Responses to Significant Comments on the 

2011 Proposed Rule on the 

National Ambient Air Quality Standards 

for Carbon Monoxide 

(February 11, 2011; 76 FR 8158)

Docket Number EPA-HQ-OAR-2008-0015

U.S. Environmental Protection Agency 

 August 2011 

 
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i 

Table of Contents 

Frequently Cited Documents .......................................................................................................... ii 

I. INTRODUCTION ........................................................................................................................1 

II. RESPONSES TO SIGNIFICANT COMMENTS ON PROPOSED RULEMAKING FOR 

 CARBON MONOXIDE NAAQS ..................................................................................................2 

 A. Comments on Primary Standards ....................................................................................2 

 1. Support for Proposed Decision to Retain the Current Standards ...............................2 

 2. Comments Recommending Revision of the Current Standards ..............................3 

 3. Comments on Evidence-based Considerations .........................................................4 

 4. Comments on Exposure and Risk Considerations ..................................................15 

 5. Additional Comments on the Interpretation of Scientific Evidence ......................24 

 6. Additional Comments on the Exposure and Risk Assessment ...............................37 

 B. Comment on Consideration of a Secondary Standard .................................................40 

 C. Comments Related to Monitoring .................................................................................41 

 1. Sampling and Analysis Methods ...........................................................................41 

 2. Near-Roadway Monitors .........................................................................................44 

 3. Other Locations .......................................................................................................48

 4. Other Monitoring Comments ..................................................................................50 

III. RESPONSES TO SIGNIFICANT COMMENTS RELATED TO IMPLEMENTATION 

OF STANDARDS .........................................................................................................................52 

 A. DESIGNATIONS ........................................................................................................52 

 B. OTHER.........................................................................................................................52 

IV. RESPONSES TO SIGNIFICANT COMMENTS RELATED TO EXCEPTIONAL 

EVENTS ..........................................................................................................................55 

V. RESPONSES TO LEGAL, ADMINISTRATIVE, AND PROCEDURAL ISSUES AND 

MISPLACED COMMENTS .........................................................................................................55 

 

VI. REFERENCES .......................................................................................................................59 

APPENDIX A ..........................................................................................................................63 
ii 

Frequently Cited Documents

The following documents are frequently cited throughout this response to comments 

document, often by means of the short names listed below: 

Preamble to the final rule: 

Preamble to the Final Rule on the Review of the National Ambient Air Quality Standards 

for Carbon Monoxide: Final Rule. To be published in the Federal Register in August or 

September, 2011. 

Proposal: 

National Ambient Air Quality Standards for Ozone: Proposed Rule. 76 FR 8158, 

February 11, 2011. 

2010 Integrated Science Assessment (ISA): 

U.S. Environmental Protection Agency (2010a) Integrated Science Assessment for 

Carbon Monoxide (Final). Washington, DC, EPA/600/R-09/019F. Available online at: 

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=218686

Risk and Exposure Assessment (REA): 

U.S. Environmental Protection Agency (2010b) Quantitative Risk and Exposure 

Assessment for Carbon Monoxide - Amended. July 2010. Office of Air Quality Planning 

and Standards, Research Triangle Park, NC. EPA Report no. EPA-452/R-10/009. 

Available online at: http://www.epa.gov/ttn/naaqs/standards/co/data/CO-REA-AmendedJuly2010.pdf

Policy Assessment (PA): 

U.S. Environmental Protection Agency (2010c) Policy Assessment for the Review of the 

Carbon Monoxide National Ambient Air Quality Standards. October 2007. Office of Air 

Quality Planning and Standards, Research Triangle Park, NC. EPA report no. EPA452/R-10-007. Available online at: 

http://www.epa.gov/ttn/naaqs/standards/co/data/20101022copafinal.pdf
 1 

Responses to Significant Comments on the 2011 Proposed Rule 

on the National Ambient Air Quality Standards 

for Carbon Monoxide 

I. INTRODUCTION

This document, together with the preamble to the final rule on the review of the 

national ambient air quality standards (NAAQS) for carbon monoxide (CO), presents the 

responses of the Environmental Protection Agency (EPA) to some of the public 

comments received on the 2011 CO NAAQS proposal notice (76 FR 8158). All 

significant issues raised in timely public comments have been addressed. Where 

comments were submitted after the close of the public comment period, EPA responded 

to the extent practicable. 

Comments were received from two organizations of state and local air agencies 

(National Association of Clean Air Agencies [NACAA], and Northeast States for 

Coordinated Air Use Management [NESCAUM]), approximately 12 State and local 

government agencies, and a council of local governments (Southeast Michigan Council 

of Governments [SEMCOG]); the American Thoracic Society and approximately 10 

environmental or public health organizations or coalitions; three industry organizations 

(Alliance of Automobile Manufacturers [AAM], American Petroleum Institute [API], and 

American Electric Power Service Corporation [AEPSC]); an organization of state 

highway officials (American Association of State Highway and Transportation Officials 

[AASHTO]); several individuals and a group of approximately 100 individuals. 

This response-to-comments document does not generally cross-reference each 

response to the commenter(s) who raised the particular issue involved, although 

commenters are identified in some cases where they provided particularly detailed 

comments that were used to frame the overall response on an issue. 

 

 The responses presented in this document are intended to augment the responses 

to comments that appear in the preamble to the final rule or to address comments not 

discussed in the preamble to the final rule. Although portions of the preamble to the final 

rule are paraphrased in this document where useful to add clarity to responses, the 

preamble itself remains the definitive statement of the rationale for the revisions to the 

standards adopted in the final rule. 

In many instances, particular responses presented in this document include cross 

references to responses on related issues that are located either in the preamble to the CO 

NAAQS final rule, or in this 2011 Response to Comments document. All issues on 

which the Administrator is taking final action in the CO NAAQS final rule are addressed 

in the CO NAAQS rulemaking record. 
 2 

 Accordingly, this Response to Comments document, together with the preamble to 

the CO NAAQS final rule and the information contained in the Integrated Science 

Assessment (EPA, 2010a), the Risk and Exposure Assessment (EPA, 2010b) and the 

Policy Assessment (EPA, 2010c), and the Notice of Proposed Rulemaking should be 

considered collectively as EPA’s response to all of the significant comments submitted 

on EPA’s 2011 CO NAAQS proposed rule. This document incorporates directly or by 

reference the significant public comments addressed in the preamble to the CO NAAQS 

final rule as well as other significant public comments that were submitted on the 2011 

proposed rule. 

 Consistent with the final decisions presented in the notice of final rulemaking, 

comments on the CO standards are addressed in sections II.A and II.B. Comments on 

monitoring are addressed below in section II.C. Comments on implementation are 

addressed in III. Comments on exceptional events are addressed in section IV. Section 

V includes responses to legal, administrative, procedural, or misplaced comments. 

II. RESPONSES TO SIGNIFICANT COMMENTS ON PROPOSED

RULEMAKING FOR CARBON MONOXIDE NAAQS

A. Comments on Primary Standards

General comments based on relevant factors that either support or oppose retention of the 

current CO primary standards are addressed in section II.B of the preamble to the final 

rule and/or in sections II.A.1 and II.A.2 of this document below. Additional comments 

about the health effects evidence and the REA are addressed in sections II.A.3-5 below. 

1. Support for the Proposed Decision to Retain the Current Standards

All of the state and local environmental agencies or governments that provided comments 

on the Administrator’s proposed conclusion that the current CO standards provide the 

requisite protection of public health with an adequate margin of safety concurred with the 

proposed decision. Additionally three industry commenters also expressed agreement 

with EPA’s proposal to retain the current standards, which they also viewed as providing 

the requisite level of public health protection. In support of this view, these commenters 

variously stated that: 

 the current evidence indicates current standards are protective for the sensitive 

group of people with heart disease; 

 the proposed conclusions give appropriate weight to epidemiological studies; 

 the REA estimates of occurrences of carboxyhemoglobin (COHb) levels above 

2% COHb in the at-risk populations are materially unchanged since last review, 

and; 

 some aspects of the exposure and dose assessment lead the REA results to provide 

an overstatement of risk (further discussed in II.A.4.below) . 
 3 

These comments received in support of retaining the current standards are generally 

addressed in Section II.B.3 of the preamble to the final rule. We additionally note here 

that EPA does not agree with commenters’ characterization of the REA results as an 

overstatement of health risk as discussed in section II.A.4 below. 

2. Comments Recommending Revision of the Current Standards

Comments received on the proposal from several organizations and individuals asserted 

that the evidence indicated the occurrence of health effects occurring at conditions below 

the current CO standards and that revisions should be made to the standards. Among 

those recommending revisions to the current standards were joint comments submitted 

from the American Lung Association, the American Thoracic Society, the Environmental 

Defense Fund (ALA et al); joint comments submitted from Physicians for Social 

Responsibility and Albert Donnay (PSR et al), signed by 27 other organizations and 

several hundred individuals; joint comments submitted from Center for Biological 

Diversity, Communities for a Better Environment, WildEarth Guardians, Coalition for a 

Safe Environment, and Alaska Center for the Environment (CBD et al); individual 

comments from Albert Donnay (Donnay) and a petition signed by 130 individuals. These 

various commenters recommended a range of lower levels for revised 1-hour and 8-hour 

standards with consideration of a revised form of 99th percentile. The recommended 

levels were at or below the lowest part of the range identified in the Policy Assessment. 

In supporting adoption of more stringent NAAQS for CO, these commenters generally 

stated that they supported comments provided by CASAC on the draft Policy Assessment 

which indicated a preference for a lower standard and recommended greater emphasis be 

given to epidemiological studies. The commenters also variously stated that: 

 the available epidemiological studies provide evidence of effects at levels below 

the current NAAQS; 

 epidemiological studies indicate that the current standards do not provide 

protection for all sensitive populations, including specifically fetuses, neonates 

and children; and; 

 epidemiological studies provide evidence indicating that current standards do not 

provide protection against chronic CO exposures. 

The NESCAUM also offered the view that a lower standard may be appropriate, “perhaps 

based on an alternate indicator”, noting CASAC’s preference, but recognized that “at this 

time the available epidemiological studies do not clearly indicate a specific level for the 

one or eight-hour standard”. 

Comments received that recommended revising the current standards are addressed in 

section II.B.3 of the preamble to the final rule. Specific aspects to some of these 

comments are additionally discussed below. 
 4 

3. Comments on Evidence­based Considerations

(1) Comment: In support of their view that the current standards fail to protect public 

health with an adequate margin of safety, one commenter (ALA et al) 

summarized findings for a number of studies of associations of respiratory 

endpoints with ambient CO concentrations, describing them as providing 

evidence of harm from CO exposure below the current standards. Two 

commenters (ALA et al and CBD et al) indicated that the Clean Air Act 

compelled EPA to revise standards in light of the epidemiological evidence, 

regardless of uncertainties. 

Response: In addressing this comment EPA notes that it is important to consider 

both the extent to which the evidence supports a causal relationship between 

ambient CO exposures and respiratory effects, as well as the extent to which there 

is evidence pertinent to such effects under air quality conditions in which the 

current standards are met. With regard to the latter point and focusing on the 

epidemiological evidence, it is the studies involving air quality conditions in 

which the current standards were met that are most informative in evaluating the 

adequacy of the standards (PA, p. 2-30). Yet the commenter provides no 

evidence that the studies they cite, some of which are conducted outside the U.S., 

focused on conditions that meet the current U.S. CO standards. And, when 

considering the publicly available information on attainment and non-attainment 

of the current standards in the study locations for the time periods relevant to the 

U.S. studies cited by the commenters, it can be documented that the current 

standards were met throughout the period of study in only two study areas 

(http://www.epa.gov/airtrends/reports.html). 

Further, as described in the ISA, EPA has determined the body of evidence for 

short-term exposure and respiratory morbidity to be only suggestive of a causal 

relationship (ISA, section 5.5.5.1). This conclusion was reached due to a lack of 

evidence on mechanism or mode of action that might lend biological plausibility 

to such a relationship for the low ambient concentrations of CO observed in 

epidemiological studies. Additionally, the inability to sufficiently rule out the 

role of chance, bias and confounding in the epidemiological associations observed 

contributed to the “suggestive” causal determination. EPA further determined 

that the evidence is inadequate to infer a causal relationship between long-term 

exposure to ambient CO and respiratory morbidity (ISA, section 5.5.5.2). Both of 

these determinations were reviewed and endorsed by CASAC in their January 

2010 letter to the Administrator (Brain and Samet, 2010a), with CASAC 

additionally stating that the evidence of a potential causal relationship between 

short-term CO exposure and adverse respiratory outcomes “borders between 

suggestive and inadequate” (Brain and Samet, 2010a). 

As noted in the ISA, PA, the proposal notice and advice received from CASAC, 

there are several aspects to the epidemiological evidence for CO that complicate 
 5 

its interpretation with regard to ambient concentrations of CO that might be 

eliciting the reported health outcomes. In particular, a major challenge relates to 

the difficulty in determining the extent to which ambient CO is independently 

associated with health effects or if CO at ambient levels is acting as a surrogate 

for the effects of another traffic-related pollutant or mixture of pollutants (e.g., 

PA, pp. 2-36 to 2-39). As noted in the ISA in interpreting the epidemiological 

evidence, “the limited amount of evidence from studies that examined the effect 

of gaseous pollutants on CO-respiratory morbidity risk estimates in two-pollutant 

models, specifically NO2, has contributed to the inability to disentangle the effects 

attributed to CO from the larger complex air pollution mix (particularly motor 

vehicle emissions), and this limits interpretation of the results observed in the 

epidemiologic studies evaluated” (ISA, p. 5-100). The ISA further noted that a 

“key uncertainty in interpreting the epidemiologic studies evaluated is the 

biological mechanism(s) that could explain the effect of CO on respiratory health” 

(ISA, p. 5-100). CASAC also acknowledged the potential for co-pollutants to 

serve as confounders to be “particularly problematic for CO” and the need to give 

consideration to the possibility of CO serving as a surrogate for a mixture of 

pollutants associated to fossil fuel combustion (Brain and Samet, 2010a). 

After considering the evidence, together with these areas of uncertainty, the 

Administrator concluded in the final rule that the epidemiological evidence does 

not lead her to identify a need for any greater protection than that provided by the 

current standards. 

EPA also disagrees with commenters (including ALA et al and CBD et al) who 

state that even if the evidence of adverse effects at and below the current standard 

is uncertain, there is sufficient evidence to warrant revision of the standards to 

provide an adequate margin of safety against adverse health effects. EPA agrees 

that section 109 is precautionary in nature, and, as discussed in the preamble (e.g., 

section I), the standard is intended to protect against risk associated with pollution 

at levels below those at which human health effects can be said to occur with 

reasonable scientific certainty. Thus, in selecting primary standards that provide 

an adequate margin of safety, the Administrator is seeking not only to prevent 

pollution levels that have been demonstrated to be harmful but also to prevent 

lower pollutant levels that may pose an unacceptable risk of harm, even if the risk 

is not precisely identified as to nature or degree. At the same time, the Clean Air 

Act (CAA) does not require the Administrator to establish a primary NAAQS at a 

zero-risk level. Rather, EPA’s task is to establish standards that are neither more 

nor less stringent than necessary. 

Accordingly, EPA disagrees with the view expressed in one comment that “the 

CAA requires that the EPA act to protect public health as soon as there is any data 

suggesting health effects from a pollutant” (CBD et al at p. 5) as well as the view 

that the information available in this review necessitates stronger standards to 

provide a margin of safety. An approach that based the standard on the existence 

of “any data suggesting health effects,” absent a careful weighing of the evidence 
 6 

and risks, may well result in standards more stringent than necessary to protect 

public health with an adequate margin of safety. In evaluating the air quality 

criteria and public comments, the Administrator has not required certainty as to 

the occurrence of adverse health effects but rather has made judgments about how 

to consider the range and magnitude of uncertainties that are inherent in the 

information and analyses. For the reasons explained above and in the preamble, 

the Administrator has concluded that the current standards are requisite to protect 

public health with an adequate margin of safety. 

(2) Comment: In support of their view that EPA’s proposed retention of the current 

standards would not be protective of sensitive populations, two commenters (PSR 

et al, Donnay) argued that the CO-associated risks identified in epidemiological 

studies of birth defects, lower birth weight, asthma and neonatal respiratory 

mortality indicate that the health risks for fetuses, infants and children are much 

higher than risks reported in adults. The commenters characterized the risk for 

birth defects and neonatal respiratory mortality to be as high as one or two orders 

of magnitude greater than those faced by adults. Additionally, one commenter, in 

citing three studies of CO poisoning and cardiovascular damage in children 

(Donnay at p. 16) suggested that, based on such studies, EPA should incorporate a 

larger margin of safety in the final rule. Another commenter (CBD et al) 

indicated that the EPA did not appropriately consider epidemiological evidence 

on negative birth and developmental outcomes, and also stated that the Clean Air 

Act compelled EPA to revise standards in light of this evidence. 

Response: As an initial matter EPA notes that, in considering the adequacy of the 

current standards, it is important to consider both the extent to which the evidence 

supports a causal relationship between ambient CO exposures and adverse health 

effects, as well as the extent to which there is evidence pertinent to such effects 

under air quality conditions in which the current standards are met. With regard 

to the latter point, and focusing on the epidemiological evidence, it is the studies 

involving air quality conditions in which the current standards were met that are 

most informative in evaluating the adequacy of the standards (PA, p. 2-30). 

Yet, of the six epidemiological studies cited by the commenters (e.g., PSR et al at 

pp. 8-9), all three of the U.S. studies (Ritz et al., 2002, 2006; Maisonet et al., 

2001), as well as a fourth study that was performed in Brazil, included conditions 

when the current CO 8-hour standard was exceeded in those study areas 

(http://www.epa.gov/airtrends/reports.html; Conceicao et al., 2001). Sufficient 

information to assess the air quality conditions in relation to the U.S. NAAQS for 

CO is not available for the other two studies cited (performed in Taiwan and 

Seoul, Korea). We additionally note that one of these latter two studies focuses 

on assessing associations between respiratory effects and long-term 

concentrations of ambient CO; EPA has concluded that the available evidence is 

inadequate to infer a causal relationship for long-term exposure and respiratory 

morbidity (ISA, p. 5-101). In light of this information, EPA disagrees with the 
 7 

commenters suggestion that these studies provide evidence of a lack of protection 

afforded by the current standards.1

 

The commenters further emphasize their view that the magnitude of the risks of 

birth defects and neonatal mortality associated with ambient CO suggested by the 

cited studies are greater than the risk faced by adults in response to similar 

increases in ambient CO, and that EPA should consequently give greater weight 

to evidence regarding birth defects and neonatal mortality. The commenters’ 

view appears to be based on their comparison of effect estimates from studies 

finding associations for these different types of health outcomes with various 

measures of ambient CO. EPA notes, however, that such a comparison of effect 

estimates for health outcomes reported in studies of adults, such as cardiovascular 

outcomes, to those from the studies of developmental and neonatal outcomes cited 

by the commenters is inappropriate and misleading with regard to the difference 

in magnitude of risks potentially posed to exposed populations by ambient CO. 

Such an isolated comparison fails to consider critical differences between the two 

types of analyses and observed risks. Such differences include differences in the 

ambient air metric associated with the effect estimate, differences in the form of 

the effect estimates across some studies, and the fact that effect estimates are 

estimates of an increase in prevalence of specific outcomes, relative to the 

underlying prevalence of the health outcomes being examined.2

 

Contrary to the commenters’ assertion as to a lack of appropriate consideration of 

birth and developmental outcomes, EPA has fully assessed the evidence regarding 

relationships between birth and developmental outcomes and exposure to ambient 

CO, including the studies cited by the commenters (ISA, section 5.4). Further, in 

reaching a decision regarding the adequacy of the current CO standards, the 

Administrator considered this assessment, as well as uncertainties and limitations 

of the evidence (preamble to final rule, section II.B.3). EPA’s assessment of the 

body of evidence for the health outcomes emphasized by the commenter, 

including that for birth outcomes and developmental effects, concluded that the 

evidence indicates a potential for susceptibility during prenatal and neonatal 

periods, but that the evidence is only “suggestive” of a causal relationship with 

ambient CO (ISA, sections 2.5.3 and 2.6.1). Specifically, the ISA notes that 

evidence is lacking on mechanism or mode of action that might lend biological 

plausibility to a causal relationship between birth outcomes and developmental 

effects and the low ambient concentrations of CO observed in epidemiological 

studies (ISA, p. 5-80). Additionally, the inability to sufficiently rule out the role 

of chance, bias and confounding in the epidemiological associations observed 

contributed to the “suggestive” causal determination (ISA, section 5.4.3, Table 1-

2). Thus, we recognize much greater uncertainty associated with a relationship 

 

1

 See comment response 4, below, for further discussion of the evidence for adverse health effects from 

chronic low level exposure to ambient CO. 

