Document YK3LeRrmDbJ2OQyEdx6gv4gk

m{| ODFEPHAERATLMTEHNT OF H EALTH RAR Asa BSHdiAoRs BBaacckground DDooccummeenntt TTooxxiiccookkiinneettiicc MMooddeell ffoorr PPeerrfflluuoorrooooccttaannee SSuullffoonnaattee ((PPFFOOSS)) aanndd PPeerrfflluuoorrooooccttaannooiicc AAcciidd ((PPFFOOAA)) aanndd IIttss UUssee iinn tthhee DDeerriivvaattiioonn ooff HHuummaann HHeeaalltthh--BBaasseedd W Waatteerr GGuuiiddaannccee VVaalluueess MMaayy 22001177 NOTE:Thefollowing model was developed by the Minnesota DepartmentofHealth (MDH), Useofor reference to this modelwithout proper attribution to MDH is prohibited, MOH snot responsibfloer changes or misuse of the model byothers. Exhibit 3749 33774499..00000011 SSTTAATTEE 0077243366224456 TaofbConltenets Table of (}ontents USEOFTabIES: crs enn List of Tables: .............................................................................................................................................................. 3 LSEOFFIUIBS. 3 List of Figures: ............................................................................................................................................................. 3 RO BRIO smsommmtstmsm-------- List of Equations: ........................................................................................................................................................ 4 -- - on " 5 Acronyms .................................................................................................................................................................... 5 ERI oosmmmmmrsmmesmmmmm--T------------ Executive Summary .................................................................................................................................................... 6 1.0 GeneralApproach and Challenges for Estimating Water GUIdanCe VIUES....vunsinn 8 1,0 General Approach and Challenges for Estimating Water Guidance Values ......................................................... 8 BOSPRCT MO sem 2,0 Simple One-Compartment TK Model ................................................................................................................ 10 2.1 Model Inputs 2 2,1 Model Inputs ................................................................................................................................................. 12 2:11 Elimination (Halfife). " 2 2.1.1 Elimination (Half-life) .............................................................................................................................. 12 2.12 VOOIFDIUHIMDUOEN ccs 14 2,1,2 Volume of Distribution ........................................................................................................................... 14 2.1.3PlacentalTransfer. I . enn 15 2,1,3 Placental Transfer ................................................................................................................................... 15 2.1.4 Breastmilk Intake and Body Weight 16 2.1.4 Breastmilk Intake and Body Weight ....................................................................................................... 16 LAE BIEII srs 36 2.1.5 Breastmilk partitioning ........................................................................................................................... 16 22 Preliminary Evaluationof Mode ............ on SE 19 2.2 Preliminary Evaluation of Model ................................................................................................................... 22.1 Comparisonwith empirical data fromFromme and colleagues (2010)... 19 2.2.1 Comparison with empirical data from Fromme and colleagues (2010) ................................................. 19 222 Comparison with empirical data from Mogandecollneagus es(2e015)n .....cvvvvves 21 2.2.2 Comparison with empirical data from Mogensen and colleagues (2015) ............................................. 21 2.23 COMPAIISON With MOGEINg FEFSOUVIEIMSET css 23 2,2.3 Comparison with modeling results from Verner .................................................................................... 23 2.3 EXPANSION Of MOG! 10 SEA SIAtE DUIBHION vss 25 2,3 Expansion of Model to Steady-State Duration .............................................................................................. 25 23.1 AGGMOOUNIDND]US. 28 2,3.1 Additional Model Inputs ......................................................................................................................... 28 23.1.1 DUBINOfBIEaSHEEAING vss 28 2.3.1.1 Duration of Breastfeeding ............................................................................................................... 28 23.1.2 Water Nake RAUC....csssssssons 8 2.3.1.2 Water Intake Rate ............................................................................................................................ 28 2.4Summaryof MOH Model Parameters. SE _-- enn: 88 2.4 Summary of MDH Model Parameters ........................................................................................................... 28 3.0 Derivation of Health-Based Water Guidance Values 5 3.0 Derivation of Health-Based Water Guidance Values ........................................................................................ 33 3.1 Reference Doses andCorrespondingSerum Concentrations . 3 3.1 Reference Doses and Corresponding Serum Concentrations ....................................................................... 33 3.2 Rive SOURCE COMEIBUFAICOKONF verse 3.2 Relative Source Contribution Factor ............................................................................................................. 34 32.1Selectionof RSC forPFS. Ed 3.2.1 Selection of RSC for PFOS ....................................................................................................................... 35 3.2.2Selectionof RSC or PFOA. % 3.2,2 Selection of RSC for PFOA ....................................................................................................................... 36 FE -- 3,3 Reasonable Maximum Exposure Scenarios ................................................................................................... 37 3.3.1Scenario HL -- EXCIUSVElY IOrMUI-FEd INANE crn 38 3.3,1 Scenario #I - Exclusively formula-fed infant ......................................................................................... 38 3.3.1.1 PFOS ................................................................................................................................................. 38 3302 PFOA sss 38 3.3.1.2 PFOA ................................................................................................................................................ 38 33.2 Scenario #2 -- Exclusivelybreasted Infant... SE} 3.3.2 Scenario #2 - Exclusively breastfed infant ............................................................................................. 39 3320 PROS... -- SE 3 3.3.2.1 PFOS ................................................................................................................................................. 39 Useofo referenceto this modelwithoutproperattributiontoMOH sprohibited. 33774499..00000022 2 STSTAATTEE 0077443366224477 33220008 w 3.3.2.2 PFOA ................................................................................................................................................ 40 33..44CConocnlculsuisoinosn/sS/uSmummarmy.a.r.y............................s..e.s..e.s..e.s..e.s..s.s.s..e.s..o............s.e.n.s..e.s.e.s..a.n.s..............s.e.e..s.e.s..e.s.e..n.s.a..s.o.n............-- .............Y ........ 4:~ 4.0 References ......................................................................................................................................................... 42 APPENDIX -Summaryofplacental andbreastmilktransferSud data... 45 APPENDIX I -Summary of placental and breastmilk transfer study data ............................................................ 45 ADP | RAEIENCES.rrrsssnnns 81 Appendix I References: ........................................................................................................................................ 47 APPENDIX 1 Pecr Reviewer BORFAPICaIINOFMAION. 48 APPENDIX II - Peer Reviewer Biographical Information ....................................................................................... 48 List of Tables: List of Tabies: Tale 1. Age-spactic volumeofdstrouton (V) dsimen actars 1s Table 1. Age-specific volume of distribution (Vd) adjustment factors ....................................................................................... 15 Tae 2. Human ik intake for exclusively brated infants and colclted corespondin bocy weg (BW). 1 Table 2. Human mill< intake for exclusively breastfed infants and calculated corresponding body weights (BW/ ................... 16 Tae3.Results of comparing MOH-madeled PFOS infant ruconcentrations Fromme tl. (010) data... 15 Table 3. Results of comparing MDH-modeled PFOS infant serum concentrations to Fromme et al. (2010) data.................... :19 Tal. Restsof comparing MOH-madeled PFOA fant serum concentrations Frome tl. (2010) ta. 20 Table 4. Results of comparing MDH-modeled PFOA infant serum concentrations to Fromme et al. (2010) data .................... 20 Ta5. CompaorfMiOHsPoFnSodel resus for cxcsivey breasted infant (sng upper exces take ot)vi. Table 5. Comparison of MDH PFOS model results for exclusively breastfed infant (using upper percentile intake rates) vs. VES BSUS. reese re 2) Verner model results ................................................................................................................................................... 23 Table6. CompaofrMiOHsPoFOnA mdel reat fo excuse reainsfantt uisingeuppder percents nae at) vi Table 6. Comparison of MDH PFOA model results for exclusively breastfed infant (using upper percentile intake rates) vs. Verne mde resus. a Verner model results ................................................................................................................................................... 24 Tae7. riking water ingestion ats forconsamers-ony an colcted<oresponding bodyweights (OW)... 28 Table 7. Drinking water ingestion rates for consumers-only and calculated corresponding body weights (BW)..................... 28 Table. SumomfMaOKmrodyel input parameters. on . fy Table 8. Summary of MDH model input parameters ................................................................................................................. 30 List of Figures: List of Fi iures Figur1e. Martanteto emtusfnlfnt. - . Figure :1. Maternal transfer to fetus/infant ................................................................................................................................. 8 Figur2e. Relative concentration comparisons of POS nbrestmik, Thomsen, 2010 and MDTKmoWdel ess... 18 Figure 2. Relative concentration comparisons of PFOS in breastmilk*, Thomsen, 20:10 and MDH TK model results............... :18 Figur3e. Relativeconcentration comparison of PFOAin breastmilk', Thomsen,2010and MOHTK model results. MN Figure 3. Relative concentration comparison of PFOA in breastmilk~, Thomsen, 2010 and MDH TK model results................ :18 Figur4e Infant POS sum concetatons predicted or axchiivly breasted nants byMOS movsd,esteimalted Figure 4. Infant PFOS serum concentrations predicted for exclusively breastfed infants by MDH's model vs. estimated nd taSN HO ure $5, FONE E81. 2010)... creer individual data points from Figure S5, Fromme et al. (20:10} ...................................................................................... 20 Figure 5. fan PFOA serum concentrations for exclusively breasted fas precicsedby MDWsod vs. ested Figure 5. Infant PFOA serum concentrations for exclusively breastfed infants predicted by MDH's model vs. estimated individu! dats pont from Figure S, Fromm et a. (2010), . 2 individual data points from Figure S6, Fromme et al. (2010) ...................................................................................... 21 igr6e. Relative Increase nnfant PROS serum concentration at 1 months of a normale 10concentraattritohn- Figure 6. Relative increase in infant PFOS serum concentration at :1:1 months of age normalized to concentration at birth - WOH mde resfo uexcllustivesly breastfedinfantvs, estima individual datapons om Figur 1 Mogenseent MDH model results for exclusively breastfed infant vs. estimated individual data points from Figure :1, Mogensen et py 2 al. (20[5) ...................................................................................................................................................................... 22 igre7. Relative ncrc3s nnfank ROR sur cancontaton 3 11 montofhas normal id concentratiaotn ih Figure 7. Relative increase in infant PFOA serum concentration at ~[ months of a~e normalized to concentration at birth WOH ade eslfoxcusivcly breastfed infant vs, esimate indus dca pnts om Figure 1 Mogenseent. MDH model results for exclusively breastfed infant vs. estimated individual data points from Figure [, Mo~ensen et a (2015). 2 al. (20~5) ........................................................................................................................................................................ i8r . Compae rison of MOH PROS model resusfor Lr excusvly breastfed fant (using upper percentile make rates) Figure 8. Comparison of MDH PFOS model results for 1-yr exclusively breastfed infant (using upper percentile intake rates) Verner model els. he vs. Verner model results.............................................................................................................................................. 