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

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

Where:

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

V. Maximum Contaminant Level Goals

A. PFOA

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

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

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

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

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

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

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

B. PFOS

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

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

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

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

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

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

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

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

Framework (USEPA, 2022a). For a detailed description of the evidence
supporting dose additivity for PFOA, PFOS, and other PFAS, see the
revised PFAS Mixtures Framework (USEPA, 2023d).
    Following EPA's data-driven approach for component-based mixtures
assessment based on dose additivity (i.e., see Figure 4-1 in USEPA,
2023d), the Agency selected the HI approach for MCLG development to
ensure the Agency is protecting against dose additive risk from
mixtures of PFHxS, HFPO-DA, PFNA, and PFBS. While a single PFAS may
occur in concentrations below where EPA might establish an individual
MCLG, PFAS tend to co-occur (see discussion in sections III.C and VII
of this preamble). Hence, there are some situations where setting an
MCLG while only considering the concentration of an individual PFAS
without considering the dose additive effects that would occur from
other PFAS that may be present in a mixture may not provide a
sufficiently protective MCLG with an adequate margin of safety. For
this proposed rule, in addition to the PFOA and PFOS assessments
discussed above, peer reviewed, publicly available assessments with
final toxicity values (i.e., RfDs, Minimal Risk Levels) are available
for HFPO-DA (USEPA, 2021b), PFBS (USEPA, 2021a), PFNA (ATSDR, 2021),
and PFHxS (ATSDR, 2021). These toxicity values (along with DWI-BW and
RSC) are used to derive the HBWCs for the HI approach for PFHxS, HFPO-
DA, PFNA, and PFBS. EPA is seeking comment on derivation of the HBWCs
for each of the four PFAS considered as part of the HI. See discussion
in section VI.C of this preamble as to why EPA is not proposing to
include PFOA and PFOS in the HI MCLG at this time.
    As discussed previously in this document, the Agency is proposing
the general HI as the most appropriate and justified approach for
considering PFAS mixtures in this rulemaking because of the level of
protection afforded for diverse endpoints. SDWA requires the Agency to
establish a health-based MCLG set at, ``a level at which no known or
anticipated adverse effects on the health of persons occur and which
allow for an adequate margin of safety.'' The Safe Drinking Water Act
defines the term ``contaminant'' very broadly to mean any ``physical,
chemical, biological, or radiological substance or matter in water
(SDWA 1401 4(A)(ii)(C)(6)).'' In this context, this proposal addresses
contaminants and certain mixtures of contaminants. A mixture of two or
more ``contaminants'' qualifies as a ``contaminant'' because the
mixture itself is ``any physical, chemical or biological or
radiological substance or matter in water.'' (emphasis added). EPA has
a long-standing history of regulating contaminants in this manner
(i.e., as contaminant groups or mixtures). For instance, the TTHM Rule
(U.S. EPA, 1979) EPA regulated total trihalomethanes as a group due to
their concurrent formation during the chlorination of drinking water;
EPA stating that the four regulated THMs were ``also indicative of the
presence of a host of other halogenated and oxidized, potentially
harmful byproducts of the chlorination process that are concurrently
formed in even larger quantities but which cannot be characterized
chemically'' (USEPA, 1979). In the Stage I and II Disinfection
Byproduct (DBPs) Rules, EPA regulates a second group of DBPs, in this
instance setting regulatory standards for a group of five haloacetic
acids (HAA5) (USEPA, 1998a; 2006a). A third example is EPA's regulation
of radionuclides, where, among other things, EPA regulates
radionuclides mixtures for gross alpha radiation that account for both
natural and man-made alpha emitters as a group rather than individually
(USEPA, 2000d). In summary, EPA has the statutory authority to regulate
groups and/or mixtures of contaminants, EPA has a history of regulating
groups and mixtures of contaminants that have improved public health
protection, and EPA has made a reasonable policy choice for
establishing an MCLG for a mixture of chemicals that are expected to
impact multiple endpoints. Because mixture component chemical HBWCs are
based on overall (i.e., not target-organ specific) RfDs, the approach
is protective against all health effects across component chemicals and
therefore meets the statutory requirements of establishing an MCLG
under SDWA. Basing the mixture MCLG on overall RfDs ensures that there
are no known or anticipated effects, and using the HI adds an
appropriate margin of safety for a class of contaminants that have been
shown to co-occur and evidence indicates that they have additive
toxicity.
2. PFAS Mixture MCLG Derivation
    To account for dose additive noncancer effects associated with
PFHxS, HFPO-DA, PFNA, and PFBS, EPA is proposing an MCLG for the
mixture of these four PFAS based on the HI approach (USEPA, 2023a). As
described in Section IV of this preamble, a mixture HI can be
calculated when HBWCs for a set of PFAS are available or can be
calculated. The health effects information including relevant studies
mentioned in this section are summarized from USEPA (2023a) and are
also described in Section III of this preamble.
    There is currently no EPA RfD available for PFHxS; however, EPA's
IRIS program is developing a human health toxicity assessment for PFHxS
(expected to undergo public comment and external peer review in 2023).
The HBWC for PFHxS is derived using an ATSDR intermediate-duration oral
Minimal Risk Level based on thyroid effects seen in male rats after
oral PFHxS exposure (ATSDR, 2021; USEPA, 2023a). ATSDR calculated an
HED of 0.0047 mg/kg/day and applied a combined UF/MF factor of 300X
(total UF of 30X and a MF of 10X for database deficiencies) to yield an
intermediate-duration oral Minimal Risk Level of 2E-05 mg/kg/day
(ATSDR, 2021). To calculate the HBWC, EPA applied an additional UF of
10 to adjust for subchronic-to-chronic duration, per Agency guidance
(USEPA, 2002), because the effect is not in a developmental population
(i.e., thyroid follicular epithelial hypertrophy/hyperplasia in
parental male rats). The resulting chronic reference value for use in
HBWC calculation was 2E-06 mg/kg/day. EPA selected a DWI-BW for adults
within the general population (0.034 L/kg/day) and applied an RSC of 20
percent (USEPA, 2022c). The resulting HBWC for PFHxS is 9 ng/L (ppt)
(USEPA, 2022c).
    Like EPA's drinking water health advisory for HFPO-DA and its
ammonium salt (USEPA, 2022d), the HBWC that the agency is using for the
HI MCLG was derived from the agency's 2021 human health toxicity
assessment, specifically the chronic RfD of 3E-06 mg/kg/day based on
liver effects observed following oral exposure of mice to HFPO-DA
(USEPA, 2021b). EPA selected a DWI-BW for lactating women (0.0469 L/kg/
day) and applied an RSC of 20 percent (USEPA, 2023a) to calculate the
HBWC for HFPO-DA. The HBWC for HFPO-DA is 10 ng/L (ppt) (USEPA, 2023a).
    There is currently no EPA RfD available for PFNA; however, EPA's
IRIS program is developing a human health toxicity assessment for PFNA.
The HBWC for PFNA is derived using an ATSDR intermediate-duration oral
Minimal Risk Level that was based on developmental effects seen in mice
after oral PFNA exposure (ATSDR, 2021; USEPA, 2023a). ATSDR calculated
an HED of 0.001 mg/kg/day and applied a combined UF/MF factor of 300X
(total UF of 30X and a MF of 10X for database