2

 With regard to the consideration of prevalence, for example, a 10% increase for a more prevalent 

outcome, such as cardiovascular disease events, would translate to a much higher impact (in terms of size 

of the population affected) than for more rare outcomes, such as birth outcomes. 
 8 

between ambient CO concentrations and these health outcomes as compared to a 

relationship with cardiovascular effects. As discussed in the previous response, 

EPA recognizes that the NAAQS are intended to provide protection against risk 

associated with pollution at levels below those at which human health effects can 

be said to occur with reasonable scientific certainty, but does not believe that the 

NAAQS should be set based on “any data suggesting health effects,” absent a 

careful weighing of the evidence and risks. 

With regard to the three studies of CO poisoning and cardiovascular damage cited 

by one commenter (Donnay at p. 16), EPA notes that these studies involve COHb 

levels many times higher than the lowest COHb levels assessed in the study of 

coronary artery disease (CAD) patients by Allred et al (1989), which EPA has 

weighed heavily in this review of the CO NAAQS. Consequently, EPA disagrees 

that these studies – or the larger evidence base as a whole- provides a basis for a 

larger margin of safety than that represented by the decision described in the 

preamble to the final rule. Further, contrary to the assertion by commenter that 

EPA considers adults to be more sensitive than children, EPA has concluded, 

based primarily on the controlled human exposure studies of CAD patients that 

people with heart disease, such as CAD, regardless of age, are particularly 

susceptible to ambient CO exposures. 

For the reasons described above and in the preamble, based on consideration of all 

of the currently available evidence, EPA considers the current standards to 

provide the requisite protection, including an adequate margin of safety, to 

potentially susceptible populations or lifestages, including pregnant women and 

infants, as well as to the widely recognized at-risk population of people with heart 

disease. 

 

(3) Comment: One commenter (Donnay) stated that EPA should conclude that there 

is biological plausibility for causal relationships between ambient CO exposure 

and a range of noncardiovascular health outcomes. In support of this view, the 

commenter stated that evidence of (a) organ and pathway effects at acute CO 

poisoning levels, as well as, (b) the role of CO in important physiologic pathways, 

also provides support for concluding that CO affects the same organs and 

pathways at much lower ambient CO exposure levels (i.e., those which exist in 

recent epidemiological studies). As a result the commenter states that EPA 

should conclude causal relationships exist between ambient CO exposure and 

infant mortality, adverse birth outcomes, childhood respiratory or immune system 

morbidity, adult mortality, and adult morbidity for a range of organ systems 

beyond the cardiovascular system and that there is evidence of such effects based 

on which EPA should revise the current NAAQS. 

Response: As an initial matter, EPA notes our use of a consistent and transparent 

basis for the framework we use to evaluate the causal nature of air pollutioninduced health effects (ISA, section 1.6). This framework establishes uniform 
 9 

language concerning causality and brings specificity to the findings. The 

standardized language employed in the framework was drawn from across the 

federal government and wider scientific community, especially from the recent 

National Academy of Sciences, Institute of Medicine document, Improving the 

Presumptive Disability Decision-Making Process for Veterans (NAS, 2008) the 

most recent comprehensive work on evaluating causality. Under this framework, 

EPA has determined the separate bodies of evidence for birth outcomes and 

developmental effects, short-term exposure and respiratory morbidity, and shortterm exposure and mortality to each be only suggestive of a causal relationship 

with ambient CO exposures (ISA, sections 5.4.3, 5.5.5.1, and 5.6.5.1). These 

determinations were reviewed and endorsed by CASAC in their January 2010 

letter to the Administrator (Brain and Samet, 2010a), although we additionally 

note CASAC’s comments that the association for short-term CO exposure and 

adverse respiratory outcomes “borders between suggestive and inadequate” (Brain 

and Samet, 2010a, p. 12). Based on EPA’s provisional consideration of the 

additional epidemiological studies cited by the commenter, in the context of the 

findings of the ISA, EPA concludes that the new information and findings do not 

materially change any of the broad scientific conclusions made in the 2010 CO 

ISA and thus do not warrant reopening the air quality criteria review. 

In considering the body of evidence for each of these outcomes, EPA disagrees 

with the commenter’s view that CO poisoning studies (e.g., studies involving 

accidental exposures to very high concentrations of nonambient CO resulting in 

very high COHb levels) address uncertainties with regard to the biological 

plausibility for CO effects at lower exposures. Rather, EPA deliberately excluded 

studies involving CO poisoning (including the more than 100 publications cited 

by the commenter) from this review, judging them to be “not directly relevant to 

ambient exposures” (ISA, pp. 1-6 and 1-7). Such high-level CO exposures 

described in clinical reports are extremely unlikely to be experienced under 

ambient exposure conditions, as demonstrated in the REA. In addition, the types 

of adverse effects (including severe neurological impairment and death) observed 

at very high COHb levels have not been demonstrated following CO or COHb 

concentrations associated with ambient exposure (ISA, section 5.3). 

The commenter also states that CO effects at the other end of the spectrum from 

CO poisoning – i.e., effects of endogenous CO – inform our consideration of the 

biological plausibility of a causal role for carbon monoxide in the identified health 

outcomes. The available literature on the topic of endogenous CO is vast. In fact, 

the commenter cites 144 reviews of endogenous CO and heme oxygenase. The 

EPA is aware of the literature on which these many reviews are based, and has 

included two timely review articles in on this topic in the ISA.3

 The important 

role played by endogenous CO in physiologic pathways and the potential for 

exogenous CO to influence these functions is described in the ISA: 

 

3

 Review articles are generally not included in the ISA. Rather than bring forward new information in the 

form of original research or new analyses, these articles typically present summaries or interpretations of 

existing studies. 
 10 

 “CO is a ubiquitous cell signaling molecule with numerous physiological 

functions.” [ISA, p. 5-12] 

 “A key issue in understanding the biological effects of environmentallyrelevant exposures to CO is whether the resulting partial pressures of CO 

(pCO) in cells and tissue can initiate cell signaling which is normally 

mediated by endogenously generated CO or perturb signaling which is 

normally mediated by other signaling molecules such as NO.” [ISA, p. 5-

9] 

Some recent animal in vivo and in vitro studies demonstrate exogenous CO effects 

on signaling pathways and tissue and cellular levels of CO under certain 

conditions (ISA, tables 5-1 and 5-2). Little is known however regarding kinetics 

or compartmentalization of CO pools. Further, there is uncertainty in 

extrapolating cell signaling results to adverse health outcomes as recognized in 

the ISA: “Whether or not environmentally-relevant exposures to CO lead to 

adverse health effects through altered cell signaling is an open question for which 

there are no definitive answers at this time” (ISA, p. 5-12). As a result of these 

considerations, the biological plausibility for causal relationships between 

ambient CO exposure and a range of noncardiovascular health outcomes is not 

firmly established. More evidence is required to definitively link altered cell 

signaling with adverse health outcomes following environmentally-relevant CO 

exposures. 

In summary, EPA does not find the issues raised by the commenter to support a 

conclusion that relevant ambient concentrations of CO are causally related to a 

broad range of health effects, and further disagrees with the commenter that there 

is cause for concern for such health effects under conditions when the current 

standards are met. For the reasons described in response to comments (1) and (2) 

above, and in the preamble, based on consideration of all of the currently 

available evidence, EPA considers the current standards to provide the requisite 

protection, including an adequate margin of safety, to potentially susceptible 

populations or lifestages, including pregnant women and infants, as well as to the 

widely recognized at-risk population of people with heart disease. 

(4) Comment: Two commenters (PSR et al; Donnay) stated that EPA should be 

concerned regarding chronic exposures to CO and that the evidence indicates that 

the current standards do not afford protection against chronic exposures. In 

arguing that a range of health effects (to neurological, respiratory and 

cardiopulmonary systems) reported to be associated with CO poisoning 

conditions are relevant to much lower ambient CO concentrations, the second 

commenter (Donnay) additionally stated that “EPA should err on the side of 

caution in establishing the CO NAAQS by making the reasonable assumption that 

chronic or repeated low level CO exposures may increase the risk of these 

outcomes.” Talking points provided by this commenter in written testimony 

accompanying their oral testimony stated that “...chronic low-level CO exposures 
 11 

result in more severe and persistent CO illnesses than single high level acute 

exposures.” (Donnay written testimony February 28, 2011, p. 5). 

Response: EPA disagrees with the commenter that it is a “reasonable assumption 

that chronic or repeated low level CO exposures may increase the risk” of a range 

of outcomes associated with CO poisoning conditions. Additional statements 

made by this commenter implied to be relevant to chronic CO exposures are that 

low CO exposures result in a slower, more gradual uptake into the blood stream 

than higher CO exposures, providing a longer period during which CO “free in 

plasma” (i.e., not bound to hemoglobin) is available for distribution into tissues. 

As an initial matter, EPA notes that, due to the strong affinity of hemoglobin (Hb) 

for CO, there is very little free CO occurring in plasma, with less than 1% of total 

body CO appearing as dissolved CO in body fluids (ISA, p. 4-12). In support of 

the commenter’s view that chronic low CO exposures result in greater uptake into 

tissues, the commenter cites a small study involving 7 individuals where control 

subjects appeared to have higher CO uptake into muscle tissue compared to COexposed subjects (ISA, p. 4-16). However, this study, in which direct measures of 

tissue CO were not reported, is in contrast with evidence from a study which 

directly measured CO liberated from tissues and demonstrated that tissue CO 

increased with increasing COHb level (ISA, Table 4-2, p. 4-16), which is 

consistent with the prevailing theory on CO pharmacokinetics. Thus, while EPA 

agrees with the commenter that the equilibrium between inhaled CO and blood 

COHb is approached more slowly at lower COHb levels compared to elevated 

COHb, a slower rate of uptake does not indicate greater total CO uptake. Rather, 

the rate and amount of uptake into tissue compartments is controlled by the blood 

to tissue CO pressure differential, which is greater at higher COHb levels. Thus, 

consistent with the lack of chronic effects observed in the CO evidence base 

(discussed below), the body of evidence does not support the commenter’s 

contention of increased uptake over time at low CO concentrations. 

EPA considered the evidence currently available on cardiovascular and 

respiratory morbidity and long-term (chronic) CO exposures and determined that 

the evidence was inadequate to determine that a causal relationship exists at 

relevant ambient CO exposures (ISA, pp. 2-6 and 2-9). EPA further considered 

the currently available evidence with regard to neurological morbidity and longterm (chronic) CO exposures, concluding that the evidence was only suggestive of 

a causal relationship with relevant ambient exposures. This conclusion is based 

on a lack of evidence, such as that which might come from mechanistic studies, 

that might lend biological plausibility to epidemiological study results and the 

inability to sufficiently rule out the role of chance, bias and confounding in the 

epidemiological associations observed (ISA, pp. 2-7, 1-14). Further, our 

conclusion regarding the evidence on chronic exposures to CO in relation to 

mortality indicates “...that there is not likely to be a causal relationship between 

relevant long-term exposures to CO and mortality” (ISA, p. 2-10). During this 

review, CASAC endorsed EPA’s conclusions regarding chronic exposures to 

ambient CO (Brain and Samet, 2010a, pp. 12, 16). Thus, EPA’s judgment is that 
 12 

the current body of evidence does not support the commenter’s view that the 

current standards fail to provide adequate public health protection against chronic 

exposures to ambient CO. 

(5) Comment: One commenter (Donnay) stated that the ISA and other documents 

developed in this review do not reflect the latest scientific knowledge useful in 

identifying ambient CO effects as required by the Clean Air Act. This commenter 

identified a number of studies not discussed in the ISA which he describes as 

relevant. Another commenter (ALA et al) also identified two studies not 

discussed in the ISA as relevant. Donnay further questioned EPA’s procedure for 

reviewing the relevant CO literature in preparation of the ISA, questioning 

“whether EPA conducted a sufficiently comprehensive literature review”, 

providing a list of articles, some of which were published prior to the cut-off date 

for the ISA and some published subsequently (Donnay, p. 8). 

Response: EPA disagrees with the comment that the ISA does not reflect the 

latest scientific knowledge on effects of ambient CO. Rather, EPA considers the 

ISA to represent a thorough review of the latest scientific knowledge pertaining to 

the effects of ambient CO, consistent with the requirements of CAA section 108. 

In their review of the second draft ISA, CASAC agreed, stating that the “CO ISA 

will be adequate for rulemaking with the incorporation of changes in response to 

the Panel’s major comments and recommendations” (Brain and Samet, 2010a). 

As to the comprehensiveness of the literature review conducted by EPA, as 

described in section 1.3 of the ISA, EPA scientists and collaborators conducted 

comprehensive literature searches in multiple health and atmospheric science 

disciplines to identify original peer-reviewed research published since the last CO 

NAAQS review. These searches focused on articles published between 1999 and 

May 2009, the cutoff date for articles to be included in the ISA. Researchers 

screened the large body of search results to identify potentially relevant articles to 

be considered in preparing the ISA. In addition to these broad searches, targeted 

searches were conducted using search strategies such as review of pre-publication 

tables of contents of relevant journals, searches on specific topics, and citation 

mapping to find papers citing known articles. Additional articles were identified 

by the public and CASAC during external review of two drafts of the ISA and 

other review documents. 

EPA notes that, in contrast to Air Quality Criteria Documents prepared during 

previous reviews, which were more encyclopedic reviews of the scientific 

literature, ISAs developed under the current NAAQS process are intended to 

present a “concise evaluation and synthesis of the most policy relevant science 

(ISA, p. 1-1). CASAC has endorsed this approach during the CO NAAQS review 

(Brain and Samet, 2009; Brain and Samet, 2010a). Policy-relevant questions 

critical to the review were identified prior to preparation of the first draft CO ISA 

through a kickoff workshop held January 28-29, 2008 (73 FR 2490) and described 

in the Integrated Review Plan (USEPA, 2008), a draft of which was the subject of 
 13 

a consultation with CASAC (73 FR 12998; Henderson, 2008). These policyrelevant questions, presented on page 1-1 of the CO ISA, formed the basis for 

EPA’s consideration of the scientific evidence. In considering the available CO 

literature, topics such as those raised by commenters (e.g., very high 

concentration exposures in humans and animals) were not found to be informative 

to assessment of the health effects of ambient CO or to the policy-relevant 

questions for this review (ISA, pp. 1-6. 1-7). Thus, these topics were not 

extensively discussed in the ISA. 

EPA has considered the articles identified by commenters and determined that 

many of them were not included in the ISA as they fall outside the scope of the 

ISA document as they were not found to be informative to assessment of the 

health effects of ambient CO or to the policy-relevant questions for this review 

(ISA, pp. 1-6, 1-7). Studies listed by commenters that fall within the scope of the 

ISA (listed in Appendix A), including recent studies published after the cutoff 

date for inclusion, have been provisionally considered in topic-specific comments 

elsewhere in this document. Based on this provisional consideration, we conclude 

that the information provided by these studies does not materially change the 

conclusions reached in the ISA. Accordingly, as discussed in section I.C of the 

preamble, EPA is not re-opening the air quality criteria for this review to further 

consider these studies. 

(6) Comment: One commenter (Donnay) questions how EPA can rely on 

consideration of the lowest tested COHb level in Allred et al (1989) study in 

judging the standards to provide adequate public health protection when EPA has 

stated that this study provided no evidence of threshold. This commenter claims 

EPA has no scientific or legal basis for their consideration of the Allred results for 

this purpose, which the commenter claims to suggest a “reckless and wanton 

disregard for public health” (Donnay, p. 2). The commenter additionally 

describes statements or actions of the World Health Organization (WHO), U.S. 

Agency for Toxic Substances and Disease Registry (ATSDR), and U.S. National 

Academies of Science, National Research Council (NRC) as indicating that 

evidence is lacking to inform EPA’s decision regarding a CO NAAQS that 

protects public health with an adequate margin of safety.

Response: EPA first notes that, as discussed in section I.A of both the proposal 

and final notice, the Clean Air Act does not require that the NAAQS be 

established at a zero-risk level, but rather at a level that reduces risk sufficiently 

so as to protect public health with an adequate margin of safety. In setting 

primary standards that are “requisite” to provide this degree of public health 

protection, the Supreme Court has affirmed that EPA’s task is to establish 

standards that are neither more nor less stringent than necessary for this purpose. 

Accordingly, a lack of evidence for a threshold effect level for exercise-induced 

myocardial ischemia resulting from CO exposure does not mean that there is no 
 14 

standard level that would be protective of public health with an adequate margin 

of safety. 

As noted in section I.A. of the final rule, in addressing the Clean Air Act 

requirement for an adequate margin of safety, the EPA considers such factors as 

the nature and severity of the health effects involved, the size of the sensitive 

population(s) at risk, and the kind and degree of the uncertainties that must be 

addressed. The selection of any particular approach to providing an adequate 

margin of safety is a policy choice left specifically to the Administrator’s 

judgment. For example, in considering the controlled human exposure studies 

that describe the effect of short-term CO exposure on exercise-induced 

myocardial ischemia in coronary artery disease patients, as described in section 

II.B.3 of the final rule, the Administrator considered the nature and severity of the 

health effects involved, as well as the kind and degree of the uncertainties in those 

studies as well as in the exposure and dose assessment. Based on such 

considerations, as well as those concerning the rest of the evidence, as discussed 

in section II.B.3 of the final rule, the Administrator judged the current standards 

to provide the requisite public health protection against effects of concern.

With regard to the commenter’s reference to a WHO publication, we note the 

citation is to an article by D. Schwela (2000) in which WHO publications are 

reviewed. As the commenter notes, the summary for CO in this article, states that 

“[a]mbient CO may have even more serious health consequences than does COHb 

formation and at lower levels than that mediated through elevated COHb levels”. 

Although somewhat unclear, this statement may be intended to reference the 

potential for effects of CO unrelated to COHb-mediated decreased oxygen 

delivery to tissues. EPA has considered the evidence that exogenous CO may 

initiate or alter cell signaling, as described in section 5.1.3 of the ISA. These 

mechanisms are likely to involve the binding of CO to reduced iron in heme 

proteins other than Hb with subsequent alteration of heme protein function. 

COHb may play a role in these processes by delivering CO to cells and tissues 

(ISA, p. 5-9), however, the role of these effects in producing health outcomes, as 

well as whether these effects occur in response to CO exposures relevant to those 

associated with ambient air is still uncertain (ISA, p. 5-12). The ATSDR report 

cited by the commenter points to a similar mechanistic pathway: “ given the 

physiological role of endogenous CO...., any exogenous source of CO exposure” 

has “the potential for producing potentially adverse effects.” The ISA states that 

ambient CO has the potential to alter cell signaling processes which may result in 

downstream health effects but notes that this is an area of uncertainty, stating that 

“[w]hether or not environmentally-relevant exposures to CO lead to adverse 

health effects through altered cell signaling is an open question for which there 

are not definitive answers at this time” (ISA, p. 5-12). Thus, EPA assessed the 

evidence for these pathways in the ISA, and Administrator took into consideration 

the possibility of adverse health effects together with the uncertainties, and 

concluded that the current standards provide the requisite protection, with an 

adequate margin of safety.
 15 

The commenter also points to the NRC’s decision to not establish an acute 

exposure guideline level (AEGL)4

 for “non-disabling” effects (an AEGL-1) for 

CO, implying that this is related to consideration of uncertainty regarding a 

threshold for effects. EPA notes, however, that that is not the basis for the NRC’s 

decision. Rather, as the NRC report describes, an AEGL-1 value was not 

recommended because susceptible persons may experience more serious effects 

(usually the basis for AEGL-2) at concentrations that do not yet cause nondisabling effects (usually the basis for the AEGL-1) in the general population 

(NRC, 2010). Thus consistent with the NRC methodology for cases such as this 

(NRC, 2001, p. 415

), the NRC did not set an AEGL-1. EPA additionally notes 

that the data on which the NRC relied for their decisions was that which focused 

on effects observed in response to elevations in COHb (e.g., Allred et al., 1989). 

