly supports considerat ion of an alternative annual standard level in the range of 12 to 11 μg/m 3 (US EPA, 2011a, p. 2 - 82). The Policy Assessment concludes that an alternative level within the range of 12 to 11 μg/m 3 would more fully take into consideration the available informa tion from all long - and short - term PM 2.5 exposure studies, including studies of susceptible at - risk populations, than would a higher level. This range would also reflect placing weight on information from studies that help to characterize the range of PM 2.5 concentrations over which we continue to have confidence in the associations observed in epidemiological studies, as well as the extent to which our confidence in the associations is appreciably less at lower concentrations.***E.O. 12866 Review

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Page 108 of 133 c. Consideration of the 24 - Hour Standard in the Policy Assessment As recognized in section III.A.3 above, an annual standard intended to serve as the primary means for providing protection from effects associated with both long - and short - term PM 2.5 exposures is not expected to provide a ppropriate protection against the effects of all short - term PM 2.5 exposures (unless established at a level so low as to undoubtedly provide more protection than necessary for long term exposures). Of particular concern are areas with high peak - to - mean rati os possibly associated with strong local or seasonal sources, or PM 2.5 - related effects that may be associated with shorter - than - daily exposure periods. As a result, the Policy Assessment concludes that it is appropriate to consider alternative 24 - hour PM 2. 5 standard levels that would supplement the protection provided by an annual standard. As outlined in section III.A.3 above, the Policy Assessment considers the available evidence from short - term PM 2.5 exposure studies, as well as the uncertainties and li mitations in that evidence, to assess the degree to which alternative annual and 24 - hour PM 2.5 standards can be expected to reduce the estimated risks attributed to short - term fine particle exposures. In considering the available epidemiological evidence, the Policy Assessment takes into account information from multi - city studies as well as single - city studies. The Policy Assessment considers the distributions of 24 - hour PM 2.5 concentrations reported in short - term exposure studies, focusing on the 98 th percentile concentrations to match the form of the 24 - hour standard as discussed in section III.E .3.b above. In recognizing that the annual and 24 - hour standards work together to provide protection from effects associated with short - term PM 2.5 exposures, the Policy Assessment also considers information on the long - term mean PM 2.5 concentrations from t hese studies. In addition to considering the epidemiological evidence, the Policy Assessment also considers air quality information, specifically peak - to - mean ratios using county - level 24 - hour and annual design values, to characterize air quality patterns in areas possibly associated with strong local or seasonal***E.O. 12866 Review

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Page 109 of 133 sources. These patterns help in understanding the extent to which different combinations of annual and 24 - hour standards would be consistent with the policy goal of setting a generally controlling annual standard with a 24 - hour standard that provides supplemental protection especially for areas with high peak - to - mean ratios (US EPA, 2011a, p. 2 - 14). In considering the information provided by the short - term exposure studies, the Policy Assessment recognizes that to the extent these studies were conducted in areas that likely did not meet one or both of the current standards, such studies do not help inform the characterization of the potential public health improvements of alternative standards set at lower levels. Therefore, in considering the short - term exposure studies to inform staff conclusions regarding levels of the 24 - hour standard that are appropriate to consider, the Policy Assessment places greatest weight on studies conducted in areas th at likely met both the current annual and 24 - hour standards. With regard to multi - city studies that evaluated effects associated with short - term PM 2.5 exposures, as summarized in Figure 3, the Policy Assessment observes an overall pattern of positive and s tatistically significant associations in studies with 98 th percentile values averaged across study areas in the range of 45.8 to 34.2 μg/m 3 (Burnett et al., 2004; Zanobetti and Schwartz, 2009; Bell et al., 2008; Dominici et al., 2006a, Burnett and Goldberg , 2003; Franklin et al., 2008). The Policy Assessment notes that, to the extent air quality distributions were reduced to reflect just meeting the current 24 - hour standard, additional protection would be anticipated for the effects observed in the three mu lti - city studies with 98 th percentile values greater than 35 μg/m 3 (Burnett et al., 2004; Burnett and Goldberg, 2003; Franklin et al., 2008). In the three additional studies with 98 th percentile values below 35 μg/m 3 , specifically 98 th percentile concentra tions of 34.2, 34.3, and 34.8 μg/m 3 , the Policy Assessment notes that these studies reported long - term mean PM 2.5 concentrations of 12.9, 13.2, and 13.4 μg/m 3 , respectively (Bell et al., 2008; Zanobetti and Schwartz, 2009; Dominici et al., 2006a). To the e xtent that consideration is given to revising the level of the annual standard, as discussed above in section***E.O. 12866 Review

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Page 110 of 133 III.E.4.b, the Policy Assessment recognizes that potential changes associated with meeting such an alternative annual standard would result in low ering risks associated with both long - and short - term PM 2.5 exposures. Consequently, in considering a 24 - hour standard that would work in conjunction with an annual standard to provide appropriate public health protection, the Policy Assessment notes that to the extent that the level of the annual standard is revised to within a range of 13 to 11 μg/m 3 , in particular in the range of 12 to 11 μg/m 3 , additional protection would be provided for the effects observed in these multi - city studies (US EPA, 2011a, p . 2 - 84). In summary, the Policy Assessment concludes that the multi - city, short - term exposure studies generally provide support for retaining the 24 - hour standard level at 35 μg/m 3 in conjunction with an annual standard level revised to within a range of 12 to 11 μg/m 3 (US EPA, 2011a, p. 2 - 84). Alternatively, in conjunction with an annual standard level of 13 μg/m 3 , the Policy Assessment concludes that the multi - city studies provide limited support for revising the 24 - hour standard level somewhat below 35 μg/m 3 , such as down to 30 μg/m 3 , based on one study (Bell et al., 2008) that reported positive and statistically significant effects with an overall 98 th percentile value below the level of the current 24 - hour standard in conjunction with an overall long - t erm mean concentration slightly less than 13 μg/m 3 (Figure 3; US EPA, 2011a, p. 2 - 84). In reaching staff conclusions regarding alternative 24 - hour standard levels that are appropriate to consider, the Policy Assessment also takes into account relevant inf ormation from single - city studies that evaluated effects associated with short - term PM 2.5 exposures. The Policy Assessment recognizes that these studies may provide additional insights regarding impacts on susceptible populations and/or on areas with isola ted peak concentrations. Although, as discussed in section III.E.4.a above, multi - city studies have advantages over single - city studies in terms of statistical power to detect associations and broader geographic coverage as well as other factors such as le ss likelihood of publication bias, reflecting differences in PM 2.5 sources, composition, and potentially other factors that could impact***E.O. 12866 Review

