OFFICE OF THE ADMINISTRATOR
                                                                 SCIENCE ADVISORY BOARD
                                   December 3, 2009

EPA-C AS AC-10-004

The Honorable Lisa P. Jackson
U.S. Environmental Protection Agency
1200 Pennsylvania Avenue, N.W.
Washington, D.C. 20460

       Subj ect: Consultation on EPA's Draft Integrated Review Plan for the National Ambient
               Air Quality Standards for Ozone

Dear Administrator Johnson:

       EPA's Clean Air Scientific Advisory Committee (CASAC), supplemented by subject-
matter-expert Panelists — collectively referred to as the CASAC Ozone Review Panel  — held a
public advisory teleconference meeting on November 13, 2009.  The purpose of the
teleconference was to conduct a consultation with staff from the Agency's National Center for
Environmental Assessment (NCEA) and EPA's Office of Air Quality Planning and Standards
(OAQPS) on the Agency's Integrated Re view Plan for the Ozone National Ambient Air Quality
Standards Review (External Review Draft, September 2009).  The Panel generally found the
Integrated Review Plan  to be a well-conceived roadmap for the upcoming Ozone National
Ambient Air Quality Standards (NAAQS) review.

       The SAB  Staff Office has developed the consultation as a mechanism to advise EPA on
technical issues that should be considered in the development of regulations, guidelines, or
technical guidance before the Agency has taken a position.  A consultation is conducted under
the normal requirements of the Federal Advisory Committee Act (FACA), as amended (5 U.S.C.,
App.), which include advance notice of the public meeting in the Federal Register.

       As is our customary practice, there will be no consensus  report from the CASAC as  a
result of this consultation,  nor does the Committee expect any formal response from the Agency.
The current CASAC roster is Enclosure A of this letter, and the CASAC Ozone Review Panel
roster is found in Enclosure B.

Finally, some Ozone Review Panel members' individual written comments are provided in
Enclosure C.



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

Enclosure A
                     U.S. Environmental Protection Agency
               Clean Air Scientific Advisory Committee (CASAC)
Dr. Jonathan M. Samet, Professor and Flora L. Thornton Chair, Department of Preventive
Medicine, University of Southern California, Los Angeles, CA
      Also Member: BOARD
Dr. Joseph Brain, Philip Drinker Professor of Environmental Physiology, Department of
Environmental Health, Harvard School of Public Health, Harvard University, Boston, MA

Dr. H. Christopher Frey, Professor, Department of Civil, Construction and Environmental
Engineering, College of Engineering, North Carolina State University, Raleigh, NC

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

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

Dr. Helen Suh, Associate Professor, Department of Environmental Health, School of Public
Health, Harvard University, Boston, MA

Dr. Kathleen Weathers, Senior Scientist, Gary Institute of Ecosystem Studies, Millbrook, NY

Enclosure B
                     U.S. Environmental Protection Agency
                    Clean Air Scientific Advisory Committee
                               Ozone Review Panel
Dr. Jonathan M. Samet, Professor and Flora L. Thornton Chair, Department of Preventive
Medicine, University of Southern California, Los Angeles, CA
Prof. Ed Avol, Professor, Preventive Medicine, Keck School of Medicine, University of
Southern California, Los Angeles, CA

Dr John Bailar, Scholar in Residence, The National Academies, Washington, DC

Dr. Michelle Bell, Associate Professor, School of Forestry and Environmental Studies, Yale
University, New Haven, CT

Dr. Joseph Brain, Philip Drinker Professor of Environmental Physiology, Department of
Environmental Health, Harvard School of Public Health, Harvard University, Boston, MA

Dr. David Chock, Retired, Environmental  Modeling Group, Physical and Environmental
Sciences Department, Research and Advanced Engineering, Ford Motor Company, Dearborn,

Dr. William Michael Foster, Professor, Pulmonary and Critical Care Medicine, Duke
University Medical Center, Durham, NC

Dr. H. Christopher Frey, Professor, Department of Civil, Construction and Environmental
Engineering, College of Engineering, North Carolina State University, Raleigh, NC

