DEQ-CFW_00000303

NC D905 `R,�sl� .AssesSm-c.n4"
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. �' 71 Z 7 x
ions and Answers Regarding Potential Health Effects Related to GenX fCaYAfiLoua.S
.,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propionic acid, ammonium salt,
CAS# 62037-80-3) Tht 6 COS# c s f r a-nwe qeA, k ego ( Fri'
c -Some eN\analKoy-N c_n
y
Pam' O\to�` Why is North Carolina providing a health assessment if the science behind GenX is still limited?.ol C�h
C.
c� there is su(• �
When there is not a federal standard an fficient scientific information available, the North ILS
Carolina Department of*alth and Human Services NC DHHS) can develop and issue a health
-rli Pw�,�osr V,6 &A-*Lw �5a,e-%, e"~r-,s fft�� 137-9Z-13-4a
assessment. This can include esta1lishing a public health goal, sowAghres referred to^as a health (FR 090,3)
pubtu c
screening level. Ohealth goal is a non -regulatory, non -enforceable level of.@ contaminant below which
3-fief ms 4&%,« He-4Lr►� c-W.�L.s . rs7*6(..sKA�
no adverse health effects would be expected over a lifetime of exposure. Although health information is ra...
use' limited for many of the newer or "emerging" perfluorinated compounds, NC DHHS has determined tha
> w«� +3 f)P°c� TV
�eaW� A there is sufficient scientific information to rovidekpr 'n health assessment for GenXAw assessmeCN+ � pub111 c he alb scree �n l resl. (4 • 7) f 3usr
NC DHHS shared a preliminary ass ssment with local partners on une 8, 26r7-firma 17
some context for understanding the he h risks that could be associated with GenX ato the lleve�p found �2O3�.ga
in the Cape Fear River during 2013-20 S. Environmental Protection Agency (EPA) is working to
provide more comprehensive health risk for this chemical. However, the timeliness of that
3
�ktM process is not sufficient to address the urg ub rns raised by identification of GenX in the
lic drinking water sup /Y)9 :s 6e . C.4V 6c?
risY_ ill kiti?
rr4"ttisimportant to notass s are bas n available data and air updated
b 3 as new information beco vailabl HHS conti to review all available health data and work
\ �b 4with federal agencies (EPA a for Di a Control and Prevention [CDC]) and academic
3 F researchers t bet r u erstan a th oci with GenX.
1 �R\Cb
L
�+ What information did NC DHHS use ir'prelimina ssessm n ?
9ucaarice ualots 64j" p�1�Mt��yass 114k (7) +0 proper �U+ . �k
In the absence of health guidance values pub fished by U.S. federal agencies, C DHHS used GenX
toxicity information available from the European Chemicals Agency (ECHA) to calculate a health
Esc ening— le o 71,00 nanograms per liter (ng/L, also referred to as parts per trillion or ppt). See
-►�•c w`rH Appendix 1 for the ca culation of the initial preliminary assessment using the information from ECHA.
f c.�vs.sn-+vrL{� 1$ %1a4 A
r >,w eAlmV44. Why�NCDHHS updatj'its preliminary assessment?
b 2rZ�-�95t�D
;i THE A�cl�,c,
Since shaVPF the initial health assessment, NC DHHS has continued to review all available health
r �r-'O T9 CO�N�muri/�s
information atQut.GenXA.Based on this review and continuing discussions and a morre4,nt r?c co�nsenssus
44
with EPA, NC DHHS has determined that sufficient data are available to update the iaWal assessment.
