UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

SEP 2 5 2009 THE ADMINISTRATOR 

Dr. Joseph D. Brain 

Chair, Carbon Monoxide Review Panel 

Dr. Jonathan M. Samet 

Chair, Clean Air Scientific Advisory Committee 

Science Advisory Board (1400F) 

U.S. Environmental Protection Agency 

1200 Pennsylvania Avenue, N. W. 

Washington, D.C. 20460 

Subject: Clean Air Scientific Advisory Committee's Peer Review of the U.S. Environmental 

Protection Agency's Integrated Science Assessment for Carbon Monoxide (First 

External Review Draft, March 2009) 

Dear Drs. Brain and Sarnet: 

Thank you very much for your letter about the Clean Air Scientific Advisory Committee 

Carbon Monoxide Review Panel's May 12 and 13,2009, review of the EPA's Integrated Science 

Assessment for Carbon Monoxide (First External Review Draft). EPA greatly appreciates the 

CASAC Panel's time and thorough review of the draft ISA. 

We are in the midst of revising the draft CO ISA and anticipate providing CASAC and 

the public with a second draft by late September 2009. Our revisions to the document will give 

full consideration to the CASAC's comments and the recommendations and responses to charge 

questions in your letter, as well as to the individual comments from CASAC panel members and 

the public. When we complete the second draft, we will provide a more detailed summary of the 

revisions, similar to the summary of changes we recently provided to CASAC for the second 

draft Particulate Matter ISA. 

Some of the more substantial changes planned for the second External Review Draft of 

the CO ISA include: 

Expanded discussion and clarification of the criteria for assessing the scientific quality 

and relevance of epidemiologic, controlled human exposure and toxicological studies, 

and for the interpretation and integration of study results to draw conclusions on 

causality; 

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In the integrative discussion of CO-related health effects, further evaluation of the 

evidence and discussion of the challenges faced in distinguishing the independent 

effects of CO fiom those of other pollutants in urban air, particularly in interpretation 

of epidemiologic study findings; 

Revised and expanded characterization of intra-urban spatial variability to focus more 

explicitly on CO monitors located at various distances from major urban sources, 

particularly roadways; 

Description of the differing capabilities for detecting low-level CO concentrations 

with the newer trace-level CO monitors in comparison with the detection capabilities 

of the standard monitors that predominate in the network. Discussion will also be 

added on the effect of monitoring limitations on exposure measurement error and its 

relevance for interpretation of epidemiologic study results; 

Incorporation of additional details in the discussion of CO's atmospheric chemistry 

and physics relating to its role in climate forcing; 

Inclusion of a summary in the health effects chapter (Chapter 5) to encapsulate 

information on relevant CO health effects; and 

Revised discussion of the evidence on potentially susceptible subpopulations, with 

emphasis on information regarding individuals with preexisting conditions, 

particularly cardiovascular disease. The ISA will more fully characterize potential 

modification of the consequences of ambient CO exposure by factors such as activity 

patterns and exposure to CO from nonambient or endogenous sources. 

Again, my thanks to you and the CASAC panel members for your review of the draft 

ISA. Your advice and detailed comments have been very valuable in guiding EPA's revisions to 

the draft ISA. The CASAC panel's work will help ensure that the best science is used in 

informing the regulatory process. 

Sincerely, 

Lisa P. Jackson 

cc: Holly Stallworth, DFO for chartered CASAC 

Ellen Rubin, DFO for CASAC CO Review Panel 

CASAC CO Review Panel