Dr. Judith Graham, Independent Consultant, Independent Consultant, Pittsboro, NC

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

Dr. Jack Harkema, Professor, Department of Pathobiology, College of Veterinary Medicine,
Michigan State University, East Lansing, MI

Dr. Daniel Jacob, Professor, Atmospheric  Sciences, School of Engineering and Applied
Sciences, Harvard University, Cambridge, MA

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

Dr. Steven Kleeberger, Professor and Lab Chief, Laboratory of Respiratory Biology, National
Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle
Park, NC

Dr. Frederick J. Miller, Independent Consultant, Independent Consultant, Gary, NC

Dr. Howard Neufeld, Professor, Dept. of Biology, Appalachian State University, Boone, NC

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

Dr. Helen Suh, Associate Professor, Department of Environmental Health, School of Public
Health, Harvard University, Boston, MA

Dr. James Ultman, Professor, Chemical Engineering, Bioengineering Program, Pennsylvania
State University, University Park, PA

Dr. Sverre Vedal, Professor, Department of Environmental and Occupational Health Sciences,
School of Public Health, University of Washington, Seattle, WA

Dr. Peter Woodbury, Senior Research Associate, Department of Crop and Soil Sciences,
College of Agriculture and Life Sciences, Cornell University, Ithaca, NY, U.S.A.
Dr. Holly Stallworth, Science Advisory Board Staff Office, Washington, D.C.

Enclosure C

                        Compendium of Individual Comments

                            CASAC Ozone Review Panel

  Integrated Review Plan for the Ozone National Ambient Air Quality Standards Review

                      (External Review Draft, September 2009)

Bell (Dr. Michelle Bell)	7
Bailar (Dr. John Bailar)	8
Chock (Dr. David Chock)	9
Graham (Dr. Judy Graham)	10
Grantz (Dr. David Grantz)	12
Neufeld (Dr. Howard Neufeld)	15
Foster (Dr. W. Michael Foster)	17
Ultman (Dr. James Ultman)	19

Bell (Dr. Michelle Bell)

Overall, the document is very thoughtful, well-written, and clear. The following are some

Please clarify the language regarding susceptible, vulnerable, and sensitive subpopulations.
These terms are used in a variety of contexts in general, so their unique uses here should be
stated explicitly, with examples. These concepts may be particularly confusing for the general
public or others who do not work in fields where such terms are used in the manner in which
EPA intends.  The text should acknowledge whether, or in what cases, these terms are not
mutually exclusive.

Establishing the policy relevant background (PRB) level [see page 39] is by no means trivial,
and the draft Review Plan acknowledges some of these limitations. The Plan notes that greater
emphasis will be placed on understanding the contribution of different components that
contribute to PRB  [see page 40]. However, given the complexities of establishing a PRB and the
wide range of approaches available, it would be helpful to have more information on how the
PRB will be determined and how sensitivity analyses might be conducted. As the document is a
plan, not a detailed methods design, some general information may be appropriate, as opposed to
specifics, although the current document could use more information.

The draft Review Plan acknowledges that the uncertainties involved in this evaluation will
include both qualitative and quantitative factors. Qualitative uncertainties will be categorized by
the approximate degree of uncertainty [see page 42]. This attention to various types of
uncertainties is appreciated, as numerical estimates will not be possible for all uncertainties. The
nature of how uncertainty will be addressed is unclear and could use more explanation. In
particular, how uncertainty analyses will be conducted for concentration-response curves and
threshold effects is vague. Even though not much detail is given on how uncertainties throughout
the system will be addressed, it seems apparent from the Plan that much thought has been given
to this issue. Given that the document is a plan, it may be appropriate to have general
information rather than specifics. Analysis of uncertainties has been conducted by EPA for a
variety of similar settings for other pollutants, such as particulate matter, so references to such
documents may be a helpful way to briefly give some details on the overall planned approach.

Bailar (Dr. John Bailar)
Comments on "Integrated Review Plan for the Ozone National Ambient Air Quality Standards
Review - External Review draft"

Overall, this draft is clear, concise, and nearly complete. I have only a few comments, none of
which require major revisions. These are not in any particular order.

