September 20, 2011

PEER REVIEW SUMMARY REPORT

External Peer Review of EPA’s Draft Document

Approach to Assessing Non-cancer Health Effects from Formaldehyde and 

Benefits from Reducing Non-cancer Health Effects as a Results of 

Implementing Formaldehyde Emission Limits for Composite Wood Products

Prepared for:

U.S. Environmental Protection Agency

National Program Chemicals Division

Office of Pollution Prevention and Toxics

1200 Pennsylvania Avenue, NW (7404T)

Washington, DC 20460

Prepared by: 

Versar, Inc. 

6850 Versar Center

Springfield, VA 22151

Contract No. EP-C-07-025

Task Order 129

Peer Reviewers:

John R. Balmes, M.D.

Glenn C. Blomquist, Ph.D.

A. Myrick Freeman III, Ph.D.

Shelby Gerking, Ph.D.

David Kriebel, Sc.D.

Frederick J. Miller, Ph.D., Fellow ATS

Rebecca T. Parkin, Ph.D., MPH
i

TABLE OF CONTENTS

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

II. CHARGE TO REVIEWERS................................................................................................3

III. INDIVIDUAL REVIEWER COMMENTS ON NON-CANCER HEALTH 

EFFECTS – DERIVATION OF CONCENTRATION-RESPONSE FUNCTIONS.......9

John R. Balmes, M.D............................................................................................................ 10

David Kriebel, Sc.D.............................................................................................................. 15

Frederick J. Miller, Ph.D., Fellow ATS................................................................................ 20

Rebecca T. Parkin, Ph.D., MPH ........................................................................................... 27

IV. INDIVIDUAL REVIEWER COMMENTS ON THE BENEFITS ASSESSMENT 

APPROACH.........................................................................................................................34

Glenn C. Blomquist, Ph.D. ................................................................................................... 35

A. Myrick Freeman III, Ph.D................................................................................................ 44

Shelby Gerking, Ph.D. .......................................................................................................... 52

V. PEER REVIEWER COMMENT TABLE ON NON-CANCER HEALTH 

EFFECTS – DERIVATION OF CONCENTRATION-RESPONSE FUNCTIONS.....61

VI. PEER REVIEWER COMMENT TABLE ON THE BENEFITS ASSESSMENT 

APPROACH.........................................................................................................................79
1

I. INTRODUCTION

In March 2008, the Sierra Club and other organizations and individuals petitioned EPA under 

Section 21 of the Toxic Substances Control Act (TSCA). The petitioners requested that EPA use 

TSCA Section 6 to adopt a newly-promulgated California Air Resources Board (CARB) 

Airborne Toxic Control Measure (ATCM)1as a national standard for formaldehyde emissions 

from hardwood plywood, particleboard, and medium-density fiberboard products. The 

petitioners expressed particular concern over the levels of formaldehyde found in emergency 

housing provided for Hurricane Katrina survivors, but noted that there are no federal regulations 

on formaldehyde emissions from composite wood products other than those applicable to 

manufactured housing regulated by the U.S. Department of Housing and Urban Development. In 

response to the petition, EPA announced in the Federal Register on June 27, 2008 (73 FR 

36504)2that EPA would initiate a proceeding to investigate whether and what type of regulatory

or other action might be appropriate to protect against risks that may be posed by formaldehyde 

emitted from composite wood products. In December 2008, EPA published an Advance Notice 

of Proposed Rulemaking (ANPR) to publicly initiate the investigation and obtain stakeholder 

input (73 FR 73620).3 

On July 7, 2010, the Formaldehyde Standards for Composite Wood Products Act (FSCWPA) 

was signed into law. This statute, which adds a Title VI to TSCA, establishes formaldehyde 

emission standards for hardwood plywood, particleboard, and medium-density fiberboard that 

are identical to the CARB ATCM Phase II standards. 4 TSCA Title VI directs EPA to 

promulgate implementing regulations by January 1, 2013 that address: sell-through dates for 

products; stockpiling; third-party testing and certification; auditing and reporting of third-party 

certifiers; recordkeeping; chain of custody; labeling; enforcement; products made with no-added 

formaldehyde (NAF) and ultra-low emitting formaldehyde (ULEF) resins; laminated products; 

finished goods; hardboard; and products containing de minimis amounts of composite wood 

products. 

In support of the implementing regulations, as with other rulemakings that are determined to be 

“significant regulatory action[s]” under Executive Order 12866—Regulatory Planning and 

Review, EPA is required to conduct an economic analysis of the costs and benefits associated 

with the rulemaking. On June 2, 2010, EPA released a draft document titled Toxicological 

Review of Formaldehyde-Inhalation Assessment: In Support of Summary Information on the 

Integrated Risk Information System (IRIS).5This draft IRIS assessment, which recently 

underwent independent scientific peer review by the National Academy of Sciences (NAS)6, 

addresses both non-cancer and cancer human health effects that may result from chronic 

inhalation exposure to formaldehyde. However, this draft IRIS assessment does not include 

concentration-response functions for non-cancer health effects, which are needed for the benefits 

assessment. Therefore, this draft report titled Approach to Assessing Non-cancer Health Effects 

from Formaldehyde and Benefits from Reducing Non-cancer Health Effects as a Result of 

Implementing Formaldehyde Emission Limits for Composite Wood Products (referred to 

 

1 Available at http://www.arb.ca.gov/toxics/compwood/compwood.htm

2 Available at http://www.gpo.gov/fdsys/pkg/FR-2008-06-27/pdf/E8-14618.pdf

3 Available at http://www.gpo.gov/fdsys/pkg/FR-2008-12-03/pdf/E8-28585.pdf

4 Available at http://www.arb.ca.gov/toxics/compwood/compwood.htm

5 Available at http://cfpub.epa.gov/ncea/iris_drafts/recordisplay.cfm?deid=223614

6 Available at http://www.nap.edu/catalog.php?record_id=13142
2

hereafter as draft Approach Document) was developed, which provides discussion of several 

non-cancer endpoints as well as a discussion of the derivation of concentration-response 

functions, uncertainties, and EPA’s proposed approach for using the concentration-response 

functions in the benefits assessment. 

Peer Reviewers:

Experts in Non-cancer Health Effects:

John R. Balmes, M.D. 

University of California, San Francisco

San Francisco, CA 94110

David Kriebel, Sc.D.

University of Massachusetts Lowell

Lowell, MA 01854

Frederick J. Miller, Ph.D., Fellow ATS

Fred J. Miller & Associates LLC

Cary, NC 27511

Rebecca T. Parkin, Ph.D., MPH

The George Washington University Medical Center

Washington DC, 20037

Experts in Environmental and Health Economics:

Glenn C. Blomquist, Ph.D.

University of Kentucky

Lexington, KY 40506

A. Myrick Freeman III, Ph.D.

Bowdoin College

Georgetown, ME 94548

Shelby Gerking, Ph.D.

University of Central Florida

Orlando, Florida 32816
3

II. CHARGE TO REVIEWERS

EPA is requesting comment on the draft document, “Approach to Assessing Non-cancer Health 

Effects from Formaldehyde and Benefits from Reducing Non-cancer Health Effects as a Result 

of Implementing Formaldehyde Emission Limits for Composite Wood Products” (draft 

Approach Document). The purpose of this draft Approach Document is to describe how EPA 

derived concentration-response functions for formaldehyde effects on sensory irritation, asthma, 

and female reproductive toxicity, as well as the approach EPA will take to use these 

concentration-response functions to estimate benefits from the contribution of reduced noncancer health effects as a result of implementing formaldehyde emission standards for composite 

wood products. The draft document describes in detail how the concentration-response functions 

were derived as well as uncertainties. The draft document also briefly describes the 

epidemiological studies that were used to derive the concentration-response functions; however, 

a detailed analysis of these studies (as well as others) is included in the 2010 draft IRIS 

assessment for formaldehyde7and is therefore not included in the draft Approach Document. The 

draft Approach Document also describes how EPA plans to use the concentration-response 

functions to estimate benefits. It provides sample calculations but not the actual benefits 

assessment. The full benefits assessment will be provided in the economic analysis that will be 

publicly available (at www.regulations.gov) when the draft proposed rule is published.

The draft IRIS assessment for formaldehyde underwent peer review by the National Academy of 

Sciences (NAS)8, and EPA requests that the peer reviewers of the draft Approach Document do 

not duplicate the efforts of the NAS. EPA is requesting comment specifically on the derivation 

of the concentration-response functions and the approach on how the Agency plans to use these 

functions to assess benefits. EPA requests that if the reviewers have comments on EPA’s 

proposed approach that they provide specific recommendations for improvements, including 

specific references and how those references are relevant to the Approach. In addition, if 

reviewers have information that EPA should have considered, please provide that information. 

Specific Charge Questions on Derivation of Concentration-Response Functions

Sensory Irritation

The literature base of residential epidemiology studies of the irritation effects with quantitative 

concentration-response data was limited, but data were available from which a concentrationresponse function could be estimated for eye irritation.

1) Please comment on whether the concentration-response function is appropriately derived 

from the studies used in the draft Approach Document.

2) Please comment on the validity of extrapolating the concentration-response function and 

using the function to estimate effects at concentrations below 100 ppb.

3) The studies considered for the concentration-response function are residential studies because 

residential exposures are the focus of the rule and the residential studies avoid some of the 

 

7 Available at http://cfpub.epa.gov/ncea/iris_drafts/recordisplay.cfm?deid=223614

8 Available at http://www.nap.edu/catalog.php?record_id=13142
4

limitations of other types of studies (e.g., controlled exposure chamber studies used high, 

acute exposures, and occupational studies reflect high exposure levels and potential dose-rate 

effects from peak exposures). Are there other studies (e.g., chamber or non-residential 

studies) that should be used as supporting evidence for the currently derived concentrationresponse function for eye irritation? If so, please provide information about the studies and 

discuss how they should be used to support the concentration-response function.

4) Are there other sensory irritation endpoints besides eye irritation for which a concentrationresponse function can and should be developed for assessing effects at concentrations below 

100 ppb? If so, please provide references of appropriate studies and a description of how the 

studies could be used to develop a concentration-response function.

Asthma

Several studies of the association between formaldehyde and asthma have been published and 

these were quantitatively summarized in a meta-analysis by McGwin et al. (2010).

5) Please comment on whether the McGwin et al. (2010) meta-analysis is an appropriate 

summary of the association between formaldehyde inhalation exposures and childhood 

asthma.

6) Please comment on whether EPA chose the appropriate function from the McGwin et al. 

paper to use in the benefits assessment.

Female Reproductive Toxicity

The literature base describing reproductive effects of formaldehyde exposure in humans is 

limited; however, there are supportive findings from the animal toxicological literature. The 

epidemiologic literature suggests an association between formaldehyde and increased risk of 

spontaneous abortion and a related delay in time to pregnancy (i.e., reduced fertility). The only 

study with quantitative concentration-response data was Taskinen et al. (1999).

The a priori hypothesis in Taskinen et al. (1999) was that formaldehyde would be associated 

with decreased fertility. The primary analyses showed that there was a statistically significant 

reduction of fertility among the women in the highest exposure group that appeared to be 

concentration dependent. Post-hoc subgroup analyses showed that stratification of the 39 

women in the highest exposure group by reported glove use yielded effect estimates whose 

confidence intervals overlapped. The FDR for the 17 women who were classified as not wearing 

gloves was 0.51 [95% CI: 0.28−0.92]. The FDR for women who were classified as always or 

sometimes wearing gloves was 0.79 [95% CI: 0.47−1.23]. 

7) In light of the results regarding glove use, in what way(s) can the Taskinen et al. results be 

used to support calculating a concentration response for formaldehyde inhalation risk to time 

to pregnancy?

8) Please comment on whether the concentration-response function is appropriately derived 

from the Taskinen et al. (1999) study.
5

Specific Charge Questions on the Benefits Assessment Approach

Sensory Irritation

The concentration-response function for the prevalence of eye irritation is based on Hanrahan et 

al. (1984). While Hanrahan does not identify the relevant time period for this relationship, Liu et 

al. (1991) produced qualitatively similar results for a two-week time period. We assumed that the 

concentration-response relationship for eye irritation is for a two-week period and multiplied the 

concentration-response function times 26 to obtain the number of cases of eye irritation 

experienced in one year. 

The concentration-response curve used is non-linear, which means that the annual approach may

not produce an exact measure of the benefits, but it is believed that the bias is probably relatively 

small given the small change in exposure.

1) Please comment on whether the concentration-response function is used appropriately in the

benefits assessment approach.

The concentration-response curve is for an acute effect occurring at a time less than the one-year 

time step of the exposure model. The willingness to pay to avoid cases of eye irritation is 

calculated for each year of analysis by multiplying the number of cases in a year by the marginal 

willingness to pay value to avoid one case. This may produce biased results, but the direction of 

that bias is unknown.

On one hand, some studies have suggested that the willingness to pay per symptom-day declines 

as the number of symptom-days avoided increases. In other words, the value to reduce two 

symptom-days of some effect is less than two times the value for one symptom-day. Therefore, 

this approach may overstate the total value. 

On the other hand, this analysis only applies values to one symptom, eye irritation, largely 

because this is the only symptom for which an effective concentration-response curve was 

derived. However, there is evidence that there are other forms of minor eye, nose, and throat 

irritation associated with formaldehyde exposure. Since eye irritation is the largest of the median 

values from the Tolley et al. (1986) study, the values used here likely represent a lower bound on 

the true effect of multiple symptoms. A reasonable upper bound of the total effect for one 

symptom-day would be sum of the willingness to pay for one symptom-day of each effect 

individually. 

2) Please comment on whether the annualized approach as opposed to the lifetime approach is 

appropriate in this context.

The concentration-response function for the prevalence of eye irritation is for a single two-week 

period. The annualized approach used an adjusted concentration-response relationship that 

consisted in multiplying the concentration-response function obtained from Hanrahan et al. 

(1984) by 26 two-week periods.

3) Please comment on whether the adjustment of the concentration-response function is 

appropriate in the annualized approach.
6

Asthma

The concentration-response relationship for asthma incidence is given as an odds ratio for 

children exposed to formaldehyde. An odds ratio is a way of comparing the difference in the 

probability of an event, in this case asthma diagnosis, occurring in groups exposed at different 

levels. The odds ratio is used to determine the willingness to pay for any change in emissions 

exposure over a 16 year period. We assume that the probability of being diagnosed with asthma 

is uniformly distributed across these 16 years. 

The use of an odds ratio implies that the concentration-response relationship is non-linear. 

However, given that the change in exposure is relatively small, the results from using this 

implied non-linear function are anticipated to be similar to the results if we were to use a linear 

function.

4) Please comment on whether the concentration-response function is used appropriately in the 

benefits assessment approach.

The valuation of asthma effects from formaldehyde exposure is based on valuing the incidence 

of asthma rather than the more standard valuation based on the exacerbation of asthma 

symptoms. The reason for this is that a statistical relationship between formaldehyde exposure 

and asthma exacerbation has not been sufficiently well established, but there is a statistical 

relationship between formaldehyde exposure and asthma occurrence or incidence. However, the 

only time that EPA has valued asthma exacerbation is for the first prospective study of the 

benefits and costs of the Clean Air Act (EPA 1999). This is probably due to a lack of an 

appropriate concentration-response relationship. The EPA’s Office of Air does include 

recommended values for the monetization of chronic asthma in its BenMAP documentation 

(EPA 2011b), which is based on an average of the results from Blumenschein and Johannesson 

(1998) and O’Conor and Blomquist (1997).

For this analysis, EPA treats prevalence as a measure of cumulative incidence by assuming that 

the disease duration is the rest of the child’s life. However, the EPA (2000a) has previously

assumed that a portion of asthmatic children will become asymptomatic as they move into 

adulthood.

5) Please comment on whether the annualized approach as opposed to the lifetime approach is 

appropriate in this context.

The concentration-response relationship is based on an odds ratio for a period of time longer than 

the one year. The exposure model produces results for one-year of exposure to formaldehyde for 

each age, housing type, and climate cohort. As a consequence, an adjustment to the simple model 

needed to be made to model the effect on individuals who are currently alive when the regulation 

takes effect.

As an upper bound estimate, we assume that the odds ratio can be applied to the one year 

reduction in the same fashion as it was applied for the 16 year time period. The problem with this 

approach is that it effectively treats the exposure as an acute effect. If the odds ratio indicates a 

particular percentage reduction in asthma cases from a reduction in formaldehyde exposure over 
7

16 years, the upper bound approach would suggest the same percentage reduction in asthma case 

in one single year if we were to witness the same reduction in formaldehyde exposure in one 

year. The lower bound approach assumes that a particular exposure reduction for one year 

produces the same effect as if that exposure reduction were spread out over the entire 16-year 

time period. 

6) Please comment on the upper and lower bound methodology used.

The prevalence data suggest that 7.2% of children age 0-4 have been told that they have asthma. 

16.4% of children aged 5-14 have been told that they have asthma. We assume that the 

probability of being diagnosed is uniformly distributed across the 0 to 16 age bracket, so that the 

incidence rate would be 1.44% for the first five years and 1.49% for the next eleven years.

Allocating cases uniformly across the age brackets provides us with a way to calculate the annual 

benefits of any exposure reduction that occurs for the entire time period, but may not be 

appropriate if the diagnosis of asthma for very young children (e.g., age 0-2) differs from older 

children.

7) Is the assumption about applying the concentration-response function to children aged 0 to 

16 appropriate, given the asthma onset studies’ focus on school-aged children and 

adolescents, and given the potential uncertainty of the Rumchev study involving younger 

children?

Female Reproductive Toxicity

The linear concentration-response function accounting for background exposures based on 

Taskinen et al. (1999) is used for the annual approach.

8) Please comment on whether the concentration-response function is used appropriately in the 

benefits assessment approach.

Monetization of delayed fertility has been discussed in the literature but has never been included 

in primary analyses of EPA rules because it was believed that the scientific knowledge on 

reproductive and developmental health effects was not strong enough to quantify risk in the 

primary benefits analysis.

While there appears to be good data on the cost of treatment, there are few studies on the 

willingness to pay to reduce delayed conception. Most economic valuation studies regarding 

fertility focus on an individual’s or a couple’s willingness to pay for infertility treatment, 

particularly in-vitro fertilization (IVF). Conceptually, the willingness to pay approach is 

preferable and could be deduced from the valuation studies. However, given that there has been 

less research on this willingness to pay values than other values and the fact that the values have 

not been used in previous economic analyses, we used the more straight-forward cost of illness 

approach for this analysis. As an upper bound, we assume that any woman who has difficulty 

conceiving (i.e., time to pregnancy exceeds 12 months) will obtain some type of fertility service. 

This may be a reasonable upper bound, but there are certainly women who have trouble 

becoming pregnant and do not seek fertility treatment. 
8

The willingness to pay for fertility treatment is treated as an expected value. The average cost of 

various cycle-based fertility treatments is multiplied times the probability of obtaining that 

treatment at various ages. There is probably a small opposite effect associated with an increase in 

pregnancy from reduced formaldehyde exposure by women who do not want to become 

pregnant, but we do not consider this effect

9) Please comment on whether the annualized approach as opposed to the lifetime approach is 

appropriate in this context.

The time period associated with the exposure-response function is longer than the time step of 

the exposure model. The Taskinen (1999) study examined the fecundity of women age 20-40. 

This causes a problem if we have an individual who does not experience the exposure reduction 

for the full time period. We can form an upper and lower bound of this willingness to pay as we 

did for asthma prevalence. The upper bound is based on the assumption that the linear 

concentration-response function holds for an acute exposure of one year. The lower bound 

assumes that an exposure reduction for one year represents 1/20th of an exposure reduction for 

the entire 20-year time period. 

10) Please comment on the upper and lower bound methodology used.

The ages used in this analysis reflect the ages reported in the Taskinen (1999) study, ages 20-40. 

However, women older than age 40 obtain fertility treatment. The value of reduced infertility

effects from reduced formaldehyde exposure is not reflected in this analysis in order to remain 

consistent with Taskinen (1999).

11) Please comment on whether the concentration-response function was applied to appropriate 

age groups given the age groups in the studies. 
9

III. INDIVIDUAL REVIEWER COMMENTS ON NON-CANCER HEALTH 

EFFECTS – DERIVATION OF CONCENTRATION-RESPONSE FUNCTIONS
10

Review By:

John R. Balmes, M.D.
11

Peer Review Comments on EPA’s Draft Document Approach to Assessing Non-cancer 

Health Effects from Formaldehyde and Benefits from Reducing Non-cancer Health Effects as 

a Results of Implementing Formaldehyde Emission Limits for Composite Wood Products

John R. Balmes, M.D. 

University of California, San Francisco

July 25, 2011

I. GENERAL IMPRESSIONS

The document is clearly and concisely written. The background subsections of Section 2: Noncancer Health Effects – Derivation of Concentration-Response Functions for sensory irritation 

(2.1.1), asthma (2.2.1), and female reproductive toxicity (2.3.1) are extremely brief, especially 

the latter two. While it is understandable that the EPA does not wish to be duplicative of the 

material in the draft IRIS document on formaldehyde or the NAS review of the IRIS document, 

some readers of the “Approach” document will not have read the IRIS and NAS documents and 

thus will benefit from a bit more background context on formaldehyde and asthma or 

formaldehyde and female reproductive toxicity.

II. RESPONSE TO CHARGE QUESTIONS

Sensory Irritation

The literature base of residential epidemiology studies of the irritation effects with quantitative 

concentration-response data was limited, but data were available from which a concentrationresponse function could be estimated for eye irritation.

1. Please comment on whether the concentration-response function is appropriately derived 

from the studies used in the draft Approach Document.

The concentration-response function (CRF) for sensory irritation is derived from one small field 

study, Hanrahan et al. (1984). Because most individuals exposed to formaldehyde from the 

products of interest will be exposed at levels below 100 ppb, the EPA is appropriately concerned 

about the form of the CRF in this range. Unfortunately, the data for exposures below 100 ppb 

are not given in the original Hanrahan paper and the regression of prevalence of eye irritation 

and formaldehyde concentration in the paper covers the range of 100-800 ppb. Another issue 

regarding CRF derivation from the Hanrahan paper is the relatively small sample size (n=61). 

The Liu et al. (1991) study, which involved a much larger population, is supportive of the 

concept that there is a CRF for formaldehyde and eye irritation at relatively low levels of 

exposure, but was not used in the actual derivation of such a CRF because of the way the authors 

aggregated their data into low, medium, and high levels of exposure.

2. Please comment on the validity of extrapolating the concentration-response function and 

using the function to estimate effects at concentrations below 100 ppb.

Given the limitations of the data available from the Hanrahan paper, the method of derivation of 

the CRF including the portion of the curve below 100 ppb is appropriate, but the extrapolation is 
12

pushing the envelope of what reasonably can be extracted from the data. The assumption that 

the reported standard deviation of the outdoor formaldehyde measurements represents the lower 

bound on the standard deviation of the indoor concentrations appears reasonable, but nonetheless 

the distribution of exposure data below 100 ppb in the Hanrahan study was assumed rather than 

based on the actual data. The EPA used the graphical display of the regression data over the 

range of 100-800 ppb in the Hanrahan paper to derive a CRF and then to infer the shape of the 

CRF below 100 ppb. Given that the Hanrahan study only included 61 subjects and that the 

formaldehyde measurements in the mobile homes were only for 30-60 minutes, the validity of 

the extrapolated CRF can be questioned even if an appropriate method was used.

