August 10, 1999
EPA-SAB-CASAC-LTR-99-003
Honorable Carol M. Browner
Administrator
U.S. Environmental Protection Agency
401 M Street SW
Washington, DC 20460
RE: C ASAC Review of the Draft Document Air Quality Criteria for
Carbon Monoxide (EPA/600/P-99/001)
Dear Ms. Browner:
The Clean Air Scientific Advisory Committee (CASAC) of EPA's Science Advisory
Board, supplemented by expert consultants (together referred to as the "Panel"), met on June 9,
1999 to review the February 1999 draft document, Air Quality Criteria For Carbon Monoxide
(EPA/600/P-99/001), in a public meeting in Research Triangle Park, NC. This was the first draft
of the new carbon monoxide (CO) Criteria Document since publication of the last CO Criteria
Document in 1991, as part of the review of the National Ambient Air Quality Standards
(NAAQS) for CO.
1. SUMMARY
As expected for a first draft of a Criteria Document, the Panel expressed the unanimous
view that the document required revision and re-review by CASAC before it could constitute an
adequate statement of the current scientific knowledge as a basis for reviewing the
appropriateness of the existing CO NAAQS.
The Panel complimented EPA personnel (referred to as "Staff) for its good work in
developing a high-quality first draft of a Criteria Document. Although attention must be given to
numerous issues raised by the Panel in order for the document to be acceptable, the extent of the
required revisions is modest and should be readily within the Staffs reach. The Panel especially
complimented Staff for following through with the agreed-upon plan to focus on how new
information might alter previous views of the effects of CO, rather than developing an exhaustive
compilation of historic information.
The Panel recommended that information be added on the evolution of CO oximetry and
its impact on interpretation of results, the implication for standard setting of the involvement of
CO in ozone chemistry, interspecies differences in CO toxicokinetics, and potentially susceptible
subpopulations. It noted the need for more analytical treatments of CO measurement methods,
current health effects data, and uncertainties regarding both exposures and health risks.
Additional recent literature on CO epidemiology and certain other topics was recommended for
inclusion. The Panel questioned the emphasis given to information on acute high-level exposures
and the health effects of CO poisoning, and the lack of justification given for its inclusion. It was
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recommended that each chapter contain a summary of whether or not, and how, new information
changes previously-held views of CO exposures and their health impacts. The Panel raised a
broad range of other specific issues and editorial points that also need to be addressed
The Panel envisions no substantive barrier to the development of an acceptably revised
CO Criteria Document and looks forward to the opportunity to review a revised document.
2. CHARGE TO CASAC
When queried at the end of the discussion of the document on June 9, Staff noted that it
felt that the charge questions had been adequately addressed by the discussions and the Panel's
comments. Accordingly, only selected summary responses to the charge questions are given
here.
2.1 Coverage - Are all pertinent issues adequately discussed? Are there any additional
issues that should be addressed in the document?
The coverage of general issues is complete. The Panel noted four specific issues that
were either omitted, or discussed inadequately:
a) The potential effect of the evolution of technology for CO-oximetry and the
variability in results among instruments on interpretation of the literature (Chapter
2).
b) The implications of the involvement of CO in ozone chemistry for standard
setting; ie, justification for its inclusion in this document (Chapter 3).
c) Advances in our understanding of the amount and variability of contributions by
vehicle emissions to general and roadside CO levels (Chapter 3).
d) The existence and implications of interspecies differences in CO
pharmacokinetics (Chapter 5).
e) Potentially important susceptible subpopulations (Chapter 6).
2.2 Scientific Relevance - Is the material focused and pertinent, given the subject matter
and scope of the document? Does the material provide EPA with the kind of critical review
and sound data useful for decisionmaking on the CO NAAQS?
The material is relevant to consideration of the CO NAAQS, and is generally reasonably
focused. Numerous of the Panelists' specific comments recommended improved focus on
specific points. The Panel noted general needs for more analytical approaches to presenting
information on measurement methodologies in Chapter 2 and on health effects in Chapter 6, and
extracting key conclusions. With revisions adequately addressing the Panel's comments, the
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document will provide a sound scientific basis for consideration of the appropriateness of the CO
NAAQS.
2.3 Scientific Accuracy - Is the material presented accurately, irrespective of other
shortcomings?
No circumstances of factually inaccurate material (other than points of minor editorial
difficulties) were noted by the Panel. On the other hand, the Panel viewed the discussions in
some areas as falling short of accurately portraying the nature and magnitude of current
uncertainties. Points in this regard were raised in Chapters 3, 4, 5 and 6.
