Federal Register/Vol. 74, No. 159/Wednesday, August 19, 2009/Notices
41883
Dated: August 5, 2009.
Matthew Leopard,
Acting Director, Information Management
Division, Office of Pollution Prevention and
Toxics.
[FR Doc. E9-19461 Filed 8-18-09; 8:45 a.m.]
BILLING CODE 6560-50-S
ENVIRONMENTAL PROTECTION
AGENCY
[EPA-HQ-OW-2009-0297; FRL-8943-9]
RIN 2040-AF08
Drinking Water: Perchlorate
Supplemental Request for Comments
AGENCY: Environmental Protection
Agency (EPA).
ACTION: Notice.
SUMMARY: The Agency is seeking
comments on additional approaches to
analyzing data related to EPA's
perchlorate regulatory determination.
These additional comments are sought
in an effort to ensure consideration of
all the potential options for evaluating
whether there is a meaningful
opportunity for human health risk
reduction of perchlorate through a
national primary drinking water rule.
EPA will make a final regulatory
determination for perchlorate after
considering comments and information
provided in the 30-day comment period
following this notice.
DATES: Comments must be received on
or before September 18, 2009.
ADDRESSES: Submit your comments,
identified by Docket ID No. EPA-HQ-
OW-2009-0297, by one of the following
methods:
• http://www.regulations.gov: Follow
the online instructions for submitting
comments.
• Mail: Water Docket, Environmental
Protection Agency, Mailcode: 2822T,
1200 Pennsylvania Ave., NW.,
Washington, DC 20460.
• Hand Delivery: Water Docket, EPA
Docket Center (EPA/DC) EPA West,
Room 3334, 1301 Constitution Ave.,
NW., Washington, DC. Such deliveries
are only accepted during the Docket's
normal hours of operation, and special
arrangements should be made for
deliveries of boxed information.
Instructions: Direct your comments to
Docket ID No. EPA-HQ-OW-2009-
0297. EPA's policy is that all comments
received will be included in the public
docket without change and may be
made available online at http://
www.regulations.gov, including any
personal information provided, unless
the comment includes information
claimed to be Confidential Business
Information (CBI) or other information
whose disclosure is restricted by statute.
Do not submit information that you
consider to be CBI or otherwise
protected through http://
www.regulations.gov or e-mail. The
http://www.regulations.gov Web site is
an "anonymous access" system, which
means EPA will not know your identity
or contact information unless you
provide it in the body of your comment.
If you send an e-mail comment directly
to EPA without going through http://
www.regulations.gov your e-mail
address will be automatically captured
and included as part of the comment
that is placed in the public docket and
made available on the Internet. If you
submit an electronic comment, EPA
recommends that you include your
name and other contact information in
the body of your comment and with any
disk or CD-ROM you submit. If EPA
cannot read your comment due to
technical difficulties and cannot contact
you for clarification, EPA may not be
able to consider your comment.
Electronic files should avoid the use of
special characters, any form of
encryption, and be free of any defects or
viruses. For additional instructions on
submitting comments, go to Unit LA of
the SUPPLEMENTARY INFORMATION section
of this document.
Docket: All documents in the docket
are listed in the http://
www.regulations.gov index. Although
listed in the index, some information is
not publicly available, e.g., CBI or other
information whose disclosure is
restricted by statute. Certain other
material, such as copyrighted material,
will be publicly available only in hard
copy. Publicly available docket
materials are available either
electronically in http://
www.regulations.gov or in hard copy at
the Water Docket, EPA/DC, EPA West,
Room 3334, 1301 Constitution Ave.,
NW., Washington, DC. The Public
Reading Room is open from 8:30 a.m. to
4:30 p.m., Monday through Friday,
excluding legal holidays. The telephone
number for the Public Reading Room is
(202) 566-1744, and the telephone
number for the EPA Docket Center is
(202) 566-2426.
FOR FURTHER INFORMATION CONTACT: Eric
Burneson, Office of Ground Water and
Drinking Water, Standards and Risk
Management Division, at (202) 564-
5250 or e-mail burneson.eric@epa.gov.
For general information, contact the
EPA Safe Drinking Water Hotline at
(800) 426-4791 or e-mail: hotline-
sdwa@epa.gov.
Abbreviations and Acronyms
>—greater than
<—less than
BW—body weight
CBI—confidential business information
CDC—Centers for Disease Control and
Prevention
DWI—drinking water intake
EPA—U.S. Environmental Protection Agency
FDA—U.S. Food and Drug Administration
FR—Federal Register
HA—Health Advisory
HRL—health reference level
IRIS—Integrated Risk Information System
kg—kilogram
L—liter
mg/kg—milligram per kilogram of body
weight
mg/L—milligrams per liter (equivalent to
parts per million [ppm])
MRL—Method Reporting Limit
NAS—National Academy of Science
NHANES—National Health and Nutrition
Examination Survey
NOAEL—no observed adverse effect level
NOEL—no observed effect level
NRC—National Research Council
OW—Office of Water
PBPK—Physiologically-Based
Pharmacokinetic
POD —point of departure
RAIU—Radioactive Iodide Uptake
RfD—reference dose
RSC—relative source contribution
SDWA—Safe Drinking Water Act
UCMR—Unregulated Contaminant
Monitoring Regulation
|ig—microgram (one-millionth of a gram)
US—United States
USDA—U.S. Department of Agriculture
SUPPLEMENTARY INFORMATION
I. General Information
A. What Should I Consider as I Prepare
My Comments for EPA ?
You may find the following
suggestions helpful for preparing your
comments:
1. Explain your views as clearly as
possible.
2. Describe any assumptions that you
used.
3. Provide any technical information
and/or data you used that support your
views.
4. If you estimate potential burden or
costs, explain how you arrived at your
estimate.
5. Provide specific examples to
illustrate your concerns.
6. Offer alternatives.
7. Make sure to submit your
comments by the comment period
deadline.
8. To ensure proper receipt by EPA,
identify the appropriate docket
identification number in the subject line
on the first page of your response. It
would also be helpful if you provided
the name, date, and Federal Register
(FR) citation related to your comments.
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II. Background
The statutory and regulatory
background for this action is described
in detail in the October 10, 2008, FR
notice discussing EPA's initial
regulatory determination for perchlorate
(USEPA, 2008a). Briefly, the Safe
Drinking Water Act (SDWA) section
1412, as amended in 1996, requires EPA
to make a determination whether to
regulate at least 5 contaminants from its
contaminant candidate list (CCL) every
5 years. Once EPA determines to
regulate a contaminant in drinking
water, EPA must issue a proposed
national primary drinking water
regulation (NPDWR) and final NPDWR
within certain set time frames. To
regulate a contaminant in drinking
water, EPA must determine that it meets
three criteria: (1) The contaminant may
have an adverse effect on human health,
(2) the contaminant is known to occur
or there is a substantial likelihood that
the contaminant will occur in public
water systems with a frequency and at
levels of public health concern, and (3)
regulation of such contaminant presents
a meaningful opportunity for health risk
reduction for persons served by public
water systems. To date, EPA has made
final regulatory determinations for 20
contaminants from CCLl and CCL2 and
has not found that any of these
contaminants meet all three criteria.
On October 10, 2008, EPA published
a preliminary regulatory determination
for perchlorate, requesting public
comment on its determination that
perchlorate did not meet the second and
third criteria for regulation. The October
2008 notice describes in detail the bases
for EPA's determination (USEPA,
2008a). EPA received extensive public
comment on that notice.
Today, the Agency is seeking
comments on additional approaches to
analyzing data related to EPA's
perchlorate regulatory determination.
The EPA is requesting the additional
comments in an effort to ensure that the
Agency considers the potential options
for evaluating whether there is a
meaningful opportunity for human
health risk reduction from perchlorate
through a national primary drinking
water rule. EPA's final decision may be
a determination to regulate. As
discussed below, the additional
alternatives under consideration could
result in health reference levels which
are much lower than the level identified
in the October 2008 notice. The public
comments EPA received pursuant to the
October 10, 2008, notice of preliminary
regulatory determination a and from the
peer review of the supporting
documents underscore the complexity
of the scientific issues regarding the
regulatory determination for perchlorate
in drinking water.
EPA received 32,795 comment letters
of which 31,632 (96%) letters were from
seven different apparent mass mailing
letter writing campaigns that did not
support the preliminary determination.
Of the remaining 1,163 comment letters
that would be considered "unique," 30
commenters provided EPA with
detailed comments. Of those 30
comment letters, six supported EPA's
preliminary determination. These
comments and other docket materials
are available electronically at http://
www.regulations.gov (Docket ID No.
EPA-HQ-OW-2008-0692).
