S,EPA
United States 0ffice of Wa,cr
Environmental Protection 0ST
Agency EPA
PUBLICATION #
EPA/822/R-22/005
Drinking Water Health Advisory:
Hexafluoropropylene Oxide (HFPO) Dimer Acid
(CASRN 13252-13-6) and HFPO Dimer Acid
Ammonium Salt (CASRN 62037-80-3), Also Known as
"GenX Chemicals"
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Drinking Water Health Advisory:
Hexafluoropropylene Oxide (HFPO) Dimer Acid (CASRN 13252-13-6) and
HFPO Dimer Acid Ammonium Salt (CASRN 62037-80-3), Also Known as
"GenX Chemicals"
Prepared by:
U.S. Environmental Protection Agency
Office of Water (4304T)
Office of Science and Technology
Health and Ecological Criteria Division
Washington, DC 20460
EPA Document Number: EPA/822/R-22/005
June 2022
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Acknowledgments
This document was prepared by the Health and Ecological Criteria Division (HECD), Office of
Science and Technology (OST), Office of Water (OW) of the U.S. Environmental Protection
Agency (EPA).
The OW scientists and managers who provided valuable contributions and direction in the
development of this health advisory are, from OST: Carlye Austin, PhD; Czarina Cooper, MPH;
Casey Lindberg, PhD; Gregory G. Miller, MS (formerly in OST; currently in Office of
Children's Health Protection [OCHP]); Brittany Jacobs, PhD; Kelly Cunningham, MS; Susan
Euling, PhD; and Colleen Flaherty, MS; and from the Office of Ground Water and Drinking
Water (OGWDW): Stanley Gorzelnik, PE; Elizabeth Berg; Daniel P. Hautman; Ashley Greene,
MS; and Ryan Albert, PhD.
The literature searches to identify information about the relative source contribution for GenX
were performed by contractors at ICF (contract number 68HE0C18D0001) and Tetra Tech
(contract number 68HERC20D0016).
This document was provided for review by staff in the following EPA Program Offices:
• Office of Water
• Office of Chemical Safety and Pollution Prevention, Office of Pollution Prevention and
Toxics
• Office of Land and Emergency Management
• Office of Policy
• Office of Children's Health Protection
• Office of Research and Development
i
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Contents
Abbreviations and Acronyms iv
Executive Summary vii
1.0 Introduction and Background 1
1.1 History under SDWA 1
1.2 Current Advisories and Guidelines 2
1.3 Uses and Sources of GenX Chemicals 3
1.4 Environmental Fate, Occurrence in Water, and Exposure to Humans 4
1.4.1 Environmental Fate and Transport in the Environment 4
1.4.2 Occurrence in Water 5
1.4.3 Exposure in Humans 9
2.0 Problem Formulation and Scope 10
2.1 Conceptual Model 10
2.2 Analysis Plan 13
2.2.1 Health Advisory Guidelines 13
2.2.2 Sources of Toxicity Information for Health Advisory Development 13
2.2.3 Approach and Scope for Health Advisory Derivation 14
2.2.4 Exposure Factors for Deriving Health Advisory 16
3.0 Health Advisory Input Values 19
3.1 Toxicity Assessment Values 19
3.2 Exposure Factors 21
3.3 Relative Source Contribution 22
3.3.1 Non-Drinking Water Sources and Routes 22
3.3.2 RSC Determination 25
4.0 Lifetime Noncancer Health Advisory Derivation 26
5.0 Analytical Methods 27
6.0 Treatment Technologies 28
6.1 Sorption Technologies 28
6.1.1 Activated Carbon 29
6.1.2 Ion Exchange 31
6.2 High Pressure Membranes 32
6.3 Point-of-Use Devices for Individual Household PFAS Removal 32
6.4 Treatment Technologies Summary 33
7.0 Consideration of Noncancer Health Risks from PFAS Mixtures 33
8.0 Health Advisory Characterization 35
8.1 Comparative Analysis of Exposure Factors for Different Populations 35
8.2 Related Compounds of Emerging Concern 36
ii
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9.0 References 38
Appendix A: Relative Source Contribution - Literature Search and Screening
Methodology 51
Appendix B: Compilation of Data on HFPO Dimer Acid Occurrence in Surface
Water Collected from Primary Literature 54
Figures
Figure 1. Conceptual Model for the Development of the Drinking Water Health Advisory
for GenX Chemicals 11
Tables
Table 1. State Guideline Values for GenX Chemicals 2
Table 2. International Guideline Values for GenX Chemicals 3
Table 3. EPA Exposure Factors for Drinking Water Intake 17
Table 4. Chronic Noncancer Toxicity Information for GenX Chemicals for Deriving the
Lifetime HA 20
Table 5. EPA Exposure Factors for Drinking Water Intake for Different Candidate
Sensitive Populations Based on the Critical Effect and Study 22
Table 6. Comparison of HA Values Using EPA Exposure Factors for Drinking Water
Intake for Different Candidate Populations 36
Table A-l. Populations, Exposures, Comparators, and Outcomes (PECO) Criteria 51
Table B-l. Compilation of Studies Describing of HFPO Dimer Acid Occurrence in Surface
Water 54
in
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Abbreviations and Acronyms
ADAF
age-dependent
EF
exposure factor
adjustment factor
EFH
Exposure Factors
AIX
anion exchange
Handbook
AF
amorphous
fluoropolymer
EGLE
Michigan Department of
Environment, Great
AFFF
aqueous film-forming
Lakes, and Energy
foam
EPA
United States
ANSI
American National
Standards Institute
Environmental Protection
Agency
ATSDR
Agency for Toxic
Eq.
equation
Substances and Disease
FDA
United States Food and
Registry
Drug Administration
BMD
benchmark dose
FEP
fluorinated ethylene
BMDL
benchmark dose lower
propylene
limit
g/L
grams per liter
bw or BW
body weight
GAC
granular activated carbon
CASRN
Chemical Abstracts
Service Registry Number
GenX chemicals
hexafluoropropy 1 ene
oxide dimer acid and its
CDC
Centers for Disease
ammonium salt
Control and Prevention
h3o+
hydronium
CCL
Contaminant Candidate
HA
Health Advisory
List
HECD
Health and Ecological
CCL 5
Fifth Safe Drinking
Criteria Division
Water Act Contaminant
HED
human equivalent dose
Candidate List
HFPO
hexafluoropropy 1 ene
cm3
cubic centimeters
oxide
CSF
cancer slope factor
HFPO dimer acid
2,3,3,3 -tetrafluoro-2-
DBP
disinfection byproduct
(heptafluoropropoxy)
DF
detection frequency
propanoic acid
DHS
Department of Health
Services
HFPO-TA
hexafluoropropy 1 ene
oxide trimer acid
DOM
dissolved organic matter
HFPO-TeA
hexafluoropropy 1 ene
DQO
data quality objective
oxide tetramer acid
dw
dry weight
HI
hazard index
DWI
drinking water intake
HIDOH
Hawai i State
DWI-BW
body weight-adjusted
HNIS
Department of Health
drinking water intake
Human Nutrition
DWTP
drinking water treatment
Information Service
plant
HQ
hazard quotient
E
EBCT
human exposure
empty bed contact time
i
mixture component
chemical
iv
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IDEM
Indiana Department of
NOAEL
no observed adverse
Environmental
effect level
Management
NOM
natural organic matter
iHA
interim Health Advisory
NR
not reported
Illinois EPA
Illinois Environmental
NSF
National Science
Protection Agency
Foundation
ITRC
Interstate Technology
OCHP
Office of Children's
and Regulatory Council
Health Protection
km
kilometers
ODH
Ohio Department of
L/kg bw-day
liters per kilogram body
Health
weight per day
OGWDW
Office of Ground Water
L/(m2hr)
liters per square meter
and Drinking Water
per hour
Ohio EPA
Ohio Environmental
LC/MS/MS
liquid
Protection Agency
chromatography/tandem
OST
Office of Science and
mass spectrometry
Technology
LOAEL
lowest observed adverse
OW
Office of Water
effect level
PAC
powdered activated
LOQ
limit of quantification
carbon
m/hr
meters per hour
PECO
populations, exposures,
MCLG
Maximum Contaminant
comparators, and
Level Goal
outcomes
mg/kg bw-day
milligrams per kilogram
PFA
perfluoroalkoxy
body weight per day
PFAS
per- and polyfluoroalkyl
MQL
method quantification
substances
limit
PFBS
perfluorobutane sulfonic
MRL
minimum reporting limit
acid
NCDEQ
North Carolina
PFCA
perfluoroalkyl carboxylic
Department of
acid
Environmental Quality
PFECA
perfluoroalkyl ether
NCDHHS
North Carolina
carboxylic acid
Department of Health and
PFOA
perfluorooctanoic acid
Human Services
PFOS
perfluorooctanesulfonic
ND
not detected
acid
nh4+
ammonium cation
Pg/g
picograms per gram
NF
nanofiltration
Pg/L
picograms per liter
ng/g
nanograms per gram
PHG
provisional health goal
ng/kg
nanograms per kilogram
pKa
acid dissociation constant
ng/L
nanograms per liter
POD
point of departure
NHANES
National Health and
PODhed
point of departure human
Nutrition Examination
equivalent dose
Survey
POE
point-of-entry
POU
V
point-of-use
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PPARa
peroxisome proliferator-
activated receptor alpha
ppt
parts per trillion
PTFE
polytetrafluoroethylene
PWS
public water system
RfD
reference dose
RO
reverse osmosis
RPF
relative potency factor
RSC
relative source
contribution
SAB
Science Advisory Board
SDWA
Safe Drinking Water Act
tl/2
half-life
TSCATS
Toxic Substances Control
Act Test Submissions
UCMR
Unregulated Contaminant
Monitoring Rule
UCMR3
Third Unregulated
Contaminant Monitoring
Rule
UCMR 5
Fifth Unregulated
Contaminant Monitoring
Rule
UF
uncertainty factor(s)
UFa
interspecies uncertainty
factor
UFc
composite uncertainty
factor
UFd
database uncertainty
factor
UFh
intraspecies uncertainty
factor
UFs
extrapolation from
sub chronic to chronic
exposure duration
uncertainty factor
Hg/L
micrograms per liter
jag/kg bw-day
micrograms per kilogram
body weight per day
Wisconsin DHS
Wisconsin Department of
Health Services
WOS
Web of Science
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Executive Summary
Hexafluoropropylene oxide (HFPO) dimer acid (2,3,3,3-tetrafluoro-2- [heptafluoropropoxy]
propanoic acid) (Chemical Abstracts Service Registry Number [CASRN] 13252-13-6) and
HFPO dimer acid ammonium salt (ammonium 2,3,3,3- tetrafluoro-2-
[heptafluoropropoxyjpropanoate) (CASRN 62037-80-3) are shorter-chain members of a group of
substances known as per- and polyfluoroalkyl substances (PFAS). HFPO dimer acid and its
ammonium salt are referred to as "GenX chemicals" because they are two of the main chemicals
associated with the GenX processing aid technology that DuPont developed to make high-
performance fluoropolymers without using perfluorooctanoic acid (PFOA) (U.S. EPA, 2021a).
In water, both HFPO dimer acid and its ammonium salt dissociate to form the HFPO dimer acid
anion (HFPO-) as a common analyte.
GenX chemicals are replacements for the longer-chain PFOA, which was phased out in the United
States by 2015 as part of an agreement between manufacturers and the U.S. Environmental
Protection Agency (EPA) under the PFOA Stewardship Program, established in 2006. GenX
chemicals are used to manufacture fluoropolymers which have many industrial applications
including in medical, automotive, electronics, aerospace, energy, and semiconductor industries.
The Chemours Company uses GenX chemicals to produce four trademarked fluoropolymers:
Teflon™ polytetrafluoroethylene (PTFE), Teflon™ perfluoroalkoxy (PFA), Teflon™ fluorinated
ethylene propylene (FEP), and Teflon™ amorphous fluoropolymer (AF) (Chemours, 2022).
Since GenX chemicals are substitutes for PFOA, products (e.g., some nonstick coatings) that were
previously made using PFOA may now rely on GenX chemicals.
GenX chemicals have been detected around the globe in surface water, groundwater, finished
drinking water, rainwater, and air emissions (U.S. EPA, 2021a). Potential sources of GenX in the
environment include industrial facilities that use GenX technology for polymer production,
facilities that produce fluoromonomers (as a byproduct), and contaminated water, air, soil, and
biosolids. GenX chemicals may also be generated as a byproduct of other manufacturing
processes including fluoromonomer production. For example, GenX chemicals have been
discharged into the Cape Fear River for several decades as a byproduct of manufacturing
(NCDEQ, 2017). GenX chemicals can enter the aquatic environment through industrial
discharges, runoff into surface water, and leaching into groundwater from soil and landfills (U.S.
EPA, 2021a). GenX chemicals are water-soluble, with solubilities of greater than 751 grams per
liter (g/L) and greater than 739 g/L for HFPO dimer acid and its ammonium salt, respectively, at
20°C (U.S. EPA, 2021a). Volatilization from water surfaces is expected to be an important fate
process for both HFPO dimer acid and its ammonium salt (U.S. EPA, 2021a). The limited data
on human serum have detected GenX chemicals in studies of workers.
EPA is issuing a lifetime noncancer drinking water Health Advisory (HA) for GenX chemicals
of 10 nanograms per liter (ng/L) or 10 parts per trillion (ppt). This is the first HA for GenX
chemicals and its finalization fulfills a commitment described in EPA's PFAS Strategic
Roadmap (U.S. EPA, 2021b). The final toxicity assessment for GenX chemicals titled Final
Human Health Toxicity Values for Hexafluoropropylene Oxide (HFPO) Dimer Acid and Its
Ammonium Salt (CASRN 13252-13-6 and CASRN 62037-80-3) Also Known as "GenX
Chemicals" (U.S. EPA, 2021a) serves as the basis of the toxicity information used to derive the
lifetime noncancer HA for GenX chemicals. This final toxicity assessment was published after a
rigorous process including draft assessment development, agency and interagency review, public
Vll
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comment, two independent peer reviews, and an independent review of data from two studies by
the National Toxicology Program. The input values for deriving the HA include 1) the final
chronic reference dose (RfD) for GenX of 0.000003 milligrams per kilogram body weight per day
(mg/kg bw-day) (U.S. EPA, 2021a); 2) a 20% relative source contribution (RSC) based on EPA's
Exposure Decision Tree approach in EPA's Methodology for Deriving Ambient Water Quality
Criteria for the Protection of Human Health (U.S. EPA, 2000a); and 3) the drinking water intake
rate of 0.0469 L/kg bw-day for lactating women, which is the sensitive population identified
based on the critical study selected for the final RfD (U.S. EPA, 2021a).
The final toxicity assessment for GenX chemicals (U.S. EPA, 2021a) derived both subchronic and
chronic RfDs based on the critical adverse effect of a constellation of liver lesions (i.e.,
cytoplasmic alteration, hepatocellular single-cell and focal necrosis, and hepatocellular apoptosis)
observed in female mice in an oral reproductive/developmental toxicity study (DuPont-18405-
1037, 2010; NTP, 2019). Using EPA's Benchmark Dose Technical Guidance Document (U.S.
EPA, 2012), EPA modeled the dose-response relationship in the range of observed data.
Additionally, EPA's Recommended Use of Body Weight4 as the Default Method in Derivation
of the Oral Reference Dose (U.S. EPA, 2011) was used to allometrically scale a toxicologically
equivalent dose from adult laboratory animals to adult humans. From benchmark dose modeling
(BMD) of the DuPont-18045-1037 (2010) study, the resulting POD human equivalent dose
(HED) is 0.01 mg/kg bw-day. The HED was divided by a composite UF (UFc) of 3,000 to obtain
the chronic RfD of 0.000003 mg/kg bw-day or 0.003 micrograms per kilogram body weight per
day (|ig/kg bw-day) for GenX chemicals (U.S. EPA, 2021a).
There is insufficient toxicity information available to derive a one-day HA for GenX chemicals
because U.S. EPA (2021a) does not have a final RfD for acute exposure (i.e., relevant to a 7 day
or less exposure period). There is also insufficient toxicity information available to derive a ten-
day HA because U.S. EPA (2021a) did not derive a final short-term exposure RfD for a 7-to-30-
day exposure on which to base a ten-day HA for GenX chemicals.
