DEQ-CFW_00070918

ra
Talking Points, August 10, 2017, GenX Discussion
DuPont describes the "GenX technology" fluoropolymer manufacturing process as including the mixing of
the "precursor", C6HF11O3, "PFPrOPrA" or "GenX" (CASN 13252-13-6; 2,3,3,3-tetrafluoro-2-
heptafluoropropoxy)-propanoic acid) with an ammonium hydroxide solution, producing the ammonium
salt "processing aid", C6HF11O3•H3N (CASN 62037-80-3; ammonium 2,3,3,3-tetrafluoro-2-
(heptafluoropropoxy)-propanoate). Documentation supplied by Chemours to the Netherlands public
health agency (2016) indicates that GenX and the processing aid (ammonium salt) are released to the
wastewater stream, and GenX and a process byproduct, "E1" (CASN 3330-15-2; CsHF11O,
heptafluoropropyl 1,2,2,2-tetrafluoroethyl ether) are released to the air. (Beekam et al. 2016)
Cape Fear River Studies, EPA studies, NCSU studies -
1. EPA NERL RTP researchers publish a journal arttcte (Nakayama et.a1. 2007) reporting on surface
water surveys collected in 2006 and analyzed fpr a suite of ltlt�AS (7 PFCAs and 3 PFSAs).
The work was part of the LCMSMS PFAS analyticaf,ethod validatioo pracess. The collected 100
samples from 80 locations in the mainstem and tributaries"of the CFR, rang" from above
Greensboro to the coast. They found PFAS in all the�su'i'faee,water samples­(LOQ :1.ng/L). The
target PFAS were C4-C12 chain -lengths, and included C8 l**—,and PFOA, and did n t'include
GenX. They did analyze for an un-related straight -chain C6, p rfl rohexanoic acid (PFHxA).
Different PFAS profiles were observed at eaeh location. The highest individual PFAS concentration
reported was 329 ng/L for C7 perfluord ptanoic'aeiz$ PFHpA). The h best JPFAS was 942 ng/L
detected in a Haw River sample above the confluen6avith.the Deep River.
2. In 2015, a journal article was pUl shed that reported work,by scientists from EPA NERL, ORNL and
others (Strynar et al. 2015). This work identified 12 novel perfiuoroalkyl ether carboxylic and
sulfonic acids to surface watergrab samples coffeoted frorn.the CFR and its tributaries in 2012.
Sample locations were those where PFAS had been ee�d previously. The objective of the study
was to use special analytical forensics to confirm the identification and sources of the previously
detected unidentified PFAS. They identified two homologous series of perfluoroalkyl ether PFAS
that differed by multiples of -CFZ or -CFZO. This work identified GenX as one of the novel PFECAs in
the CFR Bas'fq,'They suggested that the�h logous series were manufacturing products and not
degradation=related. They reported morel n 2-orders of magnitude increased concentrations of
PFAS at a sp%�rce, with evideCtee,pf significant shift in dominant chain -length from longer (>_C8) to
shorter (S0)They noted significant levels of non -covalent dimers of the perfluoroalkyl ether,
C6HF1103 (CASN 13252-13-6, later identified as "GenX"). They also report finding evidence of
Nafion, a chemicalx-ppprted to be produced at the facility located upstream of the GenX and
perfluoroalkyl ether homologous series detections.
Sun et al. (2016) paper published by NCSU, and EPA NERL (National Exposure Research Laboratory)
RTP provided analytical. Results of the paper were presented in NC in May -June 2017. The authors
reported the discovery of 7-novel perfluoroalkyl ether carboxylic acids (PFECA) in surface waters at
the intakes of 3 WTPs collected from the Cape Fear River Basin in 2013. GenX was one of the novel
PFECAs identified at the intake location of one WTP.
4. Sun et al. (2016) identifies GenX as "PFPrOPrA", perfluoro-2-propoxypropanoic acid (CASN 13525-
13-6), which is identified in DuPont documents as a C6 alternative to PFOS. The GenX was detected
in the raw water of a WTP downstream of a "PFAS manufacturer" at 631 ng/L (mean).
5. In grab WTP samples collected in 2014, Sun et al. (2016) reported that GenX, and other PFAS, were
not effectively removed in the drinking water treatment processes. The published data for this
DEQ-CFW 00070918