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Page 111 of 133 PM 2.5 - related effects, multi - city studies often present overall effect estimates rather than single - city effect estimat es. Since short - term air quality can vary considerably across cities, the extent to which effects reported in multi - city studies are associated with short - term air quality in any particular location is uncertain, especially when considering short - term conc entrations at the upper end of the distribution of daily PM 2.5 concentrations (i.e., at the 98 th percentile value). In contrast, single - city studies are more limited in terms of power and geographic coverage but the link between reported health effects and the air quality in a given study area is more straightforward to establish. Therefore, the Policy Assessment also considers evidence from single - city, short - term exposure studies to inform staff conclusions regarding alternative levels that are appropriat e to consider for a 24 - hour standard that is intended to provide supplemental protection in areas where the annual standard may not provide an adequate margin of safety against the effects of all short - term PM 2.5 exposures. As discussed above for the multi - city studies, the Policy Assessment takes into account both the 24 - hour PM 2.5 concentrations in the single - city studies, focusing on the 98 th percentile air quality values, as well as the long - term mean PM 2.5 concentrations. The Policy Assessment consider s single - city studies conducted in areas that would likely have met the current suite of PM 2.5 standards as most useful for informing staff conclusions related to the level of the 24 - hour standard (US EPA, 2011a, Figure 2 - 9). The Policy Assessment notes th at additional single - city studies summarized in that Figure 2 - 9 were conducted in areas that would likely have met one but not both of the current PM 2.5 standards. To the extent changes in air quality designed to just meet the current suite of PM 2.5 standards are undertaken, one could reasonably anticipate additional public health protection will occur in these study areas. Therefore, the Policy Assessment concludes that these studies are not helpful to inform staff conclusions regarding alternative standard levels that are appropriate to consider (US EPA, 2011a, p. 2 - 87). With regard to single - city studies that were conducted in areas that would likely have met both the current 24 - hour and annual standards, the Policy Assessment first considers studi es that reported***E.O. 12866 Review

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Page 112 of 133 positive and statistically significant associations. In considering this group of studies, the Policy Assessment notes Mar et al. (2003) reported a positive and statistically significant association for premature mortality in Phoenix with a long - term mean concentration of 13.5 μg/m 3 in conjunction with a 98 th percentile value of 32.2 μg/m 3 (US EPA, 2011a, Figure 2 - 9). To the extent that consideration is given to revising the level of the annual standard, within a range of 13 to 11 μg/m 3 , as discussed above, additional protection would be provided for the effects observed in this study (US EPA, 2011a, p. 2 - 87). Four additional studies reported positive and statistically significant associations with 98 th percentile values within a range of 3 1.2 to 25.8 μg/m 3 and long - term mean concentrations within a range of 12.1 to 8.5 μg/m 3 (Delfino et al., 1997; Peters et al., 2001; Stieb et al., 2000; and Mar et al., 2004; US EPA, 2011a, Figure 2 - 9). Delfino et al. (1997) reported statistically significa nt associations between PM 2.5 and respiratory emergency department visits for older adults (greater than 64 years old) but not young children (less than 2 years old), in one part of the study period (summer 1993) but not the other (summer 1992). Peters et al. (2001) reported a positive and statistically significant association between short - term exposure to PM 2.5 (2 - hour and 24 - hour averaging times) and onset of acute myocardial infarction in Boston. Stieb et al. (2000) reported positive and statistically s ignificant associations with cardiovascular - and respiratory - related emergency department visits in Saint John, Canada, in single pollutant models but not in multi - pollutant models (US EPA, 2004, pp. 8 - 154 and 8 - 252 to 8 - 253). Mar et al. (2004) reported a positive and statistically significant association for short - term PM 2.5 exposures in relation to respiratory symptoms among children but not adults in Spokane, however, this study had very limited statistical power because of the small number of children a nd adults evaluated. The Policy Assessment also considers short - term single - city PM 2.5 exposure studies that reported positive but nonstatistically significant associations for cardiovascular and respiratory endpoints in areas that would likely have met b oth the current 24 - hour and annual standards. The 98 th percentile values reported in these studies ranged from 31.6 to 17.2 μg/m 3 and the long - term mean concentrations ranged***E.O. 12866 Review

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Page 113 of 133 from 13.0 to 7.0 μg/m 3 (US EPA, 2011a, Figure 2 - 9). These studies included consid eration of cardiovascular - related mortality effects in Phoenix (Wilson et al., 2007), asthma medication use in children in Denver (Rabinovitch et al., 2006), hospital admissions for hemorrhagic and ischemic stroke in Edmonton, Canada (Villeneuve et al., 20 06), and hospital admissions for ischemic stroke/transient ischemic attack in Nueces County, TX (Lisabeth et al., 2008). Lastly, the Policy Assessment considers single - city studies conducted in areas that would likely have met both the current 24 - hour and annual standards that reported null findings. The 98 th percentile values reported in these studies ranged from 29.6 to 24.0 μg/m 3 and the long - term mean concentrations ranged from 10.8 to 8.5 μg/m 3 (US EPA, 2011a, Figure 2 - 9). These studies reported no as sociations with short - term PM 2.5 exposures and cardiovascular - related hospital admissions and respiratory - related emergency department visits (Slaughter et al., 2005) and cardiovascular - related emergency department visits (Schreuder et al., 2006) in Spokan e; asthma exacerbation in children in Denver (Rabinovitch et al., 2004); and hospital admissions for transient ischemic attack in Edmonton, Canada (Villeneuve et al., 2006). Viewing the evidence as a whole, the Policy Assessment observes a limited number of single city studies that reported positive and statistically significant associations for a range of health endpoints related to short - term PM 2.5 concentrations in areas that would likely have met the current suite of PM 2.5 standards. Many of these stud ies had significant limitations (e.g., limited statistical power, limited exposure data) or equivocal results (i.e., mixed results within the same study area) as briefly identified above and discussed in more detail in the Policy Assessment (US EPA, 2011a, p. 2 - 88). Other studies reported positive but not statistically significant results or null associations also in areas that would likely have met the current suite of PM 2.5 standards. Overall, the entire body of results from these single city studies is m ixed, particularly as 24 - hour 98 th percentile concentrations go below 35 μg/m 3
. Although a number of single - city studies report effects at appreciably lower PM 2.5 concentrations***E.O. 12866 Review