deficiencies) to yield an intermediate-duration oral Minimal Risk Level
of 3E-06 mg/kg/day (ATSDR, 2021). EPA did not apply an additional UF to
adjust for subchronic-to-chronic duration for PFNA because the critical
effects were observed during a developmental life stage (USEPA, 2002).
EPA used the chronic reference value of 3E-06 mg/kg/day to calculate
the HBWC for PFNA. EPA selected a DWI-BW for lactating women (0.0469 L/
kg/day) and applied an RSC of 20 percent (USEPA, 2023a). The resulting
HBWC for PFNA is 10 ng/L (ppt) (USEPA, 2023a).
    Like EPA's drinking water health advisory for PFBS (USEPA, 2022e),
the HBWC that the agency is using for the HI MCLG was derived from the
agency's 2021 human health toxicity assessment, specifically the
chronic RfD of 3E-04 mg/kg/day based on thyroid effects observed seen
in newborn mice born to mothers that had been orally exposed to PFBS
throughout gestation (USEPA, 2021a; 2023a). EPA selected a DWI-BW for
women of child-bearing age (0.0354 L/kg/day) and applied an RSC of 20
percent (USEPA, 2023a) to calculate the HBWC for PFBS. The HBWC for
PFBS is 2,000 ng/L (ppt) (USEPA, 2023a).
    As described above, the HBWCs for PFHxS, HFPO-DA, PFNA, and PFBS
are 9, 10, 10, and 2000 ppt respectively (see Section III.A of this
preamble, as well as in USEPA (2022c)). HQs are calculated by dividing
the measured component PFAS concentration in water (e.g., expressed as
ppt) by the relevant HBWC (e.g., expressed as ppt), as shown in the
equation below. Component HQs are then summed across the PFAS mixture
to yield the PFAS mixture HI MCLG. Thus, the HI accounts for
differences in toxicity among the mixture component chemicals rather
than weighting them all equally in the mixture. A PFAS mixture HI
greater than 1.0 indicates an exceedance of the health protective level
and indicates potential human health risk for noncancer effects from
the PFAS mixture in water. For more details on this approach, please
see USEPA (2023a). The proposed mixture HI MCLG for PFHxS, HFPO-DA,
PFNA, and PFBS is as follows:
[GRAPHIC] [TIFF OMITTED] TP29MR23.062

Where:

[PFASwater] = the measured component PFAS concentration
in water and
[PFASHBWC] = the HBWC of a component PFAS.

    For example, if each of the four PFAS are measured at their
respective proposed PQLs described in section VIII.A. of this preamble,
the HI calculation would be as follows:
[GRAPHIC] [TIFF OMITTED] TP29MR23.063

    In this scenario, while none of the individual PFAS contaminants
exceed their relative HBWC, when considered in the HI, the sum of the
four PFAS in the HI exceeds 1.0, and therefore is higher than the MCLG.
In the following example, if only PFNA and PFHxS were measured at 8 ppt
each, while also below their individual HWBCs, the two would sum to an
exceedance of the HI.
[GRAPHIC] [TIFF OMITTED] TP29MR23.064

    In a final example, if only a single PFAS, PFHxS were reported
above its PQL, but that value was 20, this would also result in an HI
higher than 1.0.
[GRAPHIC] [TIFF OMITTED] TP29MR23.065

    EPA requests comment on significant figure use when calculating
both the HI MCLG and the MCL (see discussion in section VI of this
preamble). EPA has set the HI MCLG and MCL using two significant
figures (i.e., 1.0). EPA requests comment on the proposed use of two
significant figures for the MCLG when considering underlying health
information and for the MCL when considering the precision of the
analytical methods.
    In conclusion, while current weight of evidence suggests that PFAS
vary in their precise structure and function, exposure to different
PFAS can result in similar health effects. As a result, PFAS exposures
are likely to result in dose-additive effects (ATSDR, 2021; USEPA,
2023a) and therefore the assumption of dose-additivity is reasonable.
While individual PFAS can pose a potential risk to human health if the
exposure level exceeds the chemical-specific toxicity value (RfD or
Minimal Risk Level) (i.e., individual PFAS HQ >1.0), mixtures of PFAS
can result in dose additive health effects when lower individual
concentrations of PFAS are present in that mixture. For example, if the
individual HQs for PFHxS, HFPO-DA, PFNA, and PFBS were each 0.9 that
would indicate that the measured concentration of each PFAS in drinking
water is below the level of appreciable risk (recall that an RfV, such
as an oral RfD, represents an estimate at which no appreciable risk of
deleterious effects exists). However, the overall HI for that mixture
would be 3.6 (i.e., sum of four HQs of 0.9). An HI of 3.6 means that
the total measured concentration of PFAS is 3.6 times the level
associated with potential health risks. Thus, setting an MCLG while
only considering the concentration of an individual PFAS without
considering the dose additive effects from other PFAS in a mixture
would not provide a sufficiently protective MCLG with an adequate
margin of safety. In order to account for dose additive noncancer
effects associated with co-occurring PFAS and PFAS in mixtures, to
protect against health impacts from likely multi-chemical exposures of
PFHxS, HFPO-DA, PFNA, and PFBS, with an adequate margin of safety, the
Agency is proposing to use of the HI approach, a commonly used
component-based mixture risk assessment method, for the MCLG for these
four PFAS (USEPA, 2022). Consistent with the statutory requirement
under 1412(b)(4)(A), establishing the MCLG for PFHxS, HFPO-DA, PFNA,
and PFBS at an HI = 1.0 ensures that MCLG is set at a level where there
are no known or anticipated adverse effect on the health of persons and
ensuring an adequate margin of safety.

VI. Maximum Contaminant Level

    Under section 1412(b)(4)(B) of SDWA, EPA must generally establish
an enforceable MCL as close to the MCLG as is feasible, taking costs
into consideration. The Agency evaluates feasibility according to
several factors including the availability of analytical methods
capable of measuring the targeted compounds in drinking water and
examining available treatment technologies capable of contaminant
removal examined under laboratory and field conditions.