In its October 2008 FRN, EPA referred
to a draft report entitled "Inhibition of
the Sodium-Iodide Symporter by
Perchlorate: An Evaluation of Lifestage
Sensitivity Using Physiologically-Based
Pharmacokinetic (PBPK) Modeling"
(USEPA, 2008b). This draft report,
which is described in Section III.A.l,
was peer reviewed during the comment
period on the regulatory determination.
The report (USEPA, 2008c) and a
summary of significant comments made
by the external peer reviewers and
EPA's responses (USEPA, 2008e) can be
found at http://cfpub.epa.gov/ncea/cfm/
recordisplay.cfm?deid=212508. The
peer review comments were
complimentary and supportive of EPA's
modeling analysis and support
document.
On January 8, 2009, EPA issued an
interim health advisory (HA) to provide
guidance to state and local officials in
their efforts to address perchlorate
contamination while EPA was
reviewing scientific issues. A draft of
the HA was peer reviewed by four
external peer reviewers. The HA peer
reviewers comments are discussed in
Section III. A. 2 of this notice. The
Interim Health Advisory (USEPA.
2008d) can be found at http://
www.epa.gov/safewater/contaminants/
unregulated/perchlorate.html and the
summary of significant comments made
by the external peer reviewers (USEPA.
2008e) can be found at http://
www.epa.gov/ogwdw/contaminants/
unregulated/pdfs/
perchlorate_ha_comment_response.pdf.
In January of this year, EPA
announced that we planned to seek
additional input from the National
Research Council (NRG) on perchlorate.
The NRG previously studied perchlorate
health implications from March, 2003
until they issued their report in January,
2005 (NRG, 2005). EPA has compiled
and evaluated additional scientific
studies relevant to perchlorate health
effects and exposure available since
publication of the 2005 NRG report. As
previously stated, EPA also has obtained
peer review and public comment on the
Agency's analysis of a number of these
studies. The Agency believes that
further review? by the NRG would
unnecessarily delay regulatory decision
making for perchlorate. Therefore, EPA
is not, at present, planning to request
additional NRG review? of issues related
to perchlorate. Instead, EPA is issuing
this notice and seeking comment on a
broad range of alternative approaches to
the interpretation of the scientific data
relevant to a regulatory determination
for perchlorate in drinking water.
However, EPA requests comment upon
whether further review? by the NRG is
warranted. EPA also notes that if the
Agency were to make a final
determination to regulate perchlorate,
the Agency, in accordance with the
SDWA, would seek review? by the
Science Advisory Board prior to
proposal of any maximum contaminant
level goal and national primary drinking
water rule.2
In issuing this supplemental notice,
EPA is not making a final regulatory
determination for perchlorate nor are we
changing the Interim Health Advisory
Level of 15 |ig/L. EPA will consider
comments on the information received
on this notice, as well as those received
on the October 10, 2008, FR notice, and
those received on the peer review? of
supporting documents before
completing its regulatory determination
for perchlorate. EPA may also revise the
Interim Health Advisory as part of this
process.
III. Alternative Approaches To
Analyzing Scientific Data Related to
Perchlorate in Drinking Water
EPA is requesting comment on key
issues related to the regulatory
determination for perchlorate in
drinking water. EPA is now considering
a broader range of alternatives for
interpreting the available data on: the
level of health concern, the frequency of
occurrence of perchlorate in drinking
water, and the opportunity for health
risk reduction through a national
!Qn November 12, 2008, EPA extended the
comment period for 15 days regarding EPA's
preliminary regulatory determination for
perchlorate.
2 The requirement for national drinking water
regulations are in SDWA Section 1412. EPA's Web
page describes the regulatory development process
(see http://www.epa.gov/safewater/standard/
setting.html). SDWA section 1412.e requires that
EPA request comment from the Science Advisory
Board prior to proposal of a maximum contaminant
level goal and national primary drinking water
regulation.
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41885
primary drinking water standard. These
alternative interpretations may impact
the Agency's final regulatory
determination for perchlorate.
Therefore, EPA seeks comment on these
issues and the alternative approaches
the Agency is considering.
A. Interpretation of the Physiologically-
Based Pharmacokinetic (PBPK)
Modeling
1. EPA's PBPK Modeling Analysis in the
October 2008 FR Notice
The NRC (NRG, 2005) found that the
inhibition of iodide uptake by the
thyroid should be used as the basis for
a perchlorate risk assessment. In the
October, 2008, FR notice, EPA describes
a Physiologically-Based
Pharmacokinetic (PBPK) modeling
analysis prepared by the Agency
utilizing a series of papers (e.g., Clewell
et al, 2007) discussing PBPK models
that estimated the effect of perchlorate
on iodide uptake for the pregnant
woman and fetus, the lactating woman
and neonate, and the young child. EPA
used the PBPK modeling analysis to
estimate the iodide uptake inhibition for
these sensitive life stages consuming
food containing perchlorate at mean
levels, and drinking water containing
perchlorate at an HRL of 15 |ig/L at the
90th percentile consumption rate.
EPA found that the predicted
radioactive iodide uptake (RAIU)
inhibition for all subgroups was
comparable to, or less than, the RAIU at
the no observed effect level (NOEL)
selected by the NRC. Based on this
outcome, EPA concluded that by
protecting the fetus of the hypothyroid
or iodide-deficient woman from the
effects of perchlorate on the thyroid, all
other life stages and subgroups would
be protected.
EPA requested comment on the model
in the October 2008 FR notice in
addition to conducting a peer review on
the application of the model to non-
adult life stages.
2. What Were the Key Scientific Issues
Raised by Commenters
Many of the public comments EPA
received on the PBPK model in response
to the October 2008 FR notice objected
to the Agency's use of a model that had
not been peer reviewed. Concurrently
with the public comment period, the
PBPK model analysis underwent a
rigorous peer review by eight experts.
Response by the PB model analysis peer
reviewers indicated that the
modifications made to the model and
the changes to physiological parameters
were an improvement over the Clewell
model, and all reviews were generally
supportive of the analysis. Based on the
external peer review? comments, the
models and the report entitled,
"Inhibition of the Sodium-Iodide
Symporter by Perchlorate: An
Evaluation of Lifestage Sensitivity Using
Physiologically-Based Pharmacokinetic
(PBPK) Modeling" were revised.
As previously discussed, comments
were also received from four peer
reviewers for the Interim Drinking
Water Health Advisory (HA) on the
application of the model in identifying
sensitive life stages. One HA peer
reviewer noted that the use of the PBPK
model did "provide an estimate of
perchlorate exposure to average weight
babies of healthy breastfeeding women."
However, this HA peer reviewer
continued on to recommend that the
exposure estimate be expanded to
include consideration of small birth
weight and preterm infants.
Another peer reviewer recommended
that the uncertainty inherent in the
modeling exercise should be made more
transparent to the public. This
uncertainty was linked to the modeling
code, the availability of data for the
many variable parameters in the model,
the combination and handling of the
data selected for use in simulations,
and, in particular, the lack of human
data for specific life stages including
pregnant women and their fetuses,
lactating women and their babies, and
bottle-fed infants for which rat data
were adapted. The inability of the
model to reflect iodide nutritional status
also was cited by three peer reviewers
as an important limitation.
Individual peer reviewers raised two
additional concerns: (1) That the use of
animal data to predict human responses
appears to run counter to the NRC
finding that animal data cannot be used
to quantitatively predict the response of
humans due to species differences, and
(2) that EPA appeared to use the PBPK
model to modify the reference dose
(RfD) for infants, justifying the
allowance of exposures that clearly
exceeded the RfD established by the
NRC.
Peer reviewers further noted that the
PBPK model and the EPA assessment
did not account for the activity of other
compounds with similar actions on the
thyroid. This issue was also raised by
EPA's Office of Inspector General (DIG)
in reference to EPA's perchlorate risk
assessment (see section III.C.2 for more
information). One reviewer stated that
the application of the PBPK model by
the Agency as cited in the Interim
Health Advisory implied an
inappropriate certainty in the results
that was not warranted. This reviewer
recommended confining the use of the
PBPK model to exploring the impact of
varying physiological parameters and
exposure data among life stages.
3. Alternative Approaches EPA Is Also
Now Considering
Based on the comments received on
the application of the PBPK model as
described in the October 2008 notice
and the Interim HA, EPA is re-
evaluating how best to incorporate the
PBPK modeling analysis into its
evaluation of perchlorate, if at all.
One approach might be to use the
PBPK modeling analysis to explore the
relative sensitivity of the various life
stages of concern to a fixed dose such
as the point of departure (POD) or the
reference dose (RfD). For example, EPA
has examined the effect of a dose equal
to the POD on RAIU for a number of
different life stages. The POD for the
perchlorate risk assessment (7 |xg/kg/
day) was recommended by the NRC.