Thus, particularly given the widely differing purposes for AEGLs and NAAQS 

and the statutory framework for NAAQS, EPA does not believe that the NRC’s 

conclusions regarding AEGLs for CO are inconsistent with the Administrator’s 

judgment as to the degree of protection afforded by the current standards. 

4.  Comments on Exposure and Risk Considerations

Included in this section are comments concerning consideration of the quantitative 

exposure and health risk assessments in the decision on the adequacy of the standards, 

which are generally not discussed in the preamble to the final rule. 

(1) Comment: One industry commenter (AAM), in concurring with EPA that the 

current standards provide a high degree of protection for the COHb levels and 

associated health effects of concern, also identified aspects of the REA that in 

their view result in the risk being overstated in the upper tail of the COHb 

distribution. 

 The reduced number of monitoring sites from which ambient CO 

measurements were drawn for the Denver study area inappropriately biases 

the exposure concentration distribution upward through giving relatively 

 

4

 Acute exposure guideline levels are established by the AEGL committee of the NRC for use in emergency 

planning. As defined by the NRC, an AEGL-1 is the airborne concentration of a substance “above which it 

is predicted that the general population, including susceptible individuals, could experience notable 

discomfort, irritation, or certain asymptomatic, nonsensory effects. However, the effects are not disabling 

and are transient and reversible upon cessation of exposure.” An AEGL-2 is defined as the airborne 

concentration of a substance “above which it is predicted that the general population, including susceptible 

individuals, could experience irreversible or other serious, long-lasting adverse health effects, or an 

impaired ability to escape.” [NRC, 2001] 

5 In cases in which the biologic criteria for the AEGL-1 value would be close to, or exceed, the AEGL-2 

value, the conclusion is reached that it is “not recommended” (NR) to develop AEGL-1 values. In these 

cases, “detectability” by itself would indicate that a serious situation exists. In instances in which the 

AEGL-1 value approaches or exceeds the AEGL-2 value, it may erroneously be believed that people 

experiencing mild irritation are not at risk when in fact they have already been exposed to extremely 

hazardous or possibly lethal concentrations. [NRC, 2001, p. 41] 
 16 

greater weight to a site (in traffic island) not representative of locations where 

people in the population spend their time. 

 In-vehicle and near-roadway CO concentrations are overestimated; there is no 

evidence of 1-hour exposure concentrations as high as 60 parts per million 

(ppm) in vehicles in areas that meet the current CO standards, indicating that 

the ratio method used for this microenvironment in the REA produces 

overestimates of exposure concentration. 

 The cities on which the REA focused are worst case situations with regard to 

ambient CO concentrations nationally. 

Response: With regard to the first REA aspect cited, AAM contend that the four 

Denver monitors used in the current REA overestimate risk relative to that 

estimated in the 2000 probabilistic NAAQS Exposure Model (pNEM) analysis 

(Johnson et al., 2000) which used ambient CO concentrations from six monitors. 

Specifically AAM charges that the approach used in the REA “biases the 

distribution upward by overstating the number of people exposed to high CO 

concentrations.” EPA first notes that all four Denver monitors used in the current 

assessment were also used in the previous CO exposure and dose assessment 

conducted by Johnson et al. (2000) (see REA, Table 5-1). The two monitors that 

were not used in the current assessment but used in the prior assessment were 

located outside of the urban core of Denver.6

 Neither of these additional monitors 

reported CO measurements for 2006, the year selected to represent as is air 

quality in the REA. In developing the exposure modeling domain (described in 

REA sections 5.3 and 5.4), EPA staff elected to maintain consistency in the 

ambient monitors chosen for the current assessment and considering the multiple 

air quality scenarios evaluated rather than attempt to be consistent with the 

ambient monitors used in the prior 2000 assessment. 

While use of the four Denver urban core monitors may result in a greater percent 

of the population at or above selected benchmarks when compared with that of a 

simulation conducted using the six monitors from the 2000 assessment (and 

assuming the added two monitors in the modeling domain have lower 

concentrations relative to the four monitors used and all other modeling 

parameters are identical), EPA staff note that the actual number of persons (and 

person-days) at or above a benchmark within the air districts defined by these four 

monitors (all other modeling parameters held constant) would likely not be 

different than if the simulation had covered a larger study area inclusive of the 

areas surrounding the other two monitors that are outside of the Denver urban 

core. This is because the simulated population residing within the census tracts 

and encompassed by the same air quality districts is identical. 

The commenter additionally states that inclusion of the microscale site at the main 

intersection in Denver overstates the number of people exposed to high CO 

 

6

 The first monitor was ID 080050002 sited in Littleton, Colorado (Arapahoe County). The second monitor 

was actually an aggregation of CO concentrations from two closely sited Boulder, Colorado monitors: ID 

080130010 and 080131001 (Johnson et al., 2000). 
 17 

concentrations and the fraction of time exposed. EPA notes, however, that the 

evidence indicates and CASAC also concludes that there is a segment of the 

population that spend some of their time in proximity to locations such as the 

microscale, near-road site where short-term CO exposures may be elevated (REA, 

section 3.1.3). The importance of capturing near-road microenvironments in 

considering ambient CO exposures was emphasized multiple times over the 

course of this review in comments received from CASAC who raised concerns 

with regard to the ability of the existing CO monitoring network to provide for 

this aspect of CO population exposures.7

 Further, a simulation from which this 

monitor was omitted would lack representation of the large spatial variation in 

short-term concentrations that the evidence indicates generally occurs across an 

urban area as a result of the steep concentration gradients near roadway locations 

where it is formed. 8

 Thus, EPA finds the use of the full set of monitors, including 

the microscale site to be appropriate.9

As an initial point of clarification with regard to the statement made in the 2nd

comment by AAM, the modeling for conditions just meeting the current 8-hour 

standard did not use 1-hour in-vehicle concentrations approaching 60 ppm. As 

clearly stated in footnote d for the table referenced by AAM in making this 

statement (REA, table 6-9, p. 6-14), the microenvironmental CO concentrations 

presented are for exposure events that ranged in duration from 1 minute to 1 

hour.10,11 In fact, the highest concentration noted in this table (for the simulation 

of conditions just meeting the current standard in Denver), which is 63.4 ppm, 

 

7

 See, for example, CASAC letter of June 24, 2009, in which they stated that “[r]elying only on EPA’s 

fixed monitoring network CO measurements may underestimate CO exposures for specific vulnerable 

populations such as individuals residing near heavily trafficked roads and who commute to work on a daily 

basis” and “[r]elevant microenvironments that are influenced by local factors, such as in-vehicles {sic} and 

in high proximity to roadways, are not well represented.” 

8

 The other three monitors in the study area are more similar to each other with regard to concentrations in 

the upper end of the distribution of 1-hour concentrations than they are to the micro-scale site monitor 

identified by commenters (REA, Table 5-18). 

9

 EPA also notes that if the micro-scale site was omitted for the simulation of conditions just meeting the 

current 8-hour standard, another of the three monitors would be identified as the design monitor and all 

monitor concentrations would be adjusted to the point where that design monitor just met the current 8-

hour standard. As these remaining three monitors are more similar to each other with regard to 

concentrations in the upper end of the distribution of 1-hour concentrations than they are to the micro-scale 

site monitor identified by AAM (REA, Table 5-18), the adjusted ambient CO concentrations would be 

generally higher across the full study area if only those three monitors were included in a simulation. This 

would be expected to contribute to a larger number of occurrences of generally higher CO exposures and 

might also include a greater percent of the CHD population with COHb levels over 2% or higher 

benchmarks. 

10 REA Table 6-9, footnote d states “The mean, standard deviation, and percentiles (p) were calculated 

using all events regardless of event duration. Note that based on the activity pattern diaries used, the length 

of an event can range from 1 minute to 1 hour.” 

11 These event-level microenvironmental concentrations were generated from a model simulation designed 

to output minute-by-minute microenvironmental concentrations. As described in sections 5.10 and 6.1 of 

the REA, these microenvironmental concentration and ratio analyses were generated using a reduced model 

run of 5,000 persons per air quality scenario and within each study area due to the magnitude of the files 

generated and the time required to process each persons’ event-level data. The full exposure model runs 

used 50,000 simulated individuals and generated summary output data files only. 
 18 

was estimated to occur for a single 2-minute exposure event and that event was in 

an outdoor microenvironment and not inside a vehicle (see REA, figure 6-3). We 

note though that most (about 95%) of the highest microenvironmental 

concentrations (≥20 ppm) simulated in Denver were associated with the in-vehicle 

microenvironment (REA, Figure 6-3). The highest estimated in-vehicle 

concentration, 56.9 ppm (REA, Table 6-9), however, was associated with a 1-

minute exposure event, not 1 hour.12 In the simulation for the Los Angeles study 

area under conditions just meeting the current standard, maximum event-level 

microenvironmental concentrations (ranging from 1-minute to 1- hour in 

duration) were much lower than Denver and estimated to be at or above 30 ppm 

(REA, Table 6-12 and Figure 6-4), with most occurring inside vehicles. The 

maximum exposure concentration was 39.8 ppm (REA, Table 6-12) occurring for 

two exposure events with duration of 5 and 10 minutes, well short of the 1 hour 

duration stated by the commenter. 

Further, EPA disagrees with the commenter’s contention that there are no data 

supporting the magnitude of the in-vehicle exposure concentrations in the REA. 

As noted in the REA (p. 6-17), “estimated upper level concentrations [for both 

study areas] for the in-vehicle microenvironment are within the maximum 

measured peak level (one minute average) concentration reported by Rodes et al. 

(1998) of 67 ppm during rush hour commutes in Los Angeles (ISA, section 

3.6.6.2).” The REA exposure concentrations are also consistent with the AAM 

statement that “both the Shikiya et al. and Rodes et al. studies report peak CO 

concentrations of the order of 50 ppm” (AAM comments at p. 5). 

EPA notes that under conditions just meeting the current standard in the Denver 

and Los Angeles study areas, the maximum 1-hour microenvironmental 

concentrations were estimated from the 5,000-person simulations (see footnote 11 

above) to be 37.1 ppm and 34.8 ppm, respectively, both of which occurred inside 

vehicles.13 These event-level results developed from the 5,000-person 

simulations are consistent with the results reported for the full model simulations 

(REA, Tables 6-7 and 6-10) and what is specifically stated in the REA regarding 

maximum 1-hour exposure concentrations14 in the Denver study area where the 

“highest 1-hour daily maximum exposure was estimated to be at or above 40 ppm 

(but below 60 ppm)” (REA, section 6.1.2, p. 6-11). Regarding the Los Angeles 

study area, the REA similarly states that “the range of the 1-hour daily maximum 

exposure distribution extends upward to 30 ppm, but less than 40 ppm.” 

 

12 The duration of the exposure event in these microenvironments was obtained from analyzing the APEX 

events file for this simulation; it is not specifically reported in the REA. 

13 These maximum 1-hour microenvironmental concentrations were not directly reported in the REA and 

are from the 5,000 person simulations, though they are consistent with the distribution of maximum 1-hour 

exposure concentrations that were reported in the REA for the full model runs. 

14 In the full model runs, the 1-hour exposure concentrations are summarized by time-averaging across all 

microenvironments persons inhabited within the clock hour. As such, the 1-hour exposure concentration 

could be comprised of a single microenvironmental concentration (duration of 60 minutes) or multiple 

microenvironments (durations of less than 60 minutes). Specific microenvironment information is not 

included in these hourly summary output files. 
 19 

Therefore, assuming that most of the highest CO exposure concentrations 

occurred inside vehicles, estimated 1-hour maximum concentrations were 

reported in the REA as mostly less than 40 ppm for the in-vehicle 

microenvironment and not “approaching 60 ppm” as charged by AAM. 

In their rationale for concluding the REA overestimated in-vehicle concentrations, 

AAM also stated that Rodes et al. (1998) “reported in-vehicle CO concentrations 

between 3 and 5.4 ppm for 2-hour measurements.” This refers to the range of 

mean values calculated in the Rodes et al. (1998) study, which, as they are mean 

concentrations over periods well longer than a few seconds, are more relevant to 

the mean of the simulated in-vehicle concentration reported in REA Table 6-9 

rather than to maximum microenvironmental concentrations. In fact the mean invehicle concentration in REA Table 6-9 is 3.5 ppm, falling toward the lower end 

of the range quoted by AAM. Even considering this excellent agreement between 

the Rodes et al (1998) mean measured in-vehicle CO concentrations and the mean 

modeled concentrations reported in the REA, we note that the Rodes et al. (1998) 

study only included measurements for a few hours of the day, all occurring within 

a 9-day period in late September and early October 1997 in Los Angeles. In the 

REA, exposure concentrations are estimated for, at a minimum, 8,260 exposure 

events15 of each simulated individual’s full year exposure profile. Throughout a 

year there are a variety of emission, meteorological, physical, and personal factors 

that influence ambient and exposure concentration variability captured by the 

model and likely not at all represented by the data typically reported in 

measurement studies. The ISA indicates that when considering four basic seasons 

of the year, the mean and maximum ambient CO concentrations are highest in 

winter for Los Angeles (ISA, Figure 3-22), a time period represented by the REA 

exposure simulations but not by the Rodes et al., (1998) study. Given that, it is 

very likely that the Rodes et al. (1998) study does not represent the upper 

percentiles of the in-vehicle concentration distribution occurring for that year of 

the study (1997), thus limiting its comparability with the REA in-vehicle 

estimates. 

AAM further compares REA estimated upper percentile in-vehicle concentrations 

from simulations for air quality that just meets the current standard to 

measurements reported by Westerdahl et al. (2005), a comparison which EPA 

notes is inappropriate. This comparison is inappropriate because the Westerdahl 

et al. (2005) study was conducted in 2003, a year having ambient CO 

concentrations well below the current NAAQS. Median ambient 1-hour 

monitoring concentrations from that 2003 study ranged from 0.6 to 1.0 ppm 

(Westerdahl et al., 2005, Table 2) and are more comparable with the REA as is air 

quality scenario that employed 2006 Los Angeles ambient monitoring data in 

which median 1-hour concentrations ranged from 0.3 to 0.7 ppm (REA, Table 5-

16). 

 

15 As described in REA section 4.4.3.2, a person could be exposed for periods as short as 1 minute with a 

maximum duration of 1-hour, depending on the duration of the person’s activity performed or their time 

spent in a particular microenvironment. 
 20 

AAM also argue that the ratio method used by EPA to estimate in-vehicle 

concentrations would tend to bias CO concentrations high, particularly in an 

urban area if ratios are generated from other less urbanized areas having low 

background concentrations. In such instances, AAM allege that the distribution 

of derived ratios would be higher than similar ratios generated in locations, such 

as urban areas, where background concentrations are typically higher. EPA 

responds, however, that the method used to estimate all microenvironmental 

concentrations (including in-vehicle) in the REA (which was derived from 

measurement studies conducted in Denver and Los Angeles, as described in the 

REA section 4.4.4.3.1) would tend to guard against the mismatching of high ratios 

with high ambient concentrations. The microenvironmental algorithm employs an 

exponential transformation of the ambient concentration (REA, sections 4.4.4.3 

[pp. 4-19 to 4-20], 4.4.4.4 and 5.9.1 [pp. 5-27 to 5-29]) that effectively produces a 

“compression” effect in which the ratio of outdoor CO to ambient monitor CO 

tends to become smaller (on average) as the ambient monitor concentration 

increases (REA, p. 5-28). Section 5.10.2 of the REA discusses the relationship 

between estimated microenvironmental concentrations and their associated 

ambient monitor concentrations, and demonstrates that the phenomenon about 

which the commenter is concerned does not occur. For example, ratios derived in 

the REA of the estimated microenvironmental concentrations to the associated 

ambient concentrations (for the in-residence and in-vehicle microenvironments) 

illustrate an inverse relationship (REA, Figure 5-3), rather than the direct 

relationship that the commenter presumes. As stated in the REA, this 

demonstrates that the high ratios “that might have occurred when randomly 

sampling from the distributions used in Table 5-22 were effectively modified by 

the ambient concentration exponential adjustment (equation 4-11), thus 

controlling for extreme ratio and high concentration combinations in estimating 

the microenvironmental concentrations (REA, p. 5-35).” 

As basis for the commenter’s statement that the study areas selected for 

assessment in the REA would be considered a “worst case” situation, they cite the 

discussion of ambient monitoring in these cities reported by the National 

Research Council (NRC, 2003). EPA notes, that the NRC report mentions these 

two cities among a list of eleven locations across the U.S.16 that were identified as 

locations where NAAQS attainment “has been a particular challenge” because of 

a combination of conditions that may favor accumulation of CO emitted into the 

ambient air, and associated increases in CO concentrations, including 

meteorological, topographical, vehicle emission, and CO transport issues (NRC, 

2003). The NRC report does not, however, identify Denver and Los Angeles as 

cities representing the worst cases among the eleven identified, nor does it refer to 

the individual “CAMP” and “Lynwood” monitors mentioned by AAM as 

reporting “worst case” CO concentrations. In fact, when considering the current 

 

16 The nine other locations identified in Table 1-1 of NRC (2003) include: Birmingham, AL; Calexico, CA; 

Fairbanks, AK; Phoenix, AZ; Spokane, WA; Las Vegas, NV; Anchorage, AK; El Paso, TX; and Kalispell, 

MT. 
 21 

8-hour CO NAAQS, the NRC report identifies a monitor in Birmingham Alabama 

(01-073-6004) as having the greatest number of exceedances during 1995-2001 

(the period examined) of the 11 locations discussed (Table 1-1, NRC, 2003). 

 

EPA does not consider the two study areas to represent “worst case” situations. 

As explained in the REA (section 5.3), study area selection criteria included “the 

prior analysis of these locations in CO NAAQS reviews, the areas having 

historically elevated CO concentrations, and the areas currently having some of 

the most complete ambient monitoring data available” (REA, p. 5-2). There are 

two benefits in using these two particular study areas for our exposure 

assessment. Minimal adjustment was needed to simulate the air quality scenario 

of just meeting the current standard, as CO monitoring concentrations had in the 

past been at levels just above and below the current CO standards in both of these 

locations, thus providing a more realistic simulation of such an air quality 

scenario, and previous CO exposure assessments had also focused on these areas. 

Further, the relationship between 1-hour and 8-hour average ambient CO 

concentrations, a characteristic EPA noted as influential in differences in the 

population occurrences of elevated end-of-hour COHb estimates for the datasets 

for these two locations for the just meeting the current standard simulations was 

described in the Policy Assessment (PA, p. 2-41). The ratios of 1-hour to 8-hour 

design values for the two study areas were not extreme among all U.S. counties in 

the most recent year for which data were available (2009). The ratio for the Los 

Angeles dataset corresponded to approximately the 25th percentile of U.S. 

counties in 2009 while the Denver dataset corresponds to the 75th percentile. 

(2) Comment: Comments from one individual (Donnay) stated that the CoburnFoster-Kane (CFK) model used by the Agency is in error and should not be used 

to estimate COHb. Specifically, in using selected results of a comparison of CFK 

model estimates to experimental COHb measurements published by Benignus et 

al. (1994), Mr. Donnay suggests the range of predicted error in the CFK model is 

“almost the 2% threshold upon which EPA’s entire risk and exposure assessment 

modeling is based” (Donnay, p. 4). 