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Page 114 of 133 than multi - city short - term exposure studies, the uncertainties and limitation s associated with the single city studies were greater and, thus, the Policy Assessment concludes there is less confidence in using these studies as a basis for setting the level of a standard. Therefore, the Policy Assessment concludes that the multi - city short - term exposure studies provide the strongest evidence to inform decisions on the level of the 24 - hour standard, and the single - city studies do not warrant consideration of 24 - hour standard levels different from those supported by the multi - city studi es (US EPA, 2011a, p. 2 - 88). In addition to considering the epidemiological evidence, the Policy Assessment takes into account air quality information based on county - level 24 - hour and annual design values to understand the implications of the alternative standard levels supported by the currently available scientific evidence, as discussed in section III.E.4.b above. As discussed in section III.A.3 above, the Policy Assessment concludes that a policy goal which includes setting the annual standard to be t he “generally controlling” standard in conjunction with setting the 24 - hour standard to provide supplemental protection, to the extent that additional protection is warranted, is the most effective and efficient way to reduce total population risk associat ed with both long - and short - term PM 2.5 exposures, resulting in more uniform protection across the U.S than the alternative of setting the 24 - hour standard to be the controlling standard. Therefore, the Policy Assessment considers the extent to which diffe rent combinations of alternative annual and 24 - hour standard levels based on the evidence would support this policy goal (US EPA, 2011a, pp 2 - 88 to 2 - 91, Figure 2 - 10). Using information on the relationship of the 24 - hour and annual design values, the Poli cy Assessment examines the implications of three alternative suites of PM 2.5 standards identified as appropriate to consider based on the currently available scientific evidence, as discussed above. The Policy Assessment concludes that an alternative suite of PM 2.5 standards that would include an annual standard level of 11 or 12 μg/m 3 and a 24 - hour standard with a level of 35 μg/m 3 (i.e., 11/35 or 12/35) would result in the annual standard being the generally controlling standard in most areas although the***E.O. 12866 Review

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Page 115 of 133 24 - hour standard would continue to be the generally controlling standard in the Northwest (US EPA, 2011a, pp. 2 - 89 to 2 - 91 and Figure 2 - 10). These Northwest counties generally represent areas where the annual mean PM 2.5 concentrations have historically be en low but where relatively high 24 - hour concentrations occur, often related to seasonal wood smoke emissions. Alternatively, combining an alternative annual standard of 13 μg/m 3 with a 24 - hour standard of 30 μg/m 3 would result in many more areas across th e country in which the 24 - hour standard would likely become the controlling standard than if an alternative annual standard of 12 or 11 μg/m 3 were paired with the current level of the 24 - hour standard (i.e., 35 μg/m 3 ). The Policy Assessment concludes that consideration of retaining the 24 - hour standard level at 35 μg/m 3 would reflect placing greatest weight on evidence from multi - city studies that reported positive and statistically significant associations with health effects classified as having a causal or likely causal relationship. In conjunction with lowering the annual standard level, especially within a range of 12 to 11 μg/m 3 , this alternative would recognize additional public health protection against effects associated with short - term PM 2.5 expos ures which would be provided by lowering the annual standard such that revision to the 24 - hour standard would not be warranted (US EPA, 2011a, p. 2 - 91). The Policy Assessment also recognizes an alternative approach to considering the evidence that provide s some support for revising the level below 35 μg/m 3 , perhaps as low as 30 μg/m 3 (US EPA, 2011a, p. 2 - 92). This alternative 24 - hour standard level would be more compatible with an alternative annual standard of 13 μg/m 3 based on placing greater weight on o ne multi - city short - term exposure study (Bell et al., 2008) that reported positive and statistically significant effects at a 98 th percentile value less than 35 μg/m 3 (i.e., 34.2 μg/m 3 ) in conjunction with a long - term mean concentration less than 13 μg/m 3 (i.e., 12.9 μg/m 3 ). Beyond evidence - based considerations, the Policy Assessment also considered the extent to which the quantitative risk assessment supports conside ration o f retaining the current 24 - hour standard***E.O. 12866 Review

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Page 116 of 133 level or provides support for lower stand ard levels. In considering simulations of just meeting the current 24 - hour standard level of 35 μg/m 3 or alternative level s of 30 or 25 μg/m 3 (in conjunction with alternative annual standard levels within a range of 13 to 11 μg/m 3 ), the Policy Assessment noted that the overall confidence in the quantitative risk estimates varied for the different standard levels evaluated and was stronge r for the highe r level s and substantially lower for the lowest level evaluated (i.e., 25 μg/m 3 ) . Ba sed on this information, the Policy Assessment concluded that the quantitative risk assessment provides support for considering a 24 - hour standard level of 35 or 30 μg/m 3 (in conjunction with an alternative standard level within a range of 13 to 11 μg/m 3 ) but does not provide strong support for considering lower alternative 24 - hour standard levels (US EPA, 2011a, pp. 2 - 102 to 2 - 103). Taken together, the Policy Assessment concludes that while it is appropriate to consider an alternative 24 - hour standard leve l within a range of 35 to 30 μg/m 3 , the currently available evidence most strongly supports consideration for retaining the current 24 - hour standard level at 35 μg/m 3 in conjunction with lowering the level of the annual standard within a range of 12 to 11 μg/m 3 (US EPA, 2011a, p. 2 - 92). d. CASAC Advice Based on its review of the second draft Policy Assessment, CASAC agreed with the general approach for translating the available epidemiological evidence, risk information, and air quality information into the basis for reaching conclusions on alternative s tandards for consideration. Furthermore, CASAC agreed “that it is appropriate to return to the strategy used in 1997 that considers the annual and the short - term standards together, with the annual standard as the controlling standard, and the short - term s tandard supplementing the protection afforded by the annual standard” and “considers it appropriate to place the greatest emphasis” on health effects judged to have evidence supportive of a causal or likely causal relationship as presented in the Integrate d Science Assessment (Samet, 2010d, p. 1).***E.O. 12866 Review

