North Carolina Department of Environmental Quality
and
North Carolina Department of Health and Human Services
Secretaries’ Science Advisory Board
Review of the North Carolina Drinking Water Provisional Health Goal for GenX
August 2018

FINAL DRAFT

 Section 1 – The Secretaries’ Science Advisory Board
The Secretaries for the North Carolina Departments of Environmental Quality (DEQ) and of
Health and Human Services (DHHS) established their Science Advisory Board (SAB) in July 2017.
It is founded on recognition that clean air, water and land are critical to quality of life, to
protect health and to promote a vibrant economy for all North Carolinians. The Board
comprises experts in toxicology, epidemiology, environmental science, environmental
engineering, medicine and other disciplines and their expertise will help guide the two agencies
in carrying out their responsibilities to protect the safety and health of the citizens. The Board
provides advice on the adverse effects of environmental contaminants, monitoring and
measuring exposure to environmental contaminants, and on their control.
The Board performs or recommends reviews and evaluations of contaminants released to the
environment; acts as consultants on DEQ’s determinations to regulate releases of
contaminants; assists both agencies in identifying contaminants of emerging concern and helps
determine whether the contaminants should be studied further; assists the Secretaries in
providing expertise to evaluate the human and environmental impacts of exposure to
hazardous contaminants; and provides input to DHHS as the agency establishes health goals for
emerging contaminants.
Specifically, the charter of the NC DEQ and NC DHHS Secretaries’ Science Advisory Board (SAB)
states the following duties of the board includes:
(a) To perform or recommend reviews and/or evaluations of matters concerning the release
of contaminants to the environment that are placed on the Board agenda by DEQ or DHHS.
(b) To advise the EMC [Environmental Management Commission] on information concerning
the regulation and evaluation of releases of contaminants that come to the attention of the
Board.
(c) To review the effects of chemicals that are proposed to be regulated by DEQ as
contaminants and to recommend the necessity and/or urgency for controlling the releases of
such chemicals that are found to cause deleterious environmental and human health effects
with priority given to the study of contaminants for which control has been deferred pending
further study.
(d) To act as consultants regarding the DEQ’s determinations to regulate releases of
contaminants and in determining factors for establishing acceptable levels for contaminants
and for remediation levels for contaminants in other media.

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 (e) To recommend concentrations of contaminants in a "range of risks" to DEQ and EMC for
regulation that will minimize adverse health responses in the exposed citizenry and to advise
the EMC of the scientific basis for these recommendations.

Section 2 – The Board’s Charge for GenX
The Departments asked the Board to review information on GenX1, including a review of the
DHHS provisional drinking water health goal and of available scientific information about health
and environmental concerns and their control, and to provide recommendations to DEQ on the
starting point for developing regulatory standards.
During the January 29, 2018 SAB meeting DEQ and DHHS were asked for clarification on the
type of deliverables the Board was requested to provide to the agencies. DEQ requested the
Board provide recommendations on a reference dose which would be used to establish water
quality standards for GenX. DHHS requested the Board review and provide recommendations
on the derivation and calculation of the health goal for GenX, including the point of departure
(POD), the calculation parameters, the uncertainty factors, and the options to use benchmark
dose (BMD) modeling in lieu of a NOAEL (No Observed Adverse Effect Level) approach, and to
provide feedback on any future modifications.

Section 3 – GenX in North Carolina
GenX is an artificial chemical and does not occur naturally. It is produced commercially for use
in manufacturing non-stick coatings and may be an unintended by-product of other processes
that produce related compounds. The Chemours (formerly DuPont) facility in Fayetteville NC
has manufactured GenX since 2009 as a replacement for PFOA and PFOS2, two chemicals which
have been associated with adverse human health effects including developmental,
reproductive, immunological, and cancer adverse health outcomes and are part of the same
broad family of chemicals known as per- and polyfluoroalkyl substances (PFAS). GenX has also
been produced as a by-product of the facility’s vinyl ether manufacturing process for more than
three decades. GenX, and previously PFOA, have been released from the DuPont/Chemours
plant in Fayetteville to air and to surface water. Public concern about GenX and related
compounds escalated in June 2017 following reports that GenX had been detected in the Cape
Fear River, which is the primary source of drinking water to the city of Wilmington and some
other communities in North Carolina. GenX and other PFAS were also found in finished
1

2

GenX is correctly the name of the manufacturing process, but is commonly used, and is used here, to refer to a
key chemical in the process: 2,3,3,3-tetrafluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)-propanoic acid (CASN
13252-13-6)
The chemical name for PFOA is perfluorooctanoic acid (CASN 335-67-1). The chemical name for PFOS is
perfluorooctane-sulfonate (CASN 1763-23-1).

2

 municipal drinking waters sourced from the Cape Fear River downstream of the
Chemours/DuPont plant. GenX has also been found in the environment close to the
Chemours/DuPont plant in Fayetteville. There are presently no federal nor state environmental
standards for GenX.
GenX, C6HF11O3, is a clear, colorless liquid with high water solubility (100,000 – 300,000 mg/L),
apparent low organic carbon partitioning capacity (estimated Kow 1.3 – 2.0)3, that under normal
environmental conditions exists as an anionic acid (2.8 pKa acid dissociation constant)4 (Hoke et
al., 2016).