A. PFOA and PFOS

    The Agency evaluated available analytical methods to determine the
lowest concentration at which PFOA and PFOS can reliably be measured in
finished drinking water. There are two analytical methods approved by
EPA for analyzing PFAS regulated under this proposed rule, USEPA
Methods 537.1 and 533. In this evaluation, EPA determined that 4.0 ppt
is the lowest concentration that PFOA and PFOS can be reliably
quantified within specific limits of precision and accuracy during
routine laboratory operating conditions. EPA has historically called
this level the ``practical quantitation level,'' also known as a PQL
(USEPA, 1987). Under UCMR5, EPA published MRLs of 4.0 ppt each for PFOA
and PFOS (USEPA, 2022g). As described in the UCMR 5 rulemaking, this
reporting level is the minimum quantitation level that, with 95 percent
confidence, can be achieved by capable analysts at 75 percent or more
of the laboratories using a specified analytical method (i.e., Method
533 and 537.1, discussed in more detail in section VIII of this
preamble). Based on the multi-laboratory data acquired for the UCMR 5
rule, EPA has defined the PQL for PFOA and PFOS to be equal to the UCMR
5 MRL of 0.0000040 mg/L or 4.0 ppt. This quantitation level provides an
allowance for the degree of measurement precision and accuracy that EPA
estimates can be achieved across laboratories nationwide. Furthermore,
the PQLs provide for consistency in data quality from a diverse group
of laboratories across the country and provide routine performance
goals that many laboratories must strive to achieve. The agency must
have a high degree of confidence in the quantified result as it may
compel utilities to make potentially costly compliance decisions in
order to comply with the MCL. Please see section VIII of this preamble
for more information on analytical methods for PFAS and a detailed
discussion of the PQL and other levels below this quantitation level
that may be appropriate for screening values.
    EPA has promulgated and successfully implemented NPDWRs with MCLs
equal to the contaminant PQLs. In 1987, EPA finalized the Phase I
Volatile Organic Compounds (VOC) rule (USEPA, 1987), where the agency
set the MCL at the PQL for benzene, carbon tetrachloride, p-
dichlorobenzene, trichloroethylene, vinyl chloride, 1,1,1-
trichloroethane, 1,1-dichloroethylene and 1,2-dichloroethane. In that
rule, EPA set the PQL at a level consistent with what was then the
``general rule of five to ten times the [method detection limit] MDL.''
While some commenters at the time stated they believed implementation
would be challenging, EPA notes that those rules have been

implemented successfully and provided an incentive for laboratories to
improve analytical capabilities and reduce method quantitation and
detection limits.
    EPA requests comment on whether setting the MCL at the PQLs for
PFOA and PFOS is similarly implementable and feasible. As in the 1987
rule, EPA recognizes that quantitation of the contaminants can be
achieved between the MDL (e.g., see Method 537.1, section 9.2.8) and
the PQL, albeit not necessarily with the same precision and accuracy
that is possible at and above the PQL. Measuring PFOA and PFOS results
below the PQLs may not be achievable from all laboratories and may not
have the same precision as higher-level measurements, nor does EPA
believe it is appropriate to make potentially costly compliance
decisions based on such lower-level measurements. Nonetheless, the
ability to know that PFOA and PFOS may be present within a certain
range at these low concentrations (i.e., below the PQLs) can be used to
inform decisions for already installed treatment (e.g., a utility can
evaluate when break though is most likely to occur or is imminent) and
to judge appropriate monitoring frequency. In addition, further support
for considering measurement levels below PQL, and the demonstrated
capability of laboratories to support screening at these lower levels,
was found within laboratory calibration standard data submitted as part
of the UCMR 5 Laboratory Approval Program.\4\ These data revealed that
49 of the 54 laboratories seeking EPA approval included a lowest PFAS
calibration standard level at 1 ppt or lower, with the median lowest
calibration level among all laboratories at 0.5 ppt. Therefore, for
almost all laboratories, the proposed PQLs for PFOA and PFOS of 4.0 ppt
are at least 4 times greater than the lowest calibration standard. This
suggests the overwhelming majority of laboratories with the necessary
instrumentation to support PFAS monitoring have the capability to
provide screening measurement results above the proposed trigger level
of \1/3\ of the MCL (i.e., 1.3 ppt for PFOS or PFOS). Hence, a utility
may use the lower-level measurements as a warning that they may be
nearing the PFOA and PFOS MCLs of 4.0 ppt prior to exceeding them and
can make informed treatment decisions about managing their systems
(e.g., replacing GAC). For more information on the proposed trigger
level, please see sections VIII and IX of this preamble. EPA requests
comment on implementation challenges and considerations for setting the
MCL at the PQLs for PFOA and PFOS, including on the costs and benefits
related to this approach.
---------------------------------------------------------------------------

    \4\ Instrument calibration for the approved methods is defined
by analyzing a set of at least five standard solutions spanning a
20-fold concentration range, in which the lowest concentration must
be at or below the quantitation level. Calibration standards below
the quantitation level must meet defined precision requirements. The
resulting calibration curve is validated by measuring standard
solutions of known concentration prepared from commercially
available reference materials. Calibration is confirmed at multiple
points, including by performing an initial calibration and initial
demonstration of capability prior to analysis, through the addition
of internal and surrogate standards, and by incorporating continuous
calibration check samples into the analysis routine.
---------------------------------------------------------------------------

    Additionally, consistent with EPA's SMF for many drinking water
contaminants, EPA is proposing to utilize a running annual average
approach to calculate compliance with this proposed rule. As a result,
a single occurrence of PFOA or PFOS that is slightly above the proposed
MCLs would not result in an MCL violation, assuming other quarterly
samples remain below the MCLs. For example, if a system had a sample
result of PFOA at 5.0 ppt and the remaining quarter sample results were
all 2.0 ppt each, the system would not be violation. In addition, when
calculating the running annual averages, if a sample result is less
than the PQL for the monitored PFAS, EPA is also proposing to use zero
to calculate the average for compliance purposes. For further
discussion on monitoring and compliance, please see section IX of this
preamble. Hence, while EPA believes utilities should endeavor for all
samples to remain below the MCL, the proposed rule allows for temporal
fluctuations in concentrations that may occur because of unexpected
events such as premature PFOA and PFOS breakthrough or temporary
increased source water concentrations. This extra buffer provides the
utilities additional operational safety margins in the event of minor
management or treatment issues. As an alternative, and as described in
more detail in section IX of this preamble, when calculating the
running annual averages, rather than using zero for sample results less
than the PQL, EPA seeks comment on instead using the proposed rule
trigger levels (i.e., 1.3 ppt for PFOA and PFOS) in the case where PFAS
are detected but below their proposed PQLs. This would have the
potential to be more protective in the long run than counting sampling
results below the PQL as zero and provide PWSs greater forewarning that
their results may exceed the MCLs.
    EPA anticipates there would not be sufficient laboratory capacity
if the quantitation level were set at a level below 4.0 ppt. The
rigorous laboratory certification and quality assurance/quality control
(QA/QC) procedures could limit the number of laboratories that can
achieve lower quantitation levels and many water systems would not be
able to secure the services of laboratories that are capable of
consistently providing precise and accurate quantitation of
concentrations of PFOA and PFOS at levels lower than 4.0 ppt. The
Agency has determined that high confidence in the accuracy of
analytical results is necessary to demonstrate that any treatment
technologies are effectively reducing levels of PFOA and PFOS to the
levels as close as feasible to the proposed MCLGs for these
contaminants. To achieve this intended purpose, the Agency is proposing
to establish the MCLs for PFOA and PFOS at this PQL of 4.0 ppt.
    While EPA anticipates potential laboratory capacity issues if the
Agency were to propose MCLs below 4.0 ppt, EPA believes there will be
sufficient laboratory capacity with the MCLs set at 4.0 ppt. As of
September 2022, as a part of the UCMR 5 laboratory approval program,
fifty-four (54) laboratories submitted applications to EPA for approval
to analyze PFOA and PFOS to quantification limits of 4.0 ppt using EPA
Method 533. Each of these 54 laboratories had acquired the analytical
equipment necessary to run both EPA Method 533 and 537.1 and
laboratories are required to achieve and demonstrate they can meet the
PFOA and PFOS PQLs of 4.0 ppt to receive EPA Method 533 approval. EPA
received strong interest from a significant number of laboratories
seeking UCMR 5 laboratory approval, demonstrating there is effective
laboratory capacity to support the program. The commercial market for
PFAS analysis is likely to remain strong and, in fact, grow as more
laboratories develop the technical capability further enhancing lab
capacity to analyze PFAS for drinking water rule compliance purposes.
The various State regulatory monitoring programs established in recent
years for PFAS incorporate laboratory certification/accreditation
programs that further elevate commercial laboratory interest and expand
laboratory capacity. Additionally, because EPA is proposing to allow
the use of existing PFAS monitoring data to meet the initial monitoring
requirements of this proposed rule where available (see section IX of
this preamble for further discussion), EPA anticipates the sudden spike
in laboratory demands that could