3. The studies considered for the concentration-response function are residential studies 

because residential exposures are the focus of the rule and the residential studies avoid some 

of the limitations of other types of studies (e.g., controlled exposure chamber studies used 

high, acute exposures, and occupational studies reflect high exposure levels and potential 

dose-rate effects from peak exposures). Are there other studies (e.g., chamber or nonresidential studies) that should be used as supporting evidence for the currently derived 

concentration-response function for eye irritation? If so, please provide information about the 

studies and discuss how they should be used to support the concentration-response function.

I do not know of other studies that would be better to use for derivation of a CRF for 

formaldehyde exposure and sensory irritation given the EPA’s interest in chronic, low-level, 

non-peak exposures.

4. Are there other sensory irritation endpoints besides eye irritation for which a concentrationresponse function can and should be developed for assessing effects at concentrations below 

100 ppb? If so, please provide references of appropriate studies and a description of how the 

studies could be used to develop a concentration-response function.

I do not know whether a CRF can be developed for other sensory irritation endpoints. 

Asthma

Several studies of the association between formaldehyde and asthma have been published and 

these were quantitatively summarized in a meta-analysis by McGwin et al. (2010).

5. Please comment on whether the McGwin et al. (2010) meta-analysis is an appropriate 

summary of the association between formaldehyde inhalation exposures and childhood 

asthma.

The McGwin et al. (2010) meta-analysis of the association between formaldehyde exposure and 

risk of asthma in childhood appears to have been well conducted, using state-of-the-art methods, 

including both fixed and random effects models and various sensitivity analyses. Because the 

meta-analysis was based on a systematic review of the literature that appears to have been 

comprehensive, the results can be considered an appropriate summary of what is known about 

the association from epidemiological studies.

6. Please comment on whether EPA chose the appropriate function from the McGwin et al. 

paper to use in the benefits assessment.
13

Exponentiating the linear slope of the fixed effects model from the McGwin et al. paper is 

appropriate, especially given that the random effects model gave essentially the same pooled 

odds ratio.

Female Reproductive Toxicity

The literature base describing reproductive effects of formaldehyde exposure in humans is 

limited; however, there are supportive findings from the animal toxicological literature. The 

epidemiologic literature suggests an association between formaldehyde and increased risk of 

spontaneous abortion and a related delay in time to pregnancy (i.e., reduced fertility). The 

only study with quantitative concentration-response data was Taskinen et al. (1999).

The a priori hypothesis in Taskinen et al. (1999) was that formaldehyde would be associated 

with decreased fertility. The primary analyses showed that there was a statistically significant 

reduction of fertility among the women in the highest exposure group that appeared to be 

concentration dependent. Post-hoc subgroup analyses showed that stratification of the 39 

women in the highest exposure group by reported glove use yielded effect estimates whose 

confidence intervals overlapped. The FDR for the 17 women who were classified as not 

wearing gloves was 0.51 [95% CI: 0.28−0.92]. The FDR for women who were classified as 

always or sometimes wearing gloves was 0.79 [95% CI: 0.47−1.23]. 

7. In light of the results regarding glove use, in what way(s) can the Taskinen et al. results be 

used to support calculating a concentration response for formaldehyde inhalation risk to time 

to pregnancy?

The results of the stratified analysis regarding glove use are suggestive of the possibility that the 

dermal route may contribute to total exposure, but are not adequate to consider modification of a 

CRF for decreased fertility based on inhalational exposures, especially given the small size of the 

two strata and the wide confidence intervals of the FDR point estimates.

8. Please comment on whether the concentration-response function is appropriately derived 

from the Taskinen et al. (1999) study.

The CRF for formaldehyde exposure and decreased fertility appears to be appropriately derived 

from the Taskinen et al. (1999) study. The adjustment for probable exposure to formaldehyde 

outside of the workplace is appropriate given the interest of the EPA in potentially controlling 

indoor exposures due to off-gassing from certain products. The use of reasonably

contemporaneous background exposure data from Finland (Jurvelin et al., 2001) for this 

adjustment is also appropriate.

III. SPECIFIC OBSERVATIONS

Page 10, 1st full paragraph; page 14, figure 4a legend; page 15, 2nd full paragraph. The use 

of “inhalation” exposure in the context of eye irritation seems inappropriate. I would eliminate 

the use of “inhalation” in all three sentences.

Page 16, paragraph. 2.2.1. Asthma is defined by the Global Initiative for Asthma (GINA) as a 
14

disease characterized by inflammation of the airways, not lungs. I would eliminate “and lungs” 

in the first sentence of this paragraph. To avoid confusion, I would not use “sensitization” when 

discussing non-allergic, neurogenic mechanisms of irritant chemical-induced asthma in the third 

sentence.

Page 20, paragraph 2.3.1. “Increased relative risk estimates (RRs) were in the range of 1.7 to 

more than 3.0.” To avoid confusion, I would cite the specific papers that reported these increased 

relative risks.

Page 22, last sentence of text. The text here refers to “estimated concentration-response 

functions” but does not explain why there is more than one CRF in Figure 6. It is not until page

24 that one learns that “Regression equations for linear and exponential fits are also provided.” 

If the two lines in Figures 6 and 7 are for both types of fits then this should be clearly indicated.

Page 26, last full sentence. The use of a contraction here (“didn’t”) is unprofessional.
15

Review By:

David Kriebel, Sc.D.
16

Peer Review Comments on EPA’s Draft Document Approach to Assessing Non-cancer 

Health Effects from Formaldehyde and Benefits from Reducing Non-cancer Health Effects as 

a Results of Implementing Formaldehyde Emission Limits for Composite Wood Products

David Kriebel, Sc.D.

University of Massachusetts Lowell

July 21, 2011

I. GENERAL IMPRESSIONS

The overall impression is of a thoughtful and well-written document. The authors have provided 

a generally clear and logical explanation of their reasoning throughout. There are a few 

exceptions, noted below, where additional explanation or documentation could improve the 

presentation.

II. RESPONSE TO CHARGE QUESTIONS

Sensory Irritation

The literature base of residential epidemiology studies of the irritation effects with quantitative 

concentration-response data was limited, but data were available from which a concentrationresponse function could be estimated for eye irritation.

1. Please comment on whether the concentration-response function is appropriately derived 

from the studies used in the draft Approach Document.

I see no problems with the derivation of the concentration-response function itself. In Section 

2.1.3, I think it would strengthen the argument to at least acknowledge the problem of 

acclimatization. There is evidence from a number of studies – notably the studies of studies 

conducting autopsies – that there is a change over weeks in the short-term irritant effects. One 

way that this will impact the calculations is that cumulative exposure is probably not the 

appropriate exposure metric. The authors may have little choice to use the simplified approach 

they have taken which assumes a constant exposure-response relationship over time, but they

could acknowledge that there is a source of uncertainty from the changes in potency of 

formaldehyde over time for various endpoints. I suspect that the irritant effects diminish with 

time exposed, but the other two chosen endpoints probably do not.

2. Please comment on the validity of extrapolating the concentration-response function and 

using the function to estimate effects at concentrations below 100 ppb.

I am comfortable with this extrapolation. However, I think that it would be appropriate to 

acknowledge that errors in exposure estimation in the studies on which the function is based 

have not been included in the uncertainty calculations. This is a general concern – for all 3 

endpoints, there were certainly errors in the exposure estimation, and the impact of these on the 

uncertainty in the exposure-response function has not been considered.
17

It might be noted that the extrapolation downwards assumes a logistic shape, which is reasonable 

but not subject to validation. It might be noted that the excellent R2for Figure 3b is a bit 

misleading since it is fitting a curve to categorical data, while the actual individual exposure data 

were of course continuous – the fit of this curve to the original data would not have been nearly 

as good. And again, see my comment just above about failure to point out that the exposure data

had error, which was not taken into consideration in the model error calculations.

3. The studies considered for the concentration-response function are residential studies 

because residential exposures are the focus of the rule and the residential studies avoid some 

of the limitations of other types of studies (e.g., controlled exposure chamber studies used 

high, acute exposures, and occupational studies reflect high exposure levels and potential 

dose-rate effects from peak exposures). Are there other studies (e.g., chamber or nonresidential studies) that should be used as supporting evidence for the currently derived 

concentration-response function for eye irritation? If so, please provide information about the 

studies and discuss how they should be used to support the concentration-response function.

I think you should use the other studies – particularly the chamber studies and the autopsy 

studies – to show the consistency of the findings across many settings. I am comfortable with the 

argument that the function should be derived from the residential studies. But I think that the 

logic of extrapolating downwards is supported by some of the other studies. Kriebel et al. Arch 

Env Hlth 2001; 56:11- 18 contains fairly detailed exposure data linked to eye irritation scores. 

While much of the data are above the range you are concerned with, there is evidence here that 

the relationship observed was valid across the full range of exposures.

4. Are there other sensory irritation endpoints besides eye irritation for which a concentrationresponse function can and should be developed for assessing effects at concentrations below 

100 ppb? If so, please provide references of appropriate studies and a description of how the 

studies could be used to develop a concentration-response function.

Both nose and throat irritation can be linked to increased risk of lower respiratory tract infection 

including bronchitis. So you could argue that these would have greater economic impacts. 

 

Asthma

Several studies of the association between formaldehyde and asthma have been published and 

these were quantitatively summarized in a meta-analysis by McGwin et al. (2010).

5. Please comment on whether the McGwin et al. (2010) meta-analysis is an appropriate 

summary of the association between formaldehyde inhalation exposures and childhood 

asthma.

I agree that it is appropriate.

6. Please comment on whether EPA chose the appropriate function from the McGwin et al. 

paper to use in the benefits assessment.

I am comfortable with the choice to exclude Rumchev, and agree with the derivation of the 

function as described.
18

Female Reproductive Toxicity

The literature base describing reproductive effects of formaldehyde exposure in humans is 

limited; however, there are supportive findings from the animal toxicological literature. The 

epidemiologic literature suggests an association between formaldehyde and increased risk of 

spontaneous abortion and a related delay in time to pregnancy (i.e., reduced fertility). The 

only study with quantitative concentration-response data was Taskinen et al. (1999).

The a priori hypothesis in Taskinen et al. (1999) was that formaldehyde would be associated 

with decreased fertility. The primary analyses showed that there was a statistically significant 

reduction of fertility among the women in the highest exposure group that appeared to be 

concentration dependent. Post-hoc subgroup analyses showed that stratification of the 39 

women in the highest exposure group by reported glove use yielded effect estimates whose 

confidence intervals overlapped. The FDR for the 17 women who were classified as not 

wearing gloves was 0.51 [95% CI: 0.28−0.92]. The FDR for women who were classified as 

always or sometimes wearing gloves was 0.79 [95% CI: 0.47−1.23]. 

7. In light of the results regarding glove use, in what way(s) can the Taskinen et al. results be 

used to support calculating a concentration response for formaldehyde inhalation risk to time 

to pregnancy?

Yes, but you could strengthen your argument. First, there is a trend in both FDR and spontaneous 

abortion across levels of formaldehyde, so you should not only focus on the effect modification 

by glove use in the high exposure group. While the high exposure is the only group for which the 

authors provided the results stratified by glove use, the fact that there is a trend across air 

concentrations suggests that glove use – not constant across exposure levels – could not be a very

important source of protection or you would not see the trend. Second, you have not correctly 

dealt with the question of whether or not there is effect modification by glove use. The overlap of 

confidence intervals is not the correct way to do this. Construct the null hypothesis that glove 

users and non-users have the same FDR and then calculate a p-value testing this null. You can do 

it with the data provided – back calculate the standard errors from the confidence intervals, or 

ask the authors for the standard errors. I am pretty sure that this p-value will be large, and then 

you will be in a strong position to say that the appropriate conclusion is to act as if glove use has 

not modified the FDR. 

8. Please comment on whether the concentration-response function is appropriately derived 

from the Taskinen et al. (1999) study.

Can’t you ask Taskinen to confirm your (and my) assumption that age was the conditioning time 

variable in their FDR calculations?

The process of adjusting for background exposure is OK, but I don’t think it strengthens the 

presentation. First, I doubt very much that the relevant background formaldehyde exposure for 

the women in this plant could have been so much higher than the levels inside the plant. My

guess is that the mean (one mean for an entire country over a long period of time? How useful is 

that?) had a wide range around it. Second, any of my graduate students could have told you that 

adding a constant to all the x values in a regression model will not change the slope.
19

III. SPECIFIC OBSERVATIONS

Page 20, section 2.3.1, 6th and 7th lines. The statement “Increased relative risk estimates (RRs) 

were in the range of 1.7 to more than 3.0” is not helpful – without explaining whose risk is being 

compared to whose, the absolute value of an RR is not useful. 

Section 2.0 Background on the Identification of Non-Cancer Health Effects, last sentence. It 

would be helpful to summarize at least briefly the logic behind focusing on these 3 endpoints. If I 

have understood the NAS comments correctly, that Committee also raised questions about these 

choices, and in particular on the decision not to use pulmonary function evidence. Given this 

concern from the NAS, I think a bit more explanation of the perceived inadequacies in the data 

for the other endpoints would strengthen this document. 
20

Review By:

Frederick J. Miller, Ph.D., Fellow ATS
21

Peer Review Comments on EPA’s Draft Document Approach to Assessing Non-cancer 

Health Effects from Formaldehyde and Benefits from Reducing Non-cancer Health Effects as 

a Results of Implementing Formaldehyde Emission Limits for Composite Wood Products

Frederick J. Miller, Ph.D., Fellow ATS

Fred J. Miller & Associates LLC

July 18, 2011

I. GENERAL IMPRESSIONS

The comments provided are related to the health assessment and concentration-response 

evaluation portion of the above cited document as this reviewer was not asked to comment on the 

economic benefits assessment approach. For the most part, the sections on sensory irritation, 

asthma, and female reproductive toxicity are clearly presented and the material is developed in a 

logical manner. Some exceptions are noted in this reviewer’s responses to the specific charge 

questions. The decision on the concentration-response functions to take forward to the economic 

benefits analyses is best documented for sensory irritation. This reviewer provides a suggestion 

for how far below 100 ppb of formaldehyde the modeling results developed by the Agency based 

on the Hanrahan et al. (1984) study can be used. The material included in support of using the 

McGwin et al. (2010) meta analysis for asthma in children does not adequately describe the short 

comings of the meta analysis. The uncertainties and conflicting results of the studies make this 

reviewer reticent to endorse the concentration-response function for the odds ratio based on the 

McGwin et al. (2010) meta analysis. The case to use background adjusted exposure data for the 

female reproductive toxicity concentration-response curve is adequately defended. However, the 

Agency does not indicate if the linear risk or the exponential risk curve will be used.

Overall, the information presented is accurate. To their credit, in a number of places, the EPA 

authors have incorporated criticisms included in the NAS report of the Agency’s draft IRIS 

assessment document. By addressing the responses to the charge questions, the Agency will be in 

a good position to move forward with the cost benefit analysis required by Executive Order 

12866 related to the Formaldehyde Standards for Composite Wood Products Act. 

II. RESPONSE TO CHARGE QUESTIONS

Sensory Irritation

The literature base of residential epidemiology studies of the irritation effects with quantitative 

concentration-response data was limited, but data were available from which a concentrationresponse function could be estimated for eye irritation.

1. Please comment on whether the concentration-response function is appropriately derived 

from the studies used in the draft Approach Document.

The draft Approach Document adequately discussed the type of data available in the literature 

from various studies and presented their strengths and weaknesses. The Agency wisely stayed 

away from using the Liu et al. (1991) study as the primary driver for the concentration-response 

function for eye irritation. The categories from that study were formed on using a ppm-hr per 
22

week metric. The eye irritation studies discussed in Section 2.1.2 for a 10 % additional risk for 

560 ppb for 3 hours (i.e., 1,680 ppm-hrs) compared to 240 ppb for 5 hours (i.e., 1,200 ppm-hrs) 

clearly show that Haber’s Law does not apply for the effects of formaldehyde exposure on eye 

irritation, which agrees with Miller et al. (Haber’s rule: a special case in a family of curves 

relating concentration and duration of exposure to a fixed level of response for a given endpoint. 

Toxicology 149:21–34, 2000). Thus, the Agency would have been hard pressed to defend a 

translation of the ppm-hrs metric of Liu et al. (1991) as the basis for developing a concentrationresponse function for eye irritation.

Rather, the Hanrahan et al. (1984) study that reported eye irritation was associated with in-home 

formaldehyde exposures (p < 0.05) (both as “burning eyes” and “eye irritation”) was used as the 

data for developing a concentration-response relationship for eye irritation. Moreover, the 

logistic regression model developed by Hanrahan et al. (1984) gave insight as to the needed 

nature of the curve if one were to extrapolate below the range of exposures reported by those 

authors (i.e., from 100 to 800 ppb). In the opinion of this reviewer, the concentration-response 

function was appropriately derived by the Agency.

2. Please comment on the validity of extrapolating the concentration-response function and 

using the function to estimate effects at concentrations below 100 ppb.

The Agency appropriately focused on the data from the Hanrahan et al. (1984) study to develop 

the concentration-response curve for eye irritation. Importantly, the Agency used a power law 

curve to fit the prevalence odds data. This ensures that the fitted curve will asymptotically 

approach zero for a zero formaldehyde exposure level and makes it reasonable to use Equation 

2.2 below 100 ppb. Given (1) the limit of detection (LOD) was 10 ppb at the time the Hanrahan 

et al. (1984) study was conducted, (2) the Agency’s assumption about the outdoor standard 

deviation of measurements being 30 ppb around a log-normal distribution of measurements, and 

(3) the known overall shape of the concentration-response curve below 100 ppb, this reviewer 

believes it would be reasonable for the Agency to use the fitted equation down to a level of about 

40 ppb, which would correspond to the LOD plus one standard deviation.

3. The studies considered for the concentration-response function are residential studies 

because residential exposures are the focus of the rule and the residential studies avoid some 

of the limitations of other types of studies (e.g., controlled exposure chamber studies used 

high, acute exposures, and occupational studies reflect high exposure levels and potential 

dose-rate effects from peak exposures). Are there other studies (e.g., chamber or nonresidential studies) that should be used as supporting evidence for the currently derived 

concentration-response function for eye irritation? If so, please provide information about the 

studies and discuss how they should be used to support the concentration-response function.

Beyond the studies considered by EPA, this reviewer knows of no chamber or epidemiology 

studies that would be useful in developing the concentration-response function for eye irritation. 

Given the definition of an inhalation RfC and the focus on extended periods of exposure, the 

residential studies were conducted in a manner that best fits the criteria for developing an RfC 

and using it in the benefits analyses that the Agency is being required to conduct.

4. Are there other sensory irritation endpoints besides eye irritation for which a concentrationresponse function can and should be developed for assessing effects at concentrations below 
23

100 ppb? If so, please provide references of appropriate studies and a description of how the 

studies could be used to develop a concentration-response function.

Sensory irritation may be indirectly reflected in pulmonary function responses measured after 

exposure to formaldehyde. However, these studies were not conducted at levels that would be 

relevant to what the Agency is being charged with investigating.

Asthma

Several studies of the association between formaldehyde and asthma have been published and 

these were quantitatively summarized in a meta-analysis by McGwin et al. (2010).

5. Please comment on whether the McGwin et al. (2010) meta-analysis is an appropriate 

summary of the association between formaldehyde inhalation exposures and childhood 

asthma.

There are many problems with the studies used in the meta analysis conducted by McGwin et al. 

(2010). Relative to the description of the metal analysis, the Agency did a reasonable job of 

pointing out many of the strengths and weakness that McGwin and colleagues noted in their 

paper, but this description could be improved. 

There are various inconsistencies in the studies selected for the meta analysis that would make 

this reviewer reticent to put much trust in the findings for applicability to the U.S. population. 

First, only one study was conducted in the U. S. and that study did not find a statistically 

significant odds ratio (OR) with exposures being in the range of 30 to 80 μg/m3of formaldehyde. 

Moreover, the sample size of the U.S. study was greater than that of 5 of the other studies 

contained in Table 1 of McGwin et al. (2010).

A Swedish study with exposures no greater than 10 μg/m3had an OR more than twice that of 

any other study even though several of those studies involved formaldehyde exposures in the 5 to 

70 μg/m3range, including another Swedish study. The Zhao et al. (2008) study results are 

inconceivable to this reviewer for inclusion in a reliable meta analysis. With school exposures (1 

to 5 μg/m3) and outdoor exposures (5 to 7 μg/m3), mean OR estimates were found to represent 

decreased risk, yet the upper bound of the 95 % confidence interval was 17 for the school OR 

and more than 2.3 million for the outdoor OR for the same set of 1,993 children having a mean 

age of 12.8 years. 

McGowan et al. (2010) state that to evaluate whether the results they found were unduly 

influenced by any individual study and to determine if there was any publication bias, an 

influence plot and a funnel plot, respectively were used. However, they did not present these 

plots in their paper. The computed values of the Q and I

2

statistics were stated to support the 

presence of moderate between-study heterogeneity. The EPA document cites values for these 

statistics but does not explain how they are calculated, but should do so. Q (better known as

Cochran’s Q) is a classical measure of heterogeneity and is calculated as the weighted sum of 

squared differences between individual study effects and the pooled effect across studies, with 

the weights being those used in the pooling method. Q is distributed as a chi-square statistic with 

k (number of studies) minus 1 degrees of freedom (d.f.). The I

2

statistic describes the percentage 
24

of variation across studies that is due to heterogeneity rather than chance and is computed as 

100* (Q – d.f.)/Q.

On page 18 of the EPA document, the overall OR for a fixed effects model is given as 1.026 but 

on page 20 the same result is stated as an OR of 1.03. The Agency needs to be consistent. If the 

data are only sufficient to give an OR with 2 digits after the decimal point, say so and change the 

value on page 18 and vice versa. For the reader to better judge the reasonableness of the meta 

analysis results, the EPA document should include Table 1 of the McGwin et al. (2010) paper in 

addition to Figure 1 from that paper.

6. Please comment on whether EPA chose the appropriate function from the McGwin et al. 

paper to use in the benefits assessment.

The EPA document does not specifically state which model result (i.e. fixed effects or random 

effects) was selected. Rather they state that the mean OR was 1.24 per 10 ug formaldehyde per 

m

3

for both models. One only determines that the Agency chose to use the random effects model 

if one calculates the transformed 95 % confidence interval for an OR for an increase of 1 ppb and 

sees that what is stated on page 18 corresponds to the confidence interval for the random effects 

model. 

The lack of significant between-study heterogeneity in the meta analysis of McGwin et al. (2010) 

supports using a fixed effects model; however, the extent of the uncertainties among the studies 

and the fact that the random effects confidence interval will always be larger than the fixed 

effects confidence interval supports the conservative selection by the Agency to use the random 

effects model results.

In view of the additional problems this reviewer discussed earlier concerning the choice of 

studies for inclusion in the meta analysis, this reviewer would be reticent to have the benefits 

assessment use only one function (i.e., the OR of 1.03 per one ppb increase in formaldehyde 

exposure with a 95 % confidence interval from 1.008 to 1.047). The single U.S. study should 

also be evaluated wherein the OR is 1.0083 per 1 ppb increase in formaldehyde exposure with a 

95 % confidence interval of 0.97 to 1.045. 

Female Reproductive Toxicity

The literature base describing reproductive effects of formaldehyde exposure in humans is 

limited; however, there are supportive findings from the animal toxicological literature. The 

epidemiologic literature suggests an association between formaldehyde and increased risk of 

spontaneous abortion and a related delay in time to pregnancy (i.e., reduced fertility). The 

only study with quantitative concentration-response data was Taskinen et al. (1999).