For cancer toxicity, one chronic 2-year study in rats evaluating the carcinogenicity of GenX
chemicals was identified (U.S. EPA, 2021a). In accordance with the Guidelines for Carcinogen
Risk Assessment (U.S. EPA, 2005b), EPA concluded that there is Suggestive Evidence of
Carcinogenic Potential following oral exposure in humans for GenX chemicals based on female
hepatocellular adenomas and carcinomas and male combined pancreatic acinar adenomas and
carcinomas observed in the chronic 2-year study in rats (U.S. EPA, 2021a). A cancer slope factor
(CSF) was not derived for GenX chemicals in the toxicity assessment. This is consistent with
EPA's guidelines which state that when the available evidence is suggestive for carcinogenicity,
a quantitative risk estimate is generally not derived unless there exists a well-conducted study
that could facilitate an understanding of the magnitude and uncertainty of potential risks, ranking
potential hazards, or setting research priorities (U.S. EPA, 2005a). Therefore, EPA did not derive
a 10"6 cancer risk concentration in the HA for GenX chemicals.
EPA developed two analytical methods to quantitatively monitor drinking water for targeted
PFAS that include HFPO dimer acid: EPA Method 533 (U.S. EPA, 2019b), which has a
quantitation limit of3.7 ng/L for HFPO dimer acid, andEPAMethod 537.1, Version 2.0 (U.S.
EPA, 2020b), which has a quantitation limit for HFPO dimer acid at 4.3 ng/L. These analytical
methods can both effectively and accurately monitor drinking water for HFPO dimer acid at
levels below the lifetime HA of 10 ng/L. Treatment technologies, including sorption-based
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processes such as activated carbon and ion exchange, along with high pressure membrane
processes such as reverse osmosis (RO), and nanofiltration (NF), are available and have been
shown to remove HFPO dimer acid in drinking water.
IX
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1.0 Introduction and Background
The Safe Drinking Water Act (SDWA) (42 U.S.C. § § 300f - 300j-27) authorizes the U.S.
Environmental Protection Agency (EPA) to develop drinking water Health Advisories (HAs).1
HAs are national non-enforceable, non-regulatory drinking water concentration levels of a
specific contaminant at or below which exposure for a specific duration is not anticipated to lead
to adverse human health effects.2 HAs are intended to provide information that tribal, state, and
local government officials and managers of public water systems (PWSs) can use to determine
whether actions are needed to address the presence of a contaminant in drinking water. HA
documents reflect the best available science and include HA values as well as information on
health effects, analytical methodologies for measuring contaminant levels, and treatment
technologies for removing contaminants from drinking water. EPA's lifetime HAs identify levels
to protect all Americans, including sensitive populations and life stages, from adverse health
effects resulting from exposure throughout their lives to contaminants in drinking water.
In October 2021, EPA published a final toxicity assessment for two per- and polyfluoroalkyl
substances (PFAS), hexafluoropropylene oxide (HFPO) dimer acid and its ammonium salt,
collectively known as "GenX chemicals" (U.S. EPA, 2021a). EPA's final Human Health
Toxicity Values for Hexafluoropropylene Oxide (HFPO) Dimer Acid and Its Ammonium Salt
(CASRN13252-13-6 and CASRN 62037-80-3) Also Known as "GenXChemicals" was an
essential step to better understanding the potential human health effects of exposure to these two
main GenX chemicals. The human health chronic reference dose (RfD) calculated in the toxicity
assessment allows EPA to develop a lifetime HA that will help communities make informed
decisions about GenX chemicals to better protect human health. The final HA for GenX
chemicals satisfies a commitment described in EPA's PFAS Strategic Roadmap (U.S. EPA,
2021b).
1.1 History under SDWA
HFPO dimer acid and its ammonium salt are not currently regulated under SDWA. GenX is a
trade name for a technology that is used to make high-performance fluoropolymers without the
use of perfluorooctanoic acid (PFOA). In 2008, DuPont de Nemours, Inc. (hereinafter DuPont)
submitted premanufacture notices to EPA under the Toxic Substances Control Act (Title 15 of
the United States Code § 2601 et seq.) for two chemicals:
• 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy) propanoic acid (Chemical Abstracts Service
Registry Number [CASRN] 13252-13-6) or HFPO dimer acid
• ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy) propanoate (CASRN 62037-80-3)
or HFPO dimer acid ammonium salt
Both HPFO dimer acid and its ammonium salt are components of the GenX processing aid
technology that DuPont developed to make high-performance fluoropolymers without using
1 SDWA § 1412(b)(1)(F) authorizes EPA to "publish health advisories (which are not regulations) or take other appropriate
actions for contaminants not subject to any national primary drinking water regulation." www.epa.gov/sites/default/files/2020-
05/documents/safe drinking water act-title xivof public health service act.pdf
2 This document is not a regulation and does not impose legally binding requirements on EPA, states, tribes, or the regulated
community. This document is not enforceable against any person and does not have the force and effect of law. No part of this
document, nor the document as a whole, constitutes final agency action that affects the rights and obligations of any person. EPA
may change any aspects of this document in the future.
1
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PFOA (U.S. EPA, 2021a). These compounds fall into the perfluoroalkyl ether carboxylic acids
(PFECAs) PFAS class or subgroup. Although not the only GenX chemicals, HFPO dimer acid
and its ammonium salt are the major chemicals associated with the GenX processing aid
technology (ECHA, 2015; U.S. EPA, 2021a). The lifetime HA for GenX chemicals derived in
this document pertains only to the two major GenX chemicals, HFPO dimer acid and its
ammonium salt, because this was the scope of the toxicity assessment for GenX chemicals (U.S.
EPA, 2021a).
HFPO dimer acid and its ammonium salt were listed on the draft fifth SDWA Contaminant
Candidate List (CCL 5) not as individual chemicals but as part of the PFAS group inclusive of
any PFAS except for PFOA and perfluorooctanesulfonic acid (PFOS) (U.S. EPA, 2021c). The
Contaminant Candidate List (CCL) is a list of contaminants that are not subject to any proposed
or promulgated National Primary Drinking Water Regulations, are known or anticipated to occur
in PWSs and may require regulation under SDWA.3 EPA is currently evaluating public
comments and additional information to inform the Final CCL 5 and any future regulatory
actions for these chemicals under SDWA.
The 1996 amendments to SDWA require that EPA issue a new list of unregulated contaminants
(once every five years) to be monitored by PWSs.4 Under the Unregulated Contaminant
Monitoring Rule (UCMR), EPA collects occurrence data for contaminants that may be present in
drinking water but do not have health-based standards set under SDWA. HFPO dimer acid is one
of 29 PFAS included for monitoring under the fifth Unregulated Contaminant Rule (UCMR 5)
between 2023 and 2025 (U.S. EPA, 202Id). The collection of drinking water occurrence data
supports EPA's future regulatory determinations and may support additional actions to protect
public health (U.S. EPA, 202Id).
1.2 Current Advisories and Guidelines
Table 1 provides drinking water guideline values for GenX chemicals that have been developed
by states. The state values range from 21 to > 700 parts per trillion (ppt) or nanograms per liter
(ng/L). This broad range of values may in part reflect differences in the level type derived, state
guidance, or use of different methods (see references for more details).
Table 1. State Guideline Values for GenX Chemicals
State11'1'
GenX Chemical
Level
(PPt |ng/L|)
Standard/Guidance
Type of Medium
Reference
Hawaii
160
Environmental Action
Levels
Groundwater
HIDOH (2020)
Illinois
21
Health-Based Guidance
Level
Drinking water;
Groundwater
Illinois EPA (2022)
Indiana
>700
Action Level
Drinking water
IDEM (2022)
3 https://www.epa.gov/ccl/basic-iiifomration-ccl-and-regulatorv-deteniiiiiation
4 SDWA § 1445 (a)(l )(D)(2)(B) — "Not later than 3 years after the date of enactment of the Safe Drinking Water Act
Amendments of 1996 and every 5 years thereafter, the Administrator shall issue a list pursuant to subparagraph (A) of not more
than 30 unregulated contaminants to be monitored by public water systems and to be included in the national drinking water
occurrence data base maintained pursuant to subsection (g)."
2
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State11'1'
GenX Chemical
Level
(ppt |ng/L|
Standard/Guidance
Type of Medium
Reference
Michigan
370
Drinking Water
Maximum Contaminant
Level
Drinking water;
Groundwater
EGLE (2020)
North
Carolina
140
Health Goal
Drinking water
NCDHHS (2017)
Ohio
21
Action Level
Drinking water
Ohio EPA and ODH
(2022)
Wisconsin
300
Recommended
Enforcement Standard
Groundwater
Wisconsin DHS
(2020)
30
Recommended Preventive
Action Limit
Groundwater
Notes:
a The information was collected via EPA regional office outreach by EPA's Office of Science and Technology (OST) in March
2022; and from the Interstate Technology and Regulatory Council's (ITRC) Standards and guidance values forPFAS in
ground-water, drinking -water, and surface -water/effluent (wastewater) PFAS Water and Soil Values Table, last updated in April
2022 (available for download here: https://pfas-1..itrcweb.org/fact-sheetsA.
b Only states with final guidelines are included in the table. Note: EPA regions report that New Jersey and New York are
developing guidelines for GenX chemicals.
Table 2 provides drinking water guideline values for GenX chemicals that have been developed
by international agencies; the Interstate Technology and Regulatory Council (ITRC) only
reported guideline values for GenX chemicals for the Netherlands (ITRC, 2022). The guidelines
presented are indicative levels for severe pollution in drinking water (660 ppt or ng/L) and
groundwater (140,000 ppt or ng/L). Other countries may be developing guidelines for GenX
chemicals.
Table 2. International Guideline Values for GenX Chemicals
Country11'1'
GenX Chemical
Level
(ppt |ng/L|)
Standard/Guidance
Type of Medium
Reference
The
Netherlands
660
Indicative Level for
Severe Pollution
Drinking water
ITRC (2022)
140,000
Indicative Level for
Severe Pollution
Groundwater
Notes:
a The information was collected from ITRC Standards and guidance values forPFAS in groundwater, drinking water, and
surface water/effluent (wastewater) PFAS Water and Soil Values Table, last updated in April 2022 (available for download
here: https://pfas-l.itrcweb.org/fact-sheets/).
b Only countries with guideline values provided in the ITRC table are included; other countries may be developing guidelines for
GenX chemicals.
1.3 Uses and Sources of GenX Chemicals
GenX chemicals are used to manufacture fluoropolymers. Since GenX chemicals are substitutes
for PFOA, products (e.g., some nonstick coatings, aqueous film-forming foam [AFFF]) that were
3
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previously made using PFOA may now rely on GenX chemicals. PFOA was phased out between
2006 and 2015 in the United States under an agreement between EPA and eight major PFAS
companies under the PFOA Stewardship Program5 established in 2006. According to the
Chemours Company,6 fluoropolymers have "countless" industrial applications, including in the
medical, automotive, electronics, aerospace, energy, and semiconductor industries.7 The
Chemours Company uses GenX chemicals to produce four trademarked fluoropolymers:
Teflon™ polytetrafluoroethylene (PTFE), Teflon™ perfluoroalkoxy (PFA), Teflon™ fluorinated
ethylene propylene (FEP), and Teflon™ amorphous fluoropolymer (AF) (Chemours, 2022).
GenX chemicals may also be generated as a byproduct of fluoromonomer production. There is a
paucity of publicly available information on specific end-use products made with GenX
chemicals.
Potential sources of GenX chemicals in the environment include industrial facilities that use
GenX technology for fluoropolymer or fluoromonomer production, and contaminated water, air,
soil, and biosolids. GenX chemicals have been detected around the globe, in surface water,
groundwater, finished drinking water, rainwater, air, soil, and sediment as further described
below and in U.S. EPA (2021a).
1.4 Environmental Fate, Occurrence in Water, and Exposure to Humans
1.4.1 Environmental Fate and Transport in the Environment
As noted in U.S. EPA (2021a), HFPO dimer acid and its ammonium salt are stable to photolysis,
hydrolysis, and biodegradation. The degradation data suggest that they will be persistent (i.e.,
have a half-life [ti/2] longer than six months) in air, water, soil, and sediments. Measured
physical-chemical and sorption data indicate that GenX chemicals are expected to run off into
surface water and to leach to groundwater from soil and landfills. Based on chemicals with
similar properties (e.g., PFOA), HFPO dimer acid and its ammonium salt might undergo long-
range atmospheric transport in the vapor phase and associate with particulates. They are not
expected to be removed during conventional wastewater treatment or conventional drinking
water treatment processes such as coagulation, flocculation, or sedimentation.
When released to the freshwater environment, HFPO dimer acid will dissociate to the HFPO
carboxylate anion and hydronium cation (H30+). The ammonium salt will dissolve to the HFPO
carboxylate anion and the ammonium cation (NH4+). Both HFPO dimer acid and its ammonium
salt are highly water-soluble and are expected to remain in water with low sorption to sediment
or soil. Based on its high vapor pressure, the HFPO dimer acid can partition to air. The
ammonium salt can also be transported in air, although the mechanism of vapor phase transport
is not well understood (DuPont CCAS, 2009). In the vapor phase, the HFPO dimer acid and its
ammonium salt are expected to be stable to direct photolysis and will undergo hydroxyl radical-
catalyzed indirect photolysis very slowly (U.S. EPA, 2021a).
5 https://www.epa.gov/assessiiig-and-iiiaiiagiiig-chemicals-under-tsca/fact-sheet-20102015-pfoa-stewardship-program
6 The GenX processing technology and associated chemicals are products of The Chemours Company, a spin-off of DuPont de
Nemours, Inc. (Chemours, 2015).
7 https://www.epa.gOv/system/files/documents/2022-03/3.18.22-request-for-corTection-letter-and-exliibits_0.pdf
4
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1.4.2 Occurrence in Water
GenX chemicals can enter the aquatic environment through industrial discharges, runoff into
surface water, and leaching into groundwater from soil and landfills (U.S. EPA, 2021a). GenX
chemicals are water-soluble, with solubilities of greater than 751 grams per liter (g/L) and
greater than 739 g/L for HFPO dimer acid and its ammonium salt, respectively, at 20°C (U.S.
EPA, 2021a). Volatilization from water surfaces is expected to be an important fate process for
both HFPO dimer acid and its ammonium salt (U.S. EPA, 2021a). Due to the limited number of
U.S. occurrence studies on GenX chemicals, this section includes studies conducted outside as
well as inside the U.S. to better understand sources and occurrence patterns in water.
1.4.2.1 Drinking Water
GenX chemicals were not included in the suite of PFAS analyzed in EPA's Third Unregulated
Contaminant Monitoring Rule (UCMR 3) monitoring; thus, national GenX chemicals occurrence
data from drinking water facilities are not available at this time (U.S. EPA, 2017a). However,
occurrence data for GenX chemicals in drinking water are available, collected using EPA
methods 533 and 537.1, from studies investigating areas known to be affected by GenX
chemicals in a subset of U.S. states. GenX chemicals have been detected in the finished drinking
water of at least nine states (ADEM, 2020; CDPHE, 2020; KYDEP, 2019; Michigan EGLE,
2021; NCDEQ, 2021, NHDES, 2021; Ohio DOH, 2021; SCDHEC, 2020; VTDEC, 2021). In
states where sampling locations were selected randomly, the percentage of total samples that had
concentrations of GenX chemicals above the reporting limit is generally well below 1%. Where
targeted sampling has been performed, some states have found GenX chemicals at relatively
higher concentrations, whereas in other states, the total number of samples with GenX chemicals
is low or there are no detections. Further, EPA is aware of four states in which state-level
monitoring efforts have found GenX chemicals in at least one finished water sample at a
concentration above 0.010 micrograms per liter ((J,g/L) (10 ng/L). For example, the Kentucky
Department for Environmental Protection (KYDEP, 2019) detected HFPO dimer acid in 11 post-
treatment samples from statewide drinking water treatment plants (DWTPs) (median
concentration of < 1.32 ng/L and maximum concentration of 29.7 ng/L). There were 10
detections of HFPO dimer acid at DWTPs that use surface water and one detection at a DWTP
that uses groundwater; all detections occurred at DWTPs that use the Ohio River and Ohio River
Alluvium as sources. Many of the DWTPs tested did not utilize treatment technologies that
remove PFAS at that time.
In addition to those data collected by some states, GenX chemicals have been detected in three
on-site production wells and one on-site drinking water well at the Chemours Washington Works
facility outside of Parkersburg, West Virginia (U.S. EPA, 2021a). EPA subsequently requested
that Chemours test for GenX chemicals in both raw and finished water at four PWSs and 10
private drinking water wells in Ohio and West Virginia near the Washington Works facility.
