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Proposed Rule2023-05471

PFAS National Primary Drinking Water Regulation Rulemaking

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Published

March 29, 2023

Issuing agencies

Environmental Protection Agency

Abstract

The Environmental Protection Agency (EPA) is committed to using and advancing the best available science to tackle per- and polyfluoroalkyl substances (PFAS) pollution, protect public health, and harmonize policies that strengthen public health protections with infrastructure funding to help communities, especially disadvantaged communities, deliver safe drinking water. In March 2021, EPA issued a final regulatory determination to regulate perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) as contaminants under Safe Drinking Water Act (SDWA). In this notice, EPA is issuing a preliminary regulatory determination to regulate perfluorohexane sulfonic acid (PFHxS), hexafluoropropylene oxide dimer acid (HFPO-DA) and its ammonium salt (also known as a GenX chemicals), perfluorononanoic acid (PFNA), and perfluorobutane sulfonic acid (PFBS), and mixtures of these PFAS as contaminants under SDWA. Through this action, EPA is also proposing a National Primary Drinking Water Regulation (NPDWR) and health-based Maximum Contaminant Level Goals (MCLG) for these four PFAS and their mixtures as well as for PFOA and PFOS. EPA is proposing to set the health-based value, the MCLG, for PFOA and PFOS at zero. Considering feasibility, including currently available analytical methods to measure and treat these chemicals in drinking water, EPA is proposing individual MCLs of 4.0 nanograms per liter (ng/L) or parts per trillion (ppt) for PFOA and PFOS. EPA is proposing to use a Hazard Index (HI) approach to protecting public health from mixtures of PFHxS, HFPO-DA and its ammonium salt, PFNA, and PFBS because of their known and additive toxic effects and occurrence and likely co-occurrence in drinking water. EPA is proposing an HI of 1.0 as the MCLGs for these four PFAS and any mixture containing one or more of them because it represents a level at which no known or anticipated adverse effects on the health of persons is expected to occur and which allows for an adequate margin of safety. EPA has determined it is also feasible to set the MCLs for these four PFAS and for a mixture containing one or more of PFHxS, HFPO-DA and its ammonium salt, PFNA, PFBS as an HI of unitless 1.0. The Agency is requesting comment on this action, including this proposed NPDWR and MCLGs, and have identified specific areas where public input will be helpful for EPA in developing the final rule. In addition to seeking written input, the EPA will be holding a public hearing on May 4, 2023.

Full Text

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<title>Federal Register, Volume 88 Issue 60 (Wednesday, March 29, 2023)</title>
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[Federal Register Volume 88, Number 60 (Wednesday, March 29, 2023)]
[Proposed Rules]
[Pages 18638-18754]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2023-05471]

[[Page 18637]]

Vol. 88

Wednesday,

No. 60

March 29, 2023

Part II

Environmental Protection Agency

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40 CFR Parts 141 and 142

PFAS National Primary Drinking Water Regulation Rulemaking; Proposed
Rule

Federal Register / Vol. 88, No. 60 / Wednesday, March 29, 2023 /
Proposed Rules

[[Page 18638]]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Parts 141 and 142

[EPA-HQ-OW-2022-0114; FRL 8543-01-OW]
RIN 2040-AG18

PFAS National Primary Drinking Water Regulation Rulemaking

AGENCY: Environmental Protection Agency (EPA).

ACTION: Preliminary regulatory determination and proposed rule; request
for public comment; notice of public hearing.

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SUMMARY: The Environmental Protection Agency (EPA) is committed to
using and advancing the best available science to tackle per- and
polyfluoroalkyl substances (PFAS) pollution, protect public health, and
harmonize policies that strengthen public health protections with
infrastructure funding to help communities, especially disadvantaged
communities, deliver safe drinking water. In March 2021, EPA issued a
final regulatory determination to regulate perfluorooctanoic acid
(PFOA) and perfluorooctane sulfonic acid (PFOS) as contaminants under
Safe Drinking Water Act (SDWA). In this notice, EPA is issuing a
preliminary regulatory determination to regulate perfluorohexane
sulfonic acid (PFHxS), hexafluoropropylene oxide dimer acid (HFPO-DA)
and its ammonium salt (also known as a GenX chemicals),
perfluorononanoic acid (PFNA), and perfluorobutane sulfonic acid
(PFBS), and mixtures of these PFAS as contaminants under SDWA. Through
this action, EPA is also proposing a National Primary Drinking Water
Regulation (NPDWR) and health-based Maximum Contaminant Level Goals
(MCLG) for these four PFAS and their mixtures as well as for PFOA and
PFOS. EPA is proposing to set the health-based value, the MCLG, for
PFOA and PFOS at zero. Considering feasibility, including currently
available analytical methods to measure and treat these chemicals in
drinking water, EPA is proposing individual MCLs of 4.0 nanograms per
liter (ng/L) or parts per trillion (ppt) for PFOA and PFOS. EPA is
proposing to use a Hazard Index (HI) approach to protecting public
health from mixtures of PFHxS, HFPO-DA and its ammonium salt, PFNA, and
PFBS because of their known and additive toxic effects and occurrence
and likely co-occurrence in drinking water. EPA is proposing an HI of
1.0 as the MCLGs for these four PFAS and any mixture containing one or
more of them because it represents a level at which no known or
anticipated adverse effects on the health of persons is expected to
occur and which allows for an adequate margin of safety. EPA has
determined it is also feasible to set the MCLs for these four PFAS and
for a mixture containing one or more of PFHxS, HFPO-DA and its ammonium
salt, PFNA, PFBS as an HI of unitless 1.0. The Agency is requesting
comment on this action, including this proposed NPDWR and MCLGs, and
have identified specific areas where public input will be helpful for
EPA in developing the final rule. In addition to seeking written input,
the EPA will be holding a public hearing on May 4, 2023.

DATES: Comments must be received on or before May 30, 2023. Comments on
the information collection provisions submitted to the Office of
Management and Budget (OMB) under the Paperwork Reduction Act (PRA) are
best assured of consideration by OMB if OMB receives a copy of your
comments on or before April 28, 2023. Public hearing: EPA will hold a
virtual public hearing on May 4, 2023, at <a href="https://www.epa.gov/sdwa/and-polyfluoroalkyl-substances-pfas">https://www.epa.gov/sdwa/and-polyfluoroalkyl-substances-pfas</a>. Please refer to the SUPPLEMENTARY
INFORMATION section for additional information on the public hearing.

ADDRESSES: You may send comments, identified by Docket ID No. EPA-HQ-
OW-2022-0114 by any of the following methods:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov/">https://www.regulations.gov/</a>
(our preferred method). Follow the online instructions for submitting
comments.
<bullet> Mail: U.S. Environmental Protection Agency, EPA Docket
Center, Office of Ground Water and Drinking Water Docket, Mail Code
2822IT, 1200 Pennsylvania Avenue NW, Washington, DC 20460.
<bullet> Hand Delivery or Courier: EPA Docket Center, WJC West
Building, Room 3334, 1301 Constitution Avenue NW, Washington, DC 20004.
The Docket Center's hours of operations are 8:30 a.m. to 4:30 p.m.,
Monday through Friday (except Federal Holidays).
Instructions: All submissions received must include the Docket ID
No. for this rulemaking. Comments received may be posted without change
to <a href="https://www.regulations.gov/">https://www.regulations.gov/</a>, including any personal information
provided. For detailed instructions on sending comments and additional
information on the rulemaking process, see the ``Public Participation''
heading of the SUPPLEMENTARY INFORMATION section of this document.

FOR FURTHER INFORMATION CONTACT: Alexis Lan, Office of Ground Water and
Drinking Water, Standards and Risk Management Division (Mail Code
4607M), Environmental Protection Agency, 1200 Pennsylvania Avenue NW,
Washington, DC 20460; telephone number 202-564-0841; email address:
<a href="/cdn-cgi/l/email-protection#a3f3e5e2f0edf3e7f4f1e3c6d3c28dc4ccd5">[email&#160;protected]</a>

SUPPLEMENTARY INFORMATION:

Executive Summary

In March 2021, EPA issued a final regulatory determination to
regulate perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic
acid (PFOS) as contaminants under Safe Drinking Water Act (SDWA). EPA
is issuing a preliminary regulatory determination to regulate
perfluorohexane sulfonic acid (PFHxS), hexafluoropropylene oxide dimer
acid (HFPO-DA) and its ammonium salt (also known as a GenX chemicals),
perfluorononanoic acid (PFNA), and perfluorobutane sulfonic acid
(PFBS), and mixtures of these PFAS as contaminants under SDWA (see
section III of this preamble for additional discussion on EPA's
preliminary regulatory determination). Through this action, EPA is also
proposing a National Primary Drinking Water Regulation (NPDWR) and
health-based Maximum Contaminant Level Goals (MCLG) for these four PFAS
and their mixtures as well as for PFOA and PFOS. Exposure to these PFAS
may cause adverse health effects, and all are likely to occur in
drinking water.
PFAS are a large family of synthetic chemicals that have been in
use since the 1940s. Many of these compounds have unique physical and
chemical properties that make them highly stable and resistant to
degradation in the environment--colloquially termed ``forever
chemicals.'' People can be exposed to PFAS through certain consumer
products, occupational contact, and/or by consuming food and drinking
water that contain PFAS (see section II.C of this preamble for
additional discussion on PFAS chemistry, production, and uses). Current
scientific evidence indicates that consuming water containing the PFAS
covered in this proposed regulation above certain levels can result in
harmful health effects. Depending on the individual PFAS, health
effects can include negative impacts on fetal growth after exposure
during pregnancy, on other aspects of development, reproduction, liver,
thyroid, immune function, and/or the nervous system; and increased risk
of cardiovascular and/or certain types of cancers, and other health
impacts (see

[[Page 18639]]

section II.B and III.B of this preamble for additional discussion on
health effects).
This proposed PFAS drinking water regulation contains several key
features. Based on a review of the best available health effects data,
EPA is proposing MCLGs that address six PFAS. An MCLG is the maximum
level of a contaminant in drinking water at which no known or
anticipated adverse effect on the health of persons would occur,
allowing an adequate margin of safety. A contaminant means any
``physical, chemical or biological or radiological substance or matter
in water.'' This proposal addresses contaminants and certain mixtures
of contaminants. Through this action, EPA is also proposing enforceable
standards which takes the form of maximum contaminant levels (MCLs) in
this proposed regulation. An MCL is the maximum level allowed of a
contaminant or a group of contaminants (i.e., mixture of contaminants)
in water which is delivered to any user of a public water system (PWS).
The SDWA generally requires EPA to set an MCL ``as close as feasible
to'' the MCLG. EPA has also included monitoring, reporting, and other
requirements to ensure regulated drinking water systems, known as a
PWS, meet the PFAS limits in the regulation.
Following a systematic review of available human epidemiological
and animal toxicity studies, EPA has determined that PFOA and PFOS are
likely to cause cancer (e.g., kidney and liver cancer) and that there
is no dose below which either chemical is considered safe (see section
IV.A and V.A through B of this preamble for additional discussion).
Therefore, EPA is proposing to set the health-based value, the MCLG,
for both of these contaminants at zero. Considering feasibility,
including currently available analytical methods to measure and treat
these chemicals in drinking water, EPA is proposing individual MCLs of
4.0 nanograms per liter (ng/L) or parts per trillion (ppt) for PFOA and
PFOS (see sections VI.C and VIII of this preamble for additional
discussion on the MCLs and practical quantitation limits [PQLs]).
Due to their widespread use and persistence, many PFAS are known to
co-occur in drinking water and the environment--meaning that these
compounds are often found together and in different combinations as
mixtures (see section III.C and VII of this preamble for additional
discussion on occurrence). PFAS disrupt signaling of multiple
biological pathways resulting in common adverse effects on several
biological systems and functions, including thyroid hormone levels,
lipid synthesis and metabolism, development, and immune and liver
function. Additionally, EPA's examination of health effects information
found that exposure through drinking water to a mixture of PFAS can be
assumed to act in a dose-additive manner (see sections III.B and IV.B
of this preamble for additional discussion on mixture toxicity). This
dose additivity means that low levels of multiple PFAS, that
individually would not likely result in adverse health effects, when
combined in a mixture are expected to result in adverse health effects.
As a result, EPA is proposing to use a Hazard Index (HI) approach to
protecting public health from mixtures of four PFAS: PFHxS, HFPO-DA and
its ammonium salt (also known as GenX chemicals), PFNA, and PFBS
because of their known and additive toxic effects and occurrence and
likely co-occurrence in drinking water. PFOA and PFOS are being
proposed for separate MCLs and not included in the HI because their
individual proposed MCLGs are zero, and the level at which no known or
anticipated adverse effects on the health of persons is expected to
occur is well below current analytical quantitation levels. Based on
our current understanding of health effects, this is not the case for
the other covered PFAS. Because of the analytical limitations for PFOA
and PFOS, the MCL for these two PFAS is set at the lowest feasible
quantitation level and any exceedance of this limit requires action to
protect public health, regardless of any mixture in which they are
found. As a result, EPA is not proposing to include PFOA or PFOS in the
HI.
The HI is a commonly used risk management approach for mixtures of
chemicals (USEPA, 1986a; 2000a). In this approach, a ratio called a
hazard quotient (HQ) is calculated for each of the four PFAS (PFHxS,
HFPO-DA and its ammonium salt (also known as GenX chemicals), PFNA, and
PFBS) by dividing an exposure metric, in this case, the measured level
of each of the four PFAS in drinking water, by a health reference value
for that particular PFAS. For health reference values, in this
proposal, EPA is using Health Based Water Concentration (HBWCs) as
follows: 9.0 ppt for PFHxS, 10.0 ppt for HFPO-DA; 10.0 ppt for PFNA;
and 2000 ppt for PFBS (USEPA, 2023a). The individual PFAS ratios (HQs)
are then summed across the mixture to yield the HI. If the resulting HI
is greater than one (1.0), then the exposure metric is greater than the
health metric and potential risk is indicated. EPA's Science Advisory
Board (SAB) opined that where the health endpoints of the chosen
compounds are similar, it is reasonable to use an HI as ``a reasonable
approach for estimating the potential aggregate health hazards
associated with the occurrence of chemical mixtures in environmental
media.'' (USEPA, 2022a). The HI provides an indication of overall
potential risk of a mixture as well as individual PFAS that are
potential drivers of risk (those PFAS(s) with high(er) ratios of
exposure to health metrics) (USEPA, 2000a; see section IV.B and V.C of
this preamble for additional discussion on the HI and its derivation).
Therefore, EPA is proposing an HI of 1.0 as the MCLGs for these four
PFAS and any mixture containing one or more of them because it
represents a level at which no known or anticipated adverse effects on
the health of persons is expected to occur and which allows for an
adequate margin of safety. EPA has determined it is also feasible to
set the MCLs for these four PFAS and for a mixture containing one or
more of PFHxS, HFPO-DA and its ammonium salt, PFNA, PFBS as an HI of
unitless 1.0 (see sections V.C and VI.B of this preamble for discussion
of the HI MCLG and MCL, respectively).
Monitoring is a core component of a NPDWR and assures that water
systems are providing necessary public health protections (see section
IX of this preamble for additional discussion on monitoring and
compliance requirements). EPA is therefore proposing requirements for
systems to monitor for PFOA, PFOS, PFHxS, HFPO-DA and its ammonium
salt, PFNA, and PFBS in drinking water that build upon EPA's
Standardized Monitoring Framework (SMF) for Synthetic Organic Compounds
(SOCs) where the monitoring frequency for any PWS depends on previous
monitoring results. This proposal includes flexibilities related to
monitoring, including flexibilities for systems to use certain,
previously collected data to satisfy initial monitoring requirements in
this proposal as well as reduced monitoring requirements in certain
circumstances (see section IX.E of this preamble for additional
discussion on monitoring waivers).
In summary, the proposed MCLs for PFOA and PFOS are 4 ng/L
(individually), and the proposed MCL of an HI of 1.0 for any mixture
containing PFHxS, HFPO-DA and its ammonium salt, PFNA, and/or PFBS.
Water systems with PFAS levels that exceed the proposed MCLs would need
to take action to provide safe and reliable drinking water. These
systems may install water treatment or consider other

[[Page 18640]]

options such as using a new uncontaminated source water or connecting
to an uncontaminated water system. Activated carbon, anion exchange
(AIX) and high-pressure membrane technologies have all been
demonstrated to remove PFAS, including PFOA, PFOS, PFHxS, HFPO-DA and
its ammonium salt, PFNA, and PFBS, from drinking water systems. These
treatment technologies can be installed at a water system's treatment
plant and are also available through in-home filter options (see
section XI of this preamble for additional discussion on available
treatment technologies).
As part of its health risk reduction and cost analysis, SDWA
requires an evaluation of quantifiable and nonquantifiable health risk
reduction benefits and costs. SDWA also requires that EPA considers
quantifiable and nonquantifiable health risk reduction benefits from
reductions in co-occurring contaminants. The SDWA also requires that
EPA determine if the benefits of the proposed rule justify the costs.
In accordance with these requirements, the EPA Administrator has
determined that the quantified and nonquantifiable benefits of the
proposed PFAS NPDWR justify the costs (see section XIII of this
preamble for additional discussion on EPA's Health Risk Reduction and
Cost Analysis [HRRCA]). Among other things, EPA evaluated which
entities which would be affected by the rule, quantified costs using
available data and statical models, and described unquantifiable costs.
EPA also quantified benefits by estimating reduced cardiovascular
events (e.g., heart attacks and strokes), developmental impacts to
fetuses and infants, and reduced cases of kidney cancer. EPA has also
quantified benefits by estimating reduced bladder cancer cases caused
by reduced disinfection byproduct (DBP) formation in some systems that
install treatment to meet the requirements of this rule. EPA has also
developed a qualitative summary of benefits expected to result from the
removal of regulated PFAS and additional co-removed PFAS contaminants.
To help communities on the frontlines of PFAS contamination, the
passage of the Infrastructure Investment and Jobs Act, also referred to
as the Bipartisan Infrastructure Law (BIL), invests over $11.7 billion
in the Drinking Water State Revolving Fund (SRF); $4 billion to the
Drinking Water SRF for Emerging Contaminants; and $5 billion to Small,
Underserved, and Disadvantaged Communities Grants. These funds will
assist many disadvantaged communities, small systems, and others with
the costs of installation of treatment when it might otherwise be cost-
challenging.
Public participation and consultations with key stakeholders are
critical in developing an implementable and public health protective
rule. EPA has engaged with many stakeholders and consulted with
entities such as the SAB, and the National Drinking Water Advisory
Council (NDWAC) in developing this proposed rule (see section XV of
this preamble on EPA's Statutory and Executive Order reviews). The
Agency is requesting comment on this action, including this proposed
NPDWR and MCLGs, and have identified specific areas where public input
will be helpful for EPA in developing the final rule (see section XIV
of this preamble on specific topics highlighted for public comment). In
addition to seeking written input, EPA will be holding a public hearing
on May 4th, 2023.

I. Public Participation

A. Written Comments

Submit your comments, identified by Docket ID No. EPA-HQ-OW-2022-
0114, at <a href="https://www.regulations.gov">https://www.regulations.gov</a> (our preferred method), or the
other methods identified in the ADDRESSES section. Once submitted,
comments cannot be edited or removed from the docket. EPA may publish
any comment received to its public docket. Do not submit to EPA's
docket at <a href="https://www.regulations.gov">https://www.regulations.gov</a> any information you consider to
be Confidential Business Information (CBI), Proprietary Business
Information (PBI), or other information whose disclosure is restricted
by statute. Multimedia submissions (audio, video, etc.) must be
accompanied by a written comment. The written comment is considered the
official comment and should include discussion of all points you wish
to make. EPA will generally not consider comments or comment contents
located outside of the primary submission (i.e., on the web, cloud, or
other file sharing system). Please visit <a href="https://www.epa.gov/dockets/commenting-epa-dockets">https://www.epa.gov/dockets/commenting-epa-dockets</a> for additional submission methods; the full EPA
public comment policy; information about CBI, PBI, or multimedia
submissions; and general guidance on making effective comments.

