60262 Federal Register / Vol. 73, No. 198 / Friday, October 10, 2008 / Notices 

FERC Online service, please e-mail 

FERCOnlineSupport@ferc.gov or call 

(866) 208–3676 (toll free). For TTY, call 

(202) 502–8659. 

Kimberly D. Bose, 

Secretary. 

[FR Doc. E8–24157 Filed 10–9–08; 8:45 am] 

BILLING CODE 6717–01–P 

DEPARTMENT OF ENERGY 

Federal Energy Regulatory 

Commission 

[Docket No. ER08–1522–000] 

WG Energy LLC; Supplemental Notice 

That Initial Market-Based Rate Filing 

Includes Request for Blanket Section 

204 Authorization 

October 6, 2008. 

This is a supplemental notice in the 

above-referenced proceeding of WG 

Energy LLC’s application for marketbased rate authority, with an 

accompanying rate tariff, noting that 

such application includes a request for 

blanket authorization, under 18 CFR 

Part 34, of future issuances of securities 

and assumptions of liability. 

Any person desiring to intervene or to 

protest should file with the Federal 

Energy Regulatory Commission, 888 

First Street, NE., Washington, DC 20426, 

in accordance with Rules 211 and 214 

of the Commission’s Rules of Practice 

and Procedure (18 CFR 385.211 and 

385.214). Anyone filing a motion to 

intervene or protest must serve a copy 

of that document on the Applicant. 

Notice is hereby given that the 

deadline for filing protests with regard 

to the applicant’s request for blanket 

authorization, under 18 CFR Part 34, of 

future issuances of securities and 

assumptions of liability, is October 27, 

2008. 

The Commission encourages 

electronic submission of protests and 

interventions in lieu of paper, using the 

FERC Online links at http:// 

www.ferc.gov. To facilitate electronic 

service, persons with Internet access 

who will eFile a document and/or be 

listed as a contact for an intervenor 

must create and validate an 

eRegistration account using the 

eRegistration link. Select the eFiling 

link to log on and submit the 

intervention or protests. 

Persons unable to file electronically 

should submit an original and 14 copies 

of the intervention or protest to the 

Federal Energy Regulatory Commission, 

888 First St., NE., Washington, DC 

20426. 

The filings in the above-referenced 

proceeding are accessible in the 

Commission’s eLibrary system by 

clicking on the appropriate link in the 

above list. They are also available for 

review in the Commission’s Public 

Reference Room in Washington, DC. 

There is an eSubscription link on the 

Web site that enables subscribers to 

receive e-mail notification when a 

document is added to a subscribed 

dockets(s). For assistance with any 

FERC Online service, please e-mail 

FERCOnlineSupport@ferc.gov or call 

(866) 208–3676 (toll free). For TTY, call 

(202) 502–8659. 

Kimberly D. Bose, 

Secretary. 

[FR Doc. E8–24160 Filed 10–9–08; 8:45 am] 

BILLING CODE 6717–01–P 

DEPARTMENT OF ENERGY 

Federal Energy Regulatory 

Commission 

[Docket No. PR08–30–000] 

Enterprise Texas Pipeline LLC; Notice 

of Petition for Rate Approval 

October 6, 2008. 

Take notice that on September 30, 

2008, Enterprise Texas Pipeline LLC 

(Enterprise Texas) filed a petition for 

rate approval pursuant to section 

284.123(b)(2) of the Commission’s 

regulations. Enterprise Texas requests 

that the Commission approve an 

incremental rate of $0.6370 per MMBtu 

for service on the Sherman Extension 

commencing on September 30, 2008. 

Any person desiring to participate in 

this rate proceeding must file a motion 

to intervene or to protest this filing must 

file in accordance with Rules 211 and 

214 of the Commission’s Rules of 

Practice and Procedure (18 CFR 385.211 

and 385.214). Protests will be 

considered by the Commission in 

determining the appropriate action to be 

taken, but will not serve to make 

protestants parties to the proceeding. 

Any person wishing to become a party 

must file a notice of intervention or 

motion to intervene, as appropriate. 

Such notices, motions, or protests must 

be filed on or before the date as 

indicated below. Anyone filing an 

intervention or protest must serve a 

copy of that document on the Applicant. 

Anyone filing an intervention or protest 

on or before the intervention or protest 

date need not serve motions to intervene 

or protests on persons other than the 

Applicant. 

The Commission encourages 

electronic submission of protests and 

interventions in lieu of paper using the 

‘‘eFiling’’ link at http://www.ferc.gov. 

Persons unable to file electronically 

should submit an original and 14 copies 

of the protest or intervention to the 

Federal Energy Regulatory Commission, 

888 First Street, NE., Washington, DC 

20426. 

This filing is accessible on-line at 

http://www.ferc.gov, using the 

‘‘eLibrary’’ link and is available for 

review in the Commission’s Public 

Reference Room in Washington, DC. 

There is an ‘‘eSubscription’’ link on the 

Web site that enables subscribers to 

receive e-mail notification when a 

document is added to a subscribed 

docket(s). For assistance with any FERC 

Online service, please e-mail 

FERCOnlineSupport@ferc.gov or call 

(866) 208–3676 (toll free). For TTY, call 

(202) 502–8659. 

Comment Date: 5 p.m. Eastern Time 

Friday October 17, 2008. 

Kimberly D. Bose, 

Secretary. 

[FR Doc. E8–24152 Filed 10–9–08; 8:45 am] 

BILLING CODE 6717–01–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

[EPA–HQ–OW–2008–0068; FRL–8727–6] 

RIN 2040–ZA02 

Drinking Water: Preliminary Regulatory 

Determination on Perchlorate 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Notice. 

SUMMARY: This action presents EPA’s 

preliminary regulatory determination 

for perchlorate in accordance with the 

Safe Drinking Water Act (SDWA). The 

Agency has determined that a national 

primary drinking water regulation 

(NPDWR) for perchlorate would not 

present ‘‘a meaningful opportunity for 

health risk reduction for persons served 

by public water systems.’’ The SDWA 

requires EPA to make determinations 

every five years of whether to regulate 

at least five contaminants on the 

Contaminant Candidate List (CCL). EPA 

included perchlorate on the first and 

second CCLs that were published in the 

Federal Register on March 2, 1998 and 

February 24, 2005. Most recently, EPA 

presented final regulatory 

determinations regarding 11 

contaminants on the second CCL in a 

notice published in the Federal Register 

on July 30, 2008. In today’s action, EPA 

presents supporting rationale and 

requests public comment on its 

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Federal Register / Vol. 73, No. 198 / Friday, October 10, 2008 / Notices 60263 

preliminary regulatory determination 

for perchlorate. EPA will make a final 

regulatory determination for perchlorate 

after considering comments and 

information provided in the 30-day 

comment period following this notice. 

EPA plans to publish a health advisory 

for perchlorate at the time the Agency 

publishes its final regulatory 

determination to provide State and local 

public health officials with technical 

information that they may use in 

addressing local contamination. 

DATES: Comments must be received on 

or before November 10, 2008. 

ADDRESSES: Submit your comments, 

identified by Docket ID No. EPA–HQ– 

OW–2008–0068, by one of the following 

methods: 

• www.regulations.gov: Follow the 

on-line 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–2008– 

0068. EPA’s policy is that all comments 

received will be included in the public 

docket without change and may be 

made available online at 

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 www.regulations.gov 

or e-mail. The 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 www.regulations.gov your email 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.B 

of the SUPPLEMENTARY INFORMATION

section of this document. 

Docket: All documents in the docket 

are listed in the 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 

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: hotlinesdwa@epa.gov. 

Abbreviations and Acronyms 

a. i.—active ingredient 

<—less than 

≤—less than or equal to 

>—greater than 

≥—greater than or equal to 

μ—microgram, one-millionth of a gram 

μg/g—micrograms per gram 

μg/kg—micrograms per kilogram 

μg/L—micrograms per liter 

ATSDR—Agency for Toxic Substances and 

Disease Registry 

AWWARF—American Water Works 

Association Research Foundation 

BMD—bench mark dose 

BMDL—bench mark dose level 

BW—body weight for an adult, assumed to be 

70 kilograms (kg) 

CASRN—Chemical Abstract Services 

Registry Number 

CBI—confidential business information 

ChE—cholinesterase 

CCL—Contaminant Candidate List 

CCL 1—EPA’s First Contaminant Candidate 

List 

CCL 2—EPA’s Second Contaminant 

Candidate List 

CDC—Centers for Disease Control and 

Prevention 

CDPH—-California Department of Public 

Health 

CFR—Code of Federal Regulations 

CMR—Chemical Monitoring Reform 

CWS—community water system 

DW—dry weight 

DWEL—drinking water equivalent level 

DWI—drinking water intake 

EPA—United States Environmental 

Protection Agency 

EPCRA—Emergency Planning and 

Community Right-to-Know Act 

FDA—United States Food and Drug 

Administration 

FQPA—Food Quality Protection Act 

FR—Federal Register 

FW—fresh weight 

g—gram 

g/day—grams per day 

HRL—health reference level 

IOC—inorganic compound 

IRIS—Integrated Risk Information System 

kg—kilogram 

L—liter 

LD50 —an estimate of a single dose that is 

expected to cause the death of 50 percent 

of the exposed animals; it is derived from 

experimental data. 

LOAEL—lowest-observed-adverse-effect level 

MA DEP—Massachusetts Department of 

Environmental Protection 

MCL—maximum contaminant level 

MCLG—maximum contaminant level goal 

mg—milligram, one-thousandth of a gram 

mg/kg—milligrams per kilogram body weight 

mg/kg/day—milligrams per kilogram body 

weight per day 

mg/L—milligrams per liter 

mg/m3—milligrams per cubic meter 

MRL—minimum or method reporting limit 

(depending on the study or survey cited) 

N—number of samples 

NAS—National Academy of Sciences 

NCEH—National Center for Environmental 

Health (CDC) 

NCFAP—National Center for Food and 

Agricultural Policy 

NCI—National Cancer Institute 

NCWS—non-community water system 

ND—not detected (or non-detect) 

NDWAC—National Drinking Water Advisory 

Council 

NHANES—National Health and Nutrition 

Examination Survey (CDC) 

NIS—sodium iodide symporter 

NOEL—no-observed-effect-level 

NPDWR—national primary drinking water 

regulation 

NPS—National Pesticide Survey 

NQ—not quantifiable (or non-quantifiable) 

NRC—National Research Council 

NTP—National Toxicology Program 

OA—oxanilic acid 

OW—Office of Water 

OPP—Office of Pesticide Programs 

PBPK—physiologically based 

pharmacokinetic 

PCR—polymerase chain reaction 

PGWDB—pesticides in ground water data 

base 

PWS—public water system 

RAIU—radioactive iodide uptake 

RED—Reregistration Eligibility Decision 

RfC—reference concentration 

RfD—reference dose 

RSC—relative source contribution 

SAB—Science Advisory Board 

SDWA—Safe Drinking Water Act 

mstockstill on PROD1PC66 with NOTICES

60264 Federal Register / Vol. 73, No. 198 / Friday, October 10, 2008 / Notices 

1The MCLG is the ‘‘maximum level of a 

contaminant in drinking water at which no known 

off anticipated adverse effect on the health of 

persons would occur, and which allows an 

adequate margin of safety. Maximum contaminant 

level goals are non-enforceable heath goals’’ (CFR 

141.2). 

2An NPDWR is a legally enforceable standard 

that applies to public water systems. An NPDWR 

sets a legal limit (called a maximum contaminant 

level or MCL) or specifies a certain treatment 

technique (TT) for public water systems for a 

specific contaminant or group of contaminants. 

3The statute authorizes a nine month extension 

of this promulgation date. 

SOC—synthetic organic compound 

SVOC—semi-volatile organic compound 

T3—triiodothyronine 

T4—thyroxine 

TDS—Total Diet Study (FDA) 

TRI—Toxics Release Inventory 

TSH—thyroid stimulating hormone 

TT—treatment technique 

UCMR 1—First Unregulated Contaminant 

Monitoring Regulation 

UF—uncertainty factor 

US—United States of America 

USDA—United States Department of 

Agriculture 

USGS—United States Geological Survey 

UST—underground storage tanks 

VOC—volatile organic compound 

WHO—World Health Organization 

SUPPLEMENTARY INFORMATION: 

I. General Information 

A. Does This Action Impose Any 

Requirements on My Public Water 

System? 

B. What Should I Consider as I Prepare My 

Comments for EPA? 

II. Purpose, Background and Summary of 

This Action 

A. What is the Purpose of This Action? 

B. Background on the CCL and Regulatory 

Determinations 

C. What Comments and Information Did 

EPA Receive Regarding Perchlorate in 

Response to the May 1, FR Notice? 

D. What is EPA’s Preliminary 

Determination on Perchlorate and What 

Happens Next? 

III. What Scientific Data and Analyses Did 

EPA Evaluate in Making a Preliminary 

Regulatory Determination for 

Perchlorate? 

A. Evaluation of Adverse Health Effects 

B. Evaluation of Perchlorate Occurrence in 

Drinking Water 

C. Evaluation of Perchlorate Exposure from 

Sources Other Than Drinking Water 

IV. Preliminary Regulatory Determination on 

Perchlorate 

A. May Perchlorate Have an Adverse Effect 

on the Health of Persons? 

B. Is Perchlorate Known to Occur or is 

There a Substantial Likelihood That 

Perchlorate Occurs at a Frequency and 

Level of Public Health Concern in Public 

Water Systems? 

C. Is There a Meaningful Opportunity for 

the Reduction of Health Risks From 

Perchlorate for Persons Served by Public 

Water Systems? 

V. EPA’s Next Steps 

VI. References 

SUPPLEMENTARY INFORMATION: 

I. General Information 

A. Does This Action Impose Any 

Requirements on My Public Water 

System? 

Today’s action seeks public comment 

on EPA’s preliminary determination 

that a national primary drinking water 

regulation is not necessary for 

perchlorate, and thus imposes no 

requirements on public water systems. 

After review and consideration of public 

comment, EPA will issue a final 

regulatory determination. 

B. 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 

citation related to your comments. 

II. Purpose, Background and Summary 

of This Action 

This section briefly summarizes the 

purpose of this action, the statutory 

requirements, previous activities related 

to the Contaminant Candidate List and 

regulatory determinations, and the 

approach used and outcome of this 

preliminary regulatory determination. 

A. What is the Purpose of This Action? 

The purpose of today’s action is to 

present EPA’s preliminary regulatory 

determination on perchlorate, the 

process and the rationale used to make 

this determination, a brief summary of 

the supporting documentation, and a 

request for public comment. 

B. Background on the CCL and 

Regulatory Determinations 

1. Statutory Requirements for CCL 

and Regulatory Determinations. The 

specific statutory requirements for the 

Contaminant Candidate List (CCL) and 

regulatory determinations can be found 

in section 1412(b)(1) of the Safe 

Drinking Water Act (SDWA). The CCL is 

a list of contaminants that are not 

subject to any proposed or promulgated 

national primary drinking water 

regulations (NPDWRs), are known or 

anticipated to occur in public water 

systems (PWSs), and may require 

regulation under the SDWA. The 1996 

SDWA Amendments also direct EPA to 

determine, every five years, whether to 

regulate at least five contaminants from 

the CCL. The SDWA requires EPA to 

publish a Maximum Contaminant Level 

Goal1 (MCLG) and promulgate an 

NPDWR2 for a contaminant if the 

Administrator determines that: 

(a) The contaminant may have an 

adverse effect on the health of persons; 

(b) 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 

(c) In the sole judgment of the 

Administrator, regulation of such 

contaminant presents a meaningful 

opportunity for health risk reduction for 

persons served by public water systems. 

