March 5, 2015

U.S. Environmental Protection Agency Headquarters, William Jefferson Clinton Building 1200 Pennsylvania Avenue, N.W., Washington, DC 20460

Dear Administrator McCarthy :

We are submitting the comments below in support of the proposed lowering of the Ozone standard, and to encourage you to set the new standard to the lower end of the proposed range. Specifically, we urge you to set the standard at 60

- 65 ppb

, in order to protect vulnerable populations from the adverse health effects of ozone with an adequate margin of safety. As detailed below, the currently proposed standard of 65

- 70 ppb do es not adequately account for excess risk encountered by pregnant women and populations who experience the cumulative effects of multiple physical and social stressors. In the attached document we discuss the evidence with regard to the inc reased risk encountered by these two vulnerable groups, the lack of explicit analysis in the risk assessment process, and the need for a larger margin of safety to adequately protect their health. In addition, we offer several recommendations for where language in the proposed rule should be altered to address this issue. Thank you for your work to protect the health of the public, and your attention to these comments in order to particularly prote c t vulnerable groups who are at increased risk for the ad verse health effects of ozone.

Sincerely,

Chris Coombe, PhD, MPH

, Assistant Research Scientist University of Michigan School of Public Health

Kelly Ferguson, PhD, MPH , Research Fellow University of Michigan School of Public Health

Patricia Koman, MPP, Senior Project Manager University of Michigan School of Public Health

Natalie Sampson, PhD, MPH , Assistant Professor College of Education, Health, & Human Services, University of Michigan

- Dearborn

Amy Schulz, PhD, MPH , Professor University of Michigan School of Public Health

Donele Wilkins, President/CEO Green Door Initiative2

March 6, 2015

Public Comment on the Federal Register, Vol. 79 No. 242 National Ambient Air Quality Standards for Ozone; Proposed Rule Published December 17, 2014 Docket ID No. EPA

- HQ

- OAR

- 2008

- 0699

The legislative history of the Clean Air Act specifies the responsibility of the E nvironmental P rotection Agency (EPA) , through the National Ambient Air Quality Standards (NAAQS), to identify and to protect with an adequate ma rgin of safety vulnerable populations who are at increased risk for adverse effects of air pollutants

. The proposed revised ozone standard published in the EPA’s NAAQS for Ozone, signed by Administrator McCarthy on November 25, 2014, would lower the standa rd from 75 ppb to a level in the range of 65

- 70ppb. These proposed standards are a step in the right direction
, and we are supportive of lowering the level from 75 ppb to this range

. However , based on evidence included in the Integrated Science Assessment (ISA) and highlighted in the Ozone Health Risk and Exposure Assessment (hereafter Ozone H REA) completed by the EPA 1 and echoing the recommendations made by the Clean Air Scientific Advisory Committee (CASAC)
, 2 the new standard should be lowered further to the range of 60

- 65 ppb to adequately protect previously unacknowledged vul nerable populations from the adverse health effects of ozone exposure with an adequate margin of safety

.

T he proposed standards do not adequately account for excess risk experienced by several important groups

. These include pregnant women
, populations experiencing cumulative effects of multiple physical and social stressors
, and pregnant women in these populations

. Due to the lack of explicit analysis of these groups in the risk assessment process , a larger margin of safety is needed to acc ount for the underestimated number of individuals in the US who are at increased risk for health effects consequent to exposure

. In the comments we present evidence that supports our recommendation for a larger margin of safety, including evidence of excess risk in these populations, and make recommendations for where language in the proposed rule should be altered.