B. Participation in Virtual Public Hearing

EPA will hold a public hearing on May 4th, 2023, to receive public
comment and will present the proposed requirements of the draft NPDWR.
The hearing will be held virtually from approximately 11 a.m. until 7
p.m. eastern time. EPA will begin registering speakers for the hearing
upon publication of this document in the Federal Register (FR). To
attend and register to speak at the virtual hearing, please use the
online registration form available at <a href="https://www.epa.gov/sdwa/and-polyfluoroalkyl-substances-pfas">https://www.epa.gov/sdwa/and-polyfluoroalkyl-substances-pfas</a>. The last day to pre-register to speak
at the hearing will be April 28, 2023. On May 3, 2023, EPA will post a
general agenda for the hearing that will list pre-registered speakers
in approximate order at: <a href="https://www.epa.gov/sdwa/and-polyfluoroalkyl-substances-pfas">https://www.epa.gov/sdwa/and-polyfluoroalkyl-substances-pfas</a>. The number of online connections available for the
hearing is limited and will be offered on a first- come, first-served
basis. To submit visual aids to support your oral comment, please
contact <a href="/cdn-cgi/l/email-protection#24746265776a74607376644154450a434b52">[email&#160;protected]</a> for guidelines and instructions. Registration
will remain open for the duration of the hearing itself for those
wishing to provide oral comment during unscheduled testimony; however,
early registration is strongly encouraged to ensure proper
accommodations and adequate timing.
EPA will make every effort to follow the schedule as closely as
possible on the day of the hearing; however, please plan for the
hearings to run either ahead of schedule or behind schedule. Please
note that the public hearing may close early if all business is
finished.
EPA encourages commenters to provide EPA with a written copy of
their oral testimony electronically by submitting it to the public
docket at <a href="http://www.regulations.gov">www.regulations.gov</a>, Docket ID: EPA-HQ-OW-2022-0114. Oral
comments will be time limited to allow for maximum participation, which
may result in the full statement not being heard. Therefore, EPA also
recommends submitting the text of your oral comments as written
comments to the rulemaking docket. Any person not making an oral
statement may also submit a written statement. Written statements and
supporting information submitted during the comment period will be
considered with the same weight as oral comments and supporting
information presented at the public hearing.
Please note that any updates made to any aspect of the hearing are
posted online at <a href="https://www.epa.gov/sdwa/and-polyfluoroalkyl-substances-pfas">https://www.epa.gov/sdwa/and-polyfluoroalkyl-substances-pfas</a>. While EPA expects the hearing to go forward as set
forth above, please monitor our website or contact <a href="/cdn-cgi/l/email-protection#f8a8beb9abb6a8bcafaab89d8899d69f978e">[email&#160;protected]</a> to
determine if there are any updates. EPA does not

[[Page 18641]]

intend to publish a document in the Federal Register announcing
updates.
If you require any accommodations such as language translation,
captioning, or other special accommodations for the day of the hearing,
please indicate this as a part of your registration and describe your
needs by April 28, 2023. EPA may not be able to arrange accommodations
without advance notice. Please contact <a href="/cdn-cgi/l/email-protection#32627473617c62766560725742531c555d44">[email&#160;protected]</a> with any
questions related to the public hearing.
This proposed rule is organized as follows:

I. General Information
A. What is EPA proposing?
B. Does this action apply to me?
II. Background
A. What are PFAS?
B. Definitions
C. Chemistry, Production and Uses
D. Human Health Effects
E. Statutory Authority
F. Statutory Framework and PFAS Regulatory History
G. Bipartisan Infrastructure Law
H. EPA PFAS Strategic Roadmap
III. Preliminary Regulatory Determinations for Additional PFAS
A. Agency Findings
B. Statutory Criterion 1--Adverse Health Effects
C. Statutory Criterion 2--Occurrence
D. Statutory Criterion 3--Meaningful Opportunity
E. EPA's Preliminary Regulatory Determination Summary for PFHxS,
HFPO-DA, PFNA, and PFBS
F. Request for Comment on EPA's Preliminary Regulatory
Determination for PFHxS, HFPO-DA, PFNA, and PFBS
IV. Approaches to MCLG Derivation
A. Approach to MCLG Derivation for Individual PFAS
B. Approach to MCLG Derivation for a PFAS Mixture
V. Maximum Contaminant Level Goals
A. PFOA
B. PFOS
C. PFAS Hazard Index: PFHxS, HFPO-DA, PFNA, and PFBS
VI. Maximum Contaminant Levels
A. PFOA and PFOS
B. PFAS Hazard Index: PFHxS, HFPO-DA, PFNA, and PFBS
C. Reducing Public Health Risk by Protecting Against Dose
Additive Noncancer Health Effects From PFAS
D. Regulatory Alternatives
E. MCL-Specific Requests for Comment
VII. Occurrence
A. UCMR 3
B. State Drinking Water Data
C. Co-Occurrence
D. Occurrence Relative to the Hazard Index
E. Occurrence Model
F. Combining State Data With Model Output To Estimate National
Exceedance of Either MCLs or Hazard Index
VIII. Analytical Methods
A. Practical Quantitation Levels (PQLs) for Regulated PFAS
IX. Monitoring and Compliance Requirements
A. What are the monitoring requirements?
B. How are PWS compliance and violations determined?
C. Can systems use previously collected data to satisfy the
initial monitoring requirement?
D. Can systems composite samples?
E. Can primacy agencies grant monitoring waivers?
F. When must systems complete initial monitoring?
G. What are the laboratory certification requirements?
X. Safe Drinking Water Act (SDWA) Right to Know Requirements
A. What are the consumer confidence report requirements?
B. What are the public notification (PN) requirements?
XI. Treatment Technologies
A. What are the best available technologies?
B. PFAS Co-Removal
C. Management of Treatment Residuals
D. What are Small System Compliance Technologies (SSCTs)?
XII. Rule Implementation and Enforcement
A. What are the requirements for primacy?
B. What are the primacy agency record keeping requirements?
C. What are the primacy agency reporting requirements?
D. Exemptions and Extensions
XIII. Health Risk Reduction and Cost Analysis
A. Affected Entities and Major Data Sources Used To Develop the
Baseline Water System Characterization
B. Overview of the Cost-Benefit Model
C. Method for Estimating Costs
D. Method for Estimating Benefits
E. Nonquantifiable Benefits of PFOA and PFOS Exposure Reduction
F. Nonquantifiable Benefits of Removal of PFAS Included in the
Proposed Regulation and Co-Removed PFAS
G. Benefits Resulting From Disinfection By-Product Co-Removal
H. Comparison of Costs and Benefits
I. Quantified Uncertainties in the Economic Analysis
J. Cost-Benefit Determination
XIV. Request for Comment on Proposed Rule
Section III--Regulatory Determinations for Additional PFAS
Section V--Maximum Contaminant Level Goals
Section VI--Maximum Contaminant Levels
Section VII--Occurrence
Section IX--Monitoring and Compliance Requirements
Section X--Safe Drinking Water Right to Know
Section XI--Treatment Technologies
Section XII--Rule Implementation and Enforcement
Section XIII--HRRCA
Section XV--Statutory and Executive Order Reviews
XV. Statutory and Executive Order Reviews
A. Executive Order 12866: Regulatory Planning and Review and
Executive Order 13563 Improving Regulation and Regulatory Review
B. Paperwork Reduction Act (PRA)
C. Regulatory Flexibility Act (RFA)
D. Unfunded Mandates Reform Act (UMRA)
E. Executive Order 13132: Federalism
F. Executive Order 13175: Consultation and Coordination With
Indian Tribal Governments
G. Executive Order 13045: Protection of Children From
Environmental Health and Safety Risks
H. Executive Order 13211: Actions That Significantly Affect
Energy Supply, Distribution, or Use
I. National Technology Transfer and Advancement Act of 1995
J. Executive Order 12898: Federal Actions To Address
Environmental Justice in Minority Populations and Low-Income
Populations
K. Consultations With the Science Advisory Board, National
Drinking Water Advisory Council, and the Secretary of Health and
Human Services
XVI. References

I. General Information

A. What is EPA proposing?

EPA is proposing for public comment a drinking water regulation
that includes six PFAS. EPA is proposing to establish MCLGs and an
NPDWR for these PFAS in public drinking water supplies. EPA proposes
MCLGs for PFOA and PFOS at zero (0) and an enforceable MCL for PFOA and
PFOS in drinking water at 4.0 ppt. Additionally, the Agency is
requesting comment on a preliminary determination to regulate
additional PFAS to include PFHxS, HFPO-DA \1\ (also known as and
referred to as ``GenX Chemicals'' in this proposal), PFNA, and PFBS.
Concurrent with this preliminary determination, EPA is proposing an HI
of 1.0 as the MCLG and enforceable MCL to address individual and
mixtures of these four contaminants where they occur in drinking water.
EPA is proposing to calculate the HI as the sum total of component PFAS
HQs, calculated by dividing the measured component PFAS concentration
in water by the relevant HBWC. In this proposal, EPA is using HBWCs of
9.0 ppt for PFHxS, 10.0 ppt

[[Page 18642]]

for HFPO-DA; 10.0 ppt for PFNA; and 2000 ppt for PFBS. The proposed
approach to calculating the HI for this set of four PFAS compounds is
designed to be protective against all adverse effects, not a single
outcome/effect, and is a health protective decision aid for use in
determining the level at which there are no adverse effects on the
health of persons with an adequate margin of safety, thus is
appropriate for MCLG development.
---------------------------------------------------------------------------

\1\ PFAS may exist in multiple forms, such as acids and organic
or metal salts. Each of these forms may be listed as a separate
entry in certain databases and have separate Chemical Abstract
Service (CAS) Registry numbers. However, PFAS are expected to
dissociate in water to their anionic form. For example, the term
``GenX Chemicals'' acknowledges the ``acid'' and ``ammonium salt''
forms of HFPO-DA as two different chemicals. In water, though, these
chemicals dissociate and therefore the resulting anion appears as a
single analyte for the purposes of detection and quantitation.
Please see ``definitions'' for more information. EPA notes that the
chemical HFPO-DA is used in a processing aid technology developed by
DuPont to make fluoropolymers without using PFOA. The chemicals
associated with this process are commonly known as GenX Chemicals
and the term is often used interchangeably for HFPO-DA along with
its ammonium salt (USEPA, 2021b).
---------------------------------------------------------------------------

The requirements in this proposal that apply to (1) PFOA, (2) PFOS,
and (3) PFHxS, HFPO-DA, PFNA, and PFBS and their mixtures are distinct
and capable of operating independently.

B. Does this action apply to me?

The preliminary regulatory determination to establish drinking
water regulations for certain PFAS and their mixtures and the proposed
regulation are proposals for public comment and are not requirements or
regulations. Instead, this action notifies interested parties of the
availability of information supporting the preliminary regulatory
determinations for four PFAS and their mixtures, the development of the
NPDWR for six PFAS, and proposed rule requirements for public comment.
If EPA proceeds to a final regulatory determination and final
regulation, once promulgated, this action will potentially affect the
following:

------------------------------------------------------------------------
Examples of potentially affected
Category entities
------------------------------------------------------------------------
Public water systems \2\............. Community water systems (CWSs);
Non-transient, non-community
water systems (NTNCWSs).
State and tribal agencies............ Agencies responsible for drinking
water regulatory development and
enforcement.
------------------------------------------------------------------------

This table is not intended to be exhaustive, but rather provides a
guide for readers regarding entities that could be affected by this
action once promulgated. To determine whether a facility or activities
could be affected by this action, this proposed rule should be
carefully examined. Questions regarding the applicability of this
action to a particular entity may be directed to the person listed in
the FOR FURTHER INFORMATION CONTACT section.
---------------------------------------------------------------------------

\2\ The term ``public water system'' means a system for the
provision to the public of water for human consumption through pipes
or other constructed conveyances, if such system has at least
fifteen service connections or regularly serves at least twenty-five
individuals. Such term includes (i) any collection, treatment,
storage, and distribution facilities under control of the operator
of such system and used primarily in connection with such system,
and (ii) any collection or pretreatment storage facilities not under
such control which are used primarily in connection with such
system.
---------------------------------------------------------------------------

II. Background

A. What are PFAS?

PFAS are a large class of specialized synthetic chemicals that have
been in use since the 1940s (USEPA, 2018a). This proposed regulation
only applies to certain PFAS: PFOA, PFOS, PFHxS, HFPO-DA, PFNA, and
PFBS. People may potentially be exposed to these PFAS through certain
consumer products such as textiles (e.g., seat covers, sail covers,
weather protection (Janousek et al., 2019)), leather shoes as well as
shoe polish/wax (Norden, 2013; Borg and Ivarsson, 2017), along with
cooking/baking wares (Blom and Hanssen 2015; KEMI, 2015; Gl[uuml]ge et
al., 2020), occupational contact, and/or by consuming food and drinking
water that contain PFAS. Due to their widespread use, physicochemical
properties, and prolonged persistence, many PFAS co-occur in exposure
media (e.g., air, water, ice, sediment), and bioaccumulate in tissues
and blood of aquatic as well as terrestrial organisms, including humans
(Domingo and Nadal, 2019; Fromme et al., 2009). Industrial workers who
are involved in manufacturing or processing fluoropolymers, or people
who live or recreate near fluoropolymer facilities, may encounter
greater exposures; particularly of PFOA, PFNA, as well as HFPO-DA.
Firefighters as well as people who live near airfields or military
bases may have especially higher exposure to PFHxS and PFBS due to the
use of aqueous foam forming film as a fire suppressant. Pregnant and
lactating women, as well as children, may be more sensitive to the
harmful effects of certain PFAS, for example, PFOA, PFOS, PFNA, and
PFBS. For example, studies indicate that PFOA and PFOS exposure above
certain levels may result in adverse health effects, including
developmental effects to fetuses during pregnancy or to breast- or
formula-fed infants, cancer, immunological effects, among others
(USEPA, 2023b; USEPA, 2023c). Other PFAS are also documented to result
in a range of adverse health effects (USEPA, 2021a; USEPA, 2021b;
ATSDR, 2021; NASEM 2022).
Although most United States production of PFOS, PFOA, and PFNA,
along with other long-chain PFAS, was phased out and then generally
replaced by production of PFBS, PFHxS, HFPO-DA and other PFAS, EPA is
aware of ongoing use of PFOS, PFOA, PFNA, and other long-chain PFAS.
Domestic production and import of PFOA has been phased out in the
United States by the companies participating in the 2010/2015 PFOA
Stewardship Program. Small quantities of PFOA may be produced,
imported, and used by companies not participating in the PFOA
Stewardship Program and some uses of PFOS are ongoing (see 40 Code of
Federal Regulations (CFR) Sec. 721.9582). EPA is also aware of ongoing
use of the chemicals available from existing stocks or newly introduced
via imports. Additionally, the environmental persistence of these
chemicals and formation as degradation products from other compounds
may still contribute to their release in the environment.

B. Definitions

The six PFAS proposed for regulation and their relevant Chemical
Abstract Service (CAS) registry numbers are:

<bullet> PFOA (C8F15CO2-; CAS: 45285-51-6)
<bullet> PFOS (C8F17SO3-; CAS: 45298-90-6)
<bullet> PFHxS (C6F13SO3-; CAS: 108427-53-8)
<bullet> HFPO-DA (C6F11O3-; CAS: 122499-17-6)
<bullet> PFNA (C9F17CO2-; CAS: 72007-68-2)
<bullet> PFBS (C4F9SO3-; CAS: 45187-15-3)

These PFAS may exist in multiple forms, such as isomers or
associated salts and each form may have a separate CAS Registry number
or no CAS at all. Additionally, these compounds have various names
under different classification systems. However, at environmentally
relevant pHs, these PFAS are expected to dissociate in water to their
anionic (negatively charged) forms. For instance, International Union
of Pure and Applied Chemistry substance 2,3,3,3-tetrafluoro-2-
(heptafluoropropoxy) propanoate (CAS: 122499-17-6), also known as HFPO-
DA, is an anionic molecule which has an ammonium salt (CAS: 62037-80-
3), a conjugate acid (CAS: 13252-13-6), a potassium salt (CAS: 67118-
55-2), and an acyl fluoride precursor (CAS: 2062-98-8), among other
variations. At environmentally relevant pHs these all dissociate into
the propanoate/anion form (CAS: 122499-17-6). Each PFAS listed has
multiple variants with differing chemical connectivity but the same
molecular composition; these are known as

[[Page 18643]]

isomers. Commonly, the isomeric composition of PFAS is categorized as
`linear,' consisting of an unbranched alkyl chain, or `branched,'
encompassing a potentially diverse group of molecules including at
least one, but potentially more offshoots from the linear molecule.
While broadly similar, isomeric molecules may have differences in
chemical properties. The proposed regulation covers all salts, isomers
and derivatives of the chemicals listed, including derivatives other
than the anionic form which might be created or identified.

C. Chemistry, Production and Uses

PFAS are most commonly and widely used to make products resistant
to water, heat, and stains. As a result, they are found in industrial
and consumer products such as clothing, food packaging, cookware,
cosmetics, carpeting, and fire-fighting foam (AAAS, 2020). Facilities
associated with PFAS releases into the air, soil, and water include
those for manufacturing, chemical as well as well as product production
and military installations (USEPA, 2016a; USEPA, 2016b).
The chemical structures of some PFAS cause them to repel water as
well as oil, remain chemically and thermally stable, and exhibit
surfactant properties. PFAS have strong, stable carbon-fluorine (C-F)
bonds, making them resistant to hydrolysis, photolysis, microbial
degradation, and metabolism (Ahrens, 2011; Beach et al., 2006; Buck et
al., 2011). These properties are what make PFAS useful for commercial
and industrial applications and purposes. However, these are also what
make some PFAS extremely persistent in the human body and the
environment (Calafat et al., 2007, 2019).
PFOA, PFOS, PFHxS, HFPO-DA, PFNA, and PFBS belong to a subset of
PFAS known as perfluoroalkyl acids (PFAAs), all of which consist of a
perfluorinated alkyl chain connected to an acidic headgroup. Humans are
exposed to PFAS due to wide-ranging commercial and industrial
applications along with long range migration from sources. The
structure of these PFAS contribute to their persistence in the
environment as well as their resistance to chemical, biological, and
physical degradation processes.
PFOA and PFOS are two of the most widely studied and longest used
PFAS. These two compounds have been detected in up to 98 percent of
human serum samples taken in biomonitoring studies that are
representative of the U.S. general population; however, since PFOA and
PFOS have been voluntarily phased out in the U.S., serum concentrations
have been declining (CDC, 2019). The sole U.S. manufacturer of PFOS
agreed to a voluntary phaseout in 2000, and the last reported
production was in 2002 (USEPA, 2000b; USEPA, 2018b; USEPA, 2021c). PFOS
has been used as a surfactant or emulsifier in firefighting foam,
circuit board etching acids, alkaline cleaners, floor polish, and as a
pesticide active ingredient for insect bait traps (HSBD, 2016). PFOA
has been used as an emulsifier and surfactant in fluoropolymers (such
as in the manufacturing of non-stick products like Teflon(copyright)),
firefighting foams, cosmetics, grease and lubricants, paints, polishes,
and adhesives (HSBD, 2016).
PFNA was historically the second most used surfactant for emulsion
polymerization (after PFOA) which was its main use (Buck et al., 2012).
Fluorinated surfactants improve the physical properties of the polymer
as well as improving the polymerization rate (Gl[uuml]ge et al., 2020).
Fluoropolymers are used in many applications because of their unique
physical properties such as resistance to high and low temperatures,
resistance to chemical and environmental degradation, and nonstick
characteristics. Fluoropolymers also have dielectric and fire-resistant
properties that have a wide range of electrical and electronic
applications, including architecture, fabrics, automotive uses, cabling
materials, electronics, pharmaceutical and biotech manufacturing, and
semiconductor manufacturing (Gardiner, 2014). Although drying processes
can release the surfactants when manufacturing is complete, surfactant
residues remain in the finished products (KEMI, 2015). Legacy stocks
may still be used and products containing PFNA may still be produced
internationally and imported to the U.S. (ATSDR, 2021).
The voluntary phase out caused a shift to alternatives such as per-
and polyfluoroalkyl ether carboxylic acids (PFECAs). The chemical HFPO-
DA is the most prevalent of these and is used in a processing aid
technology developed by DuPont to make fluoropolymers without using
PFOA. The chemicals associated with this process are commonly known as
GenX Chemicals and the term is often used interchangeably for HFPO-DA
along with its ammonium salt (USEPA, 2021b). The most common use for
GenX Chemicals is for emulsion polymerization.
Another alternative, PFBS, is mainly used as a water and stain
repellent protection for leather, textiles, carpets, and porous hard
surfaces, representing 25-50 tons/year of PFBS in mixtures (Norwegian
Environment Agency, 2017). PFBS and related chemicals are also used in
curatives for fluoroelastomers (Gl[uuml]ge et al., 2020). The curatives
are used for manufacturing O-rings, seals, linings, protective
clothing, cooking wares, and flame retardants (Norwegian Environment
Agency, 2017; Blom and Hanssen, 2015).
PFHxS is used in stain-resistant fabrics, fire-fighting foams,
flame retardants, insecticides, and as a surfactant in industrial
processes (Gl[uuml]ge et al., 2020). Additionally, particle
accelerators including the Delphi Detector at Stanford University rely
on liquid PFHxS (Gl[uuml]ge et al., 2020). PFHxS production, along with
PFOS, was phased out in 2002 nationwide however, production continues
in other countries and products containing PFHxS may be imported into
the U.S. (USEPA, 2000c). Legacy stocks may also still be used.

D. Human Health Effects

The publicly available landscape of human epidemiological and
experimental animal-based exposure-effect data from repeat-dose studies
across PFAS derive primarily from linear carboxylic and sulfonic acid
species such as PFOA, PFOS, PFHxS, PFNA, and PFBS (ATSDR, 2021). Many
other PFAS have preliminary human health effects data (Mahoney et al.,
2022) and some PFAS, such as PFBS and HFPO-DA, have sufficient data
that has allowed EPA to derive toxicity values and publish toxicity
assessments (USEPA, 2021a; USEPA, 2021b). The adverse health effects
observed following oral exposure to such PFAS are significant and
diverse and include (but are not limited to): cancer and effects on the
liver (e.g., liver cell death), growth and development (e.g., low birth
weight), hormone levels, kidney, immune system, lipid levels (e.g.,
high cholesterol), the nervous system, and reproduction. Please see
sections III.B, IV, and V of this preamble for additional discussion on
health considerations for the six PFAS EPA is proposing to regulate in
this document.

E. Statutory Authority

Section 1412(b)(1)(A) of SDWA requires EPA to establish NPDWRs for
a contaminant where the Administrator determines that the contaminant:
(1) may have an adverse effect on the health of persons; (2) is known
to occur or there is a substantial likelihood that the contaminant will
occur in PWSs with a frequency and at levels of public health concern;
and (3) where in the sole

[[Page 18644]]

judgment of the Administrator, regulation of such contaminant presents
a meaningful opportunity for health risk reduction for persons served
by PWSs.