2.4 Literature Cited - Are there any major or important omissions of pertinent literature?
The panel recommended that Staff attempt to reduce the reliance on non-peer reviewed
literature in Chapter 3. The extent to which appropriate peer-reviewed literature might have
been overlooked was not clear. Specific suggestions were given for adding overlooked literature
to Chapter 6.
2.5 Emphasis - Is the length and level of detail appropriate, given the relative importance
of the topic in the document?
The length of the document is appropriate, and the Panel commends Staff for focusing on
the extent to which recent findings alter views held at the time the last CO Criteria Document
was written. The level of detail is generally appropriate, although additional detail on specific
points is recommended in the Panel's comments. The Panel questions the emphasis given to
high-level CO exposures and the effects resulting from acute CO "poisoning". It is not apparent
that this information warrants the attention it received in the draft document.
2.6 Organization and Writing - Is the document appropriately organized to address the key
issues/topics covered? Is the document written clearly and concisely? If not, how might it be
better organized or written?
In general, the document is organized appropriately. Although minor organizational
changes were recommended in specific places, the major sections and subsections follow in
appropriate order. With revision to address the Panel's comments, the document will constitute
an appropriately clear and concise summary of the current scientific knowledge regarding CO
exposure and health risks.
The Panel recommends that, as the revisions are made, Staff review each chapter and
integrative section to ensure that clear summary statements are made regarding whether, and
how, new information has changed previously-held views of CO exposures and health risks.
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3. COMMENTS BY CHAPTER
Only selected points are summarized below; no attempt is made to recapitulate all of the
Panelist's comments. Numerous other points are raised in the comments of individual Panel
members (Please see Appendix A) and the transcript of oral comments during the June 9, 1999
meeting. The appended comments are considered an integral part of the Panel's report, and Staff
is urged to review them to develop a fuller understanding of the following points, and to note
other issues which should also be given consideration, but are not summarized herein.
It should be noted that, although the following comments intentionally focus on criticisms
and suggested changes, the Panel made numerous positive statements about the draft document,
as reflected in both their written comments and the meeting transcript.
3.1 Chapter 1: Introduction
The Panel spent little time discussing the Executive Summary and Chapter 1. The
structure and scope of these sections were considered appropriate. Some specific points were
raised by individuals in written and oral comments. In general, these Sections appropriately
introduce the document and portray appropriate summary information. It is anticipated that
these sections will be reviewed carefully for changes needed to reflect revisions of the following
material.
3.2 Chapter 2: Analytical Methods
Although the chapter contains a useful review of various measurement methods, it does
not engage in an adequate evaluative comparison of the methods. Additional statements
regarding the method(s) currently considered most effective for each measurement purpose
would be useful. Comment on the utility of existing personal CO monitors and brief guidance for
researchers conducting exposure assessments would be useful additions. Staff is advised to
inquire about the status and potential usefulness of infrared-based remote sensing methods for
obtaining average area concentrations for exposure assessment.
The subject material in Sections 2.2 and 2.4 seem duplicative, and might be combined.
There has been considerable development in CO-oximeter instrumentation over the years,
and the different methods can yield different results. This issue should be described in chapter 2,
and the type of instrument should be given throughout the document when "CO-Ox" results are
presented.
3.3 Chapter 3: Sources, Emissions, and Concentrations
This chapter stands out from others in the document by citing numerous papers presented
at meetings and unrefereed proceedings, as well as several technical reports of uncertain peer-
review history. As an example, some important conclusions are drawn from the 1997 workshop
proceedings published as an EPA document. Although this issue does not denigrate the accuracy
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or usefulness of information communicated in proceedings, it would be best to rely on peer-
reviewed publications to the extent possible, perhaps noting which, if any, of the material
presented in meetings is in press in peer-reviewed journals.
It is not clear to the non-atmospheric scientist how "mixing ratio" differs from
"concentration", or if it does not, why consistent terminology is not used throughout the
document.
In the discussion of the potential reversal of the global decline in CO, the portrayal of the
situation and its causes should be inclusive and tentative, taking care not to under-emphasize the
uncertainty involved.
The discussion of the relative contributions of CO from human activity and other sources
needs some clarification. From the information given, it is not clear that anthropogenic CO
actually constitutes 80% of global CO as stated.
The context of the discussion of the involvement of CO in ozone chemistry is not clear.
Although the chemistry facts are convincing, it is not clear what policy implications might extend
from the relationship, or if none are intended, why so much space is dedicated to the discussion.