Response: In considering this comment, EPA first notes that there are occasions 

where the CFK model may either over or underestimate % COHb in an 

individual’s blood (this is referred to here as model or prediction error). In 

general, the frequency and magnitude of prediction errors in any model are 

commonly linked to the model’s ability to represent the most, if not all, influential 

variables that affect variability in the estimated values. Such occasions of CFK 

model prediction error, which are described in the 2000 Air Quality Criteria for 

Carbon Monoxide (AQCD) (USEPA, 2000, pp. 5-14 to 5-15), can include 

specific minutes within a CO exposure time series, particularly those associated 

with substantial CO exposures, and such occasions are the focus of the 

commenter’s statements on this issue. However, EPA disagrees with the 

commenter’s limited interpretation of the published findings by Benignus et al. 
 22 

(1994), which evaluated CFK model predictions against experimental 

measurements. The commenter did not fully consider the intent of the Benignus 

et al. (1994) research and study design, its many findings and conclusions, 

conclusions drawn from other publications that evaluated the CFK model, and 

thus, the relevance of Benignus et al. (1994) to the CFK modeling done in the 

REA. 

As an initial matter, by claiming that CFK predictions are in error by “almost the 

2% threshold in % COHb” which is a benchmark used in the REA, the 

commenter is inappropriately citing a Benignus et al (1994) result for a single 

maximum underestimation by the CFK model of 3.8% in one participant at one 

time point, and implying that this study indicates that an underestimation of the 

same absolute value of the percentage COHb is likely in the REA. 

Notwithstanding the likely lower prediction error for the much lower exposures 

which are the focus of the REA, discussed in more detail below, EPA notes that 

model prediction error from the Benignus et al (1994) paper is more appropriately 

considered in terms of the percentage of the total measured (or predicted) value 

that is represented by the absolute difference in values between the measured and 

predicted values. For example, in the study by Benignus et al. (1994), for which 

the total % COHb levels of the participants ranged from about 12 to 18% COHb, 

the underestimation of 3.8% cited by the commenter represented a maximum 

prediction error for that specific time point for that individual of about 20-30% of 

the individual’s absolute COHb level.17 Thus, if it were the case that the 

individual time point errors for the higher CO exposures of Benignus et al. (1994) 

were predictive for the substantially lower exposures of the REA, this finding 

might indicate that the maximum prediction error for an REA prediction of 2% 

COHb could be as much as an increment of 0.6% COHb (i.e., 30% of 2% COHb). 

Importantly, however, the CO exposures that are the focus of Benignus et al. 

(1994), and which are substantially higher than those in the REA, are associated 

with higher prediction errors on individual time points than occur for lower CO 

exposure scenarios. For example, as described in the 2000 AQCD, Hauck and 

Neuberger (1984) compared the 5-minute time series of COHb observations with 

CFK model predictions in four individuals, each exposed to varying CO 

concentrations, while at rest and performing moderate exercise (2000 AQCD, p. 

5-14). While CO exposure concentrations in this study were still somewhat 

higher than those simulated in the REA (i.e., generally study participant were 

exposed to one hundred to hundreds of ppm), the resulting COHb time-series for a 

few subjects fell within the range of about 1% to 4% COHb (see Figures 2 and 4 

of Hauck and Neuberger, 1984), consistent with the range of % COHb estimates 

reported in the REA (REA, Tables 6-18 and 6-19). As noted in the 2000 AQCD, 

“[t]he agreement between measured and predicted COHb under these varied 

 

17 This can be calculated as the difference of the measured from predicted [3.8%] divided by the absolute 

measured value [which, while not explicitly reported is described by Figure 1 of Benignus et. al. (1994) to 

range from 12-18%]). 
 23 

conditions was very good”, with a mean difference of only 7.4% of the nominal 

(maximal predicted) value (2000 AQCD, p. 5-14).18

EPA further notes that, contrary to the commenter’s assertion, the study by 

Benignus et al. (1994) in fact finds the CFK model estimates of COHb to be 

generally consistent with actual measurements of vCOHb, providing support for 

our use of the CFK model. As shown in Table 2 of Benignus et al (1994), the 

averages of model predictions at all tested time periods were not statistically 

significantly different from the corresponding averages of venous COHb 

measurements (p>0.80, see Table 2 of Benignus et al. 1994). This finding is 

particularly significant given the fact that the CO exposure concentrations 

investigated in Benignus et al. (1994) are much higher than those assessed in the 

REA. In Benignus et al. (1994), CO exposure concentrations were specifically 

selected to be so high and occur over such a short period of time that they would 

intentionally disrupt the concentration equilibrium that would normally exist 

between the venous and arterial blood flows within study subjects if exposed to 

lower CO concentrations. The administered CO exposure concentration to study 

subjects was 6,683 ppm occurring over period of about 5 minutes (Benignus et al., 

1994). This is over one hundred times the maximum single CO exposure 

concentration estimated in the REA (i.e., 63.4 ppm for 2 minutes).19 

Further, although not mentioned in Mr. Donnay’s characterization of Benignus et 

al. (1994), EPA notes the discussion by Benignus et al. (1994) that supports the 

CFK model assumption of a single well-mixed vascular compartment and the 

model’s accurate prediction of venous COHb at low CO exposure concentrations 

and for longer durations. For example, the paper states that when inspired CO “is 

low and exposure are long, as was the case during initial experiments (Coburn et 

al., 1965), these assumptions [of a single well mixed compartment] are valid and 

the CFKE accurately predicts mean peripheral venous HbCO” (Benignus et al., 

1994, p. 1743). As discussed more fully in the response to comment II.A.5(1) 

below, in considering the lag between arterial and venous COHb, the paper 

further states that “arterial blood mean ΔHbCO began to decline within 1 min of 

exposure cessation and progressively approach the mean venous value” and 

indicates that the equilibrium between venous and arterial COHb is reestablished 

within 3 minutes or less time (Benignus et al., 1994, p. 1743 and Figure 2). The 

 

18 The absolute value of the mean percent deviation of % COHb (not total deviation in % COHb) in two 

persons experiencing this relevant range of %COHb across four experiments ranged from 5.4% to 14.1% 

(Table 3 of Hauck and Neuberger, 1984). Using this prediction error and the range of estimated % COHb 

experienced by the two study subjects, CFK model predictions could vary by an increment as little as ± 

0.05-0.14% COHb at 1%COHb or at most, an increment of ± 0.22-0.56% COHb while at 4% COHb. 

19 For added context, EPA notes that over 99% of all exposure events simulated by APEX in the REA for 

the highest CO exposure simulations in the Denver and Los Angeles study areas (Tables 6-9 and 6-12) had 

CO concentrations below 13 ppm and well below 9 ppm, respectively. While the duration of exposure 

events simulated by APEX can be as short as 1 to 5 minutes, it is certainly not the case that short-term CO 

concentrations would reach thousands of ppm during any time or would vary by such extremes over such a 

short time period as that assessed in Benignus et al. (1994) (i.e. start at 0 ppm, increase to 6,700 ppm for 5 

minutes, then decrease to 0 ppm for about 5 minutes). 
 24 

CFK model assumption of equilibrium is also supported by several studies cited 

by Benignus et al. (1994) which involved COHb levels more similar in magnitude 

to those estimated in the REA and for which CFK model estimates are 

comparable to COHb measurements obtained from venous blood of study 

subjects. CFK model evaluation studies are discussed in depth in the 2000 

AQCD. For example, based on experiments performed for 10 different CO 

exposure profiles at several exercise levels, the 2000 AQCD concluded that “the 

agreement between measured and predicted COHb under these varied conditions 

was very good” (2000 AQCD, p. 5-14). 

 

5.  Additional Comments on Interpretation of Scientific Evidence

Specific comments on the EPA’s interpretation of the scientific evidence not discussed in 

the preamble to the final rule are described and addressed in this section.

(1) Comment: One commenter (Donnay) argued that the reliance on COHb for 

judging the effects of CO is inappropriate, stating that venous COHb is “not a 

consistent or meaningful biomarker of either CO dose or effect”. In support of 

this view, the commenter first states that “vCOHb is a unreliable measure of any 

recent CO exposure”, which ”does not correlate consistently with the symptoms, 

severity or outcomes of CO poisoning” because, in the commenter’s view, 

“[venous COHb] always rises more slowly than [arterial COHb] in response to 

any level of exposure ... taking anywhere from 6 to more than 20 hours to reach 

equilibrium with arterial COHb” (Donnay, p. 4). 

Response: The EPA disagrees with the commenter’s view that COHb should not 

be relied upon as a biomarker of CO exposure, dose, and effect. The EPA accepts 

that using the measurement and estimation of COHb has limitations in terms of 

interpretation of the immediate dose following CO inhalation (discussed in 

Section 4.2 of the ISA). However, COHb measured in venous blood remains the 

most extensively validated biomarker of CO exposure and effects, and is the 

metric used in published health outcome studies (ISA p. 4-1; ISA, section 5.2.4). 

EPA agrees with the commenter that in response to changes in CO exposure 

conditions the evidence indicates there is a period where the arterial and venous 

COHb levels are not equivalent. EPA notes, however, such periods are quite 

short and, based on the relationship between magnitude of exposure and size of 

the disparity, any such disparity is expected to be small under exposure conditions 

associated with ambient CO. As discussed in the ISA (ISA, section 4.2.1), this 

disparity between venous COHb (vCOHb) and arterial COHb (aCOHb) was 

examined by Benignus et al. (1994). This study, also quoted by the commenter, 

concludes that “after rapid high concentration CO uptake (6,683 ppm CO) in 

resting adults, the CFKE-predicted group mean change in COHb became 

indistinguishable from the group mean observed change in COHb in peripheral 

venous blood within 2-5 min after the end of exposure”. Benignus et al. (1994) 

found that vCOHb and aCOHb equilibrated in less than 10 minutes in most 
 25 

subjects exposed to high concentrations of CO, highlighting the short-lived nature 

of this inequality. Importantly, the a-vCOHb disparity was proportional to the 

COHb equilibrium level. Thus, although comparisons of arterial and venous 

COHb concentrations have not been investigated after ambient exposure to CO in 

a similar experimental manner as has been done for high concentration CO 

exposures, exposure to the much lower ambient levels of CO would be expected 

to result in a much smaller difference between venous and arterial COHb making 

the venous COHb an informative measure of arterial COHb and the distribution of 

CO among critical organs, such as the heart and brain. 

(2) Comment: Some commenters (Donnay, PSR et al) questioned EPA’s reliance on 

the Allred et al. controlled human exposure study in evaluating the health effects 

of CO, with one commenter stating that the age of the study (conducted more than 

20 years ago) precludes it from meeting the CAA requirements for EPA to rely on 

the latest scientific knowledge. The commenters also argue that the study 

population was small and only included non-smoking men, making the study 

“inappropriate for use as the primary basis for a national population standard” 

(PSR, p. 5) The commenters state that the study used exposure conditions 

significantly different from the low-level exposures experienced currently, and 

that the study results show high inter-individual variability, limiting their 

biological significance. 

Response: EPA strongly disagrees with the assertion that older studies should, as 

a matter of course, be given less weight in evaluating the health effects of 

exposures to the criteria air pollutants, particularly in cases where these studies 

remain the definitive works available in the scientific literature. The study to 

which the commenter is referring (Allred et al., 1989) is a well conducted, 

extensively reviewed, multicenter investigation funded by the Health Effects 

Institute evaluating the effect of carbon monoxide on the induction of myocardial 

ischemia among a relatively large number of human subjects with coronary artery 

disease. The commenters are correct that the results of this study demonstrate 

considerable interindividual variability; however, it is important to note that even 

with this variability, the study was sufficiently powered to detect statistically 

significant CO-induced decreases in time to indicators of myocardial ischemia 

during exercise at both COHb concentrations (i.e., targeted COHb concentrations 

of 2% and 4%). As pointed out by the commenter, in order to achieve these 

COHb concentrations during a relatively short exposure period (~60 minutes), 

average exposure concentrations that were higher than typical 1-hour ambient CO 

exposure concentrations were used by necessity. Nonetheless, as is illustrated by 

the REA, the resulting COHb concentrations for the lower exposure conditions 

(which averaged 2-2.4% COHb20) fall within those that might occur in response 

to ambient CO exposures under conditions when the current 8-hour standard (the 

 

20 The average COHb level immediately upon cessation of CO exposure conditions was 2.4% and the 

average across the subjects after exercise and at the time of response measurement was 2.0% (Allred et al., 

1989). 
 26 

controlling standard) is just met (e.g., PA, Table 2-4). Further, we note that the 

study was designed by an advisory committee appointed by HEI’s Research 

Committee; three of the six advisory committee members were experts not 

affiliated with HEI. The overriding objective was to produce an independent, 

robust and high quality study that would be informative to the consideration of the 

occurrence of exercise-induced myocardial ischemia that might be associated with 

exposures that may occur under the current NAAQS (Allred et al. 1989, p. 81). 

With respect to the commenters’ view that EPA has placed undue emphasis on the 

findings of Allred et al. (1989), it is important to note the results of this study are 

supported by other similar controlled human exposure studies (see ISA, section 

5.2.4). As described in the ISA and alluded to by the commenters, differences in 

experimental protocols and analytical methods across studies (Adams et al, 1988; 

Allred et al., 1989; Anderson et al. 1973; Kleinman et al., 1989; Kleinman et al., 

1998) do not allow for an informative quantitative pooled or meta-analysis. 

Nonetheless, similar to Allred et al. (1989), these studies demonstrate decreases in 

the time to onset of angina among individuals with coronary artery disease 

following exposure to CO resulting in COHb concentrations between 3% and 6%. 

Further, a much larger body of epidemiologic studies of cardiovascular outcomes 

(described in section 5.2.1 of the ISA) is coherent with this line of evidence (ISA, 

section 5.2.6.1). In evaluating the health effects evidence for relevant exposures to 

CO, EPA has integrated evidence from across scientific disciplines, recognizing 

the strengths, limitations, and uncertainties associated with each study type, as 

well as each of the individual studies reviewed. EPA requested that CASAC 

comment on the interpretation of the evidence and the causal determination 

reached for short-term exposure to CO and cardiovascular morbidity as a part of 

the review of the second draft CO ISA. In their consensus response to the 

Agency’s charge (Brain and Samet, 2010a), CASAC stated, “The most 

compelling CO-related CVD results remain those from the 20+-year-old 

controlled human exposure studies ... More recent human epidemiology studies of 

morbidity at ambient CO levels, including data on hospital admissions, are 

consistent with and reinforce the observations from earlier controlled human 

studies.” These statements provide strong support to the Agency’s consideration 

of the study by Allred et al (1989) in the scientific evaluations and conclusions 

described in the ISA. 

Thus, EPA concludes it is appropriate to place weight on the results of the study 

by Allred et al (1989) to inform our interpretation of dose estimates from the REA 

under conditions associated with just meeting the current standard. Such 

consideration of this study is consistent with the critical role of the study in 

providing quantitative evidence regarding health effects associated with shortterm exposures to ambient CO in the ISA, and with the complexity of drawing 

quantitative conclusions from the epidemiological studies of cardiovascular 

outcomes recognized in the ISA and by CASAC (ISA, p. 2-14; PA, pp. 2-34 to 2-

39; Brain and Samet, 2010a). 
 27 

(3) Comment: One commenter (PSR et al.) contends that the weight EPA gives to 

angina-related effects in patients with coronary artery disease (CAD) in 

considering the adequacy of the NAAQS is inappropriate. In support of this view, 

the commenter cites a CASAC comment regarding consideration of the 

epidemiological studies for various cardiovascular outcomes and potential 

uncertainty associated with identification of the population most susceptible to 

CO-induced effects, as well as the commenter’s own comparison of effect 

estimates reported from epidemiological studies for various health outcomes. 

Response: As an initial matter, EPA notes that we have not limited our focus in 

this review to angina (a symptom of myocardial ischemia, which does not occur 

in all individuals with myocardial ischemia). Rather, EPA has appropriately 

focused on ischemia-related effects in patients with CAD as the population group 

most sensitive to effects of ambient CO exposures (ISA, p. 2-10; 2000 AQCD, p. 

4-3). The focus on ischemia-related effects is well-supported by the integrated 

evaluation of the evidence from controlled human exposure, toxicological and 

epidemiological evidence, rather than reliance on a singular outcome in the 

epidemiological evidence, as is implied by the commenter’s statements. In fact, 

the CO ISA concludes that “The most compelling evidence of a CO-induced 

effect on the cardiovascular system at COHb levels relevant to the current 

NAAQS comes from a series of controlled human exposure studies among 

individuals with CAD” (pg 5-47), which found decreased time to onset of 

exercise-induced angina and electrocardiogram changes indicative of myocardial 

ischemia. The findings from the epidemiological studies are coherent with this 

evidence, and the known role of CO in limiting O2 availability lends biological 

plausibility to ischemia-related health outcomes following CO exposures. 

Because the most compelling evidence is from controlled human exposure studies 

among individuals with CAD, a view endorsed by CASAC (Brain and Samet 

2010a, p. 12), the focus on ischemia-related effects in susceptible groups, 

including people with CAD and other types of heart disease is appropriate. 

In comparing effect estimates, the comment cites a single effect estimate from a 

single study of hospital visits for angina and some higher effect estimates for 

individual studies of other cardiovascular endpoints (e.g., stroke and heart attack). 

In focusing on effect estimates from individual studies, they overlook the need for 

an integrated assessment of the evidence which is provided by the ISA. In this 

assessment, EPA concludes that the epidemiological studies of CAD outcomes 

are coherent with the results of the controlled human exposure studies and that, 

given this consistent and coherent evidence from epidemiological and human 

clinical studies, along with biological plausibility provided by CO’s role in 

limiting oxygen availability, a causal relationship is likely to exist between 

relevant short-term exposures to CO and cardiovascular morbidity (ISA, p. 5-48). 

The commenter ignores the full range of epidemiological study results for 

ischemia-related outcomes. For example, Figure 5-2 of the ISA demonstrates that 

studies evaluating the association of CO concentrations and ischemia-related 
 28 

outcomes (including ischemic heart disease, angina, and myocardial infarction) 

generally report increases in the number of hospital admissions for these 

outcomes, ranging in magnitude from approximately 1% to 20% (ISA, p. 5-27). 

(4) Comment: One commenter (Donnay) stated that studies of the associations of 

effects with exhaled CO (eCO) were ignored in the CO ISA, and that eCO is a 

more consistent biomarker than COHb of both exogenous CO exposure and 

elevated endogenous CO production. This commenter further stated that EPA 

should rely more on exhaled CO (instead of COHb) as key metric for assessing 

CO effects and exposure. 

Response: The commenter provides a bibliography of additional references 

pertaining to eCO, some published after May 2009, the CO ISA reference date 

cut-off. The majority of the provided publications focus on the association of 

eCO with various diseases not resulting from CO exposure. EPA agrees that 

endogenous CO is increased by a number of diseases and health conditions (ISA, 

section 4.5) and that these diseases result in increased eCO (ISA, Figure 4-12). 

This is a result of up-regulation of heme oxygenase expression and activity and 

heme protein catabolism. However, these publications do not provide evidence of 

eCO as an indicator of CO exposure but instead as an indicator of inflammatory 

and oxidative health conditions that increase endogenous CO production and thus 

elimination. Based on EPA’s provisional consideration of these studies, in the 

context of the findings of the ISA, EPA concludes that the new information and 

findings do not materially change any of the broad scientific conclusions 

regarding effects as to the relevance of eCO as a biomarker of CO exposure made 

in the 2010 CO ISA and thus do not warrant reopening the air quality criteria 

review. 