F. Statutory Framework and PFAS Regulatory History

Section 1412(b)(1)(B)(i) of SDWA requires EPA to publish a
Contaminant Candidate List (CCL) every five years. The CCL is a list of
contaminants that are known or anticipated to occur in PWSs and are not
currently subject to any proposed or promulgated NPDWRs. EPA uses the
CCL to identify priority contaminants for regulatory decision-making
(i.e., regulatory determinations), and information collection.
Contaminants listed on the CCL may require future regulation under
SDWA. EPA included PFOA and PFOS on the third and fourth CCLs published
in 2009 (USEPA, 2009a) and 2016 (USEPA, 2016c). The Agency published
the fifth CCL (CCL 5) earlier this year and it includes PFAS as a
chemical group (USEPA, 2022b).
EPA collects data on the CCL contaminants to better understand
their potential health effects and to determine the levels at which
they occur in PWSs. SDWA 1412(b)(1)(B)(ii) requires that, every five
years and after considering public comments on a ``preliminary''
regulatory determination, EPA issue a final regulatory determination to
regulate or not regulate at least five contaminants on each CCL. In
addition, Section 1412(b)(1)(B)(ii)(III) authorizes EPA to make a
determination to regulate a contaminant not listed on the CCL so long
as the contaminant meets the three statutory criteria based on
available public health information. SDWA 1412(b)(1)(B)(iii) requires
that ``each document setting forth the determination for a contaminant
under clause (ii) shall be available for public comment at such time as
the determination is published.'' To implement these requirements, EPA
issues preliminary regulatory determinations subject to public comment
and then issues a final regulatory determination after consideration of
public comment. For any contaminant that EPA determines meets the
criteria for regulation under SDWA 1412(b)(1)(A), Section 1412(b)(1)(E)
requires that EPA propose a NPDWR within two years and promulgate a
final regulation within 18 months of the proposal (which may be
extended by 9 additional months).
EPA implements a monitoring program for unregulated contaminants
under SDWA 1445(a)(2) which requires that once every five years, EPA
issue a list of priority unregulated contaminants to be monitored by
PWSs. This monitoring is implemented through the Unregulated
Contaminant Monitoring Rule (UCMR), which collects data from CWSs and
NTNCWSs. The first four UCMRs collected data from a census of large
water systems (serving more than 10,000 people) and from a
statistically representative sample of small water systems (serving
10,000 or fewer people). Water system monitoring data for six PFAS were
collected during the third UCMR (UCMR3) between 2013 to 2015. The fifth
UCMR (UCMR5), published December 2021, requires sample collection and
analysis for 29 PFAS to occur between 2023 and 2025 using analytical
methods developed by EPA and consensus organizations. Section 2021 of
America's Water Infrastructure Act of 2018 (AWIA) (Pub. L. 115-270)
amended SDWA and specifies that, subject to the availability of EPA
appropriations for such purpose and sufficient laboratory capacity, EPA
must require all PWSs serving between 3,300 and 10,000 people to
monitor and ensure that a nationally representative sample of systems
serving fewer than 3,300 people monitor for the contaminants in UCMR 5
and future UCMR cycles. All large water systems continue to be required
to participate in the UCMR program. Section VII of this preamble
provides additional discussion on PFAS occurrence. Additionally, while
the UCMR 5 information will not be available to inform this proposal,
EPA is proposing to consider the UCMR 5 data to support implementation
of monitoring requirements under the proposed rule. Section IX of this
preamble further discusses monitoring and compliance requirements.
After careful consideration of public comments, EPA issued final
regulatory determinations for contaminants on the fourth CCL in March
of 2021 (USEPA, 2021d) which included determinations to regulate two
contaminants, PFOA and PFOS, in drinking water. EPA found that PFOA and
PFOS may have an adverse effect on the health of persons; that these
contaminants are known to occur, or that there is a substantial
likelihood that they will occur, in PWSs with a frequency and at levels
that present a public health concern; and that regulation of PFOA and
PFOS presents a meaningful opportunity for health risk reduction for
persons served by PWSs. As discussed in the final Regulatory
Determinations 4 Notice for CCL 4 contaminants (USEPA, 2021d) and EPA's
PFAS Strategic Roadmap (USEPA, 2022c), the Agency has also evaluated
additional PFAS chemicals for regulatory consideration as supported by
the best available science. The Agency preliminarily finds that
additional PFAS compounds also meet SDWA criteria for regulation. EPA's
preliminary regulatory determination for these additional PFAS is
discussed in section III of this preamble.
Section 1412(b)(1)(E) provides that the Administrator may publish a
proposed drinking water regulation concurrent ``with a determination to
regulate.'' This provision authorizes a more expedited process by
allowing EPA to make concurrent the regulatory determination and
rulemaking processes. As a result, EPA interprets the reference to
``determination to regulate'' in Section 1412(b)(1)(E) as referring to
the regulatory process in 1412(b)(1)(B)(ii) that begins with a
preliminary determination. Under this interpretation, Section
1412(b)(1)(E) authorizes EPA to issue a preliminary determination to
regulate a contaminant and a proposed NPDWR addressing that contaminant
concurrently and request public comment at the same time. This allows
EPA to act efficiently to issue a final determination to regulate
concurrently with a final NPDWR to avoid delays to address contaminants
that meet the statutory criteria. As a result, this proposal contains
both a preliminary determination to regulate four PFAS contaminants and
proposed regulations for those contaminants as well as the two PFAS
contaminants (PFOA and PFOS) for which EPA has already issued a final
Regulatory Determination. EPA developed a proposed MCLG and a proposed
NPDWR for six PFAS compounds pursuant to the requirements under section
1412(b)(1)(B) of SDWA. The proposed MCLGs and proposed NPDWR are
discussed in more detail below.

G. Bipartisan Infrastructure Law

The Agency notes that the passage of the Infrastructure Investment
and Jobs Act, also referred to as the BIL, invests over $11.7 billion
in the Drinking Water SRF; $4 billion to the Drinking Water SRF for
Emerging Contaminants; and $5 billion to Small, Underserved, and
Disadvantaged Communities Grants. These funds will assist many
disadvantaged communities, small systems, and others with the costs of
installation of treatment when it might otherwise be cost-challenging.
These funds can also be used to address emerging contaminants like PFAS
in drinking water through actions such as technical assistance, water
quality testing, and contractor training, which will allow communities
supplemental funding to meet their obligations under

[[Page 18645]]

this proposed regulation and help ensure protection from PFAS
contamination of drinking water.

H. EPA PFAS Strategic Roadmap

In October 2021, EPA published the PFAS Strategic Roadmap that
outlined the Agency's plan to ``further the science and research, to
restrict these dangerous chemicals from getting into the environment,
and to immediately move to remediate the problem in communities across
the country'' (USEPA, 2022c). Described in the Roadmap are key
commitments the Agency made toward addressing these contaminants in the
environment. With this proposal, EPA is delivering on a key commitment
in the Roadmap to ``establish a National Primary Drinking Water
Regulation'' for proposal and is working toward promulgating the final
NPDWR in Fall of 2023.

III. Preliminary Regulatory Determinations for Additional PFAS

Since 2021 when EPA determined to regulate two PFAS contaminants,
PFOA and PFOS, EPA has evaluated additional PFAS compounds for
regulatory consideration and has preliminarily determined that an
additional four individual PFAS and mixtures of these PFAS meet SDWA
criteria for regulation. Section 1401(6) defines the term
``contaminant'' to mean ``any physical, chemical or biological or
radiological substance or matter in water.'' A mixture of two or more
``contaminants'' qualifies as a ``contaminant'' because the mixture
itself is ``any physical, chemical or biological or radiological
substance or matter in water.'' (emphasis added). Therefore, pursuant
to the provisions outlined in Section 1412(b)(1)(A) and 1412(b)(1)(B)
of SDWA, the Agency is making a preliminary determination to regulate
PFHxS, HFPO-DA, PFNA, and PFBS in drinking water, and mixtures of these
PFAS contaminants. PFHxS, HFPO-DA, PFNA, and PFBS, and mixtures of
these PFAS, are known to cause adverse human health effects; there is
substantial likelihood that they will occur and co-occur in PWSs with a
frequency and at levels of public health concern, particularly when
considering them in a mixture; and in the sole judgment of the
Administrator, regulation of PFHxS, HFPO-DA, PFNA, PFBS and mixtures of
these PFAS present a meaningful opportunity for health risk reductions
for people served by PWSs. This section describes the best available
science and information used by the Agency to support this preliminary
Regulatory Determination. The proposed MCLG and enforceable standard
for these four PFAS and mixtures of these PFAS are discussed further in
sections V to VI of this preamble.

A. Agency Findings

To support the Agency's preliminary Regulatory Determination, EPA
examined health effects information from available peer reviewed human
health assessments as well as drinking water monitoring data collected
as part of the UCMR 3 and state-led monitoring efforts. EPA finds that
oral exposure to PFHxS, HFPO-DA, PFNA, and PFBS may individually and in
a mixture each result in adverse health effects, including disrupting
multiple biological pathways that result in common adverse effects on
several biological systems including the endocrine, cardiovascular,
developmental, immune, and hepatic systems (USEPA, 2023a). PFAS,
including PFHxS, HFPO-DA, PFNA, and PFBS and their mixtures are
anticipated to affect common target organs, tissues, or systems to
produce dose-additive effects from co-exposures. Additionally, based on
the Agency's evaluation of the best-available science, EPA finds that
PFHxS, HFPO-DA, PFNA, and PFBS each have a substantial likelihood to
occur in finished drinking water and that these PFAS are also likely to
co-occur as mixtures and result in increased exposure above levels of
health concern. Therefore, given this high occurrence and co-occurrence
likelihood and that adverse health effects arise as a result of both
these PFAS individually and as mixtures, the Agency is preliminarily
determining that PFHxS, HFPO-DA, PFNA, and PFBS and their mixtures may
have adverse human health effects; there is a substantial likelihood
that PFHxS, HFPO-DA, PFNA, PFBS and mixtures of these PFAS, will occur
and co-occur in PWSs with a frequency and at levels of public health
concern; and in the sole judgment of the Administrator, regulation of
PFHxS, HFPO-DA, PFNA, and PFBS, and their mixtures, presents a
meaningful opportunity for health risk reductions for persons served by
PWSs.

B. Statutory Criterion 1--Adverse Health Effects

The Agency finds that PFHxS, HFPO-DA, PFNA, PFBS and their mixtures
may have an adverse effect on the health of persons. Discussion related
to health effects for each of the four PFAS is below. For this
proposal, the Agency is developing HBWCs for PFHxS, HFPO-DA, PFNA and
PFBS, defined as a level protective of health effects over a lifetime
of exposure, including sensitive populations and life stages. Each of
the four HBWCs is used in this proposal to evaluate occurrence data and
the likelihood of potential risk to human health to justify the
agency's preliminary regulatory determinations for PFHxS, HFPO-DA, PFNA
and PFBS. The chemical-specific HBWCs are also used to assess the
potential human health risk associated with mixtures of the four PFAS
in drinking water using the HI approach. Additional details on the HBWC
for PFHxS, HFPO-DA, PFNA and PFBS are found in section IV of this
preamble. More information supporting EPA's preliminary regulatory
determination relating to adverse health effects for these PFAS and the
HI approach for mixtures is available in section V of this preamble.
1. PFHxS
Toxicity studies of oral PFHxS exposure in animals have reported
adverse health effects on the liver, thyroid, and development (ATSDR,
2021). EPA has not yet classified the carcinogenicity of PFHxS. For a
detailed discussion on adverse effects of oral exposure to PFHxS,
please see ATSDR (2021) and USEPA (2023a).
The HBWC for PFHxS is derived using a chronic reference value based
on an Agency For Toxic Substances And Disease Registry (ATSDR)
intermediate-duration oral Minimal Risk Level, which was based on
thyroid effects seen in male rats after oral PFHxS exposure (ATSDR,
2021). The most sensitive non-cancer effect observed was thyroid
follicular epithelial hypertrophy/hyperplasia in parental male rats
exposed to PFHxS for 42-44 days, identified in the critical
developmental toxicity study selected by ATSDR (no observed adverse
effect level (NOAEL) of 1 mg/kg/day) (Butenhoff et al., 2009; ATSDR,
2021). To derive the intermediate-duration Minimal Risk Level for
PFHxS, ATSDR calculated a human equivalent dose (HED) of 0.0047 mg/kg/
day from the NOAEL of 1 mg/kg/day identified in the principal study.
Then, ATSDR applied a total uncertainty factor (UF)/modifying factor
(MF) of 300X (10X UF for intraspecies variability, 3X UF for
interspecies differences, and a 10X MF for database deficiencies) to
yield an intermediate-duration oral Minimal Risk Level of 0.00002 mg/
kg/day (ATSDR, 2021). Per Agency guidance (USEPA, 2002), to calculate
the HBWC, EPA applied an additional UF of 10 to adjust for subchronic-
to-chronic duration (UF<INF>S</INF>) because the effect was not in a
developmental life stage (i.e., thyroid follicular epithelial
hypertrophy/hyperplasia in parental male rats). The

[[Page 18646]]

resulting chronic reference value was 0.000002 mg/kg/day.
No sensitive population or life stage was identified for
bodyweight-adjusted drinking water intake (DWI-BW) selection for PFHxS
because the critical effect on which the ATSDR Minimal Risk Level was
based (thyroid alterations) was observed in adult male rats. Since this
exposure life stage does not correspond to a sensitive population or
life stage, a DWI-BW for adults within the general population (0.034 L/
kg/day; 90th percentile direct and indirect consumption of community
water, consumer-only two-day average, adults 21 years and older) was
selected for HBWC derivation (USEPA, 2019a).
EPA calculated the HBWC for PFHxS using a relative source
contribution (RSC) of 0.20. This means that 20% of the exposure--equal
to the chronic reference value--is allocated to drinking water, and the
remaining 80% is attributed to all other potential exposure sources.
This was based on EPA's determination that the available data on PFHxS
exposure routes and sources did not permit quantitative
characterization of PFHxS exposure. In such cases, an RSC of 0.20 is
typically used (USEPA, 2000c). See U.S.EPA (2023a) for complete details
on the RSC determination for PFHxS.
As further described in USEPA (2023a) and section V of this
preamble below, the HBWC for PFHxS is calculated to be 9.0 ppt. This
HBWC of 9.0 ppt is also used as the health reference level (HRL) for
this preliminary regulatory determination.
2. HFPO-DA
EPA's 2021 Human Health Toxicity Assessment for GenX Chemicals
describes potential health effects associated with oral exposure to
HFPO-DA (USEPA, 2021b). Toxicity studies in animals indicate that
exposures to HFPO-DA may result in adverse health effects, including
liver and kidney toxicity and immune system, hematological,
reproductive, and developmental effects (USEPA, 2021b). There is
Suggestive Evidence of Carcinogenic Potential of oral exposure to HFPO-
DA in humans, but the available data are insufficient to derive a
cancer risk concentration in water for HFPO-DA. For a detailed
discussion on adverse effects of oral exposure to HFPO-DA, please see
USEPA (2021b).
EPA's noncancer HBWC for HFPO-DA is derived from a reference dose
(RfD) that is based on liver effects observed following oral exposure
of mice to HFPO-DA (USEPA, 2021b). The most sensitive noncancer effect
observed was a constellation of liver lesions in parental female mice
exposed to HFPO-DA by gavage for 53-64 days, identified in the critical
reproductive/developmental toxicity study selected by EPA (NOAEL of 0.1
mg/kg/day) (DuPont, 2010; USEPA, 2021b). To develop the chronic RfD for
HFPO-DA, EPA derived an HED of 0.01 mg/kg/day from the NOAEL of 0.1 mg/
kg/day identified in the principal study. EPA then applied a composite
UF of 3,000 (i.e., 10X for intraspecies variability, 3X for
interspecies differences, 10X for extrapolation from a subchronic to a
chronic dosing duration, and 10X for database deficiencies) to yield
the chronic RfD (USEPA, 2021b).
To select an appropriate DWI-BW for use in derivation of the
noncancer HBWC values for HFPO-DA, EPA considered the HFPO-DA exposure
interval used in the oral reproductive/developmental toxicity study in
mice that was the basis for chronic RfD derivation (the critical
study). In this study, parental female mice were dosed from pre-mating
through lactation, corresponding to three potentially sensitive human
adult life stages that may represent critical windows of exposure for
HFPO-DA: women of childbearing age, pregnant women, and lactating women
(Table 3-63 in USEPA, 2019a). Of these three, the DWI-BW for lactating
women (0.0469 L/kg/day) is anticipated to be protective of the other
two sensitive life stages. Therefore, EPA used the DWI-BW for lactating
women to calculate the HBWC for the proposed regulation, which is also
used for the HRL for the preliminary regulatory determination.
The HBWC value for HFPO-DA was calculated using an RSC of 0.20.
This means that 20% of the exposure--equal to the RfD--is allocated to
drinking water, and the remaining 80% is attributed to all other
potential exposure sources (USEPA, 2022d). Selection of this RSC was
based on EPA's determination that the available exposure data for HFPO-
DA did not enable a quantitative characterization of relative HFPO-DA
exposure sources and routes. In such cases, an RSC of 0.20 is typically
used (USEPA, 2000c).
As further described in USEPA (2023a) and USEPA (2022d), the HBWC
for HFPO-DA is calculated to be 10.0 ppt. This value is consistent with
EPA's 2022 drinking water health advisory for HFPO-DA (USEPA, 2022d),
but was derived from EPA's 2021 Human Health Toxicity Assessment for
HFPO-DA (USEPA, 2021b). This HBWC of 10 ppt is also used as the HRL for
this preliminary Regulatory Determination for HFPO-DA.
3. PFNA
Animal toxicity studies have reported adverse health effects,
specifically on development, reproduction, immune function, and the
liver, after oral exposure to PFNA (ATSDR, 2021). EPA has not yet
classified the carcinogenicity of PFNA. For a detailed discussion on
adverse effects of oral exposure to PFNA, please see ATSDR (2021) and
USEPA (2023a).
The HBWC for PFNA is derived using a chronic reference value based
on an ATSDR intermediate-duration oral Minimal Risk Level, which was
based on developmental effects seen in mice after oral PFHxS exposure
(ATSDR, 2021). The most sensitive non-cancer effects were decreased
body weight (BW) gain and developmental delays (i.e., delayed eye
opening, preputial separation, and vaginal opening) in mice born to
mothers that were gavaged with PFNA from gestational days (GD) 1-17,
with continued exposure through lactation and monitoring until
postnatal day (PND) 287, identified in the critical developmental
toxicity study selected by ATSDR (NOAEL of 1 mg/kg/day) (Das et al.,
2015; ATSDR, 2021). To derive the intermediate-duration Minimal Risk
Level, ATSDR calculated an HED of 0.001 mg/kg/day from the NOAEL of 1
mg/kg/day identified in the principal study. Then, ATSDR applied a
total UF/MF of 300X (total UF of 30X and a MF of 10X for database
deficiencies) to yield an intermediate-duration Minimal Risk Level of
0.000003 mg/kg/day. EPA did not apply an additional UF to adjust for
subchronic-to-chronic duration (i.e., UF<INF>S</INF>) to calculate the
chronic reference value because the critical effects were observed
during a developmental life stage (USEPA, 2002). The chronic reference
value of 0.000003 mg/kg/day was used to derive the HBWC for PFNA.
Based on the life stages of exposure in the principal study from
which the intermediate-duration Minimal Risk Level was derived (i.e.,
during gestation and lactation), EPA identified three potentially
sensitive life stages that may represent critical windows of exposure
for PFNA: women of childbearing age (13 to < 50 years), pregnant women,
and lactating women (Table 3-63 in USEPA, 2019a). The DWI-BW for
lactating women (0.0469 L/kg/day; 90th percentile direct and indirect
consumption of community water, consumer-only two-day average) was
selected to calculate the HBWC for PFNA because it is the highest of
the three DWI-BWs and is anticipated to be protective of the other two
sensitive life stages.