otherwise accompany a proposed rule such as this will instead be
distributed during the initial rule implementation timeframe. EPA
requests comment on the underlying assumptions that sufficient
laboratory capacity will be available with the MCLs set at 4.0 ppt;
that demand will be sufficiently distributed during rule implementation
to allow for laboratory capacity; and on the cost estimates related to
these assumptions.
    SDWA 1412(b)(4)(d) defines feasibility as, ``feasible with the use
of the best technology, treatment techniques and other means which the
Administrator finds, after examination for efficacy under field
conditions and not solely under laboratory conditions, are available
(taking cost into consideration).'' Further, Section 1412(b)(4)(E) of
SDWA requires identification of technologies, referred to as best
available technologies (BATs) ``which the Administrator finds to be
feasible for purposes of meeting [the MCL].'' As described in section
XI.A. of this preamble, the Agency identifies the BATs as those meeting
certain criteria including: (1) The capability of a high removal
efficiency; (2) a history of full-scale operation; (3) general
geographic applicability; (4) reasonable cost based on large and
metropolitan water systems; (5) reasonable service life; (6)
compatibility with other water treatment processes; and (7) the ability
to bring all the water in a system into compliance. In section XI of
this preamble, EPA evaluated treatment technologies for the removal of
PFOA and PFOS that would meet these criteria and determined there are
multiple technologies (i.e., GAC, AIX, RO, and NF) that are both
available and have reliably demonstrated PFAS removal efficiencies that
may exceed >99 percent and can achieve concentrations less than the
proposed MCLs for PFOA and PFOS. Based on its evaluation, the Agency
proposes to determine that it is feasible to treat PFOA and PFOS to 4.0
ppt because multiple treatment technologies are effective and available
and there are methods available to reliably quantify PFOA and PFOS at
4.0 ppt. For more information about treatment technologies, please see
section XI of this preamble. For more information about available
analytical methods, please see section VIII of this preamble.
    For purposes of its proposed feasibility determination, EPA also
considered costs when setting the MCLs for PFOA and PFOS at 4.0 ppt and
that analysis supports a finding that 4.0 ppt represents the level of
what is ``feasible'' under the standard of Section 1412(b)(4)(D). Based
on legislative history (A Legislative History of the Safe Drinking
Water Act, Committee Print, 97th Cong., 2d Sess. (1982) at 550), EPA
interprets ``taking cost into consideration'' in Section 1412(b)(4)(D)
to be limited to ``reasonable cost based on large and metropolitan
water systems.'' EPA has determined that 4.0 ppt represents what is
achievable for BATs given the standard of ``reasonable cost based on
large and metropolitan water systems.'' As discussed in section XII of
this preamble, EPA evaluated quantifiable and nonquantifiable costs for
MCLs for PFOA and PFOS at 4.0, 5.0, and 10.0 ppt. As part of that
evaluation, EPA considered capital, operational, administrative,
monitoring, and other costs. In addition to estimating national level
costs associated with the proposed rule and potential regulatory
alternatives, EPA assessed PWS level costs, costs to small systems, and
costs at the household level. For more information about EPA's cost
estimates, please see Best Available Technologies and Small System
Compliance Technologies Per- and Polyfluoroalkyl Substances (PFAS) in
Drinking Water (USEPA, 2023g). EPA considered these cost analyses, in
addition to analytical methods, quantitation levels, and treatment
technologies in coming to its proposed finding that MCLs of 4.0 ppt for
PFOA and PFOS represents levels that are as close as feasible to the
MCLGs. EPA seeks comment on its PFOA and PFOS evaluation of feasibility
for the proposal, including analytical measurement and treatment
capability, as well as reasonable costs, as defined by SDWA.

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

    To protect against the potential for dose additive health impacts
from likely multi-chemical exposures when they occur as mixtures in
drinking water, EPA is proposing an MCL for mixtures of PFHxS, HFPO-DA,
PFNA, and PFBS expressed as an HI. An HI is the sum of HQs from
multiple substances. HQs are the ratio of potential exposure to a
substance and the level at which no health effects are expected. EPA is
proposing the MCL for mixtures of PFHxS, HFPO-DA, PFNA, and PFBS as
equal to the MCLG: as proposed, the HI must be equal to or less than
1.0. SDWA section 1401(3) defines an MCL as the ``maximum permissible
level of a contaminant in water which is delivered to any user of a
public water system.'' This approach, as proposed, sets a permissible
level for the contaminant mixture (i.e., a resulting PFAS mixture HI
greater than 1.0 indicates an exceedance of the health protective level
and indicates potential human health risk for noncancer effects from
the PFAS mixture in water). If there is only one contaminant PFAS
present, the HI approach in practice also sets a permissible level for
the individual contaminant through the use of its respective HBWC (see
example and discussion in section V.C2 of this preamble). As discussed
below in this section (section VI.D. of this preamble) and in section
XIII of this preamble, the Agency is also inviting comment on whether
establishing a traditional MCLG and MCL for PFHxS, HFPO-DA, PFNA, and
PFBS instead of or in addition to the HI approach would change public
health protection, improve clarity for the rule, or change costs.
    EPA asked the SAB for advice on using an HI approach as an option
for PFAS mixture assessment under an assumption of dose additivity.
Consistent with EPA Guidance (e.g., USEPA, 2000a; USEPA, 1989) the HI
is used here as a decision aid, and determination of dose additivity
among chemicals is relaxed from the level of common MOA to common
target organ(s)/health outcome(s). Per SAB's suggestion, EPA outlines
here the validity of, and procedures for, calculating the HI given a
mixture such as this one that includes PFAS with varying levels of
available information across health outcomes.
    Consistent with advice from the SAB, EPA considers it an
appropriately health protective approach to assume dose additivity for
PFAS co-occurring in mixtures as they share similar profiles of health
effect domains (e.g., liver, thyroid, developmental, etc.). EPA's
analysis of finished water monitoring data demonstrates that PFAS often
have a substantial likelihood to co-occur in mixtures (see section
III.D of this preamble). While PFAS are well documented to co-occur,
the exact chemical composition is often site-specific in nature (i.e.,
each location of PFAS mixture is influenced by different environmental
point and diffuse sources that results in a unique PFAS profile)
(Banzhaf et al., 2017). Yet, EPA finds that PFHxS, HFPO-DA, PFNA, and
PFBS often co-occur in mixtures in drinking water, including with other
PFAS (USEPA, 2023e). To protect against the potential for dose additive
health impacts from likely multi-chemical exposures of PFHxS, HFPO-DA,
PFNA, and PFBS when they occur as mixtures in drinking water, the
Agency is proposing to use the HI approach. Both EPA's recent PFAS
mixture's framework (USEPA, 2023d), and SAB's review of the prior draft
of