The use of eCO as an indicator of clinical severity of disease is well documented 

(e.g., ISA, Figure 4-12, p. 4-25). However eCO has not been established as a 

biomarker of ambient air CO exposure. One study provided by the commenter 

elegantly describes the necessity of biomarker validation (Scherer, 2005) 

including understanding of specificity, sensitivity, population background levels, 

dose-response relationship, inter- and intra-individual variability, kinetics, 

confounding, and modifying factors. However, the use of eCO as a biomarker of 

ambient CO exposure has not been characterized with regard to these criteria. To 

date, evidence is lacking to fully characterize the response of eCO concentrations 

to inhaled CO concentrations and accordingly no quantitative models that 

describe this relationship are available, thus limiting the utility of eCO as a 

biomarker of exposure to ambient CO. As COHb has been used as the biomarker 

of CO exposure for decades the necessary validation of COHb as a biomarker has 

been conducted, including the development of multiple quantitative models 

describing its generation in response to CO exposure (see ISA, section 4.2). 
 29 

Finally, as eCO has been the focus of recent research, whereas COHb has been 

used as a marker of CO dose for many years, health effects studies have not used 

eCO as the primary dose metric when investigating the relationship between 

exogenous CO exposure and biological responses including ischemia-related 

cardiovascular outcomes, birth outcomes, or other health effects. Therefore, EPA 

does not find adequate support in the scientific evidence for the use of eCO in 

assessing CO effects and exposure. 

 (5) Comment: One commenter (Donnay) stated that EPA did not give adequate 

consideration to studies of effects other than COHb-mediated hypoxia, and the 

commenter provided a list of publications he states provide evidence of other 

measures of CO effects which should have been considered in this review, and 

which he considers to support his view that EPA should have focused less on 

COHb in this review. 

Response: The 14 publications cited by the commenter on other measures of CO 

effects include 10 studies of CO poisoning or intoxication. As discussed above 

(response to comment II.B.3(3) above), these studies are outside the scope of the 

ISA (ISA, section 1.5) because EPA judged them to be “not directly relevant to 

ambient exposures” (ISA, pp. 1-6 and 1-7). The other four studies include one 

which describes a new method for measuring COHb, an animal study 

demonstrating the role of free radicals in ototoxicity resulting from noise plus CO 

exposure, a case report describing central nervous system effects thought to be 

associated with chronic CO exposure and an epidemiologic study describing an 

association of CO exposure with indices of atherosclerosis in barbecue workers. 

One of these latter two studies was published after the cutoff date for the ISA. 

Based on EPA’s provisional consideration of these studies, in the context of the 

findings of the ISA, EPA concludes that the new information and findings do not 

materially change any of the broad scientific conclusions regarding effects 

associated with CO exposure made in the 2010 CO ISA and thus do not warrant 

reopening the air quality criteria review. Furthermore, as described in the 

response to comment (II.B.5(1) above), EPA believes that the ISA’s focus on 

COHb is appropriate, given that COHb has been extensively validated over many 

years, is well-correlated with other biomarkers, and is the basis for controlled 

human exposure studies investigating health effects of CO. 

(6) Comment: One commenter (Donnay) pointed EPA to consideration of a list of 

studies describing genetics and gene expression of heme oxygenase, by which 

endogenous CO is derived, including studies of associations between heme 

oxygenase genetic polymorphisms and susceptibility to coronary artery disease. 

In so doing, he stated that, as EPA cannot regulate endogenous CO, they should 

more tightly regulate exogenous CO exposures in order to reduce total risk. 
 30 

Response: The EPA recognizes that there are numerous conditions and disease 

states where heme oxygenase (HO-1) is induced. As discussed in the ISA, the 

resulting excess endogenous CO may react intracellularly with heme proteins or 

diffuse into the blood according to the gradient of pCO in the cell/tissue and blood 

compartments (ISA, section 5.1.3.3). Short-term increases in HO-1 often 

represent adaptive responses to stress. Longer-term increases in HO-1 are 

sometimes associated with protective responses and sometimes with 

pathophysiologic responses. While it is possible that prolonged increases in 

endogenous CO production may result in less of a reserve capacity to handle 

additional intracellular CO resulting from exogenous exposures, there is no 

experimental evidence to support this mechanism. 

Similarly, polymorphisms of the heme oxygenase gene promoter may result in 

inter-individual variation in endogenous CO levels. Since CO is a product of 

reactions catalyzed by heme oxygenase, altered expression of heme oxygenase 

could lead to more or less intracellular CO. Some studies, including some cited 

by the commenter, have linked lower HO-1 expression, which would lead to 

lower endogenous CO, to increased susceptibility to coronary artery disease (or 

adverse cardiovascular outcomes) in humans. These results are consistent with 

cytoprotective effects of CO demonstrated experimentally (see ISA, sSection 

5.3.1.2). Based on EPA’s provisional consideration of these studies, in the 

context of the findings of the ISA, EPA concludes that the new information and 

findings do not materially change any of the broad scientific conclusions 

regarding effects associated with CO exposure made in the 2010 CO ISA and thus 

do not warrant reopening the air quality criteria review. While these findings are 

intriguing and suggest that endogenous CO may play a role in susceptibility, other 

plausible mechanisms have not been ruled out. For example, iron and biliverdin, 

which are also products of heme oxygenase-catalyzed breakdown of heme and 

also bioactive, could mediate the cytoprotective effects. Conversely, iron and 

biliverdin could mediate pathophysiologic effects associated with increased HO1. 

Thus, while it is possible that prolonged increases in endogenous CO resulting 

from chronic diseases or deficits in endogenous CO resulting from genetic 

polymorphisms may provide a basis for the enhanced sensitivity of susceptible 

populations to CO-mediated health effects, additional studies are required to 

investigate the relationship between internal CO burden and associated health 

risk. As noted in the ISA, “CO may be responsible for a continuum of effects 

from cell signaling to adaptive responses to cellular injury...” (ISA, p. 5-11). 

It should be noted that the commenter cited numerous studies of “genetics and 

gene expression of CO and its primary endogenous source” (Donnay, p. 8). Only 

a minority of these studies address genetic polymorphisms of heme oxygenase in 

humans. As described above, our provisional consideration of these studies 

concludes that the study findings do not materially change any of the conclusions 

made in the ISA regarding effects associated with CO exposure and thus do not 
 31 

warrant reopening the air quality criteria review. The majority of the studies 

which were cited addressed other topics including the therapeutic effects of heme 

oxygenase achieved by transfection or gene therapy in animal models, the 

regulation of HO gene expression by cellular signaling pathways and the role of 

CO in regulating the expression of genes. These topics, while scientifically 

interesting, do not address the issue of susceptibility in human populations or the 

health effects of ambient CO exposure, and as such are outside the scope of the 

ISA. 

(7) Comment: One commenter (AAM) stated that the evidence on potentially 

beneficial effects of exposure to CO should be considered by the Administrator, 

additionally claiming the information in this area is relevant to the interpretation 

of the epidemiological results. 

Response: As the commenter recognizes, studies on therapeutic or potentially 

beneficial aspects of CO application (e.g., anti-inflammatory response) are 

discussed in the ISA (ISA, section 5.1.3.2). Accordingly, such effects are part of 

the body of evidence considered by the Administrator during this review. The 

ISA notes, however, that dose-response relationships between CO and these types 

of effects remain unexplored and that it is “unclear how these effects may be 

related to environmentally-relevant exposures” (ISA, p. 5-7). For example, 

results of controlled human exposure studies, which evaluated the potential antiinflammatory effects of exposure to 100-500 ppm CO, were mixed. One of the 

two studies reported no effect, and a second reported that two of the nineteen 

subjects experienced exacerbations of COPD. Thus, while some studies 

demonstrate the involvement of CO in potentially beneficial physiological 

processes, uncertainties regarding dose-response relationships, the link between 

these effects and environmentally relevant exposures, and the potential for 

concomitant adverse effects complicate the interpretation of this evidence with 

respect to health effects of CO in ambient air. While the commenter states that 

evidence on potentially beneficial effects of exposure to CO is relevant to the 

interpretation of epidemiological studies, we note that to the extent some 

beneficial effect is exerted by ambient CO, it would inherently be reflected in the 

studies. 

CASAC agreed with EPA’s characterization of this evidence (Brain and Samet, 

2010a, p. 13), saying that: 

There is a growing literature regarding possible therapeutic 

applications of CO at levels of ~250 ppm. These studies have been 

carried out in some animal models and in cell culture. CO is a prooxidant and has profound extended pro-inflammatory effects. 

However, in specific scenarios with distinct organ systems or 

specific cell types, CO may have short-term anti-inflammatory 

effects. Clinical trials thus far have not supported health benefits 

of CO administration. Further, there is no evidence that the 

hypothetical therapeutic results provide any insight into health 
 32 

effects of acute or chronic ambient exposures in the general 

population, and especially in subpopulations susceptible to CO 

effects. 

Thus, EPA does not believe the current evidence regarding possible therapeutic 

aspects of CO is informative to judgments regarding the adequacy of the CO 

NAAQS. 

(8) Comment: One commenter (CBD et al) asserts that EPA, in judging the adequacy 

of the current standards, was not justified in giving less weight to the 

epidemiological evidence, claiming that this type of evidence is the only type 

available for noncardiovascular effects, and consequently, should be given 

weight. The commenter argues that EPA has given weight to the epidemiological 

studies for other criteria pollutants, such as PM, after considering and rejecting 

concerns about confounding from other pollutants, unlike its approach for CO, 

and that two CO measurement issues noted by EPA in the proposal would tend to 

only underestimate any existing effect of CO. 

Response: As an initial matter, EPA notes that, contrary to the commenter’s 

assertion, epidemiological studies are not the only type of study available on 

noncardiovascular effects of CO. For example, as noted in the ISA’s summary of 

the long-standing database of CO toxicological studies on birth outcomes and 

developmental effects, “in utero or perinatal CO exposure in pregnant dams or 

pups affects outcomes in the offspring, including postnatal mortality, skeletal 

development, the ability of the developing fetus to tolerate maternal dietary 

manipulation, behavioral outcomes, neurotransmitters, brain development, the 

auditory system, myocardial development, and immune system development” 

(ISA, p. 5-63).21 In considering whether exposures associated with CO in 

ambient air might be expected to elicit such effects, the 2000 AQCD went on to 

conclude that “it is unlikely that ambient levels of CO typically encountered by 

pregnant women would cause increased fetal risk” (2000 AQCD, p. 6-44). In 

considering the full evidence base in this review regarding the potential for 

ambient concentrations of CO to elicit birth and developmental effects, we 

concluded it was only suggestive of a causal relationship. In so concluding, we 

noted uncertainty regarding the biological plausibility of ambient CO eliciting the 

effects that were associated with ambient CO in epidemiological studies and the 

inability to sufficiently rule out the role of chance, bias and confounding in those 

studies, in addition to the limited extent of the evidence and the mixed findings 

for some outcomes (ISA, pp. 1-14, 5-79, 5-80), as described in the response to 

comment II.A.3(2). 

 

21 The 2000 AQCD states that “[f]rom all of the laboratory animal studies, it is clear that severe, acute CO 

poisoning can be fetotoxic, although specification of maternal and fetal COHb levels is difficult” and that 

data reviewed in the 1991 AQCD “provide strong evidence that maternal CO exposures of 150 to 200 ppm, 

leading to approximately 15 to 25% COHb” produce a range of developmental effects with some isolated 

experiments suggesting that “some of these effects may be present at concentrations as low as 60 to 65 ppm 

(approximately 6 to 11% COHb) maintained throughout gestation” (2000 AQCD, p. 6-44). 
 33 

Thus, in considering the epidemiological studies for noncardiovascular effects, 

such as developmental effects, we have recognized uncertainties of the CO 

evidence base related to biological plausibility of such effects being elicited by 

ambient concentrations of CO, and we have also taken note of the advice offered 

by CASAC regarding potential confounding (e.g., Brain and Samet, 2010a). In so 

doing, contrary to the commenter’s assertion, EPA has considered issues of 

potential confounding in epidemiological studies using the same approach for CO 

as we have for other criteria pollutants. That approach includes the consideration 

of the full evidence base available for each pollutant for the array of health effects 

assessed. Accordingly, the Administrator’s judgment as to the weight to give to 

epidemiological studies in judging the adequacy of the current CO standards takes 

into consideration the full evidence base for CO, which includes epidemiological 

studies but is comprised largely of non-epidemiological studies and which 

provides the basis for our understanding of CO mechanisms of action, toxicity, 

and health effects, as well as the spatial and temporal variability of ambient 

concentrations and exposures. 

As noted above and elsewhere in this document, the evidence for the 

noncardiovascular effects cited by the commenter is “suggestive” of a causal 

relationship with ambient CO, yet evidence is generally lacking on mechanism or 

mode of action that might lend biological plausibility to associations of effects 

with low ambient concentrations observed in epidemiological studies. In light of 

this uncertainty, particularly careful attention must be paid to the possibility of 

confounding, and indeed CASAC commented that “the problem of co-pollutants 

serving as potential confounders is particularly problematic for CO” (Brain and 

Samet, 2010a). CASAC further stated that “consideration needs to be given to the 

possibility that in some situations CO may be a surrogate for exposure to a mix of 

pollutants generated by fossil fuel combustion” and “a better understanding of the 

possible role of co-pollutants is relevant to ... interpretation of epidemiologic 

studies on the health effects of CO” (Brain and Samet, 2010a). We recognize 

that, as the commenter notes, some study authors use statistical methods to adjust 

for multiple pollutant effects, typically through the use of two pollutant regression 

models (ISA, p. 1-11), and, in assessing the evidence in the ISA, we considered 

the results of such models. We also recognize, however, that, as also noted by 

CASAC, associations reported for CO may be related to the presence of other, 

etiologically-relevant pollutants that are correlated with CO yet absent from the 

analysis (PA, p. 2-37). We particularly recognize this potential in light of the 

understanding we draw from the larger CO evidence base and its various aspects, 

many of which differ from the evidence bases for other criteria pollutants, such as 

PM and NO2 (e.g., PA, pp. 2-36 to 2-39; 76 FR 8177-8178). 

Moreover, a central question for this review is what patterns of ambient CO 

concentrations might be expected to cause adverse health effects and whether the 

current standards provide requisite protection against such occurrences. Apart 

from uncertainty as to whether ambient CO exposure is causally related to 
 34 

noncardiovascular health effects, the two ambient CO measurement issues 

described in section II.D.2(a) of the proposed rule complicate and contribute 

uncertainty to our interpretation of the epidemiological studies with regard to the 

specific ambient CO concentrations that may have elicited the reported health 

outcomes.22 Thus, while we agree with the commenter’s statement that 

uncertainty associated with the two CO measurement issues they cite could 

contribute to an underestimation of CO effect in the epidemiological studies, 

uncertainty in the size of effect estimates (e.g., change in health risk per unit of 

exposure metric) is not the uncertainty of primary concern for the central question 

posed above. Rather, the uncertainty of concern to this question is related to what 

might be concluded from the studies with regard to what, if any, specific ambient 

concentrations of CO may have elicited the observed health outcomes. The two 

measurement issues as well as the potential for confounding and the larger issue 

of biological plausibility at ambient CO concentrations, contribute to this 

uncertainty (PA, pp. 2-37 to 2-39; 76 FR 8177-8178). 

In summary, we considered the epidemiological evidence in this review in light of 

the full evidence base for CO, just as we do for other criteria pollutants. In 

considering the extent to which associations of health outcomes with ambient CO 

concentrations in epidemiological studies inform judgments in this review as to 

the adequacy of the current NAAQS, we first consider the extent to which the full 

evidence base supports a conclusion that the relationship of the health outcomes 

with ambient concentrations may be causal. Factors contributing uncertainty to 

this conclusion for noncardiovascular health outcomes are discussed previously in 

this response and in responses to comments (1) and (2) of section II.A.3 above. 

Secondly, we consider whether the current standards were met during the study 

periods, and what might be concluded from the studies with regard to specific 

ambient concentrations eliciting the observed health outcomes.23 In so doing, we 

have identified aspects of the CO evidence base which contribute uncertainty to 

and complicate our use of the epidemiological studies in this regard. In light of 

these uncertainties and complications, these studies have been less informative to 

the Administrator in drawing conclusions regarding the adequacy of the current 

 

22 As described in the proposal (76 FR 8177-8178), the first of the two issues, the prevalence of ambient 

monitor measurements at or below detection limits, is a particular concern for the more recently available 

epidemiological studies in which ambient CO concentrations are much reduced from the past. The second 

issue relates to the use in the epidemiological studies of CO measurements from area-wide or central-site 

monitors which can obscure the significant spatial gradient that exists for CO with distance from source 

locations such as highly-trafficked roadways. 

23 As we note in the PA and proposal, it is the studies conducted under conditions when the current 

standards were met that are particularly informative to the consideration of the adequacy of the current 

standards, and the identification of such studies requires consideration of all elements of the standard 

beyond just the level. For example, even when concentration statistics reported in epidemiological studies 

(e.g., daily maximums at central site monitors, often averaged over multiple days) are below the levels of 

the current standards, CO levels stated in the form of the standards (e.g., second highest daily maximum 1-

hour and 8-hour concentration at a specific location) may, and in many studies do, exceed one of the 

standards (e.g., PA, p. 2-32). The form is an integral part of a NAAQS and its stringency. Thus, it is 

important to consider not simply the value of the air quality statistic reported compared to NAAQS level, 

but whether the air quality met the NAAQS.
 35 

standards, than have other elements of the CO evidence base. Thus, the 

Administrator has fully considered and carefully weighed the available evidence, 

giving greater weight to those aspects more fully supported in making her 

judgment on the adequacy of the current standards to provide the requisite 

protection. 

(9) Comment: Comments from AAM state their view that little weight should be 

given to the epidemiological studies of CO based on several observations that 

they have previously brought to EPA’s attention over the course of the review. 

Commenters additionally describe a recent study as suggesting that the 

epidemiological evidence relied on by EPA in the ISA is unsound. 

Response: EPA carefully considered the epidemiological studies, in light of the 

full evidence base for CO. While EPA has recognized a variety of uncertainties 

related to interpretation of CO epidemiological studies, particularly with regard to 

ambient concentrations that may elicit effects (preamble to final rule, section 

II.B.2), we also recognize the coherence of the study results for ischemia-related 

outcomes with the results of controlled human exposure studies and the biological 

plausibility provided to these studies by the known role of CO in limiting oxygen 

availability (ISA, p. 5-48). These aspects of the full evidence base contribute to 

our conclusion that a causal relationship is likely to exist between relevant shortterm exposures to CO and cardiovascular morbidity, a conclusion that has been 

favorably reviewed by the CASAC Panel, with the Panel concluding the 2010 

ISA to be “adequate for rulemaking with the incorporation of changes in response 

to the Panel’s major comments and recommendations” (Brain and Samet, 2010a). 

In evaluating the epidemiological evidence in the ISA, EPA has considered 

comments provided by the commenter on the ISA, some of which are also 

reflected in this comment submitted on the proposal. Across the documents 

prepared for this review, EPA has carefully considered the evidence, including the 

epidemiological evidence, taking particular note of potential areas of uncertainty. 

For example, in drawing conclusions on the effects of ambient CO, EPA has not 

relied on any one individual study or small cluster of studies. Rather we consider 

the group of studies available for biologically plausible health outcomes, such as 

those related to ischemia following CO exposure (ISA, p. 5-48). In so doing, we 

find the full body of epidemiological studies of emergency room visits and 

hospital admissions for ischemic heart disease to be generally consistent with 

controlled human exposure and toxicological evidence of cardiovascular 

morbidity effects, as noted above. Further, EPA agrees with commenters that 

issues related to model specification for epidemiologic studies, such as selection 

of models and approaches to adjust for meteorological and temporal variables are 

important considerations. The CO ISA describes how these issues were carefully 

considered in selecting studies for inclusion in the ISA and in interpreting the 

results of the body of epidemiologic evidence (CO ISA, Figure 1-1 and 

accompanying text on p. 1-5). Furthermore, we recognize the phenomenon of 

publication bias as a potential source of uncertainty regarding the nature of the 
 36 

association and the magnitude of health risk estimates. Specifically, it is well 

understood that studies reporting non-null findings are more likely to be published 

than reports of null findings, and, thus, publication bias can result in reporting of 

spurious associations and overestimating effects (Ioannidis, 2008). We do not 

agree, however, that publication bias limits the interpretation of published 

associations between CO and health effects. 

