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»J I J^L 1 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
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WASHINGTON, D-C, 20460
EPA-SAB-CASAC-9 1-015
July 17, 1991
OFFICE OF
The Honorable William K. Reilly
Administrator
U.S. Environmental Protection Agency
401 M Street, SW
Washington, DC 20460
Dear Mr. Redly:
At a public meeting held on April 30, 1991, the Clean Air Scientific Advisory
Committee (CASAC) completed its review of the draft EPA Air Quality Criteria for
Carbon Monoxide dated March 1990. The Committee unanimously concluded that
this document, with minor revisions (currently being incorporated by ECAO Staff).
provides a scientifically balanced and defensible summary of the current knowledge
of the effects of this pollutant and provides an adequate basis for the EPA to
make a decision as to the appropriate primary NAAQS for carbon monoxide.
The first external review draft of this document was released for public
comment on April 30, 1990 with the comment period ending on July 31. 1990.
CASAC is pleased with the responsiveness of ECAO in producing a comprehensive,
well-written document to support Agency decision-making. For the record, I have
attached brief responses to the major issues which were addressed in the
Committee charge.
The CASAC is ready to review the Staff Paper on Carbon Monoxide as soon
as it is available. The Committee urges the Agency to move forward as rapidly as
possible with completion of the Staff Paper and. ultimately, the issuance of a
reaffirmed or revised NAAQS for carbon monoxide based on the current scientific
data.
We appreciate the opportunity to present our views on this Important
environmental health issue.
Sincerely,
Roger O. McCIellan
Chairman, Clean Air
Scientific Advisory Committee
Attachment
Printed en Retried Paper
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Clean Air Scientific Advisory Committee
Review of
Draft Air Quality Criteria for Carbon Monoxide
On April 30, 1991, the Clean Air Scientific Advisory Committee convened
to review the draft document Air Quality Criteria for Carbon Monoxide, dated
March 1990. Development of this document stems from requirements of section
108 of the Clean Air Act. This section requires that the Administrator identify
pollutants that may reasonably be anticipated to endanger public health or
welfare and to issue air quality for them. These criteria must incorporate the
latest scientific information available to indicate the type and extent of
identifiable effects that may occur from exposure to the pollutant in ambient air.
Section 109 of the Act requires periodic review/revision of existing
criteria and standards. If the Administrator concludes that the revised criteria
make appropriate the proposal of new standards, such standards are to be
promulgated in accordance with section 1Q9(b). Conversely, if the Administrator
concludes that the revisions to the standards are unnecessary, they remain
unchanged.
In accordance with the Clean Air Act, EPA's Environmental Criteria and
Assessment Office is revising the criteria for carbon monoxide, incorporating
new data which have become available since the completion of the last criteria
document (1979) and the addendum to that document (1984).
The draft carbon monoxide document review consisted of a chapter by
chapter review and focused on addressing the following issues:
1) What method of analysis of blood carboxyhemogtobin levels, optical or
gas chromatography, should be used to determine lowest observed adverse
effect levels for CO? Should end-exposure or end-exercise COHb levels be
used as an input to the exposure models of COHb formation developed by
Coburn, Foster and Kane?
Due to the large amount of variability in spectroscopic measurement of
carboxyhemoglobin by CO oxymeters, gas chromatography should be the
method of choice.
Coburn-Foster-Kane-based models yield the expectant net increase in
COHb for a given exposure to CO (concentration and duration), and the level of
activity/exercise (alveolar ventilation and diffusing lung capacity for CO). Input
to the model requires the preexposure COHb level, with the post exposure level
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predicted by the modeL The model does not accurately predict the rate of
appearance of COHb at the blood sampling point because of the lag in the
delivery of CO due to lung washing and blood circulation factors,
2) How important is tissue action of CO, given the likelihood of typical
ambient exposures of the population to low levels of CO for 1 to 8 hours in
duration?
Although it is difficult to expand on the information contained within the
document, it should be noted that elevated levels of CO, particularly from bolus
exposures, may potentially affect the electron transport chain. Also, some
studies conclude that CO dissolved in plasma is more dangerous than elevated
COHb levels. Low levels of dissolved CO may be significant in cellular
respiration.
3) What fraction of the total population with ischemic heart disease (IHD) is
represented by the study populations used in the recent key clinical
investigations of Sheps, et al. (1987), Adams et al. (1988), Kleinman et al.
(1989) and Allred et al. (1989)?
The study by Allred et al. and the Coronary Artery Surgery Study
(CASS) provide a wide representation of patients with ischemic heart disease,,
and the CASS study is a good source of information on the variability of
characteristics of IHD (almost 25,000 patients enrolled). All subjects studied for
the effects of CO fall within this variability. However, since no Coronary Artery
Disease (CAD) registry was developed for the CO studies, coupled with the
change in characterization of CAD in recent years, it is difficult to assess the
representativeness of the study populations,
4) Were appropriate statistical analyses used in the key studies on subjects
with IHD? Should there be a more rigorous comparison of statistical
approaches, including discussion of primary versus secondary analyses, use of
trimmed or non-trimmed means, and choice of one- or two-tailed tests of
significance? Could other formal techniques (meta-analysis) be used to
provide a better assessment of data?
The analyses provided in the document were adequate and appropriate.
In general statistical analyses need not be uniform, but should be tailored to the
data being collected, and the distinction between one- and two-tailed tests is
insignificant, Meta-analysis is useful, but graphic presentations such as those
provided in figure 10-2 are satisfactory. However, error bars should be
highlighted and made a common basis for data presentation.
5) Could differences in the study designs utilized in the key studies on the
subjects with Ischemic Heart Disease account for some of the differences in the
results?
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It is unlikely that variations in study design resulted in variations in
results. The protocols for each study are described in sufficient detail and the
authors have done an excellent job of presenting and interpreting the results.
6) Are the small changes reported in the key studies on subjects with
Ischemic Heart Disease of clinical significance? What Is the definition of an
adverse health effect in this population?
There is a wide distribution of opinion concerning this issue. The panel
agrees that the effects observed at these levels are small performance
decrements and that they are consistent across the populations studied. It is
important to note that the ST segment changes and decrements in the time to
onset of angina appear to be a consistent response to low levels of CO
exposure. Among health professionals there is a range of views as to the
clinical significance of these changes with the dominant view being that the
changes should be considered as adverse or a harbinger of adverse effects.
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