The discussion of the atmospheric lifetime of CO could use clarification. The importances of
temperature, deposition rates, and volumetric uptake by soil need clarification.
The considerable improvement since the last Criteria Document in our understanding of
the contribution of engine emissions to general and roadside CO levels is not adequately
portrayed. The relative contributions of different vehicle categories, the variability among in-use
vehicles, and potential differences between predictions from certification testing and actual on-
road emissions should be discussed in more detail.
The material in Section 3.4 is important, but the space given to the related material in
Appendix 3 A is questionable. The appendix might best be eliminated and the most relevant
elements of that information moved into section 3.4 in condensed form.
It is not clear that the extensive discussion on indoor exposures warrants the relative
weight given to the material in the chapter. Conversely, additional attention might be given to in-
vehicle, roadway, and streetside microenvironments, in which people also spend a great deal of
time. The CO exposures in these microenvironments is probably not well-represented by
concentrations at area monitors, even though the CO sampled by are a monitors may be
dominated by contributions from mobile sources.
3.4 Chapter 4: Population Exposure
Although the focus on information developed since the last Criteria Document is
appropriate, it would be useful to present a succinct summary of historic population exposure
levels in different environments as a jumping off point for the updated discussion. It would also
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be useful to add some figures or tables to the subsequent sections to give perspective on actual
contemporary exposure levels in different environments and among different segments of the
population.
The basis for the considerable emphasis given to high-level CO exposures that lead to CO
poisoning is not intuitive, and is not made clear. The relevance of these exposures to risks over
which the Agency has some purview is questionable. If this pattern is to be followed for other
pollutants, for example, one would expect discussions of occupational dust-induced
pneumoconioses in the next particulate matter Criteria Document. These scenarios do not
approach the significance of general indoor exposures in terms of person-hours. Similarly, the
relevance of California's no-smoking policy is not made clear.
The discussion of exposure models presents the model components clearly, but does not
adequately discuss where the inputs come from, the nature and magnitude of likely error, or the
relative merits of different models.
3.5 Chapter 5: Pharmacokinetics and Mechanisms
The factors involved in the uptake and elimination of CO are described adequately, but
the information on the distribution of the body burden of CO and the exchange between
compartments needs strengthening. A table showing the distribution of CO mass in different
compartments at an example exposure level would help place the contribution of endogenous CO
and the tissue concentrations relative to blood concentration in a clearer context. The examples
should be quantitative.
Although information in the chapter is drawn from both humans and animals, there is no
mention of interspecies differences in CO uptake kinetics. The rate of uptake at a given
exposure is known to differ considerably between rodents and humans, and this difference is
certain to impact on the applicability of information from rodents to humans. This issue must be
discussed.
The relevance of the information on mechanisms and effects given in Sections 5.7 and 5.8
to mechanisms and effects expected from ambient exposures is not stated, and should be
discussed.
As described in detail in written comments and the meeting transcript, several points
regarding the interrelationships among the pharmacokinetics of CO at ambient doses,
physiological processes, and physiological clinical measurements need clarifying.
3.6 Chapter 6: Health Effects
Although the chapter appropriately avoids an exhaustive historical review of
epidemiological studies, the review of more recent studies is not sufficiently complete. Four
studies in particular, published during 1991 - 1999 and listed in Dr. Vedal's attached comments,
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should be included. The inclusion of a table of epidemiology studies listing a few key features
would help summarize the information. The present text descriptions of the studies vary
considerably in their level of detail and the features they discuss. For both the epidemiological
and non-epidemiological literature, the present text does not make it clear whether no more
literature had been published since 1991, or additional literature existed but was not considered
worthy to cite.
The description of the health effects data base is not sufficiently analytical. The validity
of the studies with respect to our knowledge of CO health effects should be discussed, and the
information should be placed in context regarding their utility in judging the adequacy of the CO
standard. For example, some recent studies suggest that the epidemiological findings are not
consistent and others appear to weaken the argument for specificity of effect. For some health
effects, the present text does not adequately compare the strengths of the individual studies, or
portray the balance of studies having positive and negative findings. There should be more
discussion of the status of our ability to determine the extent to which the effects ascribed to CO
may result from its being strongly correlated with other pollutants. More discussion of
measurement error and its potential implications for interpreting the studies would be
appropriate. Discussion of the biological plausibility of the relationship between ambient CO and
non-cardiac effects should be included. The degree of uncertainty in our understanding of the
effects of CO on the developing fetus is not adequately portrayed. Other examples of the need
for a more analytical presentation are presented in the attached comments.