Section 4 – The Board’s GenX Review Process
The Board addressed GenX at its meetings on October 23, 2017; December 4, 2017; January 29,
2018; March 19, 2018; April 30, 2018; and June 18, 2018. It invited and received comments
from concerned entities during public comment portions of those meetings. Board members
reviewed extensive documentation provided by the Departments and accompanying written
submissions and sought insights from related activities in the Netherlands, where GenX has
been found in the environment around a Chemours facility. The Board recommended
additional analyses by the Departments and received the results. The Board recognizes the
participation of staff of the Department of Agriculture and Consumer Services in its discussions.
A summary of the meetings, documents and work are provided below and related documents
are available on the SAB website at https://deq.nc.gov/news/hot-topics/genxinvestigation/secretaries-science-advisory-board.
October 23, 2017 – During this meeting, the Department of Environmental Quality and the
Department of Health and Human Services identified priority areas about which they requested
input from the Board. Issues relevant to PFAS and GenX were identified as among those
priorities.
The broad family of per- and poly-fluoroalkyl substances (PFAS) contains many compounds,
including as many as 3000 manufactured chemical structures. Some older legacy compounds,
e.g. PFOA and PFOS, have substantial health data and regulatory standards. However, the PFAS
family also contains many emerging compounds about which there are limited or no human
health or ecological effects data, and for which there are no regulatory standards. Many of
these emerging PFAS compounds have been found as environmental contaminants in North
Carolina. GenX is one of the emerging PFAS compounds for which there are no current
regulatory standards. However, there are limited health data regarding GenX that were
3

4

Kow is the octanol-water partitioning coefficient, the ratio of the equilibrium concentration of a dissolved
chemical in a two-phase system of n-octanol and water. n-Octanol serves as a surrogate to biota lipids and Kow
values are used as an indicator of a chemicals tendency to bioaccumulate, or to be taken-up by organisms from
the environment.
The pKa predicts that GenX will be in acid form (as a negative ion, or an anion) at pH levels at or below 2.8 pH.

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 deemed sufficient by DHHS to calculate a “reference dose” (RfD)5 and provisional health goal
(PHG) for drinking water. The state agencies requested the Board examine and provide input
on the current reference dose and provisional drinking water health goal for GenX.
Recommendations from the Board can aid the regulatory processes. The Division of Air Quality
(DAQ) also identified their current priorities to include researching the inhalation risks and
potential acceptable ambient levels for GenX and other emerging contaminants.
DHHS stated that health data for other emerging PFAS compounds identified in NC are
insufficient at this time to calculate a health goal. The Board was asked to consider how or if the
presence of the additional compounds may influence the calculation of a GenX provisional
health goal for drinking water. In addition, future recommendations from the Board were
requested to consider a standardized approach for addressing other emerging PFAS with
limited health data and establishing provisional health goals for drinking water.
December 4, 2017 – An interim report and discussion on the GenX investigation and actions
taken by DEQ was given and included the regulatory programs and framework, history of GenX
and PFAS production at Chemours-Fayetteville Works site, surface water monitoring results,
additional emerging compounds, enforcement actions, groundwater monitoring results,
information on air emissions from the Chemours-Fayetteville Works facility, and next steps on
emerging compounds
DHHS provided documentation of their role in drinking water recommendations. DHHS gives
guidance on public health by conducting health risk assessments, communicating those risks
and giving guidance on the levels of exposure to certain contaminants. When issuing guidance
on drinking water, DHHS follows well established methodology and rules and utilizes
established reference standards when available. In the event, such as with GenX, when no
existing health goal or standard is available, DHHS can calculate a provisional health goal for
drinking water based on health data available at that time and following methodology endorsed
by the U.S. Environmental Protection Agency (EPA). DHHS monitors and may update a
provisional health goal for drinking water based on any new information provided by further
laboratory animal studies, epidemiologic studies, or other sources. The DHHS health goal is not
regulatory or legally enforceable.
DHHS then provided information on available GenX health studies relevant to calculating a
provisional health goal for drinking water and provided documentation on how the provisional

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Reference dose (RfD) is a risk assessment term employed by the U.S. EPA to articulate non-cancer, nonmutagenic health-risk effects associated with systemic toxicity study data. The EPA states “In the case of systemic
toxicity, however, organic homeostatic, compensating, and adaptive mechanisms exist that must be overcome
before a toxic endpoint is manifested.” The EPA defines a reference dose as: “the RfD is an estimate (with
uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population (including
sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime.”
Source: https://www.epa.gov/iris/reference-dose-rfd-description-and-use-health-risk-assessments

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 health goal for drinking water for GenX was calculated including the NOAEL used as the point of
departure, uncertainty factors, and a relative source contribution.
Following the discussions, the Board noted that the methodology used by DHHS to develop the
GenX drinking water provisional health goal followed commonly accepted human health risk
assessment practices.
January 29, 2018 - Four representatives from the Netherlands, where there is also a Chemours
facility using GenX in their production operations, joined the SAB meeting via video conference
and shared their process for and considerations in calculating their GenX water quality standard
of 150 ng/L.
DHHS shared further information about the studies used as the basis of the provisional health
goal and discussed further details on the process and calculations relevant to the provisional
health goal for GenX. Information was shared about the considerations of POD, uncertainty
factors (UF) and modifying factors (MF), relative source contribution (RSC) and physicochemical
properties. In addition, information was shared on other states’ calculations for other PFAS
health goals and the Netherland’s calculation for a GenX health goal. Further, DHHS reported
that there was sufficient dose-response data to support benchmark dose modeling, but
insufficient data to determine a cancer slope factor because of the availability of a single rat
carcinogenicity study. The SAB recommended pursuing bench mark dose modeling as a
possible strategy to identify a point of departure for the health goal calculation more precise
than the one generated with the NOAEL-based approach.
During the U.S. EPA’s Office of Water update on their development of a GenX toxicity value,
they also noted they would not be developing a cancer slope factor at this time because of the
single available carcinogenicity study, which used the rat model, which have been shown to be
less sensitive than mice to adverse effects associated with some PFAS.
March 19, 2018 - The Department of Environmental Quality shared an update of the
groundwater investigations around the Chemours site. DEQ also provided information on GenX
emissions, stack testing, and rain water testing. DEQ staff have been working on the
groundwater assessment related to the Chemours facility in Bladen County. A major
component of that work has included groundwater sampling of private drinking water wells by
both Chemours and DEQ. DEQ has evaluated the current groundwater data and has looked for
sources of the contamination while also evaluating other media that may need further
investigation.
DEQ has worked collaboratively with the Departments of Agriculture & Consumer Services
(DA&CS) and DHHS to determine necessary next steps regarding other media that may need to
be assessed. One component of the collaborative effort has included reviewing the current
literature associated with the presence of perfluorinated compounds in other media to include
plant tissue.
5

