Document JNXjY6dakN24xZkwpLz2xkYBB
ST-310
ToxDocs 10-195
TOXICOLOGY ASSESSMENT AND COMPLIANCE ASSURANCE GROUP 3M COMPANY
10-195: ORAL STUDY OF MTDID 208 AND MTDID 1004 IN MALE RATS
FINAL REPORT
ToxDocs Study Number
10-195
Test Material
MTDID 208
Lot Number(s)
MTDID 1004 217 (MTDID 208)
Strategic
Tox
Lab
Study
Number
|
332 (MTDID ST-310
1004)
Other Identification Number(s) | K'PFOS (MTDID 208) NH;"PFOA (MTDID 1004)
19F/TH-NMR GID Number
Analytical
Report | See Appendices 1 & 2 for Certificate of Analysis
Study Director
Jill Hart, AAS, LATg Laboratory Administrator
Principle Investigator: (Study Monitor)
John Butenhoff, Ph.D, DABT, CIH Corporate Scientist
Testing Facility Tn-Life Start Date
3M Strategic Toxicology Laboratory 3M Center, Bldg 270, room SB314 Saint Paul, MN 55144 August 4, 2010
Tn-Life Termination Date
October 4, 2010
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"ToxDocs 10-195
TOXICOLOGY ASSESSMENT AND COMPLIANCE ASSURANCE GROUP 3M COMPANY
10-195: ORAL STUDY OF MTDID 208 AND MTDID 1004 IN MALE RATS
Compliance Statement and Signature Page
`This study was conducted
to regulatory guidelines.
for
research
and
development
purposes
and
does
not
conform
`This final report has been reviewed and approved by:
Jill'Hart, AAS, LATg
SLtabuodryaDtiorreyctAodrministrator
Dl 2. KZ
John Butenhoff, Ph.D., DABT, CIH.
Corporate Scientist Principle Investigator
Date
17 oH 22h
Date
20f 15
ST310
`ToxDocs 10-195
1 Summary p`Tehreflpuuorrpoooscetoafnteshuilsfosntautdey(wPaFsOtSo)eavnadlupaetretfhlueoarbosoocrtpantoiaotnec(hParFaOctAe)rifstriocms loofw-dose oral `AebxspoorsputrieounsoifngPbFoOtSh waantderPaFnOdAcwoamsoeilvaalsuavetheidcbley imneamsaulreiSnpgrtahgeuirecDoanwcelnetyrartaitso.ns inrat `serum at 4 hours and 24 hours after single oral administration ofeither K"PFOS (MTDID 208, 20 pkg and 1 mg/kg), NH,PFOA (MTDID 1004, 20 pg/kgand | mg/kg), or
KPFOS andNH PFOA (20 ng/kg and 1 mg/kg) concurrently.
Aslclheadtusleadppsetaurdeydtneromrimnaaltidounr.inAgttnheecsrtoupdsyy,ansdertuhmeraenwdalsivneor wmeorrtealhiatryveosctceudrraenddpsrtioorretdo frozen pending PFOS and PFOA concentration determination by LC-MS/MS. Rsoelguatridoln,esosroPfpFrOeSp/arPaFtOioAnm(iexittuhreer)a,s,stihnegluesePoFfOcSodmosoiinlgassovleuhtiiconl,e sgienngelrealPlFyOapApedaorseidngto ruseidnugcewautepr atsoavfebhkoictelhe.PFOS and PFOA in serum and liver in male rats when compared to
2 Study Objective
`The purposeofthis study ws to evaluate the absorption characteristics of peexrpfolsuuorreooucstianngesbuoltfhownaatteer(PanFdOSc)oamnodilpearsfvleuhoircoloectiannmoaatlee(SPpFraOgAu)efDraowmlleoyw-radtos.se oral AsbesrourmpatfitoenroofraPlFKO'SPFaOndS P(FMOTADIwDas20e8v)alaunadtNedHb;yPmFeaOsAur(inMgTtDheIiDr c1o0n0c4e)niardamtiinoinsstriantion; cither separately or in combination.