[[Page 18647]]

EPA calculated the HBWC for PFNA using an RSC of 0.20. This means
that 20% of the exposure--equal to the chronic reference value--is
allocated to drinking water, and the remaining 80% is attributed to all
other potential exposure sources. This was based on EPA's determination
that the available data on PFNA exposure routes and sources did not
permit quantitative characterization of PFNA exposure. In such cases,
an RSC of 0.20 is typically used (USEPA, 2000c). See USEPA (2023a) for
complete details on the RSC determination for PFNA.
As further described in USEPA (2023a), the HBWC for PFNA is
calculated to be 100 ppt. This HBWC of 10.0 ppt is also used as the HRL
for this preliminary Regulatory Determination for PFNA.
4. PFBS
EPA's 2021 PFBS Toxicity Assessment describe potential health
effects associated with oral PFBS exposure (USEPA, 2021a). Toxicity
studies of oral PFBS exposures in animals have reported adverse health
effects on development, as well as the thyroid and kidneys (USEPA,
2021a). Human and animal studies evaluated other health effects
following PFBS exposure including effects on the immune, reproductive,
and hepatic systems and lipid and lipoprotein homeostasis, but the
evidence was determined to be equivocal (USEPA, 2021a). No studies
evaluating the carcinogenicity of PFBS in humans or animals were
identified. EPA concluded that there is ``Inadequate Information to
Assess Carcinogenic Potential'' for PFBS and K+PFBS by any route of
exposure. For a detailed discussion on adverse effects of oral exposure
to PFBS, please see USEPA (2021a).
EPA's noncancer HBWC for PFBS is derived from a chronic RfD that is
based on thyroid effects observed following gestational exposure of
mice to K+PFBS (USEPA, 2021a; USEPA, 2022e). The most sensitive non-
cancer effect observed was decreased serum total thyroxine (T4) in
newborn (PND 1) mice gestationally exposed to K+PFBS from GD 1-20,
identified in the critical developmental toxicity study selected by EPA
(benchmark dose lower confidence limit HED or BMDLHED) of 0.095 mg/kg/
day) (Feng et al., 2017; USEPA, 2021a). To develop the chronic RfD for
PFBS, EPA applied a composite UF of 300 (i.e., 10X for intraspecies
uncertainty factor (UF<INF>H</INF>), 3X for interspecies uncertainty
factor (UF<INF>A</INF>), and 10X for database uncertainty factor
(UF<INF>D</INF>)) to yield a value of 0.0003 mg/kg/day (USEPA, 2021a).
To select an appropriate DWI-BW for use in deriving the noncancer
HBWC value, EPA considered the PFBS exposure interval used in the
developmental toxicity study in mice that was the basis for chronic RfD
derivation. In this study, pregnant mice were exposed throughout
gestation, which is relevant to two human adult life stages: women of
child-bearing age who may be or become pregnant, and pregnant women and
their developing embryo or fetus (Table 3-63 in USEPA, 2019a). Of these
two, EPA selected the DWI-BW for women of child-bearing age (0.0354 L/
kg/day) to derive the noncancer HBWC for PFBS because it was higher and
therefore more health-protective (USEPA, 2022e).
The HBWC value for PFBS was calculated using an RSC of 0.20. This
means that 20% of the exposure--equal to the RfD--is allocated to
drinking water, and the remaining 80% is attributed to all other
potential exposure sources (USEPA, 2022e). This was based on EPA's
determination that the available data on PFBS exposure routes and
sources did not enable a quantitative characterization of PFBS
exposure. In such cases, an RSC of 0.20 is typically used (USEPA,
2000c).
As further described in USEPA (2022e), the HBWC for PFBS is
calculated to be 2000 ppt. This value is consistent with EPA's 2022
drinking water health advisory for PFBS (USEPA, 2022d), but was derived
from EPA's 2021 PFBS Toxicity Assessment (USEPA, 2021a). This HBWC of
2000 ppt is also used as the HRL for this preliminary Regulatory
Determination for PFBS.
5. Mixtures of PFHxS, HFPO-DA, PFNA, and PFBS
PFAAs, including PFHxS, HFPO-DA, PFNA, and PFBS, disrupt signaling
of multiple biological pathways resulting in common adverse effects on
several biological systems including thyroid hormone levels, lipid
synthesis and metabolism, as well as on development, and immune and
liver function (ATSDR, 2021; EFSA, 2018, 2020; USEPA, 2023a).
Studies with PFAS and other classes of chemicals support the health
protective assumption that a mixture of chemicals with similar observed
effects should be assumed to also act in a dose additive manner unless
data demonstrate otherwise (USEPA, 2023d). Dose additivity means that
each of the component chemicals in the mixture (in this case, PFHxS,
HFPO-DA, PFNA, and PFBS) behaves as a concentration or dilution of
every other chemical in the mixture differing only in relative toxicity
(USEPA, 2000a). See additional discussion of PFAS dose additivity in
Section V.C of this preamble.

C. Statutory Criterion 2--Occurrence

With this proposal, EPA is preliminarily determining that PFHxS,
HFPO-DA, PFNA, and PFBS, both individually and as mixtures of these
PFAS, meet SDWA's second statutory criterion for regulatory
determination: there is a substantial likelihood that the contaminants
will occur and co-occur with a frequency and at levels of public health
concern in PWSs based on EPA's evaluation of the best available
occurrence information. EPA is seeking public comment on whether
additional data or studies exist which EPA should consider that support
or do not support this preliminary determination.
EPA has made its preliminary determination based on the most
recent, publicly available data, which includes UCMR 3 data and more
recent PFAS drinking water data collected by several states. Informed
by these data, EPA determined that there is a substantial likelihood
PFHxS, HFPO-DA, PFNA, and PFBS will occur and co-occur with a frequency
of public health concern. Additionally, when determining that there is
a substantial likelihood these PFAS will occur at levels of public
health concern, EPA considered both the occurrence concentration levels
for each contaminant individually, as well as their collective co-
occurrence and corresponding dose additive health effects from co-
exposures. Furthermore, the Agency notes that it does not have a
bright-line threshold for occurrence in drinking water that triggers
whether a contaminant is of public health concern. A determination of
public health concern involves consideration of a number of factors,
some of which include the level at which the contaminant is found in
drinking water, the frequency at which the contaminant is found and at
which it co-occurs with other contaminants, whether there is an
sustained upward trend that these contaminant will occur at a frequency
and at levels of public health concern, the geographic distribution
(national, regional, or local occurrence), the impacted population,
health effect(s), the potency of the contaminant, other possible
sources of exposure, and potential impacts on sensitive populations or
lifestages. Given the many possible combinations of factors, a simple
threshold is not viable and is a highly contaminant-specific decision
that takes into consideration multiple factors.
UCMR 3 monitoring occurred between 2013 and 2015 for PFHxS,

[[Page 18648]]

PFNA, and PFBS. HFPO-DA were not monitored for as part of the UCMR 3.
Under the UCMR 3, 36,972 samples from 4,920 PWSs were analyzed for
PFHxS, PFNA, and PFBS. The minimum reporting levels (MRLs) for PFHxS,
PFNA, and PFBS were 30 ppt, 20 ppt, and 90 ppt, respectively. EPA notes
that these UCMR 3 MRLs are higher than those utilized within the
majority of state monitoring data and for the upcoming UCMR 5. A total
of 233 samples and 70 systems serving a total population of
approximately 6.7 million people had reported detections (greater than
or equal to the MRL) of at least one of the three compounds. Moreover,
the large majority of these UCMR 3 reported detections were found at
concentrations at or above levels of public health concern as described
previously in section III.B of this preamble and below within this
section. USEPA (2023e) presents sample and system level summaries of
the results for the individual contaminants. More information
supporting EPA's regulatory determination relating to the occurrence of
these PFAS and their mixtures is included in section VII.A. of this
preamble.
EPA has also collected more recent finished drinking water data
from 23 states who have made their data publicly available as of August
2021 (USEPA, 2023e). EPA used this cutoff date to allow the Agency to
conduct thorough analyses of the state information. EPA further refined
this dataset based on representativeness and reporting limitations,
resulting in detailed technical analyses using a subset of the
available state data (i.e., all 23 states' data were not included
within the detailed technical analyses). For example, a few states only
reported results as a combination of analytes which was not conducive
for analyzing PFAS. In general, the state data which were more recently
collected using newer analytical methods that have lower reporting
limits than those under UCMR 3 show widespread occurrence of PFOA,
PFOS, PFHxS, PFNA, and PFBS in multiple geographic locations. These
data also show that there is a substantial likelihood that these PFAS
occur at concentrations below UCMR 3 reporting limits. Furthermore,
these data include results for more PFAS than were included in the UCMR
3, including HFPO-DA, and show that PFHxS, HFPO-DA, PFNA, and PFBS, and
mixtures of these PFAS, occur and co-occur at levels of public health
concern as they are measured at concentrations above their respective
individual HRLs or, when considering their dose additive impacts,
exceed these levels. The Agency notes that the data vary in terms of
quantity and coverage, including that some of these available data are
from targeted or site-specific sampling efforts (i.e., monitoring
specifically in areas of known or potential contamination) and thus may
be expected to have higher detection rates or not be representative of
levels found in all PWSs within the state.
Tables 1 and 2 below show the percent of samples with state
reported detections of PFHxS, HFPO-DA, PFNA, and PFBS, and the
percentage of monitored systems with detections of PFHxS, HFPO-DA,
PFNA, and PFBS, respectively, across the non-targeted or non-site
specific (i.e., monitoring not conducted specifically in areas of known
or potential contamination) state finished water monitoring data.
EPA notes that different states utilized various reporting
thresholds or limits when presenting their data, and for some states
there were no clearly defined limits publicly provided. Further, the
limits often varied within the data for each state depending on the
specific analyte, as well as the laboratory analyzing the data. When
conducting data analyses, EPA incorporated individual state-specific
reporting limits where possible. In some cases, states reported data at
concentrations below EPA's proposed rule trigger level for reduced
compliance monitoring frequency and/or PQLs described in sections
VIII.A., IX.A., and IX.B of this preamble. However, to present the best
available occurrence data, EPA collected and evaluated the data based
on the information as reported directly by the states. EPA also notes,
and as described in further detail in section VIII.A. of this preamble,
some laboratories are able to detect and measure the PFAS addressed in
this document at lower concentrations than EPA's proposed rule trigger
level and PQLs which account for differences in the capability of
laboratories across the country. As such, EPA believes this data can
reasonably support EPA's evaluation of PFOA, PFOS, PFHxS, HFPO-DA,
PFNA, and PFBS occurrence and co-occurrence in drinking water. Specific
details on state data reporting thresholds are available in Table 1
within USEPA (2023e).

Table 1--Non-Targeted State PFAS Finished Water Data--Summary of Samples With State Reported Detections \1\ of
PFHxS, HFPO-DA, PFNA, and PFBS
----------------------------------------------------------------------------------------------------------------
State PFHxS (%) PFNA (%) PFBS (%) HFPO-DA (%)
----------------------------------------------------------------------------------------------------------------
Colorado........................................ 10.8 0.9 11.0 0.2
Illinois........................................ 5.1 0.2 7.8 0.0
Kentucky........................................ 8.6 2.5 12.3 13.6
Massachusetts................................... 31.9 4.6 35.5 0.0
Michigan........................................ 2.9 0.1 5.2 0.04
New Hampshire................................... 16.6 3.3 31.4 3.8
New Jersey...................................... 24.7 8.0 24.9 N/A
North Dakota.................................... 1.6 0.0 0.0 0.0
Ohio............................................ 5.8 0.3 4.7 0.1
South Carolina.................................. 13.5 2.1 38.3 6.0
Vermont......................................... 2.2 1.7 4.8 0.2
----------------------------------------------------------------------------------------------------------------
Notes:
\1\ Detections determined by individual state reported limits which are not defined consistently across all
states.

[[Page 18649]]

Table 2--Non-Targeted State PFAS Finished Water Data--Summary of Monitored Systems With State Reported \1\
Detections of PFHxS, HFPO-DA, PFNA, and PFBS
----------------------------------------------------------------------------------------------------------------
State PFHxS (%) PFNA (%) PFBS (%) HFPO-DA (%)
----------------------------------------------------------------------------------------------------------------
Colorado........................................ 13.4 1.0 13.4 0.3
Illinois........................................ 4.3 0.2 6.6 0.0
Kentucky........................................ 8.6 2.5 12.3 13.6
Massachusetts................................... 30.2 8.4 39.4 0.0
Michigan........................................ 3.0 0.2 5.3 0.1
New Hampshire................................... 22.5 5.5 37.9 5.1
New Jersey...................................... 32.6 13.3 34.0 N/A
North Dakota.................................... 1.6 0.0 0.0 0.0
Ohio............................................ 2.2 0.3 2.4 0.1
South Carolina.................................. 20.0 6.1 56.0 10.9
Vermont......................................... 1.6 1.3 5.2 0.5
----------------------------------------------------------------------------------------------------------------
Notes:
\1\ Detections determined by individual state reported limits which are not defined consistently across all
states.

As shown in Tables 1 and 2, all states except one report sample and
system detections for at least three of the four PFAS. For those states
that reported detections, the percentage of samples and systems where
these PFAS were found ranged from 0.1 to 38.3 percent and 0.1 to 56.0
percent, respectively. While these percentages show occurrence
variability across states, several of these states demonstrate a
significant number of samples (e.g., detections of PFHxS in 31.9
percent of Massachusetts samples) and systems (e.g., detections of
HFPO-DA in 13.9 percent of monitored systems in Kentucky) with some or
all of the four PFAS, which supports the Agency's preliminary
determination that there is a substantial likelihood these PFAS and
their mixtures occur and co-occur with a frequency of public health
concern. Specific discussion related to occurrence for each of the four
PFAS is below.
1. PFHxS
The occurrence data presented above, throughout section VII. of
this preamble and discussed in the USEPA (2023e) support the Agency's
preliminary determination that there is a substantial likelihood PFHxS
occurs with a frequency and at levels of public health concern in
drinking water systems across the United States. PFHxS was found under
UCMR 3 in approximately 1.1% of systems using an MRL of 30 ppt. All
UCMR 3 reported values are greater than the HRL of 9.0 ppt.
Additionally, through analysis of available non-targeted state data all
states in Tables 1 and 2 had reported detections of PFHxS within 1.6 to
32.6 percent of their systems and reported concentrations ranging from
0.46 to 310 ppt with median sample concentrations ranging from 2.14 to
11.3 ppt. Results from targeted state monitoring data of PFHxS are also
consistent with non-targeted state data. For example, California
reported 29.2 percent of monitored systems found PFHxS, where
concentrations ranged from 1.1 to 140.0 ppt. Therefore, in addition to
the UCMR 3 results, these state data reflect PFHxS at frequencies and
levels of public health concern. EPA also evaluated PFHxS in a national
occurrence model that has been developed and utilized to estimate
national-scale PFAS occurrence for four PFAS that were included in UCMR
3 (Cadwallader et al., 2022). The model and results are described in
section VII.E of this preamble. Hundreds of systems serving millions of
people were estimated to have mean concentrations exceeding the PFHxS
HRL (9.0 ppt). Further supporting this preliminary determination, PFAS
have dose additive impacts and PFHxS co-occurs in mixtures with other
PFAS, including PFOA, PFOS, HFPO-DA, PFNA, and PFBS. More information
on PFHxS co-occurrence is available in section VII.C. and VII.D. of
this preamble.
2. HFPO-DA
The occurrence data presented above, throughout section VII of this
preamble, and discussed in the USEPA (2023e) support the Agency's
preliminary determination that there is a substantial likelihood HFPO-
DA occur with a frequency and at levels of public health concern in
drinking water systems across the United States. Through analysis of
available non-targeted state data over half of the states in Tables 1
and 2 had state reported detections of HFPO-DA within 0.1 to 13.6
percent of their systems. State reported sample results were also
reported above the HRL of 10.0 ppt with sample results ranging from 1.7
to 29.7 ppt and median sample results ranging from 1.7 to 9.7 ppt.
Additionally, targeted state monitoring in North Carolina which
conducted sampling across six finished drinking water sites where 438
samples showed HFPO-DA ranging from 9.2 to 1100 ppt, with a median
concentration of 40 ppt. Therefore, these state data demonstrate
concentrations of HFPO-DA at levels of public health concern. Further
supporting this preliminary determination, PFAS have dose additive
impacts and HFPO-DA occur in mixtures with other PFAS, including PFOA,
PFOS, PFHxS, PFNA, and PFBS. More information on HFPO-DA co-occurrence
is available in section VII.C. and VII.D. of this preamble.
3. PFNA
The occurrence data presented above, throughout section VII of this
preamble, and discussed in USEPA (2023e) support the Agency's
preliminary determination that there is a substantial likelihood PFNA
occurs with a frequency and at levels of public health concern in
drinking water systems across the United States. PFNA was found under
UCMR 3 using an MRL of 20 ppt. Thus, all UCMR 3 reported detections are
greater than the HRL of 10.0 ppt. Additionally, through analysis of
available non-targeted state data all states except one in Tables 1 and
2 had state reported detections of PFNA within 0.2 to 13.3 percent of
their systems, and state reported sample results ranging from 0.25 to
94.2 ppt with median sample results range from 2.1 to 7.46 ppt.
Targeted state monitoring data of PFNA are also consistent with non-
targeted state data; for example, Pennsylvania reported 5.8 percent of
monitored systems found PFNA, where concentrations ranged from 1.8 to
18.1 ppt. Thus, in addition to the UCMR 3 results, these state data
also reflect PFNA concentrations at levels of public health concern.
Further supporting this preliminary

[[Page 18650]]

determination, PFAS have dose additive impacts and PFNA co-occurs in
mixtures with other PFAS, including PFOA, PFOS, PFHxS, HFPO-DA, and
PFBS. More information on PFNA co-occurrence is available in section
VII.C. and VII.D. of this preamble.
4. PFBS
The occurrence data presented above, throughout section VII of this
preamble, and discussed in USEPA (2023e) support the Agency's
preliminary determination that there is a substantial likelihood PFBS
occurs with a frequency and at levels of public health concern in
drinking water systems across the United States. PFBS was found under
UCMR 3 using an MRL of 90 ppt. Additionally, through analysis of
available non-targeted state data all states except one in Tables 1 and
2 had state reported detections of PFBS within 2.4 to 56 percent of
their systems, with four states finding PFBS in over 34 percent of
their systems. Furthermore, PFBS occurred at a greater frequency in all
but one state than the other three PFAS. State reported sample results
ranged from 1 to 310 ppt with median sample results ranging from 1.99
to 7.26 ppt. Targeted state monitoring data of PFBS are consistent with
non-targeted state data. Maryland reported 51.5 percent of monitored
systems found PFBS, where concentrations ranged from 1.01 to 21.29 ppt.
Further supporting this preliminary determination, PFAS have dose
additive impacts and PFBS occurs in mixtures with other PFAS, including
PFOA, PFOS, PFHxS, HFPO-DA, and PFNA. Moreover, given the considerable
prevalence of PFBS in state data reviewed by EPA and frequency in which
it has been shown to have other PFAS co-occurring with it, PFBS may
serve as an indicator of broad contamination of other PFAS. Those other
PFAS are also likely dose additive to PFBS and other PFAS being
proposed for regulation. EPA notes that PFBS concentrations do not
exceed their HRL of 2000 ppt when considered in isolation; however,
when considering dose additivity and the elevated frequency to which
PFBS occurrence has been observed over time, EPA has determined that
PFBS is an important component of regulated PFAS mixtures and because
of their pervasiveness, there is a substantial likelihood of its
occurrence with a frequency and at levels of public health concern.
More information on PFBS co-occurrence is available in section VII.C.
and VII.D. of this preamble. Based on the occurrence and co-occurrence
information above and throughout section VII of this preamble, EPA has
preliminarily determined that there is substantial likelihood PFBS
occurs with a considerable frequency and at levels of public health
concern.
5. Preliminary Occurrence Determination for PFHxS, HFPO-DA, PFNA, and
PFBS
Through the information presented within this section and in USEPA
(2023e), along with the co-occurrence information presented in section
VII.C. and VII.D. of this preamble, EPA's evaluation of the UCMR 3 data
and state data collected more recently demonstrates that as analytical
methods improved, monitoring has increased, and minimum reporting
thresholds are lowered, there is a sustained upward trend that there is
a substantial likelihood that these contaminants will occur and co-
occur at a frequency and at levels of public health concern. The UCMR 3
results showed there were over 6.5 million people served by PWSs that
had reported detections of PFHxS, PFNA, and PFBS, with many of the
detections for PFHxS and PFNA above the HRLs. EPA's evaluation of
monitoring data from multiple states that was primarily gathered
following the UCMR 3 using improved analytical methods that could
measure more PFAS at lower concentrations found that there is even
greater demonstrated occurrence and co-occurrence of these PFAS, as
well as for HFPO-DA, at significantly greater frequencies and at levels
of public health concern. EPA anticipates that national monitoring with
newer analytical methods capable of quantifying PFAS occurrence to
lower levels, significant occurrence and co-occurrence of these PFAS
are likely to be observed.
EPA notes that it focused the evaluation of the state data on the
non-targeted monitoring efforts from 12 states, given that these types
of monitoring efforts are likely to be more representative of PFHxS,
HFPO-DA, PFNA, and PFBS occurrence as they are not specifically
conducted in areas of known or potential contamination. In these 12
states, there were reported detections of PFHxS, HFPO-DA, PFNA, or
PFBS, with nearly all states reporting detections of at least three of
these four PFAS. EPA considered the targeted state data separately
since a higher rate of detections may occur as a result of specifically
looking in areas of suspected or known contamination. For the
additional targeted state data that EPA analyzed, EPA also found that
these states reported detections at systems serving millions of
additional people, as well as at levels of public health concern,
particularly when considering PFAS mixtures and dose additive impacts.
State data detection frequency and concentration results vary for
PFHxS, HFPO-DA, PFNA, and PFBS, both between these four different PFAS
and across different states, with some states showing much higher
reported detections and concentrations of these PFAS when compared to
other states. However, given the overall results, this demonstrates the
substantial likelihood that these PFAS and their mixtures will occur at
frequencies and levels of public health concern, and where these PFAS
have been monitored they are very commonly found. Furthermore, EPA
notes that as described in section VII.C.1. of this preamble, when
evaluating only a subset of the available state data representing non-
targeted monitoring, that one or more of PFHxS, HFPO-DA, PFNA, and PFBS
were reported in approximately 13.9 percent of monitored systems; if
these results were extrapolated to the nation, one or more of these
four PFAS would be detectable in over 9,000 PWSs. Moreover, as shown in
section VII.C.2. of this preamble, PFHxS, HFPO-DA, PFNA, and PFBS
generally co-occur with each other, as well as with PFOA and PFOS,
supporting that there is substantial likelihood that these PFAS will
co-occur in mixtures with dose additive impacts. For all of these
reasons, EPA has determined that there is sufficient occurrence
information available to support this preliminary determination that
there is a substantial likelihood that PFHxS, HFPO-DA, PFNA, and PFBS
will occur at frequencies and levels of public health concern.