The POD is the lowest dose
administered in the Greer et al. (2002)
clinical study, and resulted in a "very
small decrease (1.8%) in radioiodide
uptake * * * well within the variation
of repeated measurements of normal
subjects (NRC, 2005)." The POD used
was determined by NRC to be a No
Observed Effect Level (NOEL). The NRC
stated that use of a NOEL differs from
the traditional approach to deriving an
RfD, which bases the critical effect on
an adverse outcome, and that using a
nonadverse effect that is upstream of the
adverse effect is a more conservative
and health-protective approach to
perchlorate hazard assessment. The
NRC also recommended that EPA derive
an RfD by applying a 10-fold
uncertainty factor to the POD to account
for differences between healthy adults
and the most sensitive population,
fetuses of pregnant women who might
have hypothyroidism or iodide
deficiency. When compared to the
average adult, the 7-day old breast-fed
infant and the fetus of the pregnant
woman at gestation week 40 were
identified by EPA's analysis as the most
sensitive subgroup with respect to
percent RAIU inhibition at a dose to the
lactating or pregnant women equal to
the POD. (See Table 1 for the model-
predicted RAIU inhibition and relative
sensitivity at the POD of different
subgroups compared to the average
adult, based on EPA's modified PBPK
model.)
The predicted percent RAIU
inhibition is approximately 7.8-fold
higher for the 7-day old breast-fed infant
and 6.7-fold higher for the fetus (at
gestational week 40) than for the average
adult. (Simulations at earlier gestation
weeks indicate that the fetus is more
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Federal Register/Vol. 74, No. 159/Wednesday, August 19, 2009/Notices
sensitive than the adult throughout
pregnancy, but data available for
validation of these parameters are
minimal and are considered too
quantitatively uncertain to assign exact
relative sensitivities.) The same analysis
shows that the predicted percent RAIU
inhibition is approximately one and a
half-fold higher for the bottle-fed infant
(7-60 days) compared to the average
adult, and is approximately equal for
the 1-2 year old child and the average
adult. However, the drinking water
exposure data discussed in section
III.B.3 show that infants less than six
months in age generally consume five to
eight times more water than pregnant
women or women of child bearing age
on a per body weight basis, and so will
receive a higher dose for any given
drinking water concentration.
TABLE 1—MODEL-PREDICTED RADIOACTIVE IODIDE UPTAKE (RAIU) INHIBITION AND RELATIVE SENSITIVITY OF DIFFERENT
SUBGROUPS COMPARED TO THE AVERAGE ADULT AT A DOSE EQUAL TO THE POINT-OF-DEPARTURE (POD) BASED
ON THE EPA's MODIFIED PBPK MODELS
Population or life stage
Average Adult a
Woman (child-bearing age)
Pregnant woman and Fetus (Gestation Week 40)
Lactating woman and Breast-fed infant (7 d)
Lactating woman and Breast-fed infant (30 d)
Lactating woman and Breast-fed infant (60 d)
Bottle-fed infant (60 d)
Child (0 97 yr)9
Child (2 yr)
Body weight (kg)
70
68
Mom: 79
Fetus: 3.5
Mom1 74
Infant1 3 6
Mom1 73
Infant1 4 2
Mom1 72
Infant1 5 0
Infant1 5 0
Child1 10
Child: 14
Dose1
(ng/kg-d)
7
7
7
7
Mom - 7
Infant- 7
(Mom - 2.7)
7
Mom - 7
Infant- 7
(Mom - 3.0 )
7
Mom - 7
Infant- 7
(Mom - 3.6 )
7
7
7
RAIU inhibition
1 .6%
£3.0%
C6.1%
C11%
"2.1%
d-e-\2.5%
d-e-'5.4%
d2.0%
d-e9.8%
d'e''4.4%
d2.0%
d-e7.9%
d'e''4.2%
«2.5%
"1.7%
"1.7%
Relative
sensitivity vs.
average adult
1
1.8
3.7
6.7
1.3
7.8
3.3
1.2
6.1
2.7
1.2
4.9
2.7
1.5
1.1
1.1
aThe body weight (70 kg) for the average adult is the default weight used by EPA for past regulatory determinations. All other body weights
are generated by the model.
6Maternal body weight was held at the value defined at the start of pregnancy (BW = 67.77 kg), and the "average adult" urinary clearance val-
ues as published by Merrill et al. (2005) were used.
cResults are based on using the maternal urinary clearance as published in Clewell et al. (2007), which equal about half of the average adult
clearance.
^Results are based on setting the maternal clearance rates of both perchlorate and iodide during lactation equal to that of the average adult.
Clewell et al. (2007) used an iodide clearance rate equal to that of an average adult, but a perchlorate rate only half that of the average adult.
«%RAIU inhibition given for the infant is provided based upon a value of urinary clearance scaled from the adult by BW% to approximate sur-
face-area scaling, and then multiplied by a rising fraction vs. age based on data (DeWoskin and Thompson, 2008) to reflect the reduction in glo-
merular filtration rates. Clewell et al. (2007) scaled urinary clearance by BW° 75, rather than adjusting based on GFR.
These %RAIU inhibition values are based on an internal dose to the breast-fed infant of 7 |ig/kg-day, the same as for the other subgroups.
Maternal dose rates lower than the POD are needed to provide 7 |ig/kg-day to the infant as shown in the table. These doses differ due to
changes in body weights and other PK factors with age.
a Because EPA typically uses a 10 kg child as a default assumption for its drinking water health advisories, the model was run for a child at
0.97 yr, the age at which the model-simulated body weight for a child is 10 kg.
hResults were obtained by setting urinary clearance constants for the older child equal to the average adult (Merrill et al., 2005) and scaling by
BW1.
'The dose equal to the POD is 7 |ig/kg-day which is 10-fold greater than the RfD. The predicted RAIU inhibition at the RfD would be less than
those shown in Table 1.
The modeling analysis may be used as
a tool to predict the impact of different
perchlorate drinking water
concentrations on RAIU across life
stages. Understanding the potential
impact of reducing perchlorate
concentrations may be especially
important for considering bottle-fed
infants for whom a major portion of the
diet may consist of water used to
rehydrate formula.
Another approach EPA is also
considering would be to not use the
PBPK modeling analysis to inform the
selection of the HRL for its regulatory
determination but instead apply the RfD
directly to the exposures of other
sensitive life stages to develop separate
HRLs for these life stages as described
in Section III.B.
4. Request for Comment on Alternative
Approaches
EPA Seeks Comments on the Following
Issues:
a. EPA requests comment on using the
PBPK model to evaluate the relative
sensitivity of the various life stages to
perchlorate exposure in drinking water.
b. EPA requests comment on the
utility of the PBPK model for predicting
the impact of different perchlorate
drinking water concentrations on
sensitive life stages to inform HRL
selection.
c. EPA requests suggestions for ways
to use the PBPK modeling analysis to
inform the regulatory determination for
perchlorate that are different from those
described in this notice or the October
10, 2008, notice.
B. Alternative HRLs Based Upon Body
Weight and Water Consumption of
Other Life Stages
1. Analysis and Interpretations From the
October 2008 FR Notice
In our October 2008 FR notice, EPA
requested comments on an HRL of 15
u,g/L to protect pregnant women and
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41887
their fetuses based upon the Agency's
RfD, recommended by the NRG, and the
following exposure estimates:
HRL = RfD x BW/DWI x RSC
Where:
RfD = Reference dose (0.7 |ig/kg/day)
BW = Body weight (70 kg, default value)
DWI = Drinking water intake (2 L/day,
default value)
RSC = Relative source contribution (62% for
pregnant women)
In calculating the HRL of 15 Ug/L,
EPA used adult default values for both
body weight (the mean body weight for
men and women, 70 kg) and drinking
water intake (84th percentile, 2 L/day).
The RSC is the percentage of the
reference dose remaining for drinking
water after other sources of exposure to
perchlorate have been considered (e.g.,
food). EPA used the pregnant women's
estimated 90th percentile perchlorate
intake from food to determine the RSC
of 62%. In past regulatory
determinations on most other
noncarcinogenic contaminants, EPA has
used an RSC default value of 20% for
screening purposes to estimate the HRL
when it has lacked adequate data to
develop empirical RSCs for those
contaminants (for sulfate and sodium
EPA did not use an RSC to determine
the HRL). For the October 2008 notice,
the Agency believed that sufficient
exposure data were available for
perchlorate to enable EPA to estimate a
better informed RSC and HRL that is
more appropriate for fetuses of pregnant
women (the most sensitive life stage
identified by the NRC). These exposure
data include the further analysis by EPA
of the Unregulated Contaminant
Monitoring Regulation (UCMR) data and
the Centers for Disease Control and
Prevention's (CDC's) National Health
and Nutrition Examination Survey
(NHANES) biomonitoring data, as well
as the Food and Drug Administration's
(FDA's) Total Diet Study (TDS) (73 FR
60269-72, October 10, 2008). The EPA
analysis provided a distribution of
exposure (not just a mean) specific to
almost 100 pregnant women who are
not likely to have been exposed to
perchlorate from their drinking water,
although it did not separate out iodine-
deficient pregnant women because of
data limitations. EPA estimated that for
90% of the pregnant women, exposure
to perchlorate from food is equal to, or
less than, 0.263 |o.g/kg/day (90th
percentile). This represents nearly 38%
of the RfD, leaving an RSC for water of
62%.