Chemours completed the additional testing in February 2018 and reported HFPO dimer acid
concentrations of < 0.010-0.081 (J,g/L in the PWS samples before treatment and < 0.010-0.052
[j,g/L in the private drinking water wells before treatment (U.S. EPA, 2018). Results for all
samples collected after treatment were below the reporting limit of 0.010 [j,g/L (10 ng/L)
achievable at that time (U.S. EPA, 2018). Additionally, a study by Galloway et al. (2020)
analyzed eight drinking water samples from public buildings (e.g., schools and libraries) and
private wells located more than 27 kilometers (km) northeast of the Washington Works facility.
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HFPO dimer acid was detected in only one sample, and at a concentration below the limit of
quantification (LOQ).
Three published studies evaluated the occurrence of GenX chemicals in drinking water near
Cape Fear River in North Carolina (McCord et al., 2018; Pritchett et al., 2019; Sun et al., 2016).
In finished drinking water collected from a DWTP downstream of a fluorochemical
manufacturer, McCord et al. (2018) reported an HFPO dimer acid concentration of
approximately 500 ng/L. After this sampling, the fluorochemical manufacturer diverted waste
stream emissions from one of its manufacturing lines, and subsequent measured concentrations
at this location were close to or below the North Carolina Department of Health and Human
Services (NCDHHS) provisional health goal (PHG) of 140 ng/L. Pritchett et al. (2019) reported
that according to the North Carolina Department of Environmental Quality (NCDEQ), as of
April 2018, 207 out of 837 private wells (25%) within a 5-mile radius of a PFAS manufacturing
facility in the Cape Fear River basin had levels of GenX chemicals exceeding the NCDHHS
PHG of 140 ng/L, with a maximum measured concentration of 4,000 ng/L. Sun et al. (2016)
analyzed finished drinking water from a DWTP downstream of a PFAS manufacturing site and
reported HFPO dimer acid concentrations of -475 ng/L.
Three European studies on GenX chemicals occurrence in drinking water were identified: two
studies that analyzed drinking water samples from the vicinity of the same fluorochemical plant
in the Netherlands (Brandsma et al., 2019; Gebbink et al., 2017), and a third that analyzed
drinking water from areas of Belgium and the Netherlands, some of which were in the vicinity of
known PFAS point sources (Vughs et al., 2019). Gebbink et al. (2017) detected HFPO dimer
acid in drinking water samples from three of four sites in the vicinity of the fluorochemical plant,
at concentrations of 0.25, 0.48, and 11 ng/L, respectively. All three sites at which HFPO dimer
acid was detected were downstream of the plant; the high concentration of 11 ng/L was
measured at the downstream site closest to the plant. HFPO dimer acid was not detected in
samples from two control sites nor in a sample from a site upstream of the plant. Brandsma et al.
(2019) analyzed drinking water at residential homes from six different municipalities within 50
km of the same fluorochemical plant featured in the study by Gebbink et al. (2017). The
measured levels of HFPO dimer acid ranged from 1.4 to 8.1 ng/L; the highest concentration (8.1
ng/L) was measured at the sampling site that was closest to and downstream of the plant. Vughs
et al. (2019) analyzed drinking water from 11 water suppliers at sites in Belgium and the
Netherlands, some of which were in the vicinity of a fluoropolymer manufacturing plant. HFPO
dimer acid was detected in 46% of samples, with a mean concentration of 2.9 ng/L and
maximum concentration of 28 ng/L. The study reported that concentrations above 4 ng/L were
measured in drinking water from suppliers that sourced surface water in the vicinity of the
fluoropolymer manufacturing plant in the Netherlands. However, the study did not map the
distribution of reported concentrations by geographic location or with respect to distance from
the fluoropolymer manufacturing plant.
1.4.2.2 Groundwater
Petre et al. (2021) quantified the mass transfer of PFAS, including GenX chemicals, from
contaminated groundwater to five tributaries of the Cape Fear River. All sampling sites were
located within 5 km of a manufacturing plant known known to be a major source of PFAS
contamination. HFPO dimer acid and another fluoroether (perfluoro-2-[perfluoromethoxy]
propanoic acid) together accounted for 61% of the total quantified PFAS. The study authors
6
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calculated that approximately 32 kg/year of PFAS is discharged from contaminated groundwater
to the five tributaries. These data indicate that the discharge of contaminated groundwater has led
to long-term contamination from GenX chemicals in surface water and could lead to subsequent
impacts on downstream drinking water (Petre et al., 2021).
In a European study, Vughs et al. (2019) reported that HFPO dimer acid was not detected in any
of five samples of groundwater obtained from water suppliers in the Netherlands and Belgium.
Some sampling locations were in the vicinity of a fluoropolymer manufacturing plant, but the
study did not identify the locations of sites relative to the plant.
1.4.2.3 Surface Water
Chemours has reported that GenX chemicals have been discharged into the Cape Fear River for
several decades as a byproduct of other manufacturing processes (NCDEQ, 2017). Additionally,
several studies evaluated the occurrence of GenX chemicals in surface waters, with studies
conducted in North America, Europe, Asia, and across multiple continents (see Appendix B,
Table B-l). As noted in the final toxicity assessment for GenX chemicals (U.S. EPA, 2021a),
GenX chemicals were first detected in North Carolina's Cape Fear River and its tributaries in the
summer of 2012 (Pritchett et al., 2019; Strynar et al., 2015). Since that finding, U.S. studies of
surface waters, some of which are source waters for PWSs, have reported results of sampling
efforts from contaminated areas near the Cape Fear River (McCord et al., 2018; Sun et al., 2016)
and in Ohio and West Virginia (Galloway et al., 2020).
In studies of the Cape Fear River basin by McCord et al. (2018) and Sun et al. (2018), surface
water concentrations of GenX chemicals ranged from below the NCDHHS PHG of 140 ng/L to a
maximum level of 4,560 ng/L. Sun et al. (2016) analyzed surface water from two sites upstream
of a DWTP and one site downstream. They reported a median HFPO dimer acid concentration of
304 ng/L with a maximum of 4,560 ng/L in the source water of the plant. HFPO dimer acid
levels did not exceed the quantitation limit (10 ng/L) at the two upstream locations. In source
water samples collected from the Cape Fear River near a DWTP downstream of a fluorochemical
manufacturer, McCord et al. (2018) reported initial HFPO dimer acid concentrations of
approximately 700 ng/L. After the manufacturer diverted waste stream emissions from one of its
manufacturing lines, the measured concentrations decreased to levels below the NCDHHS PHG
(140 ng/L).
In Ohio and West Virginia, Galloway et al. (2020) sampled rivers and streams located upstream,
downstream, and downwind to the north and northeast of the Chemours Washington Works
facility outside Parkersburg, West Virginia. The downwind sampling was intended to explore
potential airborne deposition. Some of the downstream sampling sites were in the vicinity of
landfills. Reported levels of HFPO dimer acid in these waters ranged from non-detectable levels
to a maximum of 227 ng/L. The highest HFPO dimer acid concentrations were measured
downwind of the facility (i.e., to the northeast). The study observed an exponentially declining
trend of HFPO dimer acid concentrations in surface water with distance from the facility in this
direction and attributed its occurrence in surface water to air dispersion of emissions from the
facility. The most distant site where HFPO dimer acid was detected was 24 km north of the
facility.
7
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In one study of sites located in highly industrialized commercial waterways (authors did not
indicate whether sampling sites were in the vicinity of known PFAS point sources), Pan et al.
(2018) detected HFPO dimer acid in 100% of samples from sites in the Delaware River (n=12),
reporting median and maximum concentrations of 2.02 ng/L and 8.75 ng/L, respectively, in
surface waters.
Globally, GenX chemicals occurrence has been reported in surface waters from Germany
(Heydebreck et al., 2015; Pan et al., 2018), China (Heydebreck et al., 2015; Li et al., 2020a; Pan
et al., 2017, 2018; Song et al., 2018), the Netherlands (Gebbink et al., 2017; Heydebreck et al.,
2015; Pan et al., 2018), the United Kingdom (Pan et al., 2018), South Korea (Pan et al., 2018),
and Sweden (Pan et al., 2018). HFPO dimer acid was also detected with a mean concentration of
30 picograms per liter (pg/L; 0.030 ng/L) in Artie seawater samples, suggesting long-range
transport (Joerss et al., 2020).
In one study of surface water collected from industrialized areas in Europe (authors did not
indicate whether sampling sites were in the vicinity of known PFAS point sources), Pan et al.
(2018) reported HFPO dimer acid detections in 100% of samples from the Thames River in the
United Kingdom (n=6 sites), the Rhine River in Germany and the Netherlands (n=20 sites), and
the Malaren Lake in Sweden (n=10 sites). Across these three river systems, median HFPO dimer
acid concentrations ranged from 0.90 to 1.38 ng/L and the highest concentration detected was
2.68 ng/L.
Heydebreck et al. (2015) detected HFPO dimer acid at 17% of sampling locations on the
industrialized non-estuarine reaches of the Rhine River, with a maximum concentration of 86.08
ng/L; however, HFPO dimer acid was not detected at locations on the Elbe River.
Gebbink et al. (2017) evaluated surface water samples upstream and downstream of a
fluorochemical production plant in the Netherlands and reported only one of three samples
upstream of the plant with detectable HFPO dimer acid concentrations (22 ng/L; method
quantification limit [MQL] = 0.2 ng/L). Downstream of the fluorochemical plant, HFPO dimer
acid was detected in 100% of samples, with a mean concentration of 178 ng/L and a range of 1.7
to 812 ng/L. Vughs et al. (2019) analyzed surface water from 11 water suppliers in the
Netherlands and Belgium, some of which were located in the vicinity of a fluoropolymer
manufacturing plant. The authors reported HFPO dimer acid detections in 77% of surface water
samples (n=13) with a mean concentration of 2.2 ng/L and a maximum of 10.2 ng/L; however,
only three samples in the study had HFPO dimer acid concentrations exceeding 1 ng/L.
Of the five studies conducted in China, one study evaluated surface water samples from an
industrialized region (authors did not indicate whether sampling sites were in the vicinity of
known PFAS point sources) (Pan et al., 2018), one study evaluated surface water river and
reservoir samples in an industrialized river basin with potential PFAS point sources (Li et al.,
2020a), and three studies examined samples from sites along the Xiaoqing river at locations
upstream, downstream, or in the vicinity of known PFAS sources (Heydebreck et al., 2015; Pan
et al., 2017; Song et al., 2018). GenX chemicals were detected in freshwater systems sampled in
all five studies, though HFPO dimer acid concentrations appeared to be positively correlated
with proximity to known PFAS point sources. Song et al. (2018), Pan et al. (2017), and
Heydebreck et al. (2015) sampled sites in the Xiaoqing River system, including one of its
tributaries, nearby a known fluoropolymer production facility. These three studies reported
8
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maximum HFPO dimer acid concentrations of 9,350, 2,060, and 3,060 ng/L, respectively. HFPO
dimer acid concentrations in samples collected upstream of the facility did not exceed 3.64 ng/L.
Other Chinese freshwater systems evaluated in the other two studies (Li et al., 2020a; Pan et al.,
2018) generally reported maximum concentrations similar to those from the upstream Xiaoqing
River system sites (< 10.3 ng/L), except for one site in Tai Lake which was reported to have a
maximum HPFO dimer acid concentration of 143 ng/L. Similarly, in a study that sampled an
industrialized river in South Korea (authors did not report whether sampling sites were in the
vicinity of known PFAS point sources), HFPO dimer acid was found in 100% of samples and the
maximum concentration found was 2.49 ng/L (Pan et al., 2018).
1.4.3 Exposure in Humans
As described in the Human Health Toxicity Values for Hexajluoropropylene Oxide (HFPO)
Dimer Acid and Its Ammonium Salt (CASRN13252-13-6 and CASRN 62037-80-3) Also Known
as "GenXChemicals" (U.S. EPA, 2021a), PFAS including GenX chemicals were analyzed in
2,682 urine samples of children > 6 years of age collected as part of the 2013-2014 National
Health and Nutrition Examination Survey (NHANES) (Calafat et al., 2019). GenX chemicals
were detected (limit of detection of 0.1 (J,g/L) in the urine in approximately 1.2% of the
population, though this limit of detection is 10-fold greater than the lifetime HA, which may lead
to the low rate of urine positivity. The finding for GenX chemicals was similar to PFOA and
PFOS which were only detected in paired urine samples for < 0.1% of the same population. In
serum samples, PFOA and PFOS were detected in > 98% of this same study population (HFPO
dimer acid was not measured), demonstrating that serum is a better biomarker than urine for
PFAS.
The Chemours Company submitted a report to EPA of their analysis of HFPO dimer acid
assessment in 24 human plasma samples. The results of their analysis are publicly available in a
truncated study report that does not appear to be peer-reviewed or be the results of an
epidemiology study. The results of their analysis found HFPO dimer acid at concentrations
ranging from 1.0 ng/mL (reporting limit) to 51.2 ng/mL in plasma samples (DuPont-
C30031 516655, 2017). HFPO dimer acid was not detected above the analytical reporting limit
of less than 1.0 ng/mL in seven of the samples. However, it is important to note that
interpretation of these results is difficult given that the publicly available information is lacking
study design details, study participant characteristics, or exposure detail (e.g., "some of these
workers are in areas with potential for exposure, others are not.")
Concern in the Cape Fear Watershed communities about the detection of GenX chemicals in
water led to the initiation of a human exposure study in this area.8 In blood samples from 344
Wilmington, North Carolina residents collected between November 2017 and May 2018
(including repeat sampling of 44 participants), GenX chemicals were not detected above the
analytical reporting limit of 2 ng/mL in any of the blood samples collected (Kotlarz et al., 2020).
It is difficult to draw conclusions about GenX exposure because discharge control of GenX
chemicals from the nearby Chemours Fayetteville Works plant began in June of 2017 and by
September of 2017, the facility stopped discharging process wastewater containing PFAS into
the Cape Fear River. Also, it is unknown whether study participants were drinking tap water,
bottled water, or filtered tap water at the time of sample collection. GenX chemicals were not
8 See GenX Exposure Study website, located at fattps:IIgenxstudy .ncsu.edu/
9
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detected in a study from the Cape Fear River that measured concentrations of GenX chemicals
and other PFAS in the urine and serum of nearby residents who had high concentrations of GenX
in their drinking water wells (Pritchett et al., 2019). The authors indicated that it was not known
if residents were using the well water or bottled water, but this finding does support the shorter
ti/2 in humans for GenX chemicals in comparison to other PFAS.
2 J Problem Formulation and Scope
2.1 Conceptual Model
A conceptual model provides useful information to characterize and communicate the potential
health risks related to GenX chemicals exposure from drinking water and to outline the scope of
the HA. The sources of GenX chemicals, the routes of exposure for biological receptors of
concern (e.g., various human activities related to tap water ingestion such as drinking, food
preparation, and consumption), the potential health effects, and exposed populations including
sensitive populations and life stages are depicted in the conceptual diagram below (Figure 1).
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STRESSOR(S)
HFPO Dimer Acid and its Ammonium Salt
Ambient
POTENTIAL
Drinking
Water
Ground
and
Industrial
Uses
Soil
Food
Air
Dust
Sediment
SOURCES
Surface
Water
RSC
Derivation
POTENTIAL
EXPOSURE
ROUTES
Final Toxicity
Assessment for
GenX Chemicals
(U.S. EPA, 2021a)
Oral
(includes drinking water, cooking with
water, incidental ingestion during
showering/bathing)
Dermal
(includes showering/bathing)
AFFECTED
HEALTH
OUTCOMES
POTENTIALLY SENSITIVE
POPULATIONS WITHIN
GENERAL POPULATION
Inhalation
(includes incidental inhalation during
showering/bathing)
Liver
Hematological
Reproductive/
Developmental
Kidney
Immune
Cancer
Adults
Women of Child-
Bearing Age
Children (including
breastfed and/or
formula-fed infants)
Pregnant Women
Lactating
Women
EF Selection
Legend
Dark Blue = Information used for
deriving HA value
Light Blue = Information available
but not used for deriving HA value
Gray - Out of scope for deriving HA
value
Figure 1. Conceptual Model for the Development of the Drinking Water Health Advisory for GenX Chemicals
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The conceptual model is intended to explore potential links between exposure to a contaminant
or stressor and the adverse health outcomes, and to outline the information sources used to
identify or derive the input values used for the HA derivation, which are the RfD, relative source
contribution (RSC), and exposure factor (EF). The conceptual model also illustrates the scope of
the GenX chemicals HA, which considers the following factors:
Stressors: The scope of this drinking water HA includes the two main GenX chemicals, the
HFPO dimer acid and its ammonium salt, consistent with the scope of the 2021 toxicity
assessment for GenX chemicals (U.S. EPA 2021a). The HFPO dimer acid and its ammonium salt
are the two current commercial products of the GenX technology.