D. Statutory Criterion 3--Meaningful Opportunity

EPA has preliminarily determined that regulation of PFHxS, HFPO-DA,
PFNA, and PFBS, both individually and in a mixture, presents a
meaningful opportunity for health risk reduction for persons served by
PWSs. EPA has made this preliminary determination after evaluating
health, occurrence, treatment, and other related information against
the three SDWA statutory criteria including consideration of the
following for the four PFAS and their mixtures:
<bullet> PFHxS, HFPO-DA, PFNA, and PFBS, individually and in a
mixture, may cause adverse human health effects on several biological
systems including the endocrine, cardiovascular, developmental, immune,
and hepatic systems. Additionally, these four PFAS, as well as other
PFAS, are likely to

[[Page 18651]]

produce dose-additive effects from co-exposures.
<bullet> The substantial likelihood that PFHxS, HFPO-DA, PFNA, and
PFBS, individually occur and co-occur together at frequencies and
levels of public health concern in PWSs as discussed in section III of
this preamble above and in section VII of this preamble, and the
corresponding significant populations served by these water systems.
<bullet> PFHxS, HFPO-DA, PFNA, and PFBS, individually and in a
mixture, are expected to be environmentally persistent.
<bullet> Validated EPA-approved measurement methods are available
to measure PFHxS, HFPO-DA, PFNA, and PFBS, individually and in
mixtures. See section VIII of this preamble for further discussion.
<bullet> Treatment technologies are available to remove PFHxS,
HFPO-DA, PFNA, and PFBS, and mixtures of these contaminants, from
drinking water. See section XI of this preamble for further discussion.
<bullet> Regulating PFHxS, HFPO-DA, PFNA, and PFBS, in addition to
PFOA and PFOS, is anticipated to reduce the overall public health risk
from all other PFAS that co-occur and are co-removed. Their regulation
is anticipated to provide public health protection at the majority of
known sites with PFAS-impacted drinking water.
<bullet> There are achievable steps to manage drinking water that
can be taken to reduce risk.
Due to the environmental persistence of these chemicals, there is
potential for toxicity at environmentally relevant concentrations as
studies show it can take years for many PFAS to leave the human body
(NIEHS, 2020). See section III of this preamble above and section V of
this preamble for discussion about the human health effects of PFHxS,
HFPO-DA, PFNA, and PFBS.
Data from both the UCMR 3 and state monitoring efforts demonstrates
occurrence or likely occurrence and co-occurrence of PFHxS, HFPO-DA,
PFNA, and PFBS, and their mixtures, at frequencies and levels of public
health concern. Under UCMR 3, 1.4% of systems serving approximately 6.7
million people had reported detections (greater than or equal to their
MRLs) of PFHxS, PFNA, and PFBS of at least one of the three compounds.
Additionally, based on the available state monitoring data presented
earlier in this section, in the 11 states shown in Table 2 that
conducted non-targeted sampling of the four PFAS, monitored systems
that reported detections of PFHxS, HFPO-DA, PFNA, and PFBS serve
approximate populations of 8.3 million, 1.8 million, 2.6 million, and
8.8 million people, respectively. Further, as demonstrated in the UCMR
3 and state data, concentrations of these PFAS, as well as PFOA and
PFOS, and their mixtures co-occur at levels of public health concern as
described in more detail in section VII.C. and VII.D. of this preamble
and USEPA (2023e).
Analytical methods are available to measure PFHxS, HFPO-DA, PFNA,
and PFBS in drinking water. EPA has published two multi-laboratory
validated drinking water methods for individually measuring PFHxS,
HFPO-DA, PFNA, and PFBS: EPA Method 537.1 which measures 18 PFAS and
EPA Method 533 which measures 25 PFAS. There are 14 PFAS which overlap
between methods and both methods measure PFOA and PFOS). Additional
discussion on analytical methods can be found in section VIII of this
preamble.
EPA's analysis, summarized in section XI of this preamble, found
there are available technologies capable of reducing PFHxS, HFPO-DA,
PFNA, and PFBS. These technologies include granular activated carbon
(GAC), AIX resins, reverse osmosis (RO), and nanofiltration (NF). See
discussion in section XI of this preamble for information about these
treatment technologies. Due to the inherent nature of sorptive and
high-pressure membrane technologies such as these, treatment
technologies that remove PFHxS, HFPO-DA, PFNA, and PFBS and their
mixtures also have been documented to co-remove other PFAS
(S[ouml]reng[aring]rd et al., 2020; McCleaf et al., 2017; Mastropietro
et al., 2021). Furthermore, as described in section VII of this
preamble, PFHxS, HFPO-DA, PFNA, and PFBS also co-occur with PFAS for
which the Agency is not currently making a preliminary regulatory
determination. Many of these other emergent co-occurring PFAS are
likely to also pose hazards to public health and the environment
(Mahoney et al., 2022). Therefore, based on EPA's findings that PFHxS,
HFPO-DA, PFNA, and PFBS have a substantial likelihood to co-occur in
drinking water with other PFAS and treating for PFHxS, HFPO-DA, PFNA,
and PFBS is anticipated to result in removing these and other PFAS,
regulation of PFHxS, HFPO-DA, PFNA, PFBS (as well as PFOA and PFOS)
also presents a meaningful opportunity to reduce the overall public
health risk from all other PFAS that co-occur and are co-removed with
PFHxS, HFPO-DA, PFNA, and PFBS.
With the ability to monitor for PFAS, identify contaminated
drinking water sources and contaminated finished drinking water, and
reduce PFAS exposure through management of drinking water, EPA has
identified meaningful and achievable actions that can be taken to
reduce the human health risk of PFAS.
EPA is preliminarily determining that regulation of PFHxS, HFPO-DA,
PFNA, and PFBS presents a meaningful opportunity for health risk
reduction for persons served by PWSs.

E. EPA's Preliminary Regulatory Determination Summary for PFHxS, HFPO-
DA, PFNA, and PFBS

The statute provides EPA significant discretion when making a
preliminary determination under Section 1412(b)(1)(A). This decision to
make a preliminary regulatory determination for PFHxS, HFPO-DA, PFNA
and PFBS and their mixtures is based on consideration of the evidence
supporting the factors individually and as a whole.
EPA's preliminary determination that PFHxS, HFPO-DA, PFNA, and PFBS
``may have an adverse effect on the health of persons'' is strongly
supported by numerous studies where multiple health effects are
demonstrated following exposure. EPA's preliminary determination
regarding occurrence is supported by evidence documenting the trend
demonstrated first by the UCMR 3 data and then subsequent state
occurrence data that measured occurrence of the four PFAS has increased
with more widespread monitoring primarily using EPA approved methods
that have, lower reporting thresholds. The statute contemplates that
there may be instances where exact occurrence may not be ``known'' and
in these instances EPA need only demonstrate that that it has a basis
to determine that there is a ``substantial likelihood that the
contaminant will occur.'' Additional nationwide monitoring data will be
conducted between 2023-2025 under the UCMR 5. This data will serve to
demonstrate whether the four PFAS are known to occur, however, EPA has
sufficient evidence now to support a preliminary determination there is
a substantial likelihood that these PFAS will occur frequently and at
concentrations where they are likely to exceed their respective HRLs
based on the increased occurrence trends documented by available
information. This finding is further supported by available dose
additive impacts and co-occurrence information that demonstrates that
there is a substantial likelihood that these PFAS co-occur in PWSs with
a frequency and at levels of public health concern at hundreds of
systems serving millions of people.

[[Page 18652]]

Finally, EPA's preliminary determination that regulating these four
PFAS presents a meaningful opportunity for health risks reductions is
strongly supported by numerous bases, including the potential adverse
human health effects and potential for exposure and co-exposure of
these PFAS, and the availability of both analytical methods to measure
and treatment technologies to remove these contaminants in drinking
water.
After considering these factors individually and together, EPA has
preliminarily determined that now is the appropriate time to exercise
its discretion under the statute to regulate the four PFAS and their
mixtures as contaminants under SDWA. EPA recognizes the public health
burden of PFHxS, HFPO-DA, PFNA, and PFBS, as well as PFOA, PFOS, and
other PFAS, a public urgency to reduce PFAS concentrations in drinking
water, and that the proposed regulation provides a mechanism to reduce
these PFAS expeditiously and efficiently for regulated utilities,
States, and Tribes. Furthermore, in addition to making this preliminary
regulatory determination, EPA is concurrently proposing an NPDWR to
include all four of these PFAS, in part to allow utilities to consider
these PFAS specifically as they design systems to remove PFAS and to
ensure that they are reducing these PFAS in their drinking water as
effectively and quickly as feasible, maximizing the protection of
drinking water for the American public.

F. Request for Comment on EPA's Preliminary Regulatory Determination
for PFHxS, HFPO-DA, PFNA, and PFBS

EPA specifically requests comment on its preliminary regulatory
determination for PFHxS, HFPO-DA, PFNA, and PFBS and their mixtures. In
particular, EPA requests comment on whether there is additional health
information the Agency should consider as to whether PFHxS, HFPO-DA,
PFNA, and PFBS and their mixtures may have an adverse effect on the
health of persons. EPA also requests comment on whether there are other
peer-reviewed health or toxicity assessments for other PFAS the Agency
should consider as part of this action. Additionally, EPA requests
comment on additional occurrence data the Agency should consider
regarding its decision that PFHxS, HFPO-DA, PFNA, and PFBS and their
mixtures occur or are substantially likely to occur in PWSs with a
frequency and at levels of public health concern. EPA also requests
public comment on its evaluation that regulation of PFHxS, HFPO-DA,
PFNA, and PFBS and their mixtures, in addition to PFOA and PFOS, will
provide protection from PFAS that will not be regulated as part of this
proposed PFAS NPDWR.

IV. Approaches to MCLG Derivation

Section 1412(a)(3) of the SDWA requires the Administrator of the
EPA to propose a MCLG simultaneously with the NPDWR. The MCLG is set,
as defined in Section 1412(b)(4)(A), at ``the level at which no known
or anticipated adverse effects on the health of persons occur and which
allows an adequate margin of safety''. Consistent with SDWA
1412(b)(3)(C)(i)(V), in developing the MCLG, EPA considers ``the
effects of the contaminant on the general population and on groups
within the general population such as infants, children, pregnant
women, the elderly, individuals with a history of serious illness, or
other subpopulations that are identified as likely to be at greater
risk of adverse health effects due to exposure to contaminants in
drinking water than the general population.'' Other factors considered
in determining MCLGs include health effects data on drinking water
contaminants and potential sources of exposure other than drinking
water. MCLGs are not regulatory levels and are not enforceable.
EPA is proposing individual MCLGs for two PFAS (PFOA and PFOS; see
USEPA, 2023b; USEPA, 2023c) and a separate MCLG to account for dose
additive noncancer effects for a mixture of four PFAS (PFHxS, HFPO-DA,
PFNA, and PFBS; see USEPA, 2023d). The derivation of the proposed MCLG
for the mixture is based on an HI approach (USEPA, 2023a).
The SAB, discussed further in section XV.K.1. of this preamble
below, supported many of EPA's conclusions presented in the PFOA and
PFOS MCLG approaches, mixtures framework, and economics benefits
documents including health effects and economic benefits analyses
(USEPA, 2022a). Regarding the Proposed Approaches to the Derivation of
Draft MCLGs for PFOA and PFOS (USEPA, 2021e; USEPA, 2021f), SAB agreed
with the selection of the UFs used in deriving the noncancer RfDs,
supported the selection of an RSC of 20%, and agreed with the
``likely'' designation for PFOA carcinogenicity.
The SAB commented that EPA should ``focus on those health outcomes
that have been concluded to have the strongest evidence'' and
``consider multiple human and animal studies for a variety of endpoints
in different populations so as to provide convergent evidence that is
more reliable than any single study or health endpoint in isolation.''
EPA applied these recommendations when deriving points of departure and
selecting critical studies used for toxicity value development in the
MCLG documents for PFOA and PFOS (USEPA, 2023b; USEPA, 2023c).
Specifically, EPA focused on the five health outcomes with the
strongest weight of evidence--liver, immune, cardiovascular,
developmental, and cancer--during quantitative analyses.
However, the SAB had a number of consensus recommendations and
identified ``methodological concerns in the draft MCLG documents for
PFOA and PFOS.'' EPA has addressed these concerns by providing
additional clarity and transparency on the systematic literature review
process and expanding the systematic review steps included in the
health effects assessment. The systematic review protocols, which were
developed to be consistent with EPA's Office of Research and
Development (ORD) Integrated Risk Information System (IRIS) Staff
Handbook (USEPA, 2022f), are available in the Appendices of the MCLG
documents for PFOA and PFOS (USEPA, 2023b; USEPA, 2023c). In order to
base the MCLG derivation on the best available science, EPA has updated
the draft MCLG documents to reflect the results of conducting an update
to the literature search and performing new evaluations of models,
methods, and data. More information is available in section XV.K.1. of
this preamble.
EPA expects to conduct a final literature search update before the
final rule is promulgated. The SAB input has made this product more
scientifically sound and ensures that it reflects the best available
science. The updated supporting information can be found in the MCLG
documents for PFOA and PFOS (USEPA, 2023b; USEPA, 2023c).

A. Approach to MCLG Derivation for Individual PFAS

To establish the MCLG, EPA assesses the peer reviewed science
examining cancer and noncancer health effects associated with oral
exposure to the contaminant. For linear carcinogenic contaminants,
where there is a proportional relationship between dose and
carcinogenicity at low concentrations, EPA has a long-standing practice
of establishing the MCLG at zero (see USEPA, 1998a; USEPA, 2000d;
USEPA, 2001). For nonlinear carcinogenic contaminants, contaminants
that are suggestive carcinogens, and non-carcinogenic contaminants, EPA
typically establishes the MCLG based on an RfD. An RfD is an estimate
of a daily exposure to the

[[Page 18653]]

human population (including sensitive populations) that is likely to be
without an appreciable risk of deleterious effects during a lifetime. A
nonlinear carcinogen is a chemical agent for which the associated
cancer response does not increase in direct proportion to the exposure
level and for which there is scientific evidence demonstrating a
threshold level of exposure below which there is no appreciable cancer
risk.
The MCLG is derived depending on the noncancer and cancer evidence
for a particular contaminant. Establishing the MCLG for a chemical has
historically been accomplished in one of three ways depending upon a
three-category classification approach (USEPA, 1985; USEPA, 1991a). The
categories are based on the available evidence of carcinogenicity after
exposure via ingestion. The starting point in categorizing a chemical
is through assigning a cancer descriptor using EPA's current Guidelines
for Carcinogen Risk Assessment (USEPA, 2005). The 2005 Guidelines
replaced the prior alphanumeric groupings although the basis for the
classifications is similar. In prior rulemakings, the Agency typically
placed Group A, B1, and B2 contaminants into Category I, Group C into
Category II, and Group D and E into Category III based on the Agency's
previous cancer classification guidelines (i.e., Guidelines for
Carcinogen Risk Assessment, published in 51 FR 33992, September 24,
1986 (USEPA, 1986b) and the 1999 draft revised final guidelines (USEPA,
1999):
<bullet> Category I chemicals have ``strong evidence [of
carcinogenicity] considering weight of evidence, pharmacokinetics, and
exposure'' (USEPA, 1985; USEPA, 1991a). EPA's 2005 Cancer descriptors
associated with this category are: ``Carcinogenic to Humans'' or
``Likely to be Carcinogenic to Humans'' (USEPA, 2005). EPA's policy
under SDWA is to set MCLGs for Category I chemicals at zero, based on
the principle that there is no known threshold for carcinogenicity
(USEPA, 1985; USEPA, 1991a; USEPA, 2016d). In cases when there is
sufficient evidence to determine a nonlinear cancer mode of action
(MOA), the MCLG is based on the RfD approach described below.
<bullet> Category II chemicals have ``limited evidence [of
carcinogenicity] considering weight of evidence, pharmacokinetics, and
exposure'' (USEPA, 1985; USEPA, 1991a). EPA's 2005 Cancer descriptor
associated with this category is: ``Suggestive Evidence of Carcinogenic
Potential'' (USEPA, 2005). The MCLG for Category II contaminants is
based on noncancer effects (USEPA, 1985; USEPA, 1991a) as described
below.
<bullet> Category III chemicals have ``inadequate or no animal
evidence [of carcinogenicity]'' (USEPA, 1985; USEPA, 1991a). EPA's 2005
Cancer descriptors associated with this category are: ``Inadequate
Information to Assess Carcinogenic Potential'' and ``Not Likely to Be
Carcinogenic to Humans'' (USEPA, 2005). The MCLG for Category III
contaminants is based on noncancer effects as described below.
For chemicals exhibiting a noncancer threshold for toxic effects
(e.g., Category II or III; e.g., see USEPA, 1985 and USEPA, 1991a) and
nonlinear carcinogens (e.g., see USEPA, 2006a), EPA establishes the
MCLG based on a toxicity value, typically an RfD, but similar toxicity
values may also be used when they represent the best available science
(e.g., ATSDR Minimal Risk Level). A noncancer MCLG is designed to be
protective of noncancer effects over a lifetime of exposure with an
adequate margin of safety, including for sensitive populations and life
stages, consistent with SDWA 1412(b)(3)(C)(i)(V) and 1412(b)(4)(A). The
calculation of a noncancer MCLG includes an oral toxicity reference
value such as an RfD (or Minimal Risk Level), DWI-BW, and RSC as
presented in the equation below:
[GRAPHIC] [TIFF OMITTED] TP29MR23.060

Where:

RfD \3\ = reference dose--an estimate (with uncertainty spanning
perhaps an order of magnitude) of a daily oral exposure of the human
population to a substance that is likely to be without an
appreciable risk of deleterious effects during a lifetime. The RfD
is equal to a point-of-departure (POD) divided by a composite UF.
---------------------------------------------------------------------------

\3\ A reference dose (RfD) is an estimate of the amount of a
chemical a person can ingest daily over a lifetime (chronic RfD) or
less (subchronic RfD) that is unlikely to lead to adverse health
effects in humans.
---------------------------------------------------------------------------

DWI-BW = An exposure factor in the form of the 90th percentile DWI-
BW for the identified population or life stage, in units of liters
of water consumed per kilogram BW per day (L/kg/day). The DWI-BW
considers both direct and indirect consumption of drinking water
(indirect water consumption encompasses water added in the
preparation of foods or beverages, such as tea or coffee). Chapter 3
of EPA's Exposure Factors Handbook (USEPA, 2019a) provides DWI-BWs
for various populations or life stages within the general population
for which there are publicly available, peer-reviewed data such as
National Health and Nutrition Examination Survey (NHANES) data.
RSC = relative source contribution--the percentage of the total
exposure attributed to drinking water sources (USEPA, 2000c), with
the remainder of the exposure allocated to all other routes or
sources.

EPA established internal protocols for the systematic review steps
of literature search, Population, Exposure, Comparator, and Outcomes
(PECO) development, literature screening, study quality evaluation, and
data extraction prior to conducting the systematic review for PFOA and
PFOS. However, EPA recognizes that while components of the protocols
were included in the November 2021 draft Proposed Approaches documents
(USEPA, 2021e; USEPA, 2021f), the protocols were only partially
described in those documents. EPA has incorporated detailed,
transparent, and complete protocols for all steps of the systematic
review process into the Proposed MCLG documents (USEPA, 2023b; USEPA,
2023c). Additionally, the protocols and methods have been updated and
expanded based on SAB recommendations to improve the transparency of
the process used to derive the MCLGs for PFOA and PFOS and to be
consistent with the ORD Staff Handbook for Developing IRIS Assessments
(USEPA, 2022f). For additional details of EPA's systematic review
methods, see USEPA (2023b, 2023c; Chapter 2 and Appendix A).
EPA evaluated strengths and limitations of each study to determine
an overall classification of high, medium, low, or uninformative with
respect to confidence in the quality and reliability of the study (this
was done for each endpoint evaluated in each study). High, medium, and
low confidence studies were prioritized for qualitative assessments,
while only high and medium confidence studies were prioritized for
quantitative assessments. Within each health outcome, the evidence from
epidemiology and animal toxicity studies was synthesized. For noncancer
health outcomes, the animal toxicological and epidemiological evidence
for each health outcome was classified as either robust, moderate,
slight, indeterminate, or compelling evidence of no effect. The weight
of evidence for each health outcome across all available evidence
(i.e., epidemiology, animal toxicity, and mechanistic studies) was
classified as either evidence demonstrates, evidence indicates
(likely), evidence suggests, evidence inadequate, or strong evidence
supports no effect. To characterize the weight of evidence for cancer
effects,

[[Page 18654]]

EPA followed recommendations of the Guidelines for Carcinogen Risk
Assessment (USEPA, 2005). Further description of the methods used to
make these determinations for PFOA and PFOS is provided in USEPA
(2023b; 2023c). Consistent with the recommendations of the SAB and to
ensure that the rule reflects the best available science, EPA continues
to evaluate the literature using systematic review methods.
The approach to select the DWI-BW and RSC for MCLG derivation
includes a step to identify sensitive population(s) or life stage(s)
(i.e., populations or life stages that may be more susceptible or
sensitive to a chemical exposure) by considering the available data for
the contaminant, including the adverse health effects reported in the
toxicity study on which the RfD was based (known as the critical effect
within the critical or principal study). Although data gaps can
complicate identification of the most sensitive population (e.g., not
all windows or life stages of exposure or health outcomes may have been
assessed in available studies), the critical effect and POD that form
the basis for the RfD (or Minimal Risk Level) can provide some
information about sensitive populations because the critical effect is
typically observed within the low dose range among the available data.
Evaluation of the critical study, including the exposure window or
interval, may identify a sensitive population or life stage (e.g.,
pregnant women, formula-fed infants, lactating women). In such cases,
EPA can select the corresponding DWI-BW for that sensitive population
or life stage from the Exposure Factors Handbook (USEPA, 2019a) to
derive the MCLG. In the absence of information indicating a sensitive
population or life stage, the DWI-BW corresponding to the general
population may be selected for use in MCLG derivation.
To account for potential aggregate risk from exposures and exposure
pathways other than oral ingestion of drinking water, EPA applies an
RSC when calculating MCLGs to ensure that total exposure to a
contaminant does not exceed the daily exposure associated with the
toxicity value, consistent with USEPA (2000c) and long-standing EPA
methodology for establishing drinking water MCLGs and NPDWRs. The RSC
represents the proportion of an individual's total exposure to a
contaminant that is attributed to drinking water ingestion (directly or
indirectly in beverages like coffee, tea, or soup, as well as from
transfer to dietary items prepared with drinking water) relative to
other exposure pathways. The remainder of the exposure equal to the RfD
(or Minimal Risk Level) is allocated to other potential exposure
sources (USEPA, 2000c). The purpose of the RSC is to ensure that the
level of a contaminant (e.g., MCLG), when combined with other
identified potential sources of exposure for the population of concern,
will not result in exposures that exceed the RfD (or Minimal Risk
Level) (USEPA, 2000c).
To determine the RSC, EPA follows the Exposure Decision Tree for
Defining Proposed RfD (or POD/UF) Apportionment in EPA's Methodology
for Deriving Ambient Water Quality Criteria for the Protection of Human
Health (USEPA, 2000c). EPA considers whether there are significant
known or potential uses/sources of the contaminant other than drinking
water, the adequacy of data and strength of evidence available for each
relevant exposure medium and pathway, and whether adequate information
on each exposure source is available to quantitatively characterize the
exposure profile. The RSC is developed to reflect the exposure to the
general population or a sensitive population within the general
population. When exposure data are available for multiple sensitive
populations or life stages, the most health-protective RSC is selected.
In the absence of adequate data to quantitatively characterize exposure
to a contaminant, EPA typically selects an RSC of 20 percent (0.2).
When scientific data demonstrating that sources and routes of exposure
other than drinking water are not anticipated for a specific pollutant,
the RSC can be raised as high as 80 percent based on the available
data, thereby allocating the remaining 20 percent to other potential
exposure sources (USEPA, 2000c).