this document discuss the strengths and limitations associated with
using an HI approach as the basis for evaluating potential health risks
associated with exposure to mixtures of PFAS, and consideration as a
metric to inform health-based decision-making for regulatory purposes
(USEPA, 2022a). For a full discussion of the strengths and limitations
identified during SAB's review and how EPA responded, please see USEPA,
2022a and 2023f. The HI approach is used regularly by EPA (and States)
to inform potential health risks of chemical mixtures associated with
contaminated sites/locations under the Comprehensive Environmental
Response, Compensation, and Liability Act (CERCLA)/the Superfund
Amendments and Reauthorization Act (SARA); as such, the application of
the HI approach under a regulatory purview is not novel for the Agency
though this is the first use of an HI approach for a SDWA National
Primary Drinking Water Regulation.
    EPA is proposing an MCL based on a HI composed of the four PFAS for
which there are validated EPA methods for measurement and treatment,
evidence of co-occurrence, the potential for similar health effects,
and the availability of finalized peer reviewed toxicity values to use
in generating the HI. For this proposal, those PFAS are PFHxS, HFPO-DA,
PFNA, and PFBS. The MCL for mixtures of PFHxS, HFPO-DA, PFNA, and PFBS
would be an HI = 1.0. In this proposal, the HBWCs that EPA uses to
calculate the HI are proposed to be 9.0 ppt for PFHxS; 10.0 ppt for
HFPO-DA; 10.0 ppt for PFNA; and 2000 ppt for PFBS (USEPA, 2023a). To
calculate the proposed HI, regulated PWSs would be required to monitor
to determine the concentrations of PFHxS, HFPO-DA, PFNA, and PFBS in
their finished drinking water. See section IX of this preamble for
proposed requirements related to monitoring and determining compliance.
See equation below for calculation of the PFHxS, HFPO-DA, PFNA, and
PFBS HI MCL:
[GRAPHIC] [TIFF OMITTED] TP29MR23.066

Where:

HFPO-DAwater = monitored concentration of HFPO-DA;
PFBSwater = monitored concentration of PFBS;
PFNAwater = monitored concentration of PFNA; and
PFHxSwater = monitored concentration of PFHxS

    See discussion in section IV of this preamble above for how EPA
derived these values for these contaminants.
    As described in section VI.A. of this preamble for PFOA and PFOS,
the Agency has similarly considered feasibility as defined by SDWA
1412(b)(4)(D) for PFHxS, HFPO-DA, PFNA, and PFBS. The Agency has
determined that there are validated analytical methods that can measure
below the HBWC for each of these PFAS. Additionally, as discussed
above, the Agency proposes to determine that it is feasible to treat
each of these PFAS to below their PQL (between 3.0-5.0 ppt) and it is
feasible to treat these PFAS to below their PQLs individually and as a
group. When identifying BATs, EPA evaluated the same factors as defined
previously in Section VI.A. and in Section XI.A. of this preamble and
has found the same technologies identified for PFOA and PFOS are also
both available and have reliably demonstrated PFAS removal efficiencies
that may exceed >99 percent and achieve concentrations less than the
proposed HI MCL for PFHxS, HFPO-DA, PFNA, and PFBS.
    As described in section VI.A. of this preamble for PFOA and PFOS,
the Agency similarly considered costs as part of its proposed
feasibility determination for PFHxS, HFPO-DA, PFNA, and PFBS and
setting the HI MCL at 1.0. EPA's analysis supports a finding that an HI
of 1.0 is ``feasible'' under standard of SDWA 1412(b)(4)(D) because it
is achievable for BATs given the standard of ``reasonable cost based on
large and metropolitan water systems.'' For more information about
EPA's cost estimates, please see Best Available Technologies and Small
System Compliance Technologies Per- and Polyfluoroalkyl Substances
(PFAS) in Drinking Water (USEPA, 2023g; USEPA, 2023h). EPA considered
these cost analyses, in addition to analytical methods, quantitation
levels, and treatment technologies in coming to its proposal that an HI
MCL of 1.0 for PFHxS, HFPO-DA, PFNA, and PFBS represents a level that
is as close as feasible to the MCLG. EPA seeks comment on its
evaluation of feasibility for the proposed HI MCL finding, including
analytical measurement and treatment capability, as well as reasonable
costs, as defined by SDWA.

C. Reducing Public Health Risk by Protecting Against Dose Additive
Noncancer Health Effects From PFAS

    As described above, PFOA and PFOS are demonstrated to have the
potential for adverse health effects at low levels of exposure. The
level at which no known or anticipated adverse effects on the health of
persons would occur is well below current analytical quantitation level
for PFOA and PFOS. To ensure maximum public health protection for these
contaminants, the statute generally requires that exposure be driven to
the lowest feasible concentration.
    Because of the analytical limitations discussed in the preceding
section VI.A of this preamble, EPA is not proposing to include PFOA and
PFOS in the HI. The only feasible way to represent PFOA and PFOS in the
HI approach would be to only consider values for PFOA and PFOS at or
above the PQL of 4.0 ppt. As a result, any measured concentration above
4.0 ppt for PFOA and PFOS would result in an exceedance of the HI of
1.0. Therefore, regulating PFOA and PFOS under a HI approach would not
add any meaningful health protection over setting an individual MCL for
these PFAS. Additionally, EPA believes that adding PFOA or PFOS to the
HI could increase potential compliance challenges with the rule as
there could be confusion created by how to consider screening level
values above detection but below quantitation (see additional
discussion in section VIII of the preamble for discussion on screening
and trigger levels). Therefore, EPA is proposing to set MCLs for PFOA
and PFOS individually and not part of the HI.
    Some PFAS (such as PFHxS, HFPO-DA, PFNA, and PFBS) have HBWCs at
thresholds higher than current analytical quantitation levels. As a
result of assuming dose-additivity, PFHxS, HFPO-DA, PFNA, and PFBS