Potential Sources of Exposure: The scope of exposure sources considered for the HA
derivation is limited to drinking water from public water facilities or private wells. Sources of
exposure to GenX chemicals include both ground and surface waters used for drinking. To
develop the RSC, information about non-drinking water sources was identified to determine the
portion of the RfD attributable to drinking water. Non-drinking water sources of GenX chemicals
for which studies were identified include foods, indoor dust, soil, air, and sediment. Consumer
products and biosolids are other potential sources of exposure but relevant studies were not
identified (see Section 3.3.1). Since GenX chemicals are replacements for PFOA, they could be
present in consumer products (e.g., stain- and water-repellent textiles). Information on specific
products containing GenX chemicals is not available, but they may be present in consumer
products within the home, workplace, schools, and daycare centers.
Potential Exposure Routes: Oral exposure to GenX chemicals from contaminated drinking
water sources (e.g., via drinking water, cooking with water, and incidental ingestion from
showering) is the focus of the HA. The drinking water HA value does not apply to other
exposure routes. However, information on other potential routes of exposure including dermal
exposure (contact of exposed parts of the body with water containing GenX chemicals during
bathing, showering, etc.) and inhalation exposure (during bathing or showering, using a
humidifier or vaporizer, etc.) was considered to develop the RSC.
Affected Health Outcomes: The toxicity assessment for GenX chemicals (U.S. EPA, 2021a)
considered all publicly available human, animal, and mechanistic studies of effects after
exposure to GenX chemicals. The evaluation identified associations between GenX chemicals
exposure and the following health outcomes: hepatic, hematological, developmental/
reproductive, renal, immune and cancer.
Potentially Sensitive Populations and Life Stages: The receptors are humans in the general
population who could be exposed to GenX chemicals from tap water through ingestion at their
homes and other places (e.g., workplaces, schools, daycare centers). Within the general
population, there are potentially sensitive populations or life stages that may be more susceptible
due to increased exposure and/or response. Potentially sensitive populations include pregnant
women, women of childbearing age, and lactating women.
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2.2 Analysis Plan
2.2.1 Health Advisory Guidelines
Assessment endpoints for HA guidelines or values can be developed, depending on the available
data, for both short-term (one-day and ten-day) and lifetime exposure using information on the
noncarcinogenic and carcinogenic toxicological endpoints of concern. Where data are available,
HAs can reflect sensitive populations or life stages that may be more susceptible and/or more
highly exposed.
One-Day HA is protective of noncancer effects for up to 1 day of exposure and is
typically based on an in vivo toxicity study with a duration of 7 days or less. It is
typically calculated for an infant.
Ten-Day HA is protective of noncancer effects for up to 10 days of exposure and is
typically based on an in vivo toxicity study with a duration of 7 to 30 days. It is
typically calculated for an infant.
Lifetime HA is designed to be protective of noncancer effects over a lifetime of
exposure and is typically based on a chronic in vivo experimental animal toxicity
study and/or human epidemiological data.
10"6 Cancer Risk Concentration is the concentration of a carcinogen in water at
which the population is expected to have a one in a million (10"6) excess cancer risk
above background after exposure to the contaminant over a lifetime. It is calculated
for carcinogens classified as known or likely human carcinogens (U.S. EPA, 1986,
2005b). Cancer risk concentrations are not derived for substances for which there is
suggestive evidence of carcinogenic potential unless the cancer risk has been
quantified.
2.2.2 Sources of Toxicity Information for Health Advisory Development
The final toxicity assessment for GenX chemicals, entitled Human Health Toxicity Values for
Hexafluoropropylene Oxide (HFPO) Dimer Acid and Its Ammonium Salt (CASRN13252-13-6
and CASRN 62037-80-3) Also Known as "GenXChemicals" published in October 2021 (U.S.
EPA, 2021a), serves as the basis of the toxicity information and chronic RfD used to derive the
lifetime noncancer HA for GenX chemicals. It also synthesizes and describes other information
on GenX chemicals including physiochemical properties and toxicokinetics. This final toxicity
assessment was published after a rigorous process of literature review, draft assessment
development, agency and interagency review, an independent peer review, public comment, an
independent expert review of data from two studies by the National Toxicology Program, and a
second independent peer review.
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2.2.3 Approach and Scope for Health Advisory Derivation
2.2.3.1 Approach for Deriving Noncancer HAs
The following equations (Eqs. 1-3) are used to derive the HAs.9 Lifetime HAs and 10"6 cancer
risk concentrations are only derived for chemicals without an existing National Primary Drinking
Water Regulation.
/ POD \
0^^ HA =(UFc,DW[-Bwj
POD is typically derived from a toxicity study of duration 7 days or less
(Eq. 1)
/ POD \
Ten-Day HA =(UFc^DWI BW)
POD is typically derived from a toxicity study of duration 7-30 days
(Eq. 2)
( R® \
Lifetime HA = I ^t,tt ^t,t I * RSC
VDWI-BW/
RfD is typically derived from a chronic study
(Eq. 3)
Where:
POD is the point of departure, typically a lowest observed adverse effect level (LOAEL), a no
observed adverse effect level (NOAEL), or a benchmark dose (BMD) (lower confidence limit;
BMDL) from the critical study.
UFc is the composite UF or total UF value after multiplying individual UFs. UFs are established
in accordance with EPA best practices (U.S. EPA, 2002) and consider uncertainties related to the
following: variation in sensitivity among the members of the human population (i.e., inter-
individual variability), extrapolation from animal data to humans (i.e., interspecies uncertainty),
extrapolation from data obtained in a study with less-than-lifetime exposure to lifetime exposure
(i.e., extrapolating from subchronic to chronic exposure), extrapolation from a LOAEL rather
than from a NOAEL, and extrapolation when the database is incomplete. For GenX chemicals,
the value of UFc was determined in the final toxicity assessment (U.S. EPA, 2021a).
DWI-BW is the 90th percentile drinking water intake (DWI), adjusted for body weight (bw), for
the selected population in units of liter per kilogram body weight per day (L/kg bw-day). The
DWI-BW considers direct and indirect consumption of tap water (indirect water consumption
encompasses water added in the preparation of foods or beverages, such as tea and coffee). For
GenX chemicals, the value of this parameter is based on the critical study identified in the GenX
chemicals final toxicity assessment (U.S. EPA, 2021a), and is identified in Chapter 3 of EPA's
Exposure Factors Handbook (EFH) (U.S. EPA, 2019a).
RfD is the chronic 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
9 https://www.epa.gov/systeiii/files/documents/2022-01/dwtable2018.pdf
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without an appreciable risk of deleterious effects during a lifetime. The value of this parameter
was derived in the final GenX chemicals toxicity assessment and is based on the critical effect
and study identified in that assessment (U.S. EPA, 2021a).
RSC is the relative source contribution—the percentage of the total oral exposure attributed to
drinking water sources (U.S. EPA, 2000a) where the remainder of the exposure is allocated to
other routes or sources. The RSC is calculated by examining other sources of exposure (e.g., air,
food, soil) and pathways of exposure in addition to drinking water using the methodology
described for calculation of an RSC described in U.S. EPA (2000a) and Section 3.3.2.
2.2.3.2 Scope of Noncanc lih Advisory Values
Adequate data are available to derive a lifetime HA for GenX chemicals. EPA's final toxicity
assessment for GenX chemicals derived subchronic and chronic RfDs but not an acute or short-
term RfD (U.S. EPA, 2021a). Due to the lack of an available short duration (30 day or less
exposure duration) toxicity value for GenX chemicals, EPA did not develop a one-day or ten-day
HA value. Specifically, EPA did not derive an RfD for durations of 7-day or less exposure period
on which to base a one-day HA or an RfD for a 7-to-30-day exposure on which to base a ten-day
HA for GenX chemicals in the toxicity assessment (U.S. EPA, 2021a). Information about the
available acute and short-term toxicity studies for HFPO dimer acid and its ammonium salt can
be found in Sections 4.1 and 4.2 and Appendix B of the toxicity assessment (U.S. EPA, 2021a).
2.2.3.3 Approach and Scope for Deriving Cancer Risk Concentrations
The following equations (Eqs. 4-5) are used to derive cancer risk concentrations.
Calculated for non-mutagenic carcinogens10 only:
lxlO-6
10 b Cancer Risk Concentration = ———^T.TT ^T.T
CSF * DWI-BW
(Eq. 4)
Calculated for mutagenic carcinogens only:
lxlO-6 v1 /Fi*ADAFi\
10 b Cancer Risk Concentration = — * > ^T.TT ^T.T
CSF \ DWI-BW; /
(Eq. 5)
Where:
CSF is the cancer slope factor—an upper bound, approximating a 95 percent confidence limit of
the increased cancer risk from a lifetime of oral exposure to a stressor. The value for this
parameter is derived in the final toxicity assessment when data are available.
DWI-BWi is the 90th percentile bw-adjusted DWI in units of L/kg bw-day for each age group
(i), considered when calculating cancer risk concentrations for mutagenic carcinogens.
10 https://www.epa.gov/system/files/documents/2022-01/dwtable2018.pdf
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ADAFi is the age-dependent adjustment factor for each age group (i), used when calculating
cancer risk concentrations for carcinogens that act via a mutagenic mode of action (U.S. EPA,
2005a,b).
Fi is the fraction of life spent in each age group (i), used when calculating cancer risk
concentrations for mutagens (U.S. EPA, 2005a).
2.2.3.4 Scope of Cancer Risk Concentration Deri vation
For cancer toxicity, EPA's toxicity assessment for GenX chemicals (U.S. EPA, 2021a) evaluated
the weight of the evidence for cancer among the available cancer studies for GenX chemicals
exposure per EPA's Guidelines for Carcinogen Risk Assessment (U.S. EPA, 2005b). Based on
the evaluation of the limited (i.e., one study) data for GenX chemicals, EPA concluded that there
is Suggestive Evidence of Carcinogenic Potential of oral exposure to GenX chemicals in
humans. EPA's conclusion is based on the findings of female hepatocellular adenomas and
hepatocellular carcinomas and male combined pancreatic acinar adenomas and carcinomas
observed in the chronic 2-year study in rats (for more information see U.S. EPA [2021a]). The
single cancer bioassay for HFPO dimer acid ammonium salt showed increased incidence of liver
tumors (females) and combined pancreatic acinar adenomas and carcinomas (males) in rats at the
high doses only. A CSF was not derived in the toxicity assessment for GenX chemicals (U.S.
EPA, 2021a). This is consistent with EPA's Guidelines for Carcinogen Risk Assessment (U.S.
EPA, 2005a) which state that when the available evidence is suggestive for carcinogenicity, a
quantitative risk estimate is generally not derived unless there exists a well-conducted study that
could facilitate an understanding of the magnitude and uncertainty of potential risks, ranking
potential hazards, or setting research priorities (U.S. EPA, 2005a). In the toxicity assessment for
GenX chemicals, EPA concluded that the available human and animal studies are not sufficient
to establish a reasonable understanding of the magnitude and uncertainty of potential risks for
exposure to GenX chemicals and tumor incidence, and therefore do not justify a quantitative
cancer assessment (U.S. EPA, 2021a). Consistent with EPA's guidelines, a CSF was not derived
in the toxicity assessment for GenX chemicals (U.S. EPA, 2021a). Therefore, EPA did not derive
a 10"6 cancer risk concentration in this HA for GenX chemicals.
2.2.4 Exposure Factors for Deriving Health A dvisory
2.2.4.1 Exposure Factor Selection
An EF, such as body weight-adjusted drinking water intake (DWI-BW), is one of the input
values for deriving a drinking water HA. EFs are factors related to human activity patterns,
behavior, and characteristics that help determine an individual's exposure to a contaminant.
EPA's EFH11 is a resource for conducting exposure assessments and provides EFs based on
information from publicly available, peer-reviewed studies. Chapter 3 of the EFH presents EFs
in the form of DWIs and DWI-BWs for various populations or life stages within the general
population (U.S. EPA, 2019a). The use of EFs in HA calculations is intended to protect sensitive
populations and life stages within the general population from adverse effects resulting from
exposure to a contaminant.
11 EPA's EFH is available at https://www.epa.gov/expobox/about-exposure-factors-handbook
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When developing HAs, the goal is to protect all ages of the general population including
potentially sensitive populations or life stages such as children. The approach to select the EF for
the drinking water HA 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. Although data gaps can make it difficult to
identify the most sensitive population (e.g., not all windows of exposure or health outcomes have
been assessed in studies of GenX chemicals), the critical effect and POD that form the basis for
the RfD can provide some information about sensitive populations because the critical effect is
typically observed at the lowest tested dose among the available data. Evaluation of the critical
study, including the exposure interval, may identify a particularly 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 EFH (U.S.
EPA, 2019a) to derive the HA. When multiple populations or life stages are identified based on
the critical effect or other health effects data (from animal or human studies), EPA selects the
population or life stage with the greatest DWI-BW because it is the most health protective. For
deriving lifetime HAs, the RSC corresponding to the sensitive life stage is also determined (see
Section 3.3), and the most health-protective RSC is selected when data are available for multiple
sensitive populations or life stages. In the absence of information indicating a sensitive
population or life stage, the DWI-BW corresponding to all ages of the general population may be
selected.
To derive a chronic HA, EPA typically uses DWI normalized to body weight (i.e., DWI-BW in L
of water consumed/kg bw-day) for all ages of the general population or for a sensitive population
or life stage, when identified. The Joint Institute for Food Safety and Applied Nutrition's Food
Commodity Intake Database (FCID) Consumption Calculator Tool12 includes the EFs from
EPA's EFH and can also be used to estimate DWI-BW for specific populations or life stages
across a designated age range. EPA uses the 90th percentile DWI-BW to ensure that the HA is
protective of the general population as well as sensitive populations or life stages (U.S. EPA,
2000a, 2016a). In 2019, EPA updated its EFs for DWI and DWI-BW based on newly available
science (U.S. EPA, 2019a).
Table 3 shows EPA EFs for some sensitive populations or life stages. Other populations or life
stages may also be considered depending on the available information regarding sensitivity to
health effects after exposure to a contaminant.
Table 3. EPA Exposure Factors for Drinking Water Intake
Population or
Life Stage
DWI-BW
(L/kg bw-day)
Description of Exposure Metric
Source
General
population (all
ages)
0.0338
90th percentile direct and indirect
consumption of community water,
consumer-only two-day average, all
ages.
2019 Exposure Factors
Handbook Chapter 3,
Table 3-21, NHANES
2005-2010 (U.S. EPA,
2019a)
12 Joint Institute for Food Safety and Applied Nutrition's FCID, Commodity Consumption Calculator is available at
https://fcid.foodrisk.org/percentiles
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Population or
Life Stage
DWI-BW
(L/kg bw-day)
Description of Exposure Metric
Source
Children
0.143
90th percentile direct and indirect
consumption of community water,
consumer-only two-day average, birth
to < 1 year.
2019 Exposure Factors
Handbook Chapter 3,
Table 3-21, NHANES
2005-2010 (U.S. EPA,
2019a)
Formula-fed
infants
0.249
90th percentile direct and indirect
consumption of community water,
formula-consumers only, 1 to < 3
months. Includes water used to
reconstitute formula plus all other
community water ingested.
Kahn et al. (2013),
Estimates ofWater
Ingestion in Formula by
Infants and Children
Based on CSFII 1994-
1996 and 1998ab
Pregnant women
0.0333
90th percentile direct and indirect
consumption of community water,
consumer-only two-day average.
2019 Exposure Factors
Handbook Chapter 3,
Table 3-63, NHANES
2005-2010 (U.S. EPA,
2019a)
Women of
childbearing age
0.0354
90th percentile direct and indirect
consumption of community water,
consumer-only two-day average, 13 to
<50 years.
2019 Exposure Factors
Handbook Chapter 3,
Table 3-63, NHANES
2005-2010 (U.S. EPA,
2019a)
Lactating women
0.0469
90th percentile direct and indirect
consumption of community water,
consumer-only two-day average.