The a priori hypothesis in Taskinen et al. (1999) was that formaldehyde would be associated 

with decreased fertility. The primary analyses showed that there was a statistically significant 

reduction of fertility among the women in the highest exposure group that appeared to be 

concentration dependent. Post-hoc subgroup analyses showed that stratification of the 39 

women in the highest exposure group by reported glove use yielded effect estimates whose 

confidence intervals overlapped. The FDR for the 17 women who were classified as not 
25

wearing gloves was 0.51 [95% CI: 0.28−0.92]. The FDR for women who were classified as 

always or sometimes wearing gloves was 0.79 [95% CI: 0.47−1.23]. 

7. In light of the results regarding glove use, in what way(s) can the Taskinen et al. results be 

used to support calculating a concentration response for formaldehyde inhalation risk to time 

to pregnancy?

The results after stratifying for glove use are indirectly supportive for an inhalation effect of 

formaldehyde on the fecundity density ratio (FDR). Those women who did not wear gloves had a 

statistically significantly decreased FDR of 0.51 (i.e., 95 % confidence interval did not include 

1). Women classified as always or sometimes wearing gloves had a FDR closer to 1 and their 

confidence interval included 1. Thus, the inclusion of women wearing gloves would tend to 

move the overall FDR closer to 1, where FDR values lower than 1 can be interpreted as an 

adverse effect in that the time to achieve conception is delayed. This was indeed the case since a 

FDR of 0.64 was found for all women in the highest exposure group. This provides evidence in 

support of the hypothesis that effects on FDR were most likely due to inhalation exposure rather 

than to dermal exposure to formaldehyde.

8. Please comment on whether the concentration-response function is appropriately derived 

from the Taskinen et al. (1999) study.

A concentration-response function can be derived from the Taskinen et al. (1999) study, and the 

selected function must be one for which there was an adjustment for background exposure levels; 

however, the EPA document does not actually state whether they will use the linear function of 

risk or the exponential function of risk equations that are discussed in the document (i.e. will the 

Agency use Eq. 2-5 or 2-6?).

The two curves presented in Figures 6 and 7 of the Agency document are not explained either in 

the figure legend or in the text. While they obviously relate to the regression of risk on 

formaldehyde concentration, their difference is not explained. The Agency clearly picked up on 

most of the criticisms provided by the NAS review of the draft IRIS document related to the 

Taskinen et al. (1999) study. However, the Agency’s section on the discussion of uncertainties 

does not comment at all on the clear possibility of confounding due to xylene exposures in the 

Finnish worker study. Also, there is no discussion of the possible magnitude or direction of any 

exposure misclassification bias in the Taskinen et al. (1999) study. If the Agency is going to use 

the Taskinen et al. (1999) study in their economic analysis, more attention to a description and 

discussion of the study’s strengths and weaknesses is needed. 
26

III. SPECIFIC OBSERVATIONS

None.
27

Review By:

Rebecca T. Parkin, Ph.D., MPH
28

Peer Review Comments on EPA’s Draft Document Approach to Assessing Non-cancer 

Health Effects from Formaldehyde and Benefits from Reducing Non-cancer Health Effects as 

a Results of Implementing Formaldehyde Emission Limits for Composite Wood Products

Rebecca T. Parkin, Ph.D., MPH

The George Washington University Medical Center

July 13, 2011

I. GENERAL IMPRESSIONS

The draft is clearly organized and, in large part, well-written. Minor inaccuracies are noted 

below. Most sections were clear, although some key issues were not mentioned or are not clear; 

these concerns are noted below. Except in a few instances as noted below, the conclusions are 

effectively supported by the text provided.

Uncertainties are important to discuss. EPA has captured many of the important ones, but may

need to add more to these sections based on this and other reviewers’ comments. Being 

thorough in all uncertainty sections is crucial to the foundations of the benefit assessments.

II. RESPONSE TO CHARGE QUESTIONS

Sensory Irritation

The literature base of residential epidemiology studies of the irritation effects with quantitative 

concentration-response data was limited, but data were available from which a concentrationresponse function could be estimated for eye irritation.

1. Please comment on whether the concentration-response function is appropriately derived 

from the studies used in the draft Approach Document.

First, I will comment on each study and then on the derivation process.

Liu et al (1991): This paper adequately describes how homes were randomly selected, but omits 

some key information related to monitoring results for the homes included. The study was 

conducted throughout California (p. 93); a very large state with a wide range of climatic 

conditions. “Summer” and “winter” sampling periods were used, but these seasons are quite 

different in different parts of the state. It is well-known that temperature and relative humidity

affect formaldehyde (HCHO) levels, but there is no mention of how these factors varied in the 

study homes or how they may have affected measured HCHO levels. Further, the Quality 

Assurance/Quality Control methods are not described, and the number of laboratories used to 

analyze the passive area monitoring samples is not stated. These omissions leave this reviewer 

without key information to assess the accuracy or validity of the HCHO levels reported. 

Residents received instructions on how to uncap, place and mail back the samplers. The use of 

the kitchen and master bedroom as monitoring sites may be most relevant for the homeowner 

and less relevant for other occupants. Although averaging the monitored levels for each home 
29

may have lost some useful variation, it is not likely that in fairly small homes (such as mobile 

homes) that this loss – except for peak exposures – would be particularly important. 

The study appropriately controls the impact of smoking indoors, and does not discuss gas 

cooking stoves or appliances, opening of windows and doors, or other factors that have been 

reported by other authors as having non-significant impacts on HCHO levels. 

More importantly, if I am reading the article correctly (p. 92), some indoor samples in this crosssectional study were taken after symptoms were recorded. This conflicts with determining the 

appropriate temporal sequence of cause preceding effect. I believe my reading is different from 

what EPA states on p. 10 of their draft, which indicates that exposures were recorded in a period 

preceding the documentation of symptoms.

Hanrahan et al (1984): This cross-sectional study, conducted in Wisconsin during July 1979, 

sampled a smaller number of mobile homes (65) than did Liu et al.; it also had a lower 

percentage of participants among those contacted (31% vs. 44%). In this study, personal 

samplers were used and 33 outdoor samples were taken (at least 1 in each mobile home park). 

The authors noted that prior to and during sampling periods home windows were closed, gas 

appliances were turned off and smoking was prohibited. 

The Quality Control and specific laboratory methods were noted (unlike in Liu et al). The 

indoor samples for each home were averaged, as in Liu et al, with similar but less specific 

sampling locations noted. It is not clear whether the residents or the researchers collected the air 

samples in this study. 

Smoking was appropriately considered, and indoor and outdoor temperature and humidity, and 

appliance and construction characteristics were noted. Some but not all of these factors’ 

influences on HCHO levels were presented in the article.

Derivation: The seasonal and cumulative averages and ranges of indoor levels, the 

concentration-response data are correctly extracted from the Liu et al. article. The method to 

estimate the average number of hours indoors seems appropriate; however, this reviewer 

wonders whether EPA attempted to determine whether the authors still have the raw data that 

could be used for a more accurate assessment of hours spent indoors.

EPA had to make many more adjustments when using the Hanrahan et al. article. First, EPA 

estimated the lower bound for the indoor levels based on the standard deviation for the outdoor 

levels; this is a reasonable approach given the missing data for the indoor levels. Second, the 

Agency assumed that the distribution of indoor levels is log-normal in order to estimate the 

number of samples with HCHO levels below 100 and 50 ppb. However, if this assumption or 

the estimated standard deviation is not correct, the numbers of samples could be quite different. 

It is not clear in Figure 2 whether the data shown are for EPA’s or the authors’ use of “eye 

irritation;” e.g., does “eye irritation” here mean the “burning eyes” AND “eye irritation” results 

in the article? If combined data were used, did EPA assume that all of these symptoms were 

distinct and not co-occurring events? Are we looking at data for the number of symptoms 

reported or the number of people with eye symptoms (meaning “burning eyes” and “eye 

irritation”) at each level of exposure? This question should also be asked of the data shown in 
30

the draft Table 1. Without knowing whether EPA combined data in Figure 2 and Table 1, it is 

difficult to comment further on this part of the draft.

The conversion of data in the article to prevalence odds seems appropriate. The display of 

estimates below 150 ppb in Figure 4b are derived from Equation 2-2 and are likely correct. This 

reviewer did not verify the mathematics.

The EPA authors have noted many key uncertainties in the two studies and how these affect their 

estimates of the relational function. However, the validity of the HCHO monitored levels 

remains a question, due to missing information in the articles; exposure misclassification is 

possible in both studies but is not discussed in the draft. 

2. Please comment on the validity of extrapolating the concentration-response function and 

using the function to estimate effects at concentrations below 100 ppb.

The validity of the extrapolation in the Hanrahan et al. paper depends in part on what data were 

used for the outcome measure. If “burning eye” AND “eye irritation” data were combined, more 

information is needed in the draft to describe what assumptions were made in the combining 

process. (See comments above.)

The validity of the estimates below 100 ppb based on the Hanrahan et al. data is strengthened by

their alignment with the results in the Liu et al. study.

However, clearer discussion of the Agency’s choice of and uncertainties in the points of 

departure would improve this portion of the draft. 

3. The studies considered for the concentration-response function are residential studies 

because residential exposures are the focus of the rule and the residential studies avoid some 

of the limitations of other types of studies (e.g., controlled exposure chamber studies used 

high, acute exposures, and occupational studies reflect high exposure levels and potential 

dose-rate effects from peak exposures). Are there other studies (e.g., chamber or nonresidential studies) that should be used as supporting evidence for the currently derived 

concentration-response function for eye irritation? If so, please provide information about the 

studies and discuss how they should be used to support the concentration-response function.

I am not aware of any other studies that should be considered for this function.

4. Are there other sensory irritation endpoints besides eye irritation for which a concentrationresponse function can and should be developed for assessing effects at concentrations below 

100 ppb? If so, please provide references of appropriate studies and a description of how the 

studies could be used to develop a concentration-response function.

I agree with EPA and NAS that eye irritation is the most sensitive sensory irritation endpoint and 

therefore is the most appropriate endpoint to use.

Asthma

Several studies of the association between formaldehyde and asthma have been published and 

these were quantitatively summarized in a meta-analysis by McGwin et al. (2010).
31

5. Please comment on whether the McGwin et al. (2010) meta-analysis is an appropriate 

summary of the association between formaldehyde inhalation exposures and childhood 

asthma.

The authors clearly built on well-accepted guidelines for systematic meta-analysis (Stroup et al., 

2000). The study selection/exclusion criteria and process used by McGwin et al. is welldocumented in their article. The variables extracted and utilized are stated. The determination to 

use a consistent metric (odds ratio per 10 μg/m3 with the related 95% confidence interval) across 

the 7 studies for which actual HCHO measurements were available is appropriate. The methods 

used to pool the odds ratios and test for heterogeneity are standard analytic approaches. Their 

evaluation of the potentially undue influence of any one study, using influence and funnel plots, 

adds strength to their analysis. The results are shown with and without Rumchev et al., allowing 

the reader to judge whether this paper should have been included or not. The data in Table 2 

indicate that the magnitude of the HCHO effect on asthma prevalence is significant whether this 

study is included or not. The presentation of the Q and I2statistics guides the reader to the key

results for interpreting the data in this table. In summary, this reviewer finds that the McGwin et 

al. meta-analysis is an appropriate summary and synthesis of the eligible studies reporting a 

quantitative relationship between HCHO and prevalence of childhood asthma.

6. Please comment on whether EPA chose the appropriate function from the McGwin et al. 

paper to use in the benefits assessment.

The Agency has chosen the appropriate function from the McGwin et al. paper. With the 

exception of the discussion of the rationale for excluding Rumchev et al., however, more 

insightful comments about the strengths of the meta-analysis would lend greater support to the 

Agency’s use of and reliance on the fixed-effects model’s OR=1.24. Deepening the discussion 

would improve the support for the Agency’s conclusions and recommendation. For example, 

McGwin et al. stated that an I2value of <50% would point to relying on the fixed-effect results 

(p. 314). Although the Agency uses the fixed-effect modeling results, correctly stating that the Q 

and I2data indicate low heterogeneity, the draft does not include the key cut-point (I2<50%) for 

the use of fixed- vs. random-effect modeling results. In this reviewer’s opinion, pointing the 

reader explicitly to this cut-point and the relevant data in McGwin et al.’s Table 2 would sharpen 

the Agency’s rationale for choosing the fixed-effect results

The discussion of uncertainties in this section includes the key issues (such as the changes in 

definition and determination of “asthma” over time) and is appropriately written.

Female Reproductive Toxicity

The literature base describing reproductive effects of formaldehyde exposure in humans is 

limited; however, there are supportive findings from the animal toxicological literature. The 

epidemiologic literature suggests an association between formaldehyde and increased risk of 

spontaneous abortion and a related delay in time to pregnancy (i.e., reduced fertility). The 

only study with quantitative concentration-response data was Taskinen et al. (1999).

The a priori hypothesis in Taskinen et al. (1999) was that formaldehyde would be associated 

with decreased fertility. The primary analyses showed that there was a statistically significant 
32

reduction of fertility among the women in the highest exposure group that appeared to be 

concentration dependent. Post-hoc subgroup analyses showed that stratification of the 39 

women in the highest exposure group by reported glove use yielded effect estimates whose 

confidence intervals overlapped. The FDR for the 17 women who were classified as not 

wearing gloves was 0.51 [95% CI: 0.28−0.92]. The FDR for women who were classified as 

always or sometimes wearing gloves was 0.79 [95% CI: 0.47−1.23]. 

7. In light of the results regarding glove use, in what way(s) can the Taskinen et al. results be 

used to support calculating a concentration response for formaldehyde inhalation risk to time 

to pregnancy?

The article (p. 208) is not clear as to whether the post-hoc analysis was adjusted for the variables 

noted in the footnote of Table VI; if not, the post-hoc results would not be directly comparable to 

the data presented there. That said, the reported post-hoc high exposure group glove/not odds 

ratios and confidence intervals expand and are consistent with the trend shown in Table VI. 

However, all of the confidence intervals overlap each other, yielding a set of non-significant 

odds ratios. If the adjusted post-hoc odds ratios are available, it would be interesting to see the 

results of a test for trends comparing high exposure-gloves not used, high exposure-gloves used, 

medium exposure, and low exposure. The trend probably is not significant, but testing its 

significance may offer more information for interpreting the concentration-response relationship.

8. Please comment on whether the concentration-response function is appropriately derived 

from the Taskinen et al. (1999) study.

Exposure measurements were available only for the middle of the study period, but the authors 

were able to verify “most” women’s self-reported exposure levels based on data from their 

workplaces. The article does not state whether this verification was completed to the same 

extent across the entire study period. This reviewer also wonders whether for some women 

(outside of the undefined “most”) the authors assumed that self-reported HCHO exposure levels 

were accurate and did not change during the study period. The Agency draft notes general 

exposure measurement concerns and agrees with Taskinen et al. regarding their modest response 

rate to the mailed questionnaire. 

Although Taskinen et al. note that reporting biases may be present in their study, they did not 

report any evaluation of their data to address that concern. For example, the response rates for 

women with pregnancies in the 1985-90 vs. 1991-95 periods were quite different. Although the 

authors note that “only a few women could not report the length of time to pregnancy,” they do 

not indicate whether more women in the earlier vs. later period were non-reporters. Also, there 

is no mention to what extent the authors believe the recall of the number of months-to-pregnancy

was accurately recalled by either group of women. Neither Taskinen et al. nor EPA adequately

discuss whether self-reported time-to-pregnancy (or spontaneous abortion) data are reliable for 

use as an outcome measure. If outcome misclassification is an issue as well as exposure 

misclassification, the odds ratios could be further compromised toward the null. Discussion of 

the reliability of self-reported outcome data should be considered for the next draft.

The Agency’s adjustment for non-occupational HCHO exposures, based on contemporaneous 

data, shifts the relationship to the right (from Figure 6 to Figure 7) but does not consider the 

variation in exposure levels found by Jurvelin et al. The draft assumes that all of the women in 
33

the study had the same non-occupational HCHO exposures. Considering the range, not just the 

mean, of Jurvelin et al.’s measurements would be more informative and would allow for the 

identification of upper and lower bounds on the concentration-response relationship. 

III. SPECIFIC OBSERVATIONS

Eye Irritation 

Page 10, last paragraph, line 4 and Figure 2, line 2. The EPA draft states that these samples 

were taken from 30-60 minutes, but the authors only mention pumps running “for approximately

one hour” (p. 1026). Does EPA have information in addition to what is in the article or is the 30-

minutes an error? 

Pages 11-12. Figure 2 in the draft has a more detailed caption, but otherwise seems to be exactly 

the same as the one in the Hanrahan et al. paper (which is data for “burning eyes”); is it the same 

as in the paper? If so, shouldn’t it clearly indicate that it is “burning eye” data? 

Page 12. Table 1 may need a clearer caption indicating whether the data shown are for “burning 

eyes” AND “eye irritation” or “eye irritation” alone. Wherever combined data are used, EPA 

should clarify this usage and possibly create a new name for combined eye symptom data. 

Further, the title of Table 1 would be more accurate if it included “...extracted and calculated 

from...” 

Asthma

Page 16, last paragraph, last 2 lines and top of page 1. The descriptive language in the 

Agency draft about using the McGwin et al.’s I2statistic would be stronger if made more 

specific; e.g., noting that McGwin et al. used a cut-point of <50% for choosing fixed- vs. 

random-effects data (page 314, top of middle column). It appears that EPA agreed with this cutpoint. 

Page 18, first complete paragraph, line 6. The Agency states that the I

2

statistic is 11.2 when 

the Rumchev et al. paper is excluded, but Table 2 in McGwin et al. shows 11.3.

Female Reproductive Toxicity

Page 22. The title on Table 2 should state which “response” (TTP) is presented.
34

IV. INDIVIDUAL REVIEWER COMMENTS ON 

THE BENEFITS ASSESSMENT APPROACH
35

Review By:

Glenn C. Blomquist, Ph.D.
36

Peer Review Comments on EPA’s Draft Document Approach to Assessing Non-cancer 

Health Effects from Formaldehyde and Benefits from Reducing Non-cancer Health Effects as 

a Results of Implementing Formaldehyde Emission Limits for Composite Wood Products

Glenn C. Blomquist, Ph.D.

University of Kentucky

July 19, 2011

I. GENERAL IMPRESSIONS

Overall, the draft Approach Document is well-written. Refreshingly, Standard English language 

is used extensively and technical terms introduced when necessary. Examples to explain terms 

such as odds ratios should make the document understandable to educated lay readers with 

varied backgrounds. The key concentration-response functions are clearly presented in the form 

of equations and graphs or tables. This draft is readable. Information presented appears to be 

accurate and representative of studies that are the source of the information. Brief descriptions 

of key studies are given in addition to the findings relevant to the topic of this draft Approach 

Document. The extensive list of references allows the reader to learn more about the studies 

from which crucial estimates are taken. Conclusions regarding concentration-response functions 

and valuation (monetization) as reflected in their use in the examples follow from the 

information and models presented in a logical and reasonable way. My assessment of 

presentation applies to the entire document. My assessment of accuracy and soundness applies 

mostly to Section 3 Benefits Assessment Approach because of my background in environmental 

and health economics.

II. RESPONSE TO CHARGE QUESTIONS

Sensory Irritation

The concentration-response function for the prevalence of eye irritation is based on 

Hanrahan et al. (1984). While Hanrahan does not identify the relevant time period for this 

relationship, Liu et al. (1991) produced qualitatively similar results for a two-week time period. 

We assumed that the concentration-response relationship for eye irritation is for a two-week 

period and multiplied the concentration-response function times 26 to obtain the number of 

cases of eye irritation experienced in one year. 

The concentration-response curve used is non-linear, which means that the annual approach 

may not produce an exact measure of the benefits, but it is believed that the bias is probably 

relatively small given the small change in exposure.

1. Please comment on whether the concentration-response function is used appropriately in 

the benefits assessment approach.

The change in exposure expected from the policy appears to be small relative to typical 

exposure. It follows that the linear approximation implied by multiplication by 26 to obtain 

annual changes in number of cases of eye irritation should produce only a small bias. It seems as 

reasonable as other approaches.
37

The concentration-response curve is for an acute effect occurring at a time less than the oneyear time step of the exposure model. The willingness to pay to avoid cases of eye irritation is 

calculated for each year of analysis by multiplying the number of cases in a year by the 

marginal willingness to pay value to avoid one case. This may produce biased results, but the 

direction of that bias is unknown.

On one hand, some studies have suggested that the willingness to pay per symptom-day declines 

as the number of symptom-days avoided increases. In other words, the value to reduce two 

symptom-days of some effect is less than two times the value for one symptom-day. Therefore, 

this approach may overstate the total value. 

On the other hand, this analysis only applies values to one symptom, eye irritation, largely 

because this is the only symptom for which an effective concentration-response curve was 

derived. However, there is evidence that there are other forms of minor eye, nose, and throat 

irritation associated with formaldehyde exposure. Since eye irritation is the largest of the 

median values from the Tolley et al. (1986) study, the values used here likely represent a lower 

bound on the true effect of multiple symptoms. A reasonable upper bound of the total effect 

for one symptom-day would be sum of the willingness to pay for one symptom-day of each 

effect individually. 

2. Please comment on whether the annualized approach as opposed to the lifetime approach is 

appropriate in this context.

I admit to being confused by the statement that eye irritation has the largest of the median values 

in the Tolley et al. (1986) study. (For full disclosure, I am one of et al.) Much of that study was 

published in Tolley, Kenkel, and Fabian Valuing Health for Policy (1994) particularly in Chapter 

4 by Kenkel, Berger, and me. In Table 4.3A on page 88, the median values for willingness to 

pay to avoid an additional symptom day are $11 for coughing, $12.50 for eye irritation, $13 for 

throat irritation, and $14 for sinus congestion. All three are similar, but eye irritation is not the 

largest. It will not make much difference, however, if either of the other two is used instead of 

$12.50 for eye irritation.

Comparing results reported in Table 4.3A and Table 4.3B suggests that willingness to pay per 

symptom-day declines as the number of symptom days avoided increases. For example, the 

median value for avoiding 30 symptom-days of eye irritation is $100 which is less than 30 times 

$12.50 (or $375). This suggests that multiplying the $12.50 times the number of days of eye 

irritation avoided will bias the annual estimate for avoiding eye irritation upwards if there are 

multiple days for individuals. Declining marginal willingness to pay for avoided illnesses is also 

found in the recent study, Bosworth, Ryan, Trudy Ann Cameron, and J.R. DeShazo. “Demand 

for Environmental Policies to Improve Health: Evaluating Community-Level Policy Scenarios”

Journal of Environmental Economics and Management 57 (2009): 293-308.

Table 4 also shows willingness to pay values for avoiding combinations of symptoms in a day. 

The willingness to pay values for avoiding combinations of symptoms in a day are less than the 

sums of the willingness to pay values for avoiding the symptoms separately. The declining 

marginal value of adding another light symptom suggest that a reasonable upper bound of the 
38

annual value of the total effect for one symptom-day would be the sum of the willingness to pay

for one symptom-day of each effect individually.

On page 34, the paragraph that begins with Tolley et al. (1986) is mostly correct. (I am a 

coauthor on that Tolley report and the Berger et al. (1987) article.) It is correct, as stated, that 

the mean willingness to pay to relieve one symptom-day of a light symptom was $25 - $50. It is 

mostly correct, as stated, that Berger et al. report higher willingness to pay values for these same 

symptoms. The difference is due to different samples. The Tolley et al. values are based on a 

sample of 176 respondents, some of whom had experienced the symptoms and some of whom 

had not. The Berger et al. values are based on a subsample of 119 who actually had experienced 

a symptom. The mean values for the subsample that had experienced the symptoms are greater 

than for the full sample for five of the seven light symptoms, nearly the same for one, and less 

for the remaining one. The mean value for eye irritation was $48.48 for the 16 who reported eye

irritation whereas the mean value was $27.73 for all 176 who responded. The values reported 

are in 1984 dollars in both the Tolley et al. report and the Berger et al. article. The median value 

for eye irritation of $12.50 that Weitzel (1990) found is also reported in Tolley, Kenkel, and 

Fabian Valuing Health for Policy (1994) in Table 4.3 on page 88. It is correct that it too is in 

1984 dollars. 