 DEQ presented to the SAB recent study results regarding a vegetable study that was conducted
in the Netherlands. The study was performed at the request of the Netherlands National
Institute for Public Health and the Environment per request from the city of Dordrecht. The
study looked at the presence of GenX in garden crops and addressed two key research
questions: 1) What are the concentrations of GenX and PFOA in selected crops from vegetable
gardens in the vicinity of the DuPont Chemours facility in the Netherlands; and 2) Is the
allowable daily intake, referred to as the “Tolerable Daily Intake” (TDI), via food from GenX and
PFOA exceeded by consumption of vegetable crops in a typical consumption pattern. Agency
staff continue to wait for an English translation of this study, but preliminary information
provided indicates that GenX was detectable in home-grown produce grown within 1 kilometer
of the Chemours site in the Netherlands, however levels did not exceed health-based limits
when looking at average daily intake for individuals. Based on this investigation, health officials
in the Netherlands recommended that vegetables within 1 km radius of the plant not be
consumed “too often” but recommended no limitations for produce grown beyond a 1kilometer radius. The results of the Netherlands’ produce study does not provide information
directly relevant to the NC situation other than as an indication that common home-grown
produce may provide an exposure pathway for PFAS released into the environment.
An additional study was presented to the SAB by DEQ that was conducted by the Minnesota
Department of Health (Scher et al., 2018). The study began in 2010 in the Minneapolis-St. Paul
area where high levels of PFAS were found in drinking water. Sources of drinking water were
ultimately utilized for irrigation for residential gardens. The Minnesota study focused on PFOA,
PFOS, PFBA, PFBS, PFPeA, PFHxA, and PFHxS6. This study found uptake and bioaccumulation of
PFAS into the terrestrial food chain, represented by home-grown produce, increased as
irrigation with PFAS-contaminated water increased. The results of this study confirmed those
of other studies indicating the fate and transport of PFAS is predominantly influenced by chainlength and functional group, resulting in the PFAS profile modification as a mixture moves from
the source though various environmental compartments, and that short-chain PFAS are more
mobile and water soluble than long-chain PFAS. They reported the preferential uptake and
bioaccumulation of short-chain PFAS by plants, and this uptake was PFAS-specific, plant
species-specific and plant tissue-specific, with preferential translocation from roots to more
distant plant structures generally increasing with decreasing chain-length. Their analysis
indicated that the home-grown produce may constitute a measurable contribution to overall
PFAS exposure for high-level produce consumers in areas where irrigation is with PFAScontaminated groundwater. These risk evaluations are specific to the exposure conditions and
populations included in this study and do not provide implications to risks specific to North
Carolina populations.

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PFBA CASN 375-22-4, PFBS CASN 375-73-5, PFPeA CASN 2706-90-3, PFHxA CASN 307-24-4, and PFHxS CASN 35546-4

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 DHHS provided information on the Peroxisome Proliferator-Activated Receptor alpha (PPARα)
mode of action (MOA) and PPARα-mediated outcomes associated with PFAS in animal studies
and the relevance of this MOA to human health. DHHS discussed findings that some cancer
outcomes in animal studies of PFAS may be mediated by the activation of PPARα and may not
be relevant to human outcomes, but also noted that PPARα activation has not been confirmed
for the hepatocellular necrosis endpoint selected by DHHS as the critical effect for the RfD and
calculation of the drinking water provisional health goal. DHHS shared information from the
EPA’s Lifetime Health Advisories (EPA 2016a, EPA 2016b) and the U.S. Centers for Disease
Control and Prevention’s (CDC) Agency for Toxic Substances and Disease Registry (ATSDR) draft
Toxicology Profile for PFAS (ATSDR 2012) which finds evidence of interspecies difference in
levels of PPARα expression and responsiveness, and PPARα-independent mechanisms involved
in PFOA and PFOS toxicity in non-cancer endpoints such as liver toxicity.
DHHS reported that the U.S. EPA Office of Water and Office of Pollution Prevention and Toxics is
working on a GenX reference dose and that DHHS is in communication with EPA as they continue
their work.
DHHS presented their progress on the benchmark dose modeling. DHHS staff received training
on use of benchmark dose modeling software from U.S. EPA staff. DHHS presented the first
stage of the work, which included data tables with each statistically significant endpoint for
GenX from the seven available GenX oral toxicity studies. The SAB provided guidance and
consultation on appropriate and significant endpoints that may be relevant to human health
and response levels for each endpoint. Recommendations informed what DHHS would use in
the benchmark dose modeling and input into the benchmark dose modeling software to
provide options for a point of departure.
April 30, 2018 - DEQ presented an update on the continuing investigation of environmental
contamination, bioaccumulation, and potential source of exposure. Well water, groundwater,
and soil testing continue. Rain water testing had spanned to a 7-mile radius from the Chemours
plant. The full extent of contamination has still not been determined. As part of a pilot study,
granulated activated carbon (GAC) filters were beginning to be installed to understand the
efficacy of this treatment method. Fish tissue, water, and sediment samples had been collected
from a private lake near the facility and were being tested as part of the continuing
investigation in environmental contamination and bioaccumulation of GenX and other PFAS.
DHHS reported that it has consulted with U.S. EPA and a member of the SAB and is continuing
to work on benchmark dose modeling in preparation for sharing results at the June 18, 2018
meeting.
June 18, 2018 - DHHS presented a summary report on the benchmark dose modeling of the
available GenX animal studies. DHHS requested that the SAB consider the results as they make
recommendations to GenX health and regulatory levels in North Carolina. The DHHS noted that
the U.S. EPA continues to work toward releasing a GenX RfD this summer.
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 DEQ, DHHS and DA&CS have continued to work collaboratively to gather information related to
the presence of perfluorinated compounds in other media. In addition to the plant tissue
information presented in March, DEQ presented sediment and fish tissue data to the SAB from
a preliminary PFAS study of a privately-owned man-made lake near the Chemours-Fayetteville
facility (DEQ 2018). Surface water, sediment and three species of fish were collected in March
and April 2018. Fish filet tissue analytical samples were prepared to represent human
exposures. All samples were analyzed for 33 PFAS. Twenty PFAS were detected collectively in
these samples, including GenX in the surface water, sediment and one species of fish, Redear
Sunfish, an insectivorous species. The same 16 PFAS, the highest number of PFAS detected in
the sampled media, were detected in the lake surface water and water collected from a surface
spring that flows into the lake. The 16 PFAS detected in the water samples included both PFOA
and PFOS, as well as short-chain and long-chain PFAS. GenX was the only PFAS detected in the
lake sediment. PFOS was also detected in the Redear Sunfish 7-fish composite and two
composite samples of Largemouth Bass, each made-up of fish of a different size range (a 5-fish
composite of smaller fish and a 2-fish composite of larger, presumably older fish). Four
additional long-chain “legacy” PFAS (11, 12, 13 and 14-chain PFAS) were detected in the two
Largemouth Bass samples and a sample made-up of a single Blue Catfish.