2. What Were the Key Issues Raised by
Public Commenters?
The comments EPA received
underscore the complexity of the
scientific issues and many were critical
of EPA's derivation of the HRL. Of those
that provided detailed comments, many
were concerned about the adequacy of
the HRL to address all sensitive life
stages (e.g., pre-term and full-term
infants). For example, a number of
commenters argued that the proposed
HRL is too high for infants because an
HRL of 15 |J.g/L would allow daily
exposures that are two to five times
higher than the RfD.
One commenter cites a March 8, 2006,
letter from the Children's Health
Protection Advisory Committee to the
EPA Administrator. The commenter
states, "* * * [T]he committee
emphasized the higher exposure of
infants to perchlorate and greater
susceptibility to serious negative effects
associated with perchlorate exposure.
Neither of these issues, however, was
given adequate consideration in the
Preliminary Determination."
Another commenter addresses EPA's
use of default values in deriving the
HRL stating, "* * * EPA continues to
use the obsolete default of 70 kg for
body weight and 2 L/day of water
consumption when these values
certainly do not apply to pregnant
women. These defaults are specifically
intended for the population in general,
and should be superseded by more
specific and appropriate values when
risk assessment is being conducted for
a defined subpopulation (U.S. EPA,
2004, 2005)."
3. Alternative Approaches for
Calculating HRLs
EPA agrees that reassessing exposure
assumptions and other life stages
warrants further consideration. The
NRC (2005) identified "the fetuses of
pregnant women who might have
hypothyroidism or iodide deficiency" as
"the most sensitive population," but
also identified infants and developing
children as additional "sensitive
populations." Infants and young
children have greater exposure to
contaminants in food and water because
of greater consumption of food and
water on a per unit body weight basis.
Therefore, these life stages may be the
most vulnerable populations when their
relative exposure is considered.
Therefore, EPA is considering
alternative approaches to deriving HRLs
by evaluating exposures at different life
stages. EPA is considering alternative
HRLs that are estimates of the maximum
concentration of perchlorate that can be
consumed in drinking water without an
individual's total perchlorate dose from
food and water exceeding the RfD.
EPA's Guidance on Selecting Age
Groups for Monitoring and Assessing
Childhood Exposures to Environmental
Contaminants (USEPA, 2005)
recommends the following 10 age
groups be considered in exposure
assessments for children.
• Less than 12 Months old: birth to <
1 month, 1 to < 3 months, 3 to < 6
months and 6 to < 12 months.
• Greater than 12 months old: 1 to <
2 years, 2 to < 3 years, 3 to < 6 years,
6 to < 11 years, 11 to < 16 years, and
16 to < 21 years.
EPA's Guidance for Risk
Characterization (USEPA, 1995)
recommends that when considering
exposure to use both high end (i.e., 90th
and 95th percentile) and central
tendency (average or median estimates)
descriptors to convey the variability in
risk levels experienced by different
individuals in the population.
Table 2 arrays the alternative HRLs at
the average 90th and 95th percentile
drinking water ingestion rates for each
of the 10 childhood life stages (as well
as for pregnant women and women of
child-bearing age, 15 to 44). The table
uses the life stage specific drinking
water intake data that are adjusted to
account for the body weight of the
individual. EPA's Child-Specific
Exposure Factors Handbook (USEPA,
2008f) recommends values for drinking
water ingestion rates for each of
recommended children's life stage based
on a study of drinking water ingestion
of the U.S. population by Kahn and
Stralka (2008). The study reports
ingestion estimates for "all individuals"
and for "consumers only." Estimates
reported for "all individuals" include
all survey participants regardless of
whether they consumed water during
the 2-day survey period. Ingestion
estimates for "consumers only" are
generated from only the respondents
who reported ingestion of drinking
water from a community water system
during the survey period. The authors
report that this group is often the
primary focus in analyses of risk due to
ingestion of water that may be
contaminated. Consequently, this is the
only group presented in Table 2.
In addition to identifying infants and
developing children as sensitive life
stages, as noted previously, the NAS
identified the fetuses of iodide deficient
pregnant women as the most sensitive
population (or life stage). To address
concerns that the default weight and
ingestion rates provided in the October
2008 notice do not apply to this group,
EPA has included an alternative HRL for
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Federal Register/Vol. 74, No. 159/Wednesday, August 19, 2009/Notices
this life stage in Table 2. This value is
calculated based on body weight and
drinking water ingestion information
specifically from pregnant women
(USEPA, 2004).
EPA notes that for six life stages in
Table 2 (birth to < 1 month, 1 to < 3
months, 3 to < 6 months, 16 to 18 years
and 18 to 21 years and for pregnant
women), the sample size used to
estimate some of the drinking water
ingestion rates (denoted in Table 2 by
foot note c) do not meet the minimum
data requirements as described in the
"Third Report on Nutrition Monitoring
in the United States" (LSRO, 1995).
However, these are the best available
data to characterize drinking water
ingestion for these specific life stages.
EPA also notes that these data clearly
show the trend that drinking water
mean ingestion rate on a per body
weight basis increases as the life stage
age decreases. To address this potential
concern regarding sample size for some
of these drinking water ingestion rates,
EPA also aggregated the three youngest
recommended age groups into one
category on Table 2 (birth to < 6
months) based on data from EPA
(USEPA, 2004). To address women of
childbearing age, EPA presents HRLs
calculated based upon drinking water
ingestion data for women ages 15 to 44.
To estimate dietary exposure to
perchlorate and to calculate RSCs, EPA
used data available from two studies
previously described by EPA, the FDA's
Total Diet Study (Murray et al, 2008)
and the NHANES-UCMR Analysis (73
FR 60269-73, October 10, 2008). In
cases where these studies did not
provide a dietary exposure estimate for
one of the recommended child-specific
life stages/age groups, EPA applied the
RSC calculated for the age group closest
to the age group of interest. This meant
that the RSCs for the age groups
between birth and 6 months, 59%, were
based on the mean dietary exposure
estimate for infants ages 6 through 11
months, 0.29 u,g/kg-day, derived from
FDA's Total Diet Study. We understand
that infant diets vary significantly
between birth and age 11 months and
that the TDS mean dietary perchlorate
exposure estimates for ages 6 through 11
months consider consumption of baby
foods that are not consumed by younger
infants (see http://www.fda.gov/Food/
FoodSafety/
FoodContaminantsAdulteration/
ChemicalContaminants/Perchlorate/
ucm077615.htm). Researchers from the
CDC (Schier et al., 2009) recently
published a study in which they
estimated exposures to perchlorate from
the consumption of infant formula. For
infants age 1 month, the researchers'
central tendency estimate of perchlorate
daily dose from consumption of bovine
milk-based infant formula with lactose
(the type of formula with the highest
concentrations of perchlorate) was also
0.29 u,g/kg-day, corresponding to an RSC
of 59%. Thus, EPA's RSC for young
infants, 59%, is supported through two
different estimates of central tendency
infant dietary perchlorate exposure.
TABLE 2—ALTERNATIVE HRLs AT THE AVERAGE, QOTH AND 95TH PERCENTILE DRINKING WATER INGESTION RATES FOR
VARIOUS LIFE STAGES
Life stage
Birth to < 1
month
1 to < 3 months
3 to < 6 months
Birth to < 6
months
6 to < 12
months
1 to < 2 years ...
2 to < 3 years ...
3 to < 6 years ...