On page 36, if the BLS Inflation Calculator is used to inflate the median value of $12.50 for eye 

irritation from 1984 dollars to 1999 dollars, the value is $20.03 as shown in Table J-10. If the 

same is done for 1984 to 2006, the value is $24.25, which rounds to $24, as reported below Table 

J-10.

Two recent studies find that different lifetime risk profiles are valued differently; see Nielsen, 

Jytte Seested, Susan Chilton, Michael Jones-Lee, and Hugh Metcalf. “How Would You Like 

Your Gain in Life Expectancy to Be Provided? An Experimental Approach” Journal of Risk and 

Uncertainty 41 (December 2010): 195-218 and Cameron, T.A., J.R. DeShazo, and P. Stiffler. 

“Demand for Health Risk Reductions: A Cross-national Comparison between the U.S. and 

Canada” Journal of Risk and Uncertainty 41 (December 2010): 245-273. Given the limited 

information on the symptoms of interest it is not clear how incorporate these finding into the 

Approach Document.

The concentration-response function for the prevalence of eye irritation is for a single twoweek period. The annualized approach used an adjusted concentration-response relationship 

that consisted in multiplying the concentration-response function obtained from Hanrahan et 

al. (1984) by 26 two-week periods.

3. Please comment on whether the adjustment of the concentration-response function is 

appropriate in the annualized approach.

It seems as reasonable as other possible approaches.

Asthma

The concentration-response relationship for asthma incidence is given as an odds ratio for 

children exposed to formaldehyde. An odds ratio is a way of comparing the difference in the 

probability of an event, in this case asthma diagnosis, occurring in groups exposed at different 

levels. The odds ratio is used to determine the willingness to pay for any change in emissions 
39

exposure over a 16 year period. We assume that the probability of being diagnosed with 

asthma is uniformly distributed across these 16 years. 

The use of an odds ratio implies that the concentration-response relationship is non-linear. 

However, given that the change in exposure is relatively small, the results from using this 

implied non-linear function are anticipated to be similar to the results if we were to use a 

linear function.

4. Please comment on whether the concentration-response function is used appropriately in 

the benefits assessment approach.

It seems as reasonable as other possible approaches.

The valuation of asthma effects from formaldehyde exposure is based on valuing the 

incidence of asthma rather than the more standard valuation based on the exacerbation of 

asthma symptoms. The reason for this is that a statistical relationship between formaldehyde 

exposure and asthma exacerbation has not been sufficiently well established, but there is a 

statistical relationship between formaldehyde exposure and asthma occurrence or incidence. 

However, the only time that EPA has valued asthma exacerbation is for the first prospective 

study of the benefits and costs of the Clean Air Act (EPA 1999). This is probably due to a lack 

of an appropriate concentration-response relationship. The EPA’s Office of Air does include 

recommended values for the monetization of chronic asthma in its BenMAP documentation 

(EPA 2011b), which is based on an average of the results from Blumenschein and 

Johannesson (1998) and O’Conor and Blomquist (1997).

For this analysis, EPA treats prevalence as a measure of cumulative incidence by assuming 

that the disease duration is the rest of the child’s life. However, the EPA (2000a) has 

previously assumed that a portion of asthmatic children will become asymptomatic as they 

move into adulthood.

5. Please comment on whether the annualized approach as opposed to the lifetime approach is 

appropriate in this context.

The approach used seems reasonable except for ignoring that some of the asthmatic children are 

likely to become asymptomatic as adults. If the incidence and prevalence data can support 

outgrowing asthma, then it should be incorporated in the estimates of valuing the incidence of 

asthma. Otherwise, the estimates will be biased upward.

I agree with the choice of the best estimate from O’Conor and Blomquist (1997) for the implied 

annual value of asthma control (page 47). It is $1,474 and is based on the risk-risk tradeoff and 

the assumed value of statistical life of roughly $6 million. The $1,474 is close to the 

nonparametric estimates of $1,500 for the 5 unit change and $1,440 for the 10 unit change. It is 

also close to the parametric estimates assuming a value of statistical life of $6 million of $1,468 

for Model 3 and $1,504 for Model 4. They are the more complete specifications of the drug 

choice logistic regression. Since surveys were done in 1995, the values are in 1995 dollars.

The implied annual value of asthma control of $1,474 in 1995 dollars is also close to the best 

estimates from our more recent work; see Glenn C. Blomquist, Mark Dickie, and Richard M. 
40

O’Conor. “Willingness to Pay for Reducing Fatality Risks and Asthma Symptoms: Values for 

Children and Adults of All Ages” Resource and Energy Economics 33 (May 2011): 410-425. In 

this recent work, we are able to estimate the willingness to pay without assuming a value of 

statistical life. As Table 5 shows, for the ordered logistic regression for willingness to pay for 

the more effective drug we have a larger sample for the preferred specification (263 in 2011 > 75 

in 1997) and the ratio of the coefficient for efficacy in controlling asthma to its standard error is 

much larger (3.14 in 2011 > 0.70 in 1997). This facilitates estimation directly from the 

willingness to pay logit rather than indirectly from the risk-risk logit and an assumed value of 

statistical life. We were also able to test for selection bias related to the choice of drug at the 

first stage of the hybrid contingent valuation. (We found we could not reject the null of no 

correlation between errors and so based estimates of willingness to pay on the logit regression 

without selection.) Lastly, we made estimates based on using only “definitely yes” as a “yes” 

instead of both “definitely yes” and “probably yes” as a “yes” as in O’Conor and Blomquist 

(1997). In Table 6 we report values that turn out to be comparable to the best estimate from our 

earlier work. For the average age adult (45 years) our estimate for the annual value of asthma 

control is $1,960 in 2007 dollars (or $1,441 in 1995 dollars). From Table 6 which reports annual 

values of asthma control by age we cautiously summarize saying that the pattern of results hints 

that values are higher for children and young adults. For the average age child (11 years) our 

estimate for annual value of asthma control is $2,842 in 2007 dollars (or $2,089 in 1995 dollars.) 

This pattern is relevant for estimating the asthma related benefits because the ages considered are 

0 – 16 and point estimates for values for children are greater than the value for the average age 

adult. The pattern suggests that estimates based on the average value for adults are probably 

underestimates, at least with respect to this factor.

The concentration-response relationship is based on an odds ratio for a period of time longer 

than the one year. The exposure model produces results for one-year of exposure to 

formaldehyde for each age, housing type, and climate cohort. As a consequence, an 

adjustment to the simple model needed to be made to model the effect on individuals who are 

currently alive when the regulation takes effect.

As an upper bound estimate, we assume that the odds ratio can be applied to the one year 

reduction in the same fashion as it was applied for the 16 year time period. The problem with 

this approach is that it effectively treats the exposure as an acute effect. If the odds ratio 

indicates a particular percentage reduction in asthma cases from a reduction in formaldehyde 

exposure over 16 years, the upper bound approach would suggest the same percentage 

reduction in asthma case in one single year if we were to witness the same reduction in 

formaldehyde exposure in one year. The lower bound approach assumes that a particular 

exposure reduction for one year produces the same effect as if that exposure reduction were 

spread out over the entire 16-year time period. 

6. Please comment on the upper and lower bound methodology used.

It seems as reasonable as other possible approaches.

The prevalence data suggest that 7.2% of children age 0-4 have been told that they have 

asthma. 16.4% of children aged 5-14 have been told that they have asthma. We assume that 

the probability of being diagnosed is uniformly distributed across the 0 to 16 age bracket, so 

that the incidence rate would be 1.44% for the first five years and 1.49% for the next eleven 
41

years. Allocating cases uniformly across the age brackets provides us with a way to calculate 

the annual benefits of any exposure reduction that occurs for the entire time period, but may 

not be appropriate if the diagnosis of asthma for very young children (e.g., age 0-2) differs 

from older children.

7. Is the assumption about applying the concentration-response function to children aged 0 to 

16 appropriate, given the asthma onset studies’ focus on school-aged children and 

adolescents, and given the potential uncertainty of the Rumchev study involving younger 

children?

It seems as reasonable as other possible approaches. A question about this and the other 

concentration-response functions and exposure is whether or not they take into account averting 

behavior. Smell leads to open windows and more time outside of house and less exposure.

Female Reproductive Toxicity

The linear concentration-response function accounting for background exposures based on 

Taskinen et al. (1999) is used for the annual approach.

8. Please comment on whether the concentration-response function is used appropriately in 

the benefits assessment approach.

It seems as reasonable as other possible approaches.

Monetization of delayed fertility has been discussed in the literature but has never been 

included in primary analyses of EPA rules because it was believed that the scientific 

knowledge on reproductive and developmental health effects was not strong enough to 

quantify risk in the primary benefits analysis.

While there appears to be good data on the cost of treatment, there are few studies on the 

willingness to pay to reduce delayed conception. Most economic valuation studies regarding 

fertility focus on an individual’s or a couple’s willingness to pay for infertility treatment, 

particularly in-vitro fertilization (IVF). Conceptually, the willingness to pay approach is 

preferable and could be deduced from the valuation studies. However, given that there has 

been less research on these willingness to pay values than other values and the fact that the 

values have not been used in previous economic analyses, we used the more straight-forward 

cost of illness approach for this analysis.

As an upper bound, we assume that any woman who has difficulty conceiving (i.e., time to 

pregnancy exceeds 12 months) will obtain some type of fertility service. This may be a 

reasonable upper bound, but there are certainly women who have trouble becoming pregnant 

and do not seek fertility treatment. 

The willingness to pay for fertility treatment is treated as an expected value. The average cost 

of various cycle-based fertility treatments is multiplied times the probability of obtaining that 

treatment at various ages. There is probably a small opposite effect associated with an increase 

in pregnancy from reduced formaldehyde exposure by women who do not want to become 

pregnant, but we do not consider this effect
42

9. Please comment on whether the annualized approach as opposed to the lifetime approach is 

appropriate in this context.

It seems as reasonable as other possible approaches.

On page 58, the choice is made to use the cost-of-illness estimates from Katz et al. (2011) for 

valuing difficulty in conceiving due to formaldehyde exposure. A strength of these estimates is 

that apparently most fertility treatment costs are paid for out-of-pocket by consumer/patients 

rather than by third parties through private or public insurance. As such, consumers reveal that 

the treatments are worth at least as much as they paid. Their maximum willingness to pay would 

be expected to be greater than these costs because of consumer surplus. (This does not take into 

account any utility or disutility of treatments.) If data were available and demand for fertility

treatment could be estimated, then a better estimate of maximum willingness to pay could be 

made. This suggests using cost-of-illness will produce an underestimate. However, if the values 

are applied to all women who are exposed to formaldehyde, benefits will tend to be 

overestimated. The reason is that not all the women whose fertility is affected will pay the 

market prices for the treatments. In other words, the price is known for the various packages of 

treatments, but the number of women who are willing to pay the price is not. The maximum 

willingness to pay for treatment for the women whose fertility is affected but choose to forgo 

treatment and the number of them are unknowns. Their values are likely to be positive, but they

are less than the costs. Katz et al. report treatment costs per successful outcome of more than 

$70,000. They also report that 72% of the women had college education. A hunch is that those 

women have above average household incomes and spend most of their time in single family

detached homes where exposure reduction is smallest. Less educated women with lower 

household incomes are probably less likely to pay for treatments at the going prices. Assuming 

that women who have below average incomes and live in mobile homes will pay the market 

prices for the same distribution of fertility treatments is likely to bias the estimate of benefits of 

reducing exposure to formaldehyde upward.

The time period associated with the exposure-response function is longer than the time step of 

the exposure model. The Taskinen (1999) study examined the fecundity of women age 20-40. 

This causes a problem if we have an individual who does not experience the exposure 

reduction for the full time period. We can form an upper and lower bound of this willingness 

to pay as we did for asthma prevalence. The upper bound is based on the assumption that the 

linear concentration-response function holds for an acute exposure of one year. The lower 

bound assumes that an exposure reduction for one year represents 1/20th of an exposure 

reduction for the entire 20-year time period. 

10. Please comment on the upper and lower bound methodology used.

It seems as reasonable as other possible approaches.

The ages used in this analysis reflect the ages reported in the Taskinen (1999) study, ages 20-

40. However, women older than age 40 obtain fertility treatment. The value of reduced 

infertility effects from reduced formaldehyde exposure is not reflected in this analysis in order 

to remain consistent with Taskinen (1999).
43

11. Please comment on whether the concentration-response function was applied to 

appropriate age groups given the age groups in the studies. 

It seems as reasonable as other possible approaches.

III. SPECIFIC OBSERVATIONS

Page 53, bottom. $4.9 instead of $4,9.

Page 56, 3rd paragraph. Monetization is misspelled.

Page 58. Van Houtven and Smith (1999) instead of 1997 and $12,500 instead of $12,50.

Page 59. Is the probability of obtaining cycle-based fertility treatment shown in Table 8, the best 

projection for future treatment? The utilization percentages given on page 916 in Katz et al. 

seem different.

Page 68. O’Conor instead of O’Connor.
44

Review By:

A. Myrick Freeman III, Ph.D.
45

Peer Review Comments on EPA’s Draft Document Approach to Assessing Non-cancer 

Health Effects from Formaldehyde and Benefits from Reducing Non-cancer Health Effects as 

a Results of Implementing Formaldehyde Emission Limits for Composite Wood Products

A. Myrick Freeman III, Ph.D.

Bowdoin College

July 15, 2011

I. GENERAL IMPRESSIONS

The general model for aggregating over time and across individuals that is outlined in Section 

3.1 is correct. For other “impressions,” see my responses to specific charge questions below.

II. RESPONSE TO CHARGE QUESTIONS

Sensory Irritation

The concentration-response function for the prevalence of eye irritation is based on 

Hanrahan et al. (1984). While Hanrahan does not identify the relevant time period for this 

relationship, Liu et al. (1991) produced qualitatively similar results for a two-week time period. 

We assumed that the concentration-response relationship for eye irritation is for a two-week 

period and multiplied the concentration-response function times 26 to obtain the number of 

cases of eye irritation experienced in one year. 

The concentration-response curve used is non-linear, which means that the annual approach 

may not produce an exact measure of the benefits, but it is believed that the bias is probably 

relatively small given the small change in exposure.

1. Please comment on whether the concentration-response function is used appropriately in 

the benefits assessment approach.

It was used appropriately.

The concentration-response curve is for an acute effect occurring at a time less than the oneyear time step of the exposure model. The willingness to pay to avoid cases of eye irritation is 

calculated for each year of analysis by multiplying the number of cases in a year by the 

marginal willingness to pay value to avoid one case. This may produce biased results, but the 

direction of that bias is unknown.

On one hand, some studies have suggested that the willingness to pay per symptom-day declines 

as the number of symptom-days avoided increases. In other words, the value to reduce two 

symptom-days of some effect is less than two times the value for one symptom-day. Therefore, 

this approach may overstate the total value. 

On the other hand, this analysis only applies values to one symptom, eye irritation, largely 

because this is the only symptom for which an effective concentration-response curve was 

derived. However, there is evidence that there are other forms of minor eye, nose, and throat 
46

irritation associated with formaldehyde exposure. Since eye irritation is the largest of the 

median values from the Tolley et al. (1986) study, the values used here likely represent a lower 

bound on the true effect of multiple symptoms. A reasonable upper bound of the total effect 

for one symptom-day would be sum of the willingness to pay for one symptom-day of each 

effect individually. 

2. Please comment on whether the annualized approach as opposed to the lifetime approach is 

appropriate in this context.

I don’t understand the question. What do you mean by the “lifetime approach”? If you mean the 

results shown in Table 3 on p. 42, then either approach is appropriate. They are just different 

ways of summarizing the data.

The concentration-response function for the prevalence of eye irritation is for a single twoweek period. The annualized approach used an adjusted concentration-response relationship 

that consisted in multiplying the concentration-response function obtained from Hanrahan et 

al. (1984) by 26 two-week periods.

3. Please comment on whether the adjustment of the concentration-response function is 

appropriate in the annualized approach.

Yes, it is appropriate.

Asthma

The concentration-response relationship for asthma incidence is given as an odds ratio for 

children exposed to formaldehyde. An odds ratio is a way of comparing the difference in the 

probability of an event, in this case asthma diagnosis, occurring in groups exposed at different 

levels. The odds ratio is used to determine the willingness to pay for any change in emissions 

exposure over a 16 year period. We assume that the probability of being diagnosed with 

asthma is uniformly distributed across these 16 years. 

The use of an odds ratio implies that the concentration-response relationship is non-linear. 

However, given that the change in exposure is relatively small, the results from using this 

implied non-linear function are anticipated to be similar to the results if we were to use a 

linear function.

4. Please comment on whether the concentration-response function is used appropriately in 

the benefits assessment approach.

It was used appropriately.

The valuation of asthma effects from formaldehyde exposure is based on valuing the 

incidence of asthma rather than the more standard valuation based on the exacerbation of 

asthma symptoms. The reason for this is that a statistical relationship between formaldehyde 

exposure and asthma exacerbation has not been sufficiently well established, but there is a 

statistical relationship between formaldehyde exposure and asthma occurrence or incidence. 

However, the only time that EPA has valued asthma exacerbation is for the first prospective 
47

study of the benefits and costs of the Clean Air Act (EPA 1999). This is probably due to a lack 

of an appropriate concentration-response relationship. The EPA’s Office of Air does include 

recommended values for the monetization of chronic asthma in its BenMAP documentation 

(EPA 2011b), which is based on an average of the results from Blumenschein and 

Johannesson (1998) and O’Conor and Blomquist (1997).

For this analysis, EPA treats prevalence as a measure of cumulative incidence by assuming 

that the disease duration is the rest of the child’s life. However, the EPA (2000a) has 

previously assumed that a portion of asthmatic children will become asymptomatic as they 

move into adulthood.

5. Please comment on whether the annualized approach as opposed to the lifetime approach is 

appropriate in this context.

Again, I don’t understand the question. What do you mean by the “lifetime approach”? The 

term is not used in the document.

The concentration-response relationship is based on an odds ratio for a period of time longer 

than the one year. The exposure model produces results for one-year of exposure to 

formaldehyde for each age, housing type, and climate cohort. As a consequence, an 

adjustment to the simple model needed to be made to model the effect on individuals who are 

currently alive when the regulation takes effect.

As an upper bound estimate, we assume that the odds ratio can be applied to the one year 

reduction in the same fashion as it was applied for the 16 year time period. The problem with 

this approach is that it effectively treats the exposure as an acute effect. If the odds ratio 

indicates a particular percentage reduction in asthma cases from a reduction in formaldehyde 

exposure over 16 years, the upper bound approach would suggest the same percentage 

reduction in asthma case in one single year if we were to witness the same reduction in 

formaldehyde exposure in one year. The lower bound approach assumes that a particular 

exposure reduction for one year produces the same effect as if that exposure reduction were 

spread out over the entire 16-year time period. 

6. Please comment on the upper and lower bound methodology used.

The approach seems reasonable. The bounds are relatively narrow, as shown in Table 7. How 

will the results be presented in the final report, as upper and lower bounds or averaged to give a 

“best” estimate?

The prevalence data suggest that 7.2% of children age 0-4 have been told that they have 

asthma. 16.4% of children aged 5-14 have been told that they have asthma. We assume that 

the probability of being diagnosed is uniformly distributed across the 0 to 16 age bracket, so 

that the incidence rate would be 1.44% for the first five years and 1.49% for the next eleven 

years. Allocating cases uniformly across the age brackets provides us with a way to calculate 

the annual benefits of any exposure reduction that occurs for the entire time period, but may 

not be appropriate if the diagnosis of asthma for very young children (e.g., age 0-2) differs 

from older children.
48

7. Is the assumption about applying the concentration-response function to children aged 0 to 

16 appropriate, given the asthma onset studies’ focus on school-aged children and 

adolescents, and given the potential uncertainty of the Rumchev study involving younger 

children?

I can’t answer this. It lies outside my area of expertise.

Female Reproductive Toxicity

The linear concentration-response function accounting for background exposures based on 

Taskinen et al. (1999) is used for the annual approach.

8. Please comment on whether the concentration-response function is used appropriately in 

the benefits assessment approach.

It was used appropriately.

Monetization of delayed fertility has been discussed in the literature but has never been 

included in primary analyses of EPA rules because it was believed that the scientific 

knowledge on reproductive and developmental health effects was not strong enough to 

quantify risk in the primary benefits analysis.

While there appears to be good data on the cost of treatment, there are few studies on the 

willingness to pay to reduce delayed conception. Most economic valuation studies regarding 

fertility focus on an individual’s or a couple’s willingness to pay for infertility treatment, 

particularly in-vitro fertilization (IVF). Conceptually, the willingness to pay approach is 

preferable and could be deduced from the valuation studies. However, given that there has 

been less research on these willingness to pay values than other values and the fact that the 

values have not been used in previous economic analyses, we used the more straight-forward 

cost of illness approach for this analysis.

As an upper bound, we assume that any woman who has difficulty conceiving (i.e., time to 

pregnancy exceeds 12 months) will obtain some type of fertility service. This may be a 

reasonable upper bound, but there are certainly women who have trouble becoming pregnant 

and do not seek fertility treatment. 

The willingness to pay for fertility treatment is treated as an expected value. The average cost 

of various cycle-based fertility treatments is multiplied times the probability of obtaining that 

treatment at various ages. There is probably a small opposite effect associated with an increase 

in pregnancy from reduced formaldehyde exposure by women who do not want to become 

pregnant, but we do not consider this effect

9. Please comment on whether the annualized approach as opposed to the lifetime approach is 

appropriate in this context.

Again, I don’t understand the question. What do you mean by the “lifetime approach”? The 

term is not used in the document. Perhaps the charge question should be "Please comment on 

the annual approach to calculating a total WTP per year as described in Section 3.4.2." My
49

answer to that question is that if a valid individual WTP per year can be obtained, equation (18) 

is the appropriate way to calculate aggregate WTP per year. But for reasons I point out in the 

Specific Observations section below (see my comments to question #3), I have serious doubts 

about the ability to obtain a valid individual WTP per year.

The time period associated with the exposure-response function is longer than the time step of 

the exposure model. The Taskinen (1999) study examined the fecundity of women age 20-40. 

This causes a problem if we have an individual who does not experience the exposure 

reduction for the full time period. We can form an upper and lower bound of this willingness 

to pay as we did for asthma prevalence. The upper bound is based on the assumption that the 

linear concentration-response function holds for an acute exposure of one year. The lower 

bound assumes that an exposure reduction for one year represents 1/20th of an exposure 

reduction for the entire 20-year time period. 

10. Please comment on the upper and lower bound methodology used.

The approach seems reasonable. How will the results be presented in the final report, as upper 

and lower bounds or averaged to give a “best” estimate?

The ages used in this analysis reflect the ages reported in the Taskinen (1999) study, ages 20-

40. However, women older than age 40 obtain fertility treatment. The value of reduced 

infertility effects from reduced formaldehyde exposure is not reflected in this analysis in order 

to remain consistent with Taskinen (1999).

11. Please comment on whether the concentration-response function was applied to 

appropriate age groups given the age groups in the studies. 

Given my reservations about using the cost-of-fertility treatment to monetize this effect (see my 

comments to question #3 in the Specific Observations section below), I have no problem in 

limiting the quantification of this effect to the age group covered in the Taskinen study.