Section 5 – GenX Considered as a Threshold-Effect Chemical
DHHS noted there were insufficient data from the available toxicology studies to quantitatively
assess the cancer endpoint related to GenX exposures. The single 2-year carcinogenicity study
used rats, which have been observed to be less sensitive to some PFAS-associated adverse
effects than mice. DHHS used non-cancer endpoints identified in the available animal studies,
which are generally assumed to have a threshold below which there are no observable adverse
effects due to homeostatic and adaptive mechanisms. The U.S. EPA IRIS7 program provides a
discussion of the approach for assessing health effects other than carcinogenicity or
mutagenicity at https://www.epa.gov/iris/reference-dose-rfd-description-and-use-health-riskassessments.
The Board identifies that the appropriate approach to determining a safe concentration for a
chemical in drinking-water depends on how it causes harm. The Board determined that the
data was insufficient to establish whether GenX is a human carcinogen. The Board judges that
based on the available science the most sensitive endpoint for GenX observed in multiple
studies is a “threshold” non-cancer endpoint, i.e., that there is some level of exposure which
does not represent a non-cancer risk to human health, and recommends that the U.S. EPA
approach for assessing threshold non-cancer risks be applied.
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IRIS is the U.S. EPA’s Integrated Risk Information System. The IRIS Program supports EPA’s mission is to protect
human health and the environment by identifying and characterizing the health hazards of chemicals found in
the environment. Available at: https://www.epa.gov/iris

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 Section 6 – Derivation of the GenX Reference Dose
To control a threshold chemical at safe levels, it is necessary to identify the daily oral exposure
amount below which it would not cause adverse health effects if consumed for a lifetime. This
is called the reference dose (RfD).
To calculate a reference dose, DHHS reviewed seven repeat oral dose studies in rodents of 28
days or longer that were provided by Chemours/DuPont during the U.S. EPA Toxic Substances
Control Act (TSCA)8 review process. DHHS focused on repeat oral dose studies because this
exposure scenario is most applicable to the potential long-term human exposure scenario from
drinking water. DHHS also consulted with toxicologists and risk assessors at U.S. EPA, the
National Institute of Environmental Health Sciences (NIEHS), and ATSDR to identify applicable
toxicology information and risk assessment procedures.
The first step in calculating a RfD is to identify a point of departure (POD). DHHS released an
initial assessment of GenX in drinking water that used a no observed adverse effect level
(NOAEL) of 1.0 mg/kg-day from a 2-year chronic study in rats as the POD (DHHS 2017). After
further review of the repeat oral dose studies and conversation with experts at U.S. EPA, an
updated assessment was provided in July 2017 that identified the NOAEL of 0.1 mg/kg-day for
liver toxicity endpoints from two sub-chronic studies in mice (28-day study and a reproductive
screen) as a more appropriate POD for calculation of a provisional health goal (PHG) for GenX in
drinking water. The sub-chronic studies were chosen as the critical studies because they
demonstrated adverse effects at the lowest doses tested and the effects were seen across
multiple studies at the same or similar doses. DHHS subsequently used the NOAEL of 0.1 mg/kgday as the POD for calculations of the RfD.
DHHS then used default uncertainty factors (UFs) recommended by U.S. EPA to derive a RfD
from the POD. An expanded discussion of default U.S. EPA uncertainty factors is provided in
Appendix A. DHHS did not apply a modifying factor (MF) because NOAELs from multiple studies
were identical, or within the same order of magnitude, with identical or similar health
endpoints (liver toxicity). Additionally, DHHS staff concluded that the uncertainty factors
discussed below adequately addressed the uncertainties of the database. The default
uncertainty factors used were the following:
•
•