The draft needs a little technical editing.  Also, there is some redundancy, which is a bit
dangerous when things are not repeated in exactly in the same way because persons who want to
bring down bigger things may exploit small differences.

There should be a little more on how variables will be selected for sensitivity testing. Also, there
should be comment on how that testing will be done. In particular, will variables be tested for
sensitivity only one by one, or will the testing examine combinations of variables
simultaneously.  This may matter if there are interactions or other relations among the variables
selected for sensitivity testing.

There should be more on the relation between concentrations of Os at central testing locations
and what people actually inhale in various circumstances (at heavy outside work, in a hospital
bed, walking to school beside a busy highway, driving to work in a closed car, etc.).

Please expand the discussion of the quality of the monitor measurements.

There should be more stress on possible differences in biologic mechanisms between chronic and
acute effects of 03.

I believe that there is only a single, very brief reference to the difference between confounders
and effect modifiers. This is a big issue and needs more exploration.

There has been  a long history of under-regulation by EPA and other regulatory agencies in that
standards often  move down and never up. In  short, future analysts are likely to have evidence
that standards should have been tighter.  EPA may be unable to regulate until pretty good
evidence of an effect is in hand, but the likelihood of a need for change in the future should be

There should be some comment on the difference between individual concentration-response
relationships and population-wide relationships, which are necessarily much flatter in slope
because they are averages of individual relationships.

Similarly, there should be some comment on estimating the effects of a change in regulatory
standard on persons whose exposures is already below the new limit - Some of them will benefit
for efforts to reduce Os in the higher exposure areas, and ignoring that will tend to underestimate
the benefits of regulation.


Chock (Dr. David Chock)

Overall, the IRP was excellently prepared.  I only have a few brief comments to make.

Ch. 3. General comments: In considering the ozone NAAQS, it is important to understand the
role of co-pollutants and climate variables which may impact the outcome of the effects. Some
of these confounders may or may not be controllable. For those that are not controllable, like the
climate variables, the potential changes in their variations in the future (like the regional changes
in climate patterns) need to be taken into consideration in standard setting. I applaud the IRP for
pointing out the need to consider uncertainties and limitations of evidence and assessments in
establishing the standard.
Specific comments: Line 6 on p. 17, "reduce" ought to be changed to "alter" because alternative
levels etc. need not only reduce estimated exposures and risks.

Ch. 4. General comments: Again, the role of climate change needs to be highlighted more since
this will be the reality of the future. Both the effects of tropospheric ozone on  climate change
and the impact of climate change on the ozone health effects on human and the response of
vegetation and ecosystem to ozone exposure need to be explored. Climate change also has an
impact on the PRB concentrations. In particular, increased methane emissions from the
permafrost and increased isoprene emissions from the biosphere with increasing temperature will
have a direct impact on background and regional ozone concentrations, respectively.
Specific comments: The role and bio-mechanism of adaptation (lines 11-12, p. 29) needs to be
explored further.  The literature in this topic may be rather limited but this is the subject that
needs to be better understood. The findings based on use of biomarkers also need to be
explicitly included as a separate bullet point on p. 29.

Ch. 5. General comments: In the human health risk assessments, the validity of using the PRB
concentrations need to be first established.  Most epidemiological studies constructed models
relative to the local mean pollutant concentrations.  The resulting models may not be valid if the
baseline concentrations are shifted, especially in light of the potential adaptation effect.  An
investigation of this approach is necessary to improve the credibility of health risk projections.

Ch. 8. Specific comments:  The statement that "in general, a monitor need not be representative
of the ambient air quality across an area of any specific size to be eligible for comparison to most
NAAQS"  (lines 12-14, p. 65) needs to be qualified. At least, the notion that some rules must be
followed needs to be mentioned.