24 Fire3.Comparson of MOM PFOA ode ress or 3. excuse breasted fan (oi app percent tak ats) Figure 9. Comparison o[ MDH PFOA model results for ~-yr exclusively breast[ed infant (usin~ upper percentile intake rates) AS vs. Verner model results .............................................................................................................................................. 25 Fire10. Cenario KLschema - ECVE Farm Fd Iam. . 26 Figure ~0. Scenario #[ schematic - Exclusively Formula-Fed Infant.......................................................................................... 26 Fre 11. Scenari#7o schem- Eaxtcuisce ressed fon. 7 Figure ~. Scenario #2 schematic - Exclusively Breastfed Infant............................................................................................... 27 Figure 12. Exposure Decsion Tre. 3 Figure 12. Exposure Decision Tree ............................................................................................................................................. 35 Figure 13. Exclusively formula ed fant PROS su concentarveart3iotinmse, bsed on 95 percent water into Figure ~3. Exclusively formula-fed infant PFOS serum concentrations over a lifetime, based on 95th percentile water intake ate, ASC of 50%, and a waterconcentrf0a0t60igo/nL rates, an RSC of 50%, and a water concentration of 0.060 og/L................................................................................. 38 Use of or reference to this model without proper tirbution to MOW s prohibited. Use of of reference to this model without proper ettribudon to MDH is prohibited. 33774499..00000033 3 STATE 07236248 STATE 07436248 Figure 14. Exclusively formula-fed infant PFOA serum concentrations avera etme, based on 95th percentile water intake Figure 14. Exclusively formula-fed infant PFOA serum concentrations over a lifetime, based on 95th percentile water intake rates, an RSCof 50and%awa,ter concentration of 0.15 ug/L BH) rates, an RSC of 50%, and a water concentration of 0.15 pg/L................................................................................... 39 Figure 15 Exclusively breastfed InfantPROSserum concentrations ver ftime, based on Upper/S5th percentile Figure 15. Exclusively breastfed infant PFOS serum concentrations over a lifetime, based on Upper/95th percentile reastmlk/ter intake rates, an RoSf50C%, 1 3WaterCONGENUiONOf 0.027 HEIL vv breastmilk/water intake rates~ an RSC of 50%, and a water concentration of 0.027 pg/L......................................... 40 Figure 16 Exclusively breastfed infant PFOAserumconcentorvaertaifoeinmes, based on Upper/5th percentile Figure 16. Exclusively breastfed infant PFOA serum concentrations over a lifetime, based on Upper/95th percentile breastmilk/wator intakerates nd an RSCof50%, and 3Water CONCONIation of 0038 WEL cee breastmilk/water intake rates and an RSC of 50%, and a water concentration of 0.035 pg/L................................... 41 List of Equations: List of Equations: Equatio1n. Standard equation forcalculatingnoncancer health based water guidance (HOG)... Ec uation 1. Standard equation for calculating noncancer health-based water guidance (nHBG) .............................................. 8 Equatio2n.Calculationof humanequivalent dose cOrTesponGIng 10a PEC serum CONCETatON.... ws Ec uation 2. Calculation of human equivalent dose corresponding to a specific serum concentration ...................................... 9 Equatio3n.Calculoaft5i0rounm CONCOntraton fom 4050 ANd IOAANEE FAT... 10 Ec uation 3. Calculation of serum concentration from dose and clearance rate ....................................................................... 10 Equation 4. Clculation of infantserumconcentration at Birth. - 2 Ec uation 4. Calculation of infant serum concentration at birth ................................................................................................ 12 Equatiosn. Calcuoflianftantisdoainl serum concentration 2 Ec uation 5. Calculation of infant's daily serum concentration .................................................................................................... Equation 6. Calculation of breastmilk concentration. 2 Ec uation 6. Calculation of breastmilk concentration ................................................................................................................ 12 Equatio7n.Calculofamattieronanl daily Serum CONENBNON. rrr 7 Ec uation 7. Calculation of maternal daily serum concentration ............................................................................................... 17 Use oof referenctoe this model without proper attribtuotMiOoHns prohibited. 33774499..00000044 a STATE 07436249 STATE 07436249 AAccrroonnyymmss aaBccIii--R- aabssrecciaittseetddmiiinlnk intake rate BWBIR BW ~- - body weight breastmilk intake body weight rate CCCDiDCC--c-oCnCefenintdteeernrssceffooirrntDDeirissveaelaassee CCoonnttrrooll CCCHRIRA-s--clcoelheneaafairdrlaaetnnhncccaeeedvrriaiansttteoeerriveasl IR ~intake rate HAs - health advisories IR - intake rate kkLO=-ArrEaaLttee~cclooonnwssettsaatnntotb((sLLennr22v/a/hhbaallelff--aliidffeev))erse effect evel LUO/kAgELl-itelorswepesrt okbilsoegrvraamblbeoaddyvewersieghetffect level U/kg-d L/k8 - L/kg-d - liters per kilogram body weight liters per kilogram body weight - liters per kilogram body weight ppeerr ddaayy mMMgDD/HHL~-- mMMiilinnlnnieegsrsaoomttsaa pDDeereppiaatrerttrmmeenntt ooff HHeeaalltthh mg/ke-d - milligram per kilogrambodyweight mg/L - milligrams per liter mg/kg-d - milligram per kilogram body weight ppeerr ddaayy mmMIggR--m-miimllleilgagrnraamimntake rate mmm MUiILR/g/dd-a:aymy--e-~ammmniillilinilltiteaekrlress rptppaeeetrerrekddiaalyyrogrsam body weight per day ng/mL- nanogram per milter mL/kg-d- milliliters per kilogram ng/mL- nanogram per milliliter body weight per day NNHHAANNEES-S- NNaattiioonnaallHHeaelatlthhaanndd NNuutrtriittiioonn EExxaammininaattiioonn SSuurrvveeyy HnNHOBBAGGEL----nnonononccoaabnnscceeerrrvahhbeelaaellttahhd--bvbaearssseeeddewwfafatetceetrrlggeuuvieidldaannccee vvaalluuee `NOOATA--ELor-gnaoniocbasneirovnabtlreanasdpvoerrtseereffect level OPPPBEBAPCPKT-p.K-e--orppfrhghlyayusnsoiiirooclolooacggnhiiieccomaanillllctyrya-a-blnbasasssp(eeaoddlrsptpoehhrraarermmfaaceocrkotikronineeaetdstiiccperfluoroalkyl substances or PFAS) PCAs -perfluorocarboxyletes PFC - perfiuorochemicals (also PFCAs - perfluorocarboxyletes referred to as perfluoroalkyl substances or PFAS) PPFFOOAA -- ppeerrfflluuoorrooooccttaannooiicc aacciidd PPPFFsOOSSA---pppeeerrrfffllluuuooorrroooosocuclttafanonneeastsueulslffoonnaattee: P= pharmacokinetic PFSAs - perfluorosulfonates PK - pharmacokinetic PPPOOWDDS --- pppouoibinlntitcoofwfaddteeeppararstrtyuursrete.em RID reference dose. PWS - public water system RfD - reference dose RRMMEE -~ rreeaassoonnaabbllee mmaaxxiimmuumm eexxppoossuurree. RRSSCC--harrleetllalatftiievvee ssoouurrccee ccoonnttrriibbuuttiioonn ffaaccttoorr tTK - htaoxlfi-cliofekinetic Wa/L-microgram TK - toxicokinetic t.tg/L- microgram ppeerr ilitteerr a(allssoo kknnoowwnn aass ppaarrttss ppeerr bbiillllioionn)) UPupggI--Rmm~iiccurrpoopggerrarampmercentile intake rate URAT - urate UPIR - upper URAT - urate anion transporter percentile intake rate anion transporter VUUaSS-EEvPPoAAl-uUUmnneiittoeefdddiSSstttaarttieebssutEEinnovnviirroonnmmeennttaall PPrrootteeccttiioonn AAggeennccyy. VVsd A-Fvo-luvmoleumoef doifstdriibsturtiiobuntion adjustment factor W-IwaRter intake rate: Vd AF - volume of distribution WIR - water intake rate adjustment factor Use oof reference to this model without proper attribution to MOH s prohibited. 33774499..00000055 5 STSTAATTEE 0077443366225500 EExxeeccuuttiivvee SSuummmmaarryy The Minnesota Department of Health (MDH) evaluates human health iss from exposure to contaminants in The Minnesota Department of Health (MDH) evaluates human health risks from exposure to contaminants in inking water. In May of 2016, the US Environmental Protection Agency (USEPA) ssued fetime health drinking water. In May of 2016, the US Environmental Protection Agency (USEPA) issued lifetime health `aaddvviissoorriieess ((HHAAss)) ooff 00..0077 upgg//LL ffoorr ppeerrfflluuoorrooooccttaannooiicc aacciidd ((PPFFOOAA)) aanndd ppeerrfflluuocrrooooccttaannee ssuullffoonnaattee ((PPFFOOSS).). AAss aa result, MDH initiated a review of the bass of the USEPA Has anda reassessment of MDH's own healthbased result, MDH initiated a review of the basis of the USEPA HAs and a reassessment of MDH's own health-based guidance values or these two chemicals, which were derived in 2007 guidance values for these two chemicals, which were derived in 2007. and PFOA have unique characteristics that are not adequately addressed when using tis traditional approach. TTrraaddititiioonnaallllyy,, nnoonnccaanncceerr hheeaalltthh--bbaasseedd wwaatteerr gguuiiddaannccee ((nnHHBBGG)) aarree ddeerriivveedd bbyy mmulutltiippllyyiinngg aa rreeffeerreennccee ddoossee ((RRFfDD,, mmgg//kkgg--dd)) bbyy aa rreellaattiivvee ssoouurrccee ccoonnttrriibbuuttiioonn ffaaccttoorr ((RRSSCC)),, ddiivviiddeedd bbyy aa wwaatteerr iinnttaakkee rraattee ((LL//kkgg--dd).). HHoowweevveerr,, PPFFOOSS and PFOA have unique characteristics that are not adequately addressed when using this traditional approach. PFOR and PFOS bioaccumulate in serum, cross the placenta, an are excreted nto breastmilk. Research has shsPihhFgooOhwwAenrnattnthhhdaaatnPt FbbmOrareStaeebsraitnomasalictlkccmcuocnamaicnneulbnlbaketerteaaatiimmnoanasjsejoo.rrruAmssloo,tuuhcrrroccoueesgsoohfftheeexexxppppoooslsasuucurrereeens,,tardr,eeusrsauiunlndlttgiinaniggrnefiinanenxiicnncyffraeaanntrettedsssehiunroutrommt-btccreoeornanmcsc,etenmtnthiitrlrksaa.tptiiaRoroentnsissceuttahlhracaarhtt faahreraeesstage shiogfhpearrtthicaunlamr acteornncael ncobnecceanutsreati(o1)nsP.FAOSlthaonudghPFeOxApoasruerdeesvdeulroinpmgeinntfaanlctyoxairceansthso;r(t-2t)eirmnf,antthsiscpoanrsticuumlaer much life-stage is of particular concern because (1) PFOS and PFOA are developmental toxicants; (2) infants consume a much alfivsof POS and PFO, ggrreeaatteerr vvoolluummee ooff lliiqquuiidd ppeerr thuunniittsbbhoooddryyt-wwteeeiriggmhhettxttphhoaasnnurooelldsdeetrrhaccthhiiolldcdrcreuenrn uring infancy can aanndd aadduullttss;; aanndd ((33)) rddeuuseeuttlooitntthhbeeodlloyonngbgueerlldiimemniinsnaattthiioaotnn take years to eliminate. half-lives of PFOS and PFOA, take years to eliminate. the short-term exposures that occur during infancy can result in body burdens that IInn ddeerriivviinngg hheeaalltthh--bbaasseedd gguuiiddaannccee,, MMDDHH uusseess aa rreeaassoonnaabbllee mmaaxxiimmuumm eexxppoossuurree ((RRMMEE)) aapppprrooaacchh.. AAnn RRMMEE Scenario depicts a realtc but maximum exposure situation e.g, 95 percentile wate intake rate) to ensure scenario depicts a realistic but maximum exposure situation (e.g., 95th percentile water intake rate) to ensure that even the most heavily exposed individuals within the populatiioln be protected. MOH used this RME that even the most heavily exposed individuals within the population will be protected. MDH used this RME approach nthe context ofa novel kinetic model to develop updatedwaterguidance values fo PFOS and PFOA. approach in the context of a novel kinetic model to develop updated water guidance values for PFOS and PFOA. In order to ensure that MOH' revised healthbased water guidance values were adequately protective of iInnfoanrtdse,r2tooneen.scuoremptahrattmMeDntH'tsoxreicvoiskeindethieca(lt1hK-)bamsoeddelwwatserdgeuviedlaonpceedvtaolupersewdiecresearduemqucaotnecleynptrroatteicotnisveofoPf FOS iaainnnnffddaannPPttsFFe,OOxacAAlouffrnsroieomv-meclobbyimirrfttephhdattrwhthimrrtooehuungfgthohtroaamxtutittlcaaaoiinkrnmiemnceeeonntnittcstoo(ifTftKssu)ttteeemaadddowyydi--estslthtaawcttaeeosncctdooanenmdvdiieitntliioaootpnneessd.d. TTwtoawwtooperrRReMMdstiEcaEtrsstsccieenergnnuaaamrtriioobcssiorwwnthece,errfeenotlerealvvotaaiwloleuundaasttbeeoddfy:a:P11F))OaaSnn bHilnifyefaftinmfteeeetoxtoifcfmdluirdesirioinvnmfkekildiyennrggifencdckioownnngtittaachmmoifnionntraaamtmteeiuddnlaawwtraaeetdtceerowr;n;atsaaetnnritdd.ut22eI))ndabbworbtierthehaasscstcoteffnneeatddraimiionnsiffn,aaannttttheeeedxxscwcillmuausustielivvareetlsleyytdabbrirtrnieendaagissvtiatffdteeudbadlirffstoohrbr,e11fgo22allmnmoowofnnteethdhwss,bi,ytffooahlllolrwoewe.edd existingbody burden through placentaltransfer by a lifetime of drinking contaminated water. In existing body burden through placental transfer foma mother at seadystae conditions both scenarios, the simulated individuals began from a mother at steady-state conditions. life with a pre- WOH conducted an expeadnidftoceusded re-evaluation ofthe available toxicological information, relying in M DH conducted an expedited and focused re-evaluation of the available toxicological information, relying in port on USEPA's 2016 health assessment documents (USEPA, 20163) (USEPA, 2016). Reference doses (RDS) of part on USEPA's 2016 health assessment documents ((USEPA, 2016a) (USEPA, 2016c)). Reference doses (RfDs) of 00..00000000005511 aanndd 00..0000000011g8 mmgg/ikkgg--dd wweerree ddeerriivveedd ffoorr PPFFOOSS aanndd PPFFOOAA,, rreessppeectcitviveelyly.. TThhee ccoorrrreessppoonnddiinngg sseerruumm concentrationsare 0.063 an0d.13 mg/L for FOS and PFOA, respectively. concentrations are 0.063 and 0.13 mg/L for PFOS and PFOA, respectively. Serum concentations are thebs measure of internal dose for PFOS and PFOA, and are therefore considered tttSohoeabrbtueemtotththcaeeol nmmecoxoespsnottstraauapprtpieporrnofopsrproraimiaraettaeelthbbsesaosiubirssecseffotso,rrmddieenearcrsilivvuuiirdneniggnogaafpnniontRRteeIfDnDrtnittahahllaatdtiofisssnepprgrfooottreeecPcostFtfiiOvdvtSereiiaoonfnfkodippnoonPtgteFenOwntaAtiit,aaelalrnhhdeceaoaalnlrtttehhaiteehnffieffenercgcettsfPso.F.rOeIIttScisooriinmmsPpipFdooOerrArtte,aadnntt ottdhooeauesctsotonlnootoaittlcrraeeelxsslupuylolttsriieunnlreessveefarrrnuoutmmmpeccaroolilnnosccdoeenuontrfctrremaastet,iio.oinnnscsTlhutthedhaianetxgeepxxpoccoseeuteeerddnetttichahoelenitsnsreegirrebuusumtmtioeccdnoornoncofceedmnnrtirtnnraokatnitnii-oogwnnawtaaaessrtsseoosrccoiciuaaorttnecedetdasiwwnwiiitntahhgsttaPhhdFeedOrRRSefDDsosrffeoPodrFOaa A, ttttohhhixrrsoiocucuoagglsohheg,ttihchteaehlelaayspprepeprlilceuiamviaticoanonttnpocoifeefnnraaitorRdRaeetloilaafotttiniivmvaeeseSSs.oooTucuhirreaccteeeeCdCxopownointstrturhiirbbetuuhtcteiioooRnnnDtr(()iRbSSutCCot)e)wdffaaatcfcrettooorrmr,e,xwwnphoohisnicuc-rhhwesaaa.ltleolrMcasDloteHusrocuaaesfsfcerrdaawccattatihsiooetnanUdooSedffErtetPshhsAseeeE&Rdx1fDoDs((uoorrreiinn tDDaheseicstciiscsMaiioeosntne,eTTotrrheereeeessppierrdrooeuccnmetesss,sscoN((nUeUlcSSseEEonPPntAAra2220ti001o006n00)))abslaisloooomnncogginaiwtwetiidotthrhwirrnieteghcceeetnhsnteut lnnRasatftDiitoo)onntaioaldlew((n2ta2i00tfe11yr33a--e2n2x00pR11oS44sCuNNarHeHpAspA.NoNEMrEtSDSi,,HoCCnuDDmseCCen2d2t001to1h7f7e)5)0Uaa%SnnEddfPollAoroccEPaalFxl pO((onSnseeauwwnred PFOA. East Metro residents, Nelson 2016) biomonitoring results to identify an RSC apportionment of 50% for PFOS and PFOA. Use of or reference to this model without proper tirbution to MOW s prohibited. 