3 Test Material Information 31 Test Substance
i |
Ee
Chemical Name | Potassium Perfluorooctanesulfonate Other Identifiers |K*PFOS
[pai [Deity
Jeo [wa
Stable under normal conditions
June 2019
3ofl4
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ToxDoes 10-195
Characterization
Handling
Precautions
Disposition
[Cndensi_e--y_ 0
`The test material is assigned as MTDID 208 and its characterization is attached as Appendix 1
`The test article will be stored tightly sealed in its original container at ambient room temperature.
Standard protective equipment will be used. Lab coats,
gloves and eye protection will be worn whilehandling the
test article.
| wromness LTE ly `Any remaining unused test article will be kept in the Study
Lo AS SRRI
ER a
Other Identifiers NH{'PFOA
EE [BgimionDue
Characterization
Storage
Handling Precautions
Disposition
32 Dose Preparation
97.99%
Stable under normal conditions
[wme2os
|
`The test material is assigned as MTDID 1004 and its
characterization is attached as Appendix 2.
`The test article will be stored tightly sealed in its original
container at ambient room temperature.
Standard protective equipment will be used. Lab coats, gloves and eye protection will be worn while handling the
test article.
Any remaining unused test article will be kept in the Study
Facility until expiration date.
Dose Preparation
Physical State of
administered material
Route of Administration
`The test materials were dissolved in
either water or com oil as 20 pg/mL or
1 mg solution.
Liquid
[Ol
|
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4 TestSystem 41 Test System Information
[Species
TR
[Stain
Tsp
[ `AgeS at Inio tiatiu onofr Treac tmente| 8[H--ar2l0anwLeaebokrsatories
`Weight at Initiation of Treatment
"Approximately 200-479 g
TACUC Animal Usage Application Number
2U0n0i8q-u0e4t5a9il mark in indelible ink
42 Animal Husbandry
DicVWater Housing Environment
"cAalgleasnitmharlosugwheoruet gthreouspt-udhyouesxecdepitn dsuorliindg-buortitnoemand wfiecreesdcbooltletcotmiomnetinabwohliicshmrcatasgiwnegrefosriunrgilneehaonudsefdeciens ctoelrlmeicntaitoinonfotri2me4.hours prior to designated study | HMaardliasnoTne,kWlIad) Raantd/tMaopuwsaet2er01w8erDeieatva(iHlaarbllaenaTdekiad, libitum throughoutthestudy. Temperature Range 72 = 3F |Humidity Range 30 - 70% M12ihnoiumrulmiogfh1td0arekxccyhcalnegesofroom air per hour
5 Study Design
Dose Group|Compound(s) | Vehicle
teem
Dosing
solution | concentration|
Dose Volume|
N|
Sex|
Euthanasia
1 Ty 17
PFOS/PFOA
hii
[[r6o[PxFOSPFOA
wie
PFOS
=o
[8 proa
water
[9 [Prosproa
ughg
20 ug/ml
[33]]
20 ugo/nmtl. | iheg
1
20 ug/ml
[3]
mg
4hrs PD.
4hus rs PD
24 hrs PD
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ToxDocs 10-195
#ros ; ~Hit 10_| pros
2
LE
[IIPFOA__| comoil | op| 20ughml | op g [3] M| 24hsPD
PFOS/PFOA
[3]
[3 [pros |
1
[15 [ProSProA oe | ii
1 mg/m; L i1E [3]
4hrsPD
[1s [pros
;
;
[18 [PPFFOOASPFOA
gke 1 mg/mL. hy
[19 Tpros7] [20Tproa |
1 1 mg/mL. 1
24hrsPD
["21_[ PFOS/PFOA
sayy
iis IF
PPEFOOSA/PFOA
wife 1mg/mL miei M| 24hrsPD
Anlelcrroatpssywewrietheubtlhoaondi(zfeodrvsiearCumO);aansdphlyixvieartsicoonllaetctdeeds.ignated times followed by gross
6 Parameters Evaluated
61 Clinical Observations
`Emaocrhalaintiymaanldwmaosrboibdsietryv.edAnimymneodtiaabtleelyfifnodlilnogwswinegredorseicnogrdaendd.throughout the study for
62 Body Weights
Aalnldapnriimoraltso nweecrreopwseyi.ghed prior to treatment for the purpose ofcalculating dose volumes
63 Serum Collection
cAotlleeuctthiaonnastiuab,esblwoiotdhowuatsanctoilcloeacgtueldvanita.thTeheabbdloomoidnsaalmapolretsa awnedretraalnlsofweerdedtotcolloatbfeolred15 to 3se0rmuimnuwtaesstartarnsofoemrrtedetmop1e.r7a-tmLuanrpdoelytphrenopcyelnetnreifmuigcerdoacten2t0r0i0fuxgegtfuobres15lambienluetdesw.itThahe.ube code and stored frozen at -70C pending analysis.