Graham (Dr. Judy Graham)

Generally, the draft is excellent. Congratulations to the authors for all the thought and hard work
that went into this. My comments hopefully offer some small improvements. Specific
comments follow.
   1.  There are several places that would benefit from a close editorial-level review
   2.  PI5, footnote 7. This defines susceptibility and vulnerability.  The definitions are fine,
       but are they necessary.  They will be difficult to keep track of. Later on, they are
       misused somewhat. Why not just use one term that covers everything.
   3.  P 15-17. This sets out issues and questions. There is a lot of overlap between pi 5 and
       16, but this is a consideration for ease of future IRP's, NOT a request to change this one.
       In any case, both groupings should explicitly call out the question of relative
       contributions of O3, photochemical oxidants, and other co-occurring pollutants to
       observed health effects. Some of this is implied (e.g. pi 6, L26-27), but as the input of
       epidemiology to the O3 NAAQS increases, there is an increasing need to attempt to
       dissect out the O3 contribution to the effects.
   4.  P21,L15.  This section  refers to discussion of "important older studies."  This section
       should be revised since  the language implies that such work will only be "discussed if
       they are open to reinterpretation... and/or to reinforce... conclusions." I strongly disagree
       with what  is written. The NAAQS must rest on the ENTIRETY of the database. The
       newer material contributes in 2 ways: to reinforce the current standard or to show cause
       for a change in the current standard.  Thus, the new material cannot stand alone. Also,
       the tendency will likely be to emphasize newer work, perhaps inappropriately.  For
       example, suppose there  is an "old" body of work showing lung cellular remodeling at 0
       .25ppm and a new study comes along at Ippm showing the same thing. The older work
       should have the discussion space, with the newer work only cited in a table, perhaps.
       One should be able to read the stand-alone document and think about an appropriate
       dose-response (or NAAQS) and not have the knowledge drivers relegated to a table or
       guidance to read the last document.
   5.  P24, L26.  I suggest revision or deletion of this sentence. Indeed it is difficult to
       extrapolate from rats to  humans for SEVERAL reasons, but not one reason (core
       temperatures) as stated here.
   6.  P24, L20ff regarding the cut point for animal studies. I fully support having a Ippm cut-
       off for considering the literature. That level was selected 3-4 CD's ago because it
       captured all the classes of health effects. It greatly simplifies the literature review effort
       and simplifies the text of the document.  The text goes on to say (L29ff):  However, in
       recognition... studies using near  ambient concentrations of O3  or other pollutants do not
       necessarily reflect... sensitive populations, studies at higher exposure levels may be
       included when they provide information [on} unreported effects.. .potential mechanisms,
       .. .exposure-response...  or other wise..." "Additionally, some in vitro studies may
       provide information ...on mechanisms ..." Including papers above Ippm should be
       exceedingly rare (in fact, I would suggest not even spending the time to review them for
       inclusion—you have plenty of work to do otherwise) for several reasons.  In addition, the
       purpose of the IRA is to be brief, so adding discussion of work not relevant to ambient
       defeats that purpose.


       a.  Ippm is NOT near ambient.  It is already very high relative to ambient (justifiably
          so because of extrapolation issue).
       b.  Mechanisms can be extremely important, especially when seeking understanding
          of causality or interpretation of adversity.  However, knowledge of mechanisms
          that will NOT occur at near ambient is only an academic exercise. For example,
          if frank edema occurs at 2ppm, what is the meaning of any mechanism studied at
          that level? Focus on MO As that are operative at near ambient (
Grantz (Dr. David Grantz)

       This document does a nice job of laying out the planned review and staff is to be
commended for this work. I have a few suggestions for improvement.

1.      There is a tendency throughout the document to assume that further review of the
literature will reveal a lower exposure threshold for ozone effects. It may be, but the document
should remain neutral in this regard. For example on page 16, line 2, this should be phrased in
terms of a reevaluation of the threshold rather than a search for effects at lower exposure levels
than previously observed.
       Similarly, the document should avoid value judgments regarding the direction of changes
and simply note the direction and probable magnitude of such changes.  For example on page 20
at the bottom of the table incorporating welfare effects, the phrase "deterioration of property"
could be changed to "effect on property." On page 34, line 18 the reference to "ecosystem stress"
could be changed to "ecosystems effects".