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Page 117 of 133 CASAC concluded that the range of levels presented in the second draft Policy Assessment (i.e., alternative annual standard levels within a range of 13 to 11 μg/m 3 and alternative 24 - hour standard levels within a range of 35 to 30 μg/m 3 ) “are supported by the epidemiological and toxicological evidence, as well as by the risk and air quality information compiled” in the Integrated Science Assessment, Risk Assessment, and second draft Policy Assessment. CASAC furthe r noted that “[a]lthough there is increasing uncertainty at lower levels, there is no evidence of a threshold (i.e., a level below which there is no risk for adverse health effects)” (Samet, 2010d, p. ii). Although CASAC supported the alternative standard level ranges presented in the second draft Policy Assessment, it did not express support for any specific levels or combinations of standards. Rather, CASAC encouraged the EPA to develop a clearer rationale in the final Policy Assessment for staff conclus ions regarding annual and 24 - hour standards that are appropriate to consider, including consideration of the combination of these standards supported by the available information (Samet, 2010d, p. ii). Specifically, CASAC encouraged staff to focus on infor mation related to the concentrations that were most influential in generating the health effect estimates in individual studies to inform alternative standard levels (Samet, 2010d, p. 2). CASAC also commented that the approach presented in the second draft Policy Assessment to identify alternative 24 - hour standard levels which focused on peak - to - mean ratios was not relevant for informing the actual level (Samet 2010d, p. 4). Further, they expressed the concern that the combinations of annual and 24 - hour sta ndard levels discussed in the second draft Policy Assessment (i.e., in the range of 13 to 11 μg/m 3 for the annual standard, in conjunction with retaining the current 24 - hour PM 2.5 standard level of 35 μg/m 3 ; alternatively, revising the level of the 24 - hour standard to 30 μg/m 3 in conjunction with an annual standard level of 11 μg/m 3 ) “may not be adequately inclusive” and “[i]t was not clear why, for example a daily standard of 30 μg/m 3 should only be considered in combination with an annual level of 11 μg/m 3 ” (Samet, 2010d, p. ii). CASAC encouraged the EPA to more clearly explain its rationale for***E.O. 12866 Review

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Page 118 of 133 identifying the 24 - hour/annual combinations that are appropriate for consideration (Samet 2010d, p. ii). In considering CASAC’s advice as well as public comment o n the second draft Policy Assessment, EPA staff conducted additional analyses and modified their conclusions regarding alternative standard levels that are appropriate to consider. The staff conclusions in the final Policy Assessment (US EPA, 2011a, sectio n 2.3.4.4) differ somewhat from the alternative standard levels discussed in the second draft Policy Assessment (US EPA, 2010f, section 2.3.4.3), upon which CASAC based its advice. Changes made in the final Policy Assessment were primarily focused on impro ving and clarifying the approach for translating the epidemiological evidence into a basis for staff conclusions on the broadest range of alternative standard levels supported by the available scientific information and more clearly articulating the ration ale for the staff’s conclusions (Wegman, 2011, pp. 1 to 2). Consistent with CASAC’s advice to consider more information from epidemiological studies, the EPA analyzed additional population - level data obtained from several study investigators. In commenting on draft staff conclusions in the second draft Policy Assessment, CASAC did not have an opportunity to review the staff analyses of distributional statistics conducted by staff to identify the broader range of PM 2.5 concentrations that were most influenti al in generating health effect estimates in epidemiological studies (Rajan et al., 2011). In addition, CASAC was not aware of the revised long - term mean PM 2.5 concentration in the WHI study as discussed in section III.D.1.a above , specifically footnote 58, or the staff’s inclusion of that value in its evaluation of the evidence (i.e., in Figure Figures 1 and 4 above and related discussion). The WHI study is the only long - term cohort study that provides information regarding effects classified as having evide nce of a causal or likely causal relationship associated with a long - term PM 2.5 concentration below 13 μg/m 3
. However, as noted in section III.D.1.a above, this study was based on only one year of air quality data and linked to effects that occurred in ear lier years. Furthermore, CASAC did not have an opportunity to review the staff’s revised rationale for the combinations of alternative standards suggested in the final Policy Assessment.***E.O. 12866 Review

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Page 119 of 133 e. Administrator’s Proposed Conclusions on the Primary PM 2.5 Standard L evels In reaching her conclusions regarding appropriate alternative standard levels to consider, the Administrator has considered the epidemiological and other scientific evidence, estimates of risk reductions associated with just meeting alternative annua l and/or 24 - hour standards, air quality analyses, related limitations and uncertainties and the advice of CASAC. As an initial matter, the Administrator agrees with the approach discussed in the Policy Assessment as summarized in sections III.A.3 and III.E .4.a above, and supported by CASAC, of considering the protection afforded by the annual and 24 - hour standards taken together for mortality and morbidity effects associated with both long - and short - term exposures to PM 2.5 . This is consistent with the appr oach taken in the review completed in 1997, in contrast to considering each standard separately, as was done in the review completed in 2006. Furthermore, based on the evidence and quantitative risk assessment, the Administrator provisionally concludes it is appropriate to set a “generally controlling” annual standard that will lower a wide range of ambient 24 - hour concentrations, with a 24 - hour standard focused on providing supplemental protection, particularly for areas with high peak - to - mean ratios possi bly associated with strong local or seasonal sources, or PM 2.5 - related effects that may be associated with shorter - than daily exposure periods. The Administrator provisionally concludes this approach would likely reduce aggregate risks associated with both long - and short - term exposures more consistently than a generally controlling 24 - hour standard and would be the most effective and efficient way to reduce total PM 2 - 5 - related population risk and so provide appropriate protection. In reaching decisions on alternative standard levels to propose, the Administrator judges that it is most appropriate to examine where the evidence of associations observed in the epidemiological studies is strongest and, conversely, where she has apprecia bly less confidence in the associations observed in the epidemiological studies. Based on the characterization and assessment of the epidemiological and other studies presented***E.O. 12866 Review