2019 Exposure Factors
Handbook Chapter 3,
Table 3-63, NHANES
2005-2010c (U.S. EPA,
2019a)
Notes: CSFII = continuing survey of food intake by individuals; L/kg bw-day = liter per kilogram body weight per day.
a The sample size does not meet the minimum reporting requirements as described in the Third Report on Nutrition Monitoring in
the United States (LSRO, 1995).
b Chapter 3.2.3 in U.S. EPA (2019a) cites Kahn et al. (2013) as the source of drinking water ingestion rates for formula-fed
infants. While U.S. EPA (2019a) provides the 95th percentile total direct and indirect water intake values, Office of
Water/Office of Science and Technology (OW/OST) policy is to utilize the 90th percentile DWI-BW. OW/OST was able to
identify the 90th percentile DWI-BW in Kahn et al. (2013) and report the value in this table.
c Estimates are less statistically reliable based on guidance published in the Joint Policy on Variance Estimation and Statistical
Reporting Standards on NHANES III and CSFII Reports: Human Nutrition Information Service (HNIS)/National Center for
Health Statistics (NCHS) Analytical Working Group Recommendations (NCHS, 1993).
2.2.4.2 Determining Proportion of RfD A tlribiituble to Drinking Water
To account for aggregate risk from exposures and exposure pathways other than oral ingestion of
drinking water, EPA applies an RSC when calculating HAs to ensure that total human exposure
to a contaminant does not exceed the daily exposure associated with the RfD. 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 is allocated to other potential exposure sources
(U.S. EPA, 2000a). The purpose of the RSC is to ensure that the level of a contaminant (e.g., HA
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value), when combined with other identified sources of exposure common to the population of
concern, will not result in exposures that exceed the RfD (U.S. EPA, 2000a).
To determine the RSC, EPA follows the Exposure Decision Tree for Defining Proposed RfD (or
POD/UF) Apportionment in EPA's guidance, Methodology for Deriving Ambient Water Quality
Criteria for the Protection of Human Health (U.S. EPA, 2000a). EPA considers whether there
are significant known or potential uses/sources 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 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 exposure.
Per EPA's guidance, in the absence of adequate data to quantitatively characterize exposure to a
contaminant, EPA typically recommends an RSC of 20%. 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% based on the available data, thereby allocating
the remaining 20% to other potential exposure sources (U.S. EPA, 2000a).
To inform the RSC determination, available information on all exposure sources and routes for
GenX chemicals was identified using the literature search and screening method described in
Appendix A. To identify information on GenX chemicals exposure routes and sources to inform
RSC determination, EPA considered primary literature published between 2003-2020 and
collected by EPA ORD as part of an effort to evaluate evidence for pathways of human exposure
to eight PFAS, including GenX chemicals. To consider more recently published information on
exposure to GenX chemicals, EPA incorporated the results of a date-unlimited gray literature
search that was conducted in February 2022 as well as an ad hoc process to identify relevant and
more recently published peer-reviewed scientific literature. The literature resulting from the
search and screening process included only final (not draft) documents and articles that were
then reviewed to inform the RSC for GenX chemicals.
3 J Health Advisory Input Tallies
3.1 Toxicity Assessment Values
Table 4 summarizes the peer-reviewed chronic noncancer toxicity values for HFPO dimer acid
and its ammonium salt from EPA's Human Health Toxicity Values for Hexafluoropropylene
Oxide (HFPO) Dimer Acid and Its Ammonium Salt (CASRN13252-13-6 and CASRN 62037-80-
3) Also Known as "GenXChemicals" (U.S. EPA, 2021a).
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Table 4. Chronic Noncancer Toxicity Information for GenX Chemicals for Deriving the
Lifetime HA
Health Assessment
GenX
Chemicals
Exposure in
Critical Study
RfD
(mg/kg
bw-day)
Critical Effect
Principal Study
Human Health Toxicity
Values for
Hexafluoropropylene
Oxide (HFPO) Dimer
Acid and Its Ammonium
Salt (CASRN 13252-13-
6 and CASRN 62037-80-
3) Also Known as "GenX
Chemicals"
(U.S. EPA, 2021a)
Pre-mating day
14 through
lactation day
21
3xl0"6
Constellation of liver
lesions (defined by the
National Toxicology
Program Pathology
Working Group to include
cytoplasmic alteration,
hepatocellular single cell
and focal necrosis, and
hepatocellular apoptosis) in
parental females
Oral reproductive
and
developmental
toxicity study
(Dupont18405-
1037, 2010)
Note: mg/kg bw-day = milligram per kilogram body weight per day.
As noted in EPA's toxicity assessment for GenX chemicals (U.S. EPA, 2021a), HFPO dimer
acid and its ammonium salt, chronic and reproductive and developmental oral animal toxicity
studies are available in rats and mice. Repeated-dose toxicity data are available for oral exposure.
The available studies report liver toxicity (e.g., increased relative liver weight, hepatocellular
hypertrophy, apoptosis, and single-cell/focal necrosis), kidney toxicity (e.g., increased relative
kidney weight), immune effects (e.g., antibody suppression), hematological effects (e.g.,
decreased red blood cell count, hemoglobin, and hematocrit), reproductive/developmental effects
(e.g., increased early deliveries, placental lesions, changes in maternal gestational weight gain,
and delays in genital development in offspring), and cancer (e.g., liver and pancreatic tumors)
after exposure to GenX chemicals. The available toxicity study findings demonstrate that the
liver is particularly sensitive to HFPO dimer acid and HFPO dimer acid ammonium salt
exposure.
The critical study selected for deriving the noncancer subchronic and chronic RfDs for HFPO
dimer acid and/or its ammonium salt was the oral reproductive/developmental toxicity study in
mice that reported a NOAEL of 0.1 milligrams per kilogram body weight per day (mg/kg bw-
day) based on liver effects (a constellation of lesions, including cytoplasmic alteration,
hepatocellular single-cell and focal necrosis, and hepatocellular apoptosis) in females (DuPont-
18405-1037, 2010; NTP, 2019). This endpoint was selected because the available health effects
studies indicate that the liver is the most sensitive target of toxicity from exposure to GenX
chemicals. Liver effects were observed in both male and female mice and rats after different
doses and durations of exposures. These adverse liver effects occurred at the lowest doses and
shortest durations of exposure to GenX chemicals among the available data (U.S. EPA, 2021).
Importantly, EPA determined that the liver lesions observed in the rodent are relevant to human
health (see U.S. EPA [2021a] for more information). Using EPA's Benchmark Dose Technical
Guidance Document (U.S. EPA, 2012), EPA modeled the dose-response relationship in the range
of observed data. Additionally, EPA's Recommended Use of Body Weight4 as the Default
Method in Derivation of the Oral Reference Dose (U.S. EPA, 2011) was used to allometrically
scale a toxicologically equivalent dose of orally administered agents from adult laboratory
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animals to adult humans. Allometric scaling addresses some aspects of cross-species
extrapolation of toxicokinetic and toxicodynamic processes (i.e., interspecies UFs). From BMD
modeling of the DuPont-18045-1037 study, the resulting PODhed is 0.01 mg/kg bw-day. For the
chronic RfD, a composite UF of 3,000 was applied based on a 10X for intraspecies variability
(UFh), 3X for interspecies differences (UFa), 10X for extrapolation from a subchronic to a
chronic dosing duration (UFs), and 10X for database deficiencies (UFd) to yield a chronic RfD
of 0.000003 mg/kg bw-day or 0.003 micrograms per kilogram body weight per day ((J-g/kg bw-
day) (see U.S. EPA [2021a] for more details).
3.2 Expo sure F actors
To identify potentially sensitive populations or life stages, EPA considered the sensitive life
stage of exposure associated with the critical effect on which the chronic RfD was based. In the
critical study selected in the toxicity assessment for GenX chemicals, parental female mice
(approximately 10 weeks old at the start of the study) were dosed daily for 2 weeks prior to
pairing, throughout gestation, and through to lactation day 20 for a total dosing duration of 53 to
65 days (Dupont 18405-1037, 2010). Therefore, exposure to GenX chemicals in the critical study
corresponds to three potentially sensitive adult female life stages, women of childbearing age,
pregnancy, and lactation (Table 5). For the calculation of the chronic HA for HFPO dimer acid
and its ammonium salt, EPA interpreted the observation of adverse liver effects in parental
females after exposure during pre-mating, pregnancy, and lactation as indicative of potentially
sensitive populations relevant to the chronic exposure scenario. The available data do not permit
a more precise identification of the most sensitive or critical window for GenX chemicals and the
adverse liver effects because studies. However, after 10-16 days of dosing during the gestation
period in mice, Blake et al. (2020) reported no significant changes in the observation of maternal
liver necrosis or liver serum enzymes changes (i.e., alkaline phosphatase, alanine
aminotransferase) in the 2 mg/kg bw-day dose group suggesting gestational dosing alone may be
insufficient to produce adverse liver effects. These studies suggest the potential for critical
windows of exposure across three potentially sensitive life stages: pre-conception or young
adulthood, pregnancy, and lactation.
Given the available information, EPA identified three potentially sensitive life stages for GenX
chemicals exposure—women of childbearing age (13 to < 50 years), pregnant women, and
lactating women (Table 5). The Eq. used to calculate a drinking water lifetime HA (Eq. 3; also
see Section 2.2.3) calculates the concentration of a contaminant in water based on the DWI for
the sensitive population identified from the available studies (Chapter 3 in U.S. EPA, 2019a).
Since all three life stages may represent critical windows of exposure to GenX chemicals and the
DWI is higher for lactating women than for women of childbearing age or pregnant women, the
DWI for lactating women was selected and is anticipated to be protective of the other two
sensitive life stages.
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Table 5. EPA Exposure Factors for Drinking Water Intake for Different Candidate
Sensitive Populations Based on the Critical Effect and Study
Population
DWI-BW
(L/kg bw-day)
Description of Exposure
Metric
Source
Women of
childbearing age
0.0354
90th percentile direct and
indirect consumption of
community water, consumer-
only two-day average, 13 to <
50 years.
2019 Exposure Factors
Handbook Chapter 3,
Table 3-63, NHANES
2005-2010 (U.S. EPA,
2019a)
Pregnant women
0.0333
90th percentile direct and
indirect consumption of
community water, consumer-
only two-day average.
2019 Exposure Factors
Handbook Chapter 3,
Table 3-63, NHANES
2005-2010 (U.S. EPA,
2019a)
Lactating women
0.0469
90th percentile direct and
indirect consumption of
community water, consumer-
only two-day average.
2019 Exposure Factors
Handbook Chapter 3,
Table 3-63, NHANES
2005-20103(U.S. EPA,
2019a)
Notes'. L/kg bw-day = liters of water consumed per kilogram body weight per day. The DWI-BW used to calculate the GenX
chemicals' lifetime HA is in bold.
a Estimates are less statistically reliable based on guidance published in the Joint Policy on Variance Estimation and Statistical
Reporting Standards on NHANES III and CSFII Reports: E1NIS/NCHS Analytical Working Group Recommendations (NCHS,
1993).
3.3 Relative Source Contribution
As stated in the analysis plan, EPA collected and evaluated information about GenX chemicals
exposure routes and sources to inform RSC determination. Results from the literature search are
described below.
3.3.1 Non-Drinking Water Sources and Routes
EPA presents information below from studies performed in the United States as well as studies
published globally for this emerging contaminant to be as comprehensive as possible, given that
the overall information is limited. While the studies from non-U.S. countries inform an
understanding of global exposure sources and trends, the RSC determination is based on the
available data for the Unites States.
3.3.1.1 Dietary Sources
HFPO dimer acid was included in a suite of individual PFAS selected as part of PF AS-targeted
reexaminations of samples collected for the U.S. Food and Drug Administration's (FDA's) Total
Diet Study (U.S. FDA, 2020a,b, 2021 a,b, 2022a,b); however, it was not detected in any of the
food samples tested. It should be noted that FDA indicated that the sample sizes were limited and
that the results should not be used to draw definitive conclusions about PFAS levels or presence
in the general food supply (U.S. FDA, 2022c). HFPO dimer acid was not detected in cow milk
samples collected from a farm with groundwater known to be contaminated with PFAS;
however, it was detected in produce (collard greens, cabbage) collected from an area near a
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PFAS production plant in FDA studies of the potential exposure to the U.S. population to PFAS
(U.S. FDA 2018, 2021c). GenX chemicals were detected at low levels in 14% of vegetable
garden crops (endive, beets, celery, lettuce, and tomatoes) grown near a PFAS manufacturing
facility in the Netherlands (Mengelers et al., 2018; NCDEQ, 2018c).
Feng et al. (2021) measured HFPO dimer acid in food samples collected from up to ten home
gardens or farms in villages within 15 km of a large fluoropolymer facility located on the
Dongzhulong River in Shandong Province, China. The authors detected HFPO dimer acid in
wheat (mean concentration: 5.53 nanograms per gram dry weight [ng/g dw]; range: 2.27-9.19
ng/g dw; detection frequency [DF] 100%), maize (mean concentration: 1.17 ng/g dw; range: not
detected (ND)-1.94 ng/g dw; DF 80%), and vegetable samples (mean concentration: 20.1 ng/g
dw; range: ND-67.2 ng/g dw; DF 82%). In fish collected at two sites along the Dongzhulong
River, HFPO dimer acid was detected at concentrations of 43.9 and 3.23 ng/g dw at sites
approximately 3 km and 15 km downstream of the fluoropolymer facility, respectively. HFPO
dimer acid was not found in eggs (home-produced and store-bought), store-bought meat or
seafood, or milk from domestic goats (Feng et al., 2021). Except for the fish sampled at two
sites, the study did not report HFPO dimer acid concentrations in food according to sampling
location or proximity to the fluoropolymer facility.
GenX chemicals were not target chemicals in EPA's National Lake Fish Tissue Study or EPA's
2015 Great Lakes Human Health Fish Fillet Tissue Study and they were not target chemicals in
EPA's 2008-2009 or 2013-2014 National Rivers and Streams Assessment studies (Stahl et al.,
2014; U.S. EPA, 2009a, 2020a, 2021e). GenX chemicals were detected in a redear sunfish fillet
composite sample collected from a privately-owned lake near a PFAS manufacturing facility in
North Carolina at a concentration of 270 nanograms per kilogram (ng/kg) (wet weight tissue)
(U.S. EPA, 2021a; NCDEQ, 2018c). GenX chemicals were not included in the National Oceanic
and Atmospheric Administration's National Centers for Coastal Ocean Science, National Status
and Trends Data (NOAA, 2022). Li et al. (2021) found HFPO dimer acid in fish collected from a
Xiaoqing River estuary impacted by PFAS discharge from fluoropolymer manufacturing
industry, at concentrations ranging from ND to 3.47 ng/g dw (mean concentration: 0.93 ng/g
dw).
5.5. /. 2 Consumer Products
Although no specific studies on the occurrence of GenX chemicals in consumer products were
identified, DuPont began transitioning to GenX processing aid technology in 2009 to work
toward eliminating long-chain PFAS as part of the company's commitment under the 2010/2015
PFOA Stewardship Program (U.S. EPA, 2021a). It is unknown if GenX chemicals in consumer
products have increased as a result of this transition.
3,3.1.3 Indoor Dust
Feng et al. (2021) detected HFPO dimer acid in indoor dust samples taken from homes from 10
villages within 15 km of a large fluoropolymer facility in Shandong Province, China, at
concentrations ranging from ND to 841 ng/g (mean concentration 159 ng/g; DF 72%).
Contaminated dust was found in homes as far as 15 km from the fluoropolymer facility and
HFPO dimer acid concentrations were highest in homes nearest to the facility. Although only
23
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one study on the occurrence of GenX chemicals in indoor dust was identified, PFAS have been
detected in indoor dust and on window films (ATSDR, 2021).
3.3.1.4 Air
PFAS have been released to air from wastewater treatment plants, waste incinerators, and
landfills (U.S. EPA, 2016a). GenX chemicals could be transported in the vapor phase or with
particulates (U.S. EPA, 2021a). When released to air or volatilized from water, GenX chemicals
are stable and short- and long-range transport has occurred (D'Ambro et al., 2021; Galloway et
al., 2020). Galloway et al. (2021) analyzed HFPO dimer acid concentrations in soil samples
downwind of and surface water samples upstream of the Chemours Washington Works facility
outside of Parkersburg, West Virginia, and results suggest atmospheric transport of HFPO dimer
acid emissions. Additionally, a study that modeled the atmospheric transport of a PFAS mixture
containing GenX chemicals from a fluoropolymer manufacturing facility in North Carolina
(D'Ambro et al., 2021) predicted that only 2.5% of total GenX (consisting of HFPO dimer acid
and HFPO dimer acid fluoride) would be deposited within 150 km of the facility (U.S. EPA,
2021a).