33774499..00000066 5 STATE o7asezst STATE 07436251 T"PThFheeOATTKKormmoPodFdeOelSl ddceeovnvceeellonoptpreeaddtibboyynMMinDDdHHrippnrrkeeiddniigccttwssatddeaarii.llyySssieenrcrueummthcceooennxccceernnetttrriaaottniioovnnissa oobvrveeearrasatmlliiiflefkettimwiameesoosffigeenxxipfpioocssaunutrr,eettthooeaaccacolocnnusslttaaatnnitotn oPfFdOaAiloyrmPatFOerSnaclosnecernutmrcaotinocnenintrdartinikoinnsg iwnactoerrp.oSraintceedtIhoessoexfccrheetimoincavila vbiraetarsatnmsfilekrwoasthe infantaswell as significant, the calculation excretion represented by the clearance of daily maternal serum concentrations excretion represented by the clearance rate. The infant's incorporated loss rate. The infant's daily intake of chemical daily intake (and thus the mother's loss) via transfer to the infant as (and thus the mother's loss) was well was accsaallccuullaatteedd from the breastmilk intake rate and the breastmilk concentration. from the breastmilk intake rate and the breastmilk concentration. AdAasstppaaarfrttrooofmf ttphhueeblmmiosodhdeeedll sddteeuvdveieellsoo,ppmmaeenwntet,l,lpparreeddpiiuccbttleeiddshsseeedrruutmomxicccooonnkcicenenentttrircaattmiiooodnnesslsffr.roomImn ttahhdedeimmtiooodnde,ellMwwDeeHrreesocclooimmcipptaeadrreeiddnpttuoot eefmmrpoipmririiscciaaxll external peer reviewers for advonihocw teo improve the model predictions. data from published studies, as well as published toxicokinetic models. In addition, external peer reviewers for advice on how to improve the model predictions. MDH solicited input from six cMMoDDncHHenddteerrraiivtveieoddnsRRIfcDDossrroofefs00p..o00n00d00i00n00g55t11oaatnnhdde 00R..I000D000(00011.8806mm3gga//nkkdg--0dd.1ffo3orrmPPgFF/OOLSSfoaarnnddPFPPOFFSOOAaA,n, drreePssFppeOecAct,tiivvreeellsyyp..ecBBtaaissveeelddy'oo)nnatthnhede assneerrRuuSmmC of 50% the MDH TK model results indicate that water concentrations concentrations corresponding to the RfDs (0.063 and 0.13 mg/L for 50%, the MDH TK model results indicate that water concentrations of 0.060 and 0.15 ug/L, respectively, are PFOS and PFOA, respectively1) and an RSC of 0.060 and 0.15 pg/L, respectively, are of `pparrnoodtteePccFttOiivAve,e ffcoohrrrotthnhieeceeexxxcclpluuosssiiuvvreeellyytffooormrmomutulhlaae--rffseeddaniindnffasannutbt sssecceqenunaearnriitoo..trHHaoonwswefeevrveertr,h,rddouuueeghttoobrttheheaesbbtimiooiaalcckccruuemmsuuulhaltatetidivvieen nnhaiatgtuuhrereer ooff PPFFOOSS exposures and PFOA, exposures to breastfed infants. chronic exposure to to breastfed infants. Consequently, the model mothers and subsequent Consequently, the model results indicate that lower health-based water transfer through breastmilk resulted in higher results indicate that lower health-based water ccoonncceennttrraattiioonnssooff 00..002277 aanndd 00..003355upgg//LL ffoorrPPFFOOSSaanndd PPFFOOAA,, rreessppeeccttiivveellyy,, aarree nneecceessssaarryy ttoo bbee pprrootteeccttiivvee ffoorr tthhee beexaxcsclleuudssiivvvaeelllyyuebbsrrefeoaarssttPffFeeOddSiiannnffaadnnttPssFccOeenAnaarwrieioor,.eTTsooeteennasstuurree0.0pp2rr7ooattneedcctt0iio.onn03oo5ff aallll sseeggmmeennttss ooff tthhee g/L, respectively. ppooppuulalattiioonn,, tthhee ffiinnaall hheeaalltthh-- based values for PFOS and PFOA were set at 0.027 and 0.035 pg/L, respectively. BRBrrMeeEaasssttcfeefneeaderidniioginwigssaisimmuppsooerrdttaainnnttgffeonrrertthaheteissnhhgoortrthteaannheddalllootnnhgg-btteaesrrmemd hhveaelaaulelttshh. oofBfybbdooettshihaganm m,oaotnthheRerMr Eaannsddceiinnnffaaarnnitto.. dAAesspisscttatastteeadrdeaaalbbioosvvteeicaabnnut maximum exposure situation to ensure that even the most heavily exposed individuals within the population RME scenario was used in generating the health-based values. By design, an RME scenario depicts a realistic but maximum exposure situation to ensure that even the most heavily exposed individuals within the population wwiillllbbee pprrootteecctteedd.. TThhee mmaajojorriittyy ooff tthhee ppooppuullaattiioonn wwoouulldd eexxppeerriieennccee lloowweerr eexxppoossuurree.. MMDDHH rreeccoommmmeennddss tthhaatt `bwrwoeomamseetnnfecceuudrirrrneegnntitlslyyrbberrceeoaamsstmtffeeeneedddiienndggb,,yaanndddocpptrroeerggsnnaaannntdt wwotoohmmeerennhewwahlhtoohpppllraaonnfettsoosibborrneeaaalsssttffeIeteedds,,uccnoolninktteiinlnyuueethttaoot ddpoootsesono.t. iEEaxxlcclhluuessaiilvvteeh cborencaesrtfnesedexincgeeisdrtehceokmnmoewnndebednbeyfidtoocftobrrseaasntdfeoetdhiengr.heAappltlhicpartoifoenssoifontahels.inIat lishuenallikteh-lybathseadt vpaoltueenstiawilllheulatltihmately result in lower body concerns exceed the result in lower body burdens and breastmilk concentrationsof PFOS and known benefits of breastfeeding. Application of the burdens and breastmilk concentrations of PFOS and PFOA so that infants can receive the final health-based values will ultimately PFOA so that infants can receive the ooppttiimmaall bbeenneefifittss ffrroomm bbrreeaassttffeeeeddiinngg.. Serum concentration corresponding to the ID is usefl for informing pubic hlth policy and interpreting population: 1bbinaaStsseeeerrddupmreeexxtcppioonosngsucursereeesnrs.tu.ramTTthhieoiissvnevvcalolaurireneilsiissnpbdobuiaanvssideeedinuddagloostnno population-basedparametersand should not be usedfo clinica assessment or the RfD is useful for informin8 public health policy and interpreting population- population-based parameters and should not be used for clinical assessment or for for interpretin8 serum levels in individuals. Use oof reference to this model without proper attribution to MOH s prohibited. 7 33774499..00000077 STSTAATTEE 0077443366225522 11..00 GGeenneerraall AApppprrooaacchh aanndd CChhaalllleennggeess ffoorr EEssttiimmaattiinngg W Waatteerr GGuuiiddaannccee VVaalluueess Pertuorooctanic cd (PFOA) and prfcrooctae slants (PFS) are boacumlatv chris ht hve Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are bioaccumulative chemicals that have Tatentaa secmte iin fx boty over eas riot Year. ree Part spo the potential to accumulate within the body over the years prior to pregnancy, cross the placenta, and partition ioral, reform andreaconcentanons wil be AVR hth ance aions into breastmilk. Therefore, serum and breastmilk concentrations will be higher than the concentrations in nironmental mei o.6. conamated water) 0 wha worn x50sd In addon tein born with an environmental media (e.g., contaminated water) to which a woman is exposed. In addition to being born with an oceing boa ure om pacer rao bas an art scl, ars my EPATTGH existing body burden from placental transfer based on maternal accumulation, infants may also experience `ssuubbsseeqquueenntt hhiigghheerr eexxppoossuurreess,, eessppeecciaiallllyy ffrroomm bbrreeaassttffeeeeddiinngg ((SSeeee FFiigguurree 1:1 bbeellooww).). aur.Motel vaneT rtoaeEur ebceeeansttoTentensr, [(THIRCRIEESS Concentration Placental Transfer Breastfeeding Sil LD T`Thhee MMDDHH ssttaannddaarrdd wwaatteerr gguuiiddaannccee mmeetthhooddoollooggyy,, bbaasseedd oonn lliifefe-s-stataggee ssppeeccififiicc ddrriinnkkiinngg wwaatteerr iinnttaakkee rraatteess,, ddooeess. torporate by nea deth or heconcemation of ernment chica bres. Ts not incorporate body-burden at birth nor the concentration of environmental chemicals in breastmilk. This acumen, hrsor, kscibs a Fameworkdevoped oY MDW tht earortes haaspec ropes document, therefore, describes a framework developed by MDH that incorporates chemical-specific properties pros and POA a ders danty protec water Bon vas of PFQS and PFOA to derive sufficiently protective water guidance values. Ayia noncaces eatbased water dance aus (HBG) luted by combining a seference dose A typical noncancer health-based water guidance value (nHBG) is calculated by combining a reference dose ((RRfDD)) wwiitthh aa wwaatteerr iinnttaakkee rraattee ((IIRR)) aanndd rreellaattiivvee ssoouurrccee ccoonnttrriibbuuttiioonn ffaaccttoorr ((RRSSCC)),, ssuummmmaarriizzeeddbbyytthhee ffoolllolowwiinngg Cavan (MD, 30081 equation (MDH, 2008): vation 1. Standard auton or calcating rancance es base wate cine (PKG), Equ~don 1o Standard equation for calculatin/.~ noncancer health-based water guidance (nHBG). HBG u(4p0) =W eeDaw e 2) (jodie) [ro X RS Cro ) a xX 1100002452. MOH HBG present concent nent chemical i criking water ht ct with MDH HBGs represent a concentration of an environmental chemical in drinking water that is associated with hhEle hr ea. andar US Ernmntl tection Gey (SEPA) and MD IBC 10 negligible human health risk. It is standard US Environmental Protection Agency (USEPA} and MDH practice to inortate upper mixpos wl cde 0 er. an adete ari of ley o st of he posed incorporate upper-end exposure levels in order to ensure an adequate margin of safety for most of the exposed ota (UXE93 3008 (MH, 3008, MON hdl fo ran het bse wort Bunce uss population ((USEPA, 2004), (MDH, 2008)). MDH's methodology for deriving health-based water guidance uses iinnttaakkeerraatteesstthhaatt aapppprrooxxiimmaattee tthhee 9955tTMh ppeerrcceenntitillee ((MMDDHH,, 22000088)) ttoo eennssuurree iinncclluussiioonn ooff mmoosstt ooff tthhee ppooppuullaattiioonn aanndd rtectancl ms who Comat 2 a aera es wate om lh sort, oth sare protection of individuals who consume a large percentage of their water from a single source, such as a private elo omitwateSoph MW oh, sad on dra ala 1 des wore doce ts well or community water supply. MDH's goal, based on data availability, is to derive water guidance that is rote of shorter 5 wel hos drains, Constnt wih in atupped Paha +n pS protective of short-term as well as chronic durations. Consistent with using data-supported higher-end exposure Tove, WE canto av bet deerind and sed Os TK levels, RME scenarios have been determined and used in MDH's TK modeling. tert forboccumultve contaminants ce often based ong arr exposures an yal conide he Criteria for bioaccumulative contaminants are often based on long-term exposures and typically consider the Tekin ssa ot humour on then lace bee dat ke nd shin, In resulting steady-state serum levels that arise from the net balance between daily intake and elimination. In 5516, OSE dered oof O.0003 milk. or 14am PFOA. rh hi eo Adsors (1A) of 2016, USEPA derived RfDs of 0.00002 mg/kg-d for PFOS and PFOA. In deriving their Health Advisories (HAs) of 00..0077 gla/gL/L,, UUSSEEPPAA cchhoossee ttoo uussee tthhee 9900th ppeerrcceenntitillee wwaatteerr iinnttaakkee rraattee ffoorr llaaccttaattiinngg wwoommeenn ((00..005544 LLj/kkgg--dd).). UUssiinngg `ththiiss iinnttaakkee rraattee aalloonngg wwiitthh aann RRSSCC ooff 00..22 iinn EEqquuaattiioonn 11 rreessuullttss iinn UUSSEEPPAA''ss lliifefetitmimee hheeaalltthh aaddvivsoirysoofof00r..00y77 upgg/L/L. Us ofr eeence to this model without proper atlutio to MON prohibit. . Use ofof reference to this model ~vithout proper ottributio# to MDH is prohibited, 33774499..00000088 SSTTAATTEE_0077443366225533 For comparison, {MOM ypicl hronicnake ate (95 percent fete take, 0.004 Kg.) sd 0 For comparison, if MDH's typical chronic intake rate (95tl~ percentile lifetime intake, 0.044 L/kg-d) is used to Cllae 3 wate alo bse on USEPA RID and RC, he resin Water conceniaion wu be 0.09 iL. calculate a water value based on USEPA's RfD and RSC, the resulting water concentration would be 0.09 lag/L. MOH determined tht the radon arcs or desing vate ikdance was ro dante10 aves the M DH determined that the traditional approach for deriving water guidance was not adequate to address the bioacurBte nature of PES and PFOA, paca rane, rsamilk ane, nd hc Me iske bioaccumulative nature of PFOS and PFOA, placental transfer, breast-milk transfer, and high early-life intake rates, To conan fer ie pus and Kinetics rthr ror by th development bas of rates. The consideration of early-life exposure and kinetics is further reinforced by the developmental basis of 06 10 for both F705 and FOR. Th te trex esd tate contin yicaly ccuvlnt to the RfDs for both PFOS and PFOA. The time to reach steady-state conditions is typically equivalent to oprosimatay fu hall es Hower, his gor pnt s bse n constant expose. Grn the approximately five half-lives. However, this general principle is based on constant exposure. Given the Scant ighr nak aes sry He, sy ha ir ele We tencysar ves ar rezchec significantly higher intake rates early in life, it is likely that long-term late life steady-state levels are reached ffaasstteerr,, aanndd eexxcceeeeddaanncceess ((ppeeaakk lleevveellss)) ooff sstteeaaddyy--ssttaattee lleevveellss mmaayy ooccccuurr,, eessppeecciaiallllyy ccoonnssiiddeerriinngg tthhee bbooddyy bbuurrddeenn rans fom mother o offspring. Useofan fant ake ate 0.285 Ug.) and a SC of 0.2 ance transferred from mother to offspring. Use of an infant intake rate (0.285 L/kg-d) and an RSC of 0.2 (since Wraraiocenta and canal posure occur would esl elcuBted water concentrationf D014 g/L transplacental and lactational exposure occur) would result in a calculated water concentration of 0.014 i,tgiL. However, i Shortt nant tak at Based onan exposure curation of oly wo month docs nok ake However, this short-term infant intake rate is based on an exposure duration of only two months, does not take iinnttoo aaccccoouunntt tthhee ddiifffefererenncceess bbeettwweeeenn PPFFOOSS aanndd PPFFOOAA ttooxxiiccookkiinneetticisc ((TTKK)) nnoorr tthhee bbooddyy bbuurrddeenn aatt bbiirrtthh,, aanndd ccoouulldd encom with h dose mic sd Gere te ID. be inconsistent with the dose metric used to derive the RfDs. FFlluuiidd iinnttaakkee rraatteess iinn iinnffaannttss aarree 77--1100 ffoolldd hhiigghheerr ppeerr uunniitt bbooddyy wweeiigghhtt tthhaann iinn oollddeerr cchhiillddrreenn aanndd aadduullttss ((UUSSEEPPAA,, S011) Give th lng lf es of PEOS and On ths gh, hotter exposures can esl n prolonged 2011). Given the long half-lives of PFOS and PFOA, these high, short-term exposures can result in prolonged levations of ternal bo burden ovr sever 5, ncluding tical tresof Gesclopent Formula fend elevations of internal body burden over several years, including critical times of development. Formula-fed and uring nantsconsume restr volume of id on pr body weight bas than ld children and als. nursing infants consume a greater volume of liquid on a per body weight basis than older children and adults. T`Thhee aavvaaiillaabbllee lliiteterraattuurree ((ee..gg..,, ((FFrroommmmee,, 22001100)),, ((HHaauugg,, 22001111)),, ((MMoonnddaall,, 22001144]),, ((MMooggeennsseenn,, 22001155))) rreeppoorrttss hhiigghheerr PS ad POA serum ulin beastie fant han maternal ser, rin dre evince ofher PFOS and PFOA serum levels in breastfed infants than in maternal serum, providing direct evidence of higher expoinnbrreaestsed infants comparetdo mathers. A phyclgialy-brsd pharmacokinetic (67) model exposures in breastfed infants compared to mothers. A physiologically-based pharmacokinetic (PBPK) model conftihe irmpmorteandce of bestia n important exposure pata or PFOS snd PROA nnn confirmed the importance of breastmilk as an important exposure pathway for PFOS and PFOA in infants {Lotasano, 201). Th mol sshd ht lng0account orbot out of exposre rest) an (Loccasano, 2013). This model also showed that failing to account for both route of exposure (breastmilk) and iinnccrreeaasseedd fflluuiidd iinnttaakkee rraatteess wwoouulldd rreessuulltt iinn aann uunnddeerreessttiimmaattiioonn ooff sseerruumm ccoonncceennttrraattiioonnss tthhrroouugghhoouutt mmuucchh ooff coy A ler ohrnacoknetc PK] dl was developed Vern and collages (Verner, 2010), whi early life. A simpler pharmacokinetic (PK) model was developed by Verner and colleagues (Verner, 2016), which in documented resi sa Scant exposure athay. oth model re code using cs,a modeing again documented breastmilk as a significant exposure pathway. Both models are coded using acslX, a modeling rogram whi anger valorslporee (as cincom). In rer 0 adres cones oArng program which is no longer available or supported (~). In order to address concerns regarding Paher, earl fe exposures, WOH crete ame ane. <cmpartrt stcointc (1) model n Microsoft ice higher, early life exposures, MDH created a simple one-compartment toxicokinetic (TK) model in Microsoft Excel 2003 vate te mprtance of gh ary He exponen formule ana breasted ants 2013 to evaluate the importance of high early life exposures in formula-fed and breastfed infants. 05 and POA are well aor nto the body andre not metabolize. Therefore, the mount th by3 PFOS and PFOA are well absorbed into the body and are not metabolized. Therefore, the amount in the body is a function how muh Goes nthoe ba cos) and how uk h cerca ar lima clearer function of how much goes into the body (dose) and how quickly the chemicals are eliminated (cleared) from `ththee bbooddyy.. MMDDHH aaggrreeeess wwiitthh UUSSEEPPAA aanndd ootthheerrss tthhaatt sseerruumm ccoonncceennttrraattiioonn iiss tthhee bbeesstt ddoossee mmeetrtriicc ffoorr ddoossee-- Tespone expo, and ik characterizoaftPiRoOnS nd ROR response, exposure, and risk characterization of PFOS and PFOA. IInn ddeerriivviinngg tthhee RRffDDss ffoorr PPFFOOSS aanndd PPFFOOAA,, tthhee UUSSEEPPAA (((UUSSEEPPAA,, 22001166aa)),, ((UUSSEEPPAA,, 22001166dd)))) uusseedd tthhee ffoolllloowwiinngg. ean calcd he Pua Squkalent doses ht wold correspond th er concerns Fon relationship to calculate the human equivalent doses that would correspond to the serum concentrations from ml tis animal studies. uation 2. Cacao of han equalen dose correspaning 3 speci ser concentration Equal:ion 2. Calculation of human equivalent dose corresponding to a specific serum concentratiom se (mn8y ) = serum concentration (-22) x larance Rae (5. ) WTietnhchco,ntSinuoius xaaptosorneitooniso,acsuumiulnagtivCcohneamnitcaplosenruem caotnc,enrteraaticones nsswheenhet3essdofsstoartpetsion With continuous exposure to bioaccumulative chemicals, serum concentrations increase until steady-state is reached. Steady-state conditions, assuming a constant exposure rate, are achieved when the rates of absorption Use for reference to this mde without rape tribution to MOH pried s 33774499..00000099 SSTTAATTEE0077443366225544 faaenn,dd weelhliimemriinenaaittniiotonankfefrroramamtettsh,heebobbdooyddyyweaarireeghee,qquuvalao.ll. uHHmooewweoevfvederir,s,taariccboountnissottnaa,nntatneedxxppeooxsspuuorrseeurareatteemaddtooreeess (nndoorttirrkeeiffnllegeccwttarreteaaelliittuyyseddudurriiinnngg eeaarrllyy wffliofaoertm,rewurmhlagaeurooierrdbibnarrteneaaackisseesttffrdeeaieeftdediiscinna,gglb)t)oradoreyejawuaslletliingifnyhccwt,oohnvnesosntltuaatmnnhtteeffllomuuoxfx..sdtTTishhsteereinbaasudidttooiioppvtnteii,ooaannnndoodffheiaaxgddhpuulloyltst euccxrhheprrooomnsniaeiccdtsrsitixtneed(aadiddvryiiynd-sksutiatanaltgsteeawkkeaiintneetehrttieciuscvseeffrodoyrrinyddeoeruriinvviginngg. ToTwhhaieetredreerffoigornureetid,,haeMMndDcDeeHHriisvddaeedtvviifceoflinlcoouoppfleetwcdtaottajeouornsngeteuif-iyccdoowammnhpcepaenarrtttthmmheeaentmntstoTTpsKktrsmmoeotonddseeeitlcilvtoiiennifccavoonarerldpplooshrriagaethtiiglnynggmettxehhpoeeonfsmmteoodhsssitngrrdeeeinlvlieiiadarbbualllaeelpsssoccapieuerelnnacctteheieoaannnv.dderccyooynnoccueenppgttss. to aid in the derivation of water guidance that is protective of all segments of the general population. 22..00 SSiimmppllee OOnnee-CCoommppaarrttmmeenntt TTKK MMooddeell tSSheearrtuumrmesccuoolntncsceennntatrraastteiioronunsms aacroeenctthehneetbrbaeetssitommneaeaassuourrreebeoolffoeewxxpptohoessuusrreeeraaunnmddcbboaanssciiessnfftoorrrataainnon8R1faDDs,.sTTohcheieraretefefodorriee,t, hawwtahtaeterRrIgDg,uuieiddvaaennncceewhvveaalnluuee rataheccaaccrtooruraeunnsntguinteltgdisonftionorgrcattahhsleeecurcculoaomntntetcrrsioibebnuurcttueiiomnonntcraooofntficnoneononmtnar-wtwaaotatirteoebnrrebleeoaxxwsppeootsdhsuueorrneesssed,,rouwwsmoeouucallondddnbbceceelnehhtaeerraaalatltnitohhcneppraroosttseeocctctiiiavvetee..dEEwqquiutahattitiohonne 2 above, RfD, even 2, above, can be when can be rearranged to calculate serum concentration based on dose and clearance. Equation 3. Calculation of serum concentratfiromn dose and cearance ate. Equat:iorl 3o Calculation of serum concenbadon from dose and clearance rate. mg Pp -- may rPe ig)) m9 Dose(~) -- Ser~tm Concentration (~-) = L Clearance wher Where: forwate ingestion for water ingestion - ose) ter te hte) water concentration) my _ Ly, mg Dose ~ = Water Intake Rate ~ x Water Concentration bose (1= e0ss)e tae ete 5) esi cocenration (2) Jotrecsmi- .for breestmilk - my _ Ly L )k9m.d9ay ( anaand Va =Vatameof bistro (12) erance Rae (gLL) = tux = Voo tameofnDistrivuion (1 Clearance Rate \k9 . day/ = Vd x k Vd=VoIumeofDistribution(~-~) In(2) k= `hhaalifl =-lIiif[ee ((dd)) in (1 T`Thhee v voluo meol offdidu sistrtrim ibbuutte iioonn ((VVdd)),, 00..2233 aannd0d0..1177 LL//kkgg ffoorr PPFFOOSS aanndd PPFFOOAA,, rreessppeecctitivveellyy,, hhaassbbeeeenncchharaaracctteerriizzeedd bbyy Several researchers (see Section 2.5.3 in (USEPA, 2016) and Section 2.63 in (USEPA, 2016a). 8combining several researchers (see Section 2.5.3 in (USEPA, 2016c) and Section 2.6.3 in (USEPA, 2016a)). By combining these Vd estimates with the hal fe of PFOS (5.4 years) and PFOA (2.3 years), USEPA (US EPA 20153, ) these Vd estimates with the half-life of PFOS (5.4 years) and PFOA (2.3 years), USEPA (US EPA 2016a, c) cleuated the following clearance rates: calculated the following clearance rates: Say xaest pPFrOosS: Te anol gd 00.2233~kLaaxx 2 -- 0.6% 93 = g0o,0000000e8r1 L k L g 5.4yr x 365 d__ g'd yr seofor reference to this model without proper ttibuton toMOH isproibited. Use of or reference to this model without proper ettribution to MDH is prohibited, 33774499..00001100 10 10 SSTTAATTE E_0077443366225555 pros 01L7oxe295 goon tLr PFOA: Baran kod L 0.693 L 0.17~99x 2.3 yr x 365 d -- = 0'00014koo d yr When afetime mean wate intake ate of 0.016 gd (USEPA, 2011) is applied to a water concentration of 1 When a lifetime mean water intake rate of 0.016 L/kg-d (USEPA, 2011) is applied to a water concentration of 1 mmgg//LL ((aarrbbiittrraarriillyy sseett ffoorr ccoommppaarriissoonn ppuurrppoosseess)),, tthhee rreessuullttiinngg sstteeaaddyy--ssttaattee sseerruumm ttoo wwaatteerr ccoonncceennttrraattiioonn rraattiiooss. re 198:1 3nd 14:1 for PROS and PFOA, respectively: are 198:1 and 114:1 for PFOS and PFOA, respectively: pros: 198 7rag serum Concentrationo ) = 00.00e 1166g(g~ ) LLa)gy)x x11m1 J~L~rG-(aWttaoetrerCCCooonncceeenntntrraate~ioonnn)) PFOS: 198 -~- (Seru,n Concentratgon) = 000000 (gor rL ) roPFOA: 18114 2r: m irag T (Serura nara Concentration) re = 0016 LyEgas) 0E0x101)0321W8at7te2rr)CConocerntreatnio)n) Ta) IInnccrreeaassiinngg tthhee lliifefetitmimee wwaatteerr iinnttaakkee rraattee ttoo tthhee 9955t"h ppeerrcceenntitillee rraattee ooff 00..004444 LL//kkgg--dd ((UUSSEEPPAA,, 22001111)) rreessuullttss iinn aa Steady tat serum to water concentration ato of 543: and 314: for ROS and PFOA, respectively, due othe steady-state serum to water concentration ratio of 543:1 and 314:1 for PFOS and PFOA, respectively, due to the increased daily exposure and absorbed dose: increased daily exposure and absorbed dose: 0s. 50 2 cramnenratn oe EE) BE trCoren) . 0044 (LLr)ym1BeEGater Concentration) 0.044(~) x 1-~-(WaeerConcentration) PFOS: 543 T (Serura Concentration) = asnoont (gLs) 000s (52) i 0044 glLy)ym1 BLGeter Goncenration) PFOA: 314 Serum Concentration) o= o0.0t44 ( \g9i"~ g)YJxx11 ~ eer (Water Conemrain Concentration) PFOA: 314 -~ (Serura Concentration) = L Very limited empirical dot exit for comparison of th ti between PFOS/PFOA water concentration and Very limited empirical data exist for comparison of the ratio between PFOS/PFOA water concentration and Human serum concentration. The caculted average PFOA concentration in fished water in the city of Lite human serum concentration. The calculated average PFOA concentration in finished water in the city of Little HHoocckkiinngg,, OOhhiioo ((33..5555 upgg//LL,, rraannggee 11..55 --77..22)) hhaass bbeeeenn ccoommppaarreedd ttoo mmeeaassuurreedd sseerruumm lleevveellss ((EEmmmmetettt,, 22000066).). DDaattaa from private well owners were lo evaluated. Emmett's evaluation included only those residents who reported from private well owners were also evaluated. Emmett's evaluation included only those residents who reported that ther soe soouf rresidcenteial drinking water was the Lite Hocking water system. also excluded anyone that their sole source of residential drinking water was the Little Hocking water system. It also excluded anyone with substantial occupational exposure. The median serum concentratioon average ining water with substantial occupational exposure. The median serum concentration to average drinking water `ccoonncceennttrraattiioonn rraattiioo ffoorr rreessiiddeennttss uussiinngg oonnllyy tthhee LLiittttllee HHoocckkiinngg wwaatteerr ssyysstteemm ((NN==228822)) wwaass 337711 u#gg//LL sseerruumm ttoo 33..5555 gI~/g/LL wwaatteerr,, oorr 110055,, wwiitthh aann iinntteerrqquuaarrttiillee rraannggee bbeettwweeeenn 6622 aanndd 116622.. FFoorr iinnddiivviidduuaallss wwhhoo uusseedd aa pprriivvaattee wweellll aass. heir only source of residential drinking wate, ratios vred rom 1210 85 (<6). their only source of residential drinking water, ratios varied from 142 to 855 (N=6). inortodaseserss the impact of eary fe exposures, MOH createad single compartment, Excel-based TK model. In order to assess the impact of early life exposures, MDH created a single compartment, Excel-based TK model. The MOH mode calculates daly serum concentraion nan infant orn with an initia serum PFOS oPFOA The MDH model calculates a daily serum concentration in an infant born with an initial serum PFOS or PFOA concentration based on the mother's serum concentration at delivery. The model was used to examine the concentration based on the mother's serum concentration at delivery. The model was used to examine the iimmppaacctt ooff aann iinnffaanntt eexxcclluussiivveellyy ccoonnssuummiinngg bbrreeaassttmmiillkk ffoorr oonnee yyeeaarr,, vveerrssuuss aa ffoorrmmuullaa--ffeedd iinnffaanntt eexxcclluussiivveellyy consuming contaminatedwater for one year. After hs fist year, both scenarios assumedafetime consuming contaminated water for one year. After this first year, both scenarios assumed a lifetime consumptionofcontaminated water Daly intake elimination, and serum concentration were calculated over a consumption of contaminated water. Daily intake, elimination, and serum concentration were calculated over a Simulation period of 20,000 ays. simulation period of 20,000 days. Useofor reference to this model without proper attribution to MOW ispribited. 