Health Effects of Ambient Concentrations of Ozone Sabine Lange, Ph.D. Toxicology Division Texas Commission on Environmental Quality 1

O 3 National Ambient Air Quality Standard 2 The EPA sets standards for 6 air pollutants (criteria air pollutants) – O 3, particulate matter, NO x, SO x, CO and lead The O 3 NAAQS is currently 75 ppb, and the EPA is proposing ppb The ozone Proposed Rule has been released, the comment period is closed, and the EPA is under a court- ordered deadline to finalize the rule by October, 2015

Ozone (O 3 ) O 3 is formed when nitrogen oxides (NO x ) and volatile organic compounds (VOCs) react with sunlight NO x is responsible for both formation and scavenging of O 3 Inhaled O 3 : – Is scavenged by antioxidants in the respiratory tract – When antioxidants are depleted, it causes a neural reaction that decreases breathing volume, and can cause inflammation, airway hyper-reactivity and other responses 3

Independent Workshop on Ozone NAAQS Science & Policy Purpose: to engage a multi-disciplinary group of science and policy experts to review the scientific evidence regarding ambient ozone’s health effects and to deliberate on the nexus between scientific findings and implications for public health Goal: to provide an independent evaluation and synthesis of key considerations for approaching the difficult and complex ozone NAAQS decision 4

Session 1 – Context of the O 3 Rule Seyed Sadredin – San Joaquin Valley Air pollution control district – Air quality in California has greatly improved in the last 40 years – Spent $40 bill in reducing air pollution, will barely meet the 84 ppb standard; could eliminate all stationary sources and passenger vehicles, and still not meet the present standard – Need more time for implementation, less chaos when changing the standard and better information to the public Henry Nickel – Special Counsel, Hunton & Williams – NAAQS are the heart of the modern clean air act – The program separates standard setting from implementation – Primary standards must be requisite to protect public health with an adequate margin of safety – level of the standard must be sufficient to protect public health, but not lower than necessary (the Goldilocks standard) – Costs cannot be considered when establishing the standard 5

Roger McClellan – Advisor, Toxicology and Human Health Risk Analysis – Policies and regulations should be informed by the science, but science alone is not sufficient – judgment is also required – It is important to look at every aspect of the standard: indicator, form, level and averaging time – Common sense and context should be used when setting the standard Tim Verslycke – Gradient – The latest ozone proposed rule will keep the secondary (welfare-based) standard the same as the primary (health-based) standard – There are benefits to plants just by meeting the current ozone standard, but little evidence for increased benefits by further lowering the level of the standard 6 Session 1 – Context of the O 3 Rule

One full day of presentations and discussion on 4 ozone science topics: – Ozone mode of action – Human clinical studies – Epidemiology studies and exposure – Evidence integration 7 Session 2 – Selected Topics of the O 3 Science

Ozone Mode of Action 8 Source: US EPA ISA 2013

Human Clinical Studies 9 These studies measure physiological effects, primarily respiratory function (forced expiratory volume in 1 second - FEV 1 ) They take into account 3 parameters, which make up O 3 dose: – O 3 concentration (in ppm) – Duration of exposure (in min) – Ventilation rate (ie. Exercise level; in L/min)

Adverse Effects – FEV 1 ATS, “reversible loss of lung function in combination with the presence of symptoms should be considered adverse.” ATS/ERS, “two-point, short-term changes of >12% and >0.2L in the FEV 1 are usually statistically significant and may be clinically important” (Pellegrino 2005) US EPA 2014b - “…a focus on the mid- to upper-end of the range of moderate levels of functional responses and higher (FEV 1 decrements ≥ 15%) is appropriate for estimating potentially adverse lung function decrements in active healthy adults, while for people with asthma or lung disease, a focus on moderate functional responses (FEV 1 decrements down to 10%) may be appropriate” 10

O 3 Dose-Response Curves 11 With M. Honeycutt from TCEQ; G. Tao, L. Rhomberg & J. Goodman from Gradient; M. Dourson from TERA Longer Exposure (6-8 hours) Shorter Exposure (≤ 3 hours)

O 3 Dose-Response Curves 12

13 D-R Curves with Sensitive Populations

14 D-R Curves with Sensitive Populations

Ozone Dose Thresholds 15

O 3 FEV 1 Dose Thresholds 16 Mean % Change in FEV 1 Short exposure dose (ppmL) Long exposure dose (ppmL) 0N/A N/A -20N/A Individual Data Dose-Response Curves