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Sub-chronic to chronic uncertainty factor (UFS): A factor of 10 to account for the
uncertainty involved in extrapolating from less than chronic NOAELs to chronic NOAELs
Interspecies uncertainty factor (UFA): A factor of 10 to account for the uncertainty
involved in extrapolating from animal data to humans

Under the Toxic Substances Control Act (TSCA) and the Pollution Prevention Act, EPA evaluates potential risks
from new and existing chemicals and finds ways to prevent or reduce pollution before it gets into the
environment. U.S. EPA TSCA program web-page available at: https://www.epa.gov/chemicals-under-tsca

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 •

Intraspecies uncertainty factor (UFH): A factor of 10 to account for the variation in
sensitivity among the members of the human population

The RfD was calculated to be 0.0001 mg/kg-day by dividing the point of departure by the
uncertainty factors.
RfD, mg/kg-day = (POD, mg/kg-d) / UFs
0.0001 mg/kg-day RfD = 0.1 mg/kg-d / (10 x 10 x 10)

DHHS presented the process used to calculate the provisional health goal for GenX in drinking
water to the SAB during the October 23, 2017 meeting. Per guidance from the SAB, DHHS then
compiled data from the seven repeat oral dose studies to be used in benchmark dose (BMD)
modeling to potentially refine the point of departure. Benchmark dose lower bound (BMDL)
values may be used rather than NOAELs or lowest observed adverse effect levels (LOAELs) as
the point of departure for derivation of toxicity values such as a reference dose. Benchmark
dose modeling work was completed by DHHS in May 2018 and presented to the SAB during the
June 18, 2018 meeting.
The modeled BMDLs for select endpoints were presented by DHHS, while they cautioned that
some of these values may be inappropriate to consider as a POD since the endpoints had very
large BMD-to-BMDL ratios, indicating poor model fit and a large confidence interval on the
BMD and perhaps inadequate data for modeling these endpoints (EPA 2012). The Board
recommended refining the modeled BMDL ranges to exclude those with BMD-to-BMDL ratios
>20. The refined range of BMDLs modeled by DHHS is 0.0492 to 25.3 mg/kg-day for selected
hematology endpoints, 0.151 to 5.55 mg/kg-day for selected hepatic endpoints, and 3.06 to 635
mg/kg-day for selected developmental endpoints. A full report of the benchmark dose
modeling efforts, results and limitations can be found in a separate document provided to the
SAB on May 26, 2018 (DHHS 2018).
Based on review of available evidence, and additional calculations undertaken by DHHS staff on
the request of the Board, the Board recommends the provisional reference dose (RfD) of
0.0001 mg/kg-day. The Board considers this is a reasonable health-based target action level for
the state. The benchmark dose modeling effort did not generate a point of departure (POD)
that deviates from the NOAEL-based approach. As additional studies on the health effects
associated with GenX become available, and the U.S. EPA’s development of a GenX toxicity
value is completed, review and refinement of the RfD and PHG should be undertaken by the
agencies.

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 Section 7 – Calculation of the DHHS GenX Provisional Health Goal for Drinking Water
To remain protective of sensitive life-stages DHHS used the 95th percentile water intake rate
and average body weight for a bottle-fed infant for calculation of a provisional health goal for
GenX in drinking water. Bottle-fed infants drink more water compared to their body weight
than other age groups and are therefore considered a sensitive population for drinking water
exposures.
In calculating health goals for exposure from drinking water, it is necessary to consider other
routes of potential exposure, including air and food for example. GenX has been measured in
samples of food (specifically fish) and rainwater in North Carolina, however data on the extent
of exposure from these other routes is limited. DHHS used a relative source contribution (RSC)
of 20% to account for other possible routes of exposure, consistent with EPA guidance (EPA
2000) when data on the extent of exposure from other routes is limited. Use of this relative
source contribution allocates 80% of a person’s GenX exposure to come from sources other
than drinking water.
Applying these factors, the DHHS provisional health goal for GenX in drinking water was
calculated to be 140 ng/L. This level is not a boundary line between a “safe” and “dangerous”
level of a chemical but is a level that represents the concentration of GenX in drinking water at
which no adverse non-cancer health effects would be anticipated over an entire lifetime of
exposure. The provisional health goal for GenX in drinking water is subject to change based on
new information but was calculated with the best currently available information and using
default factors when specific information is limited. For more details and information on the
calculation of the provisional health goal, see https://ncdenr.s3.amazonaws.com/s3fspublic/GenX/NC%20DHHS%20Risk%20Assessment%20FAQ%20Final%20Clean%20071417%20P
M.pdf.
In controlling threshold chemicals like GenX, it is necessary to account for all routes of
exposure, including air and food as well as drinking-water, for example. Exposure to GenX can
occur through all of these and GenX has been measured in samples of water, food (specifically
fish) and rainwater in North Carolina. To identify a safe concentration of GenX in drinkingwater, a proportion of the reference dose is allotted to drinking water. The Board judges that
the U.S. EPA default assumption that 20% of exposure be attributed to drinking-water is
appropriate and common U.S. EPA default values for consumption and body weight were also
used for the calculation of the GenX point of departure, reference dose and the drinking water
provisional health goal.