Finally, EPA disagrees with the commenters’ assertion that the recent study cited 

by the commenter (Koop et al., 2010) calls into question the epidemiological 

evidence for CO assessed in the ISA. EPA notes several aspects of the study by 

Koop et al. (2010) that limit its interpretation in light of the evidence base for CO. 

For example, the authors use monthly pollutant averages and monthly counts of 

hospital admissions, rather than daily data in their time-series analyses, which 

may overlook relationships in the shorter time-step data, which may have 

relevance to ambient CO. Among the health outcome categories assessed, the 

authors have omitted chronic obstructive pulmonary disease, a respiratory 

outcome that has been demonstrated to be associated with ambient concentrations 

of various air pollutants, while including tracheostomy malfunctions, an outcome 

unlikely to be associated with air pollution. Further, by focusing on hospital 

admissions, rather than physician visits or emergency department visits, it is 

likely that the authors missed all but the most severe cases of some diseases. 

While this study (Koop et al., 2010) was published after the ISA, EPA has 

provisionally considered it and concludes that it does not materially change any of 

the broad scientific conclusions regarding effects associated with CO exposure 

made in the 2010 CO ISA and thus does not warrant reopening the air quality 

criteria review. 

(10) Comment: Comments from NESCAUM stated that EPA should work toward a 

better understanding of the broad range of CO exposures, including those in 

vehicles, and the role of the CO NAAQS in addressing these exposures. They 

additionally state that current research suggests that in-cabin CO may be higher 

than ambient levels and may be a main route of CO exposure. 

Response: EPA agrees that in-vehicle exposures are an important component of 

personal exposure to ambient CO, as indicated by evidence described in the ISA 

(ISA, section 3.6.6) as well as the REA results. The ISA summarizes the current 

evidence with regard to roadway-related results (ISA, sections 3.6.6 and 3.5.1.3). 

Further, the REA which also informs our understanding, found that time spent on 

or near motor vehicle activity (e.g., in vehicles, in garages) was a major 

contributor to higher CO exposures (e.g., REA, section 6.4). Lastly, we note the 

revisions to the CO monitoring network to include near-road monitors made in the 

final rule (preamble to final rule, section IV) is expected to help to improve our 

understanding of the gradients in ambient CO concentrations in the near-road 

environment which will in turn contribute to an improved understanding of 

roadway-related exposures.
 37 

6.  Additional Comments on the Exposure and Health Risk Assessment  

Comments related to the REA for CO that are not discussed in the preamble to the final 

rule (e.g., in sections II.B) are described and addressed in this section. 

(1) Comment: One public commenter (Thomas McCurdy) expressed concern with 

how alveolar ventilation rate (VA)

24 is estimated by APEX and the resulting 

impact on estimating population COHb levels. In general, this commenter noted 

that the VA to oxygen consumption rate (VO2) relationship is variable, both within 

and between individuals, and not constant as was assumed in the REA (i.e., a 

value of 19.63), particularly noting the existence of a non-linear relationship at 

high ventilation rates. The commenter further indicated their view that accurately 

estimating VA is important because it plays a large role in estimating COHb 

levels. 

Response: EPA does not disagree with much of what the commenter states 

regarding the overall variability in the relationship between alveolar ventilation 

(VA) and oxygen consumption (VO2) rates. When modeling risk and exposure to 

any pollutant, there are always limits in representing the true variability of model 

input variables. This is a common occurrence due to the limited availability of 

input data that fully capture the influential characteristics (e.g., age, gender, 

activity level, health status/condition) driving the variability of many 

physiological variables used in the model, including the VA/VO2 relationship. 

Given the time and resources available for this review, EPA did not perform a 

literature review to evaluate or improve the point estimate of 19.63 used in the 

current REA. We add that this value has been used to estimate VA in prior CO 

exposure assessments (e.g., Johnson et al., 2000). Further, as described below, we 

have concluded that, given the relatively low influence of VA on REA results, the 

current approach was adequate to our needs in estimating exposure and dose in 

this review. 

In response to this comment, we first note that the limitations of the currently 

used relationship, particularly regarding the non-linear relationship of VA to VO2, 

was mentioned in the REA by EPA (and noted by the commenter), specifically 

“the point estimate of 19.63 used may not adequately represent the VA to VO2

relationship at higher ventilation rates” (REA, p. 7-21). More specifically, we 

agree with the commenter’s statement that the VA/VO2 relationship (if plotted as 

an x-y graph) can be “concave upward” (McCurdy, p. 2) at upper ventilation 

rates, hence this non-linearity in the VA/VO2 relationship observed at upper 

ventilation rates would lead to underestimations in VA if using a value of 19.63, 

and assuming this value is consistent with a ratio calculated while performing low 

exertion activities. In considering the VA/VO2 ratios provided by the commenter 

 

24 Alveolar ventilation rate is typically expressed as “ܸ஺

ሶ ”, though the volume associated with alveolar 

ventilation is commonly expressed as VA. For simplicity in the formatting in this document, the rate is 

expressed as VA and represents the rate, not the volume. This was also conferred to how oxygen 

consumption rate is expressed here (VO2 is used); the accent over the “V” is not included. 
 38 

(McCurdy, Table 1, p. 5), we note that the point estimate of 19.63 used in the 

REA falls within the range of these ratios, bounded by values of 17.33 and 26.69, 

representing resting and moderate activity levels, respectively. Based on this 

information alone, VA for persons simulated in the REA while at rest or 

performing low exertion level activities may be slightly overestimated in using 

the value of 19.63, while for simulated persons performing at or above moderate 

exercise, VA may be underestimated. Regarding one variable potentially affecting 

inter-personal variability, VA/VO2 is stated by McCurdy to decrease “moderately 

or greater with age” based on limited VA and VO2max

25data reported for females 

by Astrand (1960). This reported finding, if consistent in both genders and taken 

with the above remarks regarding the non-linear relationship observed while 

performing moderate to greater physical activities, suggests that there would 

likely be a lesser propensity to underestimate VA in older persons than in younger 

persons.26 

We disagree, however, with the commenter’s statement regarding the magnitude 

of importance of VA in estimating COHb levels. Specifically Mr. McCurdy states 

that because VA is used to estimate COHb levels, it “play[s] a large role in all 

conclusions regarding subsequent COHB distributions modeled”. Nowhere in 

Mr. McCurdy’s comments is provided evidence to indicate the magnitude of the 

role VA plays in the calculation of COHb levels. In reviewing a published 

sensitivity analysis of variables input to the CFK model by McCartney (1990), it 

appears that VA does not have a large influential role in the estimation of COHb 

level. In McCartney (1990), the sensitivity of COHb to changes in VA (among 

other CFK equation variables) is evaluated across five work/activity levels, 

ranging from at rest ventilation to performing moderate exercise. McCartney 

(1990) reports “the effect of VA on the equilibrium value of [COHb](t) is small 

(Figure 3 [of publication]) and would be zero in the absence of endogenously 

produced CO.” In our review of Figure 3 in McCartney (1990), we note also that 

there is a consistent trend of decreasing sensitivity of COHb level to VA with 

increasing work level, with maximum sensitivity of equilibrium values of COHb 

to VA observed while at rest (McCartney, 1990, Table V). This research suggests 

that when performing moderate or greater exercise, any inaccuracies in estimates 

of VA would have even less of an influence on estimated COHb levels using the 

CFK model than when at lower activity levels. 

In the REA, EPA staff indicated that the CO exposure concentration was one of 

the most important variables in estimating COHb levels. As noted in the REA, 

“most of the upper level exposure concentrations in this assessment are associated 

with time spent inside vehicles, where it is expected that the exertion level and 

breathing rate would be at a relatively low level” (REA, p. 7-21). The REA then 

concluded that “it may be that the point estimate [used to estimate VA from VO2] 

 

25 Maximal oxygen consumption rate (VO2max) or aerobic capacity is where oxygen consumption plateaus 

or increases only slightly with increasing exercise intensity (McArdle, 2001). 

26 Ischemia-related effects are more prevalent in older persons, and accordingly they are of greater 

importance for this assessment. 
 39 

is appropriately used for these activities [i.e., driving a vehicle] and the estimated 

maximum end-of-hour COHb associated with the in-vehicle microenvironment 

may not be adversely affected” (REA, p. 7-21). As noted above regarding the 

range of VA/VO2 ratios for low to moderate activity offered by McCurdy, driving 

a motor vehicle would be characterized as a relatively low exertion activity, 

generally supporting the value of 19.63 used to estimate VA for simulated persons 

inhabiting this particular microenvironment. 

There was limited time available to perform sensitivity analyses of the APEX 

modeling used in the REA given the review schedule, however EPA was able to 

perform three separate evaluations of input data used and their affect on COHb 

estimates (REA, section7.2.2). The input variables for which sensitivity analyses 

were performed were chosen based on careful consideration of advice from 

CASAC (Brain, 2009; Brain and Samet, 2010b; Brain and Samet, 2010c), the 

situations being simulated and the model specifications and performance. These 

model sensitivity analyses included: the spatial representation of ambient CO 

concentrations (all ambient monitors versus design monitor CO concentrations 

only), at-risk prevalence rates used (base prevalence versus increased 

undiagnosed CHD prevalence such that women equaled that of males), and the 

hemoglobin content of blood (a base level versus anemic population). Of these 

three APEX model input variables, variability in the spatial representation of 

ambient CO concentrations contributed to the greatest amount of variability in 

percentage of persons at or above selected COHb levels (REA, Tables 7-5 

through 7-8). This relative importance of ambient CO concentration and its 

influence on COHb levels was also indicated by McCartney (1990), with inspired 

CO concentration among one of the few input variables conferring nearly an 

equivalent factor of influence on equilibrium COHb values.27

Subsequent to completion of the REA, EPA performed additional analyses on the 

REA-generated APEX outputs to determine the magnitude of influence VA and 

exposure concentrations have on estimated COHb levels using the event-level 

output data generated for the REA.28 The results of an analysis of variance and 

multiple linear regression modeling indicate that the combination of endogenous 

COHb, real-time CO exposure concentrations, and CO exposure concentration 

 

27 McCartney (1990) used fractional sensitivities to evaluate the influence of input variables in the CFK 

model, such that a value of unity (or 1) “means that an error in the selected variable propagates 

unattenuated to an error in calculated [COHb](∞).” Table V of McCartney (1990) indicates maximum 

sensitivity values for the nonlinear CFK equation, with inspired CO concentration ranked 4th highest and 

having a maximum fractional sensitivity of 0.92, while the VA was ranked 11th having a maximum 

fractional sensitivity of 0.53. 

28 The additional analyses were performed using the 5,000 person APEX simulation event-level files 

generated in the REA for air quality just meeting the current standard and for both study areas. These files 

are described in Docket item EPA-HQ-OAR-2008-0015-0123. Data output to the APEX file and included 

in the analysis were end-of-event COHb, calculated endogenous end-of-event COHb from endogenous 

simulations, event CO exposure concentration, event VA, event duration, hourly averaged CO exposure 

concentrations from hours 1, 2, and 3 prior to the event, and hourly average VA from hours 1, 2, and 3 prior 

to the event. 
 40 

lags from prior hours were the most important input variables in explaining 

variability in COHb levels. While VA was a statistically significant explanatory 

variable in the statistical models, the overall contribution of variation in VA to 

variability in COHb level was negligible in comparison with the exposure 

concentration variables and COHb resulting from endogenous CO production. 

Therefore, the results of sensitivity analyses by McCartney (1990), as well as our 

own APEX model sensitivity analyses and output data evaluations, indicate that 

CO exposure concentration is a much more influential variable relative to that of 

VA in estimating a person’s COHb level. Thus, although the VA approach used in 

the REA has recognized limitations (e.g., REA, p. 7-21), the potential magnitude 

of influence of this APEX input variable is smaller than other variables, such as 

the time series of CO exposure concentrations. 

 

B.  Comment on Consideration of a Secondary Standard

General comments based on relevant factors that either support or oppose EPA’s decision 

that a secondary standard for CO is not requisite to protect the public welfare from 

adverse effects associated with CO in ambient air are addressed in section II.C of the 

preamble to the final rule and/or in this section of this document below. 

(1) Comment: In testimony at the public hearing, one commenter (Gossage) stated 

that EPA's consideration of a secondary standard lacked review of CO-related 

"hazards to transportation" which is included in CAA definition of welfare 

effects. In response to a query regarding the types of such hazards related to CO, 

another commenter stated that there were studies of CO exposure effects on the 

ability of drivers to manage the hazards of driving at exposure ranges below the 

current one-hour standard, although references for such studies were not provided. 

Response: EPA notes that it is not clear whether the neurological effects on 

drivers cited by the commenters fall within the meaning of “hazards to 

transportation” as that phrase is used in defining “welfare” for purposes of the 

NAAQS. Even assuming that these effects would constitute adverse effects on 

public welfare, as well as adverse effects on public health, EPA does not believe 

there is evidence in the air quality criteria of such effects associated with ambient 

concentrations of CO that would warrant establishment of a secondary standard 

(or revision of the primary standard), nor was such evidence provided by the 

commenter. EPA notes that the ISA characterized the evidence as only 

suggestive of a causal relationship between relevant short-term CO exposures and 

central nervous system (CNS) effects. The ISA further concluded that, while 

acute CO poisoning events (involving exposure to levels much higher than the 

NAAQS) have been known to adversely affect CNS function, controlled human 

exposures have provided limited and equivocal evidence for neurobehavioral 

effects resulting from somewhat lower levels of CO exposure. The lowest level 

evaluated in these studies, however, was associated with quite elevated COHb 
 41 

levels, in the range from 5 to 20% (PA, p. 2-16). As indicated by the REA results, 

little if any occurrence of COHb levels over 4% are expected under conditions 

associated with just meeting the current 8-hour standard (PA, Table 2-4). 

 (2) Comment: One commenter (CBD et al) stated that EPA should consider the role 

of CO in contributing to climate-related effects of ozone, objecting to EPA’s 

conclusion that indirect effects of CO on climate that are attributable to ozone 

formation should be addressed through the ozone NAAQS. 

Response: To the extent that indirect effects of CO on climate are attributable to 

ozone it would be more appropriate to address them in the review of the ozone 

NAAQS. The NAAQS for a criteria pollutant must be requisite to protect public 

health and welfare in accordance with the Clean Air Act, and EPA does not 

believe it necessary or appropriate to additionally consider the adverse effects 

attributable to one criteria pollutant in setting the standard for a different criteria 

pollutant which may also be a precursor to the first pollutant. For example, the 

NAAQS for oxides of nitrogen (long-recognized ozone precursors) are not set to 

establish requisite protection from the adverse effects of ozone. 

C.  Comments Related to Monitoring  

1. Sampling and Analysis Methods

 Comments received (API) on the proposed revision to part 50 and part 53 generally 

indicated support for the general proposed changes to update and clarify the CO Federal 

reference method (FRM). The commenter also welcomed the general upgrading of the 

analyzer performance requirements and that new candidate CO Federal equivalent 

methods (FEM) analyzers will be required to meet them. Comments on specific aspects 

of the proposed changes are addressed below.

(1) Comment: Part 50, appendix C – In section 4.2.1 (in the calibration procedure), 

EPA proposes to change the requirement for flow rate control and regulation to 

±2% from the existing ±1% requirement. The commenter questioned whether this 

relaxation was intended or an oversight. 

Response: This change is intended. In response to this comment, EPA has 

reconsidered this proposed change. However, it was again determined that the 

1% requirement for flow rate control and regulation was unnecessarily stringent 

in comparison with the level of overall uncertainty tolerable in the calibration 

system and in the monitoring instrument. This change is commensurate with the 

flow rate measurement accuracy requirement of 2% (which is unchanged from the 

existing requirement) in the succeeding section 4.2.2. 
 42 

(2) Comment: Part 50, appendix C- The commenter suggested that the numerator in 

Formula 1 (of the calibration procedure) should contain either parentheses or a 

multiplication symbol to indicate that the two terms are to be multiplied. 

Response: EPA has made a change in response to this comment. Although not 

mathematically necessary, the addition of a multiplication symbol in the 

numerator of the formula will help to clarify that the two terms are to be 

multiplied. 

(3) Comment: Part 50, appendix C – The commenter points out that in sections 4.4.5 

and 4.4.6 (of the calibration procedure), no provision is made for connecting a 

data read-out device to the CO analyzer under calibration to facilitate monitoring 

of the analyzer readings. Use of the analyzer’s visual display may not accurately 

represent the way readings are routinely recorded. 

Response: EPA has made a change in response to this comment. Typically, 

FRMs do not contain such a provision, since it seems quite obvious that such a 

device is necessary. However, the suggestion to include such an appropriate 

provision has merit and may help to improve the overall accuracy of the 

calibration. Section 4.4.3 has been revised to include a statement that the readout device used should represent the way that the routine analyzer readings are 

recorded. 

(4) Comment: Part 53, subpart B – The commenter stated they could not review the 

complete set of analyzer performance data that EPA cited as a basis for the 

proposed new FRM and FEM analyzer performance requirements because the 

cited reference (a spreadsheet of analyzer manufacturers’ published performance 

data for various analyzers) did not include the performance data from FRM 

applications received by EPA that were also used by EPA for this purpose. 

Response: In addition to the performance data included in the referenced 

spreadsheet, EPA also used data from recent CO FRM applications that EPA has 

received and processed under part 53. These latter data could not be included in 

the referenced spreadsheet because the applications and all data they contain are 

identified by their respective applicants as confidential business information 

(CBI). EPA must treat data identified as CBI in accordance with 40 CFR part 2, 

which restricts its public release pending a final determination of its status as CBI. 

Any person seeking to review data for which a claim of CBI has been made may 

file a request under the Freedom of Information Act and 40 CFR part 2. 

(5) Comment: Part 53, subpart B – The commenter stated that EPA did not provide 

or cite data to support its conclusion that the existing performance limit 

requirement for the “total of all interferents” is redundant with the individual 

interferent limits for modern CO analyzers and the proposed withdrawal of this 

total interference limit requirement. 
 43 

Response: In response to this comment, EPA has re-examined the efficacy of the 

existing total interference limit requirement for CO analyzers and has again 

determined that it is not necessary. All CO analyzers in monitoring use today are 

FRMs, which use an infrared absorption measurement principle. For these 

analyzers, only 2 interferents are listed in Table B-3 of 40 CFR part 53, and the 

analyzers’ responses to those interferences are typically well controlled. Even for 

other potential measurement principles listed in Table B-3 – none of which are 

represented in currently available CO analyzers – only a few interferences are 

listed, and they are quite unlikely to be all simultaneously elevated at typical CO 

monitoring sites. Thus, the limit for total interferences is of minimal efficacy, and 

therefore EPA believes it can be eliminated. For analyzers opting to meet the 

proposed new lower measurement range, the individual interference limit is 

reduced to 1⁄2 of the limit for the standard measurement range, again rendering the 

need for a total interference limit unnecessary. 

(6) Comment: Part 53, subpart B – Similarly, the commenter states that EPA did not 

cite or provide data to support the proposed withdrawal of the existing limit 

requirement for span drift determined at a concentration of 20 % of the upper 

range limit (URL). The commenter contends that this requirement is important 

because 20 % of the standard range of 50 ppm is 10 ppm, which is close to 

existing (and proposed) 8-hour NAAQS for CO and is closer to the 1-hour 

NAAQS than the 80% URL drift limit. Accordingly, the commenter suggests 

withdrawing the 80% URL drift limit instead of the 20 % URL limit. 

Response: EPA does not agree that the 80% URL drift limit should be withdrawn 

in place of the 20% URL limit. The purpose of the span drift limit is not to 

directly assess measurement error at a particular, mid-scale concentration level. 

That is the purpose of the 1-point quality control check for CO monitors described 

in Section 3.2.1 of appendix A of 40 CFR part 58. FRM and FEM CO analyzers 

have a measurement response function that is well defined and typically very 

nearly linear with respect to the input CO concentration. For the purpose of 

analyzer performance testing, this linear input/output functional characteristic is 

best described by its zero point and its slope, because these parameters are 

generally subject to change (drift) independently. Thus, zero drift (change in the 

zero point) and span drift (change in the slope) are tested separately. Zero drift is, 

of course, measured at zero concentration, and span drift is most accurately 

measured at a concentration near the URL. The span drift test at 80% URL (when 

the zero drift is within the specified requirement) adequately determines any 

change in the slope parameter. The currently specified test at 20% URL serves 

little, if any, purpose in regard to determining change in the slope and can 

therefore be withdrawn. 