2.      There is a tendency throughout the document to emphasize and even specifically identify
new publications as opposed to older and more solid research findings. It is important that older
data that establish important effects receive appropriate consideration, particularly on vegetation
effects in which much of the literature is older.  On page 21, lines 15-20 it is explicitly stated that
older studies will be specifically discussed if they are open to reinterpretation. A clause should
be inserted here stating that older studies will also be considered if they remain definitive, or
informative in interpreting newer studies, or otherwise relevant to policymaking. For example on
page 57, line 8, staff is correct to focus the review more broadly than on crop yield. However, it
is also important to explicitly recognize that the most complete data regarding vegetative
systems have been obtained with crops. A clause is required here to specify that the agency will
continue to include the crop data in their welfare analysis. On Page 53, line 25-26, staff has
done a good job of referencing the older OTC data obtained during the National Crop Loss
Assessment Network program and it is important that EPA continue to consider these data.
       Along with the inclusion of crop loss data and mechanistic information obtained with
crop species, it is important that the economic analysis envisioned with the FASOM model be
applied at a sufficiently small scale that local variation in air quality is brought to bear on yield
       On page 53, line  8, the Gregg et al 2003 study is a relatively weak example of the
potential power of natural gradient studies. In this case the plants actually grew better in the
more polluted environment.  There are other studies that better capture the implications of
natural gradients, including those dealing with Ponderosa pine in California, that could be cited
       On page 57, line  2, the potential effect of ozone on pollination, through  scent trials and
volatiles emitted by plants, is not yet a well-established effect of ozone and is a poor choice to
single out as an important impact.

3.      Large scale effects on ecological systems should take precedence over smaller scale
effects on individual plants or biochemical systems. For example on Page 22, line 11-13, the
clause "and ecological or welfare effects"  should be moved up  to line 11 following the phrase


"animal toxicological studies". In general throughout the document the smaller scale studies
should be seen as contributing to mechanism plausibility for significance of larger scale
ecological impact. This is analogous to the approach taken for health effects.  Similarly, on page
25, lines 27-29, it is stated that larger scale "ecosystem structure, function, and services" will
also be considered.  These should be primary and not secondary considerations.
       On page 33 line 17 an additional bullet point should be added under ecosystem services
to reflect the effects of climate change. On page 30, top of the page, a bullet point should be
added relating to climate change and interactions with health effects. On page 32, lines 24-29 the
potential ecosystem and other welfare effects should be spelled out in additional detail.  For
example the sentence beginning "this will include evaluation" on line 25 can be amended to read
".. .of ozone exposure on productivity and biodiversity of ecosystems, on yield and quality of
crop systems, and on potential impacts on services such as CO2 sequestration, watershed
protection, wildlife habitat, and greenbelt issues.

4.     On page 49 line 18 the reference to interactions between ozone  and local meteorological
conditions and climate should be modified to specify the types of interactions and their
implications for (presumably) ecosystems effects. Similarly, lines 19 and 20 should better define
what this complex relationship refers to.

5.     Page 49, line 22-26.  The description of the assessment methods and approaches
considered should be amplified considerably, since the current document is the planning
document. It is not optimal to wait for these approaches to be explained in the Scope and
Methods Plan in 2011. Again, on page 55, line 9, as this is the planning document, it is important
to describe briefly how the agency proposes to fill in the gaps in rural ozone monitoring, and
what approaches the agency plans to take for enhancing the fusion of monitoring and modeling
       Page 58, line 13. The issue of monitor  probe height in rural ecosystems is significant but
is not adequately explained here. Additional information is needed on the problems expected
because of height of available ozone measurements, and the expected ramifications with respect
to risk assessment.  Finally any approach that the agency intends to pursue to address this
problem in the admitted absence of sufficient information should be explained here.

6.     Page 54, top of the page. Crop-Risk assessment is not well explained here and how C-R
information will be obtained and applied remain unclear. Similarly on page 54, line 13-14, the
limitations of the AGSIM modeling environment and how the agency proposes to address them
could be more fully explained.
       There are repeated references in this document to the 12 hour W126 metric, but there is
no explanation as to why this metric was chosen over the many others that have been considered.
This needs further explanation (pp. 51, 54).