HFPO dimer acid and its ammonium salt are persistent in air (half-lives longer than 6 months),
and they are not readily broken down by biodegradation, direct photolysis, or hydrolysis (U.S.
EPA, 2021a). In the vapor phase, HFPO dimer acid and its ammonium salt are expected to
undergo hydroxyl radical-catalyzed indirect photolysis slowly, with a predicted average
hydroxylation rate of 8.50 x 10"13 cubic centimeters (cm3)/molecule - second (U.S. EPA, 2021a,
2022a,b). Based on a measured vapor pressure of 2.7 mm Hg at 20°C for HFPO dimer acid,
volatilization is expected to be an important fate process for this chemical (U.S. EPA, 2021a).
EPA's Toxics Release Inventory reported release data for HFPO dimer acid and its ammonium
salt in 2020 (U.S. EPA, 2022c). GenX chemicals are not listed as hazardous air pollutants (U.S.
EPA, 2022d).
GenX chemicals have been identified in air emissions. NCDEQ estimates for the Chemours
Fayetteville Works plant, located in the North Carolina Cape Fear watershed, indicate that
annual emissions of GenX chemicals could have exceeded 2,700 pounds per year during the
reporting period (2017-2018) (NCDEQ, 2018a). Rainwater samples collected within a seven-
mile radius of this facility were reported to have detectable levels of GenX chemicals (NCDEQ,
2018b), with the highest concentration of 810 ng/L found in a rainwater sample collected five
miles from the facility. The three samples collected seven miles from the plant had GenX
chemicals concentrations ranging from 45.3 to 60.3 ng/L (NCDEQ, 2018b).
3.3.1.5 Soil
When HFPO dimer acid and its ammonium salt are deposited on or applied to soil, they are
expected to run off into surface waters or rapidly leach to groundwater (U.S. EPA, 2021a). PFAS
can also be taken up from contaminated soil by plants (ATSDR, 2021). No specific studies on
the occurrence of GenX chemicals in biosolids were identified.
Two studies reported GenX chemicals concentrations in soil. In the United States, Galloway et
al. (2020) analyzed 13 soil samples for HFPO dimer acid at locations in Ohio and West Virginia
that were upstream and downwind of the Chemours Washington Works facility in order to
24
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evaluate HFPO dimer acid contamination due to atmospheric deposition. HFPO dimer acid was
detected in 5 out of 13 samples, with a maximum concentration of 8.14 ng/g dw. In China, Li et
al. (2020a) collected and analyzed residential soil samples throughout the country from 31
provincial-level administrative regions (consisting of 26 provinces, 4 municipalities, and 1
special administrative region). HFPO dimer acid was detected in 40.5% of soil samples at
concentrations up to 967 picograms per gram (pg/g) dw and a mean level of 19.1 pg/g dw. PFOA
was detected in these soils more frequently (96.6%) and at higher mean levels (354 pg/g dw),
leading the authors to conclude that HFPO dimer acid consumption was still limited at the
national scale of China, despite its use as a PFOA replacement.
One study measured concentrations of GenX chemicals in and/or on grass and leaves collected
from sites various distances from a fluoropolymer manufacturing plant in the Netherlands
(Brandsma et al., 2019). GenX chemicals concentrations ranged from 86 ng/g in leaves from a
site closest to the plant to ND furthest from the plant. A similar pattern was observed for grass
samples, except the maximum GenX chemicals concentration was lower (27 ng/g). The study
authors note that it hadn't rained for five days prior to sample collection.
Semerad et al. (2020) investigated occurrence of HFPO dimer acid in sewage sludge from 43
facilities in the Czech Republic. HFPO dimer acid was detected in 7 of 43 samples at
concentrations ranging from 0.3 to 1.2 ng/g dw. The authors raised concerns about the
agriculture use of sludge containing PFAS for growing crops.
5.5. /. 6 Sediment
HFPO dimer acid and its ammonium salt are expected to remain in water and exhibit low
partitioning to sediment (U.S. EPA, 2021a). One study evaluated the occurrence of GenX
chemicals in sediments from the North and Baltic Seas in Europe, and reported that HFPO dimer
acid was not detected in any of the 24 sediment samples taken in the North and Baltic Seas in the
vicinity of Germany (Joerss et al. (2019). An additional four studies analyzed sediments in China
(Li et al., 2020b, 2021; Song et al., 2018; Wang et al., 2019a). Of the four studies, Wang et al.
(2019a) analyzed sediment from the South China Sea coastal region in the area of the highly
industrialized Pearl River Delta and reported that HFPO dimer acid was below the LOQ in all 53
samples. Li et al. (2020b) analyzed 20 sediment samples from eight rivers and three reservoirs in
the Hai River Basin in the vicinity of several industrialized areas. HFPO dimer acid was
reportedly detected at minimal levels, but the authors did not report actual concentrations. Song
et al. (2018) analyzed concentrations of HFPO dimer acid in 24 sediment samples from the
Xiaoqing River in the vicinity of a fluoropolymer production facility. The study reported a
maximum HFPO dimer acid concentration in sediment of 22.3 ng/g dw, with median and mean
levels below the LOQ. Li et al. (2021) also analyzed sediment samples from five sites of the
Xiaoqing River estuary, and reported a mean HFPO dimer acid concentration of 0.23 ng/g dw.
3.3.2 RSC Determination
In summary, based on the physical properties, detected levels, and limited available exposure
information for GenX chemicals, multiple non-drinking water sources (foods, indoor dust, air,
soil, and sediment) are potential exposure sources. Following the Exposure Decision Tree in
EPA's Methodology for Deriving Ambient Water Quality Criteria for the Protection of Human
Health (U.S. EPA, 2000a), potential sources other than drinking water ingestion were identified
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(Box 8A in the Decision Tree). However, the available information is limited. The available
information does not allow for the quantitative characterization of the relative levels of exposure
among these different sources (Box 8B in the Decision Tree).
EPA also considered the exposure information specifically for the identified sensitive population
(lactating women). However, the literature search did not identify non-drinking water exposure
information specific to lactating women that could be used quantitatively to derive the RSC.
Since neither the available data for the general population (all ages) nor the sensitive population
enabled quantitative characterization of relative exposure sources and routes, EPA applied the
default RSC of 0.2 (see Section 2.2.4.2 above; EPA, 2000a), which means that 20% of the
exposure equal to the RfD is allocated to drinking water and the remaining 80% is reserved for
other potential exposure sources such as food, indoor dust, soil, and sediment.
4 J Lifetime Noncancer Health Advisory Derivation
The lifetime HA for HFPO dimer acid and its ammonium salt is calculated as follows:
EPA is issuing a lifetime noncancer drinking water HA for GenX chemicals of 10 ng/L (ppt).
The lifetime health advisory for GenX chemicals used a chronic RfD from the final EPA toxicity
assessment (U.S. EPA, 2021a) based on the critical effect of adverse liver effects in adults
(parental females) from a subchronic study (53-64 day exposure, depending on the time of
conception). In the assessment, a 10X UF for subchronic to chronic exposure was used to derive
the chronic RfD (U.S. EPA, 2021a). Because the critical effect identified for GenX chemicals is
not a developmental effect and the chronic RfD was used to develop the lifetime HA, the GenX
chemicals health advisory is more appropriate for the chronic exposure scenarios than shorter
duration exposure scenarios. However, application of the GenX chemicals health advisory to a
shorter-term risk assessment scenario would provide a conservative, health protective approach
in the absence of other information.
(Eq. 3)
Lifetime HA = 0.00001 ——
J_j
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5 J Analytical Methods
EPA developed two liquid chromatography/tandem mass spectrometry (LC/MS/MS) analytical
methods to quantitatively monitor drinking water for targeted PFAS that include HFPO dimer
acid: EPA Method 533 (U.S. EPA, 2019b) and EPA Method 537.1, Version 2.0 (U.S. EPA,
2020b). The methods discussed below can be used to accurately and reasonably quantitate HFPO
dimer acid at single digit ng/L levels that are nearly three times lower than the HFPO dimer acid
lifetime HA of 10 ng/L.
EPA Method 533 monitors for 25 select PFAS with published measurement accuracy and
precision data for HFPO dimer acid in reagent water, finished groundwater, and finished surface
water and a single laboratory-derived minimum reporting level or approximate quantitation limit
for HFPO dimer acid at 3.7 ng/L (0.0037 |ig/L). For further details about the procedures for this
analytical method, please see Method 533: Determination of Per- and Polyfluoroalkyl
Substances in Drinking Water by Isotope Dilution Anion Exchange Solid Phase Extraction and
Liquid Chromatography/Tandem Mass Spectrometry (U.S. EPA, 2019b).
EPA Method 537.1 (an update to EPA Method 537 [EPA, 2009c]) monitors for 18 select PFAS
with published measurement accuracy and precision data for HFPO dimer acid in reagent water,
finished groundwater, and finished surface water and a single laboratory-derived minimum
reporting level or approximate quantitation limit for HFPO dimer acid at 4.3 ng/L (0.0043 |ig/L).
For further details about the procedures for this analytical method, please see Method 537.1,
Version 2.0, Determination of Selected Per- and Polyfluorinated Alkyl Substances in Drinking
Water by Solid Phase Extraction and Liquid Chromatography/Tandem Mass Spectrometry
(LC/MS/MS) (U.S. EPA, 2020b).
Drinking water analytical laboratories have different performance capabilities dependent upon
their instrumentation (manufacturer, age, usage, routine maintenance, operating configuration,
etc.) and analyst experience. Some laboratories will effectively generate accurate, precise,
quantifiable results at lower concentrations than others. Organizations leading efforts that include
the collection of data need to establish data quality objectives (DQOs) to meet the needs of their
program. These DQOs should consider establishing reasonable quantitation limits that
laboratories can routinely meet, without recurring quality control (QC) failures that will
necessitate repeating sample analyses, increase costs, and potentially reduce laboratory capacity.
Establishing a quantitation limit that is too high may result in important lower-concentration
results being overlooked.
EPA's approach to establishing DQOs within the UCMR program serves as an example. EPA
established minimum reporting limits (MRLs) for UCMR 5,13 and requires laboratories approved
to analyze UCMR samples to demonstrate that they can make quality measurements at or below
the established MRLs. EPA calculated the UCMR 5 MRLs using quantitation-limit data from
multiple laboratories participating in an MRL-setting study. The laboratories' quantitation limits
represent their lowest concentration for which future recovery is expected, with 99% confidence,
to be between 50 and 150%. The UCMR 5-derived and promulgated MRL for HFPO dimer acid
is 0.005 |ig/L (5 ng/L).
13 Information about UCMR 5 is available at https://www.epa.gov/dwuciiir/fLflh-unregulated-contamiiiant-monitoring-rule
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6 J Treatment Technologies
This section summarizes available drinking water treatment technologies that have been
demonstrated to remove GenX chemicals. This section is not meant to provide specific guidance
for operation or design criteria. Sorption based treatment processes including granular activated
carbon (GAC), anion exchange (AIX), and powdered activated carbon (PAC) as well as high
pressure membranes such as nanofiltration (NF) and reverse osmosis (RO) have been shown to
successfully remove GenX chemicals from drinking water to below the 5 ppt EPA UCMR5
reporting limit (Heidari et al., 2021). Care should be taken when introducing one of these
processes into a well-functioning treatment train, as there can be unintended consequences
related to interactions with other treatment types and for systems unfamiliar with proper
operation and potential hazards. These treatment processes may have additional benefits on
finished water quality by removing other contaminants and disinfection by-product (DBP)
precursors. General information about these processes and treatment performance data
summaries may be found in the Drinking Water Treatability Database.14
Non-treatment means of managing GenX chemicals such as changing source waters,
consolidation, or source water protection are also viable options for reducing GenX chemical
concentrations in finished drinking water. One available resource for protecting source water
from PFAS, including GenX chemicals, is the PFAS-Source water Protection Guide and
Toolkit,15 which shares effective strategies for addressing PFAS contamination risk in source
waters.
Conventional water treatment methods such as coagulation, flocculation, sedimentation, and
biologically active carbon filtration (where the column is operated for extended periods of time)
are ineffective at removing GenX chemicals (Sun et al., 2016). Ozonation has increased
concentrations of some GenX chemicals at full-scale DWTPs, possibly due to precursor
compound oxidation (Sun et al. 2016). Medium pressure ultra-violet lamps and chlorination can
possibly decrease concentrations of GenX compounds but only to a very limited extent and the
observed results could be due to temporal and spatial fluctuations within the DWTPs monitored
(Sun et al., 2016). These processes are generally not considered as viable GenX chemicals, or
more broadly PFECA, treatment options. Boiling water will concentrate GenX chemicals and
should not be considered as an emergency action.
6.1 Sorption Technologies
Sorption is where substances present in liquids are removed by accumulation on a solid phase
(Crittenden et al., 2012). There are two main sorption technologies that are in use for PFAS
removal and have been demonstrated to remove GenX: activated carbon and ion exchange.
Activated carbon comes in two key forms distinguished by size, PAC and GAC.
There are select considerations that are similar across all sorption technologies. Common key
criteria include influent water quality and desired effluent quality. Influent water quality can
greatly impact the ability of sorption technologies to treat drinking water. Desired effluent
quality can drive both operational and capital expenditures. Pilot scale testing is highly
recommended to ensure the design effectiveness will be maximized for given source waters.
14 More information regarding treatment processes is available at https://tdb.epa.gov/tdb/fiiidtreatmentprocess
15 The PFAS Source Water Protection Guide and Toolkit are available for download at https://www, asdwa.org/pfas/
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EPA's ICR Manual for Bench- and Pilot-Scale Treatment Studies (U.S. EPA, 1996) contains
guidance on conducting pilot studies for contactors which are used for GAC and ion exchange.
Sorption technologies are largely reversible: PFAS can detach from sorbents and re-enter the
drinking water under certain conditions. In addition, direct competition with stronger sorbing
constituents can lead to effluent PFOS concentrations temporarily exceeding influent
concentration (known as chromatographic peaking). An implication for treatment plants is that
the effluent GenX chemicals concentrations can temporarily exceed influent concentrations.
Competitive sorption is especially important in co-removal systems where other PFAS are
present. When GenX was co-removed with PFOA, the total GenX quantity removed decreased
significantly. After an initial loading period absorbed GenX desorbed and then was replaced by
PFOA (Wang et al. 2019b). Competitive sorption may be controlled by changing or regeneration
of the sorptive media at appropriate intervals.
The majority of studies found that natural or dissolved organic matter (NOM/DOM) interferes
with PFAS sorption, in general, and its presence dramatically lowers treatment efficacy
(McNamara et al., 2018; Pramanik et al., 2015; Yu et al., 2012). The lowered treatment
effectiveness was found to be less pronounced for GenX chemicals than for perfluoroalkyl
carboxylic acid (PFCA) C7 and above for GAC (Park et al., 2020).
GAC can typically be regenerated when treatment performance reaches an unacceptable level..
Regeneration can be on or off site. On-site regeneration typically requires a higher spatial
footprint and capital outlay. Given water quality and other considerations, regenerated media can
become totally exhausted or "poisoned" with other contaminants not removed during
regeneration and must be replaced. However, for GAC, the loss of approximately 10 percent of
the media due to abrasion withing the reactivation process can result in a somewhat steady state
for performance as new GAC is added each time to replace the lost GAC. Most AIX resins in
current use for PFAS are single use resins and not designed to be regenerated.
6.1.1 Activated Carbon
Activated carbon is a highly porous media with high internal surface areas (U.S. EPA, 2017b).
Activated carbon can be made from a variety of materials. Designs that work with a carbon made
from one source material activated in a specific way may not be optimized for other carbon
types. It is normally used in either a granular or powdered form for water treatment. Installing
activated carbon as a treatment method may have ancillary benefits on finished water quality,
particularly with disinfectant byproduct control as well as taste and odor.