may have individual detectable or quantifiable concentrations below
their individual HBWCs, but their combined concentrations can be above
levels of health concern. As proposed, the HI MCL provides a protective
approach to avoiding these potential health risks associated with
mixtures of PFAS that are below the public health goals individually,
yet exceed the PFAS mixture limit (i.e., HI MCL = 1.0). Separating PFOA
and PFOS away from a HI approach is not meant to ignore the potential
dose additive health impacts for these compounds in mixtures. As
described in the preceding paragraph, EPA is not including PFOA and
PFOS as part of the HI approach because the Agency believes doing so
would not add meaningful health protection over setting an individual
MCL for these PFAS.
    EPA recognizes that some PFAS such as PFOA, PFOS, and PFNA have
been voluntarily phased out of production and replaced in the United
States so their relative concentrations in source waters may decrease
over time. However, other PFAS that have been shown to also cause
adverse health effects (e.g., perfluorobutanoic acid [PFBA], PFBS,
HFPO-DA) may increase in concentration as their production, use, and
discharges into source water continues. The HI framework is designed to
inform protection of human health for any source water PFAS, with
available human health assessment values, still in production and use.
Under the HI approach, additional PFAS can be added over time once more
information on health effects, analytics, exposure and/or treatment
becomes available, and merits additional regulation as determined by
EPA. As such, this approach provides a framework for Federal and State
public health agencies to consider using to address other PFAS in the
future as needed.

D. Regulatory Alternatives

    As discussed in section VI.A of this preamble above, EPA proposes
to determine that it is feasible to set MCLs for PFOA and PFOS at 4.0
ppt each and that the level is as close as feasible to the MCLGs. As
discussed in Section VI.B of this preamble, EPA proposes to determine
it is feasible to set an MCL for mixtures of PFHxS, HFPO-DA, PFNA, and
PFBS as a HI = 1.0 which is the same level as the MCLG.
    In section XIII of this preamble, the HRRCA section of this
proposal, EPA is presenting estimated costs and benefits of regulatory
alternatives for PFOA and PFOS of MCLs at 4.0, 5.0 ppt and 10.0 ppt.
Quantified costs and benefits for the proposed option and alternative
options considered are summarized in section XIII.H of this preamble,
specifically tables 66-69. Tables 70-71 summarize the non-quantified
benefits and costs and assess the potential impact of non-quantifiable
benefits and costs on the overall benefits and costs estimate.
Establishing only MCLs at 4.0 ppt for PFOA and PFOS instead of the
proposed rule (MCLs at 4.0 ppt for PFOA and PFOS and the HI) would
result in a reduction of $16 million in quantified costs and $17
million in quantified benefits at the 3% discount level and $27 million
in quantified costs and $13 million in quantified benefits at the 7%
discount level. Establishing MCLs at 5.0 ppt for PFOA and PFOS instead
of 4.0 ppt would result in a reduction of $145 million in quantified
costs and $169 million in quantified benefits at the 3% discount level
and $235 million in quantified costs and $122 million in quantified
benefits at the 7% discount level. Establishing MCLs at 10.0 ppt for
PFOA and PFOS instead of 5.0 ppt would result in a reduction of $318
million in quantified costs and $462 million in quantified benefits at
the 3% discount level and $511 million in quantified costs and $337
million in quantified benefits at the 7% discount level. EPA notes that
there would also be commensurate reduction in the nonquantifiable
benefits and costs among these options. As discussed elsewhere in this
proposal, the nonquantifiable benefits are anticipated to be
significant. EPA evaluated these regulatory alternatives in its HRRCA,
discussed in Section XIII of this preamble below and is requesting
comment on these alternatives.
    EPA considered an MCL of 5.0 ppt for PFOA and PFOS because it is 25
percent above the PQL of 4.0 ppt. A commenter in EPA's outreach
consultations for this regulation suggested the Agency consider a
buffer of approximately 20 percent if the MCL is close to the
quantitation level because water systems operate with a margin of
safety and plan for performance that maintains water quality below
quantitation levels. Therefore, in this commenter's opinion, having an
increased buffer between the PQL and the MCL may allow utilities to
manage treatment technology performance more efficiently because
utilities typically aim to achieve lower than the MCL to avoid a
violation. With the MCL at the PQL, the commenter believes that
utilities would not have the early warning that they may exceed the MCL
prior to doing so. EPA disagrees that utilities would not have early
warning prior to exceeding the MCL; see discussion above in section
VI.A of this preamble for more information. For results between the
detection limit and the PQL, EPA has determined that utilities would be
able to reliably conclude analyte presence, though this detection is
less precise regarding specific concentration. Knowledge regarding the
presence of PFOA and PFAS at concentrations below PQLs can inform
decisions related to monitoring frequency and existing treatment. EPA
requests comment on this approach.
    EPA also considered the MCL of 10.0 ppt to evaluate the national
costs and benefits and whether the expected reduction in costs would
change EPA's determination of the level at which the benefits would
justify the costs. See SDWA Section 1412(b)(6)(A). The Agency notes
that this regulatory alternative level is consistent with State-enacted
MCLs for certain PFAS (NYDOH, 2020). Because there is significant
expected occurrence of PFOA and PFOS between 4.0 ppt and 10.0 ppt,
raising the MCL from 4.0 to 10.0 would be expected to significantly
decrease the number of utilities that must take action to manage PFOA
and PFOS concentrations in their finished drinking water. However, it
would also result in millions of Americans continuing to be exposed to
levels that have the potential for harmful levels of PFOA and PFOS that
can feasibly be removed through treatment, thereby decreasing the
quantified and non-quantified benefits delivered by this proposed
regulation. Furthermore, since EPA has found proposed PFOA and PFOS
MCLs of 4.0 ppt to be feasible, the Agency must set the MCL as close to
the MCLG as feasible, the Administrator determined the costs were
justified by the benefits at a PFOA and PFOS proposed MCL at 4.0 (see
discussion in section XIII of this preamble), and setting the PFOA and
PFOS MCLs at 10.0 ppt would not reduce PFOA and PFOS exposure risks for
millions of Americans to the extent feasible, EPA preliminarily
determined that proposing PFOA and PFOS MCLs at 10.0 ppt would not be
appropriate or justifiable under the SDWA statutory criteria.
    EPA also considered the traditional approach of establishing
individual MCLGs and MCLs for PFHxS, HFPO-DA, PFNA, and PFBS in lieu of
or in addition to separate rule language for the HI approach. As noted
earlier, this action includes a preliminary determination to regulate
these additional PFAS and their mixtures. EPA's proposed HI approach
addresses both the particular PFAS and their mixtures. If EPA does not
finalize a