W4011W
The current revised health screening level is 140 ng/L for the most vulnerable population- i.e. bottle-fed
infants, the population that drinks the largest volume of water per body weight. This revised health
North Carolina Department of Health and Human Services DRAFT 7/13/201711:27 AM
pace 105 NeedL CQ
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screening level is lower than t.._ ._ _ _: '., __ _e WUal assessment for several reasons, including the
following: First, after consultation with EPA, a'8ifferent set of animal studies was identified as an
�K appropriate starting point for the assessment*This change Iovagd t& heal" screening level by 10-fold.
o� ? Since the new starting point was based on short-term rather than long-term (chronic) animal studies, an
additional uncertainty factor was added, which lowered the level by another 10-fold. In addition, while
0 the initial assessment assumed that drinking water was the only source of exposure, the revised
\�*� A101 estimate includes an assumption that only 20% of a person's GenX exposure comes from drinking water,
lowering the level another 5-fold. This 20% is a &Eerc assumption used as a default by the EPA when
information is lacking about other exposure routes; it was included based on additional review and
consultation with EPA There is limited information available about actual sources of exposure to GenX
/ in the environment. Detai the specific updates and calculations for the revised health screening level
are presented in Appendix 3. ,my ec iNd�ca�'e - a�- �Ir1t° �eneC4C ascu"`l O vv
dtd they �,- -PC nti. EP A ? wc3'u�d app( '� adu I-�'s (Posse b ly''oye�e. KOoja haz - £'Pa
add' r pp
� �� As with the�+ttxl�preliminary assessment, it is impo ant to note that this updatedH�ssment is
We i not final and is likely to be revised as new information becomes available. P*e oaal screening levels
Su� �ed -----
io for other populations are presented in Appendix 4.s�onab
�.onn+hem
I,oak. 4. What does the revised health screening level o�GenX mean?
1NAica�is
The revised health risk assessment w€ts that there co Id be an increased risk of adverse health effects
for the most vulnerable people in the population,over a lifetime of consuming water with level greeaater
than 140 ng/l. his revised health screening level is lower than the level in the .ia4iiikr4k.assessment.
Because this level is based on the most vulnerable population (bottle-fed infants), it is also protective of
adults (including older adults), pregnant women, nursing mothers, and children. See Appendix 4 for age
wcrotw'N
group calculations and pceu►s+aaal screening levels for other population. This revised health assessment
is based on evolving toxicological dataq sti co i e ed ro ' id a and is subject to further updates
based on an ongoing review and cons Itation with federal agencies and other partners.
-"I"6.s }'N�4t Alk-
ASstr+�sMt��vrs CEF+�vtrM t7v�' r.� uPo -p i,Vw' . CSA'nV &Ge �FW C4tC
`� Alt ou th ini 'al hea h ri lev was ased pon mbine�cancer nd n cancer�ndp intss his
e5 rr t h Ith tree g I el i ase on a mal s dies that inclu ed no cancer e�idp nts dnly.. ad
Cn �\ Ba ed o con ersat ons 1th PAyt ereis not enough in rma ion atti�is itx�e to identify a specifi level Loot S�
of GenX that might be associated with an increased risk for cancer. �
�' �k g �;11
o10'e
00, Does NC DHHS recommend that people stop using the municipal water for drinking or other V1751 A
purposes?
y_p `t 5
Q, T.q COa�G�c��O.v �V77/e
Z� There is not enough information about the human health effects of GenX or related chemicals to make a 3v-M-R ro
��� recommendation against using the municipal water for the general population or for any specific groupSKST Sryt
Oro g gyp\? at this time. Individuals are encouraged to consider information in the health risk assessment when A �5 `
\Al�V(;� making decisions about water use. The potential health effect from these chemicals should be balanced.4sstF%,^,, vr
'A against the health benefits of municipal water, including routin monitoring for a variety of microbialAO
�► .`t�.
North Carolina Department of Health and Human Services DRAFT 7/13/2017 11:27 AM
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and known chemical contaminants that could be present in private wells or other egtrieted sources. Wjrh �r•5S
4�0b,45r
NC DHHS supports all efforts to eliminate sources of GenX and related chemicals in the water supply. IhON,7-42,u G
&Va(44 4755, t" /?-> 3✓rrc rb
6. Does this mean the water is unsafe? wn­� .
A health screening level is not a boundary line between a "safe" and "dangerous" level of a chemical.