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Page 120 of 133 and assessed in the Integrated Science Assessment and the Policy Assessment, t he Administrator recognizes the substantial increase in the number and diversity of studies available in this review including extended analyses of the seminal studies of long - term PM 2.5 exposures (i.e., ACS and Harvard Six Cities studies) as well as impor tant new long - term exposure studies (as summarized in Figures 1 and 2). Collectively, the Administrator takes note that these studies, along with evidence available in the last review, provide consistent and stronger evidence of an association with prematu re mortality, with the strongest evidence related to cardiovascular - related mortality, at lower ambient concentrations than previously observed. The Administrator also recognizes the availability of stronger evidence of morbidity effects associated with lo ng - term PM 2.5 exposures, including evidence of cardiovascular effects from the WHI study and respiratory effects, including decreased lung function growth, from the extended analyses for the Southern California Children’s Health Study. Furthermore, the Adm inistrator recognizes new U.S. multi - city studies that greatly expand and reinforce our understanding of mortality and morbidity effects associated with short - term PM 2.5 exposures, providing stronger evidence of associations at ambient concentrations simil ar to those previously observed (as summarized in Figure 3). The newly available scientific evidence builds upon the previous scientific data base to provide evidence of generally robust associations and to provide a basis for greater confidence in the re ported associations than in the last review. The Administrator recognizes that the weight of evidence, as evaluated in the Integrated Science Assessment, is strongest for health endpoints classified as having evidence of a causal relationship. These relati onships include those between long - and short - term PM 2.5 exposures and mortality and cardiovascular effects. She recognizes that the weight of evidence is also strong for health endpoints classified as having evidence of a likely causal relationship, which include those between long - and short - term PM 2.5 exposures and respiratory effects. In addition, the Administrator makes note of the much more limited evidence for health endpoints classified as having evidence suggestive of a causal relationship, includi ng developmental, reproductive and carcinogenic***E.O. 12866 Review

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Page 121 of 133 effects. Based on information discussed and presented in the Integrated Science Assessment, the Administrator recognizes that health effects may occur over the full range of concentrations observed in the lon g - and short - term epidemiological studies and that no discernible threshold for any effects can be identified based on the currently available evidence (US EPA, 2009a, section 2.4.3). She also recognizes, in taking note of CASAC advice and the distribution al statistics analysis discussed in section III.E.4.b above and in the Policy Assessment, that there is significantly greater confidence in observed associations over certain parts of the air quality distributions in the studies, and conversely, that there is significantly diminished confidence in ascribing effects to concentrations toward the lower part of the distributions. Consistent with the general approach summarized in section III.A.3 above, and supported by CASAC as discussed in section III.E.4.d ab ove, the Administrator generally agrees that it is appropriate to consider a level for an annual standard that is somewhat below the long - term mean PM 2.5 concentrations reported in long - and short - term exposure studies, recognizing that the evidence of an association in any such study is strongest at and around the long - term average where the data in the study are most concentrated. The Administrator notes that long - term mean PM 2.5 concentrations are available for each study considered and, therefore, repre sent the most robust data set to inform her decisions on appropriate annual standard levels. In considering such long - term mean concentrations, the Administrator understands that it is appropriate to consider the weight of evidence for the health endpoints evaluated in such studies in giving weight to this information. Based on the information summarized in Figure 4 and presented in more detail in the Policy Assessment (US EPA, 2011a, chapter 2) for effects classified in the Integrated Science Assessment as having a causal or likely causal relationship with PM 2.5 exposures, the Administrator observes an overall pattern of statistically significant associations reported in studies of long - term PM 2.5 exposures with***E.O. 12866 Review

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Page 122 of 133 long - term mean concentrations ranging from so mewhat above the current standard level of 15 μg/m 3 down to the lowest mean concentration in such studies of 12.9 μg/m 3 (in Miller et al., 2007). She observes a similar pattern of statistically significant associations in studies of short - term PM 2.5 exposu res with long - term mean concentrations ranging from around 15 μg/m 3 down to 12.8 μg/m 3 (in Burnett et al., 2004). With regard to effects classified as providing evidence suggestive of a causal relationship, the Administrator observes a small number of stud ies related to developmental and reproductive effects that reported statistically significant associations for long - term PM 2.5 concentrations with long - term means mean concentrations down to 11.9 μg/m 3 (in Bell et al., 2007). 71 The Administrator also consid ers additional information from epidemiological studies, consistent with CASAC advice, to take into account the broader distribution of PM 2.5 concentrations and the degree of confidence in the observed associations over the broader air quality distribution. In considering this additional information, she considers the range from the 25 th to the 10 th percentiles, consistent with the Policy Asses sment analyses. More specifically, the Administrator recognizes the 25 th percentile as the start of the range of PM 2.5 concentrations below the mean within which the data become appreciably more sparse and, thus, where her confidence in the associations ob served in epidemiological studies begins to become appreciably less. As discussed in section III.E.4.b above and summarized in Figure 4, the Administrator takes note of additional population - level data that are available for four studies (Krewski et al., 2 009; Miller et al., 2007; Bell et al., 2008; Zanobetti and Schwartz, 2009), each of which report statistically significant associations with health endpoints classified as having evidence of a causal relationship. In considering the long - term mean PM 2.5 co ncentrations associated with the 25 th percentile values for these four studies, she observes that these values range from somewhat above to 71 With respect to suggestive evidence related t o cancer, mutagenic, and genotoxic effects, the PM 2.5 concentrations reported in studies generally included ambient concentrations that are equal to or greater than ambient concentrations observed in studies that reported mortality and cardiovascular and r espiratory effects (US EPA, 2009a, section 7.5), such that in selecting alternative standard levels that provide protection from mortality and cardiovascular and respiratory effects, it is reasonable to anticipate that protection will also be provided for carcinogenic effects.***E.O. 12866 Review

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Page 123 of 133 somewhat below 12 μg/m 3 (Figure 4). The Administrator recognizes that these four studies represent some of the stron gest evidence available within the overall body of scientific evidence and notes that three of these studies (Krewski et al., 2009; Bell et al., 2008; Zanobetti and Schwartz, 2009) were used as the basis for concentration - response functions used in the qua ntitative risk assessment (US EPA, 2010a, section 3.3.3). However, t he Administrator also recognizes that additional population - level data are available for only these four studies and, therefore, she believes that these studies comprise a more limited dat a set than one based on long - term mean PM 2.5 concentrations for which data are available for all studies considered, as discussed above. In considering this information, the Administrator notes that CASAC advised that information about the long - term PM 2.5 concentrations that were most influential in generating the health effect estimates in epidemiological studies can help to inform selection of an appropriate annual standard level. The Administrator recognizes, as summarized in section III.B.2 above, that important uncertainties remain in the evidence and information considered in this review of the primary fine particle standards. These uncertainties are generally related to understanding the relative toxicity of the different components in the fine parti cle mixture, the role of PM 2.5 in the complex ambient mixture, exposure measurement errors inherent in epidemiological studies based on concentrations measured at fixed monitor sites, and the nature, magnitude, and confidence in estimated risks related to increasingly lower ambient PM 2.5 concentrations. Furthermore, the Administrator notes that epidemiological studies have reported heterogeneity in responses both within and between cities and geographic regions across the U.S. She recognizes that this heter ogeneity may be attributed, in part, to differences in fine particle composition in different regions and cities. The Administrator also recognizes that t here are additional limitations associated with evidence for reproductive and developmental effects, i dentified as being suggestive of a causal relationship with long - term PM 2.5 exposures, including: the limited number of studies evaluating such effects; uncertainties related to identifying the relevant exposure time periods of***E.O. 12866 Review