While carrying out the process to 

make a determination, the law requires 

EPA to take into consideration the effect 

contaminants have on subgroups that 

comprise a meaningful portion of the 

general population (such as infants, 

children, pregnant women, the elderly, 

individuals with a history of serious 

illness or other subpopulations) that are 

identifiable as being at greater risk of 

adverse health effects than the general 

population. 

If EPA makes a final determination 

that a national primary drinking water 

regulation is needed, the Agency has 24 

months to publish a proposed MCLG 

and NPDWR. After the proposal, the 

Agency has 18 months to publish and 

promulgate a final MCLG and NPDWR 

(SDWA section 1412(b) (1) (E)).3

EPA published preliminary regulatory 

determinations for nine CCL 1 

contaminants on June 3, 2002, (67 FR 

38222 (USEPA, 2002a)), and final 

regulatory determinations on July 18, 

2003 (68 FR 42898 (USEPA, 2003a)). 

EPA published preliminary regulatory 

determinations for eleven CCL 2 

contaminants on May 1, 2007, (72 FR 

24016 (USEPA, 2007)) and finalized 

these regulatory determinations on July 

30, 2008 (73 FR 44251 (USEPA, 2008c)). 

As part of its May 1, 2007, FR notice of 

preliminary regulatory determinations 

for 11 contaminants, EPA also presented 

information on several contaminants 

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Federal Register / Vol. 73, No. 198 / Friday, October 10, 2008 / Notices 60265 

from the second CCL for which the 

Agency was not yet making a 

preliminary regulatory determination, 

including perchlorate. Specifically, EPA 

indicated that additional information 

was needed to more fully characterize 

perchlorate exposure and determine 

whether it is appropriate to regulate 

perchlorate in drinking water (i.e., 

whether setting a national primary 

drinking water standard would provide 

a meaningful opportunity to reduce risk 

for people served by public water 

systems). The May 1, 2007, FR notice 

describes how the Agency was 

considering additional information 

including FDA food data and CDC 

human exposure data to determine 

whether to regulate perchlorate. (See the 

May 1, 2007, FR notice at 24038 for a 

discussion regarding the information 

that EPA had on perchlorate as well as 

the additional information that was 

needed before the Agency could make a 

preliminary regulatory determination 

for perchlorate). 

C. What Comments and Information Did 

EPA Receive Regarding Perchlorate in 

Response to the May 1, FR Notice? 

Eight commenters on the Regulatory 

Determinations 2 Preliminary FR notice 

addressed perchlorate. EPA received 

comments that supported and 

comments that opposed regulating 

perchlorate. One of the commenters 

who encouraged regulation stated that 

perchlorate is known to occur in public 

water supplies in a number of States 

and ‘‘while occurrence data does [sic] 

not suggest that perchlorate occurs at 

levels of public health concern in the 

vast majority of public drinking water 

supplies, and the population at risk 

appears to be small, that group does 

include a sensitive subpopulation 

(pregnant women and developing 

fetuses) of significant concern.’’ Another 

commenter wrote ‘‘the contamination of 

water supplies by perchlorate is ongoing’’ and ‘‘perchlorate that has 

entered the soil and contaminated 

aquifers will likely lead to additional 

impacted sites.’’ A commenter wrote 

that ‘‘a number of States are moving to 

regulate perchlorate and a patchwork of 

different regulations will confuse the 

public and the regulated water 

community.’’ 

The commenters opposed to 

regulating perchlorate also cited the 

available information to support their 

recommendation. One commenter wrote 

that ‘‘the extensive scientific record 

indicates that establishing a drinking 

water standard for perchlorate would 

not yield a meaningful opportunity to 

reduce risk to human health.’’ Another 

commenter stated that perchlorate ‘‘does 

not appear, at this stage, to be a 

nationwide problem.’’ 

Several commenters also addressed 

EPA’s assessment that additional 

investigation is necessary to ascertain 

total human exposure before a 

preliminary regulatory determination 

could be made. Commenters wrote that 

the principal study on which EPA’s 

Reference Dose (RfD) is based already 

accounts for background sources of 

perchlorate and therefore EPA should 

not adjust the RfD to account for other 

non-drinking-water exposures. 

EPA has considered the perchlorate 

comments submitted in connection with 

the May 1, 2007, notice in the 

development of today’s action. EPA will 

consider these and any further 

comments submitted in response to this 

notice before preparing a final 

regulatory determination for 

perchlorate. 

D. What is EPA’s Preliminary Regulatory 

Determination on Perchlorate and What 

Happens Next? 

EPA is making a preliminary 

regulatory determination in this notice 

that a national primary drinking water 

rule is not necessary for perchlorate 

because a national primary drinking 

water regulation would not provide a 

meaningful opportunity to reduce 

health risk. EPA will make a final 

regulatory determination for perchlorate 

after considering comments and 

information provided in the 30-day 

comment period following this notice. 

One of the analyses that EPA considered 

for this preliminary determination is a 

physiologically-based pharmacokinetic 

(PBPK) model that predicts radioactive 

iodide uptake (RAIU) inhibition in the 

thyroid for various sub-populations and 

drinking water concentrations. The 

model, which is described in section 

IV.B.5, has already been published in 

peer-reviewed articles (Clewell et al., 

2007 and Merrill et al., 2005), but EPA 

subjected the model to intensive 

internal review prior to considering it 

for this regulatory determination and 

made several adjustments as a result. 

EPA believes it is appropriate to have 

these adjustments peer-reviewed. While 

the application of the model to nonadult subpopulations was part of the 

previously peer-reviewed articles, EPA 

will also ask the peer reviewers to 

comment on this issue to help EPA 

ensure that the model is appropriate for 

use in assessing health outcomes 

associated with perchlorate exposure for 

these populations. EPA intends to 

complete this review before publishing 

its final determination and will consider 

any comments from the reviewers. 

Additionally, EPA plans to publish a 

health advisory for perchlorate at the 

time the Agency publishes its final 

regulatory determination to provide 

State and local public health officials 

with information that they may use in 

addressing local contamination. 

Additionally, at the same time that 

EPA publishes a health advisory for 

perchlorate, the Agency will withdraw 

its existing January 2006 guidance 

regarding perchlorate and potential 

cleanup levels under the National Oil 

and Hazardous Substances Contingency 

Plan (National Contingency Plan, NCP) 

and will replace it with revised 

guidance. (See memorandum dated 

January 26, 2006, from Susan Parker 

Bodine to EPA Regional Administrators 

(US EPA, 2006).) Specifically, the 

January 2006 guidance, in part, 

addresses the use of preliminary 

remediation goals (PRGs) for perchlorate 

contaminated water at National Priority 

List (NPL) sites. The January 2006 

guidance recommends a PRG of 24.5 

ppb, assuming that all exposure comes 

from ground water at the site. The 

recommended PRG is based on the 

assumption that all exposure comes 

from ground water, because at the time 

the January 2006 guidance was issued 

there was insufficient information 

available on the levels of perchlorate in 

food to calculate a national relative 

source contribution (RSC). In the 

absence of such national data on the 

levels of perchlorate found in foods, the 

approach outlined in the January 2006 

guidance was considered by the Agency 

to be the most scientifically defensible. 

In addition, because the recommended 

PRG generally is the starting point for 

determining appropriate site-specific 

cleanup levels, the guidance also 

indicates that the cleanup level at any 

site should be evaluated on a case-bycase basis, and modified accordingly, 

based on site-specific information, 

including exposure to non-water 

sources, such as foods. EPA now has 

sufficient data to calculate a national 

RSC and has used this RSC to calculate 

a health reference level (HRL) for 

drinking water as part of the basis for 

today’s preliminary determination. 

When EPA issues the final regulatory 

determination for perchlorate, the final 

HRL will be the basis for the health 

advisory value in the health advisory 

document the Agency expects to issue at 

that time. Thereafter, it may be 

appropriate to use the health advisory 

value as a ‘‘to be considered’’ (TBC) 

value in developing potential cleanup 

levels for perchlorate at Superfund sites. 

In addition, some State regulations may 

be applicable or relevant and 

appropriate requirements (ARARs) 

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60266 Federal Register / Vol. 73, No. 198 / Friday, October 10, 2008 / Notices 

when establishing cleanup levels for 

perchlorate at Superfund sites. 

III. What Scientific Data and Analyses 

Did EPA Evaluate in Making a 

Preliminary Regulatory Determination 

for Perchlorate? 

This section summarizes the health 

effects, occurrence, and population 

exposure evaluation information EPA 

used to support the preliminary 

regulatory determination for 

perchlorate. EPA’s conclusions with 

respect to these data are discussed in 

Section IV. 

A. Evaluation of Precursor and Adverse 

Health Effects 

Section 1412(b)(1)(A)(i) of the SDWA 

requires EPA to determine whether a 

candidate contaminant may have an 

adverse effect on public health. EPA 

described the overall process the 

Agency used to evaluate health effects 

information in the May 1, 2007, Federal 

Register Notice (72 FR 24016 (USEPA, 

2007)). This section presents specific 

information about the potential for 

precursor and adverse health effects 

from perchlorate, including a discussion 

of an extensive report completed by the 

National Academy of Sciences (NAS) on 

the issue and other research published 

after that report. 

1. NAS Review of Perchlorate Health 

Implications and EPA’s Reference Dose 

In 2003, the National Research 

Council (NRC) of the NAS was asked to 

assess the current state of the science 

regarding potential adverse effects of 

disruption of thyroid function by 

perchlorate in humans and laboratory 

animals at various stages of life and, 

based on this review, to determine 

whether EPA’s findings in its 2002 draft 

risk assessment were consistent with the 

current scientific evidence. 

In January 2005, the NRC published 

‘‘Health Implications of Perchlorate 

Ingestion,’’ a review of the state of the 

science regarding potential adverse 

health effects of perchlorate exposure 

and mode-of-action for perchlorate 

toxicity (NRC, 2005). 

Perchlorate can interfere with the 

normal functioning of the thyroid gland 

by competitively inhibiting the 

transport of iodide into the thyroid. 

Iodide is an important component of 

two thyroid hormones, T4 and T3, and 

the transfer of iodide from the blood 

into the thyroid is an essential step in 

the synthesis of these two hormones. 

Iodide transport into the thyroid is 

mediated by a protein molecule known 

as the sodium (Na∂)-iodide (I¥) 

symporter (NIS). NIS molecules bind 

iodide with very high affinity, but they 

also bind other ions that have a similar 

shape and electric charge, such as 

perchlorate. The binding of these other 

ions to the NIS inhibits iodide transport 

into the thyroid, which can result in 

intrathyroidal iodide deficiency and 

consequently decreased synthesis of T4 

and T3. There is compensation for lowlevels of iodide deficiency, however, 

such that the body maintains blood 

serum concentrations of thyroid 

hormones within narrow limits through 

feedback control mechanisms. The 

compensation for decreased thyroid 

hormone is accomplished by increased 

secretion of the thyroid stimulating 

hormone (TSH) from the pituitary gland 

triggered by the reduced hormone 

levels, which has among its effects the 

increased production of T4 and T3 

(USEPA, 2005b). The thyroid’s ability to 

compensate in this way is limited, 

though, such that sufficiently high 

levels of perchlorate exposure result in 

a reduction of T4 and T3 blood levels 

(after thyroid iodine stores are 

depleted). Sustained changes in thyroid 

hormone and TSH secretion can result 

in thyroid hypertrophy and hyperplasia 

(i.e., abnormal growth or enlargement of 

the thyroid) (USEPA, 2005b). 

Children born with congenital 

hypothyroidism may suffer from mild 

cognitive deficits despite hormone 

remediation (Rovet, 2002; Zoeller and 

Rovet, 2004), and subclinical 

hypothyroidism and reductions in T4 

(i.e., hypothyroxinemia) in pregnant 

women have been associated with 

neurodevelopmental delays and IQ 

deficits in their children (Pop et al., 

1999, 2003; Haddow et al., 1999; 

Kooistra et al., 2006; Morreale de 

Escobar, 2000, 2004). Animal studies 

support these observations, and recent 

findings indicate that 

neurodevelopmental deficits are evident 

under conditions of hypothyroxinemia 

and occur in the absence of growth 

retardation (Auso et al., 2004; Gilbert 

and Sui, 2008; Sharlin et al., 2008; 

Goldey et al., 1995). 

Results from studies of the effects of 

perchlorate exposure on hormone levels 

have been mixed. One recent study did 

not identify any effects of perchlorate on 

blood serum hormones (Amitai et al., 

2007), while another study (Blount et 

al., 2006b) did identify such effects. The 

results of the Blount study are discussed 

further in Section III.A.2. 

The data from epidemiological studies 

of the general population provide some 

information on possible effects of 

perchlorate exposure. Based upon 

analysis of the data available at the time 

NRC (2005) acknowledged that ecologic 

epidemiological data alone are not 

sufficient to demonstrate whether or not 

an association is causal, and that these 

studies can provide evidence bearing on 

possible associations. Noting the 

limitations of specific studies, the NRC 

(2005; chapter 3) committee concluded 

that the available epidemiological 

evidence is not consistent with a causal 

association between perchlorate and 

congenital hypothyroidism, changes in 

thyroid function in normal birthweight, 

full-term newborns, or hypothyroidism 

or other thyroid disorders in adults. The 

committee considered the evidence to 

be inadequate to determine whether or 

not there is a causal association between 

perchlorate exposure and adverse 

neurodevelopmental outcomes in 

children. The committee noted that no 

studies have investigated the 

relationship between perchlorate 

exposure and adverse outcomes among 

especially vulnerable groups, such as 

the offspring of mothers who had low 

dietary iodide intake, or lowbirthweight or preterm infants (US EPA, 

2005b). 

The NRC recommended data from the 

Greer et al. (2002) human clinical study 

as the basis for deriving a reference dose 

(RfD) for perchlorate (NRC, 2005). Greer 

et al., (2002) report the results of a study 

that measured thyroid iodide uptake, 

hormone levels, and urinary iodide 

excretion in a group of 37 healthy adults 

who were administered perchlorate 

doses orally over a period of 14 days. 

Dose levels ranged from 7 to 500 μg/kg/ 

day in the different experimental 

groups. The investigators found that the 

24-hour inhibition of iodide intake 

ranged from 1.8 percent in the lowest 

dose group to 67.1 percent in the 

highest dose group. However, no 

significant differences were seen in 

measured blood serum thyroid hormone 

levels (T3, T4, total and free) in any 

dose group. The statistical no observed 

effect level (NOEL) for the perchlorateinduced inhibition of thyroid iodide 

uptake was determined to be 7 μg/kg/ 

day, corresponding to an iodide uptake 

inhibition of 1.8 percent. Although the 

NRC committee concluded that 

hypothyroidism is the first adverse 

effect in the continuum of effects of 

perchlorate exposure, NRC 

recommended that ‘‘the most healthprotective and scientifically valid 

approach’’ was to base the perchlorate 

RfD on the inhibition of iodide uptake 

by the thyroid (NRC, 2005). NRC 

concluded that iodide uptake inhibition, 

although not adverse, is the most 

appropriate precursor event in the 

continuum of possible effects of 

perchlorate exposure and would 

precede any adverse health effects of 

perchlorate exposure. The lowest dose 

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4 ‘‘There can be variability in responses among 

humans. The intraspecies uncertainty factor 

accounts for that variability and is intended to 

protect populations more sensitive than the 

population tested. In the absence of data on the 

range of sensitivity among humans, a default 

uncertainty factor of 10 is typically applied. The 

factor could be set at 1 if data indicate that sensitive 

populations do not vary substantially from those 

tested.’’ (NRC 2005, p 173) 

5While CDC researchers measured urinary 

perchlorate concentration for 2,820 NHANES 

participants, TSH and total T4 serum levels were 

only available for 2,299 of these participants. 

6WHO notes that the prevalence of goiter begins 

to increase in populations with a median urinary 

iodide level below 100 μg/L (WHO, 1994). 