regulatory determination for mixtures of these PFAS, then a more
traditional approach may be warranted. Under this alternative, the
proposed MCLG and MCL for PFHxS would be 9.0 ppt; for HFPO-DA the MCLG
and MCL would be 10 ppt; for PFNA the MCLG and MCL would be 10 ppt; and
for PFBS the MCLG and MCL would be 2000 ppt (i.e., 2.0x103 or 2.0e+3).
As discussed in section XIII of this preamble, EPA has not separately
presented changes in quantified costs and benefits for these
approaches. If EPA adds individual MCLs in addition to using the HI
approach, EPA anticipates there will be no change in costs and benefits
relative to the proposed rule (i.e., the same number of systems will
incur identical costs to the proposed option and the same benefits will
be realized). EPA has not separately quantified the benefits and costs
for the approach to regulate PFHxS, PFNA, PFBS, and HFPO-DA with
individual MCLs instead of the HI. However, EPA expects both the costs
and benefits would be reduced under this approach as fewer systems may
be triggered into treatment and its associated costs. Additionally,
systems that exceed one or more of the individual MCLs will treat to a
less stringent and public health-protective standard. Furthermore,
while EPA recognized that regulating these PFAS with individual MCLs
and MCLGs might be simpler to implement for some states or operators,
if EPA were to regulate these PFAS individually and not under the HI
MCL approach, it would not provide equivalent protection against
potential dose additive impacts for these PFAS, nor would it establish
a framework to consider potential dose additive impacts for future PFAS
components or groups as EPA develops a better understanding of the
adverse health effects of other PFAS. The Agency is requesting comment
on whether establishing a traditional MCLG and MCL for PFHxS, HFPO-DA,
PFNA, and PFBS instead of or in addition to the HI approach would
change public health protection, improve clarity of the rule, or change
costs.
    EPA also considered an alternative regulatory construct of
establishing both MCLGs and MCLs for these four PFAS in addition to
separate rule language for the HI MCL. Hence, these four PFAS would
expressly be subject to two MCLs: the individual MCLs and the HI MCL
for the mixture. However, this approach has the potential to function
the same as the proposed rule because a system cannot have MCL
violations of an individually regulated PFAS without also exceeding the
HI MCL. EPA considered this approach because it may improve the ability
to communicate about PFAS risks with PWSs and the public, while still
providing the important benefit of protection against dose additive
impacts from these PFAS with the HI approach, as well as building a
potential framework for considering future PFAS regulation. Moreover,
this approach may improve the ability to communicate about PFAS
concentrations and their relative importance with operators and the
public although there may be challenges in risk communication with
respect to those small number of facilities that would not exceed an
individual MCL but would exceed the HI MCL.
    While EPA evaluated these regulatory alternatives, EPA proposal is
based upon its proposed finding that an MCL of 4.0 ppt for PFOA and
PFOS and an HI of 1.0 for PFHxS, HFPO-DA, PFNA, and PFBS are feasible
because treatment technologies are available that treat to below these
levels and there are analytical methods that can reliably quantify at
these levels (See discussion above in Section VI.A and Section VIII of
this preamble). Additionally, EPA determined that the benefits justify
the costs with the current rule's proposed MCLs of 4.0 ppt and an HI of
1.0 for PFHxS, HFPO-DA, PFNA, and PFBS.
    When proposing an MCL, EPA must publish, and seek public comment
on, the HRRCA for the proposed MCL and each alternative standard
considered under paragraphs 5 and 6(a) of Section 1412(b) (SDWA Section
1412(b)(3)(C)(i)), including:
     the quantifiable and nonquantifiable health risk reduction
benefits attributable to MCL compliance;
     the quantifiable and nonquantifiable health risk reduction
benefits of reduced exposure to co-occurring contaminants attributable
to MCL compliance;
     the quantifiable and nonquantifiable costs of MCL
compliance including monitoring, treatment, and other costs;
     the incremental costs and benefits of each alternative
MCL;
     the effects of the contaminant on the general population
and sensitive subpopulations likely to be at greater risk of exposure;
and
    any adverse health risks posed by compliance; and
     other factors such as data quality and uncertainty.
    EPA provides this information in section XIII in this preamble. EPA
must base its action on the best available, peer-reviewed science and
supporting studies, taking into consideration the quality of the
information and the uncertainties in the benefit-cost analysis (SDWA
Section 1412(b)(3)). The following sections, as well as the health
effects discussion in sections IV and V of this preamble document the
science and studies that EPA relied upon to develop estimates of
benefits and costs and understand the impact of uncertainty on the
Agency's analysis.

E. MCL-Specific Requests for Comment

    EPA specifically requests comment on its proposal to set MCLs at
4.0 ppt for PFOA and PFOS and whether 4.0 ppt is the lowest PQL that
can be achieved by laboratories nationwide. EPA also requests comment
on implementation challenges and considerations for setting the MCL at
the PQLs for PFOA and PFOS. EPA requests comment on its evaluation of
feasibility under SDWA for the proposed PFOA and PFOS MCLs and the
proposed HI MCL. EPA also requests comment on using an HI approach for
PFHxS, HFPO-DA, PFNA, and PFBS. Additionally, EPA requests comment on
its decision to establish stand-alone MCLs for PFOA and PFOS in lieu of
including them in the HI approach. Finally, EPA specifically requests
comment on whether establishing a traditional MCLG and MCL for each of
the following: PFHxS, HFPO-DA, PFNA, and PFBS instead of or in addition
to the HI approach would change public health protection or improve
clarity of the rule; or change anticipated costs.

VII. Occurrence

    EPA relied on multiple data sources, including UCMR 3 and state
finished water data to evaluate the occurrence and probability of co-
occurrence of PFOA, PFOS, PFHxS, HFPO-DA, PFNA, and PFBS. EPA also
incorporated both the UCMR 3 and some state data into a Bayesian
hierarchical model which supported exposure estimates for select PFAS
at lower levels than were measured under UCMR 3. EPA has utilized
similar statistical approaches in past regulatory actions to inform its
decision making, particularly where a contaminant's occurrence is
infrequent or at low concentrations (USEPA, 2006b). The specific
modeling framework used to inform this regulatory action is based on
the peer-reviewed model published in Cadwallader et al. (2022).
Collectively, these data and the occurrence model informed estimates of
the number of

water systems (and associated population) expected to be exposed to
levels of PFOA and PFOS which would potentially exceed the proposed and
alternative MCLs, and to levels of PFHxS, HFPO-DA, PFNA, and PFBS that
would potentially exceed the HI.
    EPA relied on the UCMR 3 as the primary source of nationwide
occurrence data to inform the occurrence model's exposure estimates for
four PFAS: PFOA, PFOS, perfluoroheptanoic acid (PFHpA), and PFHxS.
Additionally, as described in the final regulatory determination for
PFOA and PFOS (USEPA, 2021d), EPA has also considered and evaluated
publicly-available state finished water PFAS monitoring data, including
data on PFOA, PFOS, PFHxS, HFPO-DA, PFNA, and PFBS.