Rather, it is a goal that represents the level of GenX at which no adverse n - ! erFhealth effects
would be anticipated over an entire lifetime of exposure to the most sensitive population.
-4+ha-- -4- is
7. Is it safe to eat fish from the Cape Fear River? g +Q ►'NCaCCa'I-2
6
�C4ACA-�_(i i S
There are no fish advisories related to GenX. Preliminary information from EPA suggests that GenX is not
anticipated to bioaccumulate in fish. A list of statewide and location -specific fish advisories related to
other contaminants is available at http://epi.publichealth.nc.gov/oee/fish/advisories.html.
4 t,,rC h�**-+es-1 e& `� sh e3k-ctz. and -the eu ewe& -io dlO" wV­L& kK
8. Is health information available for others g perfluorinated compounds found in the Cape issue .
Fear River?
X°
In discussions with EPA and other partn a no identifiecWata that could be used to determine ,A
a preliminary health risk assessment for
id,e I -red unet
�f$4T�kj! Se�ietttifi
needed o Mond
compounds.
perfluorinated compounds b )}e� h
s are
5
;smentso other perfluorinated
9. ealth informa vailab 4-di 0OW
Health infor on about 1 -di ne it at http:Hde v/about/di ' ns/w r-
S 15 resourc water-res s-data/water- -hom eJ1-4-dioxane.
_\j.J., D&e f
•�(,0 10. Is NC DHHS working with other agencies or researchers?
Yes. NC DHHS has been iRS" contact with officials at EPA and the CDC to gather and review o hey h
information related to GenX EPA is working to develop a health risk assessment for GenX; however, the
timeframe for that assessme t is not known. NC DHHS staff are also in contact with academic
researchers with knowledge nd experienced these compounds.
cDMQo�c�ds �N aeo�'
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-jau,v 98, "0
--)Appendix 1: Calculation of the I�N`kPreliminary Assessment � d4ea - X'W�-
The European Chemical Agency (ECHA) information included a Derived No Effect Level (DNEL) of 0.01 '0'eC10
mg/kg body weight (bw)/day for oral exposures. The ECHA assessment was performed�Sna>no
observed -adverse -effect -level (NOAEL) from a 2-year rat chronic toxicity/carcinogenicit study as the
point of departure (POD) and applying default uncertainty factors, as described below:
dwl'5k- A'o -VAe. 66-j
• No -observed -adverse -effect -level (NOAEL)) = 1.0 mg/kg body weight (bw)/day
• Total default uncertainty factors (UF) =100 (interspecies variability =10; intraspecies
variability =10)
• Formula: NOAEL/UF = DNEL
Qgf-L _ (1.Omg/kgbw/day)/100=0.01mg/kg/day
NC DHHS calculated a drinking water equivalent level (DWEL) for GenX as follows:
`' h�a��'h screen�n
• Dose (DNEL) = 0.01 mg/kg bw
• Body Weight .-�7,{8 kg (infant)
•W =�1W1 L%day(infant)
• Relative Source
• Unit Conversi
• Formula: dose
DWEL
iJW F-L
(0.01
NOTE., ng/L can
) X RSC X Unit Conversion =
70, 90
J X 106 ng/mg = 71,000 ng/L
nod- the A# -the c j o r� gna
expressed as parts per trillion or ppt
— Sout /t.cts` ;
The values used for body weight and drinking water intake were(based on infant in order to be
maximally protective, since infants consume the highest amount of water in relation to their body
weight. The initial calculation assumed that 100% of GenX exposure (relative source contribution) was
from water consumption. DWEL is the same as a health screening goal.
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7
it
Appendix 2: Calculation of 4A Revised Health Assessment C a t& xxxx
After consultation with EPA, the following were updated:
wv'h a ? ( t,JVJ,-&
• Sufficient data are available to support the use a lower no -observed -adverse -effect -level
Noe_ 4va-" (NOAEL) as a point of departure for the assessment. This'NOAEL (0.1 mg/kg/day) is 10-fold lower
.V(\4- Z�eC''S than the NOAEL used in the initial assess�nt and is based on effects on the liver in mice.
dtC �o r . Since this point of departure is based on a subchronic toxicity study rather than a chronic
11s+e d Tor What iS chroe�lG
toxicity study, an additional uncertainty factor of 10 is included in the calculations.