(7 μg/kg/day) administered in the Greer 

et al., (2002) study was considered a 

NOEL (rather than a no-observedadverse-effect level or NOAEL) because 

iodide uptake inhibition is not an 

adverse effect, but a biochemical 

precursor. The NRC further determined 

that, ‘‘the very small decrease (1.8 

percent) in thyroid radioiodide uptake 

in the lowest dose group was well 

within the variation of repeated 

measurements in normal subjects.’’ A 

summary of the data considered and the 

NRC deliberations can be found in the 

NRC report (2005). 

The NRC recommended that EPA 

apply an intraspecies uncertainty factor 

of 10 to the NOEL to account for 

differences in sensitivity between the 

healthy adults in the Greer et al., (2002) 

study and the most sensitive 

population, fetuses of pregnant women 

who might have hypothyroidism or 

iodide deficiency. Because the fetus 

depends on an adequate supply of 

maternal thyroid hormone for its central 

nervous system development during the 

first trimester of pregnancy, iodide 

uptake inhibition from low-level 

perchlorate exposure has been 

identified as a concern in connection 

with increasing the risk of 

neurodevelopmental impairment in 

fetuses of high-risk mothers (NRC, 

2005). The NRC (2005) viewed the 

uncertainty factor of 10 as conservative 

and protective of health given that the 

point of departure (the NOEL) is based 

on a non-adverse effect (iodide uptake 

inhibition), which precedes the adverse 

effect in a continuum of possible effects 

of perchlorate exposure. The NRC panel 

concluded that no additional 

uncertainty factor was needed for the 

use of a less-than-chronic study, for 

deficiencies in the database, or for 

interspecies variability. EPA’s Integrated 

Risk Information System (IRIS) adopted 

the NRC’s recommendations resulting in 

an RfD of 0.7 μg/kg/day, derived by 

applying a ten-fold total uncertainty 

factor to the NOEL of 7 μg/kg/day 

(USEPA, 2005b). 

The NRC emphasized that its 

recommendation ‘‘differs from the 

traditional approach to deriving the 

RfD.’’ The NRC recommended ‘‘using a 

nonadverse effect rather than an adverse 

effect as the point of departure for the 

perchlorate risk asessement. Using a 

nonadverse effect that is upstream of the 

adverse effect is a more conservative, 

health-protective approach to the 

perchlorate risk assessment.’’ The NRC 

also noted that the purpose of the 10- 

fold uncertainty factor is to protect 

sensitive subpopulations in the face of 

uncertainty regarding their relative 

sensitivity to perchlorate exposure. The 

NRC recognized that additional 

information on these relative 

sensitivities could be used to reduce 

this uncertainty factor in the future 

(NRC, 2005).4

2. Biomonitoring Studies 

After the NRC report was released, 

several papers were published that 

investigated whether biomonitoring data 

associated with the National Health and 

Nutrition Examination Survey 

(NHANES) could be used to discern if 

there was a relationship between 

perchlorate levels in the body and 

thyroid function. These papers also help 

to evaluate populations that might be 

considered to be more sensitive to 

perchlorate exposure. 

Blount et al., (2006b) published a 

study examining the relationship 

between urinary levels of perchlorate 

and blood serum levels of TSH and total 

T4 in 2,299 men and women (ages 12 

years and older) who participated in 

CDC’s 2001–2002 NHANES.5 Blount et 

al., (2006b) evaluated perchlorate along 

with a number of covariates known or 

likely to be associated with T4 or TSH 

levels to assess the relationship between 

perchlorate and these hormones, and 

the influence of other factors on this 

relationship. These covariates included 

gender, age, race/ethnicity, body mass 

index, serum albumin, serum cotinine (a 

marker of nicotine exposure), estimated 

total caloric intake, pregnancy status, 

post-menopausal status, premenarche 

status, serum C-reactive protein, hours 

fasting before sample collection, urinary 

thiocyanate, urinary nitrate, and use of 

selected medications. The study found 

that perchlorate was a statistically 

significant predictor of thyroid 

hormones in women, but not in men. 

After finding evidence of gender 

differences, the researchers focused on 

further analyzing the NHANES data for 

the 1,111 women participants. They 

divided these 1,111 women into two 

categories, higher-iodide and loweriodide urinary content, using a cut point 

of 100 μg/L of urinary iodide based on 

the median level the World Health 

Organization (WHO) considers 

indicative of sufficient iodide intake 6

for a population. Hypothyroid women 

were excluded from the analysis. 

According to the study’s authors, about 

36 percent of women living in the 

United States have urinary iodide levels 

less than 100 μg/L (Caldwell et al., 

2005). For women with urinary iodide 

levels less than 100 μg/L, the study 

found that urinary perchlorate is 

associated with a decrease in (a negative 

predictor for) T4 levels and an increase 

in (a positive predictor for) TSH levels. 

For women with urinary iodide levels 

greater than or equal to 100 μg/L, the 

researchers found that perchlorate is a 

significant positive predictor of TSH, 

but not a predictor of T4. The 

researchers state that perchlorate could 

be a surrogate for another unrecognized 

determinant of thyroid function. 

Also, the study reports that while 

large doses of perchlorate are known to 

decrease thyroid function, this is the 

first time an association of decreased 

thyroid function has been observed at 

these low levels of perchlorate 

exposure. The clinical significance of 

the variations in T4/TSH levels, which 

were generally within normal limits, has 

not been determined. The researchers 

noted several limitations of the study 

(e.g., assumption that urinary 

perchlorate correlates with perchlorate 

levels in the stroma and tissue and 

measurement of total T4 rather than free 

T4) and recommended that these 

findings be affirmed in at least one more 

large study focusing on women with 

low urine iodide levels. It is also not 

known whether the association between 

perchlorate and thyroid hormone levels 

is causal or mediated by some other 

correlate of both, although the 

relationship between urine perchlorate 

and total TSH and T4 levels persisted 

after statistical adjustments for some 

additional covariates known to predict 

thyroid hormone levels (e.g., total 

kilocalorie intake, estrogen use, and 

serum C-reactive protein levels). A 

planned follow-up study will include 

additional measures of thyroid health 

and function (e.g., TPO-antibodies, free 

T4). An additional paper by Blount et 

al., (2006c), discussed further in Section 

III. C. 2. a., found that almost all 

participants in the NHANES survey, 

including the participants in this group, 

had urinary levels of perchlorate 

corresponding to estimated dose levels 

that are below the RfD of 0.7 μg/kg/day. 

The Blount study suggested that 

perchlorate could be a surrogate for 

another unrecognized determinant of 

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60268 Federal Register / Vol. 73, No. 198 / Friday, October 10, 2008 / Notices 

thyroid function. There are other 

chemicals, including nitrate and 

thiocyanate, which can affect thyroid 

function. Steinmaus et al., (2007) 

further analyzed the data from NHANES 

2001–2002 to assess the impact of 

smoking, cotinine and thiocyanate on 

the relationship between urinary 

perchlorate and blood serum T4 and 

TSH. Thiocyanate is a metabolite of 

cyanide found in tobacco smoke and is 

naturally occurring in some foods, 

including cabbage, broccoli, and 

cassava. Increased serum thiocyanate 

levels are associated with increasing 

levels of smoking. Thiocyanate affects 

the thyroid by the same mechanism as 

perchlorate (competitive inhibition of 

iodide uptake). Steinmaus et al. 

analyzed the data to determine whether 

smoking status (smoker or nonsmoker), 

serum thiocyanate, or serum cotinine 

were better predictors of T4 and TSH 

changes than perchlorate, or if the 

effects reflected the combined effects of 

perchlorate and thiocyanate 

Of female subjects 12 years of age and 

older in NHANES 2001–2002, 1,203 

subjects had data on blood serum T4, 

serum TSH, urinary perchlorate, iodine 

and creatinine. Subjects with extreme 

T4 or TSH (3 individuals) or with a 

reported history of thyroid disease (91) 

were excluded from further analyses. Of 

the remaining women, 385 (35 percent) 

had urinary iodine levels below 100 

μg/l. Steinmaus, et al. evaluated serum 

cotinine as an indicator of nicotine 

exposure, with levels greater than 10 ng/ 

ml classified as high and levels less than 

0.015 ng/ml classified as low. 

The authors found no association 

between either perchlorate or T4 and 

smoking, cotinine or thiocyanate in men 

or in women with urinary iodine levels 

greater than 100 μg/l. In addition, they 

found no association between cotinine 

and T4 or TSH in women with iodine 

levels lower than 100 μg/l. However, in 

women with urinary iodine levels lower 

than 100 μg/l, an association between 

urinary perchlorate and decreased 

serum T4 was stronger in smokers than 

in non-smokers, and stronger in those 

with high urinary thiocyanate levels 

than in those with low urinary 

thiocyanate levels. Although noting that 

their findings need to be confirmed with 

further research, the authors concluded 

that for these low-iodine women the 

results suggest that at commonlyoccurring perchlorate exposure levels, 

thiocyanate in tobacco smoke and 

perchlorate interact in affecting thyroid 

function, and that agents other than 

tobacco smoke might cause similar 

interactions (Steimaus et al., 2007). 

EPA also evaluated whether health 

information is available regarding 

children, pregnant women and lactating 

mothers. The NRC report discussed a 

number of epidemiological studies that 

looked at thyroid hormone levels in 

infants. A more recent study by Amitai 

et al., (2007) assessed T4 values in 

newborns in Israel whose mothers 

resided in areas where drinking water 

contained perchlorate at ‘‘very high’’ 

(340 μg/L), ‘‘high’’ (12.94 μg/L), or 

‘‘low’’ (<3 μg/L) perchlorate 

concentrations. The mean (± standard 

deviation) T4 value of the newborns in 

the very high, high, and low exposure 

groups was 13.8 ± 3.8, 13.9 ± 3.4, and 

14.0 ± 3.5 μg/dL, respectively, showing 

no significant difference in T4 levels 

between the perchlorate exposure 

groups. This is consistent with the 

conclusions drawn by the NRC review 

of other epidemiological studies of 

newborns. The NRC (2005) also noted 

‘‘no epidemiologic studies are available 

on the association between perchlorate 

exposure and thyroid dysfunction 

among low-birthweight or preterm 

newborns, offspring of mothers who had 

iodide deficiency during gestation, or 

offspring of hypothyroid mothers.’’ 

3. Physiologically-based 

Pharmacokinetic (PBPK) Models 

PBPK models represent an important 

class of dosimetry models that can be 

used to predict internal doses to target 

organs, as well as some effects of those 

doses (e.g., radioactive iodide uptake 

inhibition in the thyroid). To predict 

internal dose level, PBPK models use 

physiological, biochemical, and 

physicochemical data to construct 

mathematical representations of 

processes associated with the 

absorption, distribution, metabolism, 

and elimination of compounds. With 

the appropriate data, these models can 

be used to extrapolate across and within 

species and for different exposure 

scenarios, and to address various 

sources of uncertainty in health 

assessments, including uncertainty 

regarding the relative sensitivities of 

various subpopulations. 

Clewell et al., (2007) developed multicompartment PBPK models describing 

the absorption and distribution of 

perchlorate for the pregnant woman and 

fetus, the lactating woman and neonate, 

and the young child. This work built 

upon Merrill et al.’s, (2005) model for 

the average adult. Related research that 

served as the basis for the more recent 

PBPK modeling efforts was discussed by 

the NRC in their January 2005 report on 

perchlorate. 

The models estimated the levels of 

perchlorate absorbed through the 

gastrointestinal tract and its subsequent 

distribution within the body. Clewell et 

al., (2007) provided estimates of internal 

dose and resulting iodide uptake 

inhibition across all life stages, and for 

pregnant and lactating women. The 

paper reported iodide uptake inhibition 

levels for external doses of 1, 10, 100, 

and 1000 μg/kg/day. Results at the lower 

two doses indicated that the highest 

perchlorate blood concentrations in 

response to an external dose would 

occur in the fetus, followed by the 

lactating woman and the neonate. 

Predicted blood levels for all three 

groups (i.e., fetus, lactating women and 

neonates) were four- to five-fold higher 

than for non-pregnant adults. Smaller 

relative differences were predicted at 

external doses of 100 and 1000 μg/kg/ 

day. The authors attributed this change 

to saturation of uptake mechanisms. The 

model predicted minimal effect of 

perchlorate on iodide uptake inhibition 

in all groups at the 1 μg/kg/day external 

dose (about one and one half times the 

RfD), estimating 1.1 percent inhibition 

or less across all groups. Inhibition was 

predicted to be 10 percent or less in all 

groups at an external dose of 10 μg/kg/ 

day (about 14 times the RfD). 

The results of the model 

extrapolations were evaluated against 

data developed in two epidemiologic 

studies performed in Chile, one 

studying school children (Tellez et al., 

2005) and another following women 

through pregnancy and lactation (Gibbs 

et al., 2004). The model predicted 

average blood serum concentrations of 

perchlorate in the women from the 

Gibbs et al., (2004) study which were 

nearly identical to their measured 

perchlorate blood serum concentrations. 

The blood serum perchlorate 

concentrations predicted from the 

Tellez et al., (2005) study were within 

the range of the measured 

concentrations, and the concentrations 

of perchlorate in breast milk predicted 

from the model were within two 

standard deviations of the measured 

concentrations. The authors concluded 

that the model predictions were 

consistent with empirical results and 

that the predicted extent of iodide 

inhibition in the most sensitive 

population (the fetus) is not significant 

at EPA’s RfD of 0.7 μg/kg-day. 

The NRC recommended that 

inhibition of iodide uptake by the 

thyroid, which is a precursor event and 

not an adverse effect, should be used as 

the basis for the perchlorate risk 

assessment (NRC, 2005). Consistent 

with this recommendation, iodide 

uptake inhibition was used by EPA as 

the critical effect in determining the 

reference dose (RfD) for perchlorate. 

Therefore, PBPK models of perchlorate 

and radioiodide, which were developed 

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7Systems serving more than 10,000 people. 

8Systems serving 10,000 people or fewer. 

9Large and small systems that purchase 100 

percent of their water supply were not required to 

participate in the UCMR 1 Assessment Monitoring 

or the UCMR 1 Screening Survey. 

10Table 1 shows perchlorate detection sat levels 

greater than and equal to the MRL of 4 μg/L. 

to describe thyroidal radioactive iodide 

uptake (RAIU) inhibition by perchlorate 

for the average adult (Merrill et al., 

2005), pregnant woman and fetus, 

lactating woman and neonate, and the 

young child (Clewell et al., 2007) were 

evaluated by EPA based on their ability 

to provide additional information 

surrounding this critical effect for 

potentially sensitive subgroups and 

reduce some of the uncertainty 

regarding the relative sensitivities of 

these subgroups. 

EPA evaluated the PBPK model code 

provided by the model authors and 

found minor errors in mathematical 

equations and computer code, as well as 

some inconsistencies between model 

code files. EPA made several changes to 

the code in order to harmonize the 

models and more adequately reflect the 

biology (see USEPA, 2008b) for more 

information. 

Model parameters describing urinary 

excretion of perchlorate and iodide were 

determined to be particularly important 

in the prediction of RAIU inhibition in 

all subgroups; therefore, a range of 

biologically plausible values available 

in the peer-reviewed literature was 

evaluated in depth using the PBPK 

models. Exposure rates were also 

determined to be critical for the 

estimation of RAIU inhibition by the 

models and were also further evaluated. 

Overall, detailed examination of 

Clewell et al., (2007) and Merrill et al., 

(2005) confirmed that the model 

structures were appropriate for 

predicting percent inhibition of RAIU 

by perchlorate in most lifestages. 

Unfortunately, the lack of biological 

information during early fetal 

development limits the applicability of 

the PBPK modeling of the fetus to a late 

gestational timeframe (i.e., near full 

term pregnancy, ∼GW 40), so EPA did 

not make use of model predictions 

regarding early fetal RAIU inhibition. 