Pregnant Women

Pregnant women were not examined in the Integrated Science Assessment (ISA) for Ozone and Related P hotochemical Oxidants. 3 P renatal development is considered as a lifestage that is more susceptible to exposures , and reproductive and developmental consequences to the fetus are considered

. However, the ISA summaries do not sufficiently address the elevated risk of ozone consequences experienced by the pregnant population
, as they omit scientific evidence showing the increased vulnerability of this population completely

. Pregnant women are an at

- risk population because of: 1) a broader range of potential health consequences, and 2) increased dose of ozone for a given exposure level.3

Identification of exposures of concern to pregnant women and reduction of exposures is of great con cern to the medical community, as illustrated by the 2013 Committee Opinion from the American College of Obstetricians and Gynecologists (ACOG) on Exposure to Toxic Environmental Agents

. 4

1. Pregnant women are at risk for a broader range of adverse health effects consequent to ozone exposure that are not applicable to the rest of the population. These include: a) preeclampsia , a hypertensive disorder of pregnancy ; and b) birth outcomes, which can be detrimental to maternal physical and mental health.

a. Preeclampsia is a hypertensive disorder that is specific to pregnancy which puts the mother at an increased r isk of mortality during pregnancy and also for an increased risk of cardiovascular disease later in her life. 5 Additionally, preeclampsia is a risk factor for adverse birth outcomes such as fetal growth restriction and preterm birth. New studies have been published since the Ozone ISA was completed demonstrating strong evidence for an association between exposure to ozone during pregnancy and the development of preeclampsia

. 6
, 7 Despite the inability to demonstrate clear causality in most epidemiologic research, a number of the studies in this realm have provided evidence for such a relationship by measuring exposure prior to delivery. 8
, 9 Notably, a systematic review and meta

- analysis of these studies showed that a 10 ppb increase in ambient ozone levels in the first or second trimester is associated with an approximately 10 percent increase in risk of developing a hypertensive disorder of pregnancy

. 6 Of additional importance mean/median ambient air concentrations of ozone from the studies included in that meta

- analysis were much lower than the current standard (22

- 40 ppb). 6 T here is mechanistic evidence from in vitro and animal studies to support a causal association between ozone exposure and hypertension or preeclampsia in pregnancy. Briefly, ozone has been shown to induce maternal and placental oxidative stress
, 10 which can lead to apoptosis of the syncytiotrophoblast and narrowing of the spiral arterioles that are crucial for sufficient placental blood flow. 11

- 14 This impaired placentation is the suspected cause of hypertensive disorders of pregnancy. 11
, 15 While not published in time to be considered in the Ozone ISA, the compelling nat ure of this new evidence for a causal relationship between ozone exposure and preeclampsia should be considered now, as part of this standard review. In particular, this can be addressed by moving toward the lower standard of 60

- 65 ppb, which provides a la rger margin of error to better protect pregnant women from adverse health effects of ozone exposures.

b. Birth outcome s , including but not limited to fetal mortality, premature birth, low birth weight, and birth defects have been associated with ozone exposure, with suggestive evidence of a causal relationship. These findings have been4 adequately summarized in the ISA of ozone
, 3 although this document excludes additiona l convincing evidence published since 2011. 8
, 16 Nevertheless
, the impact of these outcomes on the mothers themselves has not been s ufficiently emphasized. Not only are reproductive effects only applicable to women undergoing pregnancy, but in addition to negative health repercussions for the fetus, these effects can have adverse physical (e.g., C

- section) and mental 17

- 20 health consequences for the mother.

2. Pregnant women have an increased dose of ozone and other air pollutant s following exposure as compared to non

- pregnant women of the same age. This is a result of increased metabolic rate (i.e., amount of oxygen consumed) during pregnancy , which has been well

- established. 21

- 23 Since the primary route of exposure for air pollutants is through inhalation, it follows that dose would be higher in pregnant women although, to our knowledge, this has n ot been directly demonstrated in epidemiologic, animal, or modeling studies.

Additionally, pregnant women represent a large proportion of the US population. For 2013
, the National Vital Statistics Reports from the US Department of Health and Human servic es estimated 3,957,577 births. 24 This und erestimates the number of pregnancies, but otherwise translates to pregnant women accounting for 1.25% of the population that year