III. SPECIFIC OBSERVATIONS

There are a number of typographical and editorial errors. This is not a complete list:

Table of Contents. Page numbers are wrong.

Page 17. Figure 2 should be labeled figure 5.

Section 3. Why do the table and figure numbers start over instead of continuing throughout the 

report? And some of the table numbers seem to be wrong (e.g., J-10 on page 36).

Page 6. The report gives the aim of developing concentration-response relationships as being “ 

... to inform the economic benefits assessment of potential cost savings ...” This is not about 

“cost savings;” it is about welfare gains.

In some places, coefficients in the concentration-response relationships are Greek letters. In 

other places they are not.
50

Section 2.1.1, 3rd sentence in the first paragraph. Needs editing.

Page 53. Where it says “($93,095 + $58,662 + $90,852= $242,602),” it should be = $242,609.

Page 58. It says “willingness to pay of between $3,750 and $12,50 for fertility treatment.”

Page 59. The probability of using IVF should be 2.5%, not .25%.

Page 61, last paragraph. There are two references to Table 10, which should be Table 12.

Page 63. The sentence, “This is probably the largest category of value associated fertility issue 

from a reduction in formaldehyde exposure,” needs editing.

I have added the following three charge questions based on my expertise in non-market 

valuation:

(1) Please comment on the validity of the monetization of sensory irritation. The approach to 

the monetization of this effect is the same as that used in the First Prospective Section 812 

Report. In my judgement, this is a valid approach and makes the best use of the available 

empirical evidence. However, it should be noted that the effect actually valued in the First 

Prospective Section 812 Report as “Upper Respiratory Symptoms” defined as “two or more of 

the following symptoms: runny or stuffy nose; coughing; and eye irritation.” Since this 

document states that formaldehyde can cause a variety of types of sensory irritation in the upper 

respiratory system (p. 7), this is appropriate. But it should be made clear that more than simply

eye irritation is involved.

(2) Please comment on the validity of the monetization of chronic asthma. The approach to the 

monetization of this effect is the same as that used in the First Prospective Section 812 Report. 

In my judgement, this is a valid approach and makes the best use of the available empirical 

evidence. 

(3) Please comment on the validity of the monetization of reduced fertility. I have serious 

reservations about the approach taken here to monetize this effect. First, “reduced fertility” is 

not a well-defined effect. There is ambiguity as to both the degree of reduction and its duration. 

This makes determining the proper valuation difficult. 

I agree that conceptually, the willingness to pay (WTP) approach is preferable to a cost-of-illness 

or cost-of-treatment approach. However, as I read the available WTP studies, they apply to the 

more serious infertility rather than to the “subfertility” (p. 21) associated with exposure to 

formaldehyde. Thus, the available WTP studies are not suitable for benefits transfer.

The report takes a cost of treatment approach to valuation. But it is not at all clear to me that the 

“cycle-based treatments” described here are either appropriate treatments or likely to be effective 

in the face of continued formaldehyde exposures.
51

For these reasons, I recommend that this effect be described and quantified to the extent that 

evidence supports quantification, but that it be acknowledged that there is not an adequate basis 

for monetization of this effect.
52

Review By:

Shelby Gerking, Ph.D.
53

Peer Review Comments on EPA’s Draft Document Approach to Assessing Non-cancer 

Health Effects from Formaldehyde and Benefits from Reducing Non-cancer Health Effects as 

a Results of Implementing Formaldehyde Emission Limits for Composite Wood Products

Shelby Gerking, Ph.D.

University of Central Florida

July 23, 2011

I. GENERAL IMPRESSIONS

The report is, for the most part, complete and clearly written. I had no problem following the 

narrative, however, an executive summary, a conclusion and a map of the climate zones would 

have been helpful. Also, in Section 3, there are at least seven issues that warrant additional 

thought. First, the choice of the 3% discount rate, while not unreasonable, appears from out of 

nowhere. Some attention needs to be given to this choice as well as to the assumption of 

exponential discounting. Other types of discounting considered by behavioral economists may

also be appropriate. Second, the contingent valuation estimates of WTP for eye irritation are 

rather dated—those obtained by Tolley et al. are 25 years old. EPA still uses these estimates, but 

there have been a number of advances over the years in the application of stated preference 

methods aimed at reducing hypothetical bias which causes stated preference estimates to be too 

high. Third, the Dickie et al. estimates in Table J-10 may not be directly comparable to those of 

Tolley et. al. and Loehman et. al. in that they are based on the averting behavior method (which 

looks at actual purchases of goods), rather than on contingent valuation. In any case, the 

narrative might usefully reflect the fact that sound willingness to pay estimates are elusive and 

that different methods of estimating WTP often give (very) different results. Fourth, both asthma 

and eye irritation estimates rely on transferring adult WTP estimates to children. This procedure, 

which may be the only available option, may well lead to substantial inaccuracies. Parents, for 

example, may be WTP more to reduce health symptoms for their children than they are WTP to 

reduce those same symptoms for themselves. In any case, the issue of WTP for adults vs. WTP 

for kids (with citations to recent literature) should be a discussion point in the report. Fifth, the 

WTP estimates presented implicitly assume that switching to different building materials, or 

treating wood products to cut down formaldehyde off-gassing will not occur for the 30 year 

horizon analyzed. Is this assumption reasonable? In this same vein, could health effects from 

formaldehyde off-gassing be lessened by providing particularly residents of new homes with 

information that would lead them to install better ventilation systems? If so, the marginal cost of 

better ventilation (if such a strategy is appropriate) might then form the basis of a simple WTP 

estimate along the lines of the headache example given on p. 31. Sixth, the population by

housing type and climate zone apparently are assumed not to change over the next 30 years, even 

though there have been major changes in population by housing type and climate zone over the 

past 30 years. This assumption seems hard to defend, although as noted on p. 42 it would be a 

difficult task to predict these movements. Seventh, it would be helpful to develop the main 

features of the cohort x housing type x climate zone model in introductory Section 3.1. It would 

be helpful in this section to explain about the assumptions underlying this approach (some of 

these are identified above). This reorganization will clarify the narrative at a number of points 

and avoid misunderstandings created when readers simply encounter model assumptions in the 

explanation of results.

II. RESPONSE TO CHARGE QUESTIONS
54

Sensory Irritation

The concentration-response function for the prevalence of eye irritation is based on 

Hanrahan et al. (1984). While Hanrahan does not identify the relevant time period for this 

relationship, Liu et al. (1991) produced qualitatively similar results for a two-week time period. 

We assumed that the concentration-response relationship for eye irritation is for a two-week 

period and multiplied the concentration-response function times 26 to obtain the number of 

cases of eye irritation experienced in one year. 

The concentration-response curve used is non-linear, which means that the annual approach 

may not produce an exact measure of the benefits, but it is believed that the bias is probably 

relatively small given the small change in exposure.

1. Please comment on whether the concentration-response function is used appropriately in 

the benefits assessment approach.

The non-linear concentration response function is appropriately used in the benefits assessment 

approach. However, the approach used here appears to take no account of other sources of 

formaldehyde exposure, such as workplace exposures. In any case, the policy-related reductions 

in formaldehyde exposure should be treated as reductions in total exposure, not simply

reductions in home exposure. This refinement may alter the benefits calculation given the use of 

a non-linear concentration response function.

The concentration-response curve is for an acute effect occurring at a time less than the oneyear time step of the exposure model. The willingness to pay to avoid cases of eye irritation is 

calculated for each year of analysis by multiplying the number of cases in a year by the 

marginal willingness to pay value to avoid one case. This may produce biased results, but the 

direction of that bias is unknown.

On one hand, some studies have suggested that the willingness to pay per symptom-day declines 

as the number of symptom-days avoided increases. In other words, the value to reduce two 

symptom-days of some effect is less than two times the value for one symptom-day. Therefore, 

this approach may overstate the total value. 

On the other hand, this analysis only applies values to one symptom, eye irritation, largely 

because this is the only symptom for which an effective concentration-response curve was 

derived. However, there is evidence that there are other forms of minor eye, nose, and throat 

irritation associated with formaldehyde exposure. Since eye irritation is the largest of the 

median values from the Tolley et al. (1986) study, the values used here likely represent a lower 

bound on the true effect of multiple symptoms. A reasonable upper bound of the total effect 

for one symptom-day would be sum of the willingness to pay for one symptom-day of each 

effect individually. 

2. Please comment on whether the annualized approach as opposed to the lifetime approach is 

appropriate in this context.
55

A search of the review document turned up no references to “lifetime approach”, so the issue to 

be addressed here is not entirely clear. Nonetheless, it is likely that WTP per symptom day of 

eye irritation falls as the number of symptom days increase. This outcome would be a general 

implication of utility maximization under a fixed budget. As additional resources are spent to 

relieve eye irritation, the opportunity cost of foregone consumption will increase. If eye

irritation is coupled with other symptomatic discomforts, then we may have a different problem. 

On the one hand, suppose that there exists a good that will reduce eye irritation together with all 

of the other symptoms. Then, the marginal cost (inclusive of both time and money) of using the 

good to reduce these symptoms will be the WTP for all combined. On the other hand, if more 

than one good needs to be purchased to reduce all of the symptoms, then the WTP would be the 

marginal cost of the combination of goods that will do the job. In any case, it is problematic to 

simply add up CVM estimates of WTP for individual symptoms as this is likely to yield a total 

WTP value that really is upward biased. Note that the CVM estimates themselves are probably 

upward biased. 

The concentration-response function for the prevalence of eye irritation is for a single twoweek period. The annualized approach used an adjusted concentration-response relationship 

that consisted in multiplying the concentration-response function obtained from Hanrahan et 

al. (1984) by 26 two-week periods.

3. Please comment on whether the adjustment of the concentration-response function is 

appropriate in the annualized approach.

An issue here is that there appear to be different ways to interpret the Total WTP expression on 

p. 39. Should we assume that the same people experience eye irritation repeatedly for each 26 

two-week periods in the year? If this (Groundhog Day) assumption is correct, then the WTP 

value applied may well be on the high side. On the other hand, if we assume that a different set 

of people experience these symptoms in each of the two week periods, then the calculations 

presented may be more defensible. 

Asthma

The concentration-response relationship for asthma incidence is given as an odds ratio for 

children exposed to formaldehyde. An odds ratio is a way of comparing the difference in the 

probability of an event, in this case asthma diagnosis, occurring in groups exposed at different 

levels. The odds ratio is used to determine the willingness to pay for any change in emissions 

exposure over a 16 year period. We assume that the probability of being diagnosed with 

asthma is uniformly distributed across these 16 years. 

The use of an odds ratio implies that the concentration-response relationship is non-linear. 

However, given that the change in exposure is relatively small, the results from using this 

implied non-linear function are anticipated to be similar to the results if we were to use a 

linear function.

4. Please comment on whether the concentration-response function is used appropriately in 

the benefits assessment approach.

I agree that the bias from using the implied non-linear function is likely to be small, but please 

see #1 in the eye irritation section for a possible qualification.
56

The valuation of asthma effects from formaldehyde exposure is based on valuing the 

incidence of asthma rather than the more standard valuation based on the exacerbation of

asthma symptoms. The reason for this is that a statistical relationship between formaldehyde 

exposure and asthma exacerbation has not been sufficiently well established, but there is a 

statistical relationship between formaldehyde exposure and asthma occurrence or incidence. 

However, the only time that EPA has valued asthma exacerbation is for the first prospective 

study of the benefits and costs of the Clean Air Act (EPA 1999). This is probably due to a lack 

of an appropriate concentration-response relationship. The EPA’s Office of Air does include 

recommended values for the monetization of chronic asthma in its BenMAP documentation 

(EPA 2011b), which is based on an average of the results from Blumenschein and 

Johannesson (1998) and O’Conor and Blomquist (1997).

For this analysis, EPA treats prevalence as a measure of cumulative incidence by assuming 

that the disease duration is the rest of the child’s life. However, the EPA (2000a) has 

previously assumed that a portion of asthmatic children will become asymptomatic as they 

move into adulthood.

5. Please comment on whether the annualized approach as opposed to the lifetime approach is 

appropriate in this context.

A search of the review document turned up no references to “lifetime approach” so the issue to 

be addressed here is not entirely clear. Nonetheless, the report makes clear that valuation of 

asthma effects is based on valuing the incidence of asthma, rather than symptom exacerbation. 

This approach is crude for two reasons. First, there is substantial heterogeneity in cases of 

asthma. For some people, asthma is little more than an annoyance, while for others this illness is 

debilitating. Willingness to pay to avoid asthma would be expected to vary according to how 

serious a case is contemplated. Second, willingness to pay to reduce additional cases of asthma 

will not include the willingness to pay to reduce exacerbated symptoms of those who already

have asthma. Two other issues: (1) While estimates of increased incidence of asthma pertain to 

children (see p. 19), estimates of WTP to reduce asthma incidence are based on two studies of 

adults. Parents may well be willing to pay more to reduce asthma incidence among their 

children than they are WTP to protect themselves from the same illness. (2) It might be useful to 

perform a sensitivity analysis on the estimates provided to determine how much difference it 

would make to assume that a percentage of childhood asthmatics become asymptomatic when 

they become adults, rather than assume that childhood asthmatics carry their illness forward to 

adulthood. 

The concentration-response relationship is based on an odds ratio for a period of time longer 

than the one year. The exposure model produces results for one-year of exposure to 

formaldehyde for each age, housing type, and climate cohort. As a consequence, an 

adjustment to the simple model needed to be made to model the effect on individuals who are 

currently alive when the regulation takes effect.

As an upper bound estimate, we assume that the odds ratio can be applied to the one year 

reduction in the same fashion as it was applied for the 16 year time period. The problem with 

this approach is that it effectively treats the exposure as an acute effect. If the odds ratio 

indicates a particular percentage reduction in asthma cases from a reduction in formaldehyde 
57

exposure over 16 years, the upper bound approach would suggest the same percentage 

reduction in asthma case in one single year if we were to witness the same reduction in 

formaldehyde exposure in one year. The lower bound approach assumes that a particular 

exposure reduction for one year produces the same effect as if that exposure reduction were 

spread out over the entire 16-year time period. 

6. Please comment on the upper and lower bound methodology used.

The upper bound estimates are obtained by assuming that asthma onset is an acute effect of 

formaldehyde exposure particularly among older teenagers. I am uncertain as to whether this 

assumption is at variance with scientific information regarding the development of this disease 

and would defer to another panel member with greater expertise on this point. If asthma onset 

from formaldehyde exposure cannot be considered an acute effect, then the upper bound 

estimates would be less credible. Nonetheless, the upper bound estimates and the lower bound 

estimates do not differ greatly. Table 7 reports that for the three housing profiles total 

discounted upper bound WTP is $4,939,166 and the corresponding lower bound figure is 

$4,340,740. So, the upper bound estimate is about 14% larger than the lower bound estimate. 

An alternative to the lower bound estimate might be to assume that currently living children are 

unaffected by reduced formaldehyde exposure. Instead, we might assume that the reduced 

exposure applies only as “new” children as they enter the model. These “new” children are then 

assigned cases of asthma with the incidence rates described on p. 48 of the review document. 

The prevalence data suggest that 7.2% of children age 0-4 have been told that they have 

asthma. 16.4% of children aged 5-14 have been told that they have asthma. We assume that 

the probability of being diagnosed is uniformly distributed across the 0 to 16 age bracket, so 

that the incidence rate would be 1.44% for the first five years and 1.49% for the next eleven 

years. Allocating cases uniformly across the age brackets provides us with a way to calculate 

the annual benefits of any exposure reduction that occurs for the entire time period, but may 

not be appropriate if the diagnosis of asthma for very young children (e.g., age 0-2) differs 

from older children.

7. Is the assumption about applying the concentration-response function to children aged 0 to 

16 appropriate, given the asthma onset studies’ focus on school-aged children and 

adolescents, and given the potential uncertainty of the Rumchev study involving younger 

children?

I defer to another panel member here as I have no expertise in this area. 

Female Reproductive Toxicity

The linear concentration-response function accounting for background exposures based on 

Taskinen et al. (1999) is used for the annual approach.

8. Please comment on whether the concentration-response function is used appropriately in 

the benefits assessment approach.

The concentration-response function appears to have been applied correctly in the benefits 

assessment approach. Note that the concentration-response function is linear, so accounting for 

other sources of formaldehyde exposures would be less important. However, two other issues 
58

might be addressed. First, equations (18) and (19) in the text may require some clarification. 

My question relates to the term 

, , , ,

[( exp ) ( exp )] hcbaseline h c policy a b   osure      osure . Does a = 

 ? Does b =  ? If so, the notation should be changed. If not, the equation needs additional 

explanation. Second, in these equations, population refers to women who have difficulty 

conceiving. The population of women who are actively attempting to become pregnant would 

instead be more appropriate. Page 59 indicates that for the proposed rule this latter definition 

would be incorporated. I agree that this change would be appropriate. 

Monetization of delayed fertility has been discussed in the literature but has never been 

included in primary analyses of EPA rules because it was believed that the scientific 

knowledge on reproductive and developmental health effects was not strong enough to 

quantify risk in the primary benefits analysis.

While there appears to be good data on the cost of treatment, there are few studies on the 

willingness to pay to reduce delayed conception. Most economic valuation studies regarding 

fertility focus on an individual’s or a couple’s willingness to pay for infertility treatment, 

particularly in-vitro fertilization (IVF). Conceptually, the willingness to pay approach is 

preferable and could be deduced from the valuation studies. However, given that there has 

been less research on these willingness to pay values than other values and the fact that the 

values have not been used in previous economic analyses, we used the more straight-forward 

cost of illness approach for this analysis.

As an upper bound, we assume that any woman who has difficulty conceiving (i.e., time to 

pregnancy exceeds 12 months) will obtain some type of fertility service. This may be a 

reasonable upper bound, but there are certainly women who have trouble becoming pregnant 

and do not seek fertility treatment. 

The willingness to pay for fertility treatment is treated as an expected value. The average cost 

of various cycle-based fertility treatments is multiplied times the probability of obtaining that 

treatment at various ages. There is probably a small opposite effect associated with an increase 

in pregnancy from reduced formaldehyde exposure by women who do not want to become 

pregnant, but we do not consider this effect

9. Please comment on whether the annualized approach as opposed to the lifetime approach is 

appropriate in this context.

Cost-of-illness estimates are conceptually inappropriate in this context for two reasons. First, 

cost-of-illness is not a conceptually sound approach for estimating willingness to pay. This point 

is noted in the document on p. 58. In consequence, I would suggest that cost-of-illness estimates 

might be used only as a last resort. The WTP estimates obtained by Smith and van Houtven may 

well be a more defensible choice. Careful thought should be given to whether this alteration 

would be an improvement. Second, the COI estimates utilized (see equation (20) and Table 10) 

do not really pertain to the delay in conception addressed in the Taskinen study. Women (or 

couples) may be willing to pay to reduced time to conceive, but may at the same time be 

reluctant to seek fertility treatment. At a minimum, this potential misalignment should be 

addressed. 
59

The time period associated with the exposure-response function is longer than the time step of 

the exposure model. The Taskinen (1999) study examined the fecundity of women age 20-40. 

This causes a problem if we have an individual who does not experience the exposure 

reduction for the full time period. We can form an upper and lower bound of this willingness 

to pay as we did for asthma prevalence. The upper bound is based on the assumption that the 

linear concentration-response function holds for an acute exposure of one year. The lower 

bound assumes that an exposure reduction for one year represents 1/20th of an exposure 

reduction for the entire 20-year time period. 

10. Please comment on the upper and lower bound methodology used.

The Taskinen study appears to treat formaldehyde exposure as a long term exposure. In 

consequence, I am uncertain that the upper bound estimates are defensible (see the related point 

#6 in asthma above). Nonetheless, the upper and lower bound WTP estimates differ only by 

about $57,000 (see Table 12). This outcome could change of course if the analysis is redone 

along lines suggested above. Also, as with asthma, I would suggest the possibility to treat “new” 

women entering the model as those affected by the contemplated reduction in formaldehyde 

exposure. 

The ages used in this analysis reflect the ages reported in the Taskinen (1999) study, ages 20-

40. However, women older than age 40 obtain fertility treatment. The value of reduced 

infertility effects from reduced formaldehyde exposure is not reflected in this analysis in order 

to remain consistent with Taskinen (1999).

11. Please comment on whether the concentration-response function was applied to 

appropriate age groups given the age groups in the studies. 

The Taskinen study does not appear to provide a direct basis for adding women aged 40 and 

older to the analysis. However, relatively few of these women may seek to become pregnant in a 

given year. If the analysis focused on women who seek to become pregnant, exclusion of 

women over 40 years of age may not be a grave oversight. I would defer to a panel member 

more knowledgeable about fertility issues to make a judgment on this issue.

III. SPECIFIC OBSERVATIONS

The document appears to have been put together hastily as there are numerous typos and other 

glitches. Below is a list of typos that I flagged—I am certain there are more.

Page 31, first line below equation (1). ...risk reduction at age a.

Page 35, next to last line of third full paragraph. Data should be days

Page 36. Not sure why the Table is called “Table J-10”. Other tables are not numbered this 

way. Also, in this table Dickie et al. needs a date

Page 44, first line under monetization. Analysis should be analyses.
60

Page 45, Table IV. 2-17 not numbered consistently with other tables, also in two places decimal 

points are mistakenly used for commas

Page 53, last full line. Should be $4.9 million

Page 56, eighth line up from bottom. Undergoes should be undergo

Page 57, fourth full paragraph, first line. Ryan (1996) conducted a contingent ...

Page 58, first full paragraph, line 4. Respondents were asked to consider taking...

Page 59, line 8 under equation (19) (and elsewhere). The word data is plural, not singular

Page 59, line 12 under equation (19). Difficulty is misspelled

Page 59, second line up from bottom. Reduction is misspelled

Page 60, part of Table 9 appears to be missing. Also, the heading is missing a number for 

ppb.

Page 60, Table 10. The probability values are missing
61

V. PEER REVIEWER COMMENT TABLE ON NON-CANCER HEALTH 

EFFECTS – DERIVATION OF CONCENTRATION-RESPONSE FUNCTIONS
62

I. GENERAL IMPRESSIONS

NAME COMMENT RESPONSE

John R. Balmes, 

M.D. 

The document is clearly and concisely written. The background subsections of Section 2: 

Non-cancer Health Effects – Derivation of Concentration-Response Functions for sensory

irritation (2.1.1), asthma (2.2.1), and female reproductive toxicity (2.3.1) are extremely

brief, especially the latter two. While it is understandable that the EPA does not wish to be 

duplicative of the material in the draft IRIS document on formaldehyde or the NAS review 

of the IRIS document, some readers of the “Approach” document will not have read the

IRIS and NAS documents and thus will benefit from a bit more background context on 

formaldehyde and asthma or formaldehyde and female reproductive toxicity.

David Kriebel, 

Sc.D.

The overall impression is of a thoughtful and well-written document. The authors have 

provided a generally clear and logical explanation of their reasoning throughout. There are 

a few exceptions, noted below, where additional explanation or documentation could 

improve the presentation.

Frederick J. Miller, 

Ph.D., Fellow ATS

The comments provided are related to the health assessment and concentration-response 

evaluation portion of the above cited document as this reviewer was not asked to comment 

on the economic benefits assessment approach. For the most part, the sections on sensory

irritation, asthma, and female reproductive toxicity are clearly presented and the material is 

developed in a logical manner. Some exceptions are noted in this reviewer’s responses to 

the specific charge questions. The decision on the concentration-response functions to take 

forward to the economic benefits analyses is best documented for sensory irritation. This 

reviewer provides a suggestion for how far below 100 ppb of formaldehyde the modeling 

results developed by the Agency based on the Hanrahan et al. (1984) study can be used. 