B. Approach to MCLG Derivation for a PFAS Mixture

There has been a lot of work evaluating parameters that best inform
the combining of PFAS components identified in environmental matrices
into mixtures analyses. Indeed, there is currently no consensus on
whether or how PFAS should be combined for risk assessment purposes.
EPA considered several approaches to account for dose additive
noncancer effects associated with PFHxS, HFPO-DA, PFNA, and PFBS in
mixtures. PFAS can affect multiple human health endpoints and differ in
their impact (i.e., potency of effect) on target organs/systems. PFAS
disrupt signaling of multiple biological pathways resulting in common
adverse effects on several biological systems and functions, including
thyroid hormone levels, lipid synthesis and metabolism, development,
and immune and liver function (ATSDR, 2021; EFSA, 2018, 2020; EPA,
2023d). For example, one PFAS may be most toxic to the liver, and
another may be most toxic to the thyroid but both chemicals affect the
liver and the thyroid. Other chemicals regulated as groups operate
through a common MOA and predominately affect one human health
endpoint. This supports a flexible data-driven approach that
facilitates the evaluation of multiple health endpoints, such as the
HI.
EPA is proposing to establish an MCLG for a mixture of chemicals
that are expected to impact multiple endpoints. SDWA requires the
agency to establish a health-based MCLG set at, ``a level at which no
known or anticipated adverse effects on the health of persons occur and
which allow for an adequate margin of safety. EPA's SAB opined that
where the health endpoints of the chosen compounds are similar, ``the
HI methodology is a reasonable approach for estimating the potential
aggregate health hazards associated with the occurrence of chemical
mixtures in environmental media. The HI is an approach based on dose
additivity (DA) that has been validated and used by EPA'' (USEPA,
2022a). This proposal is based on the Agency's finding that the general
HI approach is the most efficient and effective approach for
establishing an MCLG for PFAS mixtures consistent with the statutory
requirement described above. This finding is based on the level of
protection afforded by both the HBWCs for the individual PFAS as
components of a mixture and the resulting HI itself, which provides an
added margin of safety with respect to potential health hazards of
mixtures of these PFAS. An HI greater than 1.0 is generally regarded as
an indicator of potential adverse health risks associated with exposure
to the mixture (USEPA, 1986a; USEPA, 1991b; USEPA, 2000a). A HI less
than or equal to 1.0 is generally regarded as having no appreciable
risk (USEPA, 1986a; USEPA, 1991b; USEPA, 2000a). The proposed MCLG is
based on using this HI of 1.0, and the HBWCs of each mixture component,
which in turn is based on its respective health-based reference value
(RfV; RfD or MRL). Because the RfV represents an estimate at which no
appreciable risk of deleterious effects exists (USEPA, 1986a, 1991a,
2000a), the use of the HBWCs means that the HI of 1.0 will ensure that
there are no known or anticipated effects on the health of persons and
allow for an adequate

[[Page 18655]]

margin of safety. In addition, the resulting HI adds an additional
margin of safety for mixtures of the four PFAS, to address the
potential for additive toxicity where the contaminants co-occur and the
HBWCs for the individual components are less than 1.0. The Agency
therefore proposes the general HI approach as the basis for the MCLG,
and because treatment to this level is also feasible, the MCL for these
PFAS, (see additional discussion in section VI of this preamble) and
welcomes public comment on its findings.
EPA considered the two main types of HI approaches: (1) the general
HI which allows for component chemicals in the mixture to have
different health effects or endpoints as the basis for the component
chemical reference values (e.g., RfDs), and (2) the target-organ
specific HI which relies on reference values based on the same organ or
organ system (e.g., liver-, thyroid-, or developmental-specific). The
general HI approach is based on the overall RfD which is protective of
all effects for a given chemical, and thus is a more health protective
indicator of risk. The target-organ specific HI approach produces a
less health protective estimate of risk than the general HI when a
contaminant impacts multiple organs because the range of potential
effects has been scoped to a specific target organ, which may be one of
the less potent effects or for which there may be significant currently
unquantified effects. Additionally, a target-organ specific HI approach
relies on toxicity values aggregated by the ``same'' target organ
endpoint/effect, and the absence of information about a specific
endpoint may result in the contaminant not being adequately considered
in a target-organ specific approach, and thus, underestimating
potential health risk. A target-organ specific HI can only be performed
for those PFAS for which a health effect specific RfD is calculated.
For example, for some PFAS a given health effect might be poorly
characterized or not studied at all, or, as a function of dose may be
one of the less(er) potent effects in the profile of toxicity for that
particular PFAS. Another limitation is that so many PFAS lack human
epidemiological or experimental animal hazard and dose-response
information across a broad(er) effect range thus limiting derivation of
target-organ specific values. A similar, effect/endpoint-specific
method called the relative potency factor (RPF) approach, which
represents the relative difference in potency of an effect/endpoint
between an index chemical and other members of the mixture, was also
considered. (Further background on all of these approaches, plus
illustrative examples, and a discussion of the advantages and
challenges associated with each approach can be found in Section 5 and
6 in USEPA, 2023d).
EPA also considered setting individual MCLGs instead of and in
addition to using a mixtures-based approach for PFHxS, HFPO-DA, PFNA,
and/or PFBS in mixtures. EPA ultimately selected the general HI
approach for establishing an MCLG for these four PFAS, as described in
greater detail below, because it provides the most health protective
endpoint for multiple PFAS in a mixture to ensure there would be no
known or anticipated adverse effects on the health of persons. EPA also
considered a target-specific HI or RPF approach but, because of
information gaps, EPA may not be able to ensure that the MCLG is
sufficiently health protective. If the Agency only established an
individual MCLG, the Agency would not provide any protection against
dose-additivity from regulated co-occurring PFAS. EPA is seeking
comments on the merits and drawbacks of each of the approaches
described above. As discussed later in this proposal, EPA is also
seeking comment on whether to set MCLGs for the individual PFAS in
addition to or instead of setting them for the mixture.
EPA is proposing use of the general HI approach. Although EPA's SAB
opined that it is reasonable to use a HI for evaluation of mixtures of
PFAS in drinking water for situations where the profile of health
effects of the chosen compounds share similarity in one or more effect
domains, the SAB emphasized that using a HI in the context of
developing regulations for PFAS should not be directly interpreted as a
quantitative estimate of mixture risk. Rather the SAB agreed that the
HI can be used as an indicator of potential health risk(s) associated
with exposure to mixtures of PFAS; see discussion in USEPA (2023d) and
Section V of this preamble for further information. EPA addresses the
full range of responses to SAB comments in a response to comment
document; that document is included in the docket for this action
(USEPA, 2023f).
EPA proposes that the general HI is the most appropriate and
justified approach for considering PFAS mixtures in this rulemaking
because of the level of protection afforded for the evaluation of
chemicals with diverse (but in many cases shared) health endpoints.
SDWA requires the agency to establish a MCLG set at, ``a level at which
no known or anticipated adverse effects on the health of persons occur
and which allow for an adequate margin of safety.'' In this context,
EPA has made a reasonable policy choice for regulating a mixture of
chemicals that are expected to adversely impact multiple health
endpoints. Because mixture component chemical HBWCs are based on
overall lowest RfDs across candidate critical effects, the approach is
protective against all health effects across component chemicals and
therefore meets the statutory requirements of establishing an MCLG
under SDWA. Basing the mixture MCLG on overall RfDs ensures that there
are no known or anticipated effects, and using the HI adds an
appropriate margin of safety for a class of contaminants that have been
shown to co-occur and evidence suggests that they may have dose
additive toxicity. Conversely, by definition, a target-organ specific
(e.g., liver-, thyroid-, or developmental-specific) HI or RPF approach
would not be protective of all health effects across the four PFAS
proposed for regulation with the mixture MCLG.
Use of the general HI approach over the target-organ specific HI
for these four PFAS is supported by EPA guidance (EPA, 2000a) and
available health assessments and toxicity values (overall RfDs).
Target-organ specific reference values and RPFs are not currently
available for HFPO-DA, PFBS, PFHxS, and PFNA.
EPA's protocol for MCLG development for the mixture of PFHxS, HFPO-
DA, PFNA, and PFBS follows existing Agency guidance, policies, and
procedures related to the three key inputs (i.e., RfD/Minimal Risk
Level, DWI-BW, and RSC) and longstanding Agency mixtures guidance
(USEPA, 1986a; USEPA, 2000a) to address dose additive health effects.
First, EPA identifies or derives a HBWC, calculated using the MCLG
equation above, for each of the four individual PFAS in the mixture.
More information on HBWCs for PFHxS, HFPO-DA, PFNA, and PFBS is
available in section III.B of this preamble. Peer reviewed, publicly
available assessments for PFHxS (ATSDR, 2021), HFPO-DA (USEPA, 2021b),
PFNA (ATSDR, 2021), and PFBS (USEPA, 2021a) provide the chronic
reference values (RfD, adjusted Minimal Risk Level) used to calculate
the HBWCs for these four PFAS. The DWI-BW and RSC for each of the four
PFAS are determined as described using the processes described for
individual PFAS (Section IV.A of this preamble). Briefly, the DWI-BW
for each of the four PFAS is selected from the EPA Exposure Factors
Handbook (USEPA, 2019a), taking into account the relevant

[[Page 18656]]

sensitive population(s) or life stage(s). RSCs are determined based on
a literature review of potential exposure sources of the four PFAS and
using the Exposure Decision Tree approach (USEPA, 2000c).
The HI is based on an assumption of dose addition (DA) among the
mixture components (Svendsgaard and Hertzberg, 1994; USEPA, 2000a). An
important aspect of the proposed `general HI' approach is that it is
based on the availability of a reference value regardless of the
critical effect for each mixture component. Unlike a target-organ
specific Hazard Index which is typically based on either shared mode-
of-action or shared health outcome of mixture components, the general
HI is based on a non-cancer reference value (RfD or Minimal Risk Level)
for the critical (usually the most sensitive) effect of each component
(USEPA, 2000a; USEPA, 1989). Importantly, while many PFAS share some
common target organs/health outcomes such as liver toxicity, the
potency--and in some cases, even the overall most sensitive target
organ--differs among PFAS. As an example, the most sensitive organ to
HFPO-DA is the liver while the most sensitive organ to PFBS is the
thyroid. Integrating the overall RfDs for each mixture PFAS in the
calculation of component HQs and a corresponding mixture HI, regardless
of the critical (most sensitive) effect, ensures health protection
under an assumption of dose additivity. The alternative may
underestimate potential health risk(s) associated with exposure to a
PFAS mixture as a given effect-specific HI might entail the use of
target-organ specific reference values that are not protective of
effects at a given mixture component's corresponding overall RfD.
Further, effect-specific RfDs are not typically derived for chemicals
beyond the critical effect for the overall RfD which might prohibit the
inclusion of a chemical in a target-organ specific HI. Recognizing the
various nuances to the HI approach, EPA welcomes public comment.
In the HI approach, an HQ is calculated as the ratio of human
exposure (E) to a health-based reference value (RfV) for each mixture
component chemical (i) (USEPA, 1986a). The HI involves the use of RfVs
for each PFAS mixture component (in this case, PFHxS, HFPO-DA, PFNA,
and PFBS), which have been selected based on sensitive health outcomes
that are protective of all other adverse health effects observed after
exposure to the individual PFAS. Thus, this approach, which protects
against all adverse effects, not only a single adverse outcome/effect
(e.g., as would be the case using other mixture approaches such as the
target-organ specific HI or RPF approach), is a health protective risk
indicator and appropriate for MCLG development. The HI is unitless; in
the HI formula, E and the RfV must be in the same units. For example,
if E is the oral intake rate (mg/kg/day), then the RfV could be the RfD
or Minimal Risk Level, which have the same units. Alternatively, the
exposure metric can be a media-specific metric such as a measured water
concentration (e.g., nanograms per liter or ng/L) and the RfV can be an
HBWC (e.g., ng/L). The component chemical HQs are then summed across
the mixture to yield the HI. A mixture HI exceeding 1.0 indicates that
the exposure metric is greater than the toxicity metric and there is
potential concern for a given environmental medium or site, in this
case, drinking water served to consumers from a PWS. The HI provides an
indication of: (1) concern for the overall mixture and (2) potential
driver PFAS (i.e., those PFAS with high[er] HQs). The HI accounts for
differences in toxicity among the mixture component chemicals rather
than weighting them all equally. For a detailed discussion of PFAS dose
additivity and the HI approach, see the PFAS Mixtures Framework (USEPA,
2023d). The HI is calculated through the following equation:
[GRAPHIC] [TIFF OMITTED] TP29MR23.061

Where:

HI = Hazard Index
HQ<INF>i</INF> = Hazard Quotient for chemical i
E<INF>i</INF> = Exposure, i.e., dose (mg/kg/day) or occurrence
concentration, such as in drinking water (mg/L), for chemical i
RfV<INF>i</INF> = Reference value (e.g., oral RfD or Minimal Risk
Level) [mg/kg/day], or corresponding HBWC; e.g., such as an MCLG for
chemical i (in milligrams per liter or mg/L)

V. Maximum Contaminant Level Goals

A. PFOA

1. Carcinogenicity Assessment and Cancer Slope Factor (CSF) Derivation
a. Summary of Cancer Health Effects
The carcinogenicity of PFOA has been observed in both human
epidemiological and animal toxicity studies. The evidence in high and
medium confidence epidemiological studies is primarily based on the
incidence of kidney and testicular cancer, as well as some medium
quality studies providing limited evidence of breast cancer associated
with exposure to PFOA. Other cancer types have been observed in human
studies, although the evidence for these is largely from low confidence
studies. The evidence of carcinogenicity in animal models was observed
in three medium or high quality chronic oral animal studies in adult
Sprague-Dawley rats which identified neoplastic lesions in the liver,
pancreas, and testes after PFOA exposure.
Since publication of the 2016 PFOA Health Effects Support Document
(HESD) (USEPA, 2016e), the evidence supporting the carcinogenicity of
PFOA has been strengthened by additional published studies. In
particular, the evidence of kidney cancer from highly exposed community
studies (Vieira et al., 2013; Barry et al., 2013) is now supported by
new evidence of renal cell carcinoma (RCC) from a nested case-control
study in the general population (Shearer et al., 2021). In animal
models, the evidence of multi-site tumorigenesis reported in two
chronic bioassays in rats (Butenhoff et al., 2012a; Biegel et al.,
2001) is now supported by new evidence from a third chronic bioassay in
rats that also reports multi-site tumorigenesis (NTP, 2020).
The available evidence indicates that PFOA has carcinogenic
potential in humans and at least one animal species. A plausible,
though not definitively causal, association between human exposure to
PFOA and kidney and testicular cancers in the general population and
highly exposed populations is supported by the available evidence. As
stated in the Guidelines for Carcinogen Risk Assessment (USEPA, 2005),
``an inference of causality is strengthened when a pattern of elevated
risks is observed across several independent studies.'' Two medium
confidence studies in independent populations provide evidence of an
association between elevated PFOA serum concentrations and kidney
cancer (Shearer et al., 2021; Vieira et al., 2013), while two studies
from the same cohort provide evidence of an association between
testicular cancer and elevated PFOA serum concentrations (Vieira et
al., 2013; Barry et al., 2013). A recent National Academies of Science,
Engineering, and Mathematics report on PFAS similarly ``concluded that
there is sufficient evidence for an association between PFAS and kidney
cancer'' (NASEM, 2022). The evidence of carcinogenicity in animals is
from three studies in rats of the same strain. The results from these
studies provide evidence of increased incidence of three tumor types
(Leydig cell tumors (LCTs), pancreatic acinar cell tumors (PACTs),

[[Page 18657]]

and hepatocellular adenomas) in males administered diets dosed with
PFOA. Importantly, site concordance is not always assumed between
humans and animal models; agents observed to produce tumors may do so
at the same or different sites in humans and animals, as appears to be
the case for PFOA (USEPA, 2005).
b. CSF Derivation
When a chemical is a linear carcinogen, a value that numerically
describes the relationship between the dose of a chemical and the risk
of cancer, is calculated. This is known as a cancer slope factor (CSF).
The CSF is the cancer risk (i.e., proportion affected) per unit of dose
(USEPA, 2005). In addition to reevaluating the CSF previously derived
and described in the 2016 HESD (USEPA, 2016e) based on LCTs in male
rats observed by Butenhoff et al. (2012a), EPA derived CSFs for
combined hepatocellular adenomas and carcinomas and pancreatic acinar
cell adenomas in male rats observed by NTP (2020) and kidney cancer in
humans reported by Shearer et al. (2021) and Vieira et al. (2013). EPA
focused on the CSFs derived from the epidemiological data consistent
with the EPA ORD handbook which states ``when both laboratory animal
data and human data with sufficient information to perform exposure-
response modeling are available, human data are generally preferred for
the derivation of toxicity values'' (USEPA, 2022f).
EPA selected the critical effect of RCCs in human males reported by
Shearer et al. (2021) as the basis of the CSF for PFOA. Shearer et al.
(2021) is a multi-center case-control epidemiological study nested
within the National Cancer Institute's (NCI) Prostate, Lung,
Colorectal, and Ovarian Screening Trial (PLCO) with median PFOA levels
relevant to the general U.S. population. The PLCO is a randomized
clinical trial of the use of serum biomarkers for cancer screening. The
cases in Shearer et al. (2021) included all the participants in the
screening arm of the PLCO trial who were newly diagnosed with RCC
during the follow-up period (N = 326) and all cases were
histopathologically confirmed. Controls were selected among
participants in the PLCO trial screening arm based on those who had
never had RCC and were individually matched to the RCC cases by age at
enrollment, sex, race/ethnicity, study center, and year of blood draw.
Additionally, analyses conducted by the authors accounted for numerous
confounders, including the potential for confounding by other PFAS.
Study design advantages of the Shearer et al. (2021) compared with the
Vieira et al. (2013) include specificity in the health outcome
considered (RCC vs. any kidney cancer), the type of exposure assessment
(serum biomarker vs. modeled exposure), source population (multi-center
vs. Ohio and West Virginia regions), and study size (324 cases and 324
matched controls vs. 59 cases and 7,585 registry-based controls). The
resulting CSF is 0.0293 (ng/kg/day)-\1\.
Selection of RCCs as the critical effect is supported by similar
findings from other studies of a highly exposed community (Barry et
al., 2013; Vieira et al., 2013), an occupational kidney cancer
mortality study (Steenland and Woskie, 2012), as well as a meta-
analysis of epidemiological literature that concluded that there was an
increased risk of kidney tumors correlated with increased PFOA serum
concentrations (Bartell et al., 2021). Further discussion of the
rationale for endpoint and study selection and descriptions of the
modeling methods are described in USEPA (2023b).
2. Assessment of Noncancer Health Effects and Reference Dose (RfD)
Derivation
The Agency has also considered noncancer effects in its assessment
of the best available science to derive the MCLG. As described in USEPA
(2023b), there is evidence from both human epidemiological and animal
toxicological studies that oral PFOA exposure may result in adverse
health effects across many health outcomes, including but not limited
to: immune, hepatic, developmental, cardiovascular, reproductive, and
endocrine outcomes. As recommended by the SAB (USEPA, 2022a), EPA has
largely focused its systematic literature review, health outcome
synthesis, and toxicity value derivation efforts ``on those health
outcomes that have been concluded to have the strongest evidence,
including the liver disease, immune system dysfunction, serum lipid
aberration, impaired fetal growth, and cancer.'' Conclusions regarding
the four noncancer adverse health outcome categories (i.e., judgements
for human, animal, and integrated evidence streams (USEPA, 2023b)) are
described in the subsections below. Descriptions of studies and the
basis for conclusions about the non-prioritized health outcomes are
described in USEPA (2023b).
a. Summary of Noncancer Health Effects
EPA determined that the evidence indicates that oral PFOA exposure
is associated with adverse hepatic effects based on the study quality
evaluation, evidence synthesis and evidence integration of the relevant
human epidemiological and animal toxicity studies. There is moderate
evidence from epidemiological studies supporting an association between
PFOA exposure and hepatic outcomes such as elevated serum liver enzymes
indicative of hepatic damage. Overall, there is consistent evidence of
a positive association between PFOA serum concentrations and alanine
aminotransferase (ALT), a liver enzyme marker. The evidence of hepatic
effects in humans was supported by robust evidence of hepatic effects
resulting from PFOA exposure in animal studies. Several studies provide
comprehensive histopathological reports of non-neoplastic hepatic
lesions (e.g., hepatocellular death and necrosis) in PFOA-treated
rodents, as well as increases in serum liver enzymes similar to the
trends observed in humans.
EPA determined that the evidence indicates that oral PFOA exposure
is associated with adverse immunological effects based on the study
quality evaluation, evidence synthesis and evidence integration of the
relevant human epidemiological and animal toxicity studies. There is
moderate evidence from epidemiological studies supporting an
association between PFOA and immune outcomes such as immunosuppression.
Overall, there is consistent evidence of an association between PFOA
serum concentrations and developmental immune effects (i.e., reduced
antibody response to vaccination in children). Associations between
PFOA and other immune system effects (e.g., hypersensitivity and
autoimmune disease) were mixed. The evidence for developmental
immunological effects in humans was supported by moderate evidence of
immunotoxicity resulting from PFOA exposure in animal studies. Studies
report varying manifestations of immune system effects including
altered immune cell populations and altered spleen and thymus
cellularity and weight. PFOA treatment resulted in reduced globulin and
immunoglobulin levels in animals that are consistent with the decreased
antibody response seen in human populations (i.e., the observed animal
and human study health outcomes are both indicators of
immunosuppression).
EPA determined that the evidence indicates that oral PFOA exposure
is associated with adverse developmental effects based on the study
quality evaluation, evidence synthesis and evidence integration of the
relevant human epidemiological and animal