6 to < 1 1 years
11 to < 1 6 years
1 6 to < 1 8 years
18 to < 21 years
Pregnant
Women8
Women Ages
15-44
RfD
(lig/kg-day)
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
RSCa
(percent)
59
59
59
59
59
44
44
60
71
84
80
80
C62
80
Mean
ingestion
rated
(mL/kg-day)b
137
119
80
95
53
27
26
24
17
13
12
13
c14
15
Alt HRL
(MS/L)
3
3
5
4
8
11
12
18
29
45
47
43
31
37
90th
Percentile
ingestion
rated
(mL/kg-day)b
C235
C228
148
184
112
56
52
49
35
26
24
29
C33
32
Alt HRL
(MS/L)
2
2
3
2
4
6
6
9
14
23
23
19
13
18
95th
Percentile
ingestion
rated
(mL/kg-day)b
C238
C285
C173
221
129
75
62
65
45
34
C32
C35
C43
39
Alt HRL
(MS/L)
2
1
2
2
3
4
5
6
11
17
18
16
10
14
aRSC calculated for nearest age range based on the mean dietary intake from TDS (see Table 5 at 73 FR 60275, October 10, 2008), RSC for
pregnant women and women ages 15^4 based on the 90th percentile dietary intake from NHANES-UCMR analysis (see Table 6 at 73 FR
60276, October 10, 2008).
b Drinking Water Ingestion Rates for consumers only in Community Water Systems taken from EPA's "Child-Specific Exposure Factors Hand-
book" (USEPA, 2008e). Except for values for infants from birth to 6 months, which are taken from Tables 5.2.A2 of EPA's "Estimated Per Capita
Water Ingestion and Body Weight in the United States—An Update" (USEPA, 2004), and for Pregnant Women and Women Ages 15-44 which
are taken from Table 6.2.A2 of EPA's "Estimated Per Capita Water Ingestion and Body Weight in the United States—An Update" (USEPA,
2004).
cThe sample sizes for the estimates of ingestion rates for these life stages do not meet the minimum data requirements as described in the
"Third Report on Nutrition Monitoring in the United States" (LSRO, 1995).
d Ingestion rate is adjusted for the self-reported body weights from the CFSII.
8The most sensitive population identified by the NRC are the fetuses of pregnant women who might have hypothyroidism or iodide deficiency.
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41889
4. Request for Comments
EPA Seeks Comments on the Following
Issues:
a. EPA requests comment on whether
the alternative HRLs described in this
notice appropriately take into account
specific and appropriate exposure
values for all potentially sensitive life
stages, including infants, children and
the fetuses of pregnant women (rather
than the 70 kg body weight and 2 liter
per day consumption used for past
regulatory determinations).
b. EPA requests comment on the
alternative HRLs in Table 2 and which
of these values would be appropriate
levels of health concern against which
to compare the levels of perchlorate
found in public water systems.
c. EPA requests comment on whether
EPA used the best available and most
appropriate data to estimate alternative
HRLs in Table 2. EPA specifically
requests comment on the drinking water
ingestion rates in Table 2 (denoted by
footnote c) where the sample size does
not meet the minimum data
requirements as described in the "Third
Report on Nutrition Monitoring in the
United States" (LSRO, 1995). Does
aggregating life stages (birth to 6
months, and women ages 15—44)
address sample size limitation and still
provide an accurate representation of
the exposure to the most vulnerable life
stages?
d. EPA requests comment on the
merits of the approach described here of
deriving HRLs for sensitive life stages
based on the RfD combined with the life
stage specific exposure data and
whether there are other approaches that
may be useful for deriving HRLs.
C. Occurrence Analysis
1. Occurrence Analysis in the October
2008 Federal Register Notice
In the October 2008 FR notice, EPA
presented information on the drinking
water occurrence of perchlorate. The
data source was EPA's UCMR 1 and the
samples were collected between 2001
and 2005. A total of 34,331 samples
were collected from 3,865 public water
systems. EPA found that 1.9% of the
samples (637 out of 34,331) had
perchlorate at, or above, the minimum
reporting level (MRL = 4 u,g/L) and that
4.1% of the systems (160 out of 3,865
systems) reported perchlorate at, or
above, the MRL in at least one sample.
The average perchlorate concentration
among systems that detected perchlorate
was 9.85 u,g/L and the median was 6.40
u,g/L.
Table 3 presents EPA's estimates of
the population served by water systems
for which the highest reported
perchlorate concentration was greater
than various threshold concentrations
ranging from 4 u,g/L (MRL) to 25 u,g/L.
The fourth column presents a high end
estimate of the population served
drinking water above a threshold. This
column presents the total population
served by those drinking water systems
in which at least one sample was found
to contain perchlorate above the
threshold concentration. EPA considers
this a high-end estimate because it is
based upon the assumption that the
entire system population is served water
from the entry point that had the highest
reported perchlorate concentration. In
fact, many water systems have multiple
entry points into which treated water is
pumped for distribution to their
consumers. For the systems with
multiple entry points, it is unlikely that
the entire service population receives
water from the one entry point with the
highest single concentration. Therefore,
EPA also is providing a less
conservative estimate of the population
served water above a threshold in the
fifth column in Table 3. EPA developed
this estimate by assuming the
population was equally distributed
among all entry points. For example, if
a system with 10 entry points serving
200,000 people had a sample from a
single entry point with a concentration
at or above a given threshold, EPA
assumed that the entry point served
one-tenth of the system population, and
added 20,000 people to the total when
estimating the population in the last
column of Table 3. This approach may
provide either an overestimate or an
underestimate of the population served
by the affected entry point. In contrast,
in the example above, EPA added the
entire system population of 200,000 to
the more conservative population
served estimate in column 4, which is
most likely an overestimate. EPA noted
that the population estimates in Table 3
are for people at all life stages and
estimated that at any one time, 1.4
percent of the population in Table 3 are
pregnant women based upon data from
the U.S. Census Bureau.
TABLE 3—UCMR 1 OCCURRENCE AND POPULATION ESTIMATES FOR PERCHLORATE ABOVE VARIOUS THRESHOLDS
Thresholds"
4 uq/L
5 uq/L
7 uq/L
10 ug/L
12 ug/L
15 ug/L
17 ug/L
20 ug/L
25 uq/L
PWSs with at least 1 detection >
threshold of interest
4 01%
(155 of 3 865)
3 16%
(122 of 3 865)
2.12%
(82 of 3 865)
1.35%
(52 of 3 865)
1.09%
(42 of 3 865)
0.80%
(31 of 3,865)
0.70%
(27 of 3,865)
0.49%
(19 of 3,865)
0 36%
(14 of 3.8651
PWS entry or sample points with at
least 1 detection > threshold of
interest15
2 48%
(371 of 14 987)
1 88%
(281 of 14 987)
1.14%
(171 of 14 987)
0.65%
(97 of 1 4 987)
0.42%
(63 of 1 4 984)
0.29%
(44 of 14,987)
0.24%
(36 of 14,987)
0.16%
(24 of 14,987)
0 12%
(18 of 14.9871
Population served
by PWSs with at
least 1 detection >
threshold of
interest c
16 6 Me
14 6 M
7.2 M
5.0 M
3.6 M
2.0 M
1.9 M
1.5 M
1 0 M
Population
estimate for entry
or sample points
having at least 1
detection >
threshold of
interest"1
5 1 M
4 0 M
2.2 M.
1.5 M.
1.2 M.
0.9 M.
0.8 M.
0.7 M.
0 4 M
Footnotes:
a All occurrence measures in this table were conducted on a basis reflecting values greater than the listed thresholds.
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Federal Register/Vol. 74, No. 159/Wednesday, August 19, 2009/Notices
bThe entry/sample-point-level population served estimate is based on the system entry/sample points that had at least 1 analytical detection
for perchlorate greater than the threshold of interest. The UCMR 1 small system survey was designed to be representative of the nation's small
systems, not necessarily to be representative of small system entry points.
cThe system-level population served estimate is based on the systems that had at least 1 analytical detection for perchlorate greater than the
threshold of interest.
d Because the population served by each entry/sample point is not known, EPA assumed that the total population served by a particular sys-
tem is equally distributed across all entry/sample points. To derive the entry/sample point-level population estimate, EPA summed the population
values for the entry/sample points that had at least 1 analytical detection greater than the threshold of interest.
8 This value does not include the population associated with 5 systems serving 200,000 people that measured perchlorate at 4 |ig/L in at least
one sample because the table only shows population estimates greater than each of the thresholds in the first column.
The Agency also evaluated
supplemental drinking water
monitoring data for perchlorate in
California and Massachusetts. EPA
believes these States' monitoring results
are generally consistent with the results
collected by EPA under UCMR 1.
Perchlorate occurrence analysis from
California and Massachusetts can be
found online at: http://
www2.cdph.ca .gov/certlic/
drinkingwater/Pages/Perchlora te.a spx
and http://www.mass.gov/dep/water/
drinking/percinfo.htm# sites
respectively.
2. What Were the Key Issues Raised by
Commenters?
EPA received comments on the
proposed decision not to regulate
perchlorate based on the population
exposed above the HRL. Some
comments objected to the Agency's
proposed HRL as being "inappropriately
high" thereby "greatly reducing the size
of the population predicted to be
exposed at a level of public health
concern * * * and significantly
minimizing the need for regulation of
perchlorate from an occurrence
standpoint."