PPP. • A relative source contribution (RSC of 20% is used to account for potential exposure to GenX/5QbChrou1c
from other_ routes like air and food. The RSC lowers the aeaa concentration in water'' `e �obtic
allowable wtt
and- •+v
Revised calculation: bchroni c /e hro�',c = tWaS e10 CI£At'
4-vta+
• No -observed -adverse -effect -level (NOAEL) = 0.1 mg/kg body weight (bw)/day
• Total default uncertainty factors (UF) =1000 (interspecies variability =10; intraspecies
variability =10; and subchronic to chr nic variability =10)
• Formula: NOAEL/UF = Reference Dose (RfD) (� • b r'vy�
(0.1 mg/kg bw/day)/1000 = 0.0001m9/k9/day
NC DHHS calculated a drinking water equivalent level (DWEL) for GenX as follows:
-�+6 is a ��,a�•4•ernn'' hire
• Dose (RfD) = 0.0001 mg/kg bw/days
• Body Weight = 7.8 kg (bottle-fed infant) icy.
,�a+er in9e6' M Intake = 1.1 L/day (bottle-fed infant) �o �r,���k5 ��P
• Relative Source Contribution = 0.2 . �m
1
• Unit Conversion =106 ng/mg
• rmul . dose (mg/kg bw/day) X body weight (kg)/intake (L/day) X RSC X Unit Conversion =
OW EL � (0.0001 mg/kg/day)X 7.8kg/(1.1L/day)X 0.2 X 106 ng/mg =140 ng/L
NOTE: ng/L can also be expressed as parts per trillion or ppt r
The values used for body weight and drinking water intake were based on the -fed infants n order to
be maximally protective, since infants consume the highest amount of water in re ation to their body
weight. For other age groups see table below. DWEL is the same as a health screening goal.
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Appendix 3: References
Beekman M, Zweers P, Muller A, de Vries W, Janssen P, Zeilmaker M. 2016. RIVM Report 2016-0174:
Evaluation of substances used in the GenX technology by Chemours, Dordrecht.
http://www.rivm.nl/Documenten en publicaties/Wetenschappeliik/Rapporten/2016/december/Evalua
tion of substances used in the GenX technology by Chemours Dordrecht.
ECHA Toxicological Summary for Ammonium 2,3,3,3-Tetrafl uo ro-2-(He ptafl uo ro pro poxy) Pro pa noate.
https•//echo europa eu/registration-dossier/-/registered-dossier/2679/7/1
Gannon et al. Absorption, distribution, metabolism, excretion, and kinetics of 2,3,3,3-tetrafluoro-2-
(heptafluoropropoxy)propanoic acid ammonium salt following a single dose in rat, mouse, and
cynomolgus monkey. Toxicology 340 (2016) 1-9. htto adx.doi.ore/10.1016/i.tox.2015.12.006
Hoke et al. Aquatic hazard, bioaccumulation and screening risk assessment for ammonium 2,3,3,3-
tetrafluoro-2-(heptafluoropropoxy)-propanoate. Chemosphere 149 (2016) 336-342.
http://dx.doi.org/10.1016/­­o.chemosphere.2016.01.009
Rae et al. Evaluation of chronic toxicity and carcinogenicity of ammonium 2,3,3,3-tetrafluoro-2-
(heptafluoropropoxy)-propanoate in Sprague—Dawley rats. Toxicology Reports. June 2015.
httos:Hdoi.org/10-1016/i.toxrep.2015.06.001
Sun et al. Legocy and Emerging Perfluoroalkyl Substances Are Important Drinking Water Contaminants in
the Cape., , F.6ar River Watershed of North Carolina. Environmental Science & Technology Letters. Nov
2016. DO1:10.1021/acs.estlett.6b00398.
USEPA. Drinking Wat
drinking-water/drink
? l hi's ISO
USEPA. TSCA Non -Co
r Health Advisories for PFOA and PFOS. https://www.epa.gov/ground-water-and-
tg-water-health-advisories-pfo — nd-pfos
�' Mtn-�arnec� S,ra�
fidential ,B.6siness Information for 8EHQ-06-16478.