. 2 5

The Federal Register 26 (Part I, Section A) states “The requirement that primary standards provide an adequate margin of safety was intended to address uncertainties associated with inconclusive scien tific and technical information available at the time of standard setting” and that factors considered in developing an adequate margin of safety include “such factors as the nature and severity of health effects, the size of sensitive population(s) at ris k, and the kind and degree of the uncertainties that must be addressed.” A number of important sensitive populations, such as children, were included in this process. However,

a dult pregnant women represent a large sensitive at

- risk population that w as not considered adequately in the ISA or in the Ozone H REA and
, thus, the standard of 0.065 to 0.070 ppm for ozone proposed in the Federal Register (Section I, part 2) was developed with an inadequate margin of safety . Consequently the lower range of 0.060 to 0.065 ppm should be set as the primary standard and the following language should be edited in the federal register to recognize the additional uncertainty in risk estimates that this sensitive population adds:

1) Part II, Section B (pg. 75246), Health Effects Information
, identifies “new epidemiologic studies published since the last review on effects associated with both short

- and long

- term exposures.” Five adverse health effects are listed that have new ( published since the 2008 review) supportive ev idence . We suggest that a 6 th effect be listed as follows:5 (6) Recent data from peer

- reviewed studies provide evidence that pregnant women are an at

- risk population. Exposure to ozone during pregnancy is associated with hypertensive disorders of pregnancy, such as preeclampsia, 6
, 7 that can have short

- and long

- term consequences to the mother including cardiovascular disease and death. 5 Birth outcomes associated with ozone exposure also have adverse physical and mental consequences to the mother. 17

-
20 In addition to these health consequences
, pregnant women may experience higher doses of ozone for a given exposure level due to elevated respiratory rates during pregnancy. 21

- 23

2) Part II, Section B, Part 2, Section c (pg. 75261), Cardiovascular Effects, examines ways in which the studies of cardiovascular effects of ozone exposure have recently expanded. Following the synopsis from the ozone ISA we suggest the following short paragraph on cardiovascular effects in pregnant women be added:

Since the publication of the ISA, we have also examined cardiovascular effects of

ozone exposure among pregnant women which differ from those of the general population. Specifically, there is adequate epidemiologic evidence that ozone exposure during pregnancy is associated with increased risk of developing preeclampsia, a hypertensive disorder of pregnancy that can lead to maternal mortality and increased ri sk of cardiovascular morbidities later in life. 6
, 7 Furthermore, previously examined t oxicological evidence demonstrating the potential for ozone to induce an inflammatory and oxidative state in tissue provide a mechanistic pathway to support these associations, as preeclampsia results from poor implantation consequent to these environments

. 11
, 15

Populations with Multiple Risk Factors

The rationale in the proposed standard and the Health Risk and Exposure Assessment for Ozone (HREA) did not adequately account for the combined effects of exposures to multiple chemical and non

- chemical (social) risk factors. Specifically, the Ozone HREA did not account for more adverse effects due to already compromised health, criteria laid out in the PM2.5 decision. In the most recent NAAQS review process for PM 2.5 , the EPA designated four ways to establish a margin of safety for at

- risk populations. 26
, 27 Vulnerability or risk was defined as meeting any one of the following criteria: 1) Higher levels of ambient exposure; 2) Higher dose at a given level of ambient exposure; 3) More adverse effects at a given level of ambient exposure; and 4) More adverse effects due to already compromised health. While these criteria were included for the PM 2.5 margin of safety determination , the EPA only included criteria 1

- 3 above for the development of the revised O zone standard. Although contained in the American Thoracic Society statement 28 and previous NAAQS reviews, the fourth cri teria was omitted from the6

CASAC correspondence with Administrator Jackson in the February 2013 to CASAC. 29 The rationale for eliminating the fourth criteria of population consequence is not discussed. We argue that this approach is inadequate. The absence of a clear methodology to account for the cumulative effects due to already compromised health from multiple social and chemical exposures contributes to an underestimate of the margin of safety and a departure from previous considerations

.