[[Page 18658]]

toxicity studies. There is moderate evidence from epidemiological
studies supporting an association between PFOA and developmental
outcomes such as fetal growth. Overall, there is consistent evidence of
a relationship between PFOA concentrations and low birth weight.
Associations between PFOA and other developmental effects (e.g.,
postnatal growth, fetal loss, and birth defects) were mixed. The
evidence for developmental effects in humans was supported by robust
evidence of developmental toxicity resulting from PFOA exposure in
animal studies. Several studies in rodents provide evidence of
decreased fetal and pup weight due to gestational PFOA exposure,
consistent with the evidence of low birth weight in humans. Other pre-
and post-natal effects observed in animal models include decreased
offspring survival and developmental delays (e.g., delayed eye
opening).
EPA determined that the evidence indicates that oral PFOA exposure
is associated with adverse cardiovascular effects based on the study
quality evaluation, evidence synthesis and evidence integration of the
relevant human epidemiological and animal toxicity studies. There is
moderate evidence from epidemiological studies supporting an
association between PFOA and cardiovascular outcomes such as
alterations in serum lipids. Overall, there is consistent evidence of
positive relationships between PFOA serum concentrations and serum
total cholesterol, low-density lipoproteins, and triglycerides. There
is also limited evidence of positive associations of PFOA with blood
pressure and hypertension among adult populations. The evidence for
cardiovascular effects in humans was supported by moderate evidence of
cardiovascular effects resulting from PFOA exposure in animal studies.
Several studies in rodents provide evidence of alterations in serum
total cholesterol and triglycerides, though the effect direction varied
with dose. Regardless, these effects indicate a disruption in lipid
metabolism resulting from PFOA treatment, consistent with the
alterations in serum lipids observed in humans.
b. RfD Derivation
The databases for the four prioritized health outcomes were
evaluated further for identification of medium and high confidence
studies and endpoints to select for dose-response modeling. EPA
prioritized endpoints with the strongest overall weight of evidence
based on human and animal evidence for POD derivation. Specifically,
EPA focused the dose response assessment on the health outcomes where
the evidence indicated that PFOA causes health effects in humans under
relevant exposure circumstances. The focus of this Federal Register
Notice (FRN) is on epidemiological studies for the four prioritized
health outcomes for which studies meeting this consideration were
available, as human data are generally preferred ``when both laboratory
animal data and human data with sufficient information to perform
exposure-response modeling are available'' (USEPA, 2023b). EPA presents
PODs and candidate RfDs for animal studies, as well as other health
outcomes determined to have sufficient strength of evidence and studies
suitable for dose-response modeling in USEPA (2023b).
EPA identified four candidate critical effects across the four
prioritized health outcomes, all of which were represented by several
candidate critical studies. These candidate critical effects are
decreased antibody production in response to vaccinations (immune), low
birth weight (developmental), increased serum total cholesterol
(cardiovascular), and elevated ALT (hepatic). As described in the
following paragraphs and in further detail in USEPA (2023b), EPA
selected studies from each health outcome to proceed with candidate RfD
derivation. For all selected candidate RfDs, the composite UF was 10
(10x for intraspecies variability). The candidate RfDs are presented in
Table 3.
Two medium confidence studies were considered for POD derivation
for the decreased antibody production in response to various
vaccinations in children Budtz-J[oslash]rgensen and Grandjean (2018);
and Timmerman et al. (2021). These candidate studies offer a variety of
PFOA exposure measures across various populations and various
vaccinations. Budtz-J[oslash]rgensen and Grandjean (2018) investigated
anti-tetanus and anti-diphtheria responses in Faroese children aged 5-7
and Timmerman et al. (2021) investigated anti-tetanus and anti-
diphtheria responses in Greenlandic children aged 7-12. Though the
Timmerman et al. (2021) study is also a medium confidence study, the
study by Budtz-J[oslash]rgensen and Grandjean (2018) has two additional
features that strengthen the confidence in this RfD: (1) the response
reported by this study was more precise in that it reached statistical
significance, and (2) the analysis considered co-exposures of other
PFAS. The RfD for anti-tetanus response in 7-year-old Faroese children
and anti-diphtheria response in 7-year-old Faroese children, both from
Budtz-J[oslash]rgensen and Grandjean (2018) were ultimately selected
for the immune outcome as they are the same and have no distinguishing
characteristics that would facilitate selection of one over the other.
Six high confidence studies (Chu et al., 2020; Govarts et al.,
2016; Sagiv et al., 2018; Starling et al., 2017; Wikstr[ouml]m et al.,
2020; Yao et al., 2021) reported decreased birth weight in infants
whose mothers were exposed to PFOA. These candidate studies offer a
variety of PFOA exposure measures across the fetal and neonatal window.
All six studies reported their exposure metric in units of ng/mL and
reported the [beta] coefficients per ng/mL or ln(ng/mL), along with 95%
confidence intervals (CIs), estimated from linear regression models. Of
the six individual studies, Sagiv et al. (2018) and Wikstr[ouml]m et
al. (2020) assessed maternal PFOA serum concentrations primarily or
exclusively in the first trimester, minimizing concerns surrounding
bias due to pregnancy-related hemodynamic effects. Therefore, the RfDs
from these two studies were considered further for candidate RfD
selection. Both were high confidence prospective cohort studies with
many study strengths including sufficient study sensitivity and largely
sound methodological approaches, analysis, and design, as well as no
evidence of bias. The RfD from Wikstr[ouml]m et al. (2020) was
ultimately selected for the developmental outcome as it was the lowest
candidate RfD from these two studies.
Three medium confidence studies were considered for POD derivation
for the cholesterol endpoint (Dong et al., 2019; Lin et al., 2019;
Steenland et al., 2009). These candidate studies offer a variety of
PFOA exposure measures across various populations. Dong et al. (2019)
investigated the NHANES population (2003-2014), while Steenland et al.
(2009) investigated effects in a high-exposure community (the C8 Health
Project study population). Lin et al. (2019) collected data from
prediabetic adults from the Diabetes Prevention Program (DPP) and DPP
Outcomes Study at baseline (1996-1999). Of the three studies, Dong et
al. (2019) and Steenland et al. (2009) exclude those prescribed
cholesterol medication, minimizing concerns surrounding confounding due
to the medical intervention altering serum total cholesterol levels.
Additionally, Dong et al. (2019) reported measured serum total
cholesterol whereas Steenland et al. (2009) reported regression
coefficients as the response variable. Since EPA prefers dose response
modeling of endpoint data, the RfD from Dong et al. (2019) was selected
for the cardiovascular outcome, as there

[[Page 18659]]

is increased confidence in the modeling results from this study.
Four medium confidence studies were selected as candidates for POD
derivation for the ALT endpoint (Gallo et al., 2012; Darrow et al.,
2016; Nian et al., 2019; Lin et al., 2010). The two largest studies of
PFOA and ALT in adults are Gallo et al. (2012) and Darrow et al.
(2016), both conducted in over 30,000 adults from the C8 Study. Gallo
et al. (2012) reported measured serum ALT levels, unlike Darrow et al.
(2016) which reported a modeled regression coefficient as the response
variable. Another difference between the two studies is reflected in
exposure assessment: Gallo et al. (2012) includes measured PFOA serum
concentrations, while Darrow et al. (2016) based PFOA exposure on
modeled PFOA serum levels. Two additional studies (Lin et al., 2010;
Nian et al., 2019) were considered by EPA for POD derivation because
they reported significant associations in general populations in the
U.S and a high exposed population in China, respectively. Nian et al.
(2019) examined a large population of adults in Shenyang (one of the
largest fluoropolymer manufacturing centers in China) part of the
Isomers of C8 Health Project. In an NHANES adult population, Lin et al.
(2010) observed elevated ALT levels per log-unit increase in PFOA.
While this is a large nationally representative population, several
methodological limitations, including lack of clarity about base of
logarithmic transformation applied to PFOA concentrations in regression
models and the choice to model ALT as an untransformed variable
preclude its use for POD derivation. While both Nian et al. (2019) and
Gallo et al. (2012) provide measured PFOA serum concentrations and a
measure of serum ALT levels, the RfD for increased ALT from Gallo et
al. (2012) was ultimately selected for the hepatic outcome as it was
conducted in a community exposed predominately to PFOA whereas Nian et
al. (2019) was in a community exposed predominately to PFOS, which
reduces concerns about confounding from other PFAS.

Table 3--Candidate Reference Doses for PFOA for the Four Prioritized
Health Outcomes
------------------------------------------------------------------------
Measurement of Candidate RfD \1\
Study reference exposure and endpoint (mg/kg/day)
------------------------------------------------------------------------
Immune
------------------------------------------------------------------------
Budtz-J[oslash]rgensen and PFOA at age five 3 x 10-
Grandjean, 2018. years and anti-
tetanus antibody
concentrations at
age seven years.
Budtz-J[oslash]rgensen and PFOA at age five 3 x 10-
Grandjean, 2018. years on anti-
diphtheria antibody
concentrations at
age seven years.
Timmerman et al., 2021....... PFOA and anti-tetanus 3 x 10-\8\
antibody
concentrations at
ages 7-10 years.
Timmerman et al., 2021....... PFOA and anti- 2 x 10-\8\
diphtheria antibody
concentrations at
ages 7-10 years.
------------------------------------------------------------------------
Developmental
------------------------------------------------------------------------
Sagiv et al., 2018........... PFOA in first 1 x 10-\7\
trimester and
decreased birth
weight.
Wikstr[ouml]m et al., 2020... PFOA in first and 3 x 10-
second trimesters
and decreased birth
weight.
------------------------------------------------------------------------
Cardiovascular
------------------------------------------------------------------------
Dong et al., 2019............ Increased serum total 3 x 10-
cholesterol.
Steenland et al., 2009....... Increased serum total 5 x 10-\8\
cholesterol.
------------------------------------------------------------------------
Hepatic
------------------------------------------------------------------------
Gallo et al., 2012........... Increased serum ALT.. 2 x 10-
Darrow et al., 2016.......... Increased serum ALT.. 8 x 10-\7\
Nian et al., 2019............ Increased serum ALT.. 5 x 10-\8\
------------------------------------------------------------------------
Notes:
\1\ RfDs are rounded to 1 significant digit.
Bolded values indicate selected health outcome-specific RfDs.

The available evidence indicates there are effects across immune,
developmental, cardiovascular, and hepatic organ systems at the same or
approximately the same level of PFOA exposure. Candidate RfDs within
the immune, developmental, and cardiovascular outcomes are the same
value (i.e., 3 x 10-8 mg/kg/day). Therefore, EPA has selected an
overall RfD for PFOA of 3 x 10-8 mg/kg/day. The immune, developmental
and cholesterol RfDs and serve as co-critical effects and are
protective of effects that may occur in sensitive populations (i.e.,
infants and children), as well as hepatic effects that may result from
PFOA exposure.
c. MCLG Derivation
Consistent with the Guidelines for Carcinogen Risk Assessment
(USEPA, 2005), EPA reviewed the weight of the evidence and determined
that PFOA is Likely to Be Carcinogenic to Humans, as ``the evidence is
adequate to demonstrate carcinogenic potential to humans but does not
reach the weight of evidence for the descriptor Carcinogenic to
Humans.'' This determination is based on the evidence of kidney and
testicular cancer in humans and LCTs, pancreatic acinar cell tumors,
and hepatocellular adenomas in rats as described in USEPA (2023b).
Consistent with the statutory definition of MCLG, EPA establishes
MCLGs of zero for carcinogens classified as Carcinogenic to Humans or
Likely to be Carcinogenic to Humans where there is insufficient
information to determine that a carcinogen has a threshold dose below
which no carcinogenic effects have been observed. In this situation,
EPA takes a health protective approach of assuming that there is no
such threshold and that carcinogenic effects should therefore be
extrapolated linearly to zero. This approach ensures that the MCLG is
set at a level where there are no anticipated adverse health effects
with a margin of safety. This is the linear default extrapolation

[[Page 18660]]

approach. Here, EPA has determined that PFOA is Likely to be
Carcinogenic to Humans based on sufficient evidence of carcinogenicity
in humans and animals and has also determined that a linear default
extrapolation approach is appropriate as there is no evidence
demonstrating a threshold level of exposure below which there is no
appreciable cancer risk (USEPA, 2005) and therefore, it is assumed that
there is no known threshold for carcinogenicity (USEPA, 2016d). Based
upon a consideration of the best available peer reviewed science and a
consideration of an adequate margin of safety, EPA proposes a MCLG of
zero for PFOA in drinking water.
EPA is seeking comment on the derivation of the proposed MCLG for
PFOA and its determination that PFOA is Likely to be Carcinogenic to
Humans and whether the proposed MCLG is set at the level at which there
are no adverse effects to the health of persons and which provides an
adequate margin of safety. EPA is also seeking comment on its
assessment of the noncancer effects associated with exposure to PFOA
and the toxicity values described in USEPA (2023b).

B. PFOS

1. Carcinogenicity Assessment and CSF Derivation
a. Summary of Cancer Health Effects
Several medium and high confidence human epidemiological studies
and one high confidence animal chronic cancer bioassay comprise the
evidence database for the carcinogenicity of PFOS. The available
epidemiology studies reported elevated risk of bladder, prostate,
kidney, and breast cancers after chronic PFOS exposure. While there are
reports of cancer incidence from epidemiological studies, the study
designs, analyses, and mixed results preclude a definitive conclusion
about the relationship between PFOS exposure and cancer outcomes in
humans. The one high confidence animal chronic cancer bioassay study
provides evidence of multi-site tumorigenesis in both male and female
rats.
While the epidemiological evidence of associations between PFOS and
cancer found mixed results across tumor types, the available study
findings support a plausible correlation between PFOS exposure and
carcinogenicity in humans. The single chronic cancer bioassay performed
in rats is positive for multi-site and -sex tumorigenesis (Thomford,
2002; Butenhoff et al., 2012b). In this study, statistically
significant increases in the incidences of hepatocellular adenomas or
combined hepatocellular adenomas and carcinomas were observed in both
male and female rats. There was also a statistically significant dose-
response trend of these tumors in both sexes. As described in USEPA
(2023c), the available mechanistic evidence is consistent with multiple
potential MOAs for this tumor type; therefore, the hepatocellular
tumors observed by Thomford (2002)/Butenhoff et al. (2012b) may be
relevant to humans. In addition to hepatocellular tumors, Thomford
(2002)/Butenhoff et al. (2012b) reported increased incidences of
pancreatic islet cell tumors with a statistically significant dose-
dependent positive trend, as well as modest increases in the incidence
of thyroid follicular cell tumors. The findings of multiple tumor types
provide additional support for potential multi-site tumorigenesis
resulting from PFOS exposure. Structural similarities between PFOS and
PFOA add to the weight of evidence for carcinogenicity of PFOS.
Notably, a similar set of noncancer effects have been observed after
exposure to either PFOA or PFOS in humans and animal studies including
similarities in hepatic, developmental, immunological, cardiovascular,
and endocrine effects.
Under the Guidelines for Carcinogen Risk Assessment (USEPA, 2005),
EPA reviewed the weight of the evidence and determined that PFOS is
Likely to Be Carcinogenic to Humans, as ``the evidence is adequate to
demonstrate carcinogenic potential to humans but does not reach the
weight of evidence for the descriptor Carcinogenic to Humans.'' As
described in USEPA (2023c), EPA determined that the available data for
PFOS surpass many of the descriptions for the descriptor of Suggestive
Evidence of Carcinogenic Potential.
b. CSF Derivation
The Thomford (2002)/Butenhoff et al. (2012b) chronic cancer study
in male and female rats is of high confidence and provides multi-dose
tumor incidence findings that are suitable for dose-response modeling
and subsequent CSF derivation. As described in USEPA (2023c), EPA
derived PODs and candidate CSFs for three endpoints reported by this
study: hepatocellular adenomas in male rats; combined hepatocellular
adenomas and carcinomas in female rats; and pancreatic islet cell
carcinomas in male rats.
EPA selected the hepatocellular adenomas and carcinomas in female
rats reported by Thomford (2002)/Butenhoff et al. (2012b) as the basis
of the CSF for PFOS because there was a statistically significant
increase in tumor incidence in the highest dose group, a trend of
increased incidence with increasing PFOS concentrations across dose
groups, and it was the most health-protective value. The resulting CSF
is 39.5 (mg/kg/day)-1. Selection of hepatocellular adenomas and
carcinomas in female rats is supported by statistically significant
increases in hepatocellular tumor incidence in the high dose group as
well as a statistically significant trend of this response observed in
the male rats. The critical effect of pancreatic islet cell carcinomas
was not selected as the basis of the CSF because the response of the
high dose group was not statistically different from the control group,
though the trend of response across dose groups was statistically
significant. Further discussion on the rationale for endpoint selection
and descriptions of the modeling methods are described in USEPA
(2023c).
In support of the selection of hepatocellular tumors as the basis
of the CSF for PFOS, a recently published study (Goodrich et al., 2022)
reports associations between hepatocellular carcinomas and PFOS serum
concentrations in humans. These findings provide further support for
both MOA conclusions in USEPA (2023c) and the ``Likely to Be
Carcinogenic to Humans'' designation. This study was published after
the systematic literature review cutoff date for the proposed MCLG for
PFOS (USEPA, 2023c), therefore EPA requests comment on the Goodrich et
al. (2022) study and whether it supports EPA's ``Likely to Be
Carcinogenic to Humans'' designation.
2. Assessment of Noncancer Health Effects and Reference Dose (RfD)
Derivation
The Agency has also considered noncancer effects in its assessment
of the best available science to derive the MCLG. As described in USEPA
(2023c), there is evidence from both human epidemiological and animal
toxicological studies that oral PFOS exposure may result in adverse
health effects across many health outcomes, including but not limited
to immune, hepatic, developmental, cardiovascular, nervous system, and
endocrine outcomes. As recommended by the SAB (USEPA, 2022a), EPA has
focused its systematic literature review, health outcome synthesis, and
toxicity value derivation efforts ``on those health outcomes that have
been concluded to have the strongest evidence, including