North Carolina Department of Health and Human Services DRAFT 7/13/2017 11:27 AM
DEQ-CFW 00000308

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Appendix 4: Calculation of population -specific screening levels
GenX
Point of Departure (POV) 0.1 mg/kg/day
�U�o5;D
„310jjj,1000 unitless
DRAFtry' 0.0001 mg/kg/day
Relative Source Contribution (RSC) 0.2 unitless
Screening level = [(Reference Dose (mg/kg/day) * RSC * Body
Adult
80 a
Pregnant Women
73 b
Lactating Women
73 d
Child (birth to <6 years)
15
Infants (birth to 12 months)
I 7.
a EPA OSWER Directive 9200.1-120 [EPA 20
b EPA EFH Table 8-29: 50th per
all pre
`EPA EFH Table 3-3: 95th p
me
d Exposure dose guidanc
ATSDR: E
during lactation (Janney a
997; Moya et
e EPA EFH Table 8-1: Weight e
rage of mean
f EPA EFH Table 3-1: Weighted
a e of 95th p,
NOAEL f
10 inter:
POD/UF
2011]
hronic mice studies
;.10 intraspecies; 10 subchronic to chronic
dose comes from drinking water to account for other potential
/ Intake ra�e (L/day)]
640
560
410
140
rs EPA 2(
Tabl Weighte ge of 50th percentile body weight for females 15-45 years of age + 5kg retained
14) [1%k2016a, EPA 2011, Janney et al. 1997, Moya et al. 2014]
Ift weig m birth to 12 months [EPA 2011, ATSDR 2016a]
% le for c mers only from birth to 12 months [EPA 2011, ATSDR 2016b]
Acronyms:
lqmlh
OF = Uncertainty Factor
RfD = Reference Dose
mg/kg/day = milligram of compound per kg o weight per day
NOAEL = No Observed Adverse Effect Level
EPA = U.S. Environmental Protection Agency
RAGS = Risk Assessment Guidance for Superfund
North Carolina Department of Health and Human Services DRAFT 7/13/2017 11:27 AM

OSWER = Office of Solid Waste and Emergency Response
EFH = Exposure Factor Handbook
ATSDR = Agency for Toxic Substances and Disease Registry
References is M;.Sk_4e `fi n cQ
[ATSDR 2016a] Agency for Toxic Substances and Disease Registry. 2016. Exposure Dose Guidance for Body Weight. Atlanta, GA: U.S. Department
of Health and Human Services, Public Health Service, October 26.
[ATSDR 2016b] Agency for Toxic Substances and Disease Registry. 2016. Exposure Dose Guidance for Water Ingestion, Version 2. Atlanta, GA: U.S.
Department of Health and Human Services, Public Health Service, October 26.
[EPA 20111 US Environmental Protection Agency. 2011. Exposure Factors Handbook: 2011 Final. Washington DC: National Center for
Environmental Assessment. EPA/600/R-09/052F. Available at: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=236252#Download
[EPA 2014] U.S. Environmental Protection Agency. Humo&&h Evaluation Manual, Supplemental Guidance: Update of Standard Default
Exposure Factors. OSWER Directive 9200.1-120. February
Janney CA, Zhang D and Sowers MF. 1997. Lactation and
Moya J, Phillips L, Sanford J, Wooton M, GrejjffifiVW Schuda L. 4. A
lactation: Potential exposure factors a ndjdffij101%p Sci Env
Am J Clin Nutr. 1997;66:1116-24.
North Carolina Department of Health and Human Services DRAFT 7/13/201711:27 AM
logical and behavioral changes during pregnancy and