The material included in support of using the McGwin et al. (2010) meta analysis for 

asthma in children does not adequately describe the short comings of the meta analysis. The 

uncertainties and conflicting results of the studies make this reviewer reticent to endorse the 

concentration-response function for the odds ratio based on the McGwin et al. (2010) meta 

analysis. The case to use background adjusted exposure data for the female reproductive 

toxicity concentration-response curve is adequately defended. However, the Agency does 

not indicate if the linear risk or the exponential risk curve will be used.

Overall, the information presented is accurate. To their credit, in a number of places, the 

EPA authors have incorporated criticisms included in the NAS report of the Agency’s draft 

IRIS assessment document. By addressing the responses to the charge questions, the 
63

Agency will be in a good position to move forward with the cost benefit analysis required 

by Executive Order 12866 related to the Formaldehyde Standards for Composite Wood 

Products Act. 

Rebecca T. Parkin, 

Ph.D., MPH

The draft is clearly organized and, in large part, well-written. Minor inaccuracies are noted 

below. Most sections were clear, although some key issues were not mentioned or are not 

clear; these concerns are noted below. Except in a few instances as noted below, the 

conclusions are effectively supported by the text provided.

Uncertainties are important to discuss. EPA has captured many of the important ones, but 

may need to add more to these sections based on this and other reviewers’ comments. 

Being thorough in all uncertainty sections is crucial to the foundations of the benefit 

assessments.

II. RESPONSE TO CHARGE QUESTIONS

CHARGE QUESTION 1: The literature base of residential epidemiology studies of the irritation effects with quantitative 

concentration-response data was limited, but data were available from which a concentration-response function could be estimated 

for eye irritation.

Please comment on whether the concentration-response function is appropriately derived from the studies used in the draft Approach 

Document.

NAME COMMENT RESPONSE

John R. Balmes, 

M.D. 

The concentration-response function (CRF) for sensory irritation is derived from one small 

field study, Hanrahan et al. (1984). Because most individuals exposed to formaldehyde 

from the products of interest will be exposed at levels below 100 ppb, the EPA is 

appropriately concerned about the form of the CRF in this range. Unfortunately, the data 

for exposures below 100 ppb are not given in the original Hanrahan paper and the 

regression of prevalence of eye irritation and formaldehyde concentration in the paper 

covers the range of 100-800 ppb. Another issue regarding CRF derivation from the 

Hanrahan paper is the relatively small sample size (n=61). The Liu et al. (1991) study, 

which involved a much larger population, is supportive of the concept that there is a CRF 

for formaldehyde and eye irritation at relatively low levels of exposure, but was not used in 

the actual derivation of such a CRF because of the way the authors aggregated their data 

into low, medium, and high levels of exposure.

David Kriebel, 

Sc.D.

I see no problems with the derivation of the concentration-response function itself. In 

Section 2.1.3, I think it would strengthen the argument to at least acknowledge the problem 
64

of acclimatization. There is evidence from a number of studies – notably the studies of 

studies conducting autopsies – that there is a change over weeks in the short-term irritant 

effects. One way that this will impact the calculations is that cumulative exposure is 

probably not the appropriate exposure metric. The authors may have little choice to use the 

simplified approach they have taken which assumes a constant exposure-response 

relationship over time, but they could acknowledge that there is a source of uncertainty

from the changes in potency of formaldehyde over time for various endpoints. I suspect that 

the irritant effects diminish with time exposed, but the other two chosen endpoints probably

do not.

Frederick J. Miller, 

Ph.D., Fellow ATS

The draft Approach Document adequately discussed the type of data available in the 

literature from various studies and presented their strengths and weaknesses. The Agency

wisely stayed away from using the Liu et al. (1991) study as the primary driver for the 

concentration-response function for eye irritation. The categories from that study were 

formed on using a ppm-hr per week metric. The eye irritation studies discussed in Section 

2.1.2 for a 10 % additional risk for 560 ppb for 3 hours (i.e., 1,680 ppm-hrs) compared to 

240 ppb for 5 hours (i.e., 1,200 ppm-hrs) clearly show that Haber’s Law does not apply for 

the effects of formaldehyde exposure on eye irritation, which agrees with Miller et al. 

(Haber’s rule: a special case in a family of curves relating concentration and duration of 

exposure to a fixed level of response for a given endpoint. Toxicology 149:21–34, 2000). 

Thus, the Agency would have been hard pressed to defend a translation of the ppm-hrs 

metric of Liu et al. (1991) as the basis for developing a concentration-response function for 

eye irritation.

Rather, the Hanrahan et al. (1984) study that reported eye irritation was associated with inhome formaldehyde exposures (p < 0.05) (both as “burning eyes” and “eye irritation”) was 

used as the data for developing a concentration-response relationship for eye irritation. 

Moreover, the logistic regression model developed by Hanrahan et al. (1984) gave insight 

as to the needed nature of the curve if one were to extrapolate below the range of exposures 

reported by those authors (i.e., from 100 to 800 ppb). In the opinion of this reviewer, the 

concentration-response function was appropriately derived by the Agency.

Rebecca T. Parkin, 

Ph.D., MPH

First, I will comment on each study and then on the derivation process.

Liu et al (1991): This paper adequately describes how homes were randomly selected, but 
65

omits some key information related to monitoring results for the homes included. The 

study was conducted throughout California (p. 93); a very large state with a wide range of 

climatic conditions. “Summer” and “winter” sampling periods were used, but these seasons 

are quite different in different parts of the state. It is well-known that temperature and 

relative humidity affect formaldehyde (HCHO) levels, but there is no mention of how these 

factors varied in the study homes or how they may have affected measured HCHO levels. 

Further, the Quality Assurance/Quality Control methods are not described, and the number 

of laboratories used to analyze the passive area monitoring samples is not stated. These 

omissions leave this reviewer without key information to assess the accuracy or validity of 

the HCHO levels reported. 

Residents received instructions on how to uncap, place and mail back the samplers. The 

use of the kitchen and master bedroom as monitoring sites may be most relevant for the 

homeowner and less relevant for other occupants. Although averaging the monitored levels 

for each home may have lost some useful variation, it is not likely that in fairly small 

homes (such as mobile homes) that this loss – except for peak exposures – would be 

particularly important. 

The study appropriately controls the impact of smoking indoors, and does not discuss gas 

cooking stoves or appliances, opening of windows and doors, or other factors that have 

been reported by other authors as having non-significant impacts on HCHO levels. 

More importantly, if I am reading the article correctly (p. 92), some indoor samples in this 

cross-sectional study were taken after symptoms were recorded. This conflicts with 

determining the appropriate temporal sequence of cause preceding effect. I believe my 

reading is different from what EPA states on p. 10 of their draft, which indicates that 

exposures were recorded in a period preceding the documentation of symptoms.

Hanrahan et al (1984): This cross-sectional study, conducted in Wisconsin during July

1979, sampled a smaller number of mobile homes (65) than did Liu et al.; it also had a 

lower percentage of participants among those contacted (31% vs. 44%). In this study, 

personal samplers were used and 33 outdoor samples were taken (at least 1 in each mobile 

home park). The authors noted that prior to and during sampling periods home windows 

were closed, gas appliances were turned off and smoking was prohibited. 
66

The Quality Control and specific laboratory methods were noted (unlike in Liu et al). The 

indoor samples for each home were averaged, as in Liu et al, with similar but less specific 

sampling locations noted. It is not clear whether the residents or the researchers collected 

the air samples in this study. 

Smoking was appropriately considered, and indoor and outdoor temperature and humidity, 

and appliance and construction characteristics were noted. Some but not all of these 

factors’ influences on HCHO levels were presented in the article.

Derivation: The seasonal and cumulative averages and ranges of indoor levels, the 

concentration-response data are correctly extracted from the Liu et al. article. The method 

to estimate the average number of hours indoors seems appropriate; however, this reviewer 

wonders whether EPA attempted to determine whether the authors still have the raw data 

that could be used for a more accurate assessment of hours spent indoors.

EPA had to make many more adjustments when using the Hanrahan et al. article. First, 

EPA estimated the lower bound for the indoor levels based on the standard deviation for the 

outdoor levels; this is a reasonable approach given the missing data for the indoor levels. 

Second, the Agency assumed that the distribution of indoor levels is log-normal in order to 

estimate the number of samples with HCHO levels below 100 and 50 ppb. However, if this 

assumption or the estimated standard deviation is not correct, the numbers of samples could 

be quite different. 

It is not clear in Figure 2 whether the data shown are for EPA’s or the authors’ use of “eye 

irritation;” e.g., does “eye irritation” here mean the “burning eyes” AND “eye irritation” 

results in the article? If combined data were used, did EPA assume that all of these 

symptoms were distinct and not co-occurring events? Are we looking at data for the 

number of symptoms reported or the number of people with eye symptoms (meaning 

“burning eyes” and “eye irritation”) at each level of exposure? This question should also be 

asked of the data shown in the draft Table 1. Without knowing whether EPA combined 

data in Figure 2 and Table 1, it is difficult to comment further on this part of the draft.

The conversion of data in the article to prevalence odds seems appropriate. The display of 
67

estimates below 150 ppb in Figure 4b are derived from Equation 2-2 and are likely correct. 

This reviewer did not verify the mathematics.

The EPA authors have noted many key uncertainties in the two studies and how these affect 

their estimates of the relational function. However, the validity of the HCHO monitored 

levels remains a question, due to missing information in the articles; exposure 

misclassification is possible in both studies but is not discussed in the draft. 

CHARGE QUESTION 2: Please comment on the validity of extrapolating the concentration-response function and using the 

function to estimate effects at concentrations below 100 ppb.

NAME COMMENT RESPONSE

John R. Balmes, 

M.D. 

Given the limitations of the data available from the Hanrahan paper, the method of 

derivation of the CRF including the portion of the curve below 100 ppb is appropriate, but 

the extrapolation is pushing the envelope of what reasonably can be extracted from the data. 

The assumption that the reported standard deviation of the outdoor formaldehyde 

measurements represents the lower bound on the standard deviation of the indoor 

concentrations appears reasonable, but nonetheless the distribution of exposure data below 

100 ppb in the Hanrahan study was assumed rather than based on the actual data. The EPA 

used the graphical display of the regression data over the range of 100-800 ppb in the 

Hanrahan paper to derive a CRF and then to infer the shape of the CRF below 100 ppb. 

Given that the Hanrahan study only included 61 subjects and that the formaldehyde 

measurements in the mobile homes were only for 30-60 minutes, the validity of the 

extrapolated CRF can be questioned even if an appropriate method was used.

David Kriebel, 

Sc.D.

I am comfortable with this extrapolation. However, I think that it would be appropriate to 

acknowledge that errors in exposure estimation in the studies on which the function is 

based have not been included in the uncertainty calculations. This is a general concern – for 

all 3 endpoints, there were certainly errors in the exposure estimation, and the impact of

these on the uncertainty in the exposure-response function has not been considered.

It might be noted that the extrapolation downwards assumes a logistic shape, which is 

reasonable but not subject to validation. It might be noted that the excellent R2for Figure 

3b is a bit misleading since it is fitting a curve to categorical data, while the actual 

individual exposure data were of course continuous – the fit of this curve to the original 

data would not have been nearly as good. And again, see my comment just above about 

failure to point out that the exposure data had error, which was not taken into consideration 
68

in the model error calculations.

Frederick J. Miller, 

Ph.D., Fellow ATS

The Agency appropriately focused on the data from the Hanrahan et al. (1984) study to 

develop the concentration-response curve for eye irritation. Importantly, the Agency used a 

power law curve to fit the prevalence odds data. This ensures that the fitted curve will 

asymptotically approach zero for a zero formaldehyde exposure level and makes it 

reasonable to use Equation 2.2 below 100 ppb. Given (1) the limit of detection (LOD) was 

10 ppb at the time the Hanrahan et al. (1984) study was conducted, (2) the Agency’s 

assumption about the outdoor standard deviation of measurements being 30 ppb around a 

log-normal distribution of measurements, and (3) the known overall shape of the 

concentration-response curve below 100 ppb, this reviewer believes it would be reasonable 

for the Agency to use the fitted equation down to a level of about 40 ppb, which would 

correspond to the LOD plus one standard deviation.

Rebecca T. Parkin, 

Ph.D., MPH

The validity of the extrapolation in the Hanrahan et al. paper depends in part on what data 

were used for the outcome measure. If “burning eye” AND “eye irritation” data were 

combined, more information is needed in the draft to describe what assumptions were made 

in the combining process. (See comments above.)

The validity of the estimates below 100 ppb based on the Hanrahan et al. data is 

strengthened by their alignment with the results in the Liu et al. study.

However, clearer discussion of the Agency’s choice of and uncertainties in the points of 

departure would improve this portion of the draft. 

CHARGE QUESTION 3: The studies considered for the concentration-response function are residential studies because residential 

exposures are the focus of the rule and the residential studies avoid some of the limitations of other types of studies (e.g., controlled 

exposure chamber studies used high, acute exposures, and occupational studies reflect high exposure levels and potential dose-rate 

effects from peak exposures). Are there other studies (e.g., chamber or non-residential studies) that should be used as supporting 

evidence for the currently derived concentration-response function for eye irritation? If so, please provide information about the 

studies and discuss how they should be used to support the concentration-response function.

NAME COMMENT RESPONSE

John R. Balmes, 

M.D. 

I do not know of other studies that would be better to use for derivation of a CRF for 

formaldehyde exposure and sensory irritation given the EPA’s interest in chronic, lowlevel, non-peak exposures.

David Kriebel, 

Sc.D.

I think you should use the other studies – particularly the chamber studies and the autopsy 

studies – to show the consistency of the findings across many settings. I am comfortable 
69

with the argument that the function should be derived from the residential studies. But I 

think that the logic of extrapolating downwards is supported by some of the other studies. 

Kriebel et al. Arch Env Hlth 2001; 56:11- 18 contains fairly detailed exposure data linked 

to eye irritation scores. While much of the data are above the range you are concerned with, 

there is evidence here that the relationship observed was valid across the full range of 

exposures.

Frederick J. Miller, 

Ph.D., Fellow ATS

Beyond the studies considered by EPA, this reviewer knows of no chamber or 

epidemiology studies that would be useful in developing the concentration-response 

function for eye irritation. Given the definition of an inhalation RfC and the focus on 

extended periods of exposure, the residential studies were conducted in a manner that best 

fits the criteria for developing a RfC and using it in the benefits analyses that the Agency is 

being required to conduct.

Rebecca T. Parkin, 

Ph.D., MPH

I am not aware of any other studies that should be considered for this function.

CHARGE QUESTION 4: Are there other sensory irritation endpoints besides eye irritation for which a concentration-response 

function can and should be developed for assessing effects at concentrations below 100 ppb? If so, please provide references of 

appropriate studies and a description of how the studies could be used to develop a concentration-response function.

NAME COMMENT RESPONSE

John R. Balmes, 

M.D. 

I do not know whether a CRF can be developed for other sensory irritation endpoints.

David Kriebel, 

Sc.D.

Both nose and throat irritation can be linked to increased risk of lower respiratory tract 

infection including bronchitis. So you could argue that these would have greater economic 

impacts. 

Frederick J. Miller, 

Ph.D., Fellow ATS

Sensory irritation may be indirectly reflected in pulmonary function responses measured 

after exposure to formaldehyde. However, these studies were not conducted at levels that 

would be relevant to what the Agency is being charged with investigating.

Rebecca T. Parkin, 

Ph.D., MPH

I agree with EPA and NAS that eye irritation is the most sensitive sensory irritation 

endpoint and therefore is the most appropriate endpoint to use.

CHARGE QUESTION 5: Several studies of the association between formaldehyde and asthma have been published and these were 

quantitatively summarized in a meta-analysis by McGwin et al. (2010).

Please comment on whether the McGwin et al. (2010) meta-analysis is an appropriate summary of the association between 

formaldehyde inhalation exposures and childhood asthma.

NAME COMMENT RESPONSE
70

John R. Balmes, 

M.D. 

The McGwin et al. (2010) meta-analysis of the association between formaldehyde exposure 

and risk of asthma in childhood appears to have been well conducted, using state-of-the-art 

methods, including both fixed and random effects models and various sensitivity analyses. 

Because the meta-analysis was based on a systematic review of the literature that appears to 

have been comprehensive, the results can be considered an appropriate summary of what is 

known about the association from epidemiological studies.

David Kriebel, 

Sc.D.

I agree that it is appropriate.

Frederick J. Miller, 

Ph.D., Fellow ATS

There are many problems with the studies used in the meta analysis conducted by McGwin 

et al. (2010). Relative to the description of the metal analysis, the Agency did a reasonable 

job of pointing out many of the strengths and weakness that McGwin and colleagues noted 

in their paper, but this description could be improved. 

There are various inconsistencies in the studies selected for the meta analysis that would 

make this reviewer reticent to put much trust in the findings for applicability to the U.S. 

population. First, only one study was conducted in the U. S. and that study did not find a 

statistically significant odds ratio (OR) with exposures being in the range of 30 to 80 μg/m3

of formaldehyde. Moreover, the sample size of the U.S. study was greater than that of 5 of 

the other studies contained in Table 1 of McGwin et al. (2010).

A Swedish study with exposures no greater than 10 μg/m3had an OR more than twice that 

of any other study even though several of those studies involved formaldehyde exposures in 

the 5 to 70 μg/m3range, including another Swedish study. The Zhao et al. (2008) study 

results are inconceivable to this reviewer for inclusion in a reliable meta analysis. With 

school exposures (1 to 5 μg/m3) and outdoor exposures (5 to 7 μg/m3), mean OR estimates 

were found to represent decreased risk, yet the upper bound of the 95 % confidence interval 

was 17 for the school OR and more than 2.3 million for the outdoor OR for the same set of 

1,993 children having a mean age of 12.8 years. 

McGowan et al. (2010) state that to evaluate whether the results they found were unduly 

influenced by any individual study and to determine if there was any publication bias, an 

influence plot and a funnel plot, respectively were used. However, they did not present 

these plots in their paper. The computed values of the Q and I

2

statistics were stated to 

support the presence of moderate between-study heterogeneity. The EPA document cites 
71

values for these statistics but does not explain how they are calculated, but should do so. Q 

(better known as Cochran’s Q) is a classical measure of heterogeneity and is calculated as 

the weighted sum of squared differences between individual study effects and the pooled 

effect across studies, with the weights being those used in the pooling method. Q is 

distributed as a chi-square statistic with k (number of studies) minus 1 degrees of freedom 

(d.f.). The I

2

statistic describes the percentage of variation across studies that is due to 

heterogeneity rather than chance and is computed as 100* (Q – d.f.)/Q.

On page 18 of the EPA document, the overall OR for a fixed effects model is given as 

1.026 but on page 20 the same result is stated as an OR of 1.03. The Agency needs to be 

consistent. If the data are only sufficient to give an OR with 2 digits after the decimal point, 

say so and change the value on page 18 and vice versa. For the reader to better judge the 

reasonableness of the meta analysis results, the EPA document should include Table 1 of 

the McGwin et al. (2010) paper in addition to Figure 1 from that paper.

Rebecca T. Parkin, 

Ph.D., MPH

The authors clearly built on well-accepted guidelines for systematic meta-analysis (Stroup 

et al., 2000). The study selection/exclusion criteria and process used by McGwin et al. is 

well-documented in their article. The variables extracted and utilized are stated. The 

determination to use a consistent metric (odds ratio per 10 μg/m3 with the related 95% 

confidence interval) across the 7 studies for which actual HCHO measurements were 

available is appropriate. The methods used to pool the odds ratios and test for 

heterogeneity are standard analytic approaches. Their evaluation of the potentially undue 

influence of any one study, using influence and funnel plots, adds strength to their analysis. 

The results are shown with and without Rumchev et al., allowing the reader to judge 

whether this paper should have been included or not. The data in Table 2 indicate that the 

magnitude of the HCHO effect on asthma prevalence is significant whether this study is 

included or not. The presentation of the Q and I2statistics guides the reader to the key

results for interpreting the data in this table. In summary, this reviewer finds that the 

McGwin et al. meta-analysis is an appropriate summary and synthesis of the eligible studies 

reporting a quantitative relationship between HCHO and prevalence of childhood asthma.

CHARGE QUESTION 6: Please comment on whether EPA chose the appropriate function from the McGwin et al. paper to use in 

the benefits assessment.

NAME COMMENT RESPONSE

John R. Balmes, 

M.D. 

Exponentiating the linear slope of the fixed effects model from the McGwin et al. paper is 

appropriate, especially given that the random effects model gave essentially the same 
72

pooled odds ratio.

David Kriebel, 

Sc.D.

I am comfortable with the choice to exclude Rumchev, and agree with the derivation of the 

function as described.

Frederick J. Miller, 

Ph.D., Fellow ATS

The EPA document does not specifically state which model result (i.e. fixed effects or 

random effects) was selected. Rather they state that the mean OR was 1.24 per 10 ug 

formaldehyde per m

3

for both models. One only determines that the Agency chose to use 

the random effects model if one calculates the transformed 95 % confidence interval for an 

OR for an increase of 1 ppb and sees that what is stated on page 18 corresponds to the 

confidence interval for the random effects model. 

The lack of significant between-study heterogeneity in the meta analysis of McGwin et al. 

(2010) supports using a fixed effects model; however, the extent of the uncertainties among 

the studies and the fact that the random effects confidence interval will always be larger

than the fixed effects confidence interval supports the conservative selection by the Agency 

to use the random effects model results.

In view of the additional problems this reviewer discussed earlier concerning the choice of 

studies for inclusion in the meta analysis, this reviewer would be reticent to have the 

benefits assessment use only one function (i.e., the OR of 1.03 per one ppb increase in 

formaldehyde exposure with a 95 % confidence interval from 1.008 to 1.047). The single 

U.S. study should also be evaluated wherein the OR is 1.0083 per 1 ppb increase in 

formaldehyde exposure with a 95 % confidence interval of 0.97 to 1.045. 

Rebecca T. Parkin, 

Ph.D., MPH

The Agency has chosen the appropriate function from the McGwin et al. paper. With the 

exception of the discussion of the rationale for excluding Rumchev et al., however, more 

insightful comments about the strengths of the meta-analysis would lend greater support to 

the Agency’s use of and reliance on the fixed-effects model’s OR=1.24. Deepening the 

discussion would improve the support for the Agency’s conclusions and recommendation. 

For example, McGwin et al. stated that an I2value of <50% would point to relying on the 

fixed-effect results (p. 314). Although the Agency uses the fixed-effect modeling results, 

correctly stating that the Q and I2data indicate low heterogeneity, the draft does not include 

the key cut-point (I2<50%) for the use of fixed- vs. random-effect modeling results. In this 

reviewer’s opinion, pointing the reader explicitly to this cut-point and the relevant data in 

McGwin et al.’s Table 2 would sharpen the Agency’s rationale for choosing the fixed-effect 

results
73

The discussion of uncertainties in this section includes the key issues (such as the changes 

in definition and determination of “asthma” over time) and is appropriately written.

CHARGE QUESTION 7: The literature base describing reproductive effects of formaldehyde exposure in humans is limited; 

however, there are supportive findings from the animal toxicological literature. The epidemiologic literature suggests an association 

between formaldehyde and increased risk of spontaneous abortion and a related delay in time to pregnancy (i.e., reduced fertility). 

The only study with quantitative concentration-response data was Taskinen et al. (1999).