One commenter believes that,
"Approximately 4% of public water
supplies serving 17 million Americans
would be in exceedance of an HRL
between 2 and 6 u,g/L. This is 15 million
more at risk individuals than currently
estimated by the Agency."
Another commenter believes that at
an HRL of 2 u,g/L, 16.6 million would
be exposed, and another commenter
states that if EPA set the HRL at 5 u.g/
L, then 5-7 times more individuals
would be exposed above the HRL than
at 15 u,g/L.
However, one commenter points out
that, "An MCL of 2 u,g/L could impact
approximately 4% of public water
systems nationally. At this level,
regional impacts in California and Texas
would be greater due to the higher
geographical concentration of detections
in those states. Yet it should be noted
that water systems in Massachusetts,
New Jersey and California have already
established regulatory limits of 2 u,g/L,
5 u,g/L and 6 u,g/L respectively, thereby
capping the population exposure
potential from community drinking
water sources in those States."
3. Numbers of Systems and Populations
That Would Be Exposed at Levels
Exceeding the Alternative Approaches
the Agency Is Considering
EPA plans to use the UCMR 1
perchlorate data to conduct analyses to
estimate the number of systems and
populations served by systems that
would be exposed to the various
alternative HRL concentrations of
perchlorate. Estimates will be made of
the populations served by systems for
which the highest reported perchlorate
concentration exceeds the various
threshold concentrations ranging from 1
u,g/L to 25 u,g/L. One limitation to the
UCMR 1 data is that the perchlorate
analytical method MRL is 4 u,g/L; only
perchlorate sample detections greater
than or equal to 4 u,g/L can be
dependably quantified and reported.
Any perchlorate sample concentration
with a value between 0 and 4 u,g/L is
recorded in the UCMR 1 data as a "non-
detection." Therefore, to estimate
perchlorate occurrence relative to
concentrations both above and below
the MRL of 4 u,g/L, while fully using all
perchlorate detection and non-detection
data, it is necessary to estimate
occurrence using modeling techniques
EPA is considering using a Bayesian
hierarchical model (a form of
probabilistic model that uses maximum
likelihood estimation techniques) to
estimate perchlorate occurrence and to
estimate the uncertainty and variability
of those occurrence estimates. For this
modeling effort, EPA could use the basic
assumption that the national
distribution of perchlorate sample
concentrations can be modeled as a
lognormal distribution. The lognormal
distribution is a fundamental
probability distribution that is used
commonly and effectively to
characterize environmental contaminant
occurrence. The basic characteristic of a
lognormal distribution is that the
logarithms of the values being evaluated
(in this case, the perchlorate
concentrations of UCMR 1 samples of
drinking water) are normally
distributed. One property of the
lognormal distribution that makes it
particularly well-suited to describing
phenomena like environmental
contaminant occurrence data is that it is
bounded by zero on the low end and it
reflects a "right-skewed" distribution—
that is, it has a tail in the upper end—
that is consistent with having a small
proportion with relatively high values.
The Bayesian model could estimate
the number of public water systems, and
populations served by systems, with at
least one estimated sample detection
greater than 1, 2, 3, 4, 5, 7, 10, 12, 15,
17, 20, and 25 u,g/L. EPA notes that
systems or entry/sample points with at
least one detect above the threshold may
not expose the population to this level
at all times. At any particular time,
perchlorate levels may be lower or
higher than the highest estimated
sample detection. However, EPA
believes this approach more closely
reflects the short term exposure during
life stages of concern (i.e., fetuses, pre-
term newborns, infants and young
children) than does the estimated mean
concentration of perchlorate at a system.
EPA underscores the fact that the
estimated total population exposed at
thresholds that lie below the perchlorate
MRL of 4 u,g/L would be equal to, if not
greater than, the corresponding high end
estimate of 16.8 million people. To
estimate the portion of the total
population that is at a childhood life
stage potentially exposed at these
thresholds, EPA could use U.S. Census
data as it did in the October 2008 FR
notice to estimate the number of
pregnant women potentially exposed
above the HRL and could also estimate
the number of infants and children
potentially exposed above the HRL
Perchlorate monitoring data from the
State of Massachusetts could be used to
help characterize the distribution of
very low perchlorate concentration
occurrence. Massachusetts monitoring
uses a modified version of the EPA
laboratory analytical method for
perchlorate that has a MRL of 1 u,g/L.
This is the only known, state-wide
monitoring program that uses an
analytical method with an MRL lower
than 4 u,g/L. Bayesian hierarchical
modeling can use the Massachusetts
data to improve the model estimates in
the lower concentration ranges.
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41891
4. Request for Comment on Alternative
Approaches
EPA Seeks Comments on the Following
Issues:
a. EPA requests comment on the
potential use of a Bayesian model to
estimate the number of public water
systems, and populations served by
such systems, with at least one
estimated sample detection greater than
1, 2, 3, 4, 5, 7, 10, 12, 15, 17, 20, and
25 ug/L.
b. EPA requests comment on using
U.S. Census data to estimate the
portions of the population that are in
the sensitive life stage at any one time.
c. EPA requests comment on how the
Agency should account for the variation
of perchlorate levels over time in public
water systems. EPA believes that
estimating the number of systems, entry
points and populations with at least one
detection above the HRL is appropriate
for the perchlorate regulatory
determination because a single quarterly
or semi-annual sample more closely
reflects the short term exposure during
life stages of concern (i.e., fetuses, pre-
term newborns, infants and young
children). However, EPA requests
comment on whether the Agency should
consider other approaches such as
estimating the number of systems, entry
points and populations with two or
more detections above HRL or some
other approach.
IV. Consideration of Studies Published
Since EPA Adopted the NAS RfD for
Perchlorate
EPA's preliminary regulatory
determination is based on NRC's (NRC,
2005) recommendation to use data from
the Greer et al. (2002) study as the basis
for the perchlorate RfD/risk assessment.
Since the publication of the NRC
report, researchers have investigated
perchlorate occurrence in humans by
analyzing for perchlorate in urine and
breast milk—such biomonitoring data
has the potential to better inform EPA's
analysis of exposure to perchlorate
through food and water and to provide
insight into the possible interactions of
other physiologic conditions (e.g.,
iodine deficiency) with perchlorate
ingestion. EPA's preliminary regulatory
determination described the
consideration of these studies, many of
which were published after the NRC
report (including, but not limited to,
Blount et al. (2006 and 2007),
Steinmaus et al. (2007), and Amitai et
al. (2007)) (73 FR 60267-68, October 10,
2008).
CDC researchers published two
biomonitoring papers using CDC's
2001-2002 NHANES data—the first
study measured perchlorate in urine
(Blount et al., 2006) and the second
examined the relationship between
urinary perchlorate and thyroid
hormone levels (Blount et al., 2007). In
the urinary biomonitoring study, the
authors found perchlorate in all samples
tested (2,820 survey participants ages
six and older) and estimated a total
daily perchlorate dose for adults (doses
for children were not calculated). The
median dose was about one tenth (0.066
ug/kg/day) of the RfD, while the 95th
percentile dose was about one third of
the RfD (0.234 ug/kg/day). In the second
study, which examined the relationship
between urinary levels of perchlorate
and blood serum levels of thyroid
hormones, Blount et al. (2007) found
that for women with low iodine levels
(urinary iodide levels less than 100 ug/
L) urinary perchlorate is associated with
a decrease in (a negative predictor for)
T4 levels and an increase in (a positive
predictor for) thyroid stimulating
hormone levels. The perchlorate
exposures at which this association was
observed are lower than anticipated
based on other studies. The study
authors indicated that further research
needs to be performed to confirm these
findings. The subsequent Steinmaus
(2007) analysis of the same NHANES
2001-2002 epidemiological data
concluded that thiocyanate in tobacco
smoke and perchlorate interact in
affecting the thyroid function in low-
iodine women. The Amitai et al. study
assessed thyroid hormone (thyroxine)
values in newborns in different
perchlorate exposure groups (low, high
and very high) and found no significant
differences.
In studies analyzing breast milk for
perchlorate, Pearce et al. (2007) and
Kirk et al. (2005, 2007) all found
perchlorate in study samples. The
objective of the Pearce et al. (2007)
study was "to determine whether breast
milk iodine concentrations in Boston-
area women are adequate for infant
nutrition, and whether breast milk
iodine concentrations may be associated
with environmental perchlorate or
cigarette smoke exposure." Pearce et al.
(2007) did not find a significant
correlation with either breast milk
perchlorate or urinary perchlorate levels
with breast milk iodine concentrations.