6.4 Gross Necropsy, Organ Weights and Tissue Collection
Fwoelrleohwairnvgesetuetdhaannasdiath,eacgorrorsesspnoencdrionpgsywewiagshtpserwfeorremreedcoorndealdl.anAilmlalssa.mplLeivsewresraempsltoersed in afreezerset to maintain -70 Cforfuture analysis. No other tissues were collected.
65 Analysis
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PFOS and MS/MS.
PFOA
concentrations
were
determined
in
all
serum
and
liver
samples
by
LC-
7 Statistical Analysis
There were no statistical analyses performed on data collected in this study.
8 RawData
`NTohteerbaowokda#ta1f5o4r82b3o,dypawgeeisgh7t8s,- o80r.gan weights and dosing volumes are recorded in 3M
9 Results
9.1 Clinical Observations
CNloinmiocratlaolibtsieersvaotcicounrsrewderdeurnionrgmtahlistshtruoduyg,haolultratthse
survived study.
until
scheduled
necropsics
92 Body Weights and Organ Weights
Body and the study.
liver
weightdataare
presented
in
Table
1.
All
animals
gained
weight
during
93 Gross Necropsy
`There were no gross lesions or other abnormalities noted in any rats during necropsy.
94 Analytical Results
PFOS and PFOA concentrations in serum and liver are presented in Table 2.
10 Discussion & Conclusion
sRoelguatridoln,esosrofPpFrOeSpa/rPaFtOioAnm(icxittuhreer)a,s,stihnegluesePFofOcSodronsoiinlgassovleuhtiiconl,e sgienngclrealPlyFOapApedaorseidngto
reduce uptakeofboth using water as vehicle.
PFOS
and
PFOA
in
serum
and
liver
in
male
rats
when
compared
to
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Body weight(BW)and liver weight (LW) data
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err] Emma See
Ea a| EEEERs E arra maa
Zomeh
fomssrhae0]72m |222|223| ee]
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Table2: ~~ PFOS and PFOA concentrations in serum and liver
"ToxDocs 10-195
=E ] l E E E ==E= e] EEE e E ESbeEbeEeS
~[| EBE = ell m i =e
C ENE===l E =EiSE E E =imlEeeE nE eB t=Eee eii E SeE-Eee EEeE
TC=1] Cl
= BE E E = E --E H l oEE--EEF|EE
E = E = =EE=EEEE [Gnoe--]
Cham am]
IC~ l] EE E=ellEEE ==E EEE
C Ba -- [~]roamronconor jEE EE E e= rl]oE EF E -- = E Eo E EEn EE
CCe1] EE E E E =]E -l Ee E E -- =EE==e E E 2EhsF|
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`Appendix 1: MTDID 208 Certificate ofAnalysis
INTERIM CERTIFICATE OF ANALYSIS
REVISION 1(9/7/00)
Centre Analytical Laboratories COA Reference #:
018A
3M Product: PFOS, Lot 217
Purity: 86.9%
Reference #: SD-018
023-
Identification
NR
Metals (ICP/MS)
Positive
1. Calcium
1. 0.005 wt/wt.%
2. Magnesium
2. 0.001 wt./wt.%
3. Sodium
4. Potassium'
3. 1439 wt/wt.%
4. 6.849 wtWL%
56.. NTirocnkel
|| 5. <W0.w001%
7. Manganese
| 6. 0.005 wt/wt.%
| 7. <w0t.0/0w1 t
IMR)
Er [| we (LC/MS)
i (GC/MS)
Tos| POAA
0.33 wt/wt.%
Bw pe A)
[PuritybyDSC
[Not Applicable _|
Inorganic Anions (IC)
21.. CFlhuloorriiddee
1. <W0.w015%
3. Bromide
2. 0.59 wt/wt.%
4. Nitrate
3. <0.040
5. Nitrite
WL/WL%
6. Phosphate
7. Sulfate'
4. <0.009
wt/wt.%
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sT-310 Organic Acids (IC)
1. TEA 2. PFPA 3. HFBA 4. NFPA Elemental Analysis 1. Carbon 2. Hydrogen 3. Nitrogen 4. Sulfur 5._Fluorine