Although quantitative outputs of EPA’s 

revised PBPK models differ somewhat 

from the published values, the EPA 

evaluation confirmed that, with 

modifications (as described in USEPA, 

2008b), the Clewell et al., (2007) and 

Merrill et al., (2005) models provide an 

appropriate basis for calculating the 

lifestage differences in the degree of 

thyroidal RAIU inhibition at a given 

level of perchlorate exposure. The 

results of EPA’s model application are 

discussed in Section IV.B.5. 

B. Evaluation of Perchlorate Occurrence 

in Drinking Water 

The primary source of drinking water 

occurrence data used to support this 

preliminary regulatory determination is 

the data provided by public water 

systems in accordance with the first 

Unregulated Contaminant Monitoring 

Regulation (UCMR 1). The Agency also 

evaluated supplemental sources of 

occurrence information. 

1. The Unregulated Contaminant 

Monitoring Regulation. In 1999, EPA 

developed the UCMR program in 

coordination with the CCL and the 

National Drinking Water Contaminant 

Occurrence Database (NCOD) to provide 

national occurrence information on 

unregulated contaminants (September 

17, 1999, 64 FR 50556 (USEPA, 1999b); 

March 2, 2000, 65 FR 11372 (USEPA, 

2000b); and January 11, 2001, 66 FR 

2273 (USEPA, 2001b)). 

EPA designed the UCMR 1 data 

collection with three parts (or tiers). 

Occurrence data for perchlorate are from 

the first tier of UCMR (also known as 

UCMR 1 List 1 Assessment Monitoring). 

EPA required all large 7 PWSs, plus a 

statistically representative national 

sample of 800 small 8 PWSs, to conduct 

Assessment Monitoring.9

Approximately one-third of the 

participating small systems were 

scheduled to monitor for these 

contaminants during each calendar year 

from 2001 through 2003. Large systems 

could conduct one year of monitoring 

anytime during the 2001–2003 UCMR 1 

period. EPA specified a quarterly 

monitoring schedule for 1,896 surface 

water systems and a twice-a-year, sixmonth interval monitoring schedule for 

1,969 ground water systems. The 

objective of the UCMR 1 sampling 

approach for small systems was to 

collect contaminant occurrence data 

from a statistically selected, nationally 

representative sample of small systems. 

The small system sample was stratified 

and population-weighted, and included 

some other sampling adjustments, such 

as including at least 2 systems from 

each State. With contaminant 

monitoring data from all large PWSs and 

a statistical, nationally representative 

sample of small PWSs, the UCMR 1 List 

1 Assessment Monitoring program 

provides a contaminant occurrence data 

set suitable for national drinking water 

estimates. 

EPA collected and analyzed drinking 

water occurrence data for perchlorate 

from 3,865 PWSs between 2001 and 

2005 under the UCMR 1. EPA found 

that 160 (approximately 4.1 percent) of 

the 3,865 PWSs that sampled and 

reported had at least 1 analytical 

detection of perchlorate (in at least 1 

sampling point) at levels greater than or 

equal to the method reporting limit 

(MRL) of 4 μg/L. These 160 systems are 

located in 26 States and 2 territories. Of 

these 160 PWSs, 8 are small systems 

(serving 10,000 or fewer people) and 

152 are large systems (serving more than 

10,000 people). These 160 systems 

reported 637 detections of perchlorate at 

levels greater than or equal to 4 μg/L, 

which is approximately 11.3 percent of 

the 5,629 samples collected by these 160 

systems and approximately 1.9 percent 

of the 34,331 samples collected by all 

3,865 systems. The maximum reported 

concentration of perchlorate was 420 

μg/L, from a single surface water sample 

from a PWS in Puerto Rico. The average 

concentration of perchlorate for those 

samples with positive detections for 

perchlorate was 9.85 μg/L and the 

median concentration was 6.40 μg/L. A 

summary of the perchlorate occurrence 

statistics in UCMR 1 is shown in Table 

1. 

TABLE 1—UCMR 1 OCCURRENCE OF PERCHLORATE AT CONCENTRATIONS >= 4 μG/L 10

System size Number of 

samples 

Samples 

w/detects 

Sampling 

points 

tested 

Sampling 

points 

w/detects 

Sampled 

systems 

Systems 

w/detects 

Small Systems ................................................................. 3,295 15 1,454 8 797 8 

Large Systems ................................................................. 31,036 622 13,533 379 3,068 152 

Total Systems ........................................................... 34,331 637 14,987 387 3,865 160 

Notes: 

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60270 Federal Register / Vol. 73, No. 198 / Friday, October 10, 2008 / Notices 

1. For both large and small systems, at 3,865 systems with data, there were 34,331 samples taken at 14,987 (entry) points resulting in 637 

(1.86%) sample detects representing 387 (2.58%) of the entry/sample points in 160 (4.14%) of the systems. 

2. For 3,068 large systems with data, there were 31,036 samples taken at 13,533 entry points resulting in 622 (2.00%) detections representing 

379 (2.80%) entry/sample points in 152 (4.95%) of the systems. 

3. For 797 small systems with data, there were 3,295 samples taken at 1,454 entry points, resulting in a total of 15 (0.455%) detections representing 8 (0.55%) entry/sample points at 8 (1%) of the systems. 

Table 2 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 μg/L (MRL) to 25 μg/L. 

The fourth column of Table 2 presents 

a high end estimate of the population 

served drinking water above a 

threshold. This column presents the 

total population served by 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 included a less conservative 

estimate of the population served water 

above a threshold in the fifth column in 

Table 2. 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 

2. 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 likely an overestimate. 

TABLE 2—UCMR 1 OCCURRENCE AND POPULATION ESTIMATES FOR PERCHLORATE ABOVE VARIOUS THRESHOLDS

Thresholds a

PWSs with at 

least 1 

detection > 

threshold of 

interest 

PWS entry or 

sample points 

with at least 1 

detection > 

threshold of 

interest b

Population 

served by 

PWSs with 

at least 1 

detection > 

threshold of 

interest c

Population 

estimate for 

entry 

or sample 

points 

having at 

least 1 

detection > 

threshold of 

interest d

4 μg/L ................................................................................................... 4.01% ......................

(155 of 3,865) .........

2.48% ......................

(371 of 14,987) .......

e 16.6 M 5.1 M 

5 μg/L ................................................................................................... 3.16% ......................

(122 of 3,865) .........

1.88% ......................

(281 of 14,987) .......

14.6 M 4.0 M 

7 μg/L ................................................................................................... 2.12% ......................

(82 of 3,865) ...........

1.14% ......................

(171 of 14,987) .......

7.2 M 2.2 M 

10 μg/L ................................................................................................. 1.35% ......................

(52 of 3,865) ...........

0.65% ......................

(97 of 14,987) .........

5.0 M 1.5 M 

12 μg/L ................................................................................................. 1.09% ......................

(42 of 3,865) ...........

0.42% ......................

(63 of 14,984) .........

3.6 M 1.2 M 

15 μg/L ................................................................................................. 0.80% ......................

(31 of 3,865) ...........

0.29% ......................

(44 of 14,987) .........

2.0 M 0.9 M 

17 μg/L ................................................................................................. 0.70% ......................

(27 of 3,865) ...........

0.24% ......................

(36 of 14,987) .........

1.9 M 0.8 M 

20 μg/L ................................................................................................. 0.49% ......................

(19 of 3,865) ...........

0.16% ......................

(24 of 14,987) .........

1.5 M 0.7 M 

25 μg/L ................................................................................................. 0.36% ......................

(14 of 3,865) ...........

0.12% ......................

(18 of 14,987) .........

1.0 M 0.4 M 

Footnotes: 

aAll occurrence measures in this table were conducted on a basis reflecting values greater than the listed thresholds. 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. dBecause 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. eThis value does not include the population associated with 5 systems serving 200,000 people that measured perchlorate at 4 μg/L in at least 

one sample. 

2. Supplemental Occurrence Data. 

The Agency also evaluated drinking 

water monitoring data for perchlorate in 

California and Massachusetts. EPA 

considers these State data to be 

supplemental for purposes of this 

regulatory determination, because they 

are not nationally representative. EPA 

believes these State’s monitoring results 

are generally consistent with the results 

collected by EPA under UCMR 1. The 

California Department of Public Health 

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(CDPH) last updated its perchlorate 

monitoring results on July 10, 2008 

(CDPH, 2008). The Massachusetts’s 

Department of Environmental Protection 

(MA DEP) last updated its draft report 

on The Occurrence and Sources of 

Perchlorate in Massachusetts in April, 

2006 (MA DEP, 2005). 

C. Evaluation of Perchlorate Exposure 

From Sources Other Than Drinking 

Water 

An important element of EPA’s 

regulatory determination process is to 

consider the contaminant exposure that 

individuals are likely to receive from 

sources other than drinking water. An 

individual’s total exposure to a 

contaminant is more relevant to his or 

her risk for adverse health effects than 

is exposure to the contaminant from 

drinking water alone. 

Because there are significant sources 

of perchlorate exposure other than 

through the drinking water route, EPA 

determined that data on exposure to 

perchlorate from these sources is critical 

to the evaluation of whether or not there 

is a meaningful opportunity for health 

risk reduction through a national 

primary drinking water rule for 

perchlorate. Dietary studies pose a 

particular challenge because there is 

great variety in the American diet and 

many foods must be analyzed to enable 

a comprehensive dietary exposure 

estimate. However, EPA believes that 

two recent studies provide a sound basis 

for evaluating total perchlorate 

exposure. These are the Food and Drug 

Administration (FDA) Total Diet Study 

and an analysis of NHANES/UCMR data 

conducted by EPA and CDC. 

FDA’s Total Diet Study (TDS) 

combines nationwide sampling and 

analysis of hundreds of food items along 

with national surveys of food intake to 

develop comprehensive dietary 

exposure estimates for a variety of 

demographic groups in the U.S. CDC’s 

NHANES data base measured 

perchlorate in the urine of a 

representative sample of Americans. 

EPA and CDC used data from the 

NHANES data base and UCMR 

monitoring to estimate perchlorate 

exposure from food and water together, 

and food alone, for different subpopulations. This section of the notice 

provides details on the results of these 

studies. Because the sources of exposure 

encompassed by each of these studies 

overlap, EPA has considered them both 

in making a regulatory determination in 

an effort to provide the most 

comprehensive basis for the preliminary 

determination. 

In this section, EPA also provides a 

brief review of other dietary and 

biomonitoring studies that, while not 

directly incorporated into our 

determination, tend to reinforce the 

results of the primary exposure studies. 

1. Food Studies. The FDA, the United 

States Department of Agriculture 

(USDA), and other researchers have 

studied perchlorate in foods. The most 

recent and most comprehensive 

information available on the occurrence 

of perchlorate in the diet has been 

published by FDA. This section 

describes two perchlorate studies 

released by FDA.—the Total Diet Study 

and FDA’s Exploratory Survey Data on 

Perchlorate in Food. 

a. FDA Total Diet Study, 2005 and 

2006. Since 1961, FDA has periodically 

conducted a broad-based food 

monitoring study known as the Total 

Diet Study (TDS). The purpose of the 

TDS is to measure substances in foods 

representative of the total diet of the 

U.S. population, and to make estimates 

of the average dietary intake of those 

substances for selected age-gender 

groups. A detailed history of the TDS 

can be found at the following Web site: 

http://www.cfsan.fda.gov/∼comm/tdstoc.html. 

Murray et al., (2008) briefly describe 

the design of the current TDS. Dietary 

intakes of perchlorate were estimated by 

combining analytical results from the 

TDS with food consumption estimates 

developed specifically for estimating 

dietary exposure from TDS results. 

While the perchlorate data for TDS 

foods were collected in 2005–2006, the 

food consumption data in the current 

TDS food list is based on results (Egan 

et al., 2007) from the USDA’s 1994–96, 

1998 Continuing Survey of Food Intakes 

by Individuals (94–98 CSFII), which 

includes data for all age groups 

collected in 1994–96, and for children 

from birth through age 9 collected in 

1998. Although over 6,000 different 

foods and beverages were included in 

the food consumption surveys, these 

foods and beverages were collapsed into 

a set of 285 representative foods and 

beverages by aggregating the foods 

according to the similarity of their 

primary ingredients and then selecting 

the specific food consumed in greatest 

quantity from each group as the 

representative TDS food for that group. 

The consumption amounts of all the 

foods in a group were aggregated and 

assigned to the representative food for 

that group. It is these 285 representative 

foods and beverages that are on the 

current TDS food list. This approach to 

estimating dietary intakes assumes that 

the analytical profiles (e.g., perchlorate 

concentrations) of the representative 

foods are similar to those of the larger 

group of foods from the original 

consumption survey to which they 

correspond. This approach provides a 

reasonable estimate of total dietary 

exposure to the analytes from all foods 

in the diet, not from the representative 

TDS foods alone. The sampled TDS 

foods are purchased at retail from 

grocery stores and fast-food restaurants. 

The foods are prepared table-ready prior 

to analyses, using distilled water when 

water is called for in the recipe. The 

analytical method developed and used 

by FDA to measure perchlorate in food 

samples has a nominal limit of detection 

(LOD) of 1.00 ppb and a limit of 

quantitation (LOQ) of 3.00 ppb 

(Krynitsky et al., 2006). 

Murray et al., (2008) reports that FDA 

included perchlorate as an analyte in 

TDS baby foods in 2005 and in all other 

TDS foods in 2006. Iodine was analyzed 

in all TDS foods from five market 

baskets surveyed in late 2003 through 

2004. Using these data collectively, FDA 

developed estimates of average dietary 

perchlorate and iodine intake for 14 agegender groups. To account for 

uncertainties associated with samples 

with no detectable concentrations of 

perchlorate or iodine (non-detects or 

NDs), FDA calculated a lower-bound 

and upper-bound for each estimate of 

average dietary exposure, assuming that 

NDs equal to zero and the LOD, 

respectively. Specifically, FDA 

multiplied these upper- and lowerbound concentrations by the average 

daily consumption amount of the 

representative food for the given 

subpopulation group to provide a range 

of average intakes for each TDS food. 

Table 3 summarizes the FDA 

estimated upper- and lower-bound 

average dietary perchlorate intakes 

(from food) for 14 age-gender groups on 

a per kilogram of body weight per day 

basis to enable direct comparison to the 

perchlorate RfD. Murray et al., (2008) 

reports that average body weights for 

each population group were based on 

self-reported body weights from 

respondents in the 94–98 CSFII. 

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11Murray et al., (2008) compared estimated 

average iodine intakes with U.S. Dietary Reference 

Intakes for iodine (NAS, 2000). The reference values 

cited by Murray et al., (2008) are as follows: 130 

μg/person/day for infants, 65 μg/person/day for 

children 1–8 years, 73 μg/person/day for children 

9–13 years, and 95 μg/person/day for the remainder 

of population. 