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Page 124 of 133 concern; and limited toxicol ogical evidence providing little information on the mode of action(s) or biological plausibility for an association between long - term PM 2.5 exposures and adverse birth outcomes. The Administrator is mindful that considering what standards are requisite to protect public health with an adequate margin of safety requires public health policy judgments that neither overstate nor understate the strength and limitations of the evidence or the appropriate inferences to be drawn from the evidence. In considering h ow to translate the available information into appropriate standard levels, the Administrator weighs the available scientific information and associated uncertainties and limitations. For the purpose of determining what standard levels are appropriate to p ropose, the Administrator recognizes, as did EPA staff in the Policy Assessment, that there is no single factor or criterion that comprises the “correct” approach to weighing the various types of available evidence and information, but rather there are var ious approaches that are appropriate to consider. The Administrator further recognizes that different evaluations of the evidence and other information before the Administrator could reflect placing different weight on the relative strengths and limitation s of the scientific information, and different judgments could be made as to how such information should appropriately be used in making public health policy decisions on standard levels. This recognition leads the Administrator to consider various approac hes to weighing the evidence so as to identify an appropriate range of alternative standard levels, rather than a single level, to propose. In so doing, the Administrator encourages extensive public comment on alternative approaches to weighing the eviden ce and other information so as to inform her public health policy judgments before reaching final decisions on appropriate standard levels. In considering the available information, the Administrator notes the advice of CASAC that the currently available scientific information , including epidemiological and toxicological evidence, as well as the risk and air quality information , provides support for considering an annual standard level within***E.O. 12866 Review

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Page 125 of 133 a range of 13 to 11 μg/m 3 and a 24 - hour standard level within a range of 35 to 30 μg/m 3 . In addition, the Administrator recognizes that the Policy Assessment concludes that the available evidence and risk based information supports consideration of alternative annual standard levels in the range of 13 to 11 μg/m 3 and f

urther concludes that the evidence most strongly supports consideration of an annual standard level in the range of 12 to 11 μg/m 3 . In considering how the annual and 24 - hour standards work together to provide appropriate public health protection, the Admin istrator observes that the Policy Assessment concludes it is appropriate to consider retaining the current 24 - hour standard level at 35 μg/m 3 in conjunction with an annual standard in the range of 12 to 11 μg/m 3 , as well as to consider an alternative 24 - ho ur standard level of 30 μg/m 3 , particularly in conjunction with an annual standard level of 13 μg/m 3
. As noted in section III.E.4.d above, the Administrator observes that CASAC did not express support for any specific levels or combinations of standards wi thin in these ranges, although she recognizes that CASAC did not have an opportunity to review additional information and analyses presented in the final Policy Assessment prepared in response to CASAC’s recommendations on the second draft Policy Assessment. Nor did CASAC have an opportunity to review the EPA staff’s revised rationale for the combinations of alternative standards presented in the final document. In consider ing the extent to which the currently available evidence and information provide support for specific standard levels within the ranges identified by CASAC and the Policy Assessment as appropriate for consideration, the Administrator initially considers st andard levels within the range of 13 to 11 μg/m 3 for the annual standard. In so doing, the Administrator first considers the long - term mean PM 2.5 concentrations reported in studies of effects classified as having evidence of a causal or likely causal relat ionship, as summarized in Figure 4 and discussed more broadly above. She notes that a level of 13 would be below most but not all the mean concentrations from the multi - city studies of long - and short - term exposures, whereas a somewhat lower level, such as 12 μg/m 3 or lower, would be below all such mean concentrations. In considering the appropriate weight to place on this information, the***E.O. 12866 Review

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Page 126 of 133 Administrator again notes that the evidence of an association in any such study is strongest at and around the long - ter m average where the data in the study are most concentrated, and that long - term mean PM 2.5 concentrations are available for each study considered and, therefore, represent the most robust data set to inform her decisions on appropriate annual standard leve ls. In considering the long - term mean PM 2.5 concentrations reported in studies of effects classified as having evidence suggestive of a causal relationship, as summarized in Figure 4 for reproductive and developmental effects, the Administrator notes that a level of 13 would be below the mean concentration in one of the three studies, while lower levels such as 12 or 11 μg/m 3 would be below the mean concentration in two or three of these studies, respectively. In considering the appropriate weight to place on this information, the Administrator notes the very limited nature of this evidence of such effects and the additional uncertainties in these epidemiological studies relative to the studies that provide evidence of causal or likely causal relationships. In considering additional distributional statistics of population - level information that were available from four of the epidemiological studies that provide evidence of effects identified as having a causal relationship with long - or short - term PM 2.5 conc entrations, the Administrator notes that a level of 12 μg/m 3 is the PM 2.5 concentration that generally corresponds with approximately the 25 th percentile of the distributions of health events data available in three of these studies. The Administrator note s that higher standard levels up to 13 μg/m 3 would reflect placing significantly less weight on this statistical information, whereas lower standard levels down to 11 μg/m 3 would reflect placing significantly more weight on this information. In considering this information, the Administrator notes that there is no bright line that delineates the start of the range of PM 2.5 concentrations below the mean within which the data become appreciably more sparse and, thus, where her confidence in the associations o bserved in epidemiological studies begins to become appreciably less. In considering mean PM 2.5 concentrations and distributional statistics from the various sets of***E.O. 12866 Review