ToxDocs 10-195 5. <0.006 WLW 6. <0.007 WLW% 7. 876wm%
1. <01 w/wt% 2. <0. wtiwtd% 3. 010 wt/w% 4. 028 w/w
1. Theoretical Value = 17.8% 1 1248 wiwe%
2. Theoretical Value = 0%
2.0244 Wiwt%
3. Theoretical Value = 0%
3174 ww%
4. Theoretical Value =5.95% | 4. 8.84 wt/wt%
5. Theoretical Value = 60% 5. 54.1 wtwt%
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INTERIM CERTIFICATE OF ANALYSIS
Centre Analytical Laboratories COA Reference #: 023018A DateofLast Analysis: 08/31/00 Expiration Date: 08/31/01 Storage Conditions: Frozen <-10C Re-assessment Date: 08/31/01
F"lPuuorirtiyde=, 010.05%9%- +(sNuMmRofimmpeutraitlieism,pu1r.i9ti3e%s+,o1rg.a4n5i%c+aLciCd/iMmSpuriimtpiuersi,ti0es.,388.%4t1P%O+IAnAo,rganic 0.33%)
Total impurity from alltests = 13.09% Purity = 100%- 13.09% = 86.9%
Potassium is expected in this salt form and is therefore not considered an impurity.
3Purity by DSC is generally not applicable to materials of low purity. No endotherm was
observed for this sample.
"iSnuolrfguarniicn atnhieosnammepltehoadppceoanrdsittioonbse.coTnhveeratneidontoreSsOul;taangdrheeenscweelldewtietchtetdhuessiunlgfturhe determination in the elemental analysis, lending confidence to this interpretation. Based on the results, the SOy is not considered an impurity.
TFA
HFBA NFPA PFPA
Trifluoroacetic acid
Heptafluorobutyric acid Nonofluoropentanoic acid Pentafluoropropanoic acid
"Theoretical value calculations based on the empirical formula, CsF17SO5K* (MW=538)
"This work was conducted under EPA Good Laboratory Practice Standards (40 CFR 160).
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INTERIM CERTIFICATE OF ANALYSIS
Centre Analytical Laboratories COA Reference #: 023018A
LC/MS Purity Profile:
-- T -- ET I SO ; 7E-- Note: The C4 and C6 values were calculated using the C4 and C6 standard calibration curves, respectively. The CS value was calculated using the average response factors from the C4 and C6 standard curves. Likewise, the C7 value was calculated using the average response factors from the C6 and C8 standard curves.
Prepared By: David. Bell Date
Scientist, Centre Analytical Laboratories
Reviewed By:
John Flaherty
-
ey eTDate
Laboratory Manager, Centre Analytical Laboratories
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Appendix 2: MTDID 1004 Certificate ofAnalysis
CERTIFICATE OF ANALYSIS
March 2, 2000
FC-143, Lot 332 Richard M. Payfer
`This sample was analyzed using GC/AED, LC/MS, "H-NMR, and GC/MS techniques.
c`Tohmeporsesiutlitosno:fthese tests show the sample to contain the following weight percent
[CC
coRcomNm--Too]
encom
T
opw
|
corcomm--|wow
|
To Additionally, the isomer distributionofthe sample was determined using
techniques and found to contain the following mole percent composition:
CF,(oCrFma.l)c-hCaiFn,(CwhFeCrEe)x,i-CmaOin0lyN6H) ) where(Ixnt+eyrnsalmamionlnyome4,thaylnxbrad0nc,h, 0 isopropylbranch,where xismainly 4
busy! branch, wherexismainly 3
''F-NMR
12.6%
E CFCC( FICC R),CFOCNH) e ntemal gemm-adiinlmyeth3,ylanbdraxn2c0h,)where x+y is
i Possible.where *Ris undefined (Alpha branch, whereis mainly 3) 140f 14