Section 8 – Ecological, Produce and Air Concerns
Ecological implications of GenX exposure are poorly understood in the natural environment
because there is very little environmental monitoring data on invertebrate, fish and wildlife
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 receptors. Laboratory studies on GenX accumulation in common carp (28-day bioconcentration
factor9, BCF <30 L/kg-tissue) and toxicity to green algae (72-hour no observed effect
concentration (NOEC) >107 mg/L), daphnids (21-day NOEC for reproduction 4.17 mg/L), and
fishes including Japanese medaka (96-hour EC50 >100 mg/L)10, rare gudgeon (96-hour EC50
>150 mg/L) and rainbow trout (90-day reproduction NOEC of 8.9 mg/L) (Hoke et al., 2016)
indicate adverse effects at exposures much greater than existing environmental
concentrations. There was no effect on bobwhite quail at dietary concentrations up to 100
mg/kg (Newsted et al., 2008). The extent to which these commonly tested species are
adequate surrogates for the diversity of free-living invertebrates, fish, and wildlife in the Cape
Fear basin is unknown.
In March and April 2018 DEQ collected surface water, sediment and fish from a privately-owned
lake less than 1-mile from the Chemours facility for a limited PFAS study (DEQ 2018). The study
identified 20 different PFAS in the study samples of the 33 PFAS included in the target analyte
list. GenX was detected in the lake surface water (968 ng/L), a surface spring feeding the lake
(1160 ng/L) and in the lake surface sediment (1,800 ng/kg dry weight sediment). GenX was also
detected in one of three species of fish collected from the lake, the insectivorous Redear
Sunfish filet composite (2,700 ng/kg wet weight tissue). Five other PFAS were also detected in
the three-fish species, including the legacy 8-carbon PFOS, as well as the legacy 11, 12, 13 and
14-carbon PFAS PFUdA, PFDoA, PFTrDA and PFTeDA11 (361 J to 2890 ng/kg-wet weight)12. These
data indicate the current-use and historical PFAS are present in environmental compartments
in the area near the Chemours facility and may be attributed to releases from the Fayetteville
facility.
There is little information on ecological toxicity benchmarks for these and most other PFAS,
limiting our ability to assess potential ecological harm related to individual PFAS exposures, or
to mixtures of PFAS compounds which may occur in areas where these compounds are
manufactured or used in production. There is also inadequate information on the potential for
ecological effects associated with additive, long-term exposures to sensitive receptors.

Air Emissions
Measured air emissions of the GenX from some processes at the Chemours/DuPont plant are
higher than previously understood or reported. GenX has also been measured in rainwater as
far as 20 miles downwind of the facility, indicating atmospheric transport and deposition of this
9

A Bioconcentration Factor (BCF) is a proportionality constant relating the chemical concentration in fish to the
concentration in water under steady-state conditions. It measures the tendency of a chemical to accumulate in
fish. Measurements of BCFs are generally undertaken in a controlled laboratory environment.
10
EC50 is the “effect concentration” of a test substance that results in specified effect to 50% of the test
population. Common measured effects include mortality, reduced growth or reduced reproduction.
11
PFUdA CASN 2058-94-8, PFDoA CASN 307-55-1, PFTrDA CASN 72629-94-8, PFTeDA CASN 376-06-7
12
A “J” flagged concentration is an estimated concentration as identified by the analytical laboratory

12

 compound. Atmospheric deposition of GenX and other PFAS may also provide a pathway for
surface water contamination and PFAS deposited on soils may be carried downward with
precipitation to contaminate groundwaters (ITRC 2018). Testing of private drinking water wells
near but upgradient of the Chemours/DuPont plant has shown concentrations of GenX. The
combination of environmental measurements and analysis by DEQ strongly indicate a causal
link between GenX air emissions and widespread groundwater contamination near the
Chemours/DuPont plant.
The Board recommends that GenX and other PFAS releases to the air be characterized to
evaluate inhalation exposures for humans, as well as the implications for contamination of soil,
surface water, groundwater and the food web.

Section 9 – The Significance of the Circumstances
Board members heard compelling testimony from citizens, some clearly distressed, expressing
profound concern for their health and that of their family members and others. The degree of
public concern calls for decisive action by the state to establish safe environmental conditions
and to give practical guidance to those who are concerned to protect their own health and that
of their family and community, especially more vulnerable persons. Large centers of population
that are, or have been, exposed (such as those of the Lower Cape Fear Basin), and people with
high levels and multi-media exposure (such as those living close to the Chemours plant in
Fayetteville), are of special concern. Comprehensive characterization of PFAS present in the
environment and identification of all routes of exposure, and the implications of additive
exposures are needed, but the science needed to undertake this task is not currently available.
Agencies and organizations with the capacity to persuade and facilitate the acquisition of this
knowledge are urged to do so to actively protect human health and the environment.
Additional studies are needed to characterize current and changes to PFAS burdens in nearby
environmental matrices that may serve as long-term sources of PFAS back into the local and
regional environment, even as local emission sources to the environment may be controlled. In
circumstances where concentrations observed in environmental matrices may not have
implications to the health of non-human ecosystem components, these concentrations may
provide long-term sources of exposure to sensitive human receptors through uptake by plants,
animals or fishes consumed by humans.

Section 10 – The Board’s Recommendations to NC DHHS
NC DHHS developed a health-protective provisional health goal for drinking water for the most
vulnerable population exposed to GenX using the best available science as federal and state
standards were not available. DHHS followed the Board’s recommendation to further evaluate
the provisional health goal developmental process by using benchmark dose modeling to
13

 possibly refine the point of departure. The Board commends the use of the current reference
dose and provisional health goal developed by DHHS as the foundation for protecting affected
and sensitive populations and providing corresponding risk assessments and advice.
Because of the issues associated with multiple routes of exposure summarized above, the
Board recommends the incorporation of local exposure patterns in designing and delivering
locally appropriate health advice for known PFAS exposures, where appropriate and possible.
Because there are certain population groups who may have higher exposure (those using water
source types more likely to be contaminated) and some sensitive population groups (such as
children and pregnant women), advice should be tailored and targeted accordingly. Such
advice, based on balanced evaluation of relevant sound evidence, is essential to assist citizens
in taking appropriate actions to protect their health, and to protect the public from undue
stress and substantive interruption of life-style.