With activated carbon, more non-polar and larger compounds tend to be more easily removed
than smaller more polar compounds. Adsorption of acids and bases on activated carbon is
dependent on the pH. Adsorption of neutral forms, as opposed to anionic forms, are generally
stronger so lowering the pH increases GenX chemical sorption. However, the acid dissociation
constant (pKa) of HFPO dimer acid is 2.84 and lowering the pH is not practical for drinking
water applications (Park et al. 2020; U.S. EPA 2021a). GenX forms a fast, weak electrostatic
bond with adsorbents and can be substituted by PFOA or other long-chain PFAS which adsorb
preferentially on activated carbon due in part to their higher hydrophobicity (Heidari et al., 2021;
Wang et al., 2019b). These differences in physical chemical properties are consistent with the
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faster adsorption kinetics but less tight binding of GenX than PFOA and result in GenX
chemicals partitioning more quickly onto activated carbon.
Based on findings with emerging PFCA PFOA replacements, cations such as aluminum,
calcium, and sodium increase PFAS sorption to activated carbons (Pereira et al., 2018) at low
pH. Anions such as fluorine, chlorine, nitrate, sulfate, and phosphate have not yet been shown to
correlate with GenX removal despite expectations that these anions would inhibit GenX
treatment (Wu et al., 2020).
Activated carbon has a maximum sorbent capacity and must be replaced or regenerated. For
carbon regenerated off-site, several organizations recommend that spent carbon should be
segregated and traceable from the time it leaves the drinking water facility through all steps at
the reactivation facility, and then returned to the same site (National Science Foundation
[NSF]/American National Standards Institute [ANSI] Standard 61 [NSF/ANSI, 2021]).
Before adding activated carbon to an existing treatment train, there are effects which should be
considered. For instance, activated carbon may change system pH or, release leachable metals
(particularly arsenic and antimony) when new carbon media is first used without acid washing,
and may require disinfection. Activated carbon may also cause unintended consequences with
disinfection efficacy depending on process placement. Activated carbon can also shift the
bromide-to-total organic carbon ratio and increase brominated (Br)-DBP concentrations as well
as concentrations relative to chlorinated DBPs (Krasner et al., 2016). Despite increased Br-DBP,
studies have indicated a decreased overall DBP risk (Wang et al., 2019c).
6.1.1.1 Powdered A ctivated Carbon
PAC is the same material as GAC but has a smaller particle size and is applied differently. PAC
is typically dosed intermittently although it can be employed continuously. PAC dosage and
type, along with dosing location, contact time, and water quality, often influence process cost as
well as treatment efficiency (Heidari et al., 2021). Sometimes PAC is combined with other
processes, particularly floe blanket reactors and membrane filters (low or high pressure),
although this is not necessary. For more information on employing PAC, please see the Drinking
Water Treatability Database.16
With GenX, PAC was found to achieve equilibrium more quickly than GAC however, total
removal capacity was similar (Wang et al., 2019b), although the steady state PAC application
cannot match the benefits of column operation of GAC in terms of percent removal. Significant
increases in GenX chemicals treatment efficiencies have been observed with smaller PAC
particle sizes (Wang et al., 2019b). Compared to GAC, competing species such as PFOA
displace GenX chemicals more rapidly on PAC (Wang et al. 2019b) which is consistent with
GenX being less tightly bound and more mobile than PFOA. For PFAS, information to date
indicates that increasing PAC dose increases removal to a point and then starts to decrease. Jar
testing is used to empirically determine the optimal PAC dosage; doses between 45-100 mg/L
are generally suitable for GenX Chemicals (Dudley, 2012; Hopkins et al., 2018; Sun et al.,
2016). These doses are high and drinking water utilities would have difficulty in maintaining
them for extended periods of time. Standardized jar testing procedures have been published
16 https://tdb.epa.gov/tdb/treatiiieiitprocess7treatiiieiitProces 700949
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(ASTM, 2019; AWWA, 2011). The AWWA published standard for PAC is ANSI/AWWA
B600-16 (AWWA, 2016).
Other key operational parameters determining PAC efficiency include contact time and loading
rate. Contact time in most plants is generally between 30 minutes and 2 hours. Sun et al. (2016)
found that the full PAC capacity for GenX chemicals is unlikely to be used in this time. While
PAC can be regenerated it rarely makes sense to do so because of the associated costs, presence
of coagulants and particulates in the sludge, and degraded removal capacities post-reactivation
(Clifford et al., 1983).
PAC poses additional safety considerations including depleting oxygen in confined or partially
enclosed areas, fire hazards including spontaneous combustion when stored with hydrocarbons
or oxidants, and inhalation hazards. PAC is also a good electrical conductor and can create
dangerous conditions when it accumulates (AWWA, 2016).
6.1.1.2 Granulated A ctivated Carbon
As a result of GenX chemicals being only moderately absorbable, GAC contactors are normally
placed as a post-filter step. Key design criteria include empty bed contact time (EBCT),
superficial velocity, and carbon type. Typical EBCTs for GenX chemicals removal are 10-20
minutes and superficial linear velocities are normally 5-15 meters per hour (m/hr). Normal
height-to-diameter ratios are around 1.5 to 2.0; lower ratios can run into problems with too
shallow beds and require more space, and higher ratios induce greater pressure drops. AWWA
has published a GAC standard (ANSI/AWWA B604-18; AWWA, 2018a); there is also an
AWWA published standard for GAC reactivation (ANSI/AWWA B605-18; AWWA, 2018b).
6.1.2 Ion Exchange
Ion exchange involves the exchange of an ion in the aqueous phase for an ion on the exchange
resin. Once the resin has exchanged all its ions for contaminants, it can either be disposed (single
use) or regenerated (i.e., restoring its ions for further use).
Resins are either cationic or anionic; cationic resins remove positively charged ions such as
sodium or calcium and anionic resins remove negatively charged ions such as sulfates and
nitrates. Cationic exchange resins do not remove GenX chemicals. The pKa of HPFO-DA is
2.84; this means that in drinking water applications GenX chemicals will predominately exist in
an anionic form and are strong acids (U.S. EPA, 2021a). Based on the pKa strongly basic anionic
exchange resins will be the most relevant. Key design parameters for GAC are also key design
parameters for AIX, although there are slight differences in operation. AIX typically uses 2-to-5-
minute EBCTs, allowing for lower capital costs and a smaller footprint; generally smaller height-
to-diameter ratios are used in exchange columns compared to GAC. Columns used in pilot
studies and scaled directly to full-scale if loading rates and EBCTs are kept constant (Crittenden
2012). For more information about AIX, please see Dixit et al. (2021), Tarleton (2014), or
Tanaka (2015), Crittenden et al. (2012), or the EPA Drinking Water Treatability Database
(2022).
Strong base acrylate resins contaminated with HFPO dimer acid have been greater than 95%
regenerated with a 10% sodium chloride solution (Dixit et al., 2020). Sodium hydroxide may be
added to the sodium chloride solution to combat organic fouling; this is referred to as 'brine
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squeeze' and helps in solubilizing NOM and unplugging pores (Dixit et al., 2021). Once PFAS-
contaminated spent brine is recovered, it must be treated or disposed. Resin regeneration may not
be practical for water utilities from safety and/or cost perspectives (Liu and Sun, 2021).
Before adding AIX to an existing treatment train, there are effects which should be considered.
For instance, AIX can increase water corrosivity which may increase heavy metals through
leaching, can release organic leachables such as the amines from which they are made, and will
increase concentrations of the counter-ion used (typically chloride).
6.2 High Pressure Membranes
NF and RO are high-pressure processes where water is forced through a membrane. The water
that transverses the membrane is known as permeate or produce water, and has few solutes left in
it; the remaining water is known as concentrate, brine, retentate, or reject water and forms a
waste stream with concentrated solutes. NF has a less dense active layer than RO, which enables
lower operating pressures but also makes it less effective at removing contaminants. NF and RO
tend to take up less space than sorption separation technologies. However, both NF and RO also
tend to have higher operating expenses, use a significant amount of energy, and generate
concentrate waste streams which require disposal. Generally, NF and RO require pre- and
posttreatment processes. Higher expenses typically associated with NF and RO are only rarely
competitive from an economic perspective for removing a specific contaminant; however, for
waters requiring significant treatment and where concentrate disposal options are reasonably
available, NF and RO may be the best option.
PFAS removal fluxes are generally 1-50 liters per square meter per hour (L/[m2hr]) at 5-85 bar
operating pressure (Mastropietro et al., 2021). Temperature can dramatically impact flux; it is
common to normalize flux to a specific reference temperature for operational purposes (U.S.
EPA, 2005c). It is also common to normalize flux to pressure ratios to identify productivity
changes attributable to fouling (U.S. EPA, 2005c). It is important to note that outside-in and
inside-out systems operating at the same flux produce differing quantities of finished water so
membrane systems with differing configurations cannot be directly compared based on flux.
Total flow per module and cost per module are more important decision support indicators for
capital planning. Unlike low pressure membranes, NF and RO systems are not manufactured as
proprietary equipment and membranes from one manufacturer are typically interchangeable with
those from others (U.S. EPA, 2005c).
High-pressure membranes may have important unintended effects when added onto a well-
functioning treatment train. For instance, high-pressure membranes may remove beneficial
minerals and increase corrosivity. Increased water corrosivity may increase heavy metals such as
iron, lead, and copper through leaching. For more information, see AWWA (2007).
6.3 Point-of-Use Devices for Individual Household PFAS Removal
Although the focus of this treatment technologies section is the different available options for
removal of PFOA at DWPs, centralized treatment technologies can also often be used in a
decentralized fashion as point-of-entry (POE) (where the distribution system meets a service
connection) or point-of-use (POU) (at a specific tap or application) treatment in cases where
centralized treatment is impractical or individual consumers wish to further reduce their
individual household risks. Many home drinking water treatment units are certified by
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independent third-party accreditation organizations against ANSI standards to verify
contaminant removal claims. NSF International has developed protocols for NSF/ANSI
Standards 53 (sorption) and 58 (RO) that establish minimum requirements for materials, design,
and construction, and performance of point-of-use systems. Previously, NSF P473 was designed
to certify PFOA reduction technologies below EPA's 2016 HA of 70 ppt for PFOA; in 2019,
these standards were retired and folded into NSF/ANSI 53 and 58. When properly maintained,
these certified systems may reduce other PFAS, including GenX chemicals, although removal
should not be automatically inferred for PFAS not specified within the protocol. It has been
reported that home under-the-sink RO filters effectively removed GenX chemicals in Cape Fear,
North Carolina (Hopkins et al., 2018). GenX specific certification procedures may be developed
by standards organizations, such as NSF and the Water Quality Association. Individuals or
systems interested in POU or POE treatment should check with standards organizations for the
most recent certification procedures.
6.4 Treatment Technologies Summary
Non-treatment management options, such as changing source waters, source water protection, or
consolidation, are viable strategies for reducing GenX chemicals concentrations in finished
drinking water. Should treatment be necessary, activated carbon, AIX, NF, or RO have been
shown to successfully remove HFPO dimer acid from drinking water to below the 4 ppt
reporting limit for UCMR 5. These processes are the best means for removing GenX chemicals
from drinking water and can be used in central treatment plants or in POU/POE applications.
Some treatment processes have been shown to increase GenX chemicals concentrations, most
likely through precursor oxidation. These treatment technologies often require pre- as well as
posttreatment and may help remove other unwanted contaminants along with DBP precursors.
Each technology may also introduce unintended consequences to an existing treatment train.
Additionally, these treatment processes are separation technologies and produce waste streams
with GenX chemicals on or in them. Boiling water will concentrate GenX chemicals and should
not be considered as an emergency action.
7 J Consideration of N oncancer Health Risks from PFAS Mixtures
EPA recently released a Draft Framework for Estimating Noncancer Health Risks Associated
with Mixtures of Per- and Polyfluoroalkyl Substances (PFAS) (U.S. EPA, 2021f) that is currently
undergoing Science Advisory Board (SAB) review. That draft document describes a flexible,
data-driven framework that facilitates practical component-based mixtures evaluation of two or
more PFAS based on current, available EPA chemical mixtures approaches and methods (U.S.
EPA, 2000b). Examples are presented for three approaches—Hazard Index (HI), Relative
Potency Factor (RPF), and Mixture BMD—to demonstrate application to PFAS mixtures. To use
these approaches, specific input values and information for each PFAS are needed or can be
developed. These approaches may help to inform PFAS evaluation(s) by federal, state, and tribal
partners, as well as public health experts, drinking water utility personnel, and other stakeholders
interested in assessing the potential noncancer human health hazards and risks associated with
PFAS mixtures.
The HI approach, for example, could be used to assess the potential noncancer risk of a mixture
of four component PFAS for which HAs, either final or interim (iHA), are available from EPA
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(PFOA, PFOS, GenX chemicals, and perfluorobutane sulfonic acid [PFBS]). In the HI approach
described in the draft framework (U.S. EPA 2021f), a hazard quotient (HQ) is calculated as the
ratio of human exposure (E) to a human health-based toxicity value (e.g., reference value [RfV])
for each mixture component chemical (i) (U.S. EPA, 1986). The HI is dimensionless, so in the
HI formula, E and the RfV must be in the same units (Eq. 6). In the context of PFAS in drinking
water, a mixture PFAS HI can be calculated when health-based water concentrations (e.g., HAs,
Maximum Contaminant Level Goals [MCLGs]) for a set of PFAS are available or can be
calculated. In this example, HQs are calculated by dividing the measured component PFAS
concentration in water (e.g., expressed as ng/L) by the relevant HA (e.g., expressed as ng/L)
(Eqs. 7, 8). The component chemical HQs are then summed across the PFAS mixture to yield the
mixture PFAS His based on interim and final HAs.
i=l i=l
(Eq. 6)
HI = HQpfqa + HQpFos + HQGenX + HQPFBS
(Eq. 7)
/[PFBSwater]\
V [pfbsha] J
(Eq. 8)
Where:
HI = hazard index
n = the number of component (i) PFAS
HQi = hazard quotient for component (i) PFAS
Ei = human exposure for component (i) PFAS
RfV = human health-based toxicity value for component (i) PFAS
HQpfas= hazard quotient for a given PFAS
[PFASwater] = concentration of a given PFAS in water
[PFASha] = HA value, interim or final, for a given PFAS
In cases when the mixture PFAS HI is greater than 1, this indicates an exceedance of the health
protective level and indicates potential human health risk for noncancer effects from the PFAS
mixture in water. When component health-based water concentrations (in this case, HAs) are
below the analytical method detection limit, as is the case for PFOA and PFOS, such individual
component HQs exceed 1, meaning that any detectable level of those component PFAS will
result in an HI greater than 1 for the whole mixture. Further analysis could provide a refined
assessment of the potential for health effects associated with the individual PFAS and their
contributions to the potential joint toxicity associated with the mixture. For more details of the
approach and illustrative examples of the RPF approach and Mixture BMD approaches please
see U.S. EPA (202If).
/[PFOAwater]\ /[PFOSwater]\ /[GenXwaterr
" V [PFOAiHA] J [ [PFOSiHA] J [ [GenXHA] ,
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8 J Health Advisory Characterization
EPA is issuing a lifetime noncancer drinking water HA for GenX chemicals of 10 ng/L or 10 ppt
based on the best available science. This is the first HA for GenX chemicals. The input values
for the HA are: 1) the final chronic RfD for GenX chemicals from the toxicity assessment (U.S.
EPA, 2021a); 2) the RSC based on exposure information collected from a literature search and
following EPA's Exposure Decision Tree (U.S. EPA, 2000a) and presented herein; and 3) the
DWI-BW, described herein, selected for the sensitive population or life stage. The final toxicity
assessment for GenX chemicals was developed from a systematic review of the available
scientific information on health effects (U.S. EPA, 2021a) and reflects response to public
comment, two expert peer reviews, and recommendations from an independent evaluation by the
National Toxicology Program's Pathology Working Group of two liver toxicity studies.
Uncertainties in the lifetime noncancer HA value are due in part to the relatively small database
of health effects information, based on animal studies, for GenX chemicals (U.S. EPA, 2021a).
There were no human epidemiology studies identified during the literature search conducted as
part of the toxicity assessment (U.S. EPA, 2021a). The mechanistic information for GenX
chemicals was reviewed as part of the toxicity assessment (see Section 6 of EPA, 2021a).
Multiple potential modes of action have been identified for effects of GenX chemicals exposure
on the liver (the critical effect), including peroxisome proliferator-activated receptor alpha
(PPARa) activation and cytotoxicity. Mechanisms and modes of action have not been elucidated
for the other health outcomes associated with GenX chemicals exposure (e.g.,
developmental/reproductive effects). However, the current data gaps in the GenX chemicals
health effects information were accounted for in the derivation of the final RfD by applying
relevant UFs including a 10X UFd.