Exercise Ventilation Rates & Durations SourcePopulationExercise Intensity Ventilation Rate (L/min)* Duration (hours)* US EPA 2009 Children (6 - < 11 years old) Sedentary4.8 (3.7-6)13.7 (13-15) Light11.3 (9.2-14)7.4 ( ) Moderate21.6 ( )2.6 ( ) High41.5 ( )0.3 ( ) Adult (21 - < 31 years old) Sedentary5.3 ( )12.5 ( ) Light11.8 ( )6.3 ( ) Moderate26.1 ( )5 ( ) High49.8 ( )0.3 ( ) US EPA 1994Non-occupational 24 hr Ventilation with 8 hrs Manual labor 1424 OccupationalManual labor228 Zuurbier 2003AdultBicycle commute23.5 ( )2 Samet 1993ChildOutdoor play16 ( )1.9 ChildBicycling27.1 ( )2.1 AdultVigorous bicycling65 ( )0.8 * Mean ventilations and times, and where available, the 10 th and 90 th percentiles in parentheses.

Ozone Concentrations 18 1 Hour Measurements 8 hr Max Ave4 hr Max Ave12 hr Max Ave24 Hr Ave

Ozone Concentrations 19 Concentration Metric 75 ppb Days (ppb) mean (SD) 70 ppb Days (ppb) mean (SD) 65 ppb Days (ppb) mean (SD) 1-hr max85.8 (3.5)77.4 (5.7)72.4 (4.7) 2-hr max average84.2 (3.2)76.2 (5.2)71.3 (4.1) 3-hr max average82.8 (2.7)75.3 (4.8)70.3 (3.7) 4-hr max average80.8 (2.2)74.3 (4.2)69.6 (3.4) 5-hr max average79.4 (1.7)73.3 (3.2)68.6 (2.6) 6-hr max average78.2 (1.3)72.4 (2.1)67.6 (1.9) 7-hr max average76.8 (0.9)71.4 (1.4)66.6 (1.1) 8-hr max average75.4 (0.6)70.2 (0.7)65.6 (0.8) 9-hr max average72.6 (4.5)69 (0.7)64.5 (1.2) 10-hr max average71.5 (3.2)97.6 (1.6)63.2 (2.0) 11-hr max average70.4 (2.2)66.2 (2.4)61.9 (2.9) 12-hr max average69.2 (1.8)64.9 (3.2)60.6 (3.5) 13-hr max average68 (1.8)63.8 (4.0)59.2 (4.2) 14-hr max average66.9 (2.1)62.7 (4.7)57.9 (4.8) 24-hr average52.2 (5.5)51.4 (8.5)46.2 (6.5) Ozone concentrations on days with maximum eight-hr concentrations of 75, 70 or 65 ppb. Note: provided are the mean maximum averages using different time metrics from 10 days with eight-hour maximum averages of 75, 70 or 65 ppb (standard deviation in parentheses). Shaded is the measured eight-hour maximum average.

O 3 Dose Calculation 20 Example: A child exercising at moderate intensity Ventilation Rate: 21.6 L/min Duration: 2.6 hours (156 minutes) Ozone concentration at 3 hour maximum average: 8 hr Max Ozone75 ppb70 ppb65 ppb 3 hr Max Ozone82.8 ppb75.3 ppb70.3 ppb Dose Calculation: 75 ppb:21.6 L/min x 156 minutes x ppm = 279 ppm x L 70 ppb:21.6 L/min x 156 minutes x ppm = 254 ppm x L 65 ppb:21.6 L/min x 156 minutes x ppm = 237 ppm x L Compare to short exposure (< 4 hours) thresholds: 5% FEV 1 decrement: 740 ppm x L 10% FEV 1 decrement: 927 ppm x L 15% FEV 1 decrement: 1467 ppm x L

Short Exposure Scenarios 21 Threshold O 3 dose for 15% FEV 1 mean decrement Threshold O 3 dose for 10% FEV 1 mean decrement Threshold O 3 dose for 5% FEV 1 mean decrement

Longer Exposure Scenarios 22 Threshold O 3 dose for 10% FEV 1 mean decrement Threshold O 3 dose for 5% FEV 1 mean decrement

Strengths of Ozone Epidemiology Studies Can assess health status in a large population over many years Can capture temporal ozone concentration variability Can make individual-level causal inference Can control for temporal trends Can deal with time-invariant subject characteristics

Limitations in Ozone Epidemiology Studies Ecological fallacy Confounding Prevalence measures (vs. incidence) Low compliance (panel studies) Exposure measurement error Disease measurement error Model misspecification Model selection bias Publication bias