(7) Comment: Part 53, subpart B - The commenter notes that new FRM and FEM 

analyzers would be subject to the new, more stringent requirements, but existing 

FRM analyzers, which have been approved based on the existing, less stringent 

requirements, would continue to be approved. EPA noted that most commercially 
 44 

available CO analyzers already meet the proposed new performance requirements 

so it is unlikely that new analyzer that are approved under the proposed new 

requirements would cost more, and thus there would be no economic impact on 

monitoring agencies. The commenter interpreted that statement to mean that EPA 

is more concerned about cost than data quality. The commenter further suggested 

that existing FRM analyzers approved under the existing performance 

requirements may provide data quality inferior to that of analyzers approved 

under the proposed new requirements and that older analyzers may be 

unacceptable for some applications that demand higher performance or higher 

data quality. A “tiered” approach was suggested to handle this situation. 

Response: In proposing more stringent performance requirements for approval of 

new FRM and FEM analyzers, EPA noted that the performance of analyzers 

approved under the existing performance requirements was fully adequate for 

most routine compliance monitoring applications, and that the proposed new 

requirements were largely to bring the base FRM and FEM performance 

requirements up to date and more commensurate with the performance of modern 

commercially available CO analyzers. The commenter indicated that these 

changes were “long overdue and welcome.” Since all currently designated FEM 

analyzers already meet the proposed new requirements, there would likely be no 

increase in cost for new analyzers that would be approved under the new 

requirements. Thus, EPA was merely pointing out that the new requirements 

were unlikely to impose a resultant economic impact on monitoring agencies. 

EPA considers such impacts when proposing rule changes. More importantly, 

this means that routine CO monitoring data quality currently being obtained is 

already of the higher level portended by the proposed new performance 

requirements. However, EPA did recognize that some special CO monitoring 

applications do require a higher level of performance than that required for 

routine applications. Therefore, EPA is, in fact, proposing a “tiered” approach by 

proposing optional, more stringent performance requirements for analyzers 

having a more sensitive, “lower range” available for such applications. 

Applicants would be able to elect to have such lower ranges approved as part of 

their FRM or FEM designation. 

2. Near­Roadway Monitors

(1) Comment: Two commenters objected to the use of a near-road network for 

judging compliance with the NAAQS (Indiana Department of Environmental 

Management [IN DEM], South Carolina Department of Health and 

Environmental Control [SC DHEC]). One commenter (IN DEM) indicated their 

view that roadside monitors did not provide a measurement that was 

“representative of ambient air quality everywhere in a city or county”. The 

second commenter, in addition to stating that data from this monitoring network 

were not appropriate for use in judging an area’s status in comparison to a 

NAAQS, further stated that such monitoring “does not provide a mechanism to 

add further protection to the general population or susceptible individuals” (SC 

DHEC). 
 45 

Response: The EPA notes that monitoring near roads for peak CO 

concentrations for compliance with the NAAQS is not a new concept, and has 

been in practice since the 1970s. The Agency believes that this final rule is 

updating the same intent that was originally presented in monitoring regulations 

introduced in the May 1979 (44 FR 27571). Similarly, the data produced at nearroad monitoring stations would likely be treated as data from existing CO 

monitors near-roads, in downtown areas, or urban street canyons have been. EPA 

disagrees with commenters regarding the protection provided by this monitoring. 

As discussed in the final rule, people who spend time on or around major roads 

(e.g., because they live there, go to school there, or commute in vehicles on major 

roads) can be exposed to elevated concentrations of ambient CO. Accordingly, 

monitoring in these locations does provide further protection to the general 

population and susceptible individuals who are exposed in these areas, and is 

appropriate for judging compliance with the NAAQS regardless of whether such 

monitoring is indicative of concentrations found throughout an urban area. 

(2) Comment: The NYS DEC commented that CO monitors, due to collocation with 

near-road NO2 monitors, will be located in a range up to 50 meters from target 

road segments. The commenter stated that “data from these sites cannot 

adequately characterize near-road emissions nor would the data be comparable 

from one site or city to another.” The commenter goes on to state that the “final 

NO2 and proposed CO regulations have preceded an understanding of how these 

data will be used for anything other than for research.” 

 Response: The EPA understands the potential influence that monitor placement 

relatively nearer or further from a target road can have on resultant measured 

pollutant concentrations. However, the Agency believes that on the whole, nearroad monitors will be representative of exposures that can occur in the near-road 

environment. Further, the EPA recognizes the existence of a gradient in the nearroad environment within which, based on a number of physical factors, pollutant 

concentrations decrease with increasing distance away from the source road. That 

was the rationale behind requiring near-road NO2 sites within which CO monitors 

are required to be collocated, to have monitor probes “...be as near as practicable 

to the outside nearest edge of the traffic lanes of the target road segment; but shall 

not be located at a distance greater than 50 meters, in the horizontal, from outside 

nearest edge of the traffic lanes of the target road segment” (40 CFR part 58, 

appendix E, section 6.4(a)). The intent is to measure the peak concentrations that 

are occurring in the near-road environment for a given urban area by being as 

close as practicable to target roads. EPA agrees that this data may be helpful to 

support research on near-road air quality and public health, which is one of the 

primary objectives for ambient monitoring networks. However, EPA believes this 

data is also useful and necessary for ensuring that near-road ambient air quality 

meets the NAAQS. 
 46 

(3) Comment: The TCEQ commented that in Texas, frontage roads are included with 

the central line traffic counts. They stated that “the EPA’s interpretation that the 

access road through lanes in Texas are not traffic lanes is incorrect...” and that the 

EPA needs to modify the interpretation to match conformity, National 

Environmental Policy Act (NEPA), and storm water reviews. 

 Response: In this rulemaking, the EPA has not taken a stance on the interpretation 

of how frontage roads are included in central line traffic counts. The regulation 

requiring near-road monitoring only references a ‘target’ road segment. In Texas’ 

case where frontage roads are included as part of a road segment, regardless of the 

physical configuration of that road, the outside edge of that road, whether it be 

frontage road or not, is the location from where measurements can appropriately 

be made to determine if a monitoring site is meeting siting criteria. Further, the 

EPA notes that siting criteria do not preclude the placement of a monitoring 

station in open space (not traffic lanes) within a road segment (e.g., between 

frontage lanes and so-called ‘through lanes’ if such a site is safely accessible and 

can meet siting criteria for probe placement in the vertical plane, and with respect 

to obstructions. 

(4) Comment: Some commenters (e.g., New York Department of Environmental 

Conservation [NYS DEC], NESCAUM, Texas Commission on Environmental 

Quality [TCEQ], AAM) expressed concern that near-road sites may not provide 

information representative of general population exposure, which one commenter 

claims is a primary monitoring objective. The AAM recommended that 

population exposure be included in siting and network design requirements, 

stating that at any new sites, there should be “human exposure to the ambient air 

for time periods corresponding to the 1-hour or 8-hour CO NAAQS.” 

Response: As an initial matter, EPA notes that as summarized in section IV.B.1 

of the final rule, 40 CFR part 58, appendix D specifies three basic objectives for 

the design of ambient air monitoring networks: a) provide air pollution data to the 

general public in a timely manner; b) support compliance with ambient air quality 

standards and emissions strategy development; and, c) provide support for air 

pollution research studies. As described in the preamble to the final rule, the 

near-road monitoring requirement will assist particularly with regard to the 

second objective. The EPA notes that, as described in the ISA and consistent with 

findings of the REA, elevated short-term exposures to ambient CO are associated 

with near-roadway locations and other locations of motor vehicle activity. The 

REA results indicated that key contributors to highest ambient CO human 

exposures are in-vehicle and near-vehicle microenvironments (e.g., REA, Figure 

6-4). While many vehicle-associated exposures may be shorter than 8 hours, the 

8-hour standard, as the controlling standard, provides control of shorter-term 

elevations in concentration which also influence people’s CO exposures and 

associated COHb levels. Thus, siting monitors in near-roadway locations will 
 47 

help ensure compliance with the NAAQS and protection of the public from 

elevations in roadway-associated ambient CO concentrations of concern. 

 (5) Comment: Several commenters (e.g., AASHTO and New York State Department 

of Transportation [NYSDOT]) recommended that state and local air monitoring 

agencies be required to cooperate with state and local transportation agencies on 

the placement of near-road monitors

 

Response: The EPA is not in a position to require state and local air agencies to 

cooperate or collaborate with their state or local transportation agencies in the 

implementation of required near-road monitoring sites by rule. However, the 

EPA strongly encourages air monitoring agencies to work with their respective 

transportation counterparts, and believes that air monitoring agencies are already 

inclined to do so. Further, the EPA believes that many candidate near-road 

monitoring stations will be in right-of-way locations, within which air agencies 

will have to work with transportation agencies to negotiate access and ensure 

safety for the travelling public, air monitoring staff, and the associated monitoring 

infrastructure. 

(6) Comment: Several commenters (e.g., AAM, NACAA) suggested that required 

near-road monitors should be phased in over a period of time. For example, 

NACAA cited a CASAC statement that there are benefits from implementing 

near-road monitors in stages, e.g., over a three year period. 

 

Response: EPA agrees with these commenters that phasing in the implementation 

of near-road CO monitors is warranted. Accordingly, in the final rule, EPA has 

required near-road CO monitors within CBSAs having populations of 2.5 million 

or more persons to be implemented by January 1, 2015, while those CBSAs 

having 1 million or more persons, but less than 2.5 million, are required to be 

operational by January 1, 2017. EPA intends to review the experience of states 

with the first round of near-road CO monitors and the data produced by such 

monitors and consider whether adjustments to the network requirements are 

warranted. 

(7) Comment: A number of commenters (e.g., AASHTO, IN DEM, NYSDOT) 

expressed concern regarding safety for the public and air agency workers at 

monitoring stations in the near-road environment. 

Response: The EPA recognizes safety as a top priority in the implementation of 

any near-road monitoring sites. This is evident in the preamble to the final rule 

promulgating the requirements for near-road NO2 monitors. By requiring CO 

monitors to be collocated with near-road NO2 monitors, network implementation 

issues such as safety will effectively be handled as the near-road NO2 network is 
 48 

installed. In an effort to support state and local air agencies in the implementation 

of near-road NO2 sites, the EPA is collaborating with U.S. Department of 

Transportation, Federal Highway Administration and several state Departments of 

Transportation (DOTs) (e.g., Florida & Texas), along with partner state and local 

air agencies, to provide technical assistance on near-road site implementation to 

the air monitoring community. Safety is a key subject in that assistance, with 

topics covering issues of right-of-way access, the use of safety features such as 

guardrails or recognition of ‘clear zones’, and how to engage DOTs or other 

transportation agencies to ensure safety of the travelling public, air monitoring 

staff, and air monitoring infrastructure at near-road monitoring sites. Further, 

monitoring by roads for CO is not a new concept to states and local air agencies. 

They have been monitoring near roads, mainly in downtown areas and in urban 

street canyons, since the late 1970s. The EPA believes that state and local air 

agencies are very aware of safety issues, in part based on existing experience, and 

the Agency is confident that state and local air agencies will be able to safely 

implement near-road monitoring sites through the use of the technical assistance 

to be provided and by working with their respective partner transportation 

agencies as necessary. 

3.  Other Locations

(1) Comment: One commenter (Safe Air for Everyone) noted that agricultural 

burning can have a significant impact on populations in and around agricultural 

areas. Particularly, the commenter state stated that “EPA should be monitoring 

the impacts of CO on agriculturally burned lands to protect citizens since crop 

residue burning occurs in all 50 states.” 

 Response: In the preamble to the final rule, the EPA notes that a nationally 

applicable network design may not always account for all locations in every area 

where monitors may be warranted. The Agency believes that a minimum 

monitoring requirement to assess agricultural burning is not practical in a 

nationally applied network design. However, in this final rule, the Agency has 

given EPA Regional Administrators the discretion to require monitoring above 

the minimum requirements as necessary to address situations where minimum 

monitoring requirements are not sufficient to meet monitoring objectives. The 

EPA believes that the assessment of agricultural burning may be another example 

of a situation where the EPA Regional Administrators may work with state and 

local air monitoring agencies to consider deploying monitoring resources to assess 

air pollution. In addition to the Regional Administrator authority, state and local 

agencies can also deploy pollutant analyzers on a temporary basis, as special 

purpose monitors, to explore potential pollution issues in areas where problems 

are suspected due to agricultural burning. The Agency believes these two flexible 

approaches (with respect to location and duration) are appropriate to assess 

impacts of agricultural burning in lieu of nationally applied minimum monitoring 

requirements near these sources. 
 49 

 

(2) Comment: NACAA stated that “EPA should also take this opportunity to 

reevaluate the existing CO monitoring network and eliminate sites that are 

redundant or no longer necessary so that resource can be transferred to higher 

priority areas.” The commenter goes on to state that “providing clear guidance 

and support for the divestment of unnecessary monitors is essential to allow state 

and local agencies to best focus limited resources, and is a necessary prerequisite 

to the relocation of existing CO monitors for inclusion in the near roadway 

network.” 

 Response: The Agency agrees with the commenter that the removal or relocation 

of redundant sites or those that are likely no longer necessary is desirable. The 

EPA will continue to work with state and local agencies to shut-down or relocate 

these monitors that meet the criteria of 40 CFR 58.14 as they are identified and 

proposed for modification. EPA will also consider revisions to maintenance plans 

where monitors are currently required but otherwise meet the criteria of 40 CFR 

58.14. 

(3) Comment: API suggested that EPA require any CO monitors recording peak 

 values that are greater than or equal to 80% of NAAQS be retained. 

 Response: Existing monitoring sites are not allowed to be shut-down unless they 

meet certain criterion with respect to their data. These rules by which a monitor 

can be considered for shut-down are maintained in 40 CFR Part 58, 58.14 System 

Modification. Among the criteria under which monitors are eligible to be shut 

down is if there is less than a 10% probability that the monitor will record an 

ambient concentration in excess of 80% of the NAAQS over the succeeding three 

years, and the monitor is not needed under the maintenance plan.29 Further, as is 

noted in the preamble to the final rule, before any monitor can be shut-down, the 

state or local air agency must also receive EPA Regional Administrator approval. 

Accordingly EPA does not believe an additional requirement to retain CO 

monitors recording peak values above 80% of the NAAQS is necessary or 

appropriate. 

(4) Comment: AASHTO asked for clarification on whether, or where, NCore sites in 

areas where near-road monitor would also be required; and for clarification on 

 

29 Other criteria include: (1) where a monitor has consistently measured lower concentrations than another 

monitor for the same pollutant in the same county (or portion of a county within a distinct attainment area, 

nonattainment area, or maintenance area, as applicable) during the previous five years under certain 

circumstances; and (2) where a monitor has not measured violations of the applicable NAAQS in the 

previous five years, and the approved SIP provides for a specific, reproducible approach to representing the 

air quality of the affected county in the absence of actual monitoring data. See 40 CFR 58.14(c). 
 50 

whether NCore sites would provide background data for conformity and NEPA 

related issues. 

 Response: NCore site information is maintained by the EPA and available to the 

public through several different mediums. One resource is EPA’s AirExplorer, 

which is an on-line tool that can be used to generate maps, data graphs, and data 

tables. AirExplorer is located at: http://www.epa.gov/airexplorer. Another 

resource is EPA’s Air Quality System (AQS) database. 

NCore sites, which represent area-wide pollutant concentrations by nature, are 

already operational throughout the country. As noted in section IV.B.2.e of the 

preamble to the final rule, upon analysis of existing NCore stations and all other 

area-wide CO monitors operating nationwide, the EPA believes that there are only 

four CBSAs that do not already have an area-wide monitor where near-road CO 

monitors are required by the final rule. The EPA’s view is that generally areawide monitors (e.g. those at sites with a spatial scale of neighborhood, urban, or 

regional) are likely appropriate to consider as being representative of broader 

urban or background concentrations, depending on their individual location. 

However, specific guidance on modeling for conformity and NEPA analyses is 

beyond the scope of this rulemaking. 

4. Other Monitoring Comments  

(1) Comment: Multiple commenters (e.g., NACAA, IN DEM, North Carolina 

Division of Air Quality [NCDAQ], SC DHEC, Wisconsin Department of Natural 

Resources [WIDNR]), stated that the EPA needs to provide full funding for any 

new monitoring requirements. 

 Response: The EPA notes that it has historically provided full or partial funding 

for the cost of installing and operating monitors used to satisfy minimum 

monitoring requirements, and the agency expects to follow this precedent for 

required monitoring associated with this rulemaking. EPA understands the 

financial hardship many state and local agencies are currently enduring, and will 

continue to identify sources of funding and work with air monitoring agencies to 

move funds to states and support the implementation of all required monitoring. 

The Agency also notes that it expects states will be in a position to relocate 

existing CO monitors to satisfy the new minimum monitoring requirements. The 

Agency believes that in some cases, states may lower operating costs by shutting 

down some existing individual CO sites, while moving those monitors to the nearroad sites required and implemented as part of the NO2 rulemaking. 

(2) Comment: Several commenters (e.g., NACAA and NESCAUM) suggested that 

EPA should support and/or facilitate the introduction of trace level instruments 

into the state and local air monitoring networks while phasing out older monitors. 

 
 51 

 Response: The EPA agrees that when possible the introduction of more sensitive 

“trace-level” instrumentation into the SLAMS network is desirable. The EPA did 

not require the use of such instruments in this rulemaking because the required 

monitors are expected to be in locations of highest ambient CO concentrations. 

However, as state and local air agencies replace their inventory of gas analyzers, 

the Agency strongly encourages the adoption of trace-level instrumentation 

instead of standard sensitivity or traditional analyzers. 

(3) Comment: NACAA suggested that there is a need to provide traffic cameras at 

near-road CO sites. 

 Response: The EPA did not propose or promulgate any requirement for state and 

local air agencies to install traffic cameras at near-road monitoring sites. The 

Agency agrees that traffic information would be very valuable in characterizing 

CO data (and other pollutant data) collected at the near-road site. In the site 

selection process for near-road monitoring sites the EPA is encouraging air 

monitoring agencies to place some additional consideration on near-road locations 

where utilities or other transportation agency infrastructure, such as traffic 

counters and/or cameras, are located. If an air agency does not place a near-road 

site at a location with or near a traffic counter and/or camera, the Agency 

encourages those state and local air agencies to consider if a traffic counter and/or 

camera is financially feasible and implementable at their site, which may be 

identified during the near-road site selection process, and/or by engaging their 

respective transportation agency. 

(4) Comment: EPA received comments suggesting that near-road monitoring sites 

should be multipolluant monitoring sites, monitoring for pollutants such as air 

toxics, elemental carbon, organic carbon, and black carbon. 

 

 Response: The EPA has envisioned that near-road monitoring stations would be 

multipollutant monitoring sites. This concept fits with the Agency paradigm to 

promote multipollutant monitoring wherever possible. Multipollutant monitoring 

is viewed by the EPA as a means to broaden the understanding of air quality 

conditions and pollutant interactions, furthering the capability to evaluate air 

quality models, develop emission control strategies, and support research, 

including health studies. With that, the EPA agrees that the monitoring of other 

pollutants such as air toxics or black carbon, for example, is encouraged whenever 

feasible for state and local air agencies. The requirement of such monitoring in 

the near-road environment, other than for CO, is outside the scope of this 

rulemaking. 

(5) Comment: It was suggested that the EPA should not claim that there are not 

 significant costs associated with the proposed monitoring network requirements. 
 52 

 Response: With the expectation that only approximately 52 (based on recent 

2010 Census counts) CO monitors are being required with this rulemaking, the 

EPA believes that in almost all cases, state and local air monitoring agencies will 

be in a position to move existing monitors or put monitors back into service at 

required near-road sites. The costs of installing the near-road monitoring site 

infrastructure are to be borne by the implementation of near-road NO2 sites. EPA 

recognizes that moving a CO monitor does have some associated costs but does 

not believe the costs associated with the monitoring requirements will be 

significant. 