TABLE 3—LOWER- AND UPPER-BOUND (ND = 0 AND LOD) PERCHLORATE INTAKES FROM FDA’S TDS RESULTS FOR

2005–2006 

Population group 

Average perchlorate intake 

from food 

(μg/kg/day) 

Lower-bound Upper-bound 

Infants—6–11 mo .................................................................................................................................................... 0.26 0.29 

Children—2 yr .......................................................................................................................................................... 0.35 0.39 

Children—6 yr .......................................................................................................................................................... 0.25 0.28 

Children—10 yr ........................................................................................................................................................ 0.17 0.20 

Teenage Girls—14–16 yr ........................................................................................................................................ 0.09 0.11 

Teenage Boys—14–16 yr ........................................................................................................................................ 0.12 0.14 

Women—25–30 yr ................................................................................................................................................... 0.09 0.11 

Men—25–30 yr ........................................................................................................................................................ 0.08 0.11 

Women—40–45 yr ................................................................................................................................................... 0.09 0.11 

Men—40–45 yr ........................................................................................................................................................ 0.09 0.11 

Women—60–65 yr ................................................................................................................................................... 0.09 0.10 

Men—60–65 yr ........................................................................................................................................................ 0.09 0.11 

Women—70+ yr ....................................................................................................................................................... 0.09 0.11 

Men—70+ yr ............................................................................................................................................................ 0.11 0.12 

Based on their analysis of TDS data, 

FDA reports that detectable levels of 

perchlorate were found in at least one 

sample in 74 percent (211 of 286) of 

TDS foods (Murray et al., 2008). The 

average estimated perchlorate intakes 

for the 14 age-gender groups range from 

0.08 to 0.39 μg/kg/day, compared with 

the RfD of 0.7 μg/kg/day. Though not 

shown here, Murray et al., (2008) 

reports that average estimated iodine 

intakes for the 14 age-gender groups 

range from 138 to 353 μg/person/day, 

and for all groups exceed the relevant 

U.S. dietary reference values used for 

assessing the nutritional status of 

populations.11

The results of the TDS dietary intake 

assessment provide an estimate of the 

average dietary perchlorate intakes by 

specific age-gender groups in the U.S. 

However, Murray et al. note that the 

current TDS design ‘‘does not allow for 

estimates of intakes at the extremes 

(i.e., upper or lower percentiles of food 

consumption) or for population 

subgroups within the 14 age/sex groups 

that may have specific nutritional needs 

(e.g., the subgroups of pregnant and 

lactating women within the groups of 

women of child bearing age).’’ 

Nevertheless, Murray et al. stated that: 

‘‘These TDS results increase 

substantially the available data for 

characterizing dietary exposure to 

perchlorate and provide a useful basis 

for beginning to evaluate overall 

perchlorate and iodine estimated dietary 

intakes in the U.S. population.’’ 

b. FDA Exploratory Survey Data on 

Perchlorate in Food, 2003–2005. Prior to 

including perchlorate in the TDS, FDA 

conducted exploratory surveys from 

October 2003 to September 2005 to 

determine the occurrence of perchlorate 

in a variety of foods. In May 2007, FDA 

provided an estimate of perchlorate 

exposure from these surveys (http:// 

www.cfsan.fda.gov/∼dms/clo4ee.html). 

Using the data from these exploratory 

studies and food and beverage 

consumption values from USDA’s 94–98 

CSFII, FDA estimated mean perchlorate 

exposures of 0.053 μg/kg/day for all ages 

(2+ years), 0.17 μg/kg/day for children 

(2–5 years), and 0.037 μg/kg/day for 

females (15–45 years). There are 

uncertainties associated with the 

preliminary exposure assessment 

because the 27 foods and beverages 

selected represent only about 32 to 42 

percent of the total diet depending on 

the population group. Additionally, the 

overall goal of the sampling plan was to 

gather initial information on occurrence 

of perchlorate in foods from various 

locations with a high likelihood of 

perchlorate contamination. With the 

preceding caveats in mind, the results of 

these exploratory studies are generally 

consistent with the more complete 

results of the 2005–2006 TDS. For the 

purpose of developing a national 

estimate of dietary perchlorate 

exposure, the results of FDA’s 

exploratory studies are superseded by 

the results of the TDS. 

c. Other Published Food Studies. 

Since publication of EPA’s May 2007 

notice, Pearce et al., (2007) published an 

analysis of perchlorate concentrations in 

17 brands of prepared ready to eat and 

concentrated liquid infant formula. 

Perchlorate concentrations in the 17 

samples ranged from 0.22 to 4.1 μg/L, 

with a median concentration of 1.5 μg/ 

L. The researchers did not estimate the 

dose infants would consume at the 

concentrations observed in the study. 

FDA also included sampling and 

analysis of infant formula in their 2008 

TDS analysis, discussed above. 

Studies, such as those published by 

Kirk et al., (2003, 2005) and Sanchez et 

al., (2005a, 2005b) have examined 

perchlorate in milk and produce. These 

studies and others were summarized in 

EPA’s May 2007 notice describing the 

status of EPA’s evaluation of perchlorate 

(72 FR 24016 (USEPA, 2007)). 

2. Biomonitoring Studies. Researchers 

have also begun to investigate 

perchlorate occurrence in humans by 

analyzing for perchlorate in urine and 

breast milk. For example, CDC has 

included perchlorate in its National 

Biomonitoring Program, which develops 

methods to measure environmental 

chemicals in humans. With this 

information, the CDC can obtain data on 

levels and trends of exposure to 

environmental chemicals in the U.S. 

population. 

a. Urinary Biomonitoring. In the 

largest study of its kind, Blount et al., 

(2006c) measured perchlorate in urine 

samples collected from a nationally 

representative sample of 2,820 U.S. 

residents as part of the 2001–2002 

NHANES. Blount et al., (2006c) detected 

perchlorate at concentrations greater 

than 0.05 μg/L in all 2,820 urine 

samples tested, with a median 

concentration of 3.6 μg/L and a 95th 

percentile of 14 μg/L. Women of 

reproductive age (15–44 years) had a 

median urinary perchlorate 

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concentration of 2.9 μg/L and a 95th 

percentile of 13 μg/L. The demographic 

with the highest concentration of 

urinary perchlorate was children (6–11 

years), who had a median urinary 

perchlorate concentration of 5.2 μg/L. 

Blount et al., (2006c) estimated a total 

daily perchlorate dose for the NHANES 

participants aged 20 and older (for 

whom a creatinine correction method 

was available) and found a median dose 

of 0.066 μg/kg/day (about one tenth of 

the RfD) and a 95th percentile dose of 

0.234 μg/kg/day (about one third of the 

RfD). Eleven adults (0.7 percent) had 

estimated perchlorate exposure greater 

than perchlorate’s RfD of 0.7 μg/kg/day 

(the highest calculated exposure was 

3.78 μg/kg/day). Because of daily 

variability in diet and perchlorate 

exposure, and the short residence time 

of perchlorate in the body, these single 

sample measurements may overestimate 

long-term average exposure for 

individuals at the upper end of the 

distribution and may underestimate the 

long-term average exposure for 

individuals at the lower end of the 

distribution. Blount et al. did not 

estimate daily perchlorate dose for 

children and adolescents due to the 

limited validation of estimation 

methods for these age groups at that 

time (Blount et al., 2006c). 

In a recent unpublished, but peer 

reviewed, study, EPA and CDC 

investigators merged the data sets from 

NHANES and UCMR 1 to identify the 

NHANES participants from counties 

which had a perchlorate detection 

during the UCMR survey (USEPA, 

2008a). The study assumes, based on 

previous analyses of perchlorate 

pharmacokinetics, that urine is the sole 

excretion pathway other than in 

lactating women. Since all NHANES 

participants’ urine contained 

perchlorate, separating out those who 

had a higher potential for additional 

exposure via drinking water from those 

who had a lower potential for drinking 

water exposure left the remainder of 

participants whose exposure was 

expected to be primarily from food. 

The advantage of a urinary 

biomonitoring study is that it analyzes 

the perchlorate actually ingested in the 

diets of a large number of individuals 

rather than using estimators of 

perchlorate ingestion from a variety of 

foods for a diverse population. The 

methodology provides a novel 

opportunity to use public water system 

occurrence and human biomonitoring 

data to directly inform EPA’s decision. 

The approach is reasonable for 

estimating perchlorate intake at various 

percentiles from food and to gain an 

understanding of the relative 

contribution from water. A limitation is 

in the use of NHANES’s spot urine 

testing, and creatinine corrections for a 

population with diverse physiological 

characteristics, to calculate the daily 

perchlorate dose. The cross sectional 

study attempts to capture a 

representative exposure, but was limited 

by the need to match up drinking water 

occurrence data with biomonitoring 

data on a county-wide basis, even 

though county and public water system 

service area boundaries often do not 

coincide. There also may have been 

some temporal mismatch between the 

occurrence and biomonitoring data. 

As noted, the primary goal of the 

study was to derive the dose of 

perchlorate coming from food alone by 

eliminating possible sources of water 

contribution. Individuals’ data were 

placed into one of three bins based on 

likelihood of perchlorate being in their 

tap water. The bins were further sorted 

by age and sex. Bin I was comprised of 

NHANES 2001–2002 data for 

individuals residing in the same 

counties as public water systems that 

had at least one positive measurement 

of perchlorate during the sample period, 

as measured in UCMR 1. Therefore, this 

bin represented those who were more 

likely to be exposed to perchlorate in 

both food and water. For the most part, 

the average perchlorate level in urine for 

all age groups was the highest in this 

bin, and the creatinine-corrected 

average dose for all individuals in this 

group was 0.101 μg/kg/day, with a 

geometric mean of 0.080 μg/kg/day. 

In contrast, Bin III was comprised of 

data for individuals considered less 

likely to have exposure to perchlorate 

via drinking water, as defined in one of 

three ways: (1) They resided in counties 

where there were no quantified 

detections of perchlorate in public 

drinking water systems sampled as part 

of UCMR (i.e., UCMR 1 results were 

below the minimum reporting limit of 4 

μg/L); or (2) they self-reported that they 

had not consumed tap water in the 

previous 24 hours regardless of where 

they resided (i.e., they may have resided 

in a county with a positive UCMR 

finding, but did not drink tap water); or 

(3) again, not considering the UCMR 

status of the county, their response to 

NHANES indicated they used a reverse 

osmosis filter which may be effective for 

removing perchlorate. Bin III thus 

represents results of urinary perchlorate 

from individuals who were less likely to 

experience perchlorate exposure via tap 

water, and were thus more likely to 

have their perchlorate exposure caused 

solely by intake from food. The average 

creatinine-corrected perchlorate dose for 

these individuals was 0.090 μg/kg/day, 

with a geometric mean of 0.062 μg/kg/ 

day. 

Finally, Bin II included individuals 

residing in counties which had not been 

sampled in UCMR. As such, there is no 

information on potential perchlorate in 

their public drinking water. The average 

creatinine-corrected perchlorate dose for 

these individuals was 0.072 μg/kg/day, 

with a geometric mean of 0.053 μg/kg/ 

day. The results for Bin II are somewhat 

anomalous, and may suggest either that 

drinking water concentrations are even 

lower in these non-monitored counties 

than in the Bin III counties or that food 

exposure for these counties was lower 

than for the counties in either Bin I or 

III. In any case, EPA’s analysis to 

determine the RSC did not focus on Bin 

II, as discussed below. 

A summary of selected results for 

individuals in Bins I and III is shown in 

Table 4. The estimates of daily 

perchlorate intake presented in Table 4 

from the NHANES–UCMR analysis are 

somewhat higher than those of Blount et 

al., (2006). The Blount et al., (2006) 

estimates were limited to adults 20 

years of age and older because 

application of the set of creatinine 

excretion equations used by Blount et 

al. to estimate perchlorate dose was 

limited to adults. Mage et al., (2007) 

provides an expanded set of equations 

that allows for estimating daily 

creatinine excretion rates for children, 

as well as for adults. Since children 

tend to have higher exposure on a per 

body weight basis than adults, it is not 

surprising that the estimates based on 

both adults and children are somewhat 

higher than the Blount estimates based 

on adults alone. The mean total 

exposure for people that are more likely 

to be exposed to perchlorate in food and 

water (Bin I) was calculated to be 0.101 

μg/kg/day. The average exposure for 

people more likely to be exposed to 

perchlorate from food alone (Bin III) was 

0.090 μg/kg/day. 

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TABLE 4—ESTIMATED DAILY PERCHLORATE INTAKES (μG/KG/DAY) FOR TWO BINS BASED ON UCMR 1 OCCURRENCE

DATA

Group Bin* Number of 

people 

Average 

(mean) 

Geometric 

mean 

50th 

percentile 

90th 

percentile 

Total ................................................................................. I 320 0.101 0.080 0.075 0.193 

III 2,063 0.090 0.062 0.058 0.167 

Age: 6–11 ......................................................................... I 52 0.152 0.132 0.131 0.237 

III 270 0.150 0.118 0.124 0.280 

Age: 12–19 ....................................................................... I 100 0.109 0.078 0.070 0.286 

III 608 0.080 0.061 0.060 0.158 

Age: 20 or more ............................................................... I 168 0.091 0.074 0.071 0.186 

III 1,185 0.085 0.057 0.055 0.143 

Females: 15–44 ............................................................... I 57 0.081 0.062 0.071 0.141 

III 505 0.093 0.055 0.052 0.143 

Pregnant Females ............................................................ I 8 0.097 0.086 0.060 0.121 

III 98 0.123 0.064 0.056 0.263 

* Bin I was comprised of individuals residing in counties which had at least one positive measurement of perchlorate somewhere in the public 

drinking water supply. Bin III was comprised of individuals considered less likely to have exposure to perchlorate via drinking water based on a 

three-part test (see text). 

Using Bin III as the dose most closely 

representing only dietary perchlorate 

exposure, one can compare results from 

the FDA TDS, shown previously in 

Table 3. For example, for females 14–16, 

women 25–30, and women 40–45 years 

old, the FDA mean food dose was 0.09– 

0.1 μg/kg/day. In the EPA–CDC 

biomonitoring study of NHANES– 

UCMR, the mean food dose for women 

of child-bearing age (15–44 years old) 

was 0.093 μg/kg/day. The results from 

calculating likely food intakes (TDS 

study) and from urinalysis from actual 

intakes (NHANES/UCMR) are in close 

agreement where comparisons can be 

made. 

b. Breast Milk. A number of studies 

have investigated perchlorate in human 

breast milk. The most recent study 

included measurements from 49 healthy 

Boston-area volunteers (10–250 days 

postpartum, median 48 days; Pearce et 

al., 2007). Perchlorate was found in all 

samples, ranging from 1.3–411 μg/L, 

with a median concentration of 9.1 

μg/L and a mean concentration of 33 

μg/L. No correlation was found between 

perchlorate and iodine concentrations 

in breast milk. EPA notes that the 

Boston-area public water systems did 

not detect perchlorate in drinking water 

samples collected for the U.S. EPA’s 

Unregulated Contaminant Monitoring 

Rule from 2001 to 2003, nor did Boston 

area systems detect perchlorate in 

samples collected in response to the 

Massachusetts DEP 2004 emergency 

regulations for perchlorate (see Section 

III.B of this notice). 

Kirk et al., (2005) analyzed 36 breast 

milk samples from 18 States (CA, CT, 

FL, GA, HI, MD, ME, MI, MO, NC, NE, 

NJ, NM, NY, TX, VA, WA, WV) and 

found perchlorate concentrations in all 

samples ranging from 1.4 to 92.2 μg/L, 

with a mean concentration of 10.5 μg/ 

L. Kirk et al., (2007) later did a smaller 

study involving 10 women, which 

included 6 samples on each of 3 days 

in a temporal study. Half the women 

were from Texas, but the others were 

from CO, FL, MO, NM, and NC. They 

found significant variation in all 

samples (n=147), with a range, mean, 

and median perchlorate concentration 

of 0.5–39.5 μg/L, 5.8 μg/L, and 4.0 

μg/L, respectively. 

Te ́llez et al., (2005) reported maternal 

parameters for participants from a study 

conducted in Chile. Breast milk samples 

indicated that a significant amount of 

perchlorate leaves the body of the 

nursing mother through breast milk, in 

addition to urine. However, the breast 

milk perchlorate levels were highly 

variable and no significant correlations 

could be established between breast 

milk perchlorate and either urine 

perchlorate or breast milk iodide 

concentrations for the individuals 

evaluated in these Chilean cities (Te ́llez 

et al., 2005). 

Blount et al., (2007) also suggests 

breast milk as an excretion pathway and 

the NHANES–UCMR study authors 

observed a difference between the 

urinary perchlorate concentration of 

breast feeding women versus pregnant 

women with an overall mean 

concentration of 0.130 μg/kg/day for 117 

pregnant women compared to a 

concentration of 0.073 μg/kg/day for the 

24 breast-feeding women (USEPA, 

2008a). 