A. UCMR 3

    As discussed in section III.B. of this preamble, UCMR 3 monitoring
occurred between 2013 and 2015 and is currently the best nationally
representative finished water dataset for any PFAS, including PFOA,
PFOS, PFNA, PFBS, and PFHxS. Under UCMR 3, 36,972 samples from 4,920
PWSs were analyzed for these five PFAS.
    PFOA was found above the UCMR 3 MRL (20 ppt) in 379 samples at 117
systems serving a population of approximately 7.6 million people
located in 28 states, tribes, or U.S. territories. PFOS was found in
292 samples at 95 systems above the UCMR 3 MRL (40 ppt). These systems
serve a population of approximately 10.4 million people located in 28
states, tribes, or U.S. territories. PFHxS was found above the UCMR 3
MRL (30 ppt) in 207 samples at 55 systems that serve a population of
approximately 5.7 million located in 25 states, tribes, and U.S.
territories. PFBS was found in 19 samples at 8 systems above the UCMR 3
MRL (90 ppt). These systems serve a population of approximately 350,000
people located in 5 states, tribes, and U.S. territories. Lastly, PFNA
was found above the UCMR 3 MRL (20 ppt) in 19 samples at 14 systems
serving a population of approximately 526,000 people located in 7
states, tribes, and U.S. territories.

B. State Drinking Water Data

    As discussed in section III.B of this preamble, the Agency has
supplemented its UCMR 3 data with more recent data collected by states
who have made their data publicly available. In general, the large
majority of these more recent state data were collected using newer
EPA-approved analytical methods and state results reflect lower
reporting limits than those in the UCMR 3. State results show continued
occurrence of PFOA, PFOS, PFHxS, PFBS, and PFNA in multiple geographic
locations. These data also show these PFAS occur at lower
concentrations and significantly greater frequencies than were measured
under the UCMR 3. Furthermore, these data include results for more PFAS
than were included in the UCMR 3, including HFPO-DA.
    EPA evaluated publicly available monitoring data from the following
23 states: Alabama, Arizona, California, Colorado, Delaware, George,
Illinois, Kentucky, Maine, Massachusetts, Maryland, Michigan, Missouri,
New Hampshire, New Mexico, New Jersey, North Carolina, North Dakota,
Ohio, Pennsylvania, Rhode Island, South Carolina, and Vermont. The data
EPA used in its analyses were collected from public state websites
through August 2021, but represent sampling conducted on or before May
2021.
    The available data are varied in terms of quantity as well as
coverage, and some are from targeted sampling efforts (i.e., monitoring
in areas of known or potential PFAS contamination) so may not be
representative of levels found in all PWSs within the state or
represent occurrence in other states. EPA further refined this dataset
based on representativeness and reporting limitations, resulting in
detailed technical analyses using a subset of the available state data
(i.e., all 23 states' data were not included within the detailed
technical analyses). USEPA (2023e) presents a comprehensive discussion
of all the available state PFAS drinking water occurrence data.
    Tables 5 and 6 in this section demonstrate the number and percent
of samples with PFOA and PFOS state reported detections, and the number
and percent of monitored systems with PFOA and PFOS state reported
detections, respectively, for the non-targeted state finished water
monitoring data. Section III.B. of this preamble describes the state
reported finished water occurrence data for PFHxS, HFPO-DA, PFNA, and
PFBS data.
    Different states utilized various reporting thresholds when
presenting their data, and for some states there were no clearly
defined limits. Further, the limits often varied within the data for
each state depending on the specific analyte, as well as the laboratory
analyzing the data. In some cases, states reported data at
concentrations below EPA's proposed rule trigger level and/or PQLs in
this document. However, to present the best available occurrence
information, EPA collected and evaluated the data based on the
information as reported directly by the states. When conducting data
analyses, EPA incorporated individual state-specific reporting limits
where possible. Specific details on state data reporting thresholds are
available in USEPA (2023e).

Table 5--Non-Targeted State PFOS and PFOA Finished Water Data--Summary of Samples With State Reported Detections
                                                       \1\
----------------------------------------------------------------------------------------------------------------
                                            PFOS samples       PFOS state       PFOA samples       PFOA state
                                             with state     reported  sample     with state     reported  sample
                  State                       reported           percent          reported           percent
                                             detections         detection        detections        detections
----------------------------------------------------------------------------------------------------------------
Alabama \2\.............................               140               N/A                80               N/A
Colorado................................                60              10.3                54               9.3
Illinois................................                55               5.2                56               5.3
Kentucky................................                33              40.7                24              29.6
Massachusetts...........................               441              49.1               506              66.5
Michigan................................                70               2.5               103               3.6
New Hampshire...........................               495              27.1             1,010              55.3
New Jersey..............................             3,512              37.2             4,379              46.4
North Dakota............................                 0               0.0                 0               0.0
Ohio....................................                93               4.9                93               4.9
South Carolina..........................                88              57.9                82              53.9

Vermont.................................                87               6.9               109               8.7
----------------------------------------------------------------------------------------------------------------
Notes:
\1\ Detections determined by individual state reported limits which are not defined consistently across all
  states.
\2\ Only reported detections.

 Table 6--Non-Targeted State PFOS and PFOA Finished Water Data--Summary of Monitored Systems With State Reported
                                                 Detections \1\
----------------------------------------------------------------------------------------------------------------
                                                               PFOS state                          PFOA state
                                           PFOS  monitored      reported       PFOA  monitored      reported
                  State                     systems with        monitored       systems with        monitored
                                           state reported    system percent    state reported    system percent
                                             detections         detection        detections        detections
----------------------------------------------------------------------------------------------------------------
Alabama \2\.............................                49               N/A                28               N/A
Colorado................................                50              12.6                45              11.3
Illinois................................                36               5.5                32               4.9
Kentucky................................                33              40.7                24              29.6
Massachusetts...........................               107              47.3               126              55.5
Michigan................................                55               2.6                82               3.8
New Hampshire...........................               189              33.8               310              55.4
New Jersey..............................               494              45.9               564              52.4
North Dakota............................                 0               0.0                 0               0.0
Ohio....................................                29               2.0                32               2.2
South Carolina..........................                42              82.4                40              78.4
Vermont.................................                35               6.3                44               7.9
----------------------------------------------------------------------------------------------------------------
Notes:
\1\ Detections determined by individual state reported limits which are not defined consistently across all
  states.
\2\ Only reported detections.

    As illustrated in Tables 5 and 6, there is a wide range in PFOA and
PFOS results between states, however in nearly half of states that
conducted non-targeted monitoring, more than 25 percent of the
monitored systems found PFOA and/or PFOS. Additionally, considering all
states in Tables 5 and 6, PFOA detected concentrations ranged from 0.51
to 153 ppt with a range of median detected concentrations from 1.98 to
9.4 ppt, and PFOS detected concentrations ranged from 0.5 to 350 ppt
with a range of median detected concentrations from 3 to 11.9 ppt.
    Monitoring data for PFOA and PFOS from states that conducted