33774499..00001111 n11 SSTTAATTEE_0077443366225566 Maternal seu concentratisotn delivery was calculate using Equation 3 above, time-weighted (rom bith to Maternal serum concentration at delivery was calculated using Equation 3 above, a time-weighted (from birth to 3300 yyeeaarrss ooff aaggee)) 9955t"u ppeerrcceenntitillee wwaatteerr iinnttaakkee rraattee ((00..004444 LL//kkgg--dd)),, aanndd tthhee ffoolllolowwiinngg cchheemmiiccaall ssppeeccififiicc ppaarraammeetteerrss:: ++ HVHaoalllffu-flmifeee::oPPfRFDOOiSSstr11i,97bu71t1ioddnaayy(Vssa:aannPddPFPOFFSOOA0A3884400kddgayysas,n,d PFOA0.17 kg, and + VCloeluarmaencoefRate (CR): OS 0.0000 Distribution (Vet): PFOS801.2L3/Lk/-kdgaanndd PPFFOOAA 0.00014 kg. 0.17 L/kg, and Clearance Rate (CR): PFOS 0.000081 L/kg-d and PFOA 0.00014 L/kg-d. TTwhaheensiiennrffa:anntt'ss serum serum concentrationa concentration at birth birth was was calculated calculated base based on on maternal maternal serum serum concentrations concentrations and and placental placental transfer: Equation 4. Calclation of infant serum concentrations ith. Equation 4 Calculation of infant serum concentration at birth. serum one. (m m2a2~y) = Maternal serum conc (m5g) x placental ransfer factor Maternal For all subsequent days, the dailypost.eimination serum concentration ws cleated 5: For all subsequent days, the daily post-elimination serum concentration was calculated as: Equation. Calculation o fant dd serum concentration Equat:ion 5, Calculation of infant's dai~y serum concentration, Serum Cone. (52) = [prev day Serum cone. (32) +--NRaeyked) Today's Intake(m9) |, Va iL) x BBooddyy wWeeiigghtt, (kg) xe-k ] Duetothe magnitude of th loss iaacaton, th calculation of daily maternal serum concentrations Due to the magnitude of the loss via lactation, the calculation of daily maternal serum concentrations incorporated the amount of chemical transftoethre rinefandt a well 3s excretion represented by the clearance incorporated the amount of chemical transferred to the infant as well as excretion represented by the clearance rraattee.. TThhee iinnffaanntt''ss ddaaiillyy iinnttaakkee ((aanndd tthhuuss tthhee mmootthheerr''ss lloossss)) wwaass ccaallccuullaatteedd ffrroomm tthhee bbrreeaassttmmiillkk iinnttaakkee rraattee aanndd the breastmilk concentration: the breastmilk concentration: Equation 6. Calculation ofbrasil concentration Equation 6, Calculation of breastmilk concentration Breasemitk con. (m2o) = Maternal serum cone. (m2g2) x breasmlk transfer actor The various model input parameters and the values used are describedinSection 2.1 below: The various model input parameters and the values used are described in Section 2.1 below. 22.,1i MMooddeell IInnppuuttss 211 Elimination (Half fe) 2,1.,]. Elimir~ation (Haiti-life) Centers for Disease Control (COC) scentists found PFOS and PFOA in th serum of nearly al of the people Centers for Disease Control (CDC) scientists found PFOS and PFOA in the serum of nearly all of the people tested, indicating widespread exposure nthe U.S. population (CDC, 2017). Is importotcoansnidter tested, indicating widespread exposure in the U.S. population (CDC, 2017). It is important to consider bbaacckkggrroouunndd eexxppoossuurreess bbeeccaauussee cchheemmicicaall hhaallff--lliivveess ccaann bbee oovveerreessttiimmaatteedd iiff bbaacckkggrroouunndd eexxppoossuurreess aarree nnoott ttaakkeenn into account (Bartel, 2012) Accurately accountifnogr ongoing background exposures isverydificult andmost into account (Bartell, 2012). Accurately accounting for ongoing background exposures is very difficult and most Studies estimating half Ie have not taken no account resulting in potential overestimation. studies estimating half-life have not taken it into account, resulting in potential overestimations. Empirical dato regarding the haltif of POS i limoocicuptatieonadlly exposed workers see Section 25.2 of Empirical data regarding the half-life of PFOS is limited to occupationally exposed workers (see Section 2.5.2 of ((UUSSEEPPAA,, 22001166c)).. TThhee aarriitthhmmeettiicc aanndd ggeeoommetertriicc mmeeaann hhaallff--lliviveess ooff PPFFOOSS iinn hhuummaannss hhaavvee bbeeeenn eessttiimmaatteedd ttoo bbee 55..44 seofor reference to this model without proper ttibuton toMOH isproibited. 2 Use of or reference to this model without proper attribution to MDH is prohibited, 12 33774499..00001122 SSTTAATTEE_0077443366225577 y`yoeecaacrrusspa((9t9i55o%%naccloownnoffiirddkeeennrccsee(Oiinnlttseeerrnvv,aal2l 0((0CC71I))).33.T.99h--i66s..99poyypeeuaalrrasst))iaaonnnddc44o..n88syyieesaatrrssoefd((99525%6%iCCn1Idi44v..i00d--u55a..8l8syy(ee2aa4rrssm))a,, rreessppeecctitivveellyy,, le, 2 female) bbaasseedd oonn with amean age of 61 yearsathetimeof occupational workers (Olsen, age of 61 years at the time of initial blood collection.Halt fife informationacross different age groups, in 2007). This population consisted of 26 individuals (24 male, 2 female) with initial blood collection. Half-life information across different age groups, in a mean sppeaavrrettriiccauulllararersiinenaffaranncthtsse,,rsiissinnnoodtteaavvveaaliliolaapbiblnlee.g. TTTKhheemohhdaaefllf--siliffeLeovvcaaclliuuseeanoooff,55.2.4401yy1ee)aa,rrss(Vwweaarsnseruu,ssee2dd01bb6yy)UU.SSEEPPAA ((UUSSEEPPAA,, 22001166c)) aanndd bbyy. several researchers in developing TK models (Loccisano, 2011), (Verner, 2016)). TThhee ddeecclliinnee (Splietholf, ooff PPFFOOSS iinn iinnffaannttss 2008). Blood spot wwaass iinnddiirreeccttllyy cards from 11 eevvaalluuaatteedd diffrent d uussiinngg nneewwbboorrnn bblloooodd ssppoottss ates were selected from an ccaorolclllheeiccvtteeedsdpbbayynnNNieenwgw 1YY9oor9rkk7 SStott.aattee 2(S00p7l.ietThwooff,h2u0n0d8r)e. dBlaonodd fsoprotyt cinadridvsidfruoalmin1f1andtifbfelroeondtsdpaottesswwereeresseelelecctteeddfforrom eacahnoaftrchheive11spdaatnensi,ngre1pr9e9s7enttoing. 220t0ot7a.lTowfo2,h6u4n0dnreedwbaonrdnfoinrftyantinsd.iAvcidcuoarldiinnfgatnot tbhloeoadutshpoortss,wteheretesempleocrtaeld tforernedascohbosef rthveed1:w1edraetceosn,sriesptreenstewnititnhga haatloftlaifl eoof 2f4,6.44y0enaerwsbfoorrnPFiOnSfa.nTtsh.isAvcaclouredinisgrteoastohneabaluythcolross,etthoettheemapdoulratlhtarel-nIdfseoebssteimrvaetde dweerrievecdofnrsoismtent with a oeohcscactclufiu-pmlpiaafaetttieiooosnfnfa4aol.lr4eetyxxheppeaooTrsssKuurfrmoeeordssPtteuFulddOiiSteeh.ss.rT. ohDDuiusugeehvoattuoloutetthahleiles fllriemieamissitatotatnaigoatenbsi.slooynofcsflottshheiisstobbllotohooedd spot adult spot analysis, half-life analysis, MDH used th adult halflife estimate derived from MDH used the adult half-life estimates for the TK model throughout all life stages. cUUonnnppcuuebnbltliirssahhteeiddonddsaatotaaveffrrrootmmimttehheeweEEraaessttcoMMneestitrrsootebbniitoowm miootnhnitietoolririimnni8gnasstttiuuoddnyy,f,acctooennsddouufcc6tt.ee3ddybbeyayrMMsDDbHaH,s,enndoototeenddgttehhoaamttetddreeiccrcreemaaessiainnngg ssseeerrruuummm concentration and 7.2 years based on individual results for concentrations over time were consistent with elimination concentration and 7.2 years based on individual results for PFOS rates PFOS (Nelson, 2016) and (MDH, 2015). This of 6.3 years based on geometric mean serum ((Nelson, 20:16) and (MDH, 20:15)). This ppPoFopOpuSullaaitnttiioohnne ccgooennnsseiirssatteleddpooopffu11l44a9t9iiionnnddiiwvveiidrduueaalilssde((n66t77ifmmiaealdleei,,n 8822 ffeemmaallee)) aanndd aammeeaann aaggee ooff 5533 yyeeaarrss.. NNoo ddaattaa the published literature. Background exposures oonn hhaallff--lIiffee ooff from the East PMFeOtrSoinstthuedygweenreeranl optotpaukleantioinntwo eacrecoiudnetnitnifitehdesinethcaelcpuulabtliisohnse.d literature. Background exposures from the East Metro study were not taken into account in these calculations. ToTrhheevrireae caaorreentssaeemvvieernraaaltl eppduubbdllriicicnaakttiiionongnsswaeetvveaarl.luuaaTtthiinenggfhhoalalllf-o-wiliiffenegoohffalPPfFFlOOifAAe iiennshthiuummmaataennsppwooeppruuellaasttuiiomonnmssareeixxzppeoodsseebddyeeEiittPhhAeerranoocdcccauurppeaatitioonnaallllyy poprrreevssi+aeenncttoee3ndd.t8abbmyeeellioanorwawste(((((dmUUeSSddEEriiPPnaAAkn,,in322g.0051,1w66ra3aa)t)en:)gr:.eT1.h5 e-9fo.ll1o)wi-nbgasheadlf-olinfedeecsrtiemaasitensg were summarized by EPA and are serum concentrations in twenty-six retired 2 3333.MM8yywweeooarrrkksaee-r(rbmssrae((sBdBseuiuardrrnoriisns3e.e5tat, asarlela..rni22ge00se00o001f,,.5s22e-00r009u22.m1aa)ccci-iobn((aUcUseSSenEEtdPPrAAao,,tni22do00ne11s6c62rare))a.o).smin820s0earudmultcsotnackeenntroavteiorntsiimne twenty-six retired after treatment of ddt2rr.r3iiennaykkteiinmangegrsnwwt-aastbtyeaesrsrteeiidnnm,oW WneteshasettstVVeiirirmireggesiinneoiixaafpsaaoennsrddeudmLLbiitecttlfoeeonrHHceoeoccankkntiridnnaggta,i,oftOOnesHHr ff((riBoBlatmarrrtatete2lil0loln0e,ettapdaaublul.llti22sc0011tva00e)k)r.e.snuCCsooovbvvaoaertriritaatltitemeedssewiinaantccfetlluerudr,detegrddeenattdhhtem eer,ewwanaattgteeeor,rf + tcc3r:ooe3nnayssteum uammrepspnttti(ioogsnenyosoomtefefmtlloro,ccitaachllemooerrtaimhhnoo,emmreeeaxgsnprrgoooes1wwe.nnd0vvb1eeeggfeoe4trtaeabb.la-leenbss7da,,saaa)efnntdeddroeefnxxilpptrdooaissftuuiforreneere,ttnoopcuetthsbheleiicnppvpuueblblrasliiscucmswwaabactotoeetnrtrlceessdnuutppwrppalaltyytieaaort,nt swwgoefornrrkkod,.mera, age, population (n=66) in 3.3 years (geometric population (n=66) in Arnsberg, Germany, that mean, range 1.0 - 14.7) - Arnsberg, Germany, that was exposed to a contaminated based on differences in plasma was exposed to a contaminated drinking water concentrations drinking water supply from a supply (e(BsBtrreiedmdeateeettsaabll..as220e01d100o)).n. EEqxuxpepsootssiuuorrneenwwaiaarsseseessattniimdmaaittneetdderffvrrioeomwms.ddrTriihnnekkiintnoggtwawlaatpteoeprrumm loaontiintoitonorreiivnnagglurreaestsueuldlttss(2aa,nn0dd08iinnsttuaabkkjeeects from ethsetimexapteossebdasaerdeaoannqdu7e3stfiornonmaairreesfearnedncinetearrveiae)wisn.cTlhudeetdotcahlilpdorepnu,laastiownelelvaasluaaduteltds.(2,008 subjects from + t2h5e-3ex0pyoseeadrasre(aavaenrdag7e32f9ro)mfora freorfemreerncLeitaereHao)ciknicnlugdreedsicdheinldtsreann,das5.w9e~ll10a.s3 adyeualtrss. average 8.5) for ffr2oeo.5rsrmim-dee3err.n0LLtuusyb-b]eeeacbcrkask,s,(eWWadNvVe,o,rnarrgeeaessdiied2dcee.l9nni)ttnssfeo[[rninnfoootstreeemriineuniirmttliiaLaellivttellleelevsveiHelnlsociiinknnindLLiguuvbbireedecucsakkidlsrreeenwssthiisddoeeannncttdhssa5wwn.e9gerer-eed1llro0eow.sw3ieedyrreenttathhiraasannl(aLlLvoiitctetallretaeigHHoenooc8c(k.Sk5iein)na8lgfos ret arle.s2id01e1n)t.s] T- hbeasaeudthoonrsa iddeecntliinfeieidn tsherreuempoletevnetlsiainl lindiivimduialstowfathhotecrhiaannoagleynsdissr:eshideenctriaoslsl-osceacttioionna(lSedaelssigent, athl.e2a0s1s1u).mpTthieonauththatoresxipdoesnutrifeiewdatshrueneifpoormtewnititahlinlimawitaattieornsdiostfrtihcte,iraanndaalypsoist:enthtiealcrboisass-siencttrioodnuacl eddesbiygn, thethe the exclusion of individuals with serum values <15 assumption that exposure was uniform within exclusion of individuals with serum values <15 ng/mL. a water ng/mL. district, and a potential bias introduced by TTcohhleeleddceetccerrdeeiaanssiiNnneggwsseeYrrourumkm Scctooanntcceeen(nStptrriaaitetiitoohnonfssf,ooff20PP0FF8OO)AA. Twwheeerreeteaamllspsoooreeavvlaaltluuraaettneeddds iionnbisinneffraavnnettssd bwbaaessreeeddcooonnnsnniseetwwebnbotorrwnnitbbhllooaoohddalssfpp-ooIttfsse of 4.1 years. collected 4.1 years. This value is in New York This value is reasonably close State {Spliethoff, reasonably close (withian facto of 2 2008). The temporal (within a factor of 2) to the trends to the adult half. Ife estimates of2.3to3.8 years. observed were consistent with a half-life of adult half-life estimates of 2.3 to 3.8 years. mDDouudeeettloottthhhereolluiimgmhiitotaautttioioannlss oofeff ttshhtiiassgebbsll.oooodd ssppoott aannaalylyssisis,,MMDDHH uusseedd tthhee aadduulltt hhaallff.-lfifee eessttiimmaattee ooff 22..33 yyeeaarrss ffoorr tthhee TTKX model throughout all life stages. Use oof reference to this model without proper attribution to MDHs prohibited. 