[Federal Register Volume 74, Number 159 (Wednesday, August 19, 2009)]
[Notices]
[Pages 41883-41893]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-19507]


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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.

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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:
    <bullet> http://www.regulations.gov: Follow the online instructions 
for submitting comments.
    <bullet> Mail: Water Docket, Environmental Protection Agency, 
Mailcode: 2822T, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    <bullet> 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 I.A 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 <a href="/cdn-cgi/l/email-protection#ceacbbbca0abbda1a0e0abbca7ad8eabbeafe0a9a1b8"><span class="__cf_email__" data-cfemail="0b697e79656e786465256e7962684b6e7b6a256c647d">[email protected]</span></a>. For general information, 
contact the EPA Safe Drinking Water Hotline at (800) 426-4791 or e-
mail: <a href="/cdn-cgi/l/email-protection#f79f98839b9e9992da84938096b7928796d9909881"><span class="__cf_email__" data-cfemail="ee86819a8287808bc39d8a998fae8b9e8fc0898198">[email protected]</span></a>.

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
[mu]g--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.

[[Page 41884]]

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 CCL1 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 \1\ 
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.
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    \1\ On November 12, 2008, EPA extended the comment period for 15 
days regarding EPA's preliminary regulatory determination for 
perchlorate.
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    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.1, 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 (NRC) on 
perchlorate. The NRC previously studied perchlorate health implications 
from March, 2003 until they issued their report in January, 2005 (NRC, 
2005). EPA has compiled and evaluated additional scientific studies 
relevant to perchlorate health effects and exposure available since 
publication of the 2005 NRC 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 
NRC would unnecessarily delay regulatory decision making for 
perchlorate. Therefore, EPA is not, at present, planning to request 
additional NRC 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 NRC 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\
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    \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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    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 [mu]g/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

[[Page 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 (NRC, 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 [micro]g/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 (OIG) 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 [mu]g/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

[[Page 41886]]

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
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                                                                                                     Relative
                                                            Dose \i\  ([mu]g/kg-       RAIU         sensitivity
     Population or life stage          Body weight (kg)              d)             inhibition      vs. average
                                                                                                       adult
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Average Adult \a\.................  70...................  7....................            1.6%               1
Woman (child-bearing age).........  68...................  7....................        \b\ 3.0%             1.8
Pregnant woman and Fetus            Mom: 79..............  7....................        \c\ 6.1%             3.7
 (Gestation Week 40).               Fetus: 3.5...........  .....................         \c\ 11%             6.7
Lactating woman and Breast-fed      Mom: 74..............  7....................        \d\ 2.1%             1.3
 infant (7 d).                      Infant: 3.6..........  Mom = 7..............     \d,e\ 12.5%             7.8
                                                           Infant = 7...........    \d,e,f\ 5.4%             3.3
                                                           (Mom = 2.7)..........
Lactating woman and Breast-fed      Mom: 73..............  7....................        \d\ 2.0%             1.2
 infant (30 d).                     Infant: 4.2..........  Mom = 7..............      \d,e\ 9.8%             6.1
                                                           Infant = 7...........    \d,e,f\ 4.4%             2.7
                                                           (Mom = 3.0 ).........
Lactating woman and Breast-fed      Mom: 72..............  7....................        \d\ 2.0%             1.2
 infant (60 d).                     Infant: 5.0..........  Mom = 7..............      \d,e\ 7.9%             4.9
                                                           Infant = 7...........    \d,e,f\ 4.2%             2.7
                                                           (Mom = 3.6 ).........
Bottle-fed infant (60 d)..........  Infant: 5.0..........  7....................        \e\ 2.5%             1.5
Child (0.97 yr) \g\...............  Child: 10............  7....................        \h\ 1.7%             1.1
Child (2 yr)......................  Child: 14............  7....................        \h\ 1.7%             1.1
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\a\ The 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.
\b\ Maternal body weight was held at the value defined at the start of pregnancy (BW = 67.77 kg), and the
  ``average adult'' urinary clearance values as published by Merrill et al. (2005) were used.
\c\ Results are based on using the maternal urinary clearance as published in Clewell et al. (2007), which equal
  about half of the average adult clearance.
\d\ 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.
\e\ %RAIU inhibition given for the infant is provided based upon a value of urinary clearance scaled from the
  adult by BW \2/3\ to approximate surface-area scaling, and then multiplied by a rising fraction vs. age based
  on data (DeWoskin and Thompson, 2008) to reflect the reduction in glomerular filtration rates. Clewell et al.
  (2007) scaled urinary clearance by BW \0.75\, rather than adjusting based on GFR.
\f\ These %RAIU inhibition values are based on an internal dose to the breast-fed infant of 7 [mu]g/kg-day, the
  same as for the other subgroups. Maternal dose rates lower than the POD are needed to provide 7 [mu]g/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.
\g\ 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.
\h\ Results were obtained by setting urinary clearance constants for the older child equal to the average adult
  (Merrill et al., 2005) and scaling by BW \1\.
\i\ The dose equal to the POD is 7 [mu]g/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 [mu]g/L to protect pregnant women and