[[Page 18661]]

the liver disease, immune system dysfunction, serum lipid aberration,
impaired fetal growth, and cancer.'' Conclusions regarding the four
noncancer adverse health outcome categories (i.e., judgements for
human, animal, and integrated evidence streams (USEPA, 2022f)) are
described in the subsections below. Descriptions and conclusions about
the non-priority health outcomes are described in USEPA (2023c).
a. Summary of Noncancer Health Effects
EPA determined that the evidence indicates that oral PFOS exposure
is associated with adverse hepatic effects based on the study quality
evaluation, evidence synthesis and evidence integration of the relevant
human epidemiological and animal toxicity studies. Specifically, there
is moderate evidence from epidemiological studies supporting an
association between PFOS exposure and hepatic outcomes such as elevated
serum liver enzymes indicative of hepatic damage. Overall, there is
consistent evidence of a positive association between PFOS serum
concentrations and ALT, a liver enzyme marker. The evidence of hepatic
effects in humans was supported by robust evidence of hepatotoxicity
resulting from PFOS exposure in animal studies. Studies in rodents
observed several manifestations of hepatic toxicity including
histopathological reports of non-neoplastic hepatic lesions (e.g.,
hepatic necrosis and inflammation) and increases in serum liver enzymes
similar to the trends observed in humans.
EPA determined that the evidence indicates that oral PFOS exposure
is associated with adverse immunological effects based on the study
quality evaluation, evidence synthesis and evidence integration of the
relevant human epidemiological and animal toxicity studies. There is
moderate evidence from epidemiological studies supporting an
association between PFOS and immune outcomes such immunosuppression.
Overall, there is generally consistent evidence of an association
between PFOS serum concentrations and reduced antibody response to
vaccination in children. Associations between PFOS and other immune
system effects (e.g., hypersensitivity and asthma) were mixed. The
evidence for immunological effects in humans was supported by moderate
evidence of immunotoxicity resulting from PFOS exposure in animal
studies. Studies in rodents report immune system effects including
altered activity of plaque-forming cells and natural killer cells,
altered spleen and thymus cellularity, and bone marrow hypocellularity
and extramedullary hematopoiesis. The alterations in plaque-forming and
natural killer cells in animals are consistent with the decreased
antibody response seen in human populations (i.e., the observed animal
and human study health outcomes are both indicators of
immunosuppression).
EPA determined that the evidence indicates that oral PFOS exposure
is associated with adverse developmental effects, based on the study
quality evaluation, evidence synthesis and evidence integration of the
relevant human epidemiological and animal toxicity studies. There is
moderate evidence from epidemiological studies supporting an
association between PFOS and developmental outcomes such as fetal
growth and gestational duration. Overall, there is consistent evidence
of a relationship between PFOS concentrations and low birth weight,
preterm birth, and gestational age. Associations between PFOS and
postnatal growth were inconsistent while there was limited evidence for
other developmental effects (e.g., fetal loss and birth defects). The
evidence for developmental effects in humans was supported by moderate
evidence of developmental toxicity resulting from PFOS exposure in
animal studies. Several studies in rodents provide evidence of
decreased fetal and pup weight due to gestational PFOS exposure,
consistent with the evidence of low birth weight in humans. Decreased
maternal BW was also observed. Other pre- and post-natal effects
observed in animal models include increased offspring mortality,
skeletal and soft tissue effects, and developmental delays (e.g.,
delayed eye opening). However, some studies reported no indications of
developmental toxicity.
EPA determined that the evidence indicates that oral PFOS exposure
is associated with adverse cardiovascular effects, based on the study
quality evaluation, evidence synthesis and evidence integration of the
relevant human epidemiological and animal toxicity studies. There is
moderate evidence from epidemiological studies supporting an
association between PFOS and cardiovascular outcomes such as
alterations in serum lipids. Overall, there is consistent evidence of
positive relationships between PFOS serum concentrations and serum
total cholesterol and low-density lipoproteins. There is also evidence
of positive associations of PFOS with blood pressure and hypertension
in adults. The evidence for cardiovascular effects in humans was
supported by moderate evidence of cardiovascular effects resulting from
PFOS exposure in animal studies. Several studies in rodents provide
evidence of alterations in serum total cholesterol and triglycerides,
though the effect direction varied with dose. Regardless, these effects
indicate a disruption in lipid metabolism resulting from PFOS
treatment, consistent with the alterations in serum lipids observed in
humans.
b. RfD Derivation
The databases for the four prioritized health outcomes were
evaluated further for identification of medium and high confidence
studies and endpoints to select for dose-response modeling. EPA
prioritized endpoints with the strongest overall weight of evidence
based on human and animal evidence for POD derivation. Specifically,
EPA focused the dose response assessment on the health outcomes where
the evidence indicated that PFOS causes health effects in humans under
relevant exposure circumstances. The focus of this FRN is on
epidemiological studies for the four prioritized health outcomes for
which studies meeting this consideration were available, as human data
are generally preferred ``when both laboratory animal data and human
data with sufficient information to perform exposure-response modeling
are available'' (USEPA, 2022f). EPA presents PODs and candidate RfDs
for animal studies, as well as other health outcomes determined to have
sufficient strength of evidence and studies suitable for dose-response
modeling in USEPA (2023c).
EPA identified four candidate critical effects across the four
prioritized health outcomes, all of which were represented by several
candidate critical studies. These candidate critical effects are
decreased antibody production in response to vaccinations (immune), low
birth weight (developmental), increased serum total cholesterol
(cardiovascular), and elevated ALT (hepatic). As described in the
following paragraphs and in further detail in USEPA (2023c), EPA
selected studies from each health outcome to proceed with candidate RfD
derivation. For all selected candidate RfDs, presented in Table 4, the
composite UF was 10 (10x for intraspecies variability).
Two medium confidence studies were considered for POD derivation
for the decreased antibody production in response to various
vaccinations in children Budtz-J[oslash]rgensen and Grandjean (2018)
and Timmerman et al. (2021). These candidate studies offer a variety

[[Page 18662]]

of PFOS exposure measures across various populations and various
vaccinations. Budtz-J[oslash]rgensen and Grandjean (2018) investigated
anti-tetanus and anti-diphtheria responses in Faroese children aged 5-7
and Timmerman et al. (2021) investigated anti-tetanus and anti-
diphtheria responses in Greenlandic children aged 7-12. Though the
Timmerman et al. (2021) study is also a medium confidence study, the
study by Budtz-J[oslash]rgensen and Grandjean (2018) has two features
that strengthen the results: (1) the response reported by this study
reached statistical significance, and (2) the analysis considered co-
exposures of other PFAS. The RfD for anti-diphtheria response in 7-
year-old Faroese children from Budtz-J[oslash]rgensen and Grandjean
(2018) was ultimately selected for the immune outcome because the
response reported by this study reached statistical significance, this
analysis considered co-exposures of other PFAS, and it was the more
health-protective of the two vaccine-specific responses reported by
Budtz-J[oslash]rgensen and Grandjean (2018).
Six high confidence studies (Chu et al., 2020; Sagiv et al., 2018;
Starling et al., 2017; Wikstr[ouml]m et al., 2020; Darrow et al., 2013;
Yao et al., 2021) reported decreased birth weight in infants whose
mothers were exposed to PFOS. These candidate studies offer a variety
of PFOS exposure measures across the fetal and neonatal window. All six
studies reported their exposure metric in units of ng/mL and reported
the [beta] coefficients per ng/mL or ln(ng/mL), along with 95% CIs,
estimated from linear regression models. Of the six individual studies,
Sagiv et al. (2018) and Wikstr[ouml]m et al. (2020) assessed maternal
PFOS serum concentrations primarily or exclusively in the first
trimester, minimizing concerns surrounding bias due to pregnancy-
related hemodynamic effects. Therefore, the RfDs from these two studies
were considered further for candidate RfD selection. Both were high
confidence prospective cohort studies with many study strengths
including sufficient study sensitivity and largely sound methodological
approaches, analysis, and design, as well as no evidence of bias. The
RfD from Wikstr[ouml]m et al. (2020) was ultimately selected for the
developmental outcome as it was the lowest candidate RfD from these two
studies.
Three medium confidence studies were considered for POD derivation
for the cholesterol endpoint (Dong et al., 2019; Lin et al., 2019;
Steenland et al., 2009). These candidate studies offer a variety of
PFOS exposure measures across various populations. Dong et al. (2019)
investigated the NHANES population (2003-2014), while Steenland et al.
(2009) investigated effects in a high-exposure community (the C8 Health
Project study population). Lin et al. (2019) collected data from
prediabetic adults from the DPP and DPP Outcomes Study at baseline
(1996-1999). Of the three studies, Dong et al. (2019) and Steenland et
al. (2009) exclude those prescribed cholesterol medication, minimizing
concerns surrounding confounding due to the medical intervention
altering serum total cholesterol levels. Additionally, Dong et al.
(2019) reported measured serum total cholesterol whereas Steenland et
al. (2009) reported modeled regression coefficients as the response
variable. Since EPA prefers dose response modeling of measured data,
the RfD from Dong et al. (2019) was selected for cardiovascular
endpoint as there is increased confidence in the modeling from this
study.
Three medium confidence studies were selected as candidates for POD
derivation for the ALT endpoint (Gallo et al., 2012; Nian et al., 2019;
Lin et al., 2010). The largest study of PFOS and ALT in adults is Gallo
et al. (2012), conducted in over 30,000 adults from the C8 Study
Project. Two additional studies (Lin et al., 2010; Nian et al., 2019)
were considered by EPA for POD derivation because they reported
significant associations in general populations in the U.S and a high
exposed population in China, respectively. Nian et al. (2019) examined
a large population of adults in Shenyang (one of the largest
fluoropolymer manufacturing centers in China) part of the Isomers of C8
Health Project. In an NHANES adult population, Lin et al. (2010)
observed elevated ALT levels per log-unit increase in PFOS. While this
is a large nationally representative population, several methodological
limitations, including lack of clarity about base of logarithmic
transformation applied to PFOS concentrations in regression models and
the choice to model ALT as an untransformed variable preclude its use
for POD derivation. The RfD from Nian et al., 2019 was ultimately
selected for the hepatic outcome as PFOS was the predominating PFAS in
this study which reduces concern about potential confounding by other
PFAS.

Table 4--Candidate Reference Doses for PFOS for the Four Prioritized
Health Outcomes
------------------------------------------------------------------------
Candidate RfD \1\
Study Endpoint (mg/kg/day)
------------------------------------------------------------------------
Immune
------------------------------------------------------------------------
Budtz-J[oslash]rgensen and PFOS at age five 3 x 10-\7\
Grandjean, 2018. years and anti-
tetanus antibody
concentrations at
age seven years.
Budtz-J[oslash]rgensen and PFOS at age five 2 x 10-
Grandjean, 2018. years on anti-
diphtheria antibody
concentrations at
age seven years.
Timmerman et al., 2021....... PFOS and anti-tetanus 2 x 10-\7\
antibody
concentrations at
ages 7-10 years.
Timmerman et al., 2021....... PFOS and anti- 1 x 10-\7\
diphtheria antibody
concentrations at
ages 7-10 years.
------------------------------------------------------------------------
Developmental
------------------------------------------------------------------------
Sagiv et al., 2018........... PFOS in first 6 x 10-\7\
trimester and
decreased birth
weight.
Wikstr[ouml]m et al., 2020... PFOS in first and 1 x 10-
second trimesters
and decreased birth
weight.
------------------------------------------------------------------------
Cardiovascular
------------------------------------------------------------------------
Dong et al., 2019............ Increased serum total 1 x 10-
cholesterol.
Steenland et al., 2009....... Increased serum total 1 x 10-\7\
cholesterol.
------------------------------------------------------------------------
Hepatic
------------------------------------------------------------------------
Gallo et al., 2012........... Increased serum ALT.. 7 x 10-\7\

[[Page 18663]]

Nian et al., 2019............ Increased serum ALT.. 2 x 10-
------------------------------------------------------------------------
Notes:
\1\ RfDs are rounded to 1 significant digit.
Bolded values indicate selected health outcome-specific RfDs.

The available evidence indicates there are effects across immune,
developmental, cardiovascular, and hepatic organ systems at the same or
approximately the same level of PFOS exposure. Candidate RfDs within
the developmental and cardiovascular outcomes are the same value (i.e.,
1 x 10-7 mg/kg/day). Therefore, EPA has selected an overall RfD for
PFOS of 1 x 10-7 mg/kg/day. The developmental and cholesterol RfDs
serve as co-critical effects and are protective of immune and hepatic
effects that may result from PFOS exposure.
c. MCLG Derivation
Consistent with the Guidelines for Carcinogen Risk Assessment
(USEPA, 2005), EPA reviewed the weight of the evidence and determined
that PFOS is Likely to Be Carcinogenic to Humans, as ``the evidence is
adequate to demonstrate carcinogenic potential to humans but does not
reach the weight of evidence for the descriptor Carcinogenic to
Humans.'' This determination is based on the evidence of hepatocellular
tumors in male and female rats, pancreatic islet cell carcinomas in
male rats, and mixed but plausible evidence of bladder, prostate,
kidney, and breast cancers in humans. As previously noted, the results
provided by one chronic cancer bioassay in rats exceeds the descriptor
of Suggestive Evidence of Carcinogenic Potential as it provides
evidence of multi-site and multi-sex tumorigenesis (Thomford, 2002;
Butenhoff et al., 2012b).
Consistent with the statutory definition of MCLG, EPA establishes
MCLGs of zero for carcinogens classified as Carcinogenic to Humans or
Likely to be Carcinogenic to Humans, described in Section V.A. of this
preamble above as the linear default extrapolation approach. EPA has
determined that PFOS is Likely to be Carcinogenic to Humans based on
sufficient evidence of carcinogenicity in humans and animals and has
also determined that a linear default extrapolation approach is
appropriate as there is no evidence demonstrating a threshold level of
exposure below which there is no appreciable cancer risk (USEPA, 2005)
and therefore, it is assumed that there is no known threshold for
carcinogenicity (USEPA, 2016d). Based upon a consideration of the best
available peer reviewed science and a consideration of an adequate
margin of safety, EPA proposes a MCLG of zero for PFOS in drinking
water.
EPA is seeking comment on the derivation of the proposed MCLG for
PFOS, its determination that PFOS is Likely to be Carcinogenic to
Humans and whether the proposed MCLG is set at the level at which there
are no adverse effects to the health of persons and which provides an
adequate margin of safety. EPA is also seeking comment on its
assessment of the noncancer effects associated with exposure to PFOS
and the toxicity values described in USEPA (2023c).

C. PFAS Hazard Index: PFHxS, HFPO-DA, PFNA, and PFBS

1. Background
Although it would be optimal to leverage whole mixture data for
human health risk assessment, such data for PFAS and other chemicals
are extremely rare, particularly at component-chemical (i.e.,
individual PFAS) proportions consistent with environmental mixtures. As
such, mixtures assessment commonly relies upon integration of toxicity
information for the individual component chemicals that co-occur in
environmental media. In order to assess the potential health risks
associated with PFAS mixtures, EPA has developed a Framework for
Estimating Noncancer Health Risks Associated with Mixtures of Per- and
Polyfluoroalkyl Substances (PFAS) (``PFAS Mixtures Framework'') (USEPA,
2023d), based on existing EPA mixtures guidelines and guidance (USEPA,
1986a, 2000a). The PFAS Mixtures Framework describes a flexible
approach that facilitates practical component-based mixtures evaluation
of two or more PFAS based on dose additivity. Studies with PFAS and
other classes of chemicals support the assumption that a mixture of
chemicals with similar apical effects should be assumed to also act in
a dose additive manner unless data demonstrate otherwise. This health
protective assumption for PFAS mixture assessment was supported by the
SAB in their recent review of the draft PFAS Mixtures Framework (USEPA,
2022a). All of the approaches described in the PFAS Mixtures Framework,
including the HI approach (Section III of this preamble), involve
integrating dose-response metrics that have been scaled based on the
potency of each PFAS in the mixture. As discussed in section XV of this
preamble, the SAB has reviewed the PFAS Mixtures Framework, and
concluded that the approaches in that document, including the HI
approach, are scientifically robust and defensible for assessing dose
additive effects from co-occurring PFAS (USEPA, 2022a).
The MOA is considered a key determinant of chemical toxicity. It
describes key changes in cellular interaction that may lead to
functional or anatomical changes. Toxicants are classified by their
type of toxic actions. Yet, because PFAS are an emerging chemical class
of note for toxicological evaluations and human health risk assessment,
MOA data may be limited or not available at all for many PFAS.
Component-based approaches for assessing risks of PFAS mixtures are
focused on evaluation of similarity of toxicity endpoint/effect rather
than similarity in MOA, consistent with EPA mixtures guidance (USEPA,
2000a). Precedents of prior research conducted on mixtures of various
chemical classes with common key events and adverse outcomes support
the use of dose additive models for estimating mixture-based effects,
even in instances where chemicals with disparate molecular initiating
events were included. Thus, in the absence of detailed characterization
of molecular mechanisms for most PFAS, it is considered a reasonable
health-protective assumption, consistent with the statute's admonition
to ensure an adequate margin of safety (1412(b)(4)(A)), that PFAS which
can be demonstrated to share one or more key events or adverse outcomes
will produce dose-additive effects from co-exposure (USEPA, 2022c,
2023a). This assumption of dose additivity and the HI approach was
supported by the SAB in its review of the draft PFAS Mixtures

[[Page 18664]]

Framework (USEPA, 2022a). For a detailed description of the evidence
supporting dose additivity for PFOA, PFOS, and other PFAS, see the
revised PFAS Mixtures Framework (USEPA, 2023d).
Following EPA's data-driven approach for component-based mixtures
assessment based on dose additivity (i.e., see Figure 4-1 in USEPA,
2023d), the Agency selected the HI approach for MCLG development to
ensure the Agency is protecting against dose additive risk from
mixtures of PFHxS, HFPO-DA, PFNA, and PFBS. While a single PFAS may
occur in concentrations below where EPA might establish an individual
MCLG, PFAS tend to co-occur (see discussion in sections III.C and VII
of this preamble). Hence, there are some situations where setting an
MCLG while only considering the concentration of an individual PFAS
without considering the dose additive effects that would occur from
other PFAS that may be present in a mixture may not provide a
sufficiently protective MCLG with an adequate margin of safety. For
this proposed rule, in addition to the PFOA and PFOS assessments
discussed above, peer reviewed, publicly available assessments with
final toxicity values (i.e., RfDs, Minimal Risk Levels) are available
for HFPO-DA (USEPA, 2021b), PFBS (USEPA, 2021a), PFNA (ATSDR, 2021),
and PFHxS (ATSDR, 2021). These toxicity values (along with DWI-BW and
RSC) are used to derive the HBWCs for the HI approach for PFHxS, HFPO-
DA, PFNA, and PFBS. EPA is seeking comment on derivation of the HBWCs
for each of the four PFAS considered as part of the HI. See discussion
in section VI.C of this preamble as to why EPA is not proposing to
include PFOA and PFOS in the HI MCLG at this time.
As discussed previously in this document, the Agency is proposing
the general HI as the most appropriate and justified approach for
considering PFAS mixtures in this rulemaking because of the level of
protection afforded for diverse endpoints. SDWA requires the Agency to
establish a health-based MCLG set at, ``a level at which no known or
anticipated adverse effects on the health of persons occur and which
allow for an adequate margin of safety.'' The Safe Drinking Water Act
defines the term ``contaminant'' very broadly to mean any ``physical,
chemical, biological, or radiological substance or matter in water
(SDWA 1401 4(A)(ii)(C)(6)).'' In this context, this proposal addresses
contaminants and certain mixtures of contaminants. A mixture of two or
more ``contaminants'' qualifies as a ``contaminant'' because the
mixture itself is ``any physical, chemical or biological or
radiological substance or matter in water.'' (emphasis added). EPA has
a long-standing history of regulating contaminants in this manner
(i.e., as contaminant groups or mixtures). For instance, the TTHM Rule
(U.S. EPA, 1979) EPA regulated total trihalomethanes as a group due to
their concurrent formation during the chlorination of drinking water;
EPA stating that the four regulated THMs were ``also indicative of the
presence of a host of other halogenated and oxidized, potentially
harmful byproducts of the chlorination process that are concurrently
formed in even larger quantities but which cannot be characterized
chemically'' (USEPA, 1979). In the Stage I and II Disinfection
Byproduct (DBPs) Rules, EPA regulates a second group of DBPs, in this
instance setting regulatory standards for a group of five haloacetic
acids (HAA5) (USEPA, 1998a; 2006a). A third example is EPA's regulation
of radionuclides, where, among other things, EPA regulates
radionuclides mixtures for gross alpha radiation that account for both
natural and man-made alpha emitters as a group rather than individually
(USEPA, 2000d). In summary, EPA has the statutory authority to regulate
groups and/or mixtures of contaminants, EPA has a history of regulating
groups and mixtures of contaminants that have improved public health
protection, and EPA has made a reasonable policy choice for
establishing an MCLG for a mixture of chemicals that are expected to
impact multiple endpoints. Because mixture component chemical HBWCs are
based on overall (i.e., not target-organ specific) RfDs, the approach
is protective against all health effects across component chemicals and
therefore meets the statutory requirements of establishing an MCLG
under SDWA. Basing the mixture MCLG on overall RfDs ensures that there
are no known or anticipated effects, and using the HI adds an
appropriate margin of safety for a class of contaminants that have been
shown to co-occur and evidence indicates that they have additive
toxicity.
2. PFAS Mixture MCLG Derivation
To account for dose additive noncancer effects associated with
PFHxS, HFPO-DA, PFNA, and PFBS, EPA is proposing an MCLG for the
mixture of these four PFAS based on the HI approach (USEPA, 2023a). As
described in Section IV of this preamble, a mixture HI can be
calculated when HBWCs for a set of PFAS are available or can be
calculated. The health effects information including relevant studies
mentioned in this section are summarized from USEPA (2023a) and are
also described in Section III of this preamble.
There is currently no EPA RfD available for PFHxS; however, EPA's
IRIS program is developing a human health toxicity assessment for PFHxS
(expected to undergo public comment and external peer review in 2023).
The HBWC for PFHxS is derived using an ATSDR intermediate-duration oral
Minimal Risk Level based on thyroid effects seen in male rats after
oral PFHxS exposure (ATSDR, 2021; USEPA, 2023a). ATSDR calculated an
HED of 0.0047 mg/kg/day and applied a combined UF/MF factor of 300X
(total UF of 30X and a MF of 10X for database deficiencies) to yield an
intermediate-durati

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