33774499..00001133 5 STSTAATTEE0704743366225588 RReessuullttss ffrroomm tthhee EEaasstt MMeettrroo bbiioommoonnititoorriinngg ssttuuddyysshhoowweedd tthhaatt ddeeccrreeaassiinngg sseerruumm ccoonncceennttrraattiioonnss oovveerr ttiimmee wweerree ccoonnssiisstteenntt years base wwiitthh d on PPFFOOAA eelliimmiinnaattiioonn individual results rraatteess ooff (Nelson, 33..22 yyeeaarrss 2016 and bb(aaMssDeeHdd,oo2nn01gg5ee)oo)m.meteBrtaricicckmgmreeoaaunnndsseeerrxupumomsccuoornencsceewnntetrrraaettiinooonntsstaaannkdden33.i.44nto yaecacorsunbtasien dthoenseincdailvciudluaatilornes.sults (Nelson, 2016 and (MDH, 2015)). Background exposures were not taken into account in these calculations. TThhee eelliimmiinnaattiioonn hhaallff--lliivveess ooff PPFFOOSS aanndd PPFFOOAA vvaarryy ggrreeaattllyy aammoonngg ddiiffffeerreenntt ssppeecciieess.. RReennaall eexxccrreettiioonn iissoonnee ooff tthhee trrouobuuutteleassorofsfeeeclrliiemmtiiinnoaanttiiaoonnn.d. rTTehhaeebsuuonnrddpeetrrilloyyniinn(ggHammnee,cch2h0aa1nn2ii)ss.mmBiaalppappreeyaaerrxsscrttooetiiinnovvnoolalvvleesgogloloocmcmeurerursulblaaurrtffdiiltotrreaasttiionoonntwwsiietthehmaacctttoiibvveeerraeennmaaalljor tfuacbtuolrarcosnetcrriebtuiotinngantdo srepeacbiseosrpditifofnere(Hncaens., 2S0e1r2u).mBailliabruymienxchraestiobneeanlsiodeonctciufrisedbaust tdheoesprniomtarsyebeimndtiongbperaotmeaijnorin ftithamhecpetoopprlrltaacassnommatna.tr.roiSSblpupeeeticicnniiegdeissftoaafeppsrpppeeeneatacririeatttsooindhhgifaafrveveeerneassnliicmmeeililsliaa.mrriSbnbeaiirntnudidmoiinnnggaalbaamfufoffmiinnniiginttieivehsasarsaainnobdude;s;ettmnhhaeeimdrrmeeefafnooltrriifeei,ea, dniitt asddpsooeetechisseesnn.opotrtLimessveeaeeerlmymsobttfoionadplplilbnaaugyymaapinnrnoatenind in total proteins are approximately70percent ower in young infants thainn adults (Sethi, 2016), however, the important role in differentiating renal elimination among various mammalian species. Levels of albumin and total proteins are approximately 70 percent lower in young infants than in adults (Sethi, 2016), however, the ppootteennttiiaall iimpamctoofpftthhiiassddififcffeerreetnnccee oonn eelliimmiinnaattiioonn iiss uunnkknnoowwnn aatt tthhiiss ttiimmee.. sHHpuuemmcaiaennssssaatpupdppieeeaadrrttthooushhaafvvaeer (tthHhaeens,sllo2o0ww1ee2s)s.tt PPTFFoOOdSSataaenn,ddrPPenFFaOOlAAorrregenananalilceelaliinmmiiionnnaatttiirooannnsrrpaaottreetaaernndd(OlloAonTn)ggeepssrttothhaealilfnf-qsliivhveaessveaammboeonenngg stththueedied both indirectly species studied both indirectly and directly for their thus far (Han, 2012). and directly for their potential To date, potential interactions with perfluorinated chemicals. Perfluorocarboxylates renal organic anion transporter (OAT) proteins have been studied interactions with perfluorinated chemicals. Perfluorocarboxylates (r(PePnFFaCClAASus))pthhaaakvveee tbbreeaeensnnp ossrttutueddriiese,dd ttoo aaggrreeaatteerr eexxtteenntt tthhaann ppeerrfflluuoorroossuullffoonnaatteess ((PPFSSAAs)s).. AAmmoonngg tthhee ccoonnffiirrmmeedd OAT1 and OAT3 reside in the basolateral membrane of the proximal tubular PPFFCCAA cells, and treheniarl PuFpCtaAkuepttraaknespwoorutledrs,faOciAliTt1ataenPdFCOAATre3narelstiduebuilnarthseecbreatsioonla.teIrnalcomntermasbtr,adnueeotfothteheiprroexxipmraesl stuiobnulianrtcheellasp,iacnald tmheemirbrPaFCnAe uopfttahkeepwrooxuildmaflactiulibtualtaerPcFelClAs,rOeAnTaAl ,tuabnudlaUrRsAeTcLrewtioounl. dInbceotnhtreatsrta,ndsupeorttoerthsienirvoelxvperdesisnioPnFCinAthreenaalpical tthmuuibebguhmullpabaerrrarrrcneeeeaanbbtossafoogtrherppetotiifoponrrnoenx((HaHimlaannat,,lubt22uu00lb11a2u2r)l)a..rreIIttacabaesppllopspr,eepaOatrrAissoTntt4hh,(aa>att9n9aa5d%kk)Uee.Ryy ArreTea1asswoonnouffolodrr the long PFCA plasma haf-ife in humans s be the transporters involved in PFCA renal the long PFCA plasma half-life in humans is tthhee high percentage of renal tubular reabsorption (>99%). EExxccrreettiioonn ooff PPFFOOSS aanndd PPFFOOAA aallssoo ooccccuurrss tthhrroouugghh bbiililarryy eexxccrreettiioonn.. RReennaall cclleeaarraannccee ooff PPFFOOAA hhaassbbeeeenn eessttiimmaatteedd tttoootbableecrrlooeuuaggrhhalnlyyce9900inppmeearrclceeennattnoodff ftthehemeattlooettaaJllaccpllaeenaaerrasanenccmeeaicinnamqmaualelese.rraaTtthss,e, wwshihgeenrrieefaaicssaniittceiissoeefsstttihimemaabttieelddlrttyoopbbaeetohonwnlalyyy44c00opmpeperarccreeenndttotofoftthhee. tirroenetnnaaaadlllucleeltleliim ahmruiiannmnaaacttneiiosoninnwiiamnnsahhldueuemmmaaaonnndnsssftesisrmannatooletetdlcJleaaeafpatrarenraaennasdddemccimoniuasclodtabrqbaeuetueisssoii.nggnlTniohfififeiaccdaasnbnitig.ltn.eiIafIincnccicardrneecasaeessqeeouddfesfftehetcceeaarllbineeillgilaiimarmygiinenpnaaatttitioh(onwGnoeaonfyufiPcPsFoF,OOm2SSp01aaa3rnn)edd.dPPtFFoOOAA in adult humans was demonstrated after administration of a bile acid sequestering agent (Genuis, 2013). T"rTehhneealsseeprrruoumcmeshhasalelffs--llaiivlveoensse.eesstWtiihmmiaalteteelddimttoiot--deddaattieenslliiikgkehetllysy rhreeappvrreeessbeeennettnbbgooattihhneeednnttreeerrgooahhreedpipanatgtiisccpeaacnniddesrrdeeinnfaafllepprrreoonccceeessssseeisns,,errlaaittmhhieenrartttihhoaannn mechanisms,anunderstanding of potential fe-stage differences in humans continuestobean renal processes alone. While limited insights have been gained regarding species differences in mechanisms, an understanding of potential life-stage differences in humans continues to be an area of elimination area of ccoonnssiiddeerraabbllee uunncceretratainintyty.. IIntthhee aabbsseennccee ooff lliffee--ssttaaggee ssppeeccififiicc rreennaall aanndd bbiililaaryy eexxccrreettiioonn iinnffoorrmmaattiioonn,, aanndd tthhee vllaaacclkkueoosfhf aihciggrhohsqsquuaalallliilttyfyee-essstttaiimgmeaas.tteess ooff PPFFOOAA aanndd PPFFOOSS hhaallff--lliviveess ffoorr iinnffaannttss,, tthhee MMODHH mmooddeell uusseess tthhee ssaammee hhaallffl-liiffee values across all life-stages. Ahvaalhlufae-lfl-uiltiffieelivvzaaedllbuueye ooVfef5r.n45.e4 ryyeeaaanrrdss ((c11o,.l99l77e11agdduaaeyysss)V)fefoorrnrePPrFF,OOS2S0ww1a6a)ss assneeldleeccbttyeeddEbPbyAy iMMn DDtHHheffiooarrsuussseeesisinnmoeonuutrrsmmoodedle,l. TThhiiss iiss tthhee ssaammee. value utilized by Verner and colleagues (Verner, 2016) and by EPA in their assessments. AAvahlhaulaeflf--uiltiffieelivvzaaedlluubeeyooEffP22.A3.3inyyeetahaerrissr((a88s44s00esddsaamyyessn))tffsoo.rr VPPeFFrOOnAAerwwaaasnsdsseecloleelccltteeeaddgubbeyysMM(VDDeHHrnefforo,rr uu2ss0ee16ii)nn ouotuuirrlimmzoeodddetelhl.e. TThhhiigissheisrtthhhaeelssalaimmfeee value value value of 3.8 years. utilized by EPA of 3.8 years. in their assessments. Verner and colleagues (Verner, 2016) utilized the higher half-life 2.1.2 Volume of Distribution T2h.1e.2voVloukm.'=emoef doifstDriisbturtibiounti(oVnd, L/kg body weight) for PFOS and PFOA isbelievedto largely represent the body's extracellular fluid volume ((USEPA, 2016) and (Han, 2012)). The values The volume of distribution (Vd, L/kg body weight) for PFOS and PFOA is extracellular fluid volume ((USEPA, 2016c) and (Han, 2012)). The values used for believed used for Vdto Vd by USEPA for PFOS and largely represent the body's by USEPA for PFOS and PlPoFFnOOgAA-wtweerermreeex00.p.22o33suaarnnedda00n..d1177arLLe//kkmgg,o, srretessapppeepccltitiicvvaeebllylye((UtUoSSEEoPPlAdA,e,r22c00h11i66lcd))reaannnaddn((dUUSSadEEuPPlAtAs,,. 220I0d11e66naat)i}..caTTlhhoeersseesiVVmaidlvavraallvuuaeelssueaasrreeweuursseeeddutffoioirrzed long-term exposure and are most applicable to older children and adults. Identical or similar values were utilized Use oof reference to this model without proper attribution to MDHs prohibited. 114 33774499..00001144 STSTAATTEE 0077443366225599 byVerner and colleagues (Verner, 201) (023 ad 0.17 for ROS an ROA, respectively) and Locisano and by Verner and colleagues (Verner, 2016) (0.23 and 0.17 for PFOS and PFOA, respectively) and Loccisano and ccoolllleeaagguueess ((LLoocccciissaannoo,, 22001133)) ((00..2222 aanndd 00..1177 ffoorr PPFFOOSS aanndd PPFFOOAA,, rreessppeecctitivveellyy)).. MOH agrees with th values of 0.23 and 0.17 hg fr FOS and FOR, respectively, or older chen and MDH agrees with the Vd values of 0.23 and 0.17 L/kg for PFOS and PFOA, respectively, for older children and dts, Infos, however, nave Higher wate content an shld, hereto, ve a higher Vd basedan adults. Infants, however, have higher water content and should, therefore, have a higher Vd based on Caracelulr volume poentil Thevolume of exracellr id a5. prcent of body weght roughly plateaus extracellular volume potential. The volume of extracellular fluid as a percent of body weight roughly plateaus rou3yneadrs of ag (FisHansen, 1963). The MoH ocel nudes an eal fe stage VE acumen actor around 3 years of age (Friis-Hansen, 1961). The MDH model includes an early-life stage Vd adjustment factor asec on formation ram Tale of Fis Hansen (1961) regarditnng oxraccluar watera percentaogef based on information from Table I of Friis-Hansen (1961) regarding the extracellular water as a percentage of ody wet (30) Agspecific Vd dsm ctor mere CHAI by MOM and ae presented he table body weight (BW). Age-specific Vd adjustment factors were calculated by MDH and are presented in the table below: below: Table 1. Age-specific volume of distribution (V) adistmen factors, Table 1. Age-specific volume of distribution (V~} adjustment factors. Sacer ister | Cl VaAda end Fao Age [ofan me]|[we s | mse wissr|| 0-1 day Extracellular Water as % of 44.5 Calculated Vd Adjustment Factor** 44.5/18.7 = 2.4 [s[ mote m |a smansrear | 1-30 days 1-3 months 39.7 32.2 39.7/18.7 = 2.1 32.2/18.7 = 1.7 3-6 months 30.1 30.1/18.7 = 1.6 6-12 months [L1a-2yyeeaarss 27.4 27.4/18.7 = 1.5 a2s5.e6 I a2s5.e6/f1s8.r7 == i1,a4 | Lowes | er | emnercae | 2-3 years 26,7 26.7/18.7 = 1.4 D[ oves a |a siereaa | 3-5 years 21.4 21.4/18.7 = [oioyes | a0 |mowraz | 5-10 years 22.0 22.0/18.7 = 1.2 10-15 years 18.7 18.7/18.7 = Sotelo 7 *from Table I of Friis-Hansen, 1961. ins ion ** calculated by MDH estraceluar water conten han adults (Fier, 2015). To avokd abrupt changes within the moe, the midpoint `TThhee aabboovvee eessttiimmaattee ffoorr yyoouunngg iinnffaannttss ((00 -- 3300 ddaayyss ooff aaggee)) iiss ccoonnssiisstteenntt wwiitthh nneewwbboorrnnss hhaavviinngg aa 22--ffoolldd hhiigghheerr extracellular water content than adults (Felter, 2015). To avoid abrupt changes within the model, the midpoint iinn ttiimmee ffoorr eeaacchh aaggee ggrroouupp wwaass sseett eeqquuaall ttoo tthhee aaggee--ssppeecicfifiicc vvoolluummee ooff ddiissttrriibbuuttiioonn aaddjjuussttmmeenntt ffaaccttoorr ((VVdd AAFF)) Value The iy Vd AF beeen ane midpoint andtnh ex we collated by nea nteplation. verl use value. The daily Vd AF between one midpoint and the next were calculated by linear interpolation. Overall, use ofthe VaAF proved model resus incompa1riemspoHcna dat se edion 22 and T3631an0d 4. of the Vd AF improved model results in comparison to empirical data (see section 2.2 and Tables 3 and 4). 21.3 Placental Transfer 2.~ .3 Placef~tal Tran~fer Several studies measured maternal an cord serum evsof OS an PFOA ear the tiof dmeliveery (Cari, Several studies measured maternal and cord serum levels of PFOS and PFOA near the time of delivery ((Cariou, 22001155)),, ((KKiimm,, 22001111)),, ((LLiiuu,, 22001111),), ((FFrroommmmee,, 22001100)),, ((MMoonnrrooyy,, 22000088)),, ((MMiiddaasscchh,, 22000077)),, aanndd ((FFeeii,, 22000077))),, tthheerreebbyy permiang om esimoaf ptlacoentnal raster ad ical dy burden n the newborn ian. See Appendioer permitting an estimation of placental transfer and initial body burden in the newborn infant. See Appendix I for more informaton. more information. The reportet mean atofcoord to maternal concentrations anged fom 0.31 (Fromme, 201010060 The reported mean ratios of cord to maternal concentrations ranged from 0.31 (Fromme, 2010) to 0.60 Teported mean ais fom thes tudes were 42nd 0.87 for FOS and POA respectively. These ales wre {(MMiiddaasscchh,, 22000077)) ffoorr PPFFOOSS aanndd ffrroomm 00..6699 ((KKiimm,, 22001111)) ttoo 11..2244 ((MMiiddaasscchh,, 22000077)) ffoorr PPFFOOAA.. TThhee aavveerraaggee ooff tthhee reported mean ratios from these studies were 0.42 and 0.87 for PFOS and PFOA, respectively. These values were uusseedd iinn tthhee MMDDHH TTKK mmooddeell.. TThhee ppllaacceennttaall ttrraannssffeerr vvaalluueess uusseedd bbyy LLoocccciissaannoo aanndd ccoolllleeaagguueess ((LLooccccaassiinnoo,, 22001122)) Snderner and coleagues (Verner, 2016) were 0.4 and 0.45, respectively, o POS and 0.45 and 0.75, and Verner and colleagues (Verner, 2016) were 0.46 and 0.45, respectively, for PFOS and 0.46 and 0.78, especie for PFOA respectively, for PFOA. Use ofr reference to this modelwithoutproper tribution to MiOprohiH bited. 33774499..00001155 115 SSTTAATTEE_0077443366226600 ~2I3.n,i1t~.a.,44k.eBBrrraeetaeasssLtor-mnriiJekkxclIrln~uttsaaikkveeelaaynrbiddreBBasootddfyyedWWeieniiflg;akhn~ttt, and data us to calculacorrespondingbody weights or the fist year of fe, were obtained Intake rates for exclusively year of life, were obtained from Table 15-1 of USEPA's breastfed infants, and data from Table 15-1 of USEPA's 2011 used 2011 Exposure Factors Handbook (EPA 2011) to calculate correspandinB body weights Exposure Factors Handbook (EPA 201].). for the first Table Table 22. Human Hum~:m mikntakefor milk inl:ake for eex~cdluussiivveellyy bbrreeaassttffeedd iirnfffaanntt:ss andarid cc:aallccuullaatt:eedd ccoorrrreessppoonnddiir~ngg bbooddyy wweeii~ghhti:ss (BW) GAArgogeuep|| ML/day| mifMkMegedaaanny| Group rnL/da mL/kg-da m<<aointh s51o0 1[15500 month Calculated || mi/day|UpUppmepire/PrkegPr-edcraecyen|nttiilee'C**aicuioted| CBBawWlcE(ukxlagt)e*d rnL/da 50 rnL/kg-day 20 Calculated BW3(kg)* BW 3.4 950 220 4.3 1 to < 3 690 140 4.9 980 190 5.2 o|m Zw [ew[= month month 3s | 70 70 06 a 3 to < 6 770 110 7.0 i000 150 6.7 I illI A Swi months 6 to < 12 620 83 77.55 i000 130 7Z77 l I l llI months Wena crn a ts ak or ob 15, USA TOEL Mean and upper percentile intake rates taken from Table 15-1, USEPA 2011 "om + (roo) ~(mL/day) + (mLikg-day) or pconis poed mean ps 2 nc dens. ~*Upper percentile is reported as mean plus 2 standard deviations. CCoonnssiisstteenntt wwiitthh guidance (MOH MMDD'Hs's 2008), tcchuuerrrrueepnnpttemmrpeeetrthhcooeddnotoliloolggeyynotofaf kuuessiinrnaggtaaesnn aRRnMMdEEcsoscrcerenenasarpiriooonfdfooirngddeebrroiivdviiynnggweppirrgoohttteesccttwiiveveerehheesaaelllttehhc-tbbeaadssefeoddr use gviinanultitdhuhaeeesnTTciKKentmm(eMoondDddeeHeldl..2tUU0op0pap8ppe)ep,rrrthpopeexerircucmeepannptteiteillretehpbeberrr9eec5aaes"sntttmpmilieeilrlkkcinenitnnatttkaikekeeerbarrytaaettaseedssadinrrendegppcrrtoeewrssroeeennssttptaaoannccddooaimmnrpgdiplidblaaeotvtdiiiooyanntwioooeffnigsmmhetetaosastswuhureereermeddesooaernleeecvssattueilmmduaeaftoteerdduse (use, 201). values intended (USEPA, 2011). to approximate the 95t~ percentile by adding two standard deviations to the mean value W Wdaiitilthhyiinbnottdhhyeewmmeoiodgedhlet,l,sttbhheeetmmwieiddeppnooioinnntteiinnmittdim ipmoeeifnfootraeenaadcchhthaaeggneeggxrrtoowuuepprwweaacssalssceeuttleeaqqtueuadallbttyoloittnhheeearmmeienaatnnerbbpooolddayytiwwoenei.iggThhittsvvaaallpuupeer..oTTahhceeh atdavhvaoeoiliyiUdcssSbEoaaPdbbryAruuwEppxtetpigbbohoostdudsryyebwweeFetaiwicggtehhoettrnscchhoHaanannneggdem ebssoiodaakpnn.oddinTkktheeeeeappnbssdotttdhhhyeeewoonevveieegxrrhtaatwlll eabbrooebddicyyratwwhlceeuwiilaggashhtettsdtttiimbmyaeetlis3sne.eer3raii8eersskingccltloeotsrshpeeeottmlooaetttaihhoneend.bdiiTisrshctcirhsreewatteeepipvgvraaholtluauecefohssriinn tsSshtiinaentggilUlseetSttioEconsPnA(bbDiiErrottxnhhpassohasaututer,33e772F0ttao1o0c)44to.11rswwBoeHedeeaykknssdwebooioffgogghkeet.ssstTtaahnttetiioohbnneoiidnlnyattshwtheeaegiyygeeehaagtrrra2o2t0u0b0p05i5rw,t,heuurwsseiianncsggaslddceaautttlaaaattrfre3ood.b3mm8yttkhhegeex, ttNNehanaetdtiiimoonnnegaaaltlnhCCebeenisnrttltheeorprweffodeorrigliHHhneteeaafrlolttorhhm ttoShlhtedaeeticcrseetainncgtsteeerr(gDoorofofnuttphah.eheuWttewaw,too2e0rpp1rrie0envv)t.iioaoBkuuoessdfggyarrtwooeuuesppiwgsseh((rt:s~e11iint0notthe<<er11p66loalaasantntddaegd11e66ingt0raoo<su<i2p2m1~iw)l)aeuurrnnemtaiiclntaintlecrrruee,laaacctehhdeeddbttyhheex88te00nkkdgginvvgaalltuhueee or the sloped for the 22 and line from 22 and older age group. Water intake rates were interpolated in a similar manner. 