[[Page 41887]]

their fetuses based upon the Agency's RfD, recommended by the NRC, and 
the following exposure estimates:
    HRL = RfD x BW/DWI x RSC

Where:

RfD = Reference dose (0.7 [mu]g/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 [mu]g/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 [mu]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 [micro]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.
    <bullet> Less than 12 Months old: birth to < 1 month, 1 to < 3 
months, 3 to < 6 months and 6 to < 12 months.
    <bullet> 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

[[Page 41888]]

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 [mu]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 [mu]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, 90th and 95th Percentile Drinking Water Ingestion Rates for Various Life Stages
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                      90th                        95th
                                                                          Mean                     Percentile                  Percentile
               Life stage                  RfD ([mu]g/     RSC \a\      ingestion      Alt HRL      ingestion      Alt HRL      ingestion      Alt HRL
                                             kg-day)      (percent)   rate \d\ (mL/   ([mu]g/L)   rate \d\ (mL/   ([mu]g/L)   rate \d\ (mL/   ([mu]g/L)
                                                                       kg-day) \b\                 kg-day) \b\                 kg-day) \b\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Birth to < 1 month......................           0.7            59           137             3       \c\ 235             2       \c\ 238             2
1 to < 3 months.........................           0.7            59           119             3       \c\ 228             2       \c\ 285             1
3 to < 6 months.........................           0.7            59            80             5           148             3       \c\ 173             2
Birth to < 6 months.....................           0.7            59            95             4           184             2           221             2
6 to < 12 months........................           0.7            59            53             8           112             4           129             3
1 to < 2 years..........................           0.7            44            27            11            56             6            75             4
2 to < 3 years..........................           0.7            44            26            12            52             6            62             5
3 to < 6 years..........................           0.7            60            24            18            49             9            65             6
6 to < 11 years.........................           0.7            71            17            29            35            14            45            11
11 to < 16 years........................           0.7            84            13            45            26            23            34            17
16 to < 18 years........................           0.7            80            12            47            24            23        \c\ 32            18
18 to < 21 years........................           0.7            80            13            43            29            19        \c\ 35            16
Pregnant Women \e\......................           0.7        \c\ 62        \c\ 14            31        \c\ 33            13        \c\ 43            10
Women Ages 15-44........................           0.7            80            15            37            32            18            39            14
--------------------------------------------------------------------------------------------------------------------------------------------------------
\a\ RSC 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 15-44 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 Handbook'' (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).
\c\ The 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.
\e\ The most sensitive population identified by the NRC are the fetuses of pregnant women who might have hypothyroidism or iodide deficiency.