Dasgupta et al., (2008) analyzed breast 

milk samples and 24 hour urine samples 

from 13 lactating women from Texas for 

perchlorate and iodine. For breast milk, 

they found perchlorate concentrations 

ranging from 0.01 to 48 μg/L, with a 

median concentration of 7.3 μg/L and a 

mean concentration of 9.3 μg/L (457 

total samples). For iodine, 

concentrations ranged from 1 to 1,200 

μg/L, with a median concentration of 43 

μg/L and a mean concentration of 120 

μg/L (447 total samples). For urine they 

found perchlorate concentrations 

ranging from 0.6 to 80 μg/L, with a 

median concentration of 3.2 μg/L and a 

mean concentration of 4.0 μg/L (110 

total samples). For iodine, 

concentrations ranged from 26 to 630 

μg/L, with a median concentration of 

110 μg/L and a mean concentration of 

140 μg/L (117 total samples) 

IV. Preliminary Regulatory 

Determination for Perchlorate 

In making preliminary regulatory 

determinations, EPA uses the criteria 

mandated by the 1996 SDWA 

Amendments. EPA has found that 

perchlorate, at sufficiently high doses, 

may have an adverse effect on the health 

of persons, and that perchlorate is found 

in a small percentage of public water 

supply systems. However, EPA has 

determined that regulation of 

perchlorate in drinking water systems 

does not present a meaningful 

opportunity to reduce health risk for 

persons served by public water systems. 

This section describes how EPA has 

evaluated these three criteria in light of 

the data presented in Section III to make 

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a preliminary regulatory determination 

for perchlorate. 

A. May Perchlorate Have an Adverse 

Effect on the Health of Persons? 

Yes. Perchlorate interacts with the 

sodium iodide symporter, reducing 

iodine uptake into the thyroid gland 

and, at sufficiently high doses, the 

amount of T4 produced and available 

for release into circulation. Sustained 

changes in thyroid hormone secretion 

can result in hypothyroidism. Thyroid 

hormones stimulate diverse metabolic 

activities in most tissues and 

individuals suffering from 

hypothyroidism experience a general 

slowing of metabolism of a number of 

organ systems. In adults, these effects 

are reversed once normal hormone 

levels are restored (NRC, 2005). 

In fetuses, infants, and young 

children, thyroid hormones are critical 

for normal growth and development. 

Irreversible changes, particularly in the 

brain, are associated with hormone 

insufficiencies during development in 

humans (Chan and Kilby, 2000 and 

Glinoer, 2007). Disruption of iodide 

uptake presents particular risks for 

fetuses and infants (Glinoer, 2007 and 

Delange, 2004). Because the fetus 

depends on an adequate supply of 

maternal thyroid hormone for its central 

nervous system development during the 

first trimester of pregnancy, iodide 

uptake inhibition from perchlorate 

exposure has been identified as a 

concern in connection with increasing 

the risk of neurodevelopmental 

impairment in fetuses of high-risk 

mothers (NRC, 2005). Poor iodide 

uptake and subsequent impairment of 

thyroid function in pregnant and 

lactating women have been linked to 

delayed development and decreased 

learning capability in infants and 

children with fetal and neonatal 

exposure (NRC, 2005) 

The NRC recommended basing the 

RfD on a precursor to an adverse effect 

rather than an adverse effect per se. The 

precursor event precedes a downstream 

adverse effect in the dose response 

continuum. In this case, NRC used 

prevention of iodide uptake inhibition, 

a precursor to adverse thyroid effects, to 

establish a level at which no adverse 

effects would be anticipated in exposed 

populations. This approach is consistent 

with the Agency’s policy on the use of 

precursor events when appropriate in 

establishing the critical effect upon 

which an RfD is based (U.S. EPA, 

2002c). 

Based on the information above, EPA 

finds that perchlorate, at sufficiently 

high doses, may have an adverse effect 

on the health of persons. 

B. Is Perchlorate Known To Occur or Is 

There a Substantial Likelihood That 

Perchlorate Occurs at a Frequency and 

at a Level of Public Health Concern in 

Public Water Systems? 

No. EPA has found that perchlorate 

occurs infrequently at levels of health 

concern in public water systems. 

Specifically, EPA established a Health 

Reference Level (HRL) as the level of 

concern and evaluated the information 

on the occurrence of perchlorate in 

public water systems presented in 

Section III.B in relation to this HRL. The 

HRL is a benchmark against which EPA 

compares the concentrations of a 

contaminant found in public water 

systems to determine if it is at a level 

of public health concern. For past 

regulatory determinations for noncarcinogens, EPA has calculated an HRL 

using the Agency’s reference dose (RfD) 

as follows: 

HRL = [(RfD × BW)/DWI] × RSC 

Where: 

RfD = Reference Dose 

BW = Body Weight for an adult assumed to 

be 70 kilograms (kg) 

DWI = Drinking Water Intake for an adult, 

assumed to be 2 L/day 

RSC = Relative Source Contribution, or the 

remaining portion of the reference dose 

available for drinking water after other 

sources of exposure have been 

considered (e.g., food, ambient air) 

In addition, EPA has used a RSC 

default value of 20 percent for screening 

purposes to estimate the HRL for past 

regulatory determinations because it has 

lacked adequate data to develop an 

empirical RSC. In the absence of such 

data, EPA has determined that it is 

appropriate to use a conservative value 

that is more likely to understate than to 

overstate the amount of contaminant 

that can be safely ingested through 

drinking water. For its two previous sets 

of regulatory determinations, EPA did 

not find contaminants at frequencies 

and levels of concern in comparison to 

the conservative screening-level HRL. 

Therefore, it was not necessary for the 

Agency to further evaluate the RSC in 

making regulatory determinations for 

these contaminants. 

However, the Agency believes that 

sufficient exposure data are 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 

subpopulations identified by the NRC). 

These exposure data include the further 

analysis by EPA of the UCMR data and 

the CDC’s NHANES biomonitoring data, 

as well as the FDA’s Total Diet Study. 

The following sections describe EPA’s 

analyses of each of these data sources to 

estimate RSCs and HRLs for this 

sensitive subpopulation. 

1. Total Diet Study for Estimation of 

an RSC. The results of FDA’s recent 

evaluation of perchlorate under the TDS 

were presented in Section III.C.1 of this 

notice. The TDS estimates are 

representative of average, national, 

dietary perchlorate exposure, for the 

age-gender groups that were selected. 

EPA used FDA’s dietary exposure 

estimates to calculate RSC values by 

subtracting the dietary estimates from 

the RfD (0.7 μg/kg/day), dividing this 

difference by the RfD, and multiplying 

the result by 100 (to convert it to a 

percentage). Because EPA believes that 

dietary ingestion is the only significant 

pathway for non-drinking-water 

perchlorate exposure, the resulting RSCs 

represent the amount of perchlorate 

exposure (as a percentage of the RfD) 

that the average individual within a 

subgroup would have to ingest via 

drinking water in order to reach a level 

of total perchlorate exposure that equals 

the RfD. These RSCs, displayed as 

percentages, are presented in Table 5. 

TABLE 5—RELATIVE SOURCE CONTRIBUTIONS REMAINING FOR WATER BASED ON TDS FOR VARIOUS SUBGROUPS

Population group 

Total perchlorate intake 

from food 

(μg/kg/day) 

RfD that 

remains 

(μg/kg/day) 

RSC remaining for drinking 

water 

(as a percentage of the 

RfD) 

Infants, 6–11 mo .......................................................................................................................... 0.26–0.29 0.41–0.44 59–63 

Children, 2 yr ............................................................................................................................... 0.35–0.39 0.31–0.35 44–50 

Children, 6 yr ............................................................................................................................... 0.25–0.28 0.42–0.45 60–64 

Children, 10 yr ............................................................................................................................. 0.17–0.20 0.50–0.53 71–76 

Teenage Girls, 14–16 yr .............................................................................................................. 0.09–0.11 0.59–0.61 84–87 

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TABLE 5—RELATIVE SOURCE CONTRIBUTIONS REMAINING FOR WATER BASED ON TDS FOR VARIOUS SUBGROUPS— 

Continued 

Population group 

Total perchlorate intake 

from food 

(μg/kg/day) 

RfD that 

remains 

(μg/kg/day) 

RSC remaining for drinking 

water 

(as a percentage of the 

RfD) 

Teenage Boys, 14–16 yr ............................................................................................................. 0.12–0.14 0.56–0.58 80–83 

Women, 25–30 yr ........................................................................................................................ 0.09–0.11 0.59–0.61 84–87 

Men, 25–30 yr .............................................................................................................................. 0.08–0.11 0.69–0.62 84–89 

Women, 40–45 yr ........................................................................................................................ 0.09–0.11 0.59–0.61 84–87 

Men, 40–45 yr .............................................................................................................................. 0.09–0.11 0.59–0.61 84–87 

Women, 60–65 yr ........................................................................................................................ 0.09–0.10 0.60–0.61 86–87 

Men, 60–65 yr .............................................................................................................................. 0.09–0.11 0.59–0.61 84–87 

Women, 70+ yr ............................................................................................................................ 0.09–0.11 0.59–0.61 84–87 

Men, 70+ yr .................................................................................................................................. 0.11–0.12 0.58–0.59 83–84 

The subpopulation that is the most 

sensitive to perchlorate exposure is the 

fetus of an iodine-deficient pregnant 

woman. The FDA TDS does not estimate 

the dietary intake of perchlorate 

specifically for pregnant women (nor 

can it specifically address iodinedeficient women); but it does present 

dietary estimates for three groups of 

women of childbearing age (Teenage 

girls 14–16, Women 25–30 and Women 

40–45). The calculated RSCs range from 

84 to 87 percent for women of 

childbearing age. Murray et al. (2008) 

suggested that perchlorate intake rates 

for pregnant and lactating women are 

‘‘likely to be somewhat higher than 

those of women of childbearing age as 

a whole.’’ If this is true, an RSC derived 

based upon the TDS mean dietary intake 

for women of childbearing age may 

underestimate the relative source 

contribution from food for pregnant 

women. 

2. Urinary Data for Estimation of an 

RSC. As described in Section III.C.2 of 

this notice, EPA and CDC researchers 

analyzed NHANES urinary data in 

conjunction with UCMR occurrence 

data at the CDC’s National Center for 

Environmental Health (NCEH) to 

evaluate exposure to perchlorate. These 

data were partitioned to provide an 

estimate of what portion of the overall 

exposure likely came from food alone. 

In this analysis, EPA and CDC 

researchers were able to characterize the 

distribution of actual perchlorate 

exposure as seen in their urine for 

pregnant women. This means that the 

analysis could determine not only the 

mean exposure, but also the exposure of 

highly exposed individuals. Results of 

this analysis, presented in Table 6, 

indicate that for pregnant women, 

exposure to perchlorate from food is 

0.263 μg/kg/day at the 90th percentile, 

representing nearly 38 percent of the 

RfD, and thus leaving an RSC for water 

of 62 percent. 

TABLE 6—DOSE REMAINING FOR WATER, AND FRACTION OF RFD (RSC) BASED ON NHANES–UCMR ANALYSIS

CALCULATIONS OF PERCHLORATE IN FOOD

Group 

Mean food 

dose 

(μg/kg/day) 

RfD that 

remains 

(μg/kg/day) 

RSC as % 

of RfD 

Median 

food dose 

(μg/kg/day) 

RfD that 

remains 

(μg/kg/day) 

RSC as % 

of RfD 

90th 

percentile 

food dose 

(μg/kg/day) 

RfD that 

remains 

(μg/kg/day) 

RSC as % 

of RfD 

Total population ..................................... 0.090 0 .61 87 0.075 0 .625 89 0.167 0 .533 76 

Ages 6–11 ............................................. 0.150 0 .55 79 0.124 0 .58 83 0.280 0 .42 60 

Ages 12–19 ........................................... 0.080 0 .62 89 0.060 0 .64 91 0.158 0 .542 77 

Ages 20 + .............................................. 0.085 0 .615 88 0.055 0 .645 92 0.143 0 .557 80 

Female 15–44 ....................................... 0.093 0 .607 87 0.052 0 .65 93 0.143 0 .557 80 

Pregnant ................................................ 0.123 0 .58 82 0.056 0 .64 91 0.263 0 .437 62 

3. HRL Derivation. EPA believes the 

NHANES–UCMR analysis is the best 

available information to characterize 

non-drinking water exposures to 

perchlorate for the most sensitive 

subpopulation. The FDA Total Diet 

Study provides a nationally 

representative estimate of the mean 

dietary exposure to perchlorate for 14 

age and gender groups, including 

women of childbearing age. However, 

this study does not provide specific 

estimates for the most sensitive 

subpopulation, the iodine-deficient 

pregnant woman and her fetus. Also, 

this study estimates only mean 

exposures, so it does not account for the 

perchlorate exposure of highly exposed 

individuals. The NHANES–UCMR 

analysis provides 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 also does not separate out 

iodine-deficient pregnant women 

because of data limitations. Table 7 

presents the HRLs developed for the 

most sensitive subpopulation using the 

TDS data and the NHANES–UCMR data. 

EPA notes that the mean RSC for 

pregnant women estimated from the 

NHANES–UCMR data is very close to, 

but slightly lower than, the mean for 

women of childbearing age estimated 

from the TDS data. This shows close 

agreement between the two data sets 

and is consistent with the suggestion in 

Murray et al. that food exposures for 

pregnant women are likely to be 

somewhat higher than for women of 

childbearing age as a whole. (Note that 

higher food exposure equates to a lower 

RSC because a smaller fraction of the 

RfD is left to be allocated to drinking 

water.) While the means are available 

(and in close agreement) from both data 

sets, EPA believes it is more protective 

to estimate the HRL for drinking water 

by subtracting the 90th percentile 

exposure in food from the reference 

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dose to assure that the highly exposed 

individuals from this most sensitive 

subpopulation are considered in the 

evaluation of whether perchlorate is 

found at levels of health concern. The 

NHANES–UCMR data allow for the 

calculation of the 90th percentile food 

exposure, which results in an HRL of 15 

μg/L for the pregnant woman. 

TABLE 7—HEALTH REFERENCE LEVELS FOR PREGNANT WOMEN USING TDS DATA AND NHANES–UCMR DATA

Subpopulation Body 

weight a

Drinking 

water consumption aSource of RSC derivation RSC 

(percent) HRL 

Women of Childbearing Age ....................... 70 kg ........ 2 liters ...... TDS mean (Table 5) .................................... 84–87 21 μg/L 

Pregnant Women ......................................... 70 kg ........ 2 liters ...... NHANES–UCMR mean (Table 6) ............... 82 20 μg/L 

Pregnant Women ......................................... 70 kg ........ 2 liters ...... NHANES–UCMR 90th percentile (Table 6) 62 15 μg/L 

Footnotes: 

a Default values used by EPA in the derivation of HRLs. 

4. Frequency of Exposure at Health 

Reference Level. The number of 

pregnant women potentially exposed to 

perchlorate in public drinking water 

above these HRLs can be estimated from 

the UCMR data. Using the data 

presented in Table 2, approximately 0.8 

percent of the systems had one or more 

detections of perchlorate at or above 15 

μg/L, the HRL determined for pregnant 

women in this analysis. These systems 

serve a total of 2.0 million persons in 

their entire service area, of which 1.0 

million are females, and thus might 

become pregnant at some point during 

their lives. However, not all water 

system customers are living in 

households that are served water from 

the entry point(s) that tested positive. 