2.15 Breastmilk partitioning 2.~ .F] BreastmiJk parl:itionin~ Several studies measured maternal serum an breastmilk concentrations of PFOS and PFOA ((Cariou, 2015), Several studies measured maternal serum and breastmilk concentrations of PFOS and PFOA ((Cariou, 2015), ((KKiimm,, 22001111)),, ((HHaauugg,, 22001111)),, ((LLiiuu,, 22001111),), ((FFrroommmmee,, 22001100)),, aanndd ((KKaarrrmmaann,, 22000077))),, tthheerreebbyy ppeerrmmititttiinngg aann eessttiimmaattee ooff pariioing from maternal serum into breastmilk andprediofcbrteaistominlk concentrations. The reported partitioning from maternal serum into breastmilk and prediction of breastmilk concentrations. The reported `mmeeaann rraattiiooss ooff bbrreeaassttmmiillkk ttoo mmaatteerrnnaall sseerruumm ccoonncceennttrraattiioonn rraannggee ffrroomm 00..00~1L ((KKaarrrrmmaann,, 22000077)) ttoo 00..001188 ((LLiiuu,, 22001111)) ffoorr PPFFOOSS aanndd ffrroomm 00..002266 ((KKiimm,, 22001111)) ttoo 00..110099 ((LLiiuu,, 22001111 ))ffoorr PPFFOOAA.. TThhee aavveerraaggeess ooff tthhee rreeppoorrtteedd mmeeaann ratio from these studies were 0.013 and 0.052 for PFOS and PFOA, respectively. MOH selected the average of ratios from these studies were 0.013 and 0.052 for PFOS and PFOA, respectively. M DH selected the average of themean values acrossstuies see Appendi for more information) o calculate PFOS and PFOA breastmilk the mean values across studies (see Appendix I for more information) to calculate PFOS and PFOA breastmilk concentration fom corresponding maternal serum concentrations in our model. The breastmilk transfer values concentrations from corresponding maternal serum concentrations in our model. The breastmilk transfer values uusseedd bbyy LLoocccciissaannoo aanndd ccoolllleeaagguueess ((LLoocccciissaannoo,, 22001133)) aanndd VVeerrnneerr aanndd ccoolllleeaagguueess ((VVeerrnneerr,, 22001166)) wweerree 00..00112222 aanndd 0.014, respectively, for PFOS and 0.038 and 0.053, respectively, fr PFOA 0.014, respectively, for PFOS and 0.038 and 0.058, respectively, for PFOA. Useofor reference to this model without proper attribution to MsO prohibH ited. 33774499..00001166 16 16 STATE o7asezst STATE 07436261 TTprhhoeepmmoasateteedrrnwnaaaltlessreerrguuumimdccaoonncnceceevnnatltrruaaettiiuoosnninaagtt dEdeqeluliiavvteeirroyynww3aas(ssccealelcSuuelclaatttieeoddn aa2.s0)aa,ssDtteeuaaeddytyo-sstttahateteemccooannccgeenntntrraaoittifiootennxcubbraaessdteeiddoeononnvittahhee btpbrhrreoeeapansostftsmameinlditlkk,w,a tathhtweeerlcclgaa3ullc5icduoualanlngtaciooteinionvooagfnlfumddeaaatiuiellysyrinnmmagalatEteeerqxrnunpaaaoltlsioussnreeerr3uuvm(misaeccdeoornniScnceekecninttniotrgrnaawtta2iioto.0nen)ssr. Diainnnuccdeoorretpopxooctrrrhaeaettteiemdodnaologrssnesspitruooefdfseccehhnoeetfmmeiedicxcabcalyrlevvttihiaaoenttcrarvlineaaasnrfeasnretctreoo ate:the infant as well as ongoing maternal exposure via drinking water and excretion represented by the clearance rate: Equation 7. Calculationof maternal diy serum concentration. .F.quat:ion 7o Calculation of maternal daily serum concentratiom Serum Cone (22) = prev. day Serum cone. (132) LnEYtSVao(15)kx Boed_yLoWlesisgthnotI(nkfoga)nt ()ng) mPParreetggennmaaannlccyyseaarnnuddmllaacccottnaacttiieoonnntararareetissoiigngnnaiiffniicdcabannrtet ammsaattmteeirrlnnkaalcl oeenllciimemniintnraaatttiioiononnrrsoo.uuAttececssoffroodrrinPPgFFOOtSSo aaLnnoddccPPsFFaOOnoAA tathnhadttcggorrleelaaetatllgyyueiimsm,ppamacacttternal ssmPeeFarrOutueSmmranccnaoodl nnscPceeFernOuntAmtr,raatcrtiieoosonnpncessecttanittvrtteahhlteieyo,eentnnshddaaononfdfdaaubrssriieixnxagmmseotomanrntilltkyhh cpllaoraccenttgcaanettiainoontnnrcpayepti(reoLirnoioosc.ddciAasacrarceneooaa,rpdp2pipn0rr1goo3xxt)ioi.mmaTLatohteceelclyyeisma11pni44oraaiacnnnaddld44dc00aotppllaeeerarrccgeeeupnnoetrtst,lloeomwdwaeeitnrrefrfonorral PFOS and PFOA, respectively, than during early pregnancy (Loccisano, 2013). The empirical data reported in SreevaetrallpousbsliocfatPiOonAs aflroomdmaotecrnaulamsdeeercurmneavsteresuins mPaRtOSe,rnal serum concentrations, in general confirming the several publications also document a decrease in maternal serum concentrations, in general confirming the greater loss of PFOA from maternal serum versus PFOS. tMMoaatcteeorrnnnaalcl sseeenrruutmmrPPaaRFtOOtdSSeilcciooovnnneccreseynnt(rtrmaaettiiaoonnnssduddreeiccnrrgpeeraaseseegddnbabynycaaybbooaunutdtanniinnedeeplpieevrreccreeynnt3t.aa5ffutteegrr/Lssiixxammnoodn3n.tt2hhssg/oofLf bbarrteesaaxssttfmeioeendtiihnnsgg)rreellaattiivvee tp((oFrFrercogoomnmnammcneeec,n,yt22r20a.01t10io0]u.n)g.s/FFLaoortar dnPPdeFFalOOivtAAe,d,reymmlai(atmvteeeerrranynnaa2lld3ssueergirrn/uugtmm)pccareoonngndcncedaenenntcctrrryaaettaaiionsodnensdsadatdenedccearrldeievdaaiesstreeiydodn3abb.5lyy p21116g.15/.pL5earppnceederrcnc3ete.nn2attfptaaegttr/ddLseeilaxliitvmvseeoirrxnyytm((hmomsneeotaahfnns)dduurriinngg cbpbrorreeenacgasenstntafftneerceeayddtiii2nno.ggn6s((pmdmgeee/cLaarnnaeanaadsteddadeet lbldiviyeevlairevbyreoy2ruy.t32323lu.a83gg//ppLLegraa/Lcnn)eddnat11n.7.df7godl/aemgcLirLperaaaettsgessnidixaxnammcnooynatnthdthhsdr)sio.t)i.uogOOnhvavelserir2axa6lmlll,potetnhhrtecehetstnoottotaafallfltmmaecartatatseteiirxronnnma.alol nPPtFFhOOsAAossfeerruumm concentrations decreased by about 38 percent from pregnancy through six months of lactation. cDDoeelcclrreeeaaagssueeesss ii(nnMmmoanatdteaerlrn,naa2ll0PP14FF)OOSSreaapnnoddrtPPeFFdOOaAAnssaeevrreuurmmagcceooonnfcceetnnhttreraaettiipooennrsscehhnaatvveepeaarllssmoo bbeeoeennofrreebnpproeorarttsettedfdebbeyydhioonttghh,eerrwss.h.iMMcohonnwddoaaulll daannrddesult nbcinroaelalanensat11gm88uielaasknndd(iMn33to66ankppedeearrrlacc,tee2enns0tt1sdd4eee)eccrrreTeepaaabosslreeeteoo2dvv)eeawrrnessraixxeveaairnnnaddcgoettrwwpoeeofllrvtvaheetreemmdeoonnpnttethohrssc,t,ehnerrteeMspsppDeeercHtcmitmvivoeoelndyltey.hl. ,WW ofmhhbaeetrneearuusnpptafppleeeePrrdFppinOeegSrrc,csewenenthritiuicllemeh infant would infant result cbcbrooreennacacsesetntfntmetreriadalktitiiniongon,ntaddkAeeedccjrrruaeestaaetsssmeeed(dsnetbbeyyoTf11a22tbhppleeeermr2cc)eeownnttedraaefofettueiensrrlcessoixxrpmmmoeoraoannnttethhidssnfioanofntftobbbrrthreeeeaaasssMtftfeeDmcieHdldkiimnniggontdaaaennkldd,e m2a244taeptpeseerrrn(ccsaeeelnenPttTFaaaOfbftStleeersre2oo)rnnureemesyyueelaatrreodoffin breastfeeding. Adjustment of the model to Sremsapleecdteecr.eases in maternal FOS serum smaller decreases in maternal PFOS serum concentration (9 use mean infant concentration (9 and 17 percent after sx and tielve months, breastmilk intake rates (see Table 2) resulted and 17 percent after six and twelve months, in respectively). Incorporation of upper pInrcoodrupcoerdataio4n8opfeurcpepnetr percentile infant breastmilk dpeecrrceeansteilieninmfaatnetrbnraelassetmruilmk intake rates (see Tabl cinotnackeentrraatetsio(nseaefTerabsliex 22m))onninttthhhseeofMMDDbrHHeammsototfdeeeelldffioonrrg PPaFFnOOdAAa 73 p(ppsereeorredcceeuTnanctbetldddeeeacc2)rr4,ee8aasssmpeaeelraalceffetrtenrdrtedoocennrceeeraeyyseaeaesarse.r.iinWW nhmhmaeetanneterttnrhhnaeeallmmPosoFeddOreueAlml swwecaarossunaamcdecjdnuotsnrjtcaeetdinuottnr0osacatcoftiontoensnresiidswdideexerrrmemmoeoenbaatshnnesrinnovffefoadnbntr(te4bba0rrsaeetanfaesdsettmmd6ii1nillkkgpeiianrnntctadaekknaeet7rar3aafttteeessr six and twelve months, respectively). (see Table 2), smaller decreases in maternal six and twelve months, respectively). PFOA serum concentration were observed (40 and 61 percent after TcTohhnoocmmesnsteernnataainnoddnsccioonllltleeeaangguuNeeossrssvppeeecgicifiafiicncaamlllloyytsshteuurdisied(dTtthhhoeemsiimemnpp,aacc2t0t1oo0f)f.bbrrreeeaaasststffteemeeiddliiknnggsaoomnnplPPeFFsOOSSweaarnnedd cPPoFFlOlOeAActbberrdeeaamsosttnmmtihilllkky from caaaobnbodnoucu7tet.n8ttwtwrpaooetriwwoceeenenestkkissnppurtepnmttooNnttotwwrhweelleovvgfeeiabmmrnoeoanmnstttohhftessheedaariffsnttege(.rrTbhbMioirrDmtthhHs..eDDunes,epep2ud0ur1tWaa0ett)bii.oPonBlnorareDatiateegsssitmtooiifflzkPePsrFFaOO(mSSWpeaalbennPsddlwoPPDeFFirOOgeAAtciwwozeelerlerreec,teee2sds0t1tiim7mm)oaattnteoethddlyttoofrbboeem33..88 aaaWpneppdbprPr7ool.xxo8iitmmpDaeaitrtgecetetitnhhzteerpiddesaartatamawoiiennnbtFF-hibiggaouusrfreeebdr22etfrarosoootmfmeuestthdeheidengppto.apMeaexDrtbHrbypayucTTshdeheoodotmmW asrsreeebonnPmaaIonnpdtdoDtccisgoo,liltllieizeameaagrgguu(eeeWsss,e((abTTnPhhdoIoommmtDasspeeigsnni.tieezTttehara,e.l.,22a020p10p171r0)0o,)xt.oimated data WebPIotDigitizer is a web-based tool used to extract data from plots, images, and maps. The approximated data Useofor reference to this model without proper attribution to MOHsprohibited. 33774499..00001177 717 STATE o7ase262 STATE 07436262 was then compared to the depuration rates predicted by the MDH model see Figres 2 and3 below) The MOH model prediction closely resembled the empirical data. was then compared to the depuration rates predicted by model predictions closely resembled the empirical data. the MDH model (see Figures 2 and 3 below). The MDH Figur2e. Relativeconcentration comparisonsofPFOS in breastmilk", Thomsen, 2010 and MOH TK model results. Figure 2. Rel~tive concentration cornp~risons qf PF05 in bre~stmiik ~ Thom+_~en, 20_t0 and MDH TK model results. P:s --_-- 3 Ew f w 2 x ------MTMOhOoMHmMsMeoonddeeetllalUM.pep2ae0n1r0BtreeBsrte1st ) ........................................................................................................................................................... ~ Th~rnsen et al. 2010....................................................................... o pr w 10 0 50 aw 0 x `*no*rmnaloizerdttmooccooonnclceenztnrtraeattiidoonniinn f~irrsstt ssaammplpele. Doaaryss FiFgiguurere 3&. RReellaattiivvee ccoonncceennttrraattiioonn ccoommppaorriissoonnooff PPFFOOAA iinn bbrreeaassttmmiilfkk"~,, TThhoommsseonn,, 22001100 aonndd MMDDHH TTKK mmooddeelfrreessuutl~t5so. ] O0 gg w i 3 o s0 w 1% o so: } og 150 ramatotconicenevatdoninfst some *normalized to concentration in ~rst sample --TMhOomHsMeondeetlalU.pp2e01r0Ste Brcstrie 7) MOH Model (on Src) wo.;.' (.x} x0250 x3oo: 0/~,so PY4(y} onsDavs Useoforreferetontcheis modelwithoutproperattrtioMbOHustproihiboitend. 33774499..00001188 18 18 SSTTAATTEE_0077443366226633 22.22 PPr~eelliim miinnaarryy EEvvaalhu.alattiioosn oo~f Mboloddeell MMDDHH uusseedd aavvaaiillaabbllee eemmpipririiccaall ddaattaa,, (Mogensen, 2015)duringchronic a aass nd wweellll aass rreessuullttss,, ffrroomm ootthheerr early fe exposure conditi mmooddeellss ooff PPFFOOSS ons to ascertain waahnneddthPPeFFrOOAAth((e(FFsrrioommmplmmee,e,,on22e001-100)),, c(Momopgaerntsemne,nt20M1D5)H) dmuordinegl cphrroodnuicceasnadpepraorlpyriliafeteerxepsoulstus.reFcoornedaictiohnmsotdoelasccoemrptaairniswohne,tthheer mthoethseirm'psles,eornuem- concentration compartment concentration at delivery was assumed to be at steady-state MDH model produces appropriate results. For at delivery was assumed to be at steady-state and her ongoing exposure (estimated each model comparison, the mother's and her ongoing exposure (estimated from the serum from the pmpuuabbdlleiisshshepeeddcimmaalattreeerrqnnuaaellsstsseerrfuuomrmdccaootnnacceiennntsrtroaatmtiieoonnc))asddeuusr,riinbngugttthhneeotllaaalcclttaadttaiiotoann wppeeerrriieoodadvwwaiaalssabiilnneccllfuoudrdeeuddseii,nn itthnhceeluMMdDiDnHHg immnododideveildl..uaMMlDDHH aallssoo maternal:chid paired data. made special requests for data maternal:child paired data. in some cases, but not all data were available for use, including individual 222.:21.~ CCoomrrp~aprairissoonn wwiitthh eemmpipririiccaall ddaattaa ffrroomm FFrroommrmnee aanndd ccoolilleeaasguueess ((22001100)) FfFrorololmmomwmienegaabnnidrdthcc.oollTlleheaeagrgueueewsseiirnnevvee5ss0ttiigpgaaarttteeiddcimmpaaatntteesrr,nntaahlleaamnnaddjoiinrniffatannyttobbfoowddhyyicbbhuurreddxecelnnusssioovffelPPyFFOObSrSeaaansntddfePPdFFOOthAAedidurruiirninnfgagtntthhsee(3ss7iiixxnfmmoaonnntthtshss. were exclusively brea6sprtedofmienadntl,y breast6pfaretiadll,y breastfed, following birth. There were 50 participants, the majority of which exclusively were exclusively breastfed, 6 predominantly breastfed, 6 partially breastfed, and 1 infant received no breastfed their infants (37 and 1 infant received no infants mbbroreenaatssthmtsmilipklko)s.).tdBBelllooioovdderccyoo.nnccMeeenndttriraaatntiiooannnssdww9ee5rreepcceoorllclleeenccttteielddeffbrroroemmas33t88mi---l4k477commnocotetnhhteerrrasstdiduournrisinnwggepprrreeeggrnneaapnoncrcyty,e,daafttoddre4ell4iivveemrroyyt,,haaennrdds.aatt ssiixx months post-delivery. Median and 95th percentile breastmilk concentrations were reported for 44 mothers. TThhee MMDDHH mmooddeell wwaass eevvaalluuaatteeddbbyyininsseerrttiinngg tthhee mmeeaann oorr 9595th ppeerrcceenntitillee mmaatteerrnnaall sseerruumm ccoonncceennttrartaiotniaoatnt ddeelliivveerryy aanndd aalllloowwiinngg tthhee mmooddeell ttoo pprreeddiicctt tthhee iinnffaanntt sseerruumm ccoonncceennttrraattiioonn aatt ddeelliivveerryy aanndd aatt 66 mmoonnththss.. TThhee MMDDHH mwmeooiddgeheltl siinnfccooorrreppxoocrrlaauttseeidvdeeleiyitthbhreeerrattshhteefemmdeeiaannfnaonotrrstth(heTeabuulppeppe2e)rr. ppeerrcceenntitillee bbrreeaassttmmiillkk iinnttaakkee rraatteess aanndd ccoorrrreessppoonnddiinngg bbooddyy. weights for exclusively breastfed infants (Table 2). iBBnllfooaoonddtsccaootnncc1ee8nntmtroraantttiioohnnsssawwfeteerrreebirrreetpph.oorrTttehededffmooerra33n33 affenettdaall9cc5oorrddpessracemanptilelmse, m44p0a0tienlinrffnaaeannlttssasanatdts,siiixxnfmmaonotnntbthlhossoaadtfcteeorrncbbieirrnttthhr,,aaatninoddns2244at six months of age reported by infants at 19 months after months of age reported by Fromme birth. The Fromme and colleagues mean and 95th and colleagues (Fromme, percentile (Fromme, 2010) and maternal 2010) and those predicted and infant blood those predicted by the MDH model are concentrations at six by the MDH model are ssuummmmarairizzeedd bbeellooww ffoorr PPFFOOSS ((TTaabbllee 33,, FFiigguurree 44)).. TTaabbllee 33.o RReessuullttss ooff ccoommppaarriinnf.