plant indicates a slight elevation of the GenX concentration in the finished water, relative to the
raw intake water. The WTP was not utilizing an activated carbon treatment.
Sun et al. (2016) also reported on batch reactor GAC adsorption studies utilizing grab CFR surface
waters collected in 2014 downstream of a PFAS manufacturing facility. The water samples included
C4-C10 PFCA, C4-C8 PFSA, and C3-C8 mono- and poly -ether PFECA PFAS. Carbon removal
efficiencies increased with increasing chain -length and increasing individual PFAS concentration.
PFSA were more effectively removed that PFCA of the same chain -length. The authors reported
that the overall removal efficiencies of the PFECAs present at the highest concentrations was
minimal (-5 - <15%).
In addition to GenX, the Sun et al. (2016) study reported other novel and legacy PFAS detected in
the CFRB waters & 3 WTPs, including C4-C10 PFCA and PFSA PFAS, and C8 PFOS and its
degradation product PFOA. Not all detected PFAS could be quantified due to a lack of calibration
standards source. Some of the PFAS that cou.ldnot be quantified had peak areas <_15 times that of
GenX, indicating they were likely present at much higher concentrations.
GenX Toxicology Studies -
1. PFAS compounds of all types are indicated to be quickly (-within minutes) and efficiently,(100%)
adsorbed on oral exposure, including by humans. PFAS bioaccumulate by bindingao proteins,
predominantly in the blood and other protein -rich organs (liver, kidneys). This means of
bioaccumulation is atypical of most env ronme-vital contaminants that accumulate in lipids, and for
which the K. partitioning coefficient carr be used to estimate bioaccumulation potential and food
chain magnification. KoW values cannot be used to predict the bioaccumulation potential of PFAS.
The rate of uptake and el'
including comparisons be
complicates;.the ability to
bioaccumulation paramel
considerations important
values.
The single available carcinoi
Chemours and DuPont serer
PFAS effects -to rats and mic
year carcinogenicity study ri
and tumors of ttteoancreas
a of some clan=
As and mice.In
ighly variable across test species,
and humans. This
apolate animal data to humans, to estimate body burden and
n humans, and decisianS on,;Wropnate uncertainty factors - all
n identifying the critical -effect dose for development of toxicity
nicity study (-gat 2-yr chronic exposure study) performed by
sts used rats-.(fe et al, 2015). Other studies that have compared
have indicated& -hat mice are more sensitive to some PFAS. The rat 2-
Dse-related increase in liver tumor incidence in females,
in males.
4. The Rae et al. (2015)2 year rat -fudy data also indicated histopathological cellular and sub -cellular
changes in the liver and kidneys that are responses known to be indicative of tumor promotion,
including cellular necrosis and lipid accumulation. These observations strengthen the causation
relationship of GenX exposure and tumor incidence.
5. Other non -cancer -related effects seen in the rat 2-year chronic exposure study (Rae et al, 2015)
included changes to red blood cells mass and function, and hemoglobin and protein levels.
Biomarkers of liver damage and observations of generalized cellular damage were reported,
including liver cell enlargement and increased liver mass. Again, these adverse effects and tumor
responses were reported in rats which have shown decreased levels of adverse biological response
to some PFAS relative to other test species.
6. The Gannon et al. (2016) study by Chemours/DuPont scientists exposed rats to a single dose of
GenX to track elimination kinetics over a 7-day study period. The exposure concentrations were
orders of magnitude (-6) higher than environmentally -relevant concentrations (10 and 30 mg/kg).
DEQ-CFW 00070919

3
Based on recovery concentrations in urine, the authors proposed that GenX was completely
eliminated within the 7-day period. There is concern that the elevated exposure concentrations
likely saturated tissue and cellular uptake mechanisms, and re -adsorption mechanisms in the
kidneys, resulting in urine elimination concentrations that prevented detection of exposure and
elimination concentration differences and potential tissue uptake. The authors did not perform
tissue analyses to confirm that GenX was not taken into tissues or organs. Because of the study
design including a single exposure regime, extreme exposure concentrations relative to likely
environmental exposure concentrations, and no confirmatory tissue data, this study does not
adequately address GenX tissue uptake. Additionally, kinetics based on a single dose may not be
representative of typical human environmental exposure regimes that are characterized by
multiple sources of exposure to multiple classes of PFAS, contributing to cumulative chronic
exposures. Chronic cumulative exposures uptake kinetics may not be reflected by a single dose
exposure.
7. A 2017 article reports (Wang et al. 2017) on Z&ayoral expdtaresto mice. They identified many
DNA expression changes in liver cells, as well at-.,.generalizedt +ereniargement and biomarkers of
liver damage, liver cell necrosis, liver cell enlarddffient an&jn uctio of inflammatory responses.
Much of the gene expression alterations were celltxlar=l'undtons assocaatel with cancer pathway
induction (alterations to lipid metabolism, liver cell necrosis and inflammatory responses),
providing further support for the potential carcinogenicity a# GenX. The mechanistic pathways
observed in the liver responses support a non-PPAR related ;pathway for tumor lntfuc lion, which
has been observed in other PFAS cancer studle"nd has been proposed as a cancer pathway of
questionable relevance to human cancer induction: Additional studies are needed to confirm
tumor response and define the cancer mode of action. The authors noted that the response levels
observed in their mouse subjects were ,rnore sensiti tha ,,the same responses observed for PFOA
in other studies.
8. Chemours has provided DWM With the raw to*1ty study data fir Gannon et al., and Rae et al.
published papers. It is currently under internal .review.
9. In 2017, the Netherlands publhchealth agency analyzed;the concentrations of GenX and PFOA in
grass and leaves at'Slocations nears GenX-production facility. The limited study indicated that
GenX and PFtJA,are taken -up by plants. The brief notes on methodology noted that the samples
were extracted (i.e., not- surface wipe oa _rinse). The sampling locations ranged from 50-3000
meters from the facility. ff"ves had higher concentration than the grass, ranging from 86
pg/kg to 4.3 pg/kg GenX and ©19'10 28 pg/kg PFOA. The PFOA and GenX concentrations did not
e,,
directly corrwith distance.,;Hirt the highest concentrations were at the 50 m locations for
both. Background locations distant from the facility (85 km) were non -detect. The PH agency
stated that the data "represented' a warning signal for consumers of locally grown food". The PH
agency also studied theptatce:of PFOA from soil to edible plants and identified that PFOA was
taken up from soil and distributed to the ingested portions of crops, with the ratio of uptake
varying by crop and identified as —1% for tuber crops to 3.5% for other crops. There is no data
from this study for the uptake of GenX from soils to plants. (RIVM 2017)
10. In a study published DuPont and Chemours scientists, Hoke et al. (2016) report on 28-day GenX
bioconcentration studies on common carp. They exposed the carp to 2.OeO4 and 2.OeO5 ng/L
dissolved GenX. No GenX was detected in the fish tissue at the end of the study, but the tissue
reporting limits were elevated (5.5e05 ng/kg). They also reported a reproductive -effect LOEC = 8.1
mg/L GenX in a Daphnia magna 21-day reproduction test, a NOEC >107 mg/L for a 72-hr static
green algae (Pseudokirchneriella subcapitata) growth test, and >8.9 mg/L NOEC and ECso for a
rainbow trout 90-day early life -stage test, evaluated as hatching success, mobility and growth
parameters. While the fish tissue bioconcentration test did not provide useful data due to the
DEQ-CFW 00070920