There is scientific consensus that the effects of exposures to environmental contaminants differ based on vulnerabilities such as underlying health status and the presence of co

pollutants. 30 Furthermore, there is i ncreasing recognition that social conditions can amplify the adverse effect s of environmental agents on health
, 30
, 31 contributing to exces s risk and racial, ethnic and socioeconomic disparities in health. The methodologies used in the current Ozone H REA do not adequately account for vulnerabilities that accrue through the combined effects of multiple social and physical environmental exposur es. This point is also explained by the CASAC in the Federal Register (Part II, Section C, Part 2b) , wh ich note s , “Although the E PA indicates less confidence in the likelihood of adverse health effects as O 3 exposures decline, it also notes that controlled human exposure studies that provided the basis for health benchmark concentrations have not evaluated at

- risk populations .” 26

To evaluate the potential i mplications of these uncertainties, in the HREA a limited number of sensitivity analyses were conducted

. For example, in models estimating exposures of concern among children who did not spend any time in school (to mimic children spending large amounts of time outdoors in the summer ; Section 5.4.3.1 ), the number experiencing exposures of concern increased by approximately 30%. 1 These models suggest that populations experiencing multiple vulnerabilities (e.g.
, heightened exp osure due to increased outdoor activity, increased dose due to heightened respiration, and asthma combined ) may experience more frequent exposures of concern than indicated by models that d o not account for multiple vulnerabilities. As a result of these uncertainties, a larger margin of safety is needed to adequately protect public health in vulnerable populations
, and w e support a rule that establishes an ozone standard between 60

- 65 ppb.

Several reports have highlighted the importance of understanding the aggregation of risks from multiple environmental stressors. These include the National Research Council's (NRC) 1994 report Science and Judgment in Risk Assessment
, 32 the 1997 report by the Presidential/ Congressional Commission on Ris k Assessment and Risk Management entitled Risk Assessment and Risk Management in Regulatory Decision

- Making
, 33 and most recentl y the National Research Council’s 2009 report on Science and Decisions

. 30 Individuals who experience multiple social, physical and chemical environmental stressors are at increased risk of disease. The Ozone HREA s uggests that communities with ozone monitors differ little in terms of demographic characteristics from the national population

. 1 However, this analysis does not address population level variations in susceptibilities to ad verse effects of ozone exposure.7

The proposed ozone regulatory standards not e guidance from the Amer ican Thoracic Society (ATS) regarding definitions of adverse effects at the population level. Specifically, g uidance from ATS states that “Exposure to air pollution that increases the risk of an adverse effect to the entire population is adverse, even though it may not incr e ase the risk of any individual to an unacceptable level. For example, a population of asthmatics c ould have a distribution of lung funct ion su c h that no individual has a level associated with clinically important impairment. Exposure to air pollution could shi ft the distribution to levels that still do not bring any individuals to a level that is associated with clinically relevant effects. However this wou ld be considered to be adverse because individuals w i thin the population would have diminished reserve function, and therefore would be at increased risk fo r further environmental insult ” (Part II, Section B, Part 3). 26
, 34

For example, a recent multicity time series study cited in the Federal Register followed four cohorts of Medicare enrollees with chronic conditions that m ight predispose them to ozone related effects from 1985

- 2006. 35 This study reported an association between long term (warm season) exposure to ozone and elevated risk of mortality in the cohort that had previously experienced an emergency hospital admission due to chronic obstructive pulmonary disease

. To the exten t that such s usceptibilities are differentially distributed within and between communities, there may be differential health effects at any given level of ozone exposure, 36

- 42 and communities may experience the combined effects of multiple vulnerabilities associated wi th adverse effects. Thus, lowering the ozone standards would prevent heightened effects on health, and ultimately, to health disparities in these communities

. The purpose of selecting primary standards that provide an adequate margin of safety is to both prevent pollution levels that have been demonstrated as harmful, and to prevent lower pollution levels that may pose an unacceptable risk of harm, even if the risk is not precisely identified. The EPA’s c urrent me thods for identifying populations at risk do not adequately account for multiple amplifying risk factors , including physical, social, and chemical exposures, and their combined impact on health effects associated with exposure to ozone

. Consequently, the standa rds set with these methods are inadequate to protect health in communities with these multiple risk factors. Thus, the primary standard should be set in the lower range of the standard recommended by CASAC (60

- 65ppb)

.
Pregnant Women Experiencing Multiple Risk Factors

The EPA should recognize that pregnant women living in communities that experience multiple chemical and non