~g MMDDHH-.m-mododeelleedd PPFFOOSS iinnffaanntt sseerruumm ccoonncceenntrtraattiioonnss ttoo FFrroommmmee eett aa.l, ((22001100)} ddaattaa., [ConcWieatnCetomanrlcaentstreiartoiuomnn |FFrroommmmeeeettala.l. 22001100| MMDDHHTTKKMMooddeell* | RRataitiooooffMMooddeellttoo MMeeaassuurreedd| AtAMbtaibteitrrtnhha9l 5-%seperurcmMeMneetaialnne|| 35 63..51 g/L ug/Llag/L Fr 3.5 pI~ailL 95th Percentile 6.1 lag/L e6t.1o I~gm/eLasured value) AAtt G6mmoonnt9th5h"ss perceMMneetaialnne|| 36.23pugg//LL (set to measured a2994g 2.9 pg/L~ value) o00.s791p8a Breas9t5th Percentile 4.9 p.g/Lb 0.78b Breastmilk AtGmont9h5"s At6months perMMceeedndtiiiaalnne|| 000...000468 upggg///LLL ((mmeeddiiaann)) | 0.038 pg/L" 0.064 g/t" 000.989505 infant - serum 95th Percentile 0.08 pg/L 0.80 Atbirth Infant - At birth serum 95% per cMMeneetaialnne|| 11 2.2 pg/L ug/L L21..a45776 pupgg//gLl#" 134 121.34 95th Percentile AtGmonths Mean|33 g/t 2W3W.7R5it6hhpeVIVJl.Atdg?/ALA#FF WWiittshhoaousutt VVdAAAFF| | W1i.2th 1W1i2th VAAF Vd AF WithoutVdAF 165 Without Vd AF At 6 95"percentie| months Mean 95th Percentile 8.1 793.7 7.9 g/t I.tg/La IJ.g/Lb nau5.45 pg/L~ 11.3 pg/Lb | ose 1.12a 0.98b Le1.65a 1.4b nRInafftaainnott@:MMataemterornnnatalhl ssseerruumm WhVAAF Without VdAF Ratio @695mopnetrhcseMMneteiaalnne 1.03 With 11361.3~ Vd AF Without 21391.9a Vd AF bF*aMTcDOkHcmtmioooddi9ee5lnItignhnccPlluduedodersecddeembmnaotatisetleerermnaoalnl1ll.oom2ss9ssovvtiaaebrrresaeesrtmumiclkc5ao5s nwwecllee1cai.sr6nobltniogontoligtng eeoxxmpfopdsoeueresedrdu.ruirinn2gg.3bloacttaotio.n. Ongoing Ongoing exposewes exposure was exmoted estimated by by back calculating a dose based on maternal serum concentration at time o/delivery, Use oof reference to this model without proper attribution to MsD prohibH ited. 1 33774499..00001199 STSTAATTEE 0077443366228644 Bunt cnenttn nd ftsecretin cutedyg he etl tu corentbyonhe ea #Breastmilk concentration and infant serum concentration calculated by multiplying the maternal serum concentration by the breastmilk gent votesot pee transferfactor and placental transferfactor, respectively. tment aoorTobe 1 aModel utilized mean breastmilk intake rate for infant (see Table 2). ot iepet neesh ple oe oe1 bMadel utilized upper percen tile breastmilk in take rate for infan t (see Table 2). PPFFOOSS ccoonncceennttrraattiioonnss wweerree oobbttaaiinneedd ffoorr 1144 iinnddiivviidduuaall iinnffaannttss ffrroomm ccoorrdd bblloooodd aanndd aatt aaggee 66 mmoonntthhss ((FFrroommmmee eett 1.2010, Figure S5 Std data cllcted at 13 months ater birth as ot used because breoieeing hod al. 20:10, Figure $5). Study data collected at :19 months after birth was not used because breastfeeding had cone dngoing pours wer uncertain, MOH ses WeSPIXD1gcrcetre an approximation of the ceased and ongoing exposures were uncertain. MDH used WebPIotDigitizer to create an approximation of the dota presented n Fre 55 and compared he spproxmate rests othe MOH model bed on per data presented in Figure $5 and compared the approximated results to the MDH model based on upper percent tak aes (UPR) and tan ream tak ats (VIR) and with ad without th nrporton percentile intake rates (UPIR) and mean breastmilk intake rates (MIR), and with and without the incorporation GFaVAF. Resaruprlestentsed in Figure. of a Vd AF. Results are presented in Figure 4. FesitgiumraetedInnfantdFOiSdsodetrapuuomicnotanscfelnotmratiigonrsepr55e,dFircotmfeomrdeeextcu.si(v2e0l1y0)b,reastfedinfos y MDH model vs, = 3~2 2 oo EHgi] s. Pr - --- mmm TTT 7% wrens UPR wa wMIR wa/sVaoAF & ,8 . AAggee ((yyrrss)) UPR preBes te es 8 0 wth an itcprVA * UPIR - upperpercentile breastmilk intake rates (see Table 2), with and without incorporating a VdAF. ne enh ote ts0 ih dbtoo g *~ MIR - mean breastmilk intake rates (see TaMe 2), with and without incorporating a Vd AF. Ota or tra essere tdFn 0 015 4 rd rn. Data points are individual serum measurements estimatedJ:rom Fromme et at, 2010 at birth and 6 months. MOH 50 evaluated s model ouput fo PFObAycomparing them to data presented i Fromme, 2010, Bod MDH also evaluated its model outputs for PFOA by comparing them to data presented in Fromme, 20:10. Blood concetaotfoFnOsR were report for 3 fetal cord samp, 0 infant t i months fer bit and 24 concentrations of PFOA were reported for 33 fetal cord samples, 40 infants at six months after birth, and 24 infants at 19 months ter bith. Th mean and 95 percent maternal and infant blood concentrations at sx infants at 19 months after birth. The mean and 95th percentile maternal and infant blood concentrations at six monthof ag reported oy Fromm and colleagues (rome, 010), and hos predced by the MDH model, months of age reported by Fromme and colleagues (Fromme, 2010), and those predicted by the MDH model, re summarizebelo of PFOA (Table 3, igure 5 are summarized below for PFOA (Table 4, Figure 5). Table. Reals of coparing MOM nade OR Infant serum concentrations o Forme al. (2010) dt. Table 4. Result~~ of comparin~ MDH-modeled PFOA infant serum concentrations to Fromme et a}. (20:10}. data. Concanaton | fromm etal 2010 MON TK Model* [Ratio of dl to Nasured Concentration Fromme et al. 2010 Voters Maternal - AtAbt ibrirtthh M Meeaann | 2.3pg/L sso arcemile | 52140 sau 95th Percentile Mmonths ean | 1740 Lier: oss: At 6 months Mean SS parcels | ug. 15h ois 95th Percentile Sess emors omc Breastmilk Aomonths Mean | Donryaecca | 0057s : At 6 months Mean 1.7 3.9 p.g/L NA {only detected in 2% of samples) MDH TK Model* 22.33 pI~gg/L 5.2 p.giL ((sseett ttoo mmeeaassuurreeddvvaalluuee)) 1.1 ~/L ~ 1.9 t~/L~ @6 months 0.057 pg/L#~ Ratio of Model to Measured 0.65 ~ 0.49b @6 months 9955t"h PPeerrcceenntitillee| 00..2255 upgg//LL. 00..1100 pI~gg//L~Lb 00.4400"~ Useofor erentoctheis model withoutproper attrtioMbOHuistproihiobitned PB) 2O 33774499..00002200 SSTTAATTEE_0077443366226655 Concomation | Fromme sta 2010 WOTR" Rati of Woe tired Concentration Fromme et al. 2010 MDH TK Model* Ratio of Model to Measured a Infant - Mon ven [17,00 2001 12 At birth Mean 1.7 pgiL 2.0 p.8iL~ 1.2 9955t"h PPeerrcceenntitillee| 33..77 plagg//LL 44.55 pI.tegniLt~ 11.22 HAE WihoutvaAr|WAAVOAE Without ViAF AAtt 66mmoonntthhss MMeeaann| 88..00uI~gg//LL 9955L"hPPerecrecnetnitillee |1199..55ppgg//LL With Vd AF 779.9m Fts/La 2211..22 Ig!/g/tL"b Without Vd AF With Vd AF 112.27 p7.g/gLa | 00.9999a 333B.1aIp!gg/Llb [11.11b 16 Without Vd AF 1.6a 11.77b aes Infant:Maternal serum to @% mons winvigr wihrvaar Ratio @6 months ean | 7 7a fi Mean 4.7 With Vd AF 7.2a Without Vd AF 11.5~ 05 parce | 50 Tn a 95Lh Percentile 5.0 11.2b 17.4b Bde dc mater or SE 48 ri Brn Go HAA BERT *MDH model included maternal loss via breastmi/k as well as ongoing exposure during lactation (using back calculated dose based on etree ttre oon maternal serum concan tration at time o[ delivery). ents emton ro ose Cue yh eT A CEN BA #Breastmilk concentration and inj~ant serum concentration calculated by multiplying the maternal serum concentration by the breostmilk ne om ean trans[er[actor and placental trans[er [actor, respectively. en et opoe oe "Model utilized mean breastmilk intake rate[or in[ant (see Table 2). or het pene mon ee ot oo, bModel utilized upper percentile intake rate/or inJont (see Table 2). 970A concentrations were obtained fom the cord blood of 8 india infaatbnitth and fr lod PFOA concentrations were obtained from the cord blood of 14 individual infants at birth and from blood ample at a6gmoneths (Frm et 3. 2010, gure 5) MON used WebPlrDigtizer to crete an samples at age 6 months (Fromme et al. 20:[0, Figure $6). MDH used WebPIotDigitizer to create an vpronmatonaf he dota and compared the sppronmatedesuts othe MOH model ess based n Upper approximation of the data and compared the approximated results to the MDH model results based on upper ppeerrcceenntitilleebbrreeaassttmmililkk iinnttaakkee rraatteess wwiitthh ((ssoolliidd lliinnee)) aanndd wwiitthhoouutt ((ddootttteedd lliinnee)) iinncclluussiioonn ooff tthhee VVdd AAFF.. Figure 5. fot FO serum concentrations for excise breastfed fons predicted by MOH model Figure 5. tn~bnt PFOA z~erum concentmtionz~ /~r e~xc/usive/y bre~z~fed in/bnts predicted by MDH'~ model VSo emaed nial oto pos rom Figure 35. Fromme t a. (2010 estim~t~d individual dot~ poklts.t}'om f:Tgure 56, Eromme e~ ~/o {20I os Fo mm mmTm TT wevans 2i5. oT ---- 5 PJetRuwNsasATsi |go - NN S---- _ gol --__--- io = - o o os: os AAggee ((yyrrss)) UP ppseeees ke es Toe2, wandwt cy OA * UPIR - upperpercendle breastmilk intake rates (see Table 2), with end without incorporating a VdAF. Soap tisto essere rr t a re rs 070 thc mos, ** MIR - mean breastmi!k intake rates (see Table 2), with and without incorporating a Vd AF. Data points are individual serum measurements estimated~rom Fromme et of, 2010 at birth and 5 months. 22.2 Comparison with empirical data rom Weogensen and colleagues (2015) 2.2,2 Comparison with empirical data from Mogensen and c:oileagues (2015) Emote or measured sear concentrations of POS and PFOA were amined na Faroese ith cohort at Estimated or measured serum concentrations of PFOS and PFOA were examined in a Faroese birth cohort at deny and at ages 11, 15, nd 60 months 0 detertmheipnacet of breasticding (Mogensen, 013 The delivery and at a~es 11, $8, and 60 months to determine the impact of breastfeedin~ (Mo~ensen, 2015). The authors imate seus concentrations a th rom maternal ss concentrations ung fekrs of 073 ond authors estimated serum concentrations at birth from maternal serum concentrations using factors of 0.72 and 0.34101 FOS and PFOA respectively, bascaloi between cord and maternal pregnancy serum 0.34 for PFOS and PFOA, respectively, based on ratios between cord and maternal pregnancy serum Comeetaions pews atmatentor same chore. Colder were essed sce or aren concentrations previously estimated for the same cohort. Children were breastfed exclusively for a median dduurraattiioonn ooff 44..55 mmoonntthhss,, ffoolllolwoweedd bbyy ppaarrttiiaall bbrreeaassttffeeeeddiinngg wwiitthh ssuupppplleemmeennttaarryy bbaabbyy ffoooodd ffoorr aa mmeeddiiaann oof4f4 [ET ------ n 21 33774499..00002211 SSTTAATTEE_0077443366226666 months. MOHused WebPlotDigtier estate serum concentrations for POS and PFOA a bith and at 11 months. MDH used WebPIotDigitizer to estimate serum concentrations for PFOS and PFOA at birth and at 11 monthosf age rom tsectries presented in Figure 1 of Mogensen etl. 2015. Th relative magnitude change months of age from trajectories presented in Figure 1 of Mogensen et el. 2015. The relative magnitude change in serum concentrations fom bith t 11 montofhags or th eleven hidren who were at last partially in serum concentrations from birth to :NL months of age for the eleven children who were at least partially breasted was compared t the magritude in relate change predicted by the MOH model (excuse breast breastfed was compared to the magnitude in relative change predicted by the MDH model (exclusive breast ffeeeeddiinngg)).. TThhee ccoommppaarriissoonnss ffoorr PPFFOOSS aanndd PPFFOOAA aarree pprreesseenntteedd bbeellooww iinn FFiigguurreess 66 aanndd 77,, rreessppeectcitivveellyy.. Figure 6 Relative increase n nant FOSsera concentration at 11 months ofage normed to concenration Figure 6. Reiedve in~re~se in infant ?FO.~ serum con,:antrat:ion ~',. .~ ~ months o[ age norm~fized ~:o ~oncent:r~don aMtogbietnhseMnOtHalmo(d20e1l5)r. esoruexcllustivesly bested infant. scimated individu! deto point from Figure 1 at birth - MDH model results ~or exclusively bteest~ed in]~ent vs~ estimated individual dote points.from fTgure i~ Imi" m zw Ezfi o Ew $Tw = : Cem om TT wwewmavaans.: eT mT _ m= mm MnRTawonVd AF mT AAggee ((ddaayyss)) UPR oper ke res Toe 2 wien out coping VA ~ UPIR upperpercentile breostmilk intake rotes (see Table 2), with and without incorporating a VdAR kan eee ite rts oe 2 ih nd wilOBI UAE ~ MIR - mean breostmflk intake rates (see Table 2), with and without incorporating o Vd AR Overs edera sen tem ogee to, 513. 1 mah clotheto concretion bh Data points are individual serum measurements estimated.from Mogensen et a!, 2015 at 21 months, relative to concentration at birth Figure 7 Reloive increase in nfont PFOA serum concentration at L1 ronthsof age normalized to concentration Figure 7o Relative increase, in infant PFOA s'erum concentretion at ~ months o~f age norm~Uized to concentration aa~t bMirrtthh -- MMDDHH mmooddeell rree.ssuult~t:ss ~foorer xecxlduussiivveelfyybbrreeaasstf~eeddininf]aennt~ vvss.~eesstt~immaat~eedd iinnddiivviidduuaol/ddoattaappoaiinn~t:ssffrroomm FFiigguurree 1.~,, Mogensenetol (2015) Mogensen e~ el. (20t.~). ~.200 ......... $f=E35PEo,w)ww . z=wo eerw esm wm em me w m 3:.Tm T jmww avouenves e i mmm T TY MIR wovar. AAggee ((ddaayyss)) UP gps rc eo te tes ule 2, wh deta pg VIA ~ UPIR - upperpercentile breastmilk intake rates (see Table 2), with and without incorporating a VdAF. meanest mabe es Tobe ih wD PI UO ~ MIR - mean breastmi/k intake rates (see Table 2), with and without incorporating a Vd eps are nlera rts temMogens to, 013 1 maths ltt o conch nttin ob Data points are individual serum measurements estimated