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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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