- chemical exposures (i.e., psychosocial stressors) are particularly vulnerable, and their risks should be recognized in the final o zone rule, as well as in assessment documents (e.g., economic benefits, H REA and ISA) for future NAAQS reviews

. This is consistent with the ACOG Committee Opinion on Exposure to Toxic Environmental agents, which state: “Many environmental facto r s8

harmful t o reproductive health disproportionately affect vulnerable and underserved populations, which leaves some populations, including underserved women, more vulnerable to adverse reproductive and developmental health effects than other populations .” 4 P regnancy can be a time of increased vulnerability to air pollution exposure due to physiological changes that are occurring and increased dose as well as broader range of potential adverse health effects, as described above

. As has been underscored in a recent report from the National Research Council
, the effects of low

- dose exposures to environmental contaminants “may be quite different b ased on vulnerabilities” such as underlying health status and the presence of “additional ” or “ background ” environmental exposure. 30

As one ex ample, there is growing evidence that ozone contributes to metabolic disorders in animal models
, 43 and that metabolic disorders exacerbate other adverse health effects of exposure to ozone

. 44
, 45 Furthermore, l ow income women of any race/ethnicity and women of color across socioeconomic status experience excess risk of metabolic disorders 46 and those metabolic disorders are associated with adverse birth outcome s

. 47 Recogni zing that p regnant women who live in low income and/or medically underserved communities are both more likely to experience adverse health effects due to underlying health issues or additional exposures to other environmental toxins, 48
, 49 it is particularly important to provide an additional margin o f error to protect pregnant women residing in such communities

.
Conclusions

The failure to explicitly account for the vulnerability of pregnant women as well as populations exposed to multiple chemical and non

- chemical stressors, such as those in low income communities and communities of color, underestimates the adverse health effects of ozone. For this reason the propos ed ozone standard should be set at the 60

- 65 ppb range to incorporate a larger margin of safety

. By the HREA’s own calculations (Table ES7) 37 s etting the Ozone Standard toward the lower end of the proposed range (60

- 65 ppb) , rather than the higher end of 65

- 70 ppb would, by 2025, prevent an additional (over the 65

- 70 ppb):

 1300

- 3700 short

- term exposure related deaths,

 64
, 000 to 840 ,000 asthma attacks in children

 770 ,000 to 900,000 missed school days

 1300

- 3700 premature deaths

 2900 to 3700 asthma

- related emergency room visits , and

 115,000 to 160 ,000 missed workdays.

These numbers underestimate the actual positive impact of the lower standard because the ISA and HREA do not include pregnant women and communities exposed to multiple chemical and non

- chemical exposures as vulnerable populations. Under the Clean Air Act, EPA has a duty to protect at

- risk populations with an adequate margin of safety. To do so,9

EPA must fully assess th e risk to pregnant women , populations experiencing the cumulative effects of multiple social and chemical exposures, and, particularly, pregnant women within those populations

. In conclusion, we ask that you:

 Select a standard in the 60

- 65 ppb range in order to provide an adequate margin of safety for these at

- risk populations

.

 Strengthen the discussion in the Federal Register with regards to pregnant women, as described specifically above, and to populations with multiple risk factors.

 In future HRE As, more adequately account for the vulnerabilities of pregnant women and populations exposed to multiple chemical and social exposures, using for example, the population level criteria for risk suggested by the American Thoracic Society described above.

We are happy to meet with you to discuss or clarify any aspect of our comments.

Respectively submitted,

Chris Coombe, PhD, MPH, Assistant Research Scientist University of Michigan School of Public Health

Kelly Ferguson, PhD, MPH, Research Fellow University of Michigan School of Public Health

Patricia Koman, MPP, Senior Project Manager University of Michigan School of Public Health

Natalie Sampson, PhD, MPH, Assistant Professor College of Education, Health, & Human Services, University of Michi gan

- Dearborn

Amy Schulz, PhD, MPH, Professor University of Michigan School of Public Health

Donele Wilkins, President/CEO Green Door Initiative10

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