Several difficulties with the comparison of data from rats and humans in Figure 6-3 were
raised and are noted in the individual comments and transcript. The Figure and accompanying
explanation need either extensive revision or elimination.
3.7 Chapter 7: Integrative Summary and Conclusions
For many topics, this chapter does a reasonable job of integrating the foregoing
information. Because this chapter is intended to integrate and summarize key aspects of
preceding information, attention will need to be given to the extent to which changes influencing
interpretations or conclusions in preceding chapters will necessitate changes here.
It is not apparent that the information presented in Sections 7.6 and 7.7 on health effects
and susceptible populations represents the most appropriate summary and integration of the
information presented in Chapter 6. The balance between presentation of acute, high-level
effects and effects of lower ambient exposures is questionable. As noted before, it is not clear
that the information on CO poisoning is central to understanding health risks from environmental
exposures. The issue of susceptibility is raised in this chapter in greater detail than before.
Although susceptibility is an important topic for integration, it would seem appropriate to include
more detail on susceptible populations in Chapter 6, as a platform from which to extract key
points in Chapter 7. The more detailed information in the preceding chapter could clarify the
extent to which our current view of potential susceptible populations is speculative.
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4. CONCLUSIONS
The Panel was unanimous in its opinion that the document needs revision and re-review
by CASAC.
The Panel was complimentary of the document as a first review draft, and supportive of
the focus of the present document on updating our information on exposures and health risks
from CO since publication of the last Criteria Document. With revision along the lines suggested
by the Panel's comments and discussions with Staff at the meeting, the document can represent
an adequate synthesis of the present scientific information on CO, and serve as an adequate basis
for the Agency's development of a Staff Paper focused on the appropriateness of the present CO
NAAQS.
We appreciate the opportunity to review this draft document and to provide comments
and advice to the Agency. We look forward to your response.
Sincerely,
Dr. Joe L. Mauderly, Chair
Clean Air Scientific Advisory Committee
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U.S. Environmental Protection Agency
Science Advisory Board
Clean Air Scientific Advisory Committee (CASAC)
CASAC Carbon Monoxide Review Panel
Chair
Dr. Joe Mauderly, DVM, Director of External Affairs, Senior Scientist, and Director of National
Environmental Respiratory Center, Lovelace Respiratory Research Institute, Albuquerque, NM
Members
Mr. John Elston, Administrator, Office of Air Quality Management, State of New Jersey, Department of
Environmental Protection and Energy, Trenton, NJ
Dr. Philip K. Hopke, R.A. Plane Professor of Chemistry, Clarkson University, Potsdam, NY
Dr. Eva J. Pell, Steimer Professor of Agriculture Sciences, Buckhout Laboratory, The Pennsylvania State
University, University Park, PA
Dr. Arthur C. Upton, M.D., Director, Independent Peer Review, CRESP, Environmental and
Occupational Health Sciences Institute, Piscataway, NJ
Dr. Sverre Vedal, M.D., Professor of Medicine, Vancouver General Hospital, Vancouver, BC Canada
Dr. Warren White, Senior Research Associate, Washington University, Chemistry Department, St. Louis,
MO
Consultants for Carbon Monoxide NAAQS Review
Dr. Stephen M. Ayres, M.D., Director, International Health Programs, Virginia Commonwealth
University/Medical College of Virginia, VA
Dr. Thomas E. Dahms, Professor and Director, Anesthesiology Research, Department of
Anesthesiology, St. Louis University School of Medicine, St. Louis, MO
Dr. Victor G. Laties, Professor Emeritus, Department of Environmental Medicine, University of
Rochester Medical Center, Rochester, NY
Dr. Brian Leaderer, Professor, Division of Environmental Health Sciences, Yale University School of
Medicine, New Haven, CT
Dr. Lawrence D. Longo, M.D., Professor, School of Medicine, Department of Physiology, Center for
Perinatal Biology, Departments of Physiology and Gynecology and Obstetrics, School of
Medicine, Loma Linda University, Loma Linda, CA (did not attend this meeting)
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Science Advisory Board Staff
Mr. Robert Flaak, Designated Federal Officer (DFO) and Team Leader, Committee Operations Staff, US
Environmental Protection Agency, Science Advisory Board (1400), Washington, DC 20460
Ms. Diana Pozun, Management Assistant, US Environmental Protection Agency, Science Advisory Board
(1400), Washington, DC 20460
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NOTICE
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Additional copies and further information are available from the SAB Staff.
in
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