The a priori hypothesis in Taskinen et al. (1999) was that formaldehyde would be associated with decreased fertility. The primary 

analyses showed that there was a statistically significant reduction of fertility among the women in the highest exposure group that 

appeared to be concentration dependent. Post-hoc subgroup analyses showed that stratification of the 39 women in the highest 

exposure group by reported glove use yielded effect estimates whose confidence intervals overlapped. The FDR for the 17 women 

who were classified as not wearing gloves was 0.51 [95% CI: 0.28−0.92]. The FDR for women who were classified as always or 

sometimes wearing gloves was 0.79 [95% CI: 0.47−1.23]. 

In light of the results regarding glove use, in what way(s) can the Taskinen et al. results be used to support calculating a 

concentration response for formaldehyde inhalation risk to time to pregnancy?

NAME COMMENT RESPONSE

John R. Balmes, 

M.D. 

The results of the stratified analysis regarding glove use are suggestive of the possibility

that the dermal route may contribute to total exposure, but are not adequate to consider 

modification of a CRF for decreased fertility based on inhalational exposures, especially

given the small size of the two strata and the wide confidence intervals of the FDR point 

estimates.

David Kriebel, 

Sc.D.

Yes, but you could strengthen your argument. First, there is a trend in both FDR and 

spontaneous abortion across levels of formaldehyde, so you should not only focus on the 

effect modification by glove use in the high exposure group. While the high exposure is the 

only group for which the authors provided the results stratified by glove use, the fact that 

there is a trend across air concentrations suggests that glove use – not constant across 

exposure levels – could not be a very important source of protection or you would not see 

the trend. Second, you have not correctly dealt with the question of whether or not there is 

effect modification by glove use. The overlap of confidence intervals is not the correct way

to do this. Construct the null hypothesis that glove users and non-users have the same FDR 

and then calculate a p-value testing this null. You can do it with the data provided – back 

calculate the standard errors from the confidence intervals, or ask the authors for the 
74

standard errors. I am pretty sure that this p-value will be large, and then you will be in a 

strong position to say that the appropriate conclusion is to act as if glove use has not 

modified the FDR. 

Frederick J. Miller, 

Ph.D., Fellow ATS

The results after stratifying for glove use are indirectly supportive for an inhalation effect of 

formaldehyde on the fecundity density ratio (FDR). Those women who did not wear gloves 

had a statistically significantly decreased FDR of 0.51 (i.e., 95 % confidence interval did 

not include 1). Women classified as always or sometimes wearing gloves had a FDR closer 

to 1 and their confidence interval included 1. Thus, the inclusion of women wearing gloves 

would tend to move the overall FDR closer to 1, where FDR values lower than 1 can be 

interpreted as an adverse effect in that the time to achieve conception is delayed. This was 

indeed the case since a FDR of 0.64 was found for all women in the highest exposure 

group. This provides evidence in support of the hypothesis that effects on FDR were most 

likely due to inhalation exposure rather than to dermal exposure to formaldehyde.

Rebecca T. Parkin, 

Ph.D., MPH

The article (p. 208) is not clear as to whether the post-hoc analysis was adjusted for the 

variables noted in the footnote of Table VI; if not, the post-hoc results would not be directly 

comparable to the data presented there. That said, the reported post-hoc high exposure 

group glove/not odds ratios and confidence intervals expand and are consistent with the 

trend shown in Table VI. However, all of the confidence intervals overlap each other, 

yielding a set of non-significant odds ratios. If the adjusted post-hoc odds ratios are 

available, it would be interesting to see the results of a test for trends comparing high 

exposure-gloves not used, high exposure-gloves used, medium exposure, and low exposure. 

The trend probably is not significant, but testing its significance may offer more 

information for interpreting the concentration-response relationship.

CHARGE QUESTION 8: Please comment on whether the concentration-response function is appropriately derived from the 

Taskinen et al. (1999) study.

NAME COMMENT RESPONSE

John R. Balmes, 

M.D. 

The CRF for formaldehyde exposure and decreased fertility appears to be appropriately 

derived from the Taskinen et al. (1999) study. The adjustment for probable exposure to 

formaldehyde outside of the workplace is appropriate given the interest of the EPA in 

potentially controlling indoor exposures due to off-gassing from certain products. The use 

of reasonably contemporaneous background exposure data from Finland (Jurvelin et al., 

2001) for this adjustment is also appropriate.

David Kriebel, 

Sc.D.

Can’t you ask Taskinen to confirm your (and my) assumption that age was the conditioning 

time variable in their FDR calculations?
75

The process of adjusting for background exposure is OK, but I don’t think it strengthens the 

presentation. First, I doubt very much that the relevant background formaldehyde exposure 

for the women in this plant could have been so much higher than the levels inside the plant. 

My guess is that the mean (one mean for an entire country over a long period of time? How 

useful is that?) had a wide range around it. Second, any of my graduate students could have 

told you that adding a constant to all the x values in a regression model will not change the 

slope.

Frederick J. Miller, 

Ph.D., Fellow ATS

A concentration-response function can be derived from the Taskinen et al. (1999) study, 

and the selected function must be one for which there was an adjustment for background 

exposure levels; however, the EPA document does not actually state whether they will use 

the linear function of risk or the exponential function of risk equations that are discussed in 

the document (i.e. will the Agency use Eq. 2-5 or 2-6?).

The two curves presented in Figures 6 and 7 of the Agency document are not explained 

either in the figure legend or in the text. While they obviously relate to the regression of 

risk on formaldehyde concentration, their difference is not explained. The Agency clearly 

picked up on most of the criticisms provided by the NAS review of the draft IRIS document 

related to the Taskinen et al. (1999) study. However, the Agency’s section on the 

discussion of uncertainties does not comment at all on the clear possibility of confounding 

due to xylene exposures in the Finnish worker study. Also, there is no discussion of the 

possible magnitude or direction of any exposure misclassification bias in the Taskinen et al. 

(1999) study. If the Agency is going to use the Taskinen et al. (1999) study in their 

economic analysis, more attention to a description and discussion of the study’s strengths 

and weaknesses is needed. 

Rebecca T. Parkin, 

Ph.D., MPH

Exposure measurements were available only for the middle of the study period, but the 

authors were able to verify “most” women’s self-reported exposure levels based on data 

from their workplaces. The article does not state whether this verification was completed to 

the same extent across the entire study period. This reviewer also wonders whether for 

some women (outside of the undefined “most”) the authors assumed that self-reported 

HCHO exposure levels were accurate and did not change during the study period. The 

Agency draft notes general exposure measurement concerns and agrees with Taskinen et al. 

regarding their modest response rate to the mailed questionnaire. 
76

Although Taskinen et al. note that reporting biases may be present in their study, they did 

not report any evaluation of their data to address that concern. For example, the response 

rates for women with pregnancies in the 1985-90 vs. 1991-95 periods were quite different. 

Although the authors note that “only a few women could not report the length of time to 

pregnancy,” they do not indicate whether more women in the earlier vs. later period were 

non-reporters. Also, there is no mention to what extent the authors believe the recall of the 

number of months-to-pregnancy was accurately recalled by either group of women. 

Neither Taskinen et al. nor EPA adequately discuss whether self-reported time-topregnancy (or spontaneous abortion) data are reliable for use as an outcome measure. If 

outcome misclassification is an issue as well as exposure misclassification, the odds ratios 

could be further compromised toward the null. Discussion of the reliability of self-reported 

outcome data should be considered for the next draft.

The Agency’s adjustment for non-occupational HCHO exposures, based on 

contemporaneous data, shifts the relationship to the right (from Figure 6 to Figure 7) but 

does not consider the variation in exposure levels found by Jurvelin et al. The draft 

assumes that all of the women in the study had the same non-occupational HCHO 

exposures. Considering the range, not just the mean, of Jurvelin et al.’s measurements 

would be more informative and would allow for the identification of upper and lower 

bounds on the concentration-response relationship. 

III. SPECIFIC OBSERVATIONS ON THE DOCUMENT

NAME COMMENT RESPONSE

John R. Balmes, 

M.D. 

Page 10, 1st full paragraph; page 14, figure 4a legend; page 15, 2nd full paragraph. The 

use of “inhalation” exposure in the context of eye irritation seems inappropriate. I would 

eliminate the use of “inhalation” in all three sentences.

Page 16, paragraph. 2.2.1. Asthma is defined by the Global Initiative for Asthma (GINA) 

as a disease characterized by inflammation of the airways, not lungs. I would eliminate 

“and lungs” in the first sentence of this paragraph. To avoid confusion, I would not use 

“sensitization” when discussing non-allergic, neurogenic mechanisms of irritant chemicalinduced asthma in the third sentence.

Page 20, paragraph 2.3.1. “Increased relative risk estimates (RRs) were in the range of 

1.7 to more than 3.0.” To avoid confusion, I would cite the specific papers that reported 
77

these increased relative risks.

Page 22, last sentence of text. The text here refers to “estimated concentration-response 

functions” but does not explain why there is more than one CRF in Figure 6. It is not until 

page 24 that one learns that “Regression equations for linear and exponential fits are also 

provided.” If the two lines in Figures 6 and 7 are for both types of fits then this should be 

clearly indicated.

Page 26, last full sentence. The use of a contraction here (“didn’t”) is unprofessional.

David Kriebel, 

Sc.D.

Page 20, section 2.3.1, 6th and 7th lines. The statement “Increased relative risk estimates 

(RRs) were in the range of 1.7 to more than 3.0” is not helpful – without explaining whose 

risk is being compared to whose, the absolute value of an RR is not useful. 

Section 2.0 Background on the Identification of Non-Cancer Health Effects, last 

sentence. It would be helpful to summarize at least briefly the logic behind focusing on 

these 3 endpoints. If I have understood the NAS comments correctly, that Committee also 

raised questions about these choices, and in particular on the decision not to use pulmonary

function evidence. Given this concern from the NAS, I think a bit more explanation of the 

perceived inadequacies in the data for the other endpoints would strengthen this document. 

Frederick J. Miller, 

Ph.D., Fellow ATS

None.

Rebecca T. Parkin, 

Ph.D., MPH

Eye Irritation 

Page 10, last paragraph, line 4 and Figure 2, line 2. The EPA draft states that these 

samples were taken from 30-60 minutes, but the authors only mention pumps running “for 

approximately one hour” (p. 1026). Does EPA have information in addition to what is in 

the article or is the 30-minutes an error? 

Pages 11-12. Figure 2 in the draft has a more detailed caption, but otherwise seems to be 

exactly the same as the one in the Hanrahan et al. paper (which is data for “burning eyes”); 

is it the same as in the paper? If so, shouldn’t it clearly indicate that it is “burning eye” 

data? 

Page 12. Table 1 may need a clearer caption indicating whether the data shown are for 
78

“burning eyes” AND “eye irritation” or “eye irritation” alone. Wherever combined data are 

used, EPA should clarify this usage and possibly create a new name for combined eye 

symptom data. Further, the title of Table 1 would be more accurate if it included 

“...extracted and calculated from...” 

Asthma

Page 16, last paragraph, last 2 lines and top of page 1. The descriptive language in the 

Agency draft about using the McGwin et al.’s I2 statistic would be stronger if made more 

specific; e.g., noting that McGwin et al. used a cut-point of <50% for choosing fixed- vs. 

random-effects data (page 314, top of middle column). It appears that EPA agreed with this 

cut-point. 

Page 18, first complete paragraph, line 6. The Agency states that the I2 statistic is 11.2 

when the Rumchev et al. paper is excluded, but Table 2 in McGwin et al. shows 11.3.

Female Reproductive Toxicity

Page 22. The title on Table 2 should state which “response” (TTP) is presented.
79

VI. PEER REVIEWER COMMENT TABLE ON 

THE BENEFITS ASSESSMENT APPROACH
80

I. GENERAL IMPRESSIONS

NAME COMMENT RESPONSE

Glenn C. 

Blomquist, Ph.D.

Overall, the draft Approach Document is well-written. Refreshingly, Standard English 

language is used extensively and technical terms introduced when necessary. Examples to 

explain terms such as odds ratios should make the document understandable to educated lay

readers with varied backgrounds. The key concentration-response functions are clearly 

presented in the form of equations and graphs or tables. This draft is readable. Information 

presented appears to be accurate and representative of studies that are the source of the 

information. Brief descriptions of key studies are given in addition to the findings relevant 

to the topic of this draft Approach Document. The extensive list of references allows the 

reader to learn more about the studies from which crucial estimates are taken. Conclusions 

regarding concentration-response functions and valuation (monetization) as reflected in 

their use in the examples follow from the information and models presented in a logical and 

reasonable way. My assessment of presentation applies to the entire document. My

assessment of accuracy and soundness applies mostly to Section 3 Benefits Assessment 

Approach because of my background in environmental and health economics.

A. Myrick Freeman 

III, Ph.D.

The general model for aggregating over time and across individuals that is outlined in 

Section 3.1 is correct. For other “impressions,” see my responses to specific charge 

questions below.

Shelby Gerking, 

Ph.D.

The report is, for the most part, complete and clearly written. I had no problem following 

the narrative, however, an executive summary, a conclusion and a map of the climate zones 

would have been helpful. Also, in Section 3, there are at least seven issues that warrant 

additional thought. First, the choice of the 3% discount rate, while not unreasonable, 

appears from out of nowhere. Some attention needs to be given to this choice as well as to 

the assumption of exponential discounting. Other types of discounting considered by 

behavioral economists may also be appropriate. Second, the contingent valuation 

estimates of WTP for eye irritation are rather dated—those obtained by Tolley et al. are 25 

years old. EPA still uses these estimates, but there have been a number of advances over 

the years in the application of stated preference methods aimed at reducing hypothetical 

bias which causes stated preference estimates to be too high. Third, the Dickie et al. 

estimates in Table J-10 may not be directly comparable to those of Tolley et. al. and 

Loehman et. al. in that they are based on the averting behavior method (which looks at 

actual purchases of goods), rather than on contingent valuation. In any case, the narrative 

might usefully reflect the fact that sound willingness to pay estimates are elusive and that 
81

different methods of estimating WTP often give (very) different results. Fourth, both 

asthma and eye irritation estimates rely on transferring adult WTP estimates to children. 

This procedure, which may be the only available option, may well lead to substantial 

inaccuracies. Parents, for example, may be WTP more to reduce health symptoms for their 

children than they are WTP to reduce those same symptoms for themselves. In any case, 

the issue of WTP for adults vs. WTP for kids (with citations to recent literature) should be a 

discussion point in the report. Fifth, the WTP estimates presented implicitly assume that 

switching to different building materials, or treating wood products to cut down 

formaldehyde off-gassing will not occur for the 30 year horizon analyzed. Is this 

assumption reasonable? In this same vein, could health effects from formaldehyde offgassing be lessened by providing particularly residents of new homes with information that 

would lead them to install better ventilation systems? If so, the marginal cost of better 

ventilation (if such a strategy is appropriate) might then form the basis of a simple WTP 

estimate along the lines of the headache example given on p. 31. Sixth, the population by

housing type and climate zone apparently are assumed not to change over the next 30 years, 

even though there have been major changes in population by housing type and climate zone 

over the past 30 years. This assumption seems hard to defend, although as noted on p. 42 it 

would be a difficult task to predict these movements. Seventh, it would be helpful to 

develop the main features of the cohort x housing type x climate zone model in 

introductory Section 3.1. It would be helpful in this section to explain about the 

assumptions underlying this approach (some of these are identified above). This 

reorganization will clarify the narrative at a number of points and avoid misunderstandings 

created when readers simply encounter model assumptions in the explanation of results.

II. RESPONSE TO CHARGE QUESTIONS

CHARGE QUESTION 1: The concentration-response function for the prevalence of eye irritation is based on Hanrahan et al. 

(1984). While Hanrahan does not identify the relevant time period for this relationship, Liu et al. (1991) produced qualitatively 

similar results for a two-week time period. We assumed that the concentration-response relationship for eye irritation is for a twoweek period and multiplied the concentration-response function times 26 to obtain the number of cases of eye irritation experienced 

in one year. 

The concentration-response curve used is non-linear, which means that the annual approach may not produce an exact measure of 

the benefits, but it is believed that the bias is probably relatively small given the small change in exposure.

Please comment on whether the concentration-response function is used appropriately in the benefits assessment approach.
82

NAME COMMENT RESPONSE

Glenn C. 

Blomquist, Ph.D.

The change in exposure expected from the policy appears to be small relative to typical 

exposure. It follows that the linear approximation implied by multiplication by 26 to obtain 

annual changes in number of cases of eye irritation should produce only a small bias. It 

seems as reasonable as other approaches.

A. Myrick Freeman 

III, Ph.D.

It was used appropriately.

Shelby Gerking, 

Ph.D.

The non-linear concentration response function is appropriately used in the benefits 

assessment approach. However, the approach used here appears to take no account of other 

sources of formaldehyde exposure, such as workplace exposures. In any case, the policyrelated reductions in formaldehyde exposure should be treated as reductions in total 

exposure, not simply reductions in home exposure. This refinement may alter the benefits 

calculation given the use of a non-linear concentration response function.

CHARGE QUESTION 2: The concentration-response curve is for an acute effect occurring at a time less than the one-year time 

step of the exposure model. The willingness to pay to avoid cases of eye irritation is calculated for each year of analysis by 

multiplying the number of cases in a year by the marginal willingness to pay value to avoid one case. This may produce biased

results, but the direction of that bias is unknown.

On one hand, some studies have suggested that the willingness to pay per symptom-day declines as the number of symptom-days 

avoided increases. In other words, the value to reduce two symptom-days of some effect is less than two times the value for one 

symptom-day. Therefore, this approach may overstate the total value. 

On the other hand, this analysis only applies values to one symptom, eye irritation, largely because this is the only symptom for which 

an effective concentration-response curve was derived. However, there is evidence that there are other forms of minor eye, nose, and 

throat irritation associated with formaldehyde exposure. Since eye irritation is the largest of the median values from the Tolley et al. 

(1986) study, the values used here likely represent a lower bound on the true effect of multiple symptoms. A reasonable upper bound 

of the total effect for one symptom-day would be sum of the willingness to pay for one symptom-day of each effect individually. 

Please comment on whether the annualized approach as opposed to the lifetime approach is appropriate in this context.

NAME COMMENT RESPONSE

Glenn C. 

Blomquist, Ph.D.

I admit to being confused by the statement that eye irritation has the largest of the median 

values in the Tolley et al. (1986) study. (For full disclosure, I am one of et al.) Much of 

that study was published in Tolley, Kenkel, and Fabian Valuing Health for Policy (1994) 

particularly in Chapter 4 by Kenkel, Berger, and me. In Table 4.3A on page 88, the median 
83

values for willingness to pay to avoid an additional symptom day are $11 for coughing, 

$12.50 for eye irritation, $13 for throat irritation, and $14 for sinus congestion. All three 

are similar, but eye irritation is not the largest. It will not make much difference, however, 

if either of the other two is used instead of $12.50 for eye irritation.

Comparing results reported in Table 4.3A and Table 4.3B suggests that willingness to pay

per symptom-day declines as the number of symptom days avoided increases. For 

example, the median value for avoiding 30 symptom-days of eye irritation is $100 which is 

less than 30 times $12.50 (or $375). This suggests that multiplying the $12.50 times the 

number of days of eye irritation avoided will bias the annual estimate for avoiding eye 

irritation upwards if there are multiple days for individuals. Declining marginal willingness 

to pay for avoided illnesses is also found in the recent study, Bosworth, Ryan, Trudy Ann 

Cameron, and J.R. DeShazo. “Demand for Environmental Policies to Improve Health: 

Evaluating Community-Level Policy Scenarios” Journal of Environmental Economics and 

Management 57 (2009): 293-308.

Table 4 also shows willingness to pay values for avoiding combinations of symptoms in a 

day. The willingness to pay values for avoiding combinations of symptoms in a day are 

less than the sums of the willingness to pay values for avoiding the symptoms separately. 

The declining marginal value of adding another light symptom suggest that a reasonable 

upper bound of the annual value of the total effect for one symptom-day would be the sum 

of the willingness to pay for one symptom-day of each effect individually.

On page 34, the paragraph that begins with Tolley et al. (1986) is mostly correct. (I am a 

coauthor on that Tolley report and the Berger et al. (1987) article.) It is correct, as stated, 

that the mean willingness to pay to relieve one symptom-day of a light symptom was $25 -

$50. It is mostly correct, as stated, that Berger et al. report higher willingness to pay values 

for these same symptoms. The difference is due to different samples. The Tolley et al. 

values are based on a sample of 176 respondents, some of whom had experienced the 

symptoms and some of whom had not. The Berger et al. values are based on a subsample 

of 119 who actually had experienced a symptom. The mean values for the subsample that 

had experienced the symptoms are greater than for the full sample for five of the seven light 

symptoms, nearly the same for one, and less for the remaining one. The mean value for eye 

irritation was $48.48 for the 16 who reported eye irritation whereas the mean value was 
84

$27.73 for all 176 who responded. The values reported are in 1984 dollars in both the 

Tolley et al. report and the Berger et al. article. The median value for eye irritation of 

$12.50 that Weitzel (1990) found is also reported in Tolley, Kenkel, and Fabian Valuing 

Health for Policy (1994) in Table 4.3 on page 88. It is correct that it too is in 1984 dollars. 

On page 36, if the BLS Inflation Calculator is used to inflate the median value of $12.50 for 

eye irritation from 1984 dollars to 1999 dollars, the value is $20.03 as shown in Table J-10. 

If the same is done for 1984 to 2006, the value is $24.25, which rounds to $24, as reported 

below Table J-10.

Two recent studies find that different lifetime risk profiles are valued differently; see 

Nielsen, Jytte Seested, Susan Chilton, Michael Jones-Lee, and Hugh Metcalf. “How Would 

You Like Your Gain in Life Expectancy to Be Provided? An Experimental Approach” 

Journal of Risk and Uncertainty 41 (December 2010): 195-218 and Cameron, T.A., J.R. 

DeShazo, and P. Stiffler. “Demand for Health Risk Reductions: A Cross-national

Comparison between the U.S. and Canada” Journal of Risk and Uncertainty 41 (December 

2010): 245-273. Given the limited information on the symptoms of interest it is not clear 

how incorporate these finding into the Approach Document.

A. Myrick Freeman 

III, Ph.D.

I don’t understand the question. What do you mean by the “lifetime approach”? If you 

mean the results shown in Table 3 on p. 42, then either approach is appropriate. They are 

just different ways of summarizing the data.

Shelby Gerking, 

Ph.D.

A search of the review document turned up no references to “lifetime approach”, so the 

issue to be addressed here is not entirely clear. Nonetheless, it is likely that WTP per 

symptom day of eye irritation falls as the number of symptom days increase. This outcome 

would be a general implication of utility maximization under a fixed budget. As additional 

resources are spent to relieve eye irritation, the opportunity cost of foregone consumption 

will increase. If eye irritation is coupled with other symptomatic discomforts, then we may

have a different problem. On the one hand, suppose that there exists a good that will reduce 

eye irritation together with all of the other symptoms. Then, the marginal cost (inclusive of 

both time and money) of using the good to reduce these symptoms will be the WTP for all 

combined. On the other hand, if more than one good needs to be purchased to reduce all of 

the symptoms, then the WTP would be the marginal cost of the combination of goods that 

will do the job. In any case, it is problematic to simply add up CVM estimates of WTP for 

individual symptoms as this is likely to yield a total WTP value that really is upward 
85

biased. Note that the CVM estimates themselves are probably upward biased. 

CHARGE QUESTION 3: The concentration-response function for the prevalence of eye irritation is for a single two-week period. 

The annualized approach used an adjusted concentration-response relationship that consisted in multiplying the concentrationresponse function obtained from Hanrahan et al. (1984) by 26 two-week periods.

Please comment on whether the adjustment of the concentration-response function is appropriate in the annualized approach.

NAME COMMENT RESPONSE

Glenn C. 

Blomquist, Ph.D.