Section 11 - Board’s Recommendations to NC DEQ
NC DEQ provided an overview of drinking water standards and development of regulations
covering the North Carolina Drinking Water Act, what constitutes a public water system, the
Federal Safe Drinking Water Act, the federal regulation development process and
considerations, and considerations and constraints for development of state regulations. In
addition, NC DEQ provided an overview of how North Carolina groundwater and surface water
standards are developed and applied including the criteria to protect designated uses, how the
standards are calculated, and the associated state and for surface water, the federal review
processes. DEQ discussed that surface water standards protect surface water for a variety of
uses and include health related criteria for fish consumption and water supply. Groundwater
standards protect groundwater as a resource for human consumption based on health-related
criteria and do not consider the cost of treatment. The standards are set through a triennial
review process.
The Board commends the reference dose developed by DHHS to DEQ as the foundation for
establishing health-protective environmental standards. As additional validated studies to
address long-term exposure concerns become are available for GenX and other PFAS, this value
should be re-evaluated and modified as needed to protect sensitive populations and the
environment.

Section 12 – Concluding Remarks
GenX is an ‘emerging hazard’, meaning one about which current scientific studies are few and
new information is being produced. The Board judges that the available evidence is adequate
to inform the adoption of the reference dose and the provisional health goal described here
14

 and in the accompanying full report. Because there is ongoing research in North Carolina,
nationally and internationally, and there are likely to be other studies:
•

•

•

•

•

The Board councils that the recommendations made here be reviewed within three
years by the Board and Departments with a view to ensuring the adequacy of health
protection and the efficacy and cost-effectiveness of control measures. This will require
ongoing monitoring and evaluation of environment and health conditions by the
Departments.
That DEQ and DHHS collaborate with the NC Department of Agriculture and Consumer
Services and others to improve understanding of the relevance to local populations of
exposure to GenX through foodstuffs, in particular with a view to determining whether
standards for foodstuffs and/or guidance to local populations on food-related exposures
are necessary and can be scientifically justified.
That DEQ encourage and support efforts to more fully understand the ecological and
environmental impacts of GenX, but also the long-term low-level additive exposures to
mixtures of PFAS, including their persistence, environmental fate, and effects on
ecological receptors.
That the Departments recognize the concern of population members that exposure to
GenX has occurred concurrent with exposure to other related emissions from the
Chemours/DuPont plant and support efforts to understand possible interaction among
the toxicity of and exposure to the associated chemicals and potential approaches to
their combined regulation.
That the Departments further recognize the concern of population members about the
accumulation of these chemicals in the environment (for example in soils, river
sediments and through bioaccumulation in animals) causing continuing human
exposure.

15

 References
ATSDR (Agency for Toxic Substances and Disease Registry), 2012. Toxicological Profile for
Perfluoroalkyls, Draft. Division of Toxicology and Human Health Sciences Environmental
Toxicology Branch, Atlanta, Georgia. 2012.
DEQ (North Carolina Department of Environmental Quality), 2018. Preliminary PFAS Study in
Man-made Lake Near A PFAS Manufacturing Facility (in preparation). Presentation slides
available at: https://deq.nc.gov/news/hot-topics/genx-investigation/secretaries-scienceadvisory-board
DHHS (North Carolina Department of Health and Human Services), 2017. DHHS Drinking Water
Advisory Decision Matrix. Presented to the NC SAB December 4, 2017. Available at:
https://deq.nc.gov/news/hot-topics/genx-investigation/secretaries-science-advisory-board
DHHS (North Carolina Department of Health and Human Services), 2018. Benchmark Dose
Modeling Report for GenX, May 26, 2018. Available at: https://deq.nc.gov/news/hottopics/genx-investigation/secretaries-science-advisory-board
EPA (United States Environmental Protection Agency), 2000. Methodology for Deriving Ambient
Water Quality Criteria for Protection of Human Health. United States Environmental Protection
Agency, Office of Water. October 2000.
https://www.nj.gov/drbc/library/documents/EPA_human-health-criteria2000.pdf
EPA (United States Environmental Protection Agency), 2012. Benchmark Dose Technical
Guidance. EPA/100/R-12/001. June 2012.
EPA (United States Environmental Protection Agency), 2016a. Drinking Water Health Advisory
for Perfluorooctane Sulfonate (PFOS). United States Environmental Protection Agency, Office of
Water, Health and Ecological Criteria Division Washington, DC 20460. EPA 822-R-16-004. May
2016.
EPA (United States Environmental Protection Agency), 2016b. Drinking Water Health Advisory
for Perfluorooctanoic Acid (PFOA). United States Environmental Protection Agency, Office of
Water, Health and Ecological Criteria Division Washington, DC 20460. EPA 822-R-16-005. May
2016.
Hoke, RA, Ferrell, BD, Sloman, TL, Buck, RC, Buxton, WL. 2016. Aquatic hazard, bioaccumulation
and screening risk assessment for ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoate. Chemosphere 149:336-342. http://dx.doi.org/10.1016/j.chemosphere.2016.01.009
ITRC (Interstate Technology & Regulatory Council). Environmental Fate and Transport for Perand Polyfluoroalkyl Substances, March 2018. Washington, D.C. Accessed at: https://pfas1.itrcweb.org/