III. RESPONSES TO SIGNIFICANT COMMENTS RELATED TO

IMPLEMENTATION OF STANDARDS

A.  Designations

(1) Comment: Several commenters (including state transportation agencies, AAM, 

AASHTO, AEPSC and SEMCOG) commented on, and sought clarification of, 

issues related to designation of nonattainment areas that could occur in the future 

following changes in the monitoring network. For example, several commenters 

raised questions about whether such nonattainment areas would be large, or very 

localized. 

Response: EPA is not revising the CO NAAQS. Accordingly, EPA will not be 

undertaking the designation process set forth in CAA section 107(d)(1). EPA has 

no knowledge as to whether the new monitoring network will produce air quality 

data such that the Administrator will deem it appropriate to initiate the 

redesignation process. EPA also notes that the CAA and judicial decisions make 

clear that the economic and technical feasibility of attaining ambient standards are 

not to be considered in setting or revising NAAQS (although such factors may be 

considered in the development of State plans to implement the standards). 

Accordingly, EPA believes it is unnecessary and would be premature to address 

in this action issues as to the scope of potential nonattainment areas or the process 

or factors to be considered if the Administrator finds it appropriate to initiate 

redisignations. 

 

    B.   Other

(1) Comment: Several commenters, including NESCAUM, state that there are many 

CO monitoring sites currently required by maintenance plans that are no longer 

needed. These sites have consistently measured levels of CO well below the 

current NAAQS, and they represent a resource drain in light of state budget 

constraints. States associated with NESCAUM urge EPA to develop a procedure 

that would allow states to shut down those sites earlier than the dates of existing 

agreements, as appropriate. This could be achieved using a simple approach, 
 53 

possibly based on existing design value data being below a chosen threshold. 

Given that the nature of the agreements varies widely from state to state and 

across EPA regions, it is desirable to have a consistent national approach to the 

expeditious closing of these sites. 

Response: The EPA currently provides a process for the shutting down of 

monitors which is provided at 40 CFR 58.14, titled “system modification.” In 

order for a monitor to be shut down, a state, or where appropriate a local, agency 

must develop and implement a plan and schedule to modify the monitoring 

network that complies with the findings of the network assessments required 

every 5 years by section 58.10(e). The state, or local agency, is then required to 

consult with the appropriate EPA Regional Administrator during the development 

of the schedule to modify the monitoring program, and is required to make the 

plan and schedule available to the public for 30 days prior to submission to the 

EPA Regional Administrator. 

Plans containing modifications to NCore Stations or PAMS Stations are required 

to be submitted to the EPA Administrator. The Regional Administrator is 

required to provide an opportunity for public comment and is required to approve 

or disapprove submitted plans and schedules within 120 days. 

40 CFR 58.14(c) provides that a State, or where appropriate a local, agency’s 

requests for a SLAMS monitor station discontinuation, subject to review of the 

Regional Administrator, will be approved if any of the following criteria are met 

and if the requirements of appendix D of 40 CFR 58 continue to be met. Other 

requests for discontinuation may also be approved on a cases-by-case basis if 

discontinuance of the affected monitor does not compromise data collection 

needed for implementation of a NAAQS and if the requirements of appendix D of 

40 CFR 58 continue to be met. 

More specifically, as it relates to the shutting down of monitors in maintenance 

areas, 40 CFR 58.14(c)(1) states the following: “Any PM2.5, O3, CO, PM10, SO2, 

Pb, or NO2, SLAMS monitor which has shown attainment during the previous 

five years, that has a probability of less than 10 percent of exceeding 80 percent of 

the applicable NAAQS during the next three years based on the levels, trends, and 

variability observed in the past, and which is not specifically required by an 

attainment plan or maintenance plan. In a nonattainment or maintenance area, if 

the most recent attainment or maintenance plan adopted by the state and approved 

by the EPA contains a contingency measure to be triggered by an air quality 

concentration and the monitor to be discontinued is the only SLAMS monitor 

operating in the nonattainment or maintenance area, the monitor may not be 

discontinued.” 

EPA is willing to work with States to identify reasonable approaches to 

demonstrating that a monitor meets the criteria of 40 CFR 58.14(c)(1), and to 

consider revisions to maintenance plans that currently require monitors that 

otherwise meet those criteria. 
 54 

(2) Comment: Two state agencies (IN DEM and SC DHEC) submitted comments 

stating that if violations are measured by a roadside monitor, states do not possess 

the necessary authority to implement the required controls to establish attainment 

or meet their obligations for state implementation plan development. The 

commenters stated that a significant percentage of vehicles that travel major urban 

roadways are registered outside of the state and are regulated at the federal level. 

Transportation control measures could be implemented to reduce congestion and 

vehicle miles traveled, but only at the local level and would not achieve 

substantial reductions in CO. Commenters further state that, until U.S. EPA 

petitions Congress for the necessary revisions t the Clean Air Act, granting 

authority to states to have control over mobile sources, a means to develop an 

attainment strategy for roadside CO and NO2 must be established. 

Response: As noted above, EPA is not revising the CO NAAQS. Accordingly, 

EPA will not be undertaking the designation process set forth in CAA section 

107(d)(1), or requiring SIP submissions pursuant to CAA section 110. EPA has 

no knowledge as to whether the new monitoring network will produce air quality 

data such that the Administrator will deem it appropriate to initiate the 

redesignation process. 

EPA agrees that it is a federal responsibility to implement regulations that reduce 

emissions from new light- and heavy-duty motor vehicles. However, if it 

becomes necessary to achieve additional reductions in ambient CO, states have 

authority that can be used to reduce emissions from in-use light- and heavy-duty 

vehicles. For example, CAA section 177 allows states to adopt California’s 

standards that apply to new motor vehicles or new motor vehicle engines. States 

can also implement programs to retrofit older heavy-duty diesel vehicles to reduce 

their CO emissions. States can also implement regulations to reduce or eliminate 

long-duration idling of heavy-duty diesel vehicles. They can implement an 

inspection and maintenance program for light-duty vehicles. Additionally, states 

can implement a wide range of programs to improve transportation efficiency 

(e.g., working with freight shippers). 

It is EPA’s belief that a number of states have already achieved reductions in CO 

emissions from on-road sources. EPA anticipates that if an area were to be 

designated nonattainment for the CO NAAQS, the state would evaluate a variety 

of control measures to reduce emissions from mobile sources (which include 

nonroad engines), as well as other sources that are contributing to the 

nonattainment problem. 

If any areas are designated nonattainment at some point in the future, EPA 

expects that each state with a designated CO nonattainment area would develop a 

SIP that brings the area into attainment by the applicable deadline and that each 

state would evaluate the potential for controlling emissions from all sources that 

are contributing to the nonattainment problem. 
 55 

IV. RESPONSES TO SIGNIFICANT COMMENTS RELATED TO

EXCEPTIONAL EVENTS

(1) Comment: Several state departments of transportation (including those from New 

York, Texas, Virginia, and Washington) and the American Association of State 

Highway and Transportation Officials commented that the proposed monitoring 

requirements for near-road CO monitors would result in “hotspot” monitoring 

rather than monitoring of background concentration levels and that the 

Exceptional Events Rule should, therefore, be revised to recognize temporary 

traffic-related activities, such as construction and traffic congestion caused by 

accidents, as potential exceptional events. 

Response: The Exceptional Events Rule (EER) and the accompanying preamble 

(72 FR 13560, March 22, 2007) created a regulatory process containing 

definitions, procedural requirements, requirements for state demonstrations, and 

criteria for EPA approval for the exclusion of air quality data from regulatory 

decisions under the EER. EPA believes that these criteria and procedures 

sufficiently address any exceptional events claim that may arise for the CO 

NAAQS, and that additions or modifications to the EER, specific to CO, are not 

needed. EPA further recognizes that temporary traffic-related activities or 

conditions could be potential exceptional events, and, therefore, created a data 

flag (i.e., Qualifier Code and Qualifier Description) in the Air Quality System 

(AQS) for “unique traffic disruption.” EPA believes that the general rule criteria 

and specific AQS flagging mechanisms provide sufficient flexibility to identify 

and address near-road exceptional events. 

In addition, EPA has developed draft implementation guidance products, 

available by request at EEGuidanceComments@epa.gov, that clarify the criteria 

on which exclusion of event-affected data depend, describe the administrative 

process and associated timing for submittal and review of demonstrations, and 

provide answers to frequently asked questions, including questions regarding 

temporary activities and “hot-spot” (i.e., microscale) monitors. 

V. RESPONSES TO LEGAL, ADMINISTRATIVE, AND PROCEDURAL

ISSUES AND MISPLACED COMMENTS

(1) Comment: Two commenters (PSR et al and Donnay) suggest that the rule be 

found subject to Executive Order 13045 (62 FR 19885, April 23, 1997), 

concerning the protection of children from environmental health and safety risks. 

Response: EPA found that the proposed rule was not subject to E.O. 13045 

because it was not “economically significant” as defined in E.O. 12866, and 

because the Agency does not believe the environmental health or safety risks 

addressed by this action present a disproportionate risk to children. Likewise, 
 56 

EPA finds that the final rule is not subject to EO 13045 for the same reasons. 

EPA notes that a rule must be “economically significant” to be subject to EO 

13045. Accordingly, the fact that the rule is not economically significant is a 

sufficient reason why it is not subject to EO 13045. However, EPA has carefully 

considered the risks from ambient CO for children. For the reasons discussed in 

the preamble (section II.B) and elsewhere in this document (e.g., see responses to 

comments at II.A.3(1), II.A.3(2) and II.A.5(8)), EPA disagrees with the 

commenters’ view that there is evidence establishing that a range of health 

effects, including developmental and respiratory effects, are occurring as a result 

of exposures to CO in ambient air at or below the current standards, or that 

children are at a disproportionate risk from adverse health effects from ambient 

CO. EPA believes the current CO NAAQS provide the requisite protection for 

children, with an adequate margin of safety. 

(2) Comment: Some comments stated that EPA failed to properly characterize 

CASAC's advice and to comply with its obligation under the CAA to respond to 

comments from CASAC. 

 

Response: EPA believes the preamble to the proposed and final rules and this 

Response to Comments document fairly and adequately characterize CASAC's 

advice and that it has fully complied with its obligations under CAA section 

307(d)(3) to "summarize and provide a reference to any pertinent findings, 

recommendations, and comments by [CASAC] and, if the proposal differs in any 

important respect from any of these recommendations, an explanation of the 

reasons for such differences." 

 EPA has explained in the preamble to the proposed and final rules that CASAC 

expressed a "preference" for a lower standard, stating that “[i]f the 

epidemiological evidence is given additional weight, the conclusion could be 

drawn that health effects are occurring at levels below the current standard, which 

would support the tightening of the current standard” and further advised that 

"revisions that result in lowering the standard should be considered" (see e.g., 76 

FR 8183). However, EPA disagrees with the comment that "[i]t is evident ... that 

the CASAC believes the current standards are likely to be inadequate" (CBD et al, 

p. 7). The CASAC Panel explained its views at greater length in its response to 

charge questions on the draft Policy Assessment (Brain and Samet, 2010d, p. 12): 

While there have been no new controlled human exposures designed 

to examine effects of CO at COHb levels below 2%, there have been 

numerous improvements to the exposure and COHb dosimetry models 

employed to provide exposure and risk estimates. The Staff analysis 

indicates that some of the uncertainties identified in previous reviews 

of the standard have been reduced. Based on their overall analysis, 

they conclude that the body of evidence and the quantitative exposure 

and dose estimates provide support for a standard at least as 
 57 

protective as the current standards. I.e. the data provide support for 

retaining or revising the current 8-hr standard. 

 Overall the Panel agrees with this conclusion. If the epidemiological 

evidence is given additional weight, the conclusion could be drawn 

that health effects are occurring at levels below the current standard, 

which would support the tightening of the current standard. The PA 

should include an analysis the number of exceedances that would 

have occurred if the standard had been based on the epidemiological 

data." 

Based on this statement, and others, from CASAC, EPA explained in the proposed 

notice that "the Administrator considers the advice of CASAC, including both 

their overall agreement with the Policy Assessment conclusion that the current 

evidence and quantitative exposure and dose estimates provide support for 

retaining the current standard, as well as their view that in light of the 

epidemiological studies, revisions to lower the standards should be considered 

and their preference for a lower standard" (76 FR 8183). EPA believes this, and 

other statements in the proposed and final notices, and this Response to 

Comments document, fairly and adequately summarize CASAC's advice. 

Moreover, EPA believes it has acted consistent with CASAC's advice in 

considering a lower standard. Ultimately, after giving a balanced assessment of 

the various lines of evidence, including further consideration of the 

epidemiological evidence, and its associated uncertainties (also noted by 

CASAC), the Administrator concluded that the current standards are requisite to 

protect public health with adequate margin of safety. Even if, for the sake of 

argument (despite CASAC's explicit recognition that the evidence supports either 

retaining or revising the standard), this conclusion were considered to differ in an 

important respect with the advice of CASAC, EPA has fully explained the basis 

for the Administrator's conclusion. 

(3) Comment: Two commenters stated that the Office of Management and Budget 

“classifies the CO NAAQS as a ‘major’ and ‘economically significant’ rule” 

(PSR at 10; Donnay at 60), and that therefore EPA is required to publish a 

Regulatory Impact Analysis (RIA), as EPA did during the last review. Another 

commenter (NYSDOT at 4) suggested that “if there are changes to CO attainment 

and nonattainment designations as a result of near-road monitors, those impacts 

and added costs should be fully evaluated and accounted for in this rule-making 

effort in accordance with Executive Order 13563.” 

Response: As noted in Section V of the preamble, under Executive Order 12866 

(58 FR 51735, October 4, 1993), this action is a "significant regulatory action” 

because it was deemed to “raise novel legal or policy issues.” Accordingly, EPA 

submitted this action to the Office of Management and Budget (OMB) for review 

under Executive Orders 12866 and 13563 (76 FR 3821, January 21, 2011). 

However, this action is not an “economically significant action” within the 
 58 

meaning of section 3(f)(1) of EO 12866, and therefore section 6(a)(3)(C) of EO 

12866 does not apply to this rulemaking and EPA was not required to prepare an 

RIA, which includes, to the extent feasible, a quantification of the costs and 

benefits of the rulemaking. Likewise, this rule is not a “major rule” for purposes 

of the Congressional Review Act. 

As noted above, EPA has no knowledge as to whether the new monitoring 

network will produce air quality data such that the Administrator will deem it 

appropriate to initiate the redesignation process. However, EPA notes that the 

CAA and judicial decisions make clear that the economic and technical feasibility 

of attaining ambient standards are not to be considered in setting or revising 

NAAQS (although such factors may be considered in the development of State 

plans to implement the standards). EPA acknowledges that we could have 

prepared an RIA, even though an RIA was not required under EO 12866 and EO 

13563. However, in light of the facts that EPA was not proposing to change the 

standard, that evidence is limited on current ambient concentrations near roads, 

and that any RIA would be irrelevant to a decision whether to change the 

standard, as well as EPA’s limited resources for preparing RIAs, EPA chose not 

to prepare an RIA for this action. 
 59 

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 63 

Appendix A. Studies cited by public commenters that were not included in the 

2010 CO ISA (e.g., published after document closure). These studies were 

provisionally considered by EPA, as discussed in section I.C of the preamble to 

the final rule and in this document.

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32: 224-227. 

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Thorax 55: 138-142. 

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1005. http://dx.doi.org/10.1053/rmed.2001.1196. 

Bruske, I.; Hampel, R.; Socher, M. M.; Ruckerl, R.; Schneider, A.; Heinrich, J., . . . 

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cell count in patients with chronic pulmonary disease. Inhalation Toxicology 22: 

245-252. http://dx.doi.org/10.3109/08958370903207274. 

Cakmak, S.; Dales, R. E.; Judek, S. (2006) Do gender, education, and income modify the 

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Canova, C.; Torresan, S.; Simonato, L.; Scapellato, M. L.; Tessari, R.; Visentin, A., . . . 

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http://dx.doi.org/10.1183/09031936.00043709. 
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Cavaliere, F.; Volpe, C.; Gargaruti, R.; Poscia, A.; Di Donato, M.; Grieco, G.; Moscato, 

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9: 51. http://dx.doi.org/10.1186/1471-2466-9-51. 

Chatkin, G.; Chatkin, J. M.; Aued, G.; Petersen, G. O.; Jeremias, E. T.; Thiesen, F. V. 

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36: 332-338. 

Chen, Y. H.; Lin, S. J.; Lin, M. W.; Tsai, H. L.; Kuo, S. S.; Chen, J. W., . . . Chau, L. Y. 

(2002) Microsatellite polymorphism in promoter of heme oxygenase-1 gene is 

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Chen, Y. H.; Chau, L. Y.; Lin, M. W.; Chen, L. C.; Yo, M. H.; Chen, J. W.; Lin, S. J. 

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myocardial infarction in a tropical city: Kaohsiung, Taiwan. Journal of 

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Cheng, S.; Lyass, A.; Massaro, J. M.; O'Connor, G. T.; Keaney, J. F.; Vasan, R. S. (2010) 

Exhaled carbon monoxide and risk of metabolic syndrome and cardiovascular 

disease in the community. Circulation 122: 1470-1477. 

http://dx.doi.org/10.1161/CIRCULATIONAHA.110.941013. 

Chow, S.; Campbell, C.; Sandrini, A.; Thomas, P. S.; Johnson, A. R.; Yates, D. H. (2009) 

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1091-1097. http://dx.doi.org/10.1016/j.rmed.2009.04.009. 

Ciarleglio, G.; Refini, R. M.; Pieroni, M. G.; Martino, V. A.; Bargagli, E.; Rottoli, P.; 

Sestini, P. (2008) Exhaled carbon monoxide in sarcoidosis. Sarcoidosis Vasculitis 

and Diffuse Lung Diseases 25: 46-50. 
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Clark, N. A.; Demers, P. A.; Karr, C. J.; Koehoorn, M.; Lencar, C.; Tamburic, L.; Brauer, 

M. (2010) Effect of early life exposure to air pollution on development of 

childhood asthma. Environmental Health Perspectives 118: 284-290. 

http://dx.doi.org/10.1289/ehp.0900916. 

Conceicao, G. M. S.; Miraglia, S.; Kishi, H. S.; Saldiva, P. H. N.; Singer, J. M. (2001) 

Air pollution and child mortality: a time-series study in Sao Paulo, Brazil. 

Environmental Health Perspectives 1093: 347-350. 

Cope, K. A.; Solga, S. F.; Hummers, L. K.; Wigley, F. M.; Diehl, A. M.; Risby, T. H. 

(2006) Abnormal exhaled ethane concentrations in scleroderma. Biomarkers 11: 

70-84. http://dx.doi.org/10.1080/13547500500515046. 

Cui, Y.; Zhang, Z. F.; Froines, J.; Zhao, J.; Wang, H.; Yu, S. Z.; Detels, R. (2003) Air 

pollution and case fatality of SARS in the People's Republic of China: an ecologic 

study. Environmental Health 2: 15-19. 

Cunnington, A. J. and Hormbrey, P. (2002) Breath analysis to detect recent exposure to 

carbon monoxide. Postgraduate Medical Journal 78: 233-237. 

Currie, J.; Neidell, M.; Schmieder, J. F. (2009) Air pollution and infant health: Lessons 

from New Jersey. Journal of Health Economics 28: 688-703. 

http://dx.doi.org/10.1016/j.jhealeco.2009.02.001. 

Czogała, J.; Nowak, J.; Wardas, W. (2001) Determination of carbon monoxide in blood 

by means of microdiffusion. Roczniki Państwowego Zakładu Higieny 52: 347-

351. 

Dales, R. E.; Cakmak, S.; Doiron, M. S. (2006) Gaseous air pollutants and hospitalization 

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