Epidemiology - Heterogeneity 25

Weight-of-Evidence Evaluation Approach 1 Define causal question Develop study selection criteria 2 Develop and apply criteria for review of individual studies 3Integrate and evaluate evidence4 Draw conclusions based on inferences

Evidence Integration and Evaluation Phase 3

EPA’s Causal Determinations Health Outcome Short-term ExposureLong-term Exposure 2008 Review 2015 Review 2008 Review 2015 Review Respiratory effects (including mortality) Causal Suggestive Likely to be causal All-cause mortalitySuggestive Likely to be causal Little evidence Suggestive Cardiovascular effects (including mortality) Suggestive Likely to be causal No conclusion Suggestive

Session 3 – Socioeconomic Costs Daniel Millimet – Southern Methodist University – Historical evidence of economic impacts of environmental regulation – NAAQS regulatory costs have historically impacted businesses, but only the subset of businesses that have high air pollution regulatory costs John Morrall – Mercatus Center at George Mason University – Health effects of regulatory costs – changing economic conditions can have negative impacts on health – Health-health analysis – considers both the intended health consequences of a regulation (the health benefits) and the unintended health consequences of a regulation (the health dis-benefits) – Example calculation (based on published literature) – using 1 life lost for every $25 million increase in costs: By the EPA’s calculations, 900 lives are saved from decreasing ozone, with a standard at 60 ppb But using the above calculation (1 life lost/$25 mill in costs), 2000 lives would be lost from the economic cost to attain 60 ppb – uses EPA’s cost estimate 29

EPA compliance costs estimate for 65 ppb ozone standard level 30

NERA compliance costs estimate for 65 ppb ozone standard level 31

NERA Economic Impact Analysis: GDP

NERA economic impact analysis by sector

Session 4 – Policy Panel Discussion Considerations of the legal framework: In terms of litigating the decisions of the Administrator, the EPA is given the highest level of deference on matters of technical or scientific expertise, and the course give absolute deference to the agency for the scientific conclusions Supreme Court Justice Breyer, in Whitman v American Trucking Association, stated: – The statue also permits the Administrator to take account of comparative health risks. That is to say, she may consider whether a proposed rule promotes safety overall. A rule likely to cause more harm to health than it prevents is not a rule that is “requisite to protect public health”. This suggests that the health dis-benefits should be considered in making this decision The policy panelists were concerned that the way the decision is currently being made (no guidance or evidence of consistent decision making, behind- the-curtain considerations of costs) will lead to cynicism in how people view the law and the government 35

Session 4 – Policy Panel Discussion Context of the decision This decision is being made in a very different environment from that when the Clean Air Act (CAA) was written: – In 1970 there had been some terrible air pollutions events, and now we have had 45 years of improving air quality – In 1970 there was a lot of pollution control “low hanging fruit” available to clean the air, and now the low and middle hanging fruit are gone, and we have to go for the fruit at the top of the tree – In 1970 the country was 25 years into its best years of economic growth, and now we are coming off of the worst economic downturn since the Great Depression, and economic analysts say that growth will be slower – In 1970 the benefits of economic growth were more widely shared, and now even if the average wealth increases, the largest share of those gains goes to those at the very top – Now the CAA would likely be written to take into account cost, background concentrations, security of the energy infrastructure, in addition to protecting public health and welfare 36

Session 4 – Policy Panel Discussion The EPA Administrator’s decision: The EPA produced many large, comprehensive documents in it’s re- evaluation of the ozone NAAQS. We have had the luxury of looking at and criticizing these documents, and of discussing the uncertainties – it is amazing that we have so much data available to criticize (ie. there is a wealth of data in the ozone literature) The Administrator has to draw a bright line across all of the uncertainties, and she has to make a decision despite uncertainties Setting the NAAQS is the quintessential decision based on the Administrator’s discretion – no criteria for making the decisions reproducible, doesn’t have to follow CASAC’s advise The discussion really comes down to certainty and uncertainty – what data are we sure of, what are we less sure of? How sure do you have to be to set a national standard at a certain level? Costs are considered “behind-the-curtain”, and then the science and uncertainty are used to justify the decision 37

Session 4 – Policy Panel Discussion Take-home messages: The panel considered this workshop to be unique: bringing together experts in science, economics, policy and law to discuss the complex and multi-faceted NAAQS decision The concerns raised in the workshop (about implementation, the ozone science, and the cost of the rule) are valid For the Administrator to consider comments and arguments, they must be part of the record (ie. comments made in the docket), and once the comment period is over, there is still opportunity for further discussion with different groups in the federal government (EPA, OMB) 38