16

 Newsted, JL, Beach, SA, Gallagher, SP, Giesy, JP. 2008. Acute and chronic effects of
perfluorobutane sulfonate (PFBS) on the Mallard and Northern Bobwhite Quail. Arch Environ
Contam Toxicol 54(3):535–545. DOI 10.1007/s00244-007-9039-8.
OEEB (Occupational & Environmental Epidemiology Branch, Epidemiology Section, Division of
Public Health, North Carolina Department of Health and Human Services). 2018. GenX Toxicity
Study Summary Tables for Benchmark Dose Modeling. February 2018.
Rushing, BR, Hu, Q, Franklin, JN, McMahen, RL, Dagnino, S, Higgins, CP, Strynar, MJ, DeWitt, JC.
2017. Evaluation of the Immunomodulatory Effects of 2,3,3,3-Tetrafluoro-2(Heptafluoropropoxy)-Propanoate in C57BL/6 Mice. Toxicological Sciences 156:179–189.
https://doi.org/10.1093/toxsci/kfw251
Scher, DP, Kelly, JE, Huset, CA, Barry, KM, Hoffbeck, RW, Yingling, VL, Messing, RB. 2018.
Occurrence of perfluoroalkyl substances (PFAS) in garden produce at homes with a history of
PFAS-contaminated drinking water. Chemosphere 196: 548-555. Sheng, N, Cui, R, Wang, Jin.,
Guo, Y, Wang, Jia., Dai, J. 2017. Cytotoxicity of novel fluorinated alternatives to long-chain
perfluoroalkyl substances to human liver cell line and their binding capacity to human liver fatty
acid binding protein. Archives of Toxicology, 92:359-369. 10.1007/s00204-017-2055-1
Wang, J, Wang, X, Sheng, N, Zhou, X, Cui, R, Zhang, H, Dai, J. 2017. RNA-sequencing analysis
reveals the hepatotoxic mechanism of perfluoroalkyl alternatives, HFPO2 and HFPO4, following
exposure in mice. Journal of Applied Toxicology, 37: 436-44. https://doi.org/10.1002/jat.3376.

17

 Appendix A
Review of Uncertainty Factors Used in Calculation of the NC DHHS
Provisional Drinking Water Health Goal for GenX

18

 Review of Uncertainty Factors (UFs) Used in Calculation of the NC DHHS Provisional Drinking
Water Health Goal for GenX
Standard uncertainty factors and modifying factors (Section 1.2.2.2.4:
https://www.epa.gov/iris/reference-dose-rfd-description-and-use-health-risk-assessments)
i. Intraspecies UF: Factor of 10 to account for the variation in sensitivity among the
members of the human population. In general, intraspecies variability in sensitivity
to toxic effects can be due to a variety of factors, including age, sex, disease status,
nutrition, genetics, etc.
Used in GenX Provisional Health Goal calculation to account for potential sensitivity
differences within the human population. There is no information available to justify
use of any number besides the default factor of 10.
ii. Interspecies UF: Factor of 10 to account for the uncertainty involved in extrapolating
from animal data to humans. Interspecies differences in sensitivity to toxic effects
can be due to a variety of factors such as difference in metabolism and kinetics.
Used in GenX Provisional Health Goal calculation (only rat and mice studies
available). There is a large interspecies difference in half-life of legacy PFAS such as
PFOS and PFOA, but there is not enough information to determine if this large
interspecies variability would also occur with GenX. In the absence of data on the
human half-life for GenX, DHHS used the default interspecies uncertainty factor of
10.
DHHS was recently made aware that in the absence of PBPK modeling or chemicalspecific data, EPA accounts for interspecies differences in calculating oral reference
doses using allometric scaling, as outlined in a guidance document titled
“Recommended Use of Body Weight3/4 as the Default Method in Derivation of the
Oral Reference Dose”. This approach uses a dosimetric adjustment factor and a
reduced interspecies uncertainty factor to replace the former default interspecies
uncertainty factor of 10. DHHS is including this information in the interest of
providing the SAB with all information needed to make fully informed
recommendations.
iii. Sub chronic-chronic UF: Factor of 10 to account for the uncertainty involved in
extrapolating from less than chronic NOAELs to chronic NOAELs. It is generally
assumed that longer exposure times would result in adverse effects at lower
concentrations due to accumulation of the toxicant or inability of an organism to
repair injury from the substance.
Used in GenX Provisional Health Goal calculation because the NOAEL from 28-day
mice study and a reproductive screen in mice with a sub-chronic exposure duration
was used as opposed to a NOAEL from a chronic (ex: 2 year) study. Sub-chronic
19

 studies were used because adverse effects were observed at lower doses, and these
effects were consistently seen across multiple studies at the same or similar doses
(ex: the 90-day study in mice and the 90-day study in rats). To be health protective,
studies with adverse effects at the lowest doses tested were used as the critical
studies for determining the point of departure.
iv. LOAEL-NOAEL UF: Factor of 10 to account for the uncertainty involved in
extrapolating from LOAELs to NOAELs.
Not used in GenX Provisional Health Goal calculation because NOAELs were available
so an additional uncertainty factor was deemed unnecessary.
v. Modifying factor: additional uncertainty factor that is greater than zero and less
than or equal to 10. The magnitude of the MF depends upon the professional
assessment of scientific uncertainties of the study and data base not explicitly
treated above; e.g., the completeness of the overall data base and the number of
species tested. The default value for the MF is 1.
Not used in GenX Provisional Health Goal calculation. Professional judgement from
DHHS staff determined that a modifying factor was not necessary based on the
following justification: Seven repeated dose oral studies ≥ 28 days in duration in two
rodent species were reviewed, including a 2-year chronic study in rats and a
reproductive/developmental toxicity screen in mice. NOAELs from several studies
were identical or within the same order of magnitude with identical or similar health
endpoints (liver toxicity). Additionally, DHHS staff concluded that the uncertainty
factors discussed above adequately addressed the uncertainties of the database.

20

 Appendix 

NC DHHS Benchmark Dose Modeling Report for GenX, May 26, 2018.

21

22

Appendix 

DHHS BMD Report Supplemental Documentation June 8, 2018

23

24