Regarding EPA's RSC selection, uncertainties exist due to the current lack of information to
allow for a quantitative exposure characterization among exposure sources including for
lactating women, the sensitive population selected for deriving the HA. There is also uncertainty
in the EF that EPA selected since it is possible that additional toxicity information may reveal
more sensitive populations or life stages for GenX chemicals. This final HA is based on a recent
toxicity assessment and recent literature searches of the publicly available scientific information
regarding health effects, exposure, analytical methods, and treatment technologies for GenX
chemicals.
8.1 Comparative Analysis of Exposure Factors for Different Populations
The exposure duration in the critical study identified in the toxicity assessment for GenX
chemicals (U.S. EPA, 2021a) is from pre-mating, through gestation, and to day 21 of lactation
and the adverse liver effects were observed in the dams (not their offspring). Therefore, three
potentially sensitive life stages of adult females—pregnant women, women of childbearing age
(13 to < 50 years), and lactating women were identified (Table 5). The DWI-BW for lactating
women was selected since it is the most health protective.
To evaluate whether all ages of the general population would be protected by the resulting
lifetime HA value for GenX chemicals, based on the DWI-BW for lactating women, EPA
calculated HAs using the 90th percentile DWI-BW for four populations: the general population
(all ages), pregnant women, women of childbearing age, and lactating women. The HA values
(rounded to one significant figure) using the EF for general population, pregnant women, or
35
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women of childbearing age are all 0.00002 mg/L (20 ppt) which is higher than the GenX HA
value calculated using the EF for lactating women (0.00001 mg/L [10 ppt]) (Table 6). The
comparison of the four candidate HA values indicates that the lifetime noncancer HA derived
using the DWI-BW for lactating women is protective of the other candidate sensitive populations
or life stages as well as the general population (all ages).
Table 6. Comparison of HA Values Using EPA Exposure Factors for Drinking Water
Intake for Different Candidate Populations.
Population
DWI-BW
(L/kg bw-day)
HA two sig figs/
HA one sig fig
(mg/L)
Description of Exposure
Metric
Source
General
population, all ages
0.0338
0.000018/
0.00002
90th percentile direct and
indirect consumption of
community water,
consumer-only two-day
average, all ages.
2019 Exposure
Factors Handbook
Chapter 3, Table 3-
21, NHANES 2005-
2010 (U.S. EPA,
2019a)
Pregnant women
0.0333
0.000018/
0.00002
90th percentile direct and
indirect consumption of
community water,
consumer-only two-day
average.
2019 Exposure
Factors Handbook
Chapter 3, Table 3-
63, NHANES 2005-
2010 (U.S. EPA,
2019a)
Women of
childbearing age
0.0354
0.000017/
0.00002
90th percentile direct and
indirect consumption of
community water,
consumer-only two-day
average, 13 to < 50 years.
2019 Exposure
Factors Handbook
Chapter 3, Table 3-
63, NHANES 2005-
2010 (U.S. EPA,
2019a)
Lactating women
0.0469
0.000013/
0.00001
90th percentile direct and
indirect consumption of
community water,
consumer-only two-day
average.
2019 Exposure
Factors Handbook
Chapter 3, Table 3-
63, NHANES 2005-
2010a(U.S. EPA,
2019a)
Notes'. L/kg bw-day = liters of water consumed per kilogram body weight per day. Sig fig = significant figure. The DWI-BW
used to calculate the GenX chemicals' lifetime HA is in bold. EPA HAs are rounded to one significant figure.
a Estimates are less statistically reliable based on guidance published in the Joint Policy on Variance Estimation and Statistical
Reporting Standards onNELANES III and CSFII Reports: HNIS/NCHS Analytical Working Group Recommendations (NCHS,
1993).
8.2 Related Compounds of Emerging Concern
This HA addresses the two chemicals that are the two current commercial products of the GenX
technology: the HFPO dimer acid and its ammonium salt. During the synthesis of HFPO dimer
acid, which is manufactured from hexafluoropropene oxide (HFPO), other chemicals including
the HFPO trimer acid (HFPO-TA) and HFPO tetramer acid (HFPO-TeA) can be produced in the
synthesis process (Geng et al., 2016). These same HFPO chemicals are byproducts of longer
36
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chain perfluoropolyether synthesis. Health effects are indicated from in vivo and in vitro studies
of the liver (Sheng et al., 2018) and the endocrine system after exposure to HFPO-TA and the
HFPO-TeA (Xin et al., 2019). While some information is available on the occurrence and
bioaccumulation of HFPO-TA (Pan et al., 2017), more research is needed to improve our
understanding of the exposure information and health effects for HFPO-TA and HFPO-TeA.
37
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45
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Appendix A: Relative Source Contribution - Literature Search and
Screening Methodology
In support of U.S. Environmental Protection Agency's (EPA's) human health toxicity
assessment for hexafluoropropylene oxide dimer acid (HPFO) and its ammonium salt (GenX
chemicals) (EPA, 2021a), literature searches were conducted of four databases (PubMed,
Toxline, Web of Science (WOS), and Toxic Substances Control Act Test Submissions
(TSCATS) to identify publicly available literature using Chemical Abstracts Service Registry
Number (CASRN), synonyms, and additional relevant search strings (see EPA (2021a) for
details). Due to the limited search results, additional databases were searched for information on
physicochemical properties, health effects, toxicokinetics, and mechanism of action. The initial
date-unlimited database searches were conducted in July 2017 and January/February 2018, with
updates completed in February 2019, October 2019, and March 2020. In addition, available
information on toxicokinetics; acute, short-term, subchronic, and chronic toxicity; developmental
and reproductive toxicity; neurotoxicity; immunotoxicity; genotoxicity; and cancer in animals
was submitted with premanufacture notices to EPA by DuPont/Chemours, the manufacturer of
GenX chemicals, as required under Toxic Substances Control Act pursuant to a consent order
(EPA, 2009b) or reporting requirements (15 U.S.C. § 2607.8(e)). The results of the literature
searches of publicly available sources and submitted studies from DuPont/Chemours are
available through EPA's Health & Environmental Resource Online website at
https://hero.epa.eov/hero/index.cfm/proiect/paee/proiect id/2627.
The GenX chemicals literature search results and all studies submitted from DuPont/Chemours
were imported into SWIFT-Review (Sciome, LLC, Research Triangle Park, NC) and filtered
through the Evidence Stream tags to identify human studies and non-human (i.e., those not
identified as human) studies. Studies identified as human studies were further categorized into
seven major PFAS pathways (Cleaning Products, Clothing, Environmental Media, Food
Packaging, Home Products/Articles/Materials, Personal Care Products, and Specialty Products)
as well as an additional category for Human Exposure Measures. Non-human studies were
grouped into the same seven major PFAS pathway categories, except that the Environmental
Media category did not include soil, wastewater, or landfill.
Application of the SWIFT-Review tags identified 52 studies for title and abstract screening. An
additional three references were identified through gray literature sources that were included to
supplement the search results. Title and abstract screening to determine relevancy followed the
populations, exposures, comparators, and outcomes (PECO) criteria in Table A-l:
Table A-l. Populations, Exposures, Comparators, and Outcomes (PECO) Criteria
PECO Element
Inclusion Criteria
Population
Adults (including women of childbearing age) and/or children in the general
populations from any country
Exposure
Primary data from peer-reviewed studies collected in any of the following media:
ambient air, consumer products, drinking water, dust, food, food packaging,
groundwater, human blood/serum/urine, indoor air, landfill, sediment, soil, surface
water (freshwater), wastewater/biosolids/sludge
Comparator
Not applicable
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PECO Element
Inclusion Criteria
Outcome
Measured concentrations of GenX chemicals (or measured emissions from food
packaging and consumer products only)
The title and abstract of each study were independently screened for relevance by two screeners
using litstream™. A study was included as relevant if it was unclear from the title and abstract
whether it met the inclusion criteria. When two screeners did not agree if a study should be
included or excluded, a third reviewer was consulted to make a final decision. The title and
abstract screening resulted in 24 studies tagged as relevant (i.e., data on occurrence of GenX
chemicals in one of the media of interest were presented in the study) that were further screened
with full-text review using the same inclusion criteria. Of these 24 studies, 4 contain only human
biomonitoring data and are not discussed further here. Based on full-text review, 15 studies were
identified as relevant and are summarized below. At the full-text review stage, two additional
studies were identified as only containing biomonitoring data.
To supplement the primary literature database, EPA also searched the following gray literature
sources in February 2022 for information related to relative exposure of GenX chemicals for all
potentially relevant routes of exposure (oral, inhalation, dermal) and exposure pathways relevant
to humans:
• EPA's (2021a) Human Health Toxicity Values for Hexajluoropropylene Oxide (HFPO)
Dimer Acid and Its Ammonium Salt (CASRN13252-13-6 and CASRN 62037-80-3) Also
Known as "GenX Chemicals "
• Agency for Toxic Substances and Disease Registry's (ATSDR's) ToxicologicalProfiles
• Centers for Disease Control and Prevention's (CDC's) national reports on human
exposures to environmental chemicals
• EPA's CompTox Chemicals Dashboard
• EPA's fish tissue studies
• EPA's Toxics Release Inventory
• EPA's Unregulated Contaminant Monitoring Rule data
• Relevant documents submitted under the Toxics Substances Control Act and relevant
reports from EPA's Office of Chemical Safety and Pollution Prevention
• U.S. Food and Drug Administration's (FDA's) Total Diet Studies and other similar
publications from FDA, U.S. Department of Agriculture, and Health Canada
• National Oceanic and Atmospheric Administration's (NOAA's) National Centers for
Coastal Ocean Science data collections
• National Science Foundation direct and indirect food and/or certified drinking water
additives
• PubChem compound summaries
• Relevant sources identified in the relative source contribution discussions (section 5) of
EPA's Proposed Approaches to the Derivation of a Draft Maximum Contaminant Level
Goal for Perfluorooctanoic Acid (PFOA)/Perfluorooctane Sulfonic Acid (PFOS) in
Drinking Water
• Additional sources, as needed
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EPA has included available information from these gray literature sources for GenX chemicals
relevant to their uses, chemical and physical properties, and for occurrence in drinking water
(directly or indirectly in beverages like coffee, tea, commercial beverages, or soup), ambient air,
foods (including fish and shellfish), incidental soil/dust ingestion, and consumer products. EPA
has also included available information specific to GenX chemicals below on any regulations
that may restrict levels of GenX chemicals in media (e.g., water quality standards, air quality
standards, food tolerance levels).
EPA incorporated 3 references (Feng et al., 2021; Li et al., 2021; and Semerad et al., 2020) that
were not identified in the contractor's RSC literature search strategy; these references were
provided by Chemours as part of their outreach to EPA on uses and sources for GenX chemicals
in April 2022.
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Appendix R: Compilation of Data on BDFPO Dimer Acid Occurrence
In Surface Water Collected from Primary Literature
This appendix includes a table resulting from the efforts to identify and screen primary literature
(i.e., peer-reviewed journal articles), described in Appendix A, as well as extract data that may
be relevant to informing the RSC derivation for GenX chemicals.
Table B-l. Compilation of Studies Describing of HFPO Dimer Acid Occurrence in Surface
Water
Study
Location
Site Details
Results
North America
Sun etal. (2016)
United States (North
Carolina, Cape Fear
River Basin)
Source waters of three
community drinking water
treatment plants, two
upstream and one
downstream of a PFAS
manufacturing plant (LOQ =
10 ng/L)
Community A (upstream): DF
0%
Community B (upstream): DF
NR median (range) = ND
(ND-10 ng/L)
Community C (downstream):
DF NR mean = 631 ng/L,
median (range) = 304 (55-
4,560) ng/L
McCord et al.
(2018)
United States (North
Carolina, Cape Fear
River Basin)
Source water of a drinking
water treatment plant near
the industrial waste outfall
of a fluorochemical
manufacturer, before and
after the manufacturer
diverted a waste stream
(exact values NR, estimated
values from Figure 3)
Before waste diversion
(estimated): DF NR measured
concentration = ~ >700 ng/L
After waste diversion
(estimated): DRNR measured
concentration = < 140 ng/L
Galloway et al.
(2020)
United States (Ohio
and West Virginia,
Ohio River Basin)
Rivers and tributaries
located upstream,
downstream, and downwind
of a fluoropolymer
production facility; some
sample locations potentially
impacted by local landfills
DF = 21/24 unique sites with
detections > LOQ, median3
(range) = 46.7 (ND-227) ng/L
Europe
Gebbink et al.
(2017)
The Netherlands
Upstream and downstream
of the Dordrecht
fluorochemical production
plant; two control sites
Control sites: DF 0%
Upstream of plant (n=3): DFa
33%, point = 22 ng/L
Downstream of plant (n=13):
DF 100%, mean3
(range) = 178 (1.7-812) ng/L
(MQL = 0.2)
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Study
Location
Site Details
Results
Vughs et al.
(2019)
The Netherlands and
Belgium
Thirteen surface water
samples collected from
eleven water suppliers, some
near a fluoropolymer
manufacturing plant. The
study did not map the
distribution of reported
concentrations by
geographic location or with
respect to distance from the
fluoropolymer
manufacturing plant.
DF 77%, mean (range) = 2.2
(ND-10.2) ng/L (LOQ = 0.2
ng/L)
Asia
Pan et al. (2017)
China (Xiaoqing
River and tributary)
Upstream and downstream
of a fluoropolymer
production plant in an
industrialized region
Upstream of plant in the
Xiaoqing River (n=6): DFa
100%, median3 (range) = 2.10
(1.61-3.64) ng/L
Tributary directly receiving
plant effluent (n=4): DFa
100%, median3 (range) =
1,855 (2.34-2,060) ng/L
Downstream of plant in the
Xiaoqing River receiving
tributary waters (n=8): DFa
100%, median3 (range) = 311
(118-960) ng/L
Song etal.
(2018)
China (Xiaoqing
River)
Near the Dongyue group
industrial park, including a
fluoropolymer production
plant
DF NR, mean, median (range)
= 519,36.7 (
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Study
Location
Site Details
Results
Pan et al. (2018)
United States
(Delaware River)
Sampling sites along
industrialized river systems
that were not proximate to
known point sources of
PFAS from fluorochemical
facilities
Delaware River (n=12): DF
100%, mean, median (range) =
3.32,2.02 (0.78-8.75) ng/L
United Kingdom
(Thames River),
Germany and the
Netherlands (Rhine
River), Sweden
(Malaren Lake)
Sampling sites along
industrialized river systems
that were not proximate to
known point sources of
PFAS from fluorochemical
facilities
Thames River (n=6): DF
100%, mean, median (range) =
1.12, 1.10 (0.70-1.58) ng/L
Rhine River (n=20): DF
100%, mean, median (range) =
0.99,0.90 (0.59-1.98) ng/L
Malaren Lake (n=10): DF
100%, mean, median (range) =
1.47, 1.38 (0.88-2.68) ng/L
South Korea (Han
River), China (Liao,
Huai, Yellow,
Yangtze, and Pearl
Rivers; Chao and Tai
Lakes)
Sampling sites along
industrialized river systems
that were not proximate to
known point sources of
PFAS from fluorochemical
facilities
Han River (n=6): DF 100%,
mean, median (range) = 1.38,
1.16 (0.78-2.49) ng/L
Liao River (n=6): DF 100%,
mean, median (range) = 1.44,
0.88 (0.62-4.51) ng/L
Huai River (n=9): DF 100%,
mean, median (range) = 1.66,
1.40 (0.83-3.62) ng/L
Yellow River (n=15): DF
67%, mean, median (range) =
1.01, 1.30 (
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Study
Location
Site Details
Results
All locations
Sampling sites were not
proximate to known point
sources of any
fluorochemical facilities
All locations (n=160): DF
96%, mean, median (range) =
2.55, 0.95 (0.18-144) ng/L
(LOQ = 0.05 ng/L; MDL =
0.38 ng/L)
Notes:
DF = detection frequency; LOQ = limit of quantification; ND = not detected.; ng/L = nanograms per liter; NR = not reported;
MQL = method quantification limit; MDL = method detection limit.
a The DF, median and/or mean was not reported in the study and was calculated in this synthesis. Mean values were only
calculated if DF = 100%.
b The DF in Li et al. (2020a) was reported as 82.5% in the main article. The DF of 80% shown in this table is based on the
supporting information data, which show only 32/40 samples with data > MDL.
c The Xiaoqing River results reported in Heydebreck et al. (2015) included samples from Laizhou Bay. EPA considered
freshwater samples only.
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