7.     Page 51, line 21. Reference to the overlap between 8 hour and  12 hour forms of the
standard are unclear. The definition of the overlap is not obvious from the sentence.
       There are inaccuracies on page 53, line 19 and following. The reference to compounding
of effects appears to suggest that these would be more severe in mature trees than in seedlings
and saplings, but actually the reverse is true. Page 56, line 15, the decrease in stream flow in


forested ecosystems referred to in this section depends on total tree water use, not on water use
efficiency.  Water use efficiency is generally defined as the ratio of carbon uptake to water loss
and in itself has no effect on water flow.

8.      Page 64, line 22, it is useful to reference the potential differences in ultraviolet and
chemiluminensence-based monitors. However in this planning document it is important to
describe what these differences may be and the ramifications for interactions with other ambient
contaminants.  In particular this discussion should be used to illuminate the discussion on the
following page regarding the ability of ecosystem scientists to use other types of monitoring
systems that are more portable for description of effects in remote areas.

9.      A few minor comments:
       Page 51 line 5, the phrasing "it under predicted higher" is awkward and should be
reworded. Page 53, line 24 and page 54, line 5~reference to "then" and "at that time" require
some specification of a date. On line 22 the awkward reference to "agricultural crops and fruit
and vegetable species" can be changed to "agronomic and horticultural crop species." Page 55,
line 17, the word "adjust" could be changed to "simulate" or something else that does not
suggest that the basic data are going to be altered. Page 57, line 28, the phrase "will  once more
evaluate" is somewhat negative. The words "once more" can be eliminated.

Neufeld (Dr. Howard Neufeld)

I would like to commend EPA staff for putting out a quality document for our evaluation.
Rather than repeat the comments of my colleagues, David Grantz and Peter Woodbury, I will
detail those items that I picked up on that have not yet been emphasized in their summaries.
However, I will occasionally re-iterate a point to emphasize its importance.

First, just two typos I found:
Pg 15, line 21 - change "susceptible" to "susceptibility"
Pg 24, line 7 - "lag of effects" should be just "lag effects"

Pg 21 -1 agree with Dave Grantz that older studies should be discussed if their work remains
       definitive. As Dave emphasizes, much of the vegetation literature is "older", yet it is still
       the best work done to date.

Although I didn't mention it during the conference call, on page 25, lines 27-28, the document
refers to ecosystem services and functions.  These are never explicitly defined, and perhaps
should be. On page 33, lines 17-20, they are more explicitly laid out, but it seems an eclectic
selection at best. Why were these ones selected?  Are "services" the only ecosystem attributes
that are of consequence? Earlier the document mentions functions. What functions? Should
items such as the tightness of nutrient cycles, energy balances, and so on, be included? These
concepts should be clarified.

On page 51, the document specifies a 12 hr W126 exposure metric.  Dave has already questioned
why this particular metric, and I would add, why only 12 hrs? High elevation ecosystems are
subject to elevated ozone for nearly 24 hrs/day and there is some evidence that plants can open
their stomata  in the dark (or fail to close them), making them prone to ozone uptake at these
times.  Furthermore, there is some suggestion that biochemical defenses may be reduced at night
because of their dependence on current photosynthates in the day.

The overlap comment on line 21 is confusing and should be cleared up.

Gradient studies need careful review. Gregg et al., to their credit, went to great  lengths to try
and pinpoint a lack of ozone as the main factor causing greater growth in a more polluted  area
(due to greater ozone scavenging by NOx in the city).  But gradient studies done in the field,
rather than with potted plants, can  suffer from an inability to assign single-factor causation
because there are  simultaneous multiple environmental gradients that cannot be  statistically
separated. Nonetheless, with proper caution, they can yield some useful information.

When assessing economic risks, we need to consider that farmers may have switched to more
resistant crop varieties,  and that past estimates of the economic impacts of ozone due to lowered
productivity may have to be adjusted. Along these same lines, ozone can have impacts on the
genetic make-up of a population which is not evident to the eye (as foliar injury is, for  example),
so we should  not ignore this hidden cost of ozone. This is particularly important in wild
populations of plants, for which we have little background data on genetic variability.


I further support the use of the NCLAN data since those studies remain perhaps the best multi-
species crop studies done with respect to ozone impacts.