The objective of the Kirk et al. (2005)
study was to determine the amount of
perchlorate to which children are
exposed by measuring perchlorate and
iodide levels in cow and human breast
milk and then comparing these numbers
to corresponding levels of perchlorate in
drinking water in the area. Kirk et al.
(2005) did not find a correlation
between the levels of perchlorate in
breast milk and perchlorate in drinking
water, but speculated that there was a
correlation between higher levels of
perchlorate and lower levels of iodine in
breast milk. The objective of the Kirk et
al. (2007) study was to determine the
variability of perchlorate, thiocyanate,
and iodide in breast milk in serially
collected samples (6 samples on each of
the 3 study days) involving 10 women.
The authors concluded that "Iodine
intake may be inadequate in a
significant fraction of this study
population. Perchlorate and thiocyanate
appear to be common in human milk.
The role of these chemicals in reducing
breast milk iodide is in need of further
investigation."
Blount et al. (2007) suggested breast
milk as an excretion pathway and
Dasgupta et al. (2008) compared a
woman's daily intake of iodine and
perchlorate with the concentrations of
each in her breast milk. The Dasgupta et
al. study found that a higher proportion
of perchlorate enters the breast milk
compared with a small proportion of
iodine.
Of those commenters that provided
detailed comments to the October 2008
FR notice, many commenters believe
that EPA's RfD is not adequately
protective of human health. One
commenter stated that "[T]he EPA
reference dose for perchlorate is based
on data from Greer et al. (2002) that
observed the inhibition of radioiodide
uptake. Ginsberg and Rice (2005)
identified several problems with the
Greer et al. study that suggest the need
for reevaluation of the value that serves
as the foundation for regulatory
decision-making," and that, "* * * the
results of the Blount study more closely
reflect our understanding of the
biological and toxicological processes
pertaining to thyroid homeostasis, both
in terms of thyroid hormone variability
and the role of iodine." The commenter
"[Sjtrongly recommends that the CDC
data analyzed in the study of Blount et
al. (2006) and Blount et al. (2007) be
used as the basis for the derivation of a
new reference dose."
Other commenters agree, stating that
the use of the Greer et al. (2002) study
"* * * is based on a limited clinical
study of short duration and small
sample size not representative of the
variability in the human population,"
and the "[U]se of these limited data to
calculate a regulatory trigger level has
been widely criticized as inadequate
* * * and no longer reflects the best
available data."
Another commenter believes that
"[Additional important data on
pregnant women and their offspring
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Federal Register/Vol. 74, No. 159/Wednesday, August 19, 2009/Notices
have become available since the time of
development of the EPA RfD in 2005
which would necessitate a
reconsideration of the existing value
* * * in addition EPA has discussed
other data relevant to deriving an
updated RfD in this Federal Register
notice including Amitai et al., 2007,
Blount et al., 2006, and studies
discussing PBPK models."
One commenter concludes by stating,
"* * * [T]hat EPA has based its
argument for not regulating perchlorate
contamination in public water systems
on a literature that is both limited and
ill focused. We believe that EPA has not
performed a sufficiently 'thorough
review' of the literature, that it has
omitted important information, and that
it has failed to perform its due diligence
in the interpretation and analysis of the
information that it did present. To
correct this, EPA must employ the CDC
study (Blount et al., 2006a) as the point
of departure for RfD determination, and
must focus on the neonate and infant as
the most sensitive population."
One commenter does not believe that
additional analysis is warranted and
that EPA should issue a final
determination as soon as possible,
stating that "EPA has an extraordinary
wealth of comprehensive, authoritative
scientific information relating to
perchlorate's health effects,
supplemented by extensive occurrence
and exposure data. The Agency is
therefore exceptionally well-positioned
to issue a well-considered regulatory
determination." The commenter
continues by stating,
* * * EPA has ample scientific and
technical data to make a final determination
on or before the planned date of December
2008 * * *. [P]erchlorate is one of the most
well-studied chemicals with detailed
information on the mechanism of action,
dose-response, and health effects. This issue
also is not new. EPA released its first draft
risk assessment on perchlorate in 1998,
followed by a second in 2002. The 2005 NAS
report was a comprehensive review of the
science. The animal and human studies that
have been published since the NAS report
reduce the uncertainty and reinforce the NAS
panel's finding that there will not be any
adverse health effects from perchlorate at
environmentally-relevant concentrations.
New studies published since the NAS
report increase the weight of evidence that
the current RfD protects human health
including the most sensitive members of our
population. In addition, testimony by
Congressional members and witnesses alike
have discussed the lengthy amount of time
that EPA has spent studying the health
effects, urging the agency to issue a
determination as soon as practicable. We join
them in urging EPA to issue the final
determination promptly.
An additional key scientific issue was
raised by EPA's OIG in the report
released for public comment "OIG
Scientific Analysis of Perchlorate
(External Review Draft)" (EPA, 2008g).
The report states,
The OIG Analysis concludes that a single
chemical risk assessment of perchlorate is
not sufficient to assess and characterize the
combined human health risk from all four
NIS stressors, (i.e., thiocyanate, nitrate,
perchlorate and lack of iodide) and that
* * * Only a cumulative risk assessment can
fully characterize the nature and sources of
risk affecting this public health issue.
Furthermore, a cumulative risk assessment
allows an informed environmental decision
to be made on how to mitigate the risk
effectively.
The report goes on to say,
Potentially lowering the perchlorate
drinking water limit from 24.5 ppb to 6 ppb
does not provide a meaningful opportunity to
lower the public's risk. By contrast,
addressing moderate and mild iodide
deficiency occurring in about 29% of the U.S.
pregnant and nursing population appears to
be the most effective approach of increasing
TIU [total iodide uptake] to healthy levels
during pregnancy and nursing, thereby
reducing the frequency and severity of
permanent mental deficits in children.
The draft report, and comments
submitted by EPA's Office of Water and
Office of Research and Development,
can be found in the Docket to this
notice.
EPA agrees that additional important
data have become available since the
RfD was derived in 2005. However, EPA
has evaluated the new data and has
decided to make the regulatory
determination based upon the current
RfD. EPA will continue to evaluate any
new perchlorate data to determine its
relevance to the regulatory
determination in accordance with the
SDWA.
V. Next Steps
The Agency will consider the
information and comments submitted in
response to this supplemental notice, as
well as comments received on the
October 10, 2008, FR notice, and all
peer review comments before issuing a
final regulatory determination for
perchlorate and intends to do so as
expeditiously as possible. EPA believes
that the alternative analyses presented
in this notice could lead the Agency to
make a determination to regulate
perchlorate.
VI. References
Amitai Y, Winston G, Sack }, Wasser }, Lewis
M, Blount BC, Valentin-Blasini L, Fisher
N, Israeli A, and Leventhal A. (2007).
Gestational exposure to high perchlorate
concentrations in drinking water and
neonatal thyroxine levels. Thyroid. 17(9):
843-850.
Blount, B.C., J.L. Pirkle, J.D. Osterloh, L.
Valentin-Blasini, and K.L. Caldwell.
2006. Urinary perchlorate and thyroid
hormone levels in adolescent and adult
men and women living in the United
States. Environmental Health
Perspectives. Vol. 114, No. 12. pp. 1865-
1871.
Blount, B.C., L. Valentin-Blasini, J.D.
Osterloh, J.P. Mauldin, and J.L. Pirkle.
2007. Perchlorate Exposure of the US
Population, 2001-2002. /. Exposure Sci.
Environ. Epidemiol. (2007) 17, 400^407.
Dasgupta, P.K., A.B. Kirk, J.V. Dyke, and
S.I. Ohira. 2008. Intake of Iodine and
Perchlorate Excretion in Human Milk.
Environ. Sci. Technol. Advance online
publication accessed September 18,
2008.
DeWoskin R. and C. Thompson. 2008.
Renal clearance parameters for PBPK
model analysis of early lifestage
differences in the disposition of
environmental toxicants. Regul Toxicol
Pharmacol 2008 Jun;51(l):66-86.
Ginsberg G, Rice D, 2005. The NAS
Perchlorate Review: Questions Remain
about the Perchlorate RfD. Environ
Health Perspectives 113(9):1117-1119.
Greer, M.A., G. Goodman, R.C. Pleuss, and
S.E. Greer. 2002. Health effect
assessment for environmental
perchlorate contamination: the dose
response for inhibition of thyroidal
radioiodide uptake in humans. Environ
Health PerspectVol. 110. pp. 927-937.
Kahn, H.D., and K. Stralka. 2008. Estimated
daily average per capita water ingestion
by child and adult age categories based
on USDA's 1994-1996 and 1998
continuing survey of food intakes by
individuals. Journal of Exposure Science
and Environmental Epidemiology (2009)
19(4):396-J04.