Table 2 also provides a more refined 

estimate of the potentially exposed 

population by factoring in an estimate of 

the portion of the system population 

served by each entry point (as described 

in Section III.B.1. of this notice). Using 

this second approach, which is likely to 

be more accurate, the number of people 

served by entry points which exceed the 

HRL is 0.9 million, of which 0.45 

million are females. EPA estimates that 

at any one time, 1.4 percent of the 

population from Table 2 served by water 

systems (or entry points) that detected 

perchlorate at levels greater than 15 

μg/L (Table 7) are pregnant women. This 

estimate is based on the number of live 

births (4,059,000, Ventura et al., 2004) 

as a percentage of the total U.S. 

population in 2000 (281,421,906, U.S. 

Census Bureau, 2002). Therefore, a best 

estimate of about 16,000 pregnant 

women (with a high end estimate of 

28,000) could be exposed at levels 

exceeding the HRL at any given time. 

Based on this analysis, EPA concludes 

that perchlorate occurs infrequently at 

levels of health concern in public water 

systems. There are a small percentage of 

public water systems (0.8 percent) 

where drinking water above the HRL, in 

combination with perchlorate from 

food, may result in exposures to 

pregnant women at levels that exceed 

the EPA reference dose for perchlorate. 

However, as explained in section IV.C, 

these exposures to perchlorate in 

drinking water at concentrations above 

the HRL do not rise to the level of a 

meaningful opportunity for public 

health risk reduction through a national 

primary drinking water regulation. 

5. Consideration of Sensitive 

Subpopulations 

In making a regulatory determination, 

the SDWA requires EPA to take into 

consideration the effect of contaminants 

on subgroups that comprise a 

meaningful portion of the general 

population that are identifiable as being 

at greater risk of adverse health effects 

due to exposure to contaminants in 

drinking water than the general 

population. 

As noted above, in past regulatory 

determinations, EPA has calculated a 

screening level HRL based on drinking 

water consumption and body weight 

information for adults in general, 

combined with default assumptions 

about RSC, in the absence of robust 

empirical data. For this preliminary 

perchlorate determination, EPA has 

improved on this approach by using 

body weight, drinking water and food 

exposure data for pregnant women, in 

order to protect the most sensitive 

subpopulation identified by the NRC 

(i.e., the fetuses of these women). In 

addition, EPA has used 90th percentile 

rather than mean food exposure data to 

ensure that the HRL protects highly 

exposed pregnant women and their 

fetuses. However, infants, developing 

children, and people with iodine 

deficiency or thyroid disorders were 

also identified as sensitive 

subpopulations by the NRC. Because 

infants and children eat and drink more 

on a per body weight basis than adults, 

eating a normal diet and drinking water 

with 15 μg/L of perchlorate may result 

in exposure that is greater than the 

reference dose in these groups. To 

address this concern, the potential effect 

of this intake on inhibition of iodide 

uptake in these subgroups (i.e., relative 

sensitivity) was evaluated using PBPK 

modeling, as discussed in Section 

III.A.3. Because the NRC (NRC, 2005) 

found that the inhibition of iodide 

uptake by the thyroid, which is a nonadverse precursor to any adverse effect, 

should be used as the basis for 

perchlorate risk assessment, evaluating 

iodide uptake inhibition is important for 

determining whether the HRL of 15 

μg/L (derived for pregnant women) is 

also an appropriate health reference 

level for the other sensitive 

subpopulations. Reducing some of the 

uncertainty regarding the relative 

sensitivities of these subpopulations 

will help to address the concerns that 

some groups may be exposed above the 

reference dose (calculated using groupspecific body weight and intake 

information), particularly if PBPK 

modeling predicts that at the HRL, these 

groups do not experience precursor 

effects (RAIU inhibition) that exceed the 

no effect level from which the reference 

dose was derived. 

a. Published PBPK Models. The 

Clewell et al. (2007) and Merrill et al. 

(2005) PBPK models predict the 

distribution and elimination of 

perchlorate after it is ingested. The 

models also predict the level of RAIU 

inhibition that would result from 

different levels of perchlorate exposure 

for different subpopulations, including 

children and infants. 

Clewell et al. (2007) predicted that at 

a perchlorate dose of 0.001 mg/kg/day (1 

μg/kg/day), approximately one and one 

half times the RfD, iodide uptake 

inhibition in the most sensitive 

populations, i.e., fetuses and infants, 

was no greater than 1.1 percent. This is 

below the level (1.8 percent) of 

inhibition at the NRC identified noeffect level (NOEL) in healthy adults 

and recommended as the point of 

departure for calculating the RfD, 

applying a 10-fold intraspecies 

uncertainty factor. The fact that for all 

subpopulations the predicted RAIU at a 

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60278 Federal Register / Vol. 73, No. 198 / Friday, October 10, 2008 / Notices 

12The model does not exactly match the average 

measured inhibition at each exposure 

concentration. At the point of departure (7 μg/kg/ 

day), the model predicts a value of 2.1 percent for 

adults, rather than the 1.8 percent from the Greer 

et al. (2002) study. Thus, the model slightly overpredicts the level of inhibition for this group at this 

exposure level, though this relationship may not 

hold true for other sub-groups and exposure levels. 

In any event, the difference between the average 

measured value of 1.8 percent and the modelpredicted value of 2.1 percent is well within the 

statistical uncertainty in the data. 

level slightly above the RfD is still 

below the RAIU at the NOEL is 

consistent with the NRC’s conclusion 

that the RfD would protect even the 

most sensitive sub-populations. 

However, because the Clewell model 

does not account for reduced urinary 

clearance that occurs in young infants, 

EPA modified the model as discussed in 

Section III.A.3 to address this and other 

limitations. 

b. Results of EPA’s Application of the 

Published Models. EPA evaluated the 

published models (Clewell et al., 2007, 

and Merrill et al., 2005) and used them 

to further explore the relationship 

between water concentrations and 

iodide uptake inhibition in different 

subpopulations. As noted in Section 

III.A.3 and discussed in more detail in 

EPA’s description of the model (USEPA, 

2008b), EPA determined that it was 

appropriate to make several changes to 

the models’ computer codes in order to 

harmonize them and more adequately 

reflect the biology. EPA considered in 

detail the data currently available for 

parameters determined to be 

particularly important to the models’ 

predictions, and modified the model 

parameters describing exposure as well 

as urinary excretion of perchlorate and 

iodide. These modifications resulted in 

predicted RAIU inhibition rates that 

were up to 1.5 times the predicted 

inhibition rates in the earlier versions of 

the model. EPA believes its revisions 

have improved the predictive power of 

the model and has used its results as the 

basis for the following discussion. 

Consistent with both the unmodified 

Clewell model and the NRC’s 

conclusions, EPA’s analysis identified 

the near-term fetus (gestation week 40 

fetus) as the most sensitive subgroup, 

with a percent RAIU inhibition that was 

5-fold higher than the percent inhibition 

of the average adult at a dose equal to 

the point of departure (7 μg/kg/day). 

After correcting the model for reduced 

urinary clearance in infants, the same 

analysis shows that the predicted 

percent RAIU inhibition is 

approximately 1-to 2-fold higher for the 

breast-fed and bottle-fed infant (7–60 

days) than for the average adult, and is 

slightly lower for the 1–2 year old child 

than for the average adult. While 

uncertainty remains regarding the 

model’s predictions, EPA believes that it 

is a useful tool, in conjunction with 

appropriate exposure information, for 

evaluating the relative sensitivity of 

particular subpopulations (infants and 

children) that can inform our 

assessment of whether the HRL is an 

appropriate health reference level for all 

subpopulations (not just pregnant 

women). 

EPA thus applied the adjusted model 

to the HRL of 15 μg/L to determine the 

predicted percent RAIU inhibition 

(Table 8). Iodide uptake inhibition 

levels for all other subpopulations, 

including infants and children, were 

estimated to be not greater than 2.0 

percent at the 15 μg/L drinking water 

concentration and not greater than 2.2 

percent when also considering 

perchlorate in food. The highest iodide 

update inhibition level (2.2 percent) was 

seen for the 7 day bottle fed infant; all 

other subpopulations, including the 60 

day bottle fed infant as well as the 7 and 

60 day breast fed infant had inhibition 

levels below 1.4 percent when also 

considering perchlorate in food. The 2.2 

percent inhibition level for 7-day old 

bottle fed infants is comparable to the 

1.8 percent inhibition level that the NRC 

identified as a no effect level in healthy 

adults and recommended as the point of 

departure for calculating the RfD.12

Table 8 also shows the exposure to 

each subpopulation in μg/kg of body 

weight. EPA notes that for some 

subgroups, the modeled exposure 

exceeds the RfD, though not for the most 

sensitive subgroup (i.e., pregnant 

women and their fetuses) from which 

the HRL was derived. EPA has used 

these exposure estimates as one input 

into the PBPK model to reduce the 

uncertainty associated with the relative 

sensitivities of other subgroups, 

particularly infants and children. EPA 

believes use of the model enhances its 

assessment beyond considering 

exposure alone by predicting the 

resulting iodide uptake inhibition that 

may result from that exposure. As noted 

above, the NRC concluded that the 

‘‘most health protective and 

scientifically valid approach’’ was to 

base the point of departure for the RfD 

on the inhibition of iodide uptake by the 

thyroid (NRC, 2005), a non-adverse 

precursor effect. The predicted RAIU 

inhibition for all subgroups is 

comparable to or less than the RAIU at 

the NOEL selected by the NRC. 

Therefore EPA believes the HRL of 15 

μg/L, derived for pregnant women, is 

also an appropriate health reference 

level for other sub-populations, against 

which to evaluate monitored levels of 

perchlorate occurrence in drinking 

water systems. 

TABLE 8—PREDICTED PERCENT RADIOACTIVE IODIDE UPTAKE (RAIU) INHIBITION AND CORRESPONDING PERCHLORATE

INTAKE FROM WATER AT 15 μG/L WITH AND WITHOUT FOOD INTAKE

Body weight 

(kg) a

90th 

Percentile 

water intake 

(L/day) b

Perchlorate 

intake from 

only water 

at 15 μg/L 

(μg/kg-day) 

Percent RAIU 

inhibition 

from only 

water at 15 

μg/L 

TDS estimated perchlorate intake from 

food (μg/kgday) c

Perchlorate 

intake from 

food and 

water at 15 

μg/L (μg/kgday) 

Percent RAIU 

inhibition 

from food 

and water at 

15 μg/L 

Average adult ..................................... 70 2.24 0.48 0 .15 0.10 0.58 0 .18 

Non-pregnant woman ........................ 66 2.11 0.48 0 .21 0.10 0.58 0 .26 

Pregnant woman: 

Mom—GW 13 ............................. 69 2.18 0.50 0 .49 0.10 0.60 0 .59 

Mom—GW 20 ............................. 71 2.34 0.50 0 .49 0.10 0.60 0 .59 

Mom—GW 40 ............................. 78 2.57 0.50 0 .47 0.10 0.60 0 .57 

Fetus—GW 40 g .......................... 3 .5 .................... .................... 0 .90 .................... .................... 1 .1 

Breast-fed infant: 

Mom—7 d ................................... 74 2.96 0.60 0 .18 0.10 0.70 0 .21 

Infant—7 d .................................. 3 .6 d 0.52 1.36 1 .1 (d) 1.59 1 .3 

Mom—60 d ................................. 72 2.96 0.61 0 .17 0.10 0.71 0 .20 

Infant—60 d ................................ 5 d 0.74 1.27 0 .73 (d) 1.48 0 .84 

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TABLE 8—PREDICTED PERCENT RADIOACTIVE IODIDE UPTAKE (RAIU) INHIBITION AND CORRESPONDING PERCHLORATE

INTAKE FROM WATER AT 15 μG/L WITH AND WITHOUT FOOD INTAKE—Continued 

Body weight 

(kg) a

90th 

Percentile 

water intake 

(L/day) b

Perchlorate 

intake from 

only water 

at 15 μg/L 

(μg/kg-day) 

Percent RAIU 

inhibition 

from only 

water at 15 

μg/L 

TDS estimated perchlorate intake from 

food (μg/kgday) c

Perchlorate 

intake from 

food and 

water at 15 

μg/L (μg/kgday) 

Percent RAIU 

inhibition 

from food 

and water at 

15 μg/L 

Bottle-fed infant: 

Infant—7 d .................................. 3 .6 e 0.84 3.53 2 .0 1.42 μg/L 3.87 2 .2 

Infant—60 d ................................ 5 e 1.14 3.42 1 .3 1.42 μg/L 3.74 1 .4 

Child: 

6–12 mo f .................................... 9 .2 1.03 1.68 0 .46 0.275 1.96 0 .53 

1–2 yrf ........................................ 11 .4 0.64 0.84 0 .23 0.370 1.21 0 .33 

a Calculations for a 70 kg ‘‘average’’ adult are shown, while the body weight (BW) for the non-pregnant woman is from U.S. EPA 2004 (based 

on CSFII 94–96, 98) and BWs for the child are mean values from Kahn and Stralka (2008). BWs for pregnant and breast feeding moms, fetuses, 

bottle and breast fed infants are predicted weights (functions of age or gestation week) using growth equations from Gentry et al. (2002) as implemented in the PBPK models (Clewell et al. 2007; non-pregnant value is BW at day 0 of gestation). bWater intake levels for adults other than the lactating mother are based on normalized 90th percentile values for total water intake (direct and 

indirect) multiplied by the age- or gestation-week-dependent BW, as follows: 0.032 L/kg-day for average adult and non-pregnant woman; 0.033 L/ 

kg-day for the pregnant woman. A fixed ingestion rate was used for the lactating mother because, while her BW is expected to drop during the 

weeks following the end of pregnancy, the demands of breast-feeding will be increasing. Values are from Kahn and Stralka (2008), except values 

for women are from U.S. EPA (2004). cThe dietary values used correspond to the midpoint of the range of lower- and upper-bound average perchlorate levels for each subgroup, as 

identified from the FDA TDS in Murray et al. (2008), except for the bottle-fed infant. EPA used 1.42 μg/L as the concentration of perchlorate in 

infant formula. This is based on an average of available FDA TDS data, with 1⁄2 LOD included in the average for the samples in which perchlorate was not detected. dThe breast-fed infants are assumed to have no direct exposure via food or water. The prediction for breast-fed infants in this table results 

from the dose from both food and water to the mother providing breast milk to the infant. Breast-fed infant ‘‘water intake’’ is the breast milk ingestion rate obtained by fitting an age-dependent function to the breast-milk ingestion data (L/kg-day) from Arcus-Arth et al. (2005). Urinary clearance rates for the lactating woman equal to that of the average adult were used, consistent with data presented in Delange (2004). eFor the bottle-fed infant, normalized total water intake (direct and indirect, L/kg-day) was described as a smooth function of infant age fit to 

the results from Kahn and Stralka (2008), and multiplied by BW(age). For the 7-day-old infant, the data used to fit the function included the 90th 

percentile community water-consumers only intake (0.235 L/kg-day, N=40) for the <1 month old infant. For the 60-day-old infant, the 90th percentile community water-consumers only intake (0.228 L/kg-day, N=114) for the 1- to <3 months-old infant was used. fFor the 6- to 12-month and 1- to 2-year-old children, EPA set the water ingestion based on published exposure tables and selected the age at 

which the model-predicted BW (from growth equations) matched the exposure-table mean. This approach resulted in model predictions for a 9.6- 

month-old child (to represent 6- to 12-month-old children) and a 1.3-year old (to represent 1- to 2-year-old children). g Due to data limitations, RAIU inhibition is calculated only for fetuses at GW 40. 

c. Modeling Uncertainties 

EPA recognizes that there are 

uncertainties associated with this 

modeling, as there are for any modeling 

effort. For example, this analysis does 

not take into account within-group 

variability in pharmacokinetics, 

uncertainty in model parameters and 

predictions, or population differences in 

pharmacodynamics (PD) of receptor 

binding and upregulation. Also, the 

NRC identified fetuses of pregnant 

women that are hypothyroid or iodine 

deficient as the most sensitive 

subpopulation. The model predictions 

of RAIU inhibition in the various 

subgroups are average inhibition for 

typical, healthy individuals, not for 

hypothyroid or iodine deficient 

individuals. However, EPA did not rely 

on this analysis for determining the 

HRL. Rather, the HRL of 15 μg/L was 

calculated directly from the RfD to 

protect the most sensitive 

subpopulation, the fetuses of pregnant 

women, using high end exposure 

assumptions (e.g., estimated 90th 

percentile drinking water consumption 

and estimated 90th percentile 

perchlorate dietary (food) exposure). 