I agree that the oxidation of floral scent story, while intriguing, remains untested at this time, so I
would not overly emphasize it yet. I understand further experiments are being conducted to test
the speculations resulting from those initial studies.

Monitor location and height are important on a local scale, and with forests, impacts will be hard
to assess unless we know the depletion of ozone through the canopy to the forest floor. This
varies with forest type,  season, topography, and so on, and perhaps is an area in need of further

Finally, there may be trends where peak concentrations of ozone are becoming less frequent, and
the baseline ozone is rising, making moderate ozone exposures relatively more abundant.  How
this changing ozone dynamic will affect plant responses (where one mantra has been that the
high ozone concentrations have greater effects than lower ones) is yet to be determined.

Thank you for the opportunity to make these comments.

Foster (Dr. W. Michael Foster)

Summary Comments on Section 5.5.2 Approach to Health Risk Assessment Based on
Controlled Human Exposure Studies

       This section of the document overviews the planned review as staff understands and
appreciates controlled human exposure studies. I have a few suggestions that may be helpful or
perhaps to be taken into consideration.

              Maximal expired volume during the initial second of a forced expiratory
              maneuver from maximum lung capacity (FEVi), is a single mechanical lung
              index, and perhaps the most basic to collect, as an indicator of a health effect.
              This index is the basis  of the analysis proposed in Section 5.5.2.

              Initial acute influences of exposure to ozone in chamber studies upon the airway
              are reflective of airway and lung irritant responses, and not unlike the similar
              effects of many inhaled irritants leading to cough.
               Acute changes in the FEVi have little relationship, nor prognostic value, with
               airway inflammation that results in humans exposed in laboratory studies to
               ozone. This has been known for some time; in fact there is an inverse
               relationship in humans exposed to ozone whereby the smaller the decrement in
               the FEVi mechanical index, the more severe is the ongoing lung and tissue
               inflammation that results.

               Lung and airway inflammation and hyperreactive airways responses, indices and
               outcomes that do not develop acutely, do not correlate with FEVi changes, are
               however present 3 to 30 h post-exposure, and have been demonstrated and
               validated in numerous laboratory studies of humans. These health outcomes are
               of key concern, as represent delayed injury and inflammation to the airway and
               lung, and are appreciated as the major clinical  features leading to emergency
               room visits, and hospitalization that ensue post-exposure during ambient
               exposure to ozone.
               Whether FEVi effects have any relevance, and/or airway and lung effects
               related to tissue inflammation and bio-marker responses, are more reflective of
               exposure to ozone, it is now completely accepted that host (genetic) factors have
               higher indices of success for predicting human susceptibility to adverse health
               response. Identifying host factors with relevance and predictability to health
               outcomes would enable risk assessment of the population.

               Endeavors or sponsorship to model mechanical and irritant derived effects (i.e.,
               FEVi) from previous laboratory studies as proposed in Section 5.5.2., would


seem to have little value or impact with regards to protecting segments of the
population. Validity and reproducibility of human laboratory exposure studies to
date, with genetic, pulmonary inflammatory, and airway reactivity outcomes, are
more supportive of a basis for advice/consultation as EPA re- reviews a policy
plan for action.

Ultman (Dr. James Ultman)

This document is well-organized and clearly written.  I especially appreciated the summary of
the previous exposure and risk assessment that the new review will be build on.  Most of my
comments regard some details that I  feel should be  added to  the IRP.   My only technical
suggestion (and it is a general one) is that any new method that is used for analysis in the risk
assessment be validated.
Detailed Comments

Page   Lines

21     15-16    What will form the basis of reinterpretation of the older studies? Given the
importance of clinical studies at low exposure levels, it would be particularly useful to perform
meta analyses that include all (new and old) relevant data sets.

22     17-21    Please give the specific cut-off date for inclusion of new studies.

24     17       State the specific populations that will be studied. How were these population

27     11-13   Please give a short list of oxidants that will be  considered in addition to ozone.

40     28-29      What  approaches in addition  to the  quadratic roll-back method will be
considered.  How will the quadratic roll-back and other possible approaches be validated?

41     17-18    Why do cities in the Northwest appear to be excluded from consideration?