It seems as reasonable as other possible approaches.

A. Myrick Freeman 

III, Ph.D.

Yes, it is appropriate.

Shelby Gerking, 

Ph.D.

An issue here is that there appear to be different ways to interpret the Total WTP 

expression on p. 39. Should we assume that the same people experience eye irritation 

repeatedly for each 26 two-week periods in the year? If this (Groundhog Day) assumption 

is correct, then the WTP value applied may well be on the high side. On the other hand, if 

we assume that a different set of people experience these symptoms in each of the two 

week periods, then the calculations presented may be more defensible. 

CHARGE QUESTION 4: The concentration-response relationship for asthma incidence is given as an odds ratio for children 

exposed to formaldehyde. An odds ratio is a way of comparing the difference in the probability of an event, in this case asthma 

diagnosis, occurring in groups exposed at different levels. The odds ratio is used to determine the willingness to pay for any change 

in emissions exposure over a 16 year period. We assume that the probability of being diagnosed with asthma is uniformly distributed 

across these 16 years. 

The use of an odds ratio implies that the concentration-response relationship is non-linear. However, given that the change in 

exposure is relatively small, the results from using this implied non-linear function are anticipated to be similar to the results if we 

were to use a linear function.

Please comment on whether the concentration-response function is used appropriately in the benefits assessment approach.

NAME COMMENT RESPONSE

Glenn C. 

Blomquist, Ph.D.

It seems as reasonable as other possible approaches.

A. Myrick Freeman 

III, Ph.D.

It was used appropriately.

Shelby Gerking, I agree that the bias from using the implied non-linear function is likely to be small, but 
86

Ph.D. please see #1 in the eye irritation section for a possible qualification.

CHARGE QUESTION 5: The valuation of asthma effects from formaldehyde exposure is based on valuing the incidence of asthma 

rather than the more standard valuation based on the exacerbation of asthma symptoms. The reason for this is that a statistical 

relationship between formaldehyde exposure and asthma exacerbation has not been sufficiently well established, but there is a

statistical relationship between formaldehyde exposure and asthma occurrence or incidence. However, the only time that EPA has 

valued asthma exacerbation is for the first prospective study of the benefits and costs of the Clean Air Act (EPA 1999). This is 

probably due to a lack of an appropriate concentration-response relationship. The EPA’s Office of Air does include recommended 

values for the monetization of chronic asthma in its BenMAP documentation (EPA 2011b), which is based on an average of the 

results from Blumenschein and Johannesson (1998) and O’Conor and Blomquist (1997).

For this analysis, EPA treats prevalence as a measure of cumulative incidence by assuming that the disease duration is the rest of the 

child’s life. However, the EPA (2000a) has previously assumed that a portion of asthmatic children will become asymptomatic as they 

move into adulthood.

Please comment on whether the annualized approach as opposed to the lifetime approach is appropriate in this context.

NAME COMMENT RESPONSE

Glenn C. 

Blomquist, Ph.D.

The approach used seems reasonable except for ignoring that some of the asthmatic 

children are likely to become asymptomatic as adults. If the incidence and prevalence data 

can support outgrowing asthma, then it should be incorporated in the estimates of valuing 

the incidence of asthma. Otherwise, the estimates will be biased upward.

I agree with the choice of the best estimate from O’Conor and Blomquist (1997) for the 

implied annual value of asthma control (page 47). It is $1,474 and is based on the risk-risk 

tradeoff and the assumed value of statistical life of roughly $6 million. The $1,474 is close 

to the nonparametric estimates of $1,500 for the 5 unit change and $1,440 for the 10 unit 

change. It is also close to the parametric estimates assuming a value of statistical life of $6 

million of $1,468 for Model 3 and $1,504 for Model 4. They are the more complete 

specifications of the drug choice logistic regression. Since surveys were done in 1995, the 

values are in 1995 dollars.

The implied annual value of asthma control of $1,474 in 1995 dollars is also close to the 

best estimates from our more recent work; see Glenn C. Blomquist, Mark Dickie, and 

Richard M. O’Conor. “Willingness to Pay for Reducing Fatality Risks and Asthma 
87

Symptoms: Values for Children and Adults of All Ages” Resource and Energy Economics

33 (May 2011): 410-425. In this recent work, we are able to estimate the willingness to pay

without assuming a value of statistical life. As Table 5 shows, for the ordered logistic 

regression for willingness to pay for the more effective drug we have a larger sample for 

the preferred specification (263 in 2011 > 75 in 1997) and the ratio of the coefficient for 

efficacy in controlling asthma to its standard error is much larger (3.14 in 2011 > 0.70 in 

1997). This facilitates estimation directly from the willingness to pay logit rather than 

indirectly from the risk-risk logit and an assumed value of statistical life. We were also 

able to test for selection bias related to the choice of drug at the first stage of the hybrid 

contingent valuation. (We found we could not reject the null of no correlation between 

errors and so based estimates of willingness to pay on the logit regression without 

selection.) Lastly, we made estimates based on using only “definitely yes” as a “yes” 

instead of both “definitely yes” and “probably yes” as a “yes” as in O’Conor and Blomquist 

(1997). In Table 6 we report values that turn out to be comparable to the best estimate from 

our earlier work. For the average age adult (45 years) our estimate for the annual value of 

asthma control is $1,960 in 2007 dollars (or $1,441 in 1995 dollars). From Table 6 which 

reports annual values of asthma control by age we cautiously summarize saying that the 

pattern of results hints that values are higher for children and young adults. For the average 

age child (11 years) our estimate for annual value of asthma control is $2,842 in 2007 

dollars (or $2,089 in 1995 dollars.) This pattern is relevant for estimating the asthma 

related benefits because the ages considered are 0 – 16 and point estimates for values for 

children are greater than the value for the average age adult. The pattern suggests that 

estimates based on the average value for adults are probably underestimates, at least with 

respect to this factor.

A. Myrick Freeman 

III, Ph.D.

Again, I don’t understand the question. What do you mean by the “lifetime approach”? 

The term is not used in the document.

Shelby Gerking, 

Ph.D.

A search of the review document turned up no references to “lifetime approach” so the 

issue to be addressed here is not entirely clear. Nonetheless, the report makes clear that 

valuation of asthma effects is based on valuing the incidence of asthma, rather than 

symptom exacerbation. This approach is crude for two reasons. First, there is substantial 

heterogeneity in cases of asthma. For some people, asthma is little more than an 

annoyance, while for others this illness is debilitating. Willingness to pay to avoid asthma 

would be expected to vary according to how serious a case is contemplated. Second, 

willingness to pay to reduce additional cases of asthma will not include the willingness to 
88

pay to reduce exacerbated symptoms of those who already have asthma. Two other issues: 

(1) While estimates of increased incidence of asthma pertain to children (see p. 19), 

estimates of WTP to reduce asthma incidence are based on two studies of adults. Parents 

may well be willing to pay more to reduce asthma incidence among their children than they

are WTP to protect themselves from the same illness. (2) It might be useful to perform a 

sensitivity analysis on the estimates provided to determine how much difference it would 

make to assume that a percentage of childhood asthmatics become asymptomatic when they

become adults, rather than assume that childhood asthmatics carry their illness forward to 

adulthood. 

CHARGE QUESTION 6: The concentration-response relationship is based on an odds ratio for a period of time longer than the one 

year. The exposure model produces results for one-year of exposure to formaldehyde for each age, housing type, and climate cohort. 

As a consequence, an adjustment to the simple model needed to be made to model the effect on individuals who are currently alive 

when the regulation takes effect.

As an upper bound estimate, we assume that the odds ratio can be applied to the one year reduction in the same fashion as it was 

applied for the 16 year time period. The problem with this approach is that it effectively treats the exposure as an acute effect. If the 

odds ratio indicates a particular percentage reduction in asthma cases from a reduction in formaldehyde exposure over 16 years, the 

upper bound approach would suggest the same percentage reduction in asthma case in one single year if we were to witness the same 

reduction in formaldehyde exposure in one year. The lower bound approach assumes that a particular exposure reduction for one

year produces the same effect as if that exposure reduction were spread out over the entire 16-year time period. 

Please comment on the upper and lower bound methodology used.

NAME COMMENT RESPONSE

Glenn C. 

Blomquist, Ph.D.

It seems as reasonable as other possible approaches.

A. Myrick Freeman 

III, Ph.D.

The approach seems reasonable. The bounds are relatively narrow, as shown in Table 7. 

How will the results be presented in the final report, as upper and lower bounds or averaged 

to give a “best” estimate?

Shelby Gerking, 

Ph.D.

The upper bound estimates are obtained by assuming that asthma onset is an acute effect of 

formaldehyde exposure particularly among older teenagers. I am uncertain as to whether 

this assumption is at variance with scientific information regarding the development of this 

disease and would defer to another panel member with greater expertise on this point. If 

asthma onset from formaldehyde exposure cannot be considered an acute effect, then the 

upper bound estimates would be less credible. Nonetheless, the upper bound estimates and 
89

the lower bound estimates do not differ greatly. Table 7 reports that for the three housing 

profiles total discounted upper bound WTP is $4,939,166 and the corresponding lower 

bound figure is $4,340,740. So, the upper bound estimate is about 14% larger than the 

lower bound estimate. An alternative to the lower bound estimate might be to assume that 

currently living children are unaffected by reduced formaldehyde exposure. Instead, we 

might assume that the reduced exposure applies only as “new” children as they enter the 

model. These “new” children are then assigned cases of asthma with the incidence rates 

described on p. 48 of the review document. 

CHARGE QUESTION 7: The prevalence data suggest that 7.2% of children age 0-4 have been told that they have asthma. 16.4% of 

children aged 5-14 have been told that they have asthma. We assume that the probability of being diagnosed is uniformly distributed 

across the 0 to 16 age bracket, so that the incidence rate would be 1.44% for the first five years and 1.49% for the next eleven years.

Allocating cases uniformly across the age brackets provides us with a way to calculate the annual benefits of any exposure reduction 

that occurs for the entire time period, but may not be appropriate if the diagnosis of asthma for very young children (e.g., age 0-2) 

differs from older children.

Is the assumption about applying the concentration-response function to children aged 0 to 16 appropriate, given the asthma onset 

studies’ focus on school-aged children and adolescents, and given the potential uncertainty of the Rumchev study involving younger 

children?

NAME COMMENT RESPONSE

Glenn C. 

Blomquist, Ph.D.

It seems as reasonable as other possible approaches. A question about this and the other 

concentration-response functions and exposure is whether or not they take into account 

averting behavior. Smell leads to open windows and more time outside of house and less 

exposure.

A. Myrick Freeman 

III, Ph.D.

I can’t answer this. It lies outside my area of expertise.

Shelby Gerking, 

Ph.D.

I defer to another panel member here as I have no expertise in this area. 

CHARGE QUESTION 8: The linear concentration-response function accounting for background exposures based on Taskinen et 

al. (1999) is used for the annual approach.

Please comment on whether the concentration-response function is used appropriately in the benefits assessment approach.

NAME COMMENT RESPONSE

Glenn C. 

Blomquist, Ph.D.

It seems as reasonable as other possible approaches.
90

A. Myrick Freeman 

III, Ph.D.

It was used appropriately.

Shelby Gerking, 

Ph.D.

The concentration-response function appears to have been applied correctly in the benefits 

assessment approach. Note that the concentration-response function is linear, so accounting 

for other sources of formaldehyde exposures would be less important. However, two other 

issues might be addressed. First, equations (18) and (19) in the text may require some 

clarification. My question relates to the term 

, , , ,

[( exp ) ( exp )] hcbaseline h c policy a b   osure      osure . Does a =  ? Does b =  ? If so, 

the notation should be changed. If not, the equation needs additional explanation. Second, 

in these equations, population refers to women who have difficulty conceiving. The 

population of women who are actively attempting to become pregnant would instead be 

more appropriate. Page 59 indicates that for the proposed rule this latter definition would 

be incorporated. I agree that this change would be appropriate. 

CHARGE QUESTION 9: Monetization of delayed fertility has been discussed in the literature but has never been included in 

primary analyses of EPA rules because it was believed that the scientific knowledge on reproductive and developmental health effects 

was not strong enough to quantify risk in the primary benefits analysis.

While there appears to be good data on the cost of treatment, there are few studies on the willingness to pay to reduce delayed 

conception. Most economic valuation studies regarding fertility focus on an individual’s or a couple’s willingness to pay for infertility 

treatment, particularly in-vitro fertilization (IVF). Conceptually, the willingness to pay approach is preferable and could be deduced 

from the valuation studies. However, given that there has been less research on these willingness to pay values than other values and 

the fact that the values have not been used in previous economic analyses, we used the more straight-forward cost of illness approach 

for this analysis.

As an upper bound, we assume that any woman who has difficulty conceiving (i.e., time to pregnancy exceeds 12 months) will obtain 

some type of fertility service. This may be a reasonable upper bound, but there are certainly women who have trouble becoming

pregnant and do not seek fertility treatment. 

The willingness to pay for fertility treatment is treated as an expected value. The average cost of various cycle-based fertility 

treatments is multiplied times the probability of obtaining that treatment at various ages. There is probably a small opposite effect 

associated with an increase in pregnancy from reduced formaldehyde exposure by women who do not want to become pregnant, but 

we do not consider this effect

Please comment on whether the annualized approach as opposed to the lifetime approach is appropriate in this context.
91

NAME COMMENT RESPONSE

Glenn C. 

Blomquist, Ph.D.

It seems as reasonable as other possible approaches.

On page 58, the choice is made to use the cost-of-illness estimates from Katz et al. (2011) 

for valuing difficulty in conceiving due to formaldehyde exposure. A strength of these 

estimates is that apparently most fertility treatment costs are paid for out-of-pocket by 

consumer/patients rather than by third parties through private or public insurance. As such, 

consumers reveal that the treatments are worth at least as much as they paid. Their 

maximum willingness to pay would be expected to be greater than these costs because of 

consumer surplus. (This does not take into account any utility or disutility of treatments.) 

If data were available and demand for fertility treatment could be estimated, then a better 

estimate of maximum willingness to pay could be made. This suggests using cost-of-illness 

will produce an underestimate. However, if the values are applied to all women who are 

exposed to formaldehyde, benefits will tend to be overestimated. The reason is that not all 

the women whose fertility is affected will pay the market prices for the treatments. In other 

words, the price is known for the various packages of treatments, but the number of women 

who are willing to pay the price is not. The maximum willingness to pay for treatment for 

the women whose fertility is affected but choose to forgo treatment and the number of them 

are unknowns. Their values are likely to be positive, but they are less than the costs. Katz 

et al. report treatment costs per successful outcome of more than $70,000. They also report 

that 72% of the women had college education. A hunch is that those women have above 

average household incomes and spend most of their time in single family detached homes 

where exposure reduction is smallest. Less educated women with lower household 

incomes are probably less likely to pay for treatments at the going prices. Assuming that 

women who have below average incomes and live in mobile homes will pay the market 

prices for the same distribution of fertility treatments is likely to bias the estimate of 

benefits of reducing exposure to formaldehyde upward.

A. Myrick Freeman 

III, Ph.D.

Again, I don’t understand the question. What do you mean by the “lifetime approach”? 

The term is not used in the document. Perhaps the charge question should be "Please 

comment on the annual approach to calculating a total WTP per year as described in 

Section 3.4.2." My answer to that question is that if a valid individual WTP per year can 

be obtained, equation (18) is the appropriate way to calculate aggregate WTP per year. But 

for reasons I point out in the Specific Observations section below (see my comments to 

question #3), I have serious doubts about the ability to obtain a valid individual WTP per 
92

year.

Shelby Gerking, 

Ph.D.

Cost-of-illness estimates are conceptually inappropriate in this context for two reasons. 

First, cost-of-illness is not a conceptually sound approach for estimating willingness to pay. 

This point is noted in the document on p. 58. In consequence, I would suggest that cost-ofillness estimates might be used only as a last resort. The WTP estimates obtained by Smith 

and van Houtven may well be a more defensible choice. Careful thought should be given 

to whether this alteration would be an improvement. Second, the COI estimates utilized 

(see equation (20) and Table 10) do not really pertain to the delay in conception addressed 

in the Taskinen study. Women (or couples) may be willing to pay to reduced time to 

conceive, but may at the same time be reluctant to seek fertility treatment. At a minimum, 

this potential misalignment should be addressed. 

CHARGE QUESTION 10: The time period associated with the exposure-response function is longer than the time step of the 

exposure model. The Taskinen (1999) study examined the fecundity of women age 20-40. This causes a problem if we have an 

individual who does not experience the exposure reduction for the full time period. We can form an upper and lower bound of this 

willingness to pay as we did for asthma prevalence. The upper bound is based on the assumption that the linear concentrationresponse function holds for an acute exposure of one year. The lower bound assumes that an exposure reduction for one year 

represents 1/20th of an exposure reduction for the entire 20-year time period. 

Please comment on the upper and lower bound methodology used.

NAME COMMENT RESPONSE

Glenn C. 

Blomquist, Ph.D.

It seems as reasonable as other possible approaches.

A. Myrick Freeman 

III, Ph.D.

The approach seems reasonable. How will the results be presented in the final report, as 

upper and lower bounds or averaged to give a “best” estimate?

Shelby Gerking, 

Ph.D.

The Taskinen study appears to treat formaldehyde exposure as a long term exposure. In 

consequence, I am uncertain that the upper bound estimates are defensible (see the related 

point #6 in asthma above). Nonetheless, the upper and lower bound WTP estimates differ 

only by about $57,000 (see Table 12). This outcome could change of course if the analysis 

is redone along lines suggested above. Also, as with asthma, I would suggest the 

possibility to treat “new” women entering the model as those affected by the contemplated 

reduction in formaldehyde exposure.

CHARGE QUESTION 11: The ages used in this analysis reflect the ages reported in the Taskinen (1999) study, ages 20-40. 

However, women older than age 40 obtain fertility treatment. The value of reduced infertility effects from reduced formaldehyde 

exposure is not reflected in this analysis in order to remain consistent with Taskinen (1999).
93

Please comment on whether the concentration-response function was applied to appropriate age groups given the age groups in the 

studies. 

NAME COMMENT RESPONSE

Glenn C. 

Blomquist, Ph.D.

It seems as reasonable as other possible approaches.

A. Myrick Freeman 

III, Ph.D.

Given my reservations about using the cost-of-fertility treatment to monetize this effect (see 

my comments to question #3 in the Specific Observations section below), I have no 

problem in limiting the quantification of this effect to the age group covered in the 

Taskinen study.

Shelby Gerking, 

Ph.D.

The Taskinen study does not appear to provide a direct basis for adding women aged 40 

and older to the analysis. However, relatively few of these women may seek to become 

pregnant in a given year. If the analysis focused on women who seek to become pregnant, 

exclusion of women over 40 years of age may not be a grave oversight. I would defer to a 

panel member more knowledgeable about fertility issues to make a judgment on this issue.

III. SPECIFIC OBSERVATIONS ON THE DOCUMENT

NAME COMMENT RESPONSE

Glenn C. 

Blomquist, Ph.D.

Page 53, bottom. $4.9 instead of $4,9.

Page 56, 3rd paragraph. Monetization is misspelled.

Page 58. Van Houtven and Smith (1999) instead of 1997 and $12,500 instead of $12,50.

Page 59. Is the probability of obtaining cycle-based fertility treatment shown in Table 8,

the best projection for future treatment? The utilization percentages given on page 916 in 

Katz et al. seem different.

Page 68. O’Conor instead of O’Connor.

A. Myrick Freeman 

III, Ph.D.

There are a number of typographical and editorial errors. This is not a complete list:

Table of Contents. Page numbers are wrong.

Page 17. Figure 2 should be labeled figure 5.
94

Section 3. Why do the table and figure numbers start over instead of continuing throughout 

the report? And some of the table numbers seem to be wrong (e.g., J-10 on page 36).

Page 6. The report gives the aim of developing concentration-response relationships as 

being “ ... to inform the economic benefits assessment of potential cost savings ...” This is 

not about “cost savings;” it is about welfare gains.

In some places, coefficients in the concentration-response relationships are Greek letters. 

In other places they are not.

Section 2.1.1, 3rd sentence in the first paragraph. Needs editing.

Page 53. Where it says “($93,095 + $58,662 + $90,852= $242,602),” it should be = 

$242,609.

Page 58. It says “willingness to pay of between $3,750 and $12,50 for fertility treatment.”

Page 59. The probability of using IVF should be 2.5%, not .25%.

Page 61, last paragraph. There are two references to Table 10, which should be Table 12.

Page 63. The sentence, “This is probably the largest category of value associated fertility

issue from a reduction in formaldehyde exposure,” needs editing.

I have added the following three charge questions based on my expertise in nonmarket valuation:

(1) Please comment on the validity of the monetization of sensory irritation. The approach 

to the monetization of this effect is the same as that used in the First Prospective Section 

812 Report. In my judgement, this is a valid approach and makes the best use of the 

available empirical evidence. However, it should be noted that the effect actually valued in 

the First Prospective Section 812 Report as “Upper Respiratory Symptoms” defined as 

“two or more of the following symptoms: runny or stuffy nose; coughing; and eye 

irritation.” Since this document states that formaldehyde can cause a variety of types of 
95

sensory irritation in the upper respiratory system (p. 7), this is appropriate. But it should be 

made clear that more than simply eye irritation is involved.

(2) Please comment on the validity of the monetization of chronic asthma. The approach 

to the monetization of this effect is the same as that used in the First Prospective Section 

812 Report. In my judgement, this is a valid approach and makes the best use of the 

available empirical evidence. 

(3) Please comment on the validity of the monetization of reduced fertility. I have serious 

reservations about the approach taken here to monetize this effect. First, “reduced fertility” 

is not a well-defined effect. There is ambiguity as to both the degree of reduction and its 

duration. This makes determining the proper valuation difficult. 

I agree that conceptually, the willingness to pay (WTP) approach is preferable to a cost-ofillness or cost-of-treatment approach. However, as I read the available WTP studies, they

apply to the more serious infertility rather than to the “subfertility” (p. 21) associated with 

exposure to formaldehyde. Thus, the available WTP studies are not suitable for benefits 

transfer.

The report takes a cost of treatment approach to valuation. But it is not at all clear to me 

that the “cycle-based treatments” described here are either appropriate treatments or likely

to be effective in the face of continued formaldehyde exposures.

For these reasons, I recommend that this effect be described and quantified to the extent 

that evidence supports quantification, but that it be acknowledged that there is not an 

adequate basis for monetization of this effect.

Shelby Gerking, 

Ph.D.

The document appears to have been put together hastily as there are numerous typos and 

other glitches. Below is a list of typos that I flagged—I am certain there are more.

Page 31, first line below equation (1). ...risk reduction at age a.

Page 35, next to last line of third full paragraph. Data should be days

Page 36. Not sure why the Table is called “Table J-10”. Other tables are not numbered 
96

this way. Also, in this table Dickie et al. needs a date

Page 44, first line under monetization. Analysis should be analyses.

Page 45, Table IV. 2-17 not numbered consistently with other tables, also in two places 

decimal points are mistakenly used for commas

Page 53, last full line. Should be $4.9 million

Page 56, eighth line up from bottom. Undergoes should be undergo

Page 57, fourth full paragraph, first line. Ryan (1996) conducted a contingent ...

Page 58, first full paragraph, line 4. Respondents were asked to consider taking...

Page 59, line 8 under equation (19) (and elsewhere). The word data is plural, not 

singular

Page 59, line 12 under equation (19). Difficulty is misspelled

Page 59, second line up from bottom. Reduction is misspelled

Page 60, part of Table 9 appears to be missing. Also, the heading is missing a number 

for ppb.

Page 60, Table 10. The probability values are missing