4
elevated reporting limits, the suite of aquatic toxicity tests for the other standard aquatic toxicity
testing organisms did not indicate that GenX is acutely or chronically toxic at the selected test
concentrations to these organisms.
General PFAS, PFOS/PFOA Toxicology -
1. PFAS compounds are rapidly absorbed (minutes) and accumulate by binding to proteins in the
blood and other protein -rich tissues (liver, kidneys). PFAS can cross the placenta and accumulate in
breast milk.
2. Most of the health -effect studies for PFAS have focused on PFOS and PFOA, which are being
phased out in favor of shorter -chain PFAS that are suggested to be less toxic, less bioaccumulative
and more rapidly eliminated. Commonly reported epidemiological (human) health effects of
PFOS/PFOA exposure include: increased serum lipid levels,.increased uric acid levels (an indication
of deficits in kidney function), indicators of liver damage, increased "incidence of thyroid disease
(with possible implications of endocrine effect $ HBP during pteg-nancy, and ulcerative colitis.
Decreased birth weight and decreased fertility 'h0d been reported in some studies. While
increased incidences of kidney, testicular and prostate cancers have been reported associated with
human exposures, the evidence of carcinogenicity o€ PFAS is considered '14conclusive". There is
some evidence that PFAS compounds may have endocrine disruptor ("hormarrai)y active"
toxicants) effects in humans, but that has not been confirmed.
3. The most sensitive effects of PFOS/PFDA expos t'reported in ariitnai studies are developmental
effects and liver damage. Development effects reported include beftavioral and neurological
changes, skeletal effects, delayed onset of puberty ar►dt delayed attainment of developmental
milestones. Animal tests indicate perfluoroalkyl compoundsaffect the regulation of genes involved
in a broad;range of complex biological responses associated ith.,lipid metabolism, glucose and
lipid regulation, cholesteri lsynthesis, regulatif signal transdd ction pathways and nervous
system functions, fatty -acid metabolism, hormone regulation and immune and inflammation
responses. Suppression of genesinvolved in criticalsystenms influencing the regulation of cellular
communication, c€*ll adhesion, growth and apoptosis (controlled cell death) have also been
reported. These path pl(cat -"' are all irned in controlling cellular perturbations involved in the
control and }progression o tumor deve"I"' ment. Biological membrane function may also be
affected.:,
slm/Chemours/Talking Points
DEQ-CFW 00070921

5
Abbreviations:
CFRB = Cape Fear River Basin
EC50 = concentration at which there is a statistically significant non -lethal effect to 50% of the test
organisms as compared to the control response level
LCMSMS = Liquid chromatography tandem mass spectrometer analytical instrument system
LOEC = lowest observed (statistically significant) effect concentration
NERL = EPA's National Exposure Research Laboratory, RTP
NOEC = no observed (statistically significant) effect concentration
ORNL = Oak Ridge National Laboratory, TN
PFAS = polyfluoroalkyl and perfluoroalkyl substances
PFAA = perfluoroalkyl acids
PFCA = perfluoroalkyl carboxylic acid, PFAAs
PFSA = perfluoroalkyl sulfonic acid, PFAAs
PFOS = perfluorooctane sulfonic acid, C8 PFSA
PFOA = perfluorooctanoic acid, C8 PFCA
DEQ-CFW 00070922