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Page 127 of 133 epidemiological studies noted above, the Administrator recognizes that such studies typic ally report concentrations based on composite monitor distributions, in which concentrations may be averaged across multiple ambient monitors that may be present within each area included in a given study. Thus, as noted above, a policy approach that uses data based on composite monitors to identify potential alternative standard levels would inherently build in a margin of safety of some degree relative to an alternative standard level based on information from measurements at the monitor within an area th at records the highest concentration, or the “ maximum monitors in an area, monitor”, since , once a standard is set, concentrations at appropriate maximum monitors within an area are generally used to determine if an area meets a given standard. The Administ rator also recognizes that judgments about the appropriate weight to place on any of the factors considered discussed above should reflect consideration not only of the relative strength of the evidence but also on the important uncertainties that remain in the evidence and information being considered in this review. The Administrator notes that the extent to which thes e uncertainties influence judgments about appropriate annual and daily standard levels within the range of 11 to 13 μg/m 3 would likely be greater for standard levels in the lower part of the range which would necessarily be based on fewer available studies than would higher levels within the range. Based on the above considerations, the Administrator concludes that it is appropriate to propose to set a level for the primary annual PM 2.5 standard within the range of 12 to 13 μg/m 3 . The Administrator provisio nally concludes that a standard set within this range would reflect alternative approaches to appropriately placing the most weight on the strongest available evidence, while placing less weight on much more limited evidence and on more uncertain analyses of information available from a relatively small number of studies. Further, she provisionally concludes that a standard level within this range would reflect alternative approaches to appropriately providing an adequate margin of safety for the population s at risk for the serious health effects classified as having evidence of a causal or***E.O. 12866 Review

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Page 128 of 133 likely causal relationship, depending , in part , on the emphasis placed on margin of safety considerations. The Administrator recognizes that setting an annual standard le vel at the lower end of this range would reflect an approach that places more emphasis on the strength of the evidence, including the analysis of the distribution of air quality concentrations most influential for generating health effect estimates in the studies, and more emphasis on margin of safety considerations, than would setting a level at the upper end . of this range. Conversely, an approach that would support a level at the upper end of this range would place greater weight on the remaining uncerta inties in the evidence to avoid potentially overestimating public health improvements , and would generally support a view that the uncertainties remaining in the evidence are too great to warrant setting a lower annual standard level. While the Administrat or recognizes that CASAC advised, and the Policy Assessment concluded, that the available scientific information provides support for considering a range that extended down to 11 μg/m 3 , she concludes that proposing such an extended range would reflect a pu blic health policy approach that places more weight on relatively limited evidence and more uncertain information and analyses than she considers appropriate at this time. Nonetheless, the Administrator solicits comment on a level down to 11 μg/m 3 as well as on approaches for translating scientific evidence and rationales that would support such a level. Such an approach might reflect a view that the uncertainties associated with the available scientific information warrant a highly precautionary public hea lth policy response that would incorporate a large margin of safety. The Administrator recognizes that potential air quality changes associated with meeting an annual standard set at a level within the range of 12 to 13 μg/m 3 will result in lowering risks associated with both long - and short - term PM 2.5 exposures. However, the Administrator recognizes that such an annual standard intended to serve as the primary means for providing protection from effects associated with both long - and short - term PM 2.5 expos ures would not by itself be expected to offer requisite protection with an adequate margin of safety against the effects of all short - term PM 2.5 exposures. As a***E.O. 12866 Review

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Page 129 of 133 result, in conjunction with proposing an annual standard level in the range of 12 to 13 μg/m 3 , the Administrator provisionally concludes that it is appropriate to continue to provide supplemental protection by means of a 24 - hour standard set at the appropriate level, particularly for areas with high peak - to - mean ratios possibly associated with stro ng local or seasonal sources, or for PM 2.5 - related effects that may be associated with shorter - than - daily exposure periods. Based on the approach discussed in section III.A.3 above, the Administrator has relied upon evidence from the short - term exposure s tudies as the principal basis for selecting the level of the 24 - hour standard. In considering these studies as a basis for the level of a 24 - hour standard, and having selected a 98 th percentile form for the standard, the Administrator agrees with the focus in the Policy Assessment of looking at the 98 th percentile values, as well as at the long - term mean PM 2.5 concentrations in these studies. In considering the information provided by the short - term exposure studies, the Administrator recognizes that to the extent these studies were conducted in areas that likely did not meet one or both of the current standards, such studies do not help inform the characterization of the potential public health improvements of alternative standards set at lower levels. By r educing the PM 2.5 concentrations in such areas to just meet the current standards, the Administrator anticipates that additional public health protection will occur. Therefore, the Administrator has focused on studies that reported positive and statistical ly significant associations in areas that would likely have met both the current 24 - hour and annual standards. She has also considered whether or not these studies were conducted in areas that would likely have met an annual standard level of 12 to 13 μg/m 3 to inform her decision regarding an appropriate 24 - hour standard level. As discussed in section III.E.4.a, the Administrator concludes that multi - city, short - term exposure studies provide the strongest data set for informing her decisions on appropriate 24 - hour standard levels. The Administrator views the single - city, short - term exposure studies as a much more limited data set providing mixed results and, therefore, she has less confidence***E.O. 12866 Review

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Page 130 of 133 in using these studies as a basis for setting the level of a 24 - ho ur standard. With regard to the limited number of single - city studies that reported positive and statistically significant associations for a range of health endpoints related to short - term PM 2.5 concentrations in areas that would likely have met the curre nt suite of PM 2.5 standards, the Administrator recognizes that many of these studies had significant limitations (e.g., limited statistical power, limited exposure data) or equivocal results (mixed results within the same study area) that make them unsuita ble to form the basis for setting the level of a 24 - hour standard. With regard to multi - city studies that evaluated effects associated with short - term PM 2.5 exposures, the Administrator observes an overall pattern of positive and statistically significant associations in studies with 98 th percentile values averaged across study areas in the range of 45.8 to 34.2 μg/m 3 (Burnett et al., 2004; Zanobetti and Schwartz, 2009; Bell et al., 2008; Dominici et al., 2006a, Burnett and Goldberg, 2003; Franklin et al., 2008). The Administrator notes that, to the extent air quality distributions are reduced to reflect just meeting the current 24 - hour standard, additional protection would be anticipated for the effects observed in the three multi - city studies with 98 th pe rcentile values greater than 35 μg/m 3 (Burnett et al., 2004; Burnett and Goldberg, 2003; Franklin et al., 2008). In the three additional studies with 98 th percentile values below 35 μg/m 3 , specifically 98 th percentile concentrations of 34.2, 34.3, and 34.8 μg/m 3 , the Administrator notes that these studies reported long term mean PM 2.5 concentrations of 12.9, 13.2, and 13.4 μg/m 3 , respectively (Bell et al., 2008; Zanobetti and Schwartz, 2009; Dominici et al., 2006a). In proposing to revise the level of the a nnual standard to within the range of 12 to 13 μg/m 3 , as discussed above, the Administrator recognizes that additional protection would be provided for the short - term effects observed in these multi - city studies in conjunction with an annual standard level of 12 μg/m 3 , and in two of these three studies in conjunction with an annual standard level of 13 μg/m 3 . Based on this, it would be reasonable to conclude that revision to the 24 - hour standard would not be warranted***E.O. 12866 Review