Kirk, A.B., P.K. Martinelango, K. Tian, A.
Dutta, E.E. Smith, and P.K. Dasgupta.
2005. Perchlorate and iodide in dairy
and breast milk. Environmental Science
and Technology. Vol. 39, No. 7. pp.
2011-2017.
Kirk, A.B., J.V. Dyke, C.F. Martin, and P.K.
Dasgupta. 2007. Temporal patterns in
perchlorate, thiocyanate and iodide
excretion in human milk. Environ Health
Perspect Online Vol. 115, No. 2. pp. 182-
186.
Life Sciences Research Office, Federation
of American Societies for Experimental
Biology Prepared for the Interagency
Board for Nutrition Monitoring and
Related Research. 1995. Third Report on
Nutrition Monitoring in the United
States: Volume 1. U.S. Government
Printing Office, Washington DC.
Murray, C.W III, S.K. Egan, H. Kim, N.
Beru, P.M. Bolger. 2008. US Food and
Drug Administration's Total Diet Study:
Dietary Intake of Perchlorate and Iodine.
Journal of Exposure Science and
Environmental Epidemiology, advance
online publication January 2, 2008.
National Research Council (NRG). 2005.
Health Implications of Perchlorate
Ingestion. National Academies Press,
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Federal Register/Vol. 74, No. 159/Wednesday, August 19, 2009/Notices
41893
Board on Environmental Studies and
Toxicology. January 2005. 276 p.
Pearce, E.N., A.M. Leung, B.C. Blount, H.R.
Bazrafshan, X. He, S. Pino, L. Valentin-
Blasini, L.E. Braverman. 2007. Breast
milk iodine and perchlorate
concentrations in lactating Boston-area
women. / Clin Endocrin Metab Vol. 92,
No. 5, pp. 1673-1677
Schier, J.G., A.F. Wolkin, L.Valentin-
Blasini, M.G. Belson, S.M. Kieszak, C.S.
Rubin, B.C. Blount. Journal of Exposure
Science and Environmental
Epidemiology, advance online
publication 18 March 2009; doi: 10.10387
jes.2009.18.
Steinmaus, C., M.D. Miller, R. Howd. 2007.
Impact of smoking and thiocyanate on
perchlorate and thyroid hormone
associations in the 2001-2002 National
Health and Nutrition Examination
Survey. Environ Health Perspect
115(9):1333-8.
USEPA. 1995. Guidance for Risk
Characterization. Science Policy Council,
February, 1995.
USEPA. 2004. Estimated Per Capita Water
Ingestion and Body Weight in the United
States—An Update. Office of Science
and Technology, Washington, DC; EPA/
822/R-00-001.
USEPA. 2005. Guidance on Selecting Age
Groups for Monitoring and Assessing
Childhood Exposures to Environmental
Contaminants. National Center for
Environmental Assessment, Washington,
DC; EPA/630/P-03/003F.
USEPA. 2008a. Drinking Water:
Preliminary Regulatory Determination on
Perchlorate, Federal Register, Vol. 73,
No. 198. p. 60262, October 10, 2008.
USEPA. 2008b. Inhibition of the Sodium-
Iodide Symporter by Perchlorate: An
Evaluation of Lifestage Sensitivity Using
Physiologically-Based Pharmacokinetic
(PBPK) Modeling. Office of Research and
Development, Washington, DC; EPA/
600/R-08/106A.
USEPA. 2008c. External letter peer review
of EPA's draft report, Inhibition of the
Sodium-Iodide Symporter by
Perchlorate: An Evaluation of Lifestage
Sensitivity Using Physiologically-based
Pharmacokinetic (PBPK) Modeling.
National Center for Environmental
Assessment, Washington, DC; November
12, 2008.
USEPA. 2008d. Interim Drinking Water
Health Advisory for Perchlorate. Office
of Science and Technology, Washington,
DC; EPA 822-R-08-025.
USEPA. 2008e. Comment Response
Summary Report, Peer Review of
Drinking Water Health Advisory for
Perchlorate. Office of Science and
Technology, Washington, DC; December
2008.
USEPA. 2008f. Child-Specific Exposure
Factors Handbook. National Center for
Environmental Assessment, Washington,
DC; EPA/600/R-06/096F.
USEPA. 2008g. Scientific Analysis of
Perchlorate (External Review Draft).
Office of Inspector General, Washington,
DC; Assignment No. 2008-0010.
Dated: August 5, 2009.
Peter S. Silva,
Assistant Administrator, Office of Water.
[FR Doc. E9-19507 Filed 8-18-09; 8:45 am]
BILLING CODE 6560-50-P
ENVIRONMENTAL PROTECTION
AGENCY
[EPA-HQ-OPPT-2009-0496; FRL-8429-5]
National Advisory Committee for Acute
Exposure Guideline Levels for
Hazardous Substances; Notice of
Public Meeting
AGENCY: Environmental Protection
Agency (EPA).
ACTION: Notice.
SUMMARY: A meeting of the National
Advisory Committee for Acute Exposure
Guideline Levels for Hazardous
Substances (NAC/AEGL Committee)
will be held on September 9-11, 2009,
in Research Triangle Park, NC. At this
meeting, the NAC/AEGL Committee will
address, as time permits, the various
aspects of the acute toxicity and the
development of Acute Exposure
Guideline Levels (AEGLs) for the
following chemicals: Cadmium;
carbofuran; carbon dioxide; dichlorovos;
dicrotophos; dimethyl phosphate;
fenamiphos; gasoline; hydrogen
selenide; lead; methamidophos; methyl
iodide; mevinphos; monocrotophos;
nerve agent GB; phosgene;
phosphamidon; red phosphorus; ricin;
tetrachloroethylene; 1,1,1-
trichloroethylene; and
trimethylphosphite.
DATES: A meeting of the NAC/AEGL
Committee will be held from 10 a.m. to
5 p.m. on September 9, 2009; from 8
a.m. to 5 p.m. on September 10, 2009;
and from 8 a.m. to noon on September
11, 2009.
ADDRESSES: The meeting will be held at
the EPA Main Campus, 109 T.W.
Alexander Dr., Research Triangle Park,
NC 27711.
FOR FURTHER INFORMATION CONTACT: Paul
S. Tobin, Designated Federal Officer
(DFO), Risk Assessment Division
(7403M), Office of Pollution Prevention
and Toxics, 1200 Pennsylvania Ave.,
NW., Washington, DC 20460-0001;
telephone number: (202) 564-8557; e-
mail address: tobin.paul@epa.gov.
To request accommodation of a
disability, please contact the DFO,
preferably at least 10 days prior to the
meeting, to give EPA as much time as
possible to process your request.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
This action is directed to the public
in general. This action may be of
particular interest to anyone who may
be affected if the AEGL values are
adopted by government agencies for
emergency planning, prevention, or
response programs, such as EPA's Risk
Management Program under the Clean
Air Act and Amendments Section 112r.
It is possible that other Federal agencies
besides EPA, as well as State agencies
and private organizations, may adopt
the AEGL values for their programs. As
such, the Agency has not attempted to
describe all the specific entities that
may be affected by this action. If you
have any questions regarding the
applicability of this action to a
particular entity, consult the person
listed under FOR FURTHER INFORMATION
CONTACT.
B. How Can I Get Copies of this
Document and Other Related
Information?
1. Docket. EPA has established a
docket for this action under docket
identification (ID) number EPA-HQ-
OPPT-2009-0496. All documents in the
docket are listed in the docket index
available at http://www.regulations.gov.
Although listed in the index, some
information is not publicly available,
e.g., Confidential Business Information
(CBI) or other information whose
disclosure is restricted by statute.
Certain other material, such as
copyrighted material, will be publicly
available only in hard copy. Publicly
available docket materials are available
electronically at http://
www.regulations.gov, or, if only
available in hard copy, at the OPPT
Docket. The OPPT Docket is located in
the EPA Docket Center (EPA/DC) at Rm.
3334, EPA West Bldg., 1301
Constitution Ave., NW., Washington,
DC. The EPA/DC Public Reading Room
hours of operation are 8:30 a.m. to 4:30
p.m., Monday through Friday, excluding
legal holidays. The telephone number of
the EPA/DC Public Reading Room is
(202) 566-1744, and the telephone
number for the OPPT Docket is (202)
566-0280. Docket visitors are required
to show photographic identification,
pass through a metal detector, and sign
the EPA visitor log. All visitor bags are
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and subject to search. Visitors will be
provided an EPA/DC badge that must be
visible at all times in the building and
returned upon departure.
2. Electronic access. You may access
this Federal Register document
electronically through the EPA Internet
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