The PBPK modeling was used to 

provide information on the potential 

effects of exposure at the HRL for other 

subgroups, such as infants and children. 

In addition, the predicted inhibitions 

are averages for the subgroup as a 

whole, given the exposure assumptions 

used in the model. Thus, some members 

of a group would be expected to have 

RAIU inhibition greater than indicated 

in Table 8 for a particular perchlorate 

concentration, while others would have 

lesser inhibition. EPA was able to 

partially address this variability by 

using 90th percentile water 

consumption rates and mean body 

weights in the analysis to consider the 

highly exposed portions of the various 

subgroups. Most members of the 

subgroups would be expected to have 

exposures less than those indicated in 

Table 8. 

There is also some uncertainty 

regarding the water intake rates, 

particularly for infants. EPA described 

water intake by infants as a smooth 

function fit to the 90th percentile 

community water-consumers intake-rate 

data (intake per unit BW) of Kahn and 

Stralka (2008), which is then multiplied 

by the age-dependent BW to account for 

the changes occurring over the first 

weeks of life. This resulted in an 

estimated 90th percentile water intake 

rate of 0.84 L/day for the 7-day bottle 

fed infant and used by EPA in PBPK 

model simulations. General information 

on water and formula intake for 7-day 

old infants is also available in 

guidelines for healthy growth and 

nutrition of the American Academy of 

Pediatrics (AAP, 2008). The values 

estimated using the guidelines from the 

AAP (0.126 L/kg-day assuming 80% is 

the percent water used in preparation of 

formula) for 7-day-old infants are close 

to the mean consumers-only intake rate 

for the 1–30 day-old infants from Kahn 

and Stralka (2008; 0.137 L/kg-day 

N=40). 

However, FDA has suggested an 

alternate approach, using the caloric 

intake requirement of a 7-day old infant 

as the basis for calculating consumption 

(FDA, 2008). This would likely yield a 

lower estimate of intake than the 0.84 L/ 

day EPA has used in the model. If intake 

is lower, this would yield a lower 

prediction of RAIU inhibition, as can be 

seen from the value predicted for the 7- 

day old breast fed infant (1.4 percent). 

EPA plans to ask specifically for 

feedback on the consumption estimates 

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60280 Federal Register / Vol. 73, No. 198 / Friday, October 10, 2008 / Notices 

for 7-day old bottle-fed infants when the 

model revisions are peer reviewed. 

There is also uncertainty regarding 

the appropriate duration of exposure 

(i.e., days, weeks, months) to compare to 

the perchlorate RfD, which EPA defines 

as ‘‘an estimate (with uncertainty 

spanning perhaps an order of 

magnitude) of a daily exposure to the 

human population (including sensitive 

subgroups) that is likely to be without 

an appreciable risk of deleterious effects 

during a lifetime.’’ Reference values, 

like the RfD, are derived based on an 

assumption of continuous exposure 

throughout the duration specified, while 

intake levels may rapidly change day to 

day or during certain life stages. For 

comparability with the RfD, continuous 

perchlorate exposure was assumed in 

EPA’s modeling analysis. Using 

perchlorate levels predicted for a 

continuous exposure (constant rate of 

introduction to the stomach), rather 

than incorporating changes in exposure 

and other input parameters over time 

(i.e., simulating the timing and quantity 

of specific ingestion events during the 

day), substantially reduced the effects of 

parameter uncertainty in the modeling. 

RAIU inhibition, on the other hand, is 

evaluated as the change in thyroid 

uptake of a pulse of iodide 

(radiolabeled, from an IV injection) at a 

time 24 hours after the pulse is 

administered. Thus, it represents the 

inhibition on a given day. This was true 

in the Greer study on which the RfD is 

based, and it is also true in the model. 

For all lifestages except the developing 

infant, the day-to-day variation in RAIU 

inhibition at the levels under 

consideration will have little or no 

effect. However, the effects of short-term 

inhibition in the infant (and fetus) may 

be of greater consequence than in the 

adult, although infants may also have 

less short-term variability in their diet 

and intake levels than adults. To 

address this concern, we present the 

results for the infant at both 7 days and 

60 days after birth. The model predicts 

a fairly smooth variation in effect 

between these two ages. 

d. Summary of Modeling Analysis 

In deciding whether to regulate 

perchlorate, EPA focused attention on 

the most sensitive subpopulation, a 

pregnant woman and her fetus. EPA 

calculated an HRL of 15 μg/L for 

pregnant women using RSC information 

derived from an analysis of NHANES 

and UCMR data. EPA also conducted 

PBPK modeling to evaluate predicted 

biological outcomes associated with 

drinking water concentrations at the 

health reference level for different 

sensitive subpopulations. For pregnant 

women, EPA assumed a 90th percentile 

water ingestion rate of 0.033 L/kg-day, 

a food intake rate that represented the 

midpoint of the range of average 

perchlorate dietary exposures reported 

in Murray et al. (2008), and used the 

Clewell et al. (2007) PBPK model-fitted 

body weight. EPA believes that the 

model-fitted body weight provides a 

more realistic weight for the pregnant 

woman than EPA’s 70 kg default 

assumption for adults. In addition, 

rather than using the default assumption 

of 2L/day water ingestion, EPA used a 

90th percentile water ingestion rate 

normalized for body weight and based 

on data specifically for pregnant women 

(USEPA 2004b). Using these 

assumptions, the model predicted that 

the pregnant woman’s dose of 

perchlorate would not exceed the 

reference dose if she consumed drinking 

water with a concentration of 15 μg/L or 

less, which is consistent with the 

derivation of the HRL from the reference 

dose, based on average body weight, 

90th percentile water consumption, and 

90th percentile food exposure for 

pregnant women. The model further 

predicted that the percent inhibition in 

the fetus of a pregnant woman 

consuming drinking water with 15 μg/ 

L perchlorate (in combination with a 

normal diet) is 1.1 percent, below the 

1.8 percent that the NRC determined to 

be a no-effect level in healthy adults. 

EPA evaluated other subpopulations to 

estimate iodide uptake inhibition and 

determined that 7-day old bottle-fed 

infants were predicted to have a 2.2 

percent inhibition level, after also 

accounting for food exposure, and all 

other subpopulations, including 60-day 

old bottle-fed infants, 7 and 60 day old 

breast-fed infants, and children, were 

predicted to have levels of inhibition of 

1.4 percent or less, after accounting for 

food. All of these levels are comparable 

to or below the 1.8 percent no effect 

inhibition level from the Greer study. 

Based on the health protective 

approach for deriving the RfD (i.e., use 

of a NOEL rather than a NOAEL as the 

point of departure), the conservative 

assumptions used in deriving the RSC 

and corresponding HRL (use of 90th 

percentile food exposure data 

specifically from pregnant women), and 

the PBPK modeling analysis of RAIU 

inhibition in potentially sensitive 

subpopulations, EPA believes drinking 

water with perchlorate concentrations at 

or below the HRL of 15 μg/L is 

protective of all subpopulations. Based 

upon the HRL and the analysis of 

drinking water occurrence, EPA 

concludes that perchlorate does not 

occur at a frequency and level of health 

concern to warrant a national drinking 

water regulation. 

C. Is There a Meaningful Opportunity 

for the Reduction of Health Risks From 

Perchlorate for Persons Served by Public 

Water Systems? 

The Agency does not believe that a 

national primary drinking water 

regulation for perchlorate presents a 

meaningful opportunity for health risk 

reduction for persons served by public 

water systems. EPA has found that 

perchlorate occurs infrequently above 

levels of health concern. Only 31 out of 

3,865 systems (0.8 percent) detected 

perchlorate in drinking water above the 

HRL of 15 μg/L. EPA’s best estimate is 

that 0.9 million people (with an upper 

bound estimate of 2 million people) may 

be consuming water containing 

perchlorate at levels that could exceed 

the HRL for perchlorate and the Agency 

estimates that fewer than 30,000 of them 

are pregnant women at any given time. 

EPA’s RfD was derived by applying a 

10 fold uncertainty factor to the dose 

corresponding to a non-statistically 

significant mean 1.8 percent decline in 

RAIU in healthy adults following two 

weeks of daily exposure to perchlorate 

(Greer et al., 2002). Because iodide 

uptake inhibition is not an adverse 

effect but a precursor biochemical 

change, this point of departure (7 ug/kg/ 

day) is a NOEL which provides for a 

more conservative and health-protective 

approach to perchlorate hazard 

assessment. After taking perchlorate in 

the diet into consideration, at the HRL 

of 15 μg/L for perchlorate in drinking 

water, the models predicted that the 

percent RAIU inhibition in fetuses 

would be 1.1 percent, while the 

inhibition in all other subgroups except 

the 7-day-old bottle fed infant would be 

no greater than 1.4 percent. For the 7- 

day-old bottle fed infant, the predicted 

inhibition is 2.2 percent. All of these 

values are comparable to or below the 

percent inhibition at the NOEL in the 

Greer study. 

Based on these analyses, EPA has 

determined that a national primary 

drinking water regulation for 

perchlorate would not present a 

meaningful opportunity for health risk 

reduction for persons served by public 

water systems. 

V. EPA’s Next Steps 

EPA requests comment on this 

preliminary determination that a 

national primary drinking water 

regulation for perchlorate would not 

present a meaningful opportunity for 

health risk reduction for persons served 

by public water systems. EPA also 

requests comment upon the scientific 

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Federal Register / Vol. 73, No. 198 / Friday, October 10, 2008 / Notices 60281 

data and supporting analyses for this 

determination. In past regulatory 

determinations, EPA has qualitatively 

but not quantitatively evaluated the 

health effects of exposure at the HRL on 

infants and children. Because the 

evaluation of the potential impacts of 

exposure at the HRL of 15 μg/L on 

infants and children is a novel 

approach, EPA specifically requests 

comment on its use of the revised PBPK 

model to evaluate these potential 

impacts. 

EPA will respond to the public 

comments it receives on the preliminary 

determination and will review the 

comments from the peer review of its 

model application. After considering 

comments, EPA plans to issue a final 

regulatory determination for perchlorate 

by December 2008. EPA also plans to 

publish a health advisory for 

perchlorate at the time of the final 

determination to provide information to 

Federal, Regional, State, and local 

public health officials regarding 

potential health risks from perchloratecontaminated drinking water. 

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Drinking Water Contaminant Candidate 

List; Notice. Federal Register. Vol. 63, 

No. 40. p. 10273, March 2, 1998. 

USEPA. 1999b. Revisions to the Unregulated 

Contaminant Monitoring Regulation for 

Public Water Systems. Federal Register. 

Vol. 64, No. 180. p. 50556, September 17, 

1999. 

USEPA. 2000b. Unregulated Contaminant 

Monitoring Regulation for Public Water 

Systems: Analytical Methods for 

Perchlorate and Acetochlor; 

Announcement of Laboratory Approval 

and Performance Testing (PT) Program 

for the Analysis of Perchlorate; Final 

Rule and Proposed Rule. Federal 

Register. Vol. 65, No. 42. p. 11372, 

March 2, 2000. 

USEPA. 2001b. Unregulated Contaminant 

Monitoring Regulation for Public Water 

Systems; Analytical Methods for List 2 

Contaminants; Clarifications to the 

Unregulated Contaminant Monitoring 

Regulation. Federal Register. Vol. 66, 

No. 8. p. 2273, January 11, 2001. 

USEPA. 2002a. Announcement of 

Preliminary Regulatory Determinations 

for Priority Contaminants on the 

Drinking Water Contaminant Candidate 

List. Federal Register. Vol. 67, No. 106. 

p. 38222, June 3, 2002. 

USEPA. 2002b. Perchlorate Environmental 

Contamination: Toxicological Review 

and Risk Characterization. EPA/635/R– 

02/003. National Center for 

Environmental Assessment, Office of 

Research and Development, U.S. EPA. 

USEPA. 2002c. A review of the reference 

dose and reference concentration 

processes. Risk Assessment Forum, 

Washington, DC; EPA/630/P–02/0002F. 

Available from: http://www.epa.gov/iris/ 

backgr-d.htm. 

USEPA. 2003a. Announcement of Regulatory 

Determinations for Priority 

Contaminants on the Drinking Water 

Contaminant Candidate List. Federal 

Register. Vol. 68, No. 138. p. 42897, July 

18, 2003. 

USEPA. 2004a. Drinking Water Contaminant 

Candidate List 2; Notice. Federal 

Register. Vol. 69, No. 64. p. 17406, April 

2, 2004. 

USEPA. 2004b. Estimated Per Capita Water 

Ingestion and Body Weight in the United 

States—An Update Based on Data 

Collected by the United States 

Department of Agriculture’s 1994–1996 

and 1998 Continuing Survey of Food 

Intakes by Individuals. EPA–822–R–00– 

001. Office of Science and Technology, 

Office of Water, U.S. EPA. 

USEPA. 2005a. Notice—Drinking Water 

Contaminant Candidate List 2; Final 

Notice. Federal Register. Vol. 70, No. 36. 

p. 9071, February 24, 2005. 

USEPA. 2005b. ‘‘Integrated Risk Information 

System (IRIS), Perchlorate and 

Perchlorate Salts.’’ February 2005. 

Available on the Internet at: http:// 

www.epa.gov/iris/subst/1007.htm. 

Accessed February 2, 2005. 

USEPA 2006. Assessment Guidance for 

Perchlorate. Memorandum from Susan 

Bodine, Assistant Administrator of the 

Office of Solid Waste and Emergency 

Response, to EPA Regional 

Administrators. Available on the Internet 

at: http://www.epa.gov/fedfac/pdf/ 

perchlorate_guidance.pdf. Accessed 

August 20, 2008 

USEPA. 2007. Drinking Water: Regulatory 

Determinations Regarding Contaminants 

on the Second Drinking Water 

Contaminant Candidate List— 

Preliminary Determinations. Federal 

Register. 72 FR 24016. May 1, 2007. 

USEPA, 2008a Evaluation of Perchlorate 

Exposure from Food and Drinking Water: 

Results of NHANES Biomonitoring Data 

and UCMR 1 Occurrence Data Merge. 

USEPA. 2008b. Inhibition of the SodiumIodide Symporter by Perchlorate: 

Evaluation of Lifestage Sensitivity Using 

Physiologically-Based Pharmacokinetic 

Modeling. {NOTE: Final title/reference 

info for the document will be provided 

before publication.} 

USEPA. 2008c. Drinking Water: Regulatory 

Determinations Regarding Contaminants 

on the Second Drinking Water 

Contaminant Candidate List—Final 

Determinations. Federal Register. 73 FR 

44251. July 30, 2008. 

Ventura SJ, Abma JC, Mosher WD, Henshaw 

S. Estimated pregnancy rates for the 

United States, 1990–2000: an update. 

National vital statistics reports; vol 52 no 

23. Hyattsville, Maryland: National 

Center for Health Statistics. 2004. 

Zoeller, R.T., and J. Rovet. 2004. Timing of 

thyroid hormone action in the 

developing brain: clinical observations 

and experimental findings. J 

Neuroendocrinology 16: 809–18. 

Dated: October 3, 2008. 

Stephen L. Johnson, 

Administrator. 

[FR Doc. E8–24042 Filed 10–9–08; 8:45 am] 

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