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Page 131 of 133 in either case. However, the Administra tor has less confidence in judging that a level of 35 μg/m 3 would be appropriate in conjunction with an annual level at the upper end of the range. Based on the above considerations related to the epidemiological evidence, the Administrator provisionally c oncludes that it is appropriate to retain the level of the 24 - hour standard at 35 μg/m 3 , in conjunction with a revised annual standard level in the proposed range of 12 to 13 μg/m 3
. In addition to considering the epidemiological evidence, the Administrator also has taken into account air quality information based on county - level 24 - hour and annual design values to understand the implications of retaining the 24 - hour standard level at 35 μg/m 3 in conjunction with an annual standard level within the proposed range of 12 to 13 μg/m 3 . She has considered whether this suite of standards would meet a public health policy goal which includes setting the annual standard to be the “generally controlling” standard in conjunction with setting the 24 - hour standard to pro vide supplemental protection to the extent that additional protection is warranted. As discussed above, the Administrator provisionally concludes that this approach is the most effective and efficient way to reduce total population risk associated with bot h long - and short - term PM 2.5 exposures, resulting in more uniform protection across the U.S. than the alternative of setting the 24 - hour standard to be the controlling standard. In considering the air quality information, the Administrator observes that a suite of PM 2.5 standards that includes an annual standard level of 12 μg/m 3 and a 24 - hour standard level of 35 μg/m 3 (i.e., 12/35) would result in the annual standard as the generally controlling standard in most regions across the country, except for certain areas in the Northwest, where the annual mean PM 2.5 concentrations have historically been low but where relative ly high 24 - hour concentrations occur, often related to seasonal wood smoke emissions (US EPA, 2011a, pp. 2 - 89 to 2 - 91, Figure 2 - 10). Although not explicitly delineated on Figure 2 - 10 in the Policy Assessment, an annual standard of 13 μg/m 3 would be somewha t less likely to be the generally controlling standard in some regions of the U.S. outside the***E.O. 12866 Review

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Page 132 of 133 Northwest in conjunction with a 24 - hour standard level of 35 μg/m 3
. Taking the above considerations into account, the Administrator proposes to revise the level of the primary annual PM 2.5 standard from 15.0 μg/m 3 to within the range of 12.0 to 13.0 μg/m 3 and to retain the 24 - hour standard level at 35 μg/m 3 . In the Administrator’s judgment, such a suite of primary PM 2.5 standards and the rationale supporting such levels could reasonably be judged to reflect alternative approaches to the appropriate consideration of the strength of the available evidence and other information and their associated uncertainties and the advice of CASAC. The Administrator recognizes that the final suite of standards selected from within the proposed range of annual standard levels, or the broader range of annual standard levels on which public comment is solicited, must be clearly responsive to the issues raised by the D.C. Circuit’s remand of the 2006 primary annual PM 2.5 standard. Furthermore, the final suite of standards will reflect the Administrator’s ultimate judgment in the final rulemaking as to the suite of primary PM 2.5 standards that would be requisite to protect the public health with an adequate margin of safety from effects associated with fine particle exposures. The final judgment to be made by the Administrator will appropriately consider the requirement for a standard that is neither more nor less stringent than necess ary and will recognize that the CAA does not require that primary standards be set at a zero - risk level, but rather at a level that reduces risk sufficiently so as to protect public health with an adequate margin of safety. Having reached her provisional judgment to propose revising the annual standard level from 15.0 to within a range of 12.0 to 13.0 μg/m 3 and to propose retaining the 24 - hour standard level at 35 μg/m 3 , the Administrator solicits public comment on this range of levels and on approaches to considering the available evidence and information that would support the choice of levels within this range. The Administrator also solicits public comment on alternative annual standard levels down to 11 μg/m 3 and on the combination of annual and 24 - hou r standards that commenters may believe is appropriate, along with the approaches and rationales used to support such levels. In addition, given the importance the***E.O. 12866 Review

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Page 133 of 133 evidence from epidemiologic studies plays in considering the appropriate annual and 24 - hour levels, the Administrator solicits public comment on issues related to translating epidemiological evidence into standards, including approaches for addressing the uncertainties and limitations associated with this evidence. F. Administrator’s Proposed Decisi ons on Primary PM 2.5 Standards For the reasons discussed above, and taking into account the information and assessments presented in the Integrated Science Assessment, Risk Assessment, and Policy Assessment, the advice and recommendations of CASAC, and pub lic comments to date, the Administrator proposes to revise the current primary PM 2.5 standards. Specifically, the Administrator proposes to revise: (1) the level of the primary annual PM 2.5 standard to a level within the range of 12.0 to 13.0 μg/m 3 and (2) the form of the primary annual PM 2.5 standard to one based on the highest appropriate area - wide monitor in an area, with no allowance for spatial averaging. In conjunction with revising the primary annual PM 2.5 standard to provide protection from effects associated with long - and short - term PM 2.5 exposures, the Administrator proposes to retain the level and form of the primary 24 - hour PM 2.5 standard to provide supplemental protection for areas with high peak PM 2.5 concentrations. The Administrator provisionally concludes that such a revised suite of standards, including a revised annual standard together with the current 24 - hour standard, could provide requisite protection against health effects potentially associa ted with long - and short - term PM 2.5 exposures. The Administrator is not proposing any revisions to the current PM 2.5 indicator and the annual and 24 - hour averaging times for the primary PM 2.5 standards. Data handling conventions are specified in proposed r evisions to appendix N, as discussed in section VII below. The Administrator solicits comment on all aspects of this proposed decision. Formatted: Font: Italic, No underline

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