[[Page 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 [mu]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 [mu]g/L 
and the median was 6.40 [mu]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 [mu]g/L 
(MRL) to 25 [mu]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
----------------------------------------------------------------------------------------------------------------
                                                                                                  Population
                                                         PWS entry or      Population served  estimate for entry
                                  PWSs with at least  sample points with    by PWSs with at    or sample points
          Thresholds a               1 detection >        at least 1       least 1 detection   having at least 1
                                     threshold of         detection >       > threshold of        detection >
                                       interest          threshold of         interest c         threshold of
                                                          interest b                              interest d
----------------------------------------------------------------------------------------------------------------
4 [mu]g/L.......................  4.01%.............  2.48%.............  16.6 M e..........  5.1 M.
                                  (155 of 3,865)....  (371 of 14,987)...
5 [mu]g/L.......................  3.16%.............  1.88%.............  14.6 M............  4.0 M.
                                  (122 of 3,865)....  (281 of 14,987)...
7 [mu]g/L.......................  2.12%.............  1.14%.............  7.2 M.............  2.2 M.
                                  (82 of 3,865).....  (171 of 14,987)...
10 [mu]g/L......................  1.35%.............  0.65%.............  5.0 M.............  1.5 M.
                                  (52 of 3,865).....  (97 of 14,987)....
12 [mu]g/L......................  1.09%.............  0.42%.............  3.6 M.............  1.2 M.
                                  (42 of 3,865).....  (63 of 14,984)....
15 [mu]g/L......................  0.80%.............  0.29%.............  2.0 M.............  0.9 M.
                                  (31 of 3,865).....  (44 of 14,987)....
17 [mu]g/L......................  0.70%.............  0.24%.............  1.9 M.............  0.8 M.
                                  (27 of 3,865).....  (36 of 14,987)....
20 [mu]g/L......................  0.49%.............  0.16%.............  1.5 M.............  0.7 M.
                                  (19 of 3,865).....  (24 of 14,987)....
25 [mu]g/L......................  0.36%.............  0.12%.............  1.0 M.............  0.4 M.
                                  (14 of 3,865).....  (18 of 14,987)....
----------------------------------------------------------------------------------------------------------------
Footnotes:
\a\ All occurrence measures in this table were conducted on a basis reflecting values greater than the listed
  thresholds.

[[Page 41890]]

 
\b\ The 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.
\c\ The 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 system 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.
\e\ This value does not include the population associated with 5 systems serving 200,000 people that measured
  perchlorate at 4 [mu]g/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/Perchlorate.aspx 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 [mu]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 [mu]g/L, 16.6 
million would be exposed, and another commenter states that if EPA set 
the HRL at 5 [mu]g/L, then 5-7 times more individuals would be exposed 
above the HRL than at 15 [mu]g/L.
    However, one commenter points out that, ``An MCL of 2 [mu]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 [mu]g/L, 
5 [mu]g/L and 6 [mu]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 [mu]g/L to 
25 [mu]g/L. One limitation to the UCMR 1 data is that the perchlorate 
analytical method MRL is 4 [mu]g/L; only perchlorate sample detections 
greater than or equal to 4 [mu]g/L can be dependably quantified and 
reported. Any perchlorate sample concentration with a value between 0 
and 4 [mu]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 [mu]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 [mu]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 [mu]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 [mu]g/L. This is the only known, state-wide monitoring 
program that uses an analytical method with an MRL lower than 4 [mu]g/
L. Bayesian hierarchical modeling can use the Massachusetts data to 
improve the model estimates in the lower concentration ranges.

[[Page 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 [mu]g/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 [mu]g/
kg/day) of the RfD, while the 95th percentile dose was about one third 
of the RfD (0.234 [mu]g/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 [mu]g/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 ``[S]trongly 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 ``[A]dditional important data on 
pregnant women and their offspring

[[Page 41892]]

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[hyphen]studied chemicals 
with detailed information on the mechanism of action, 
dose[hyphen]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[hyphen]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 J, Wasser J, 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. Valent[iacute]n-
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. Valent[iacute]n-Blasini, J.D. Osterloh, J.P. 
Mauldin, and J.L. Pirkle. 2007. Perchlorate Exposure of the US 
Population, 2001-2002. J. 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(1):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 Perspect Vol. 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):396-404.
    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 (NRC). 2005. Health Implications of 
Perchlorate Ingestion. National Academies Press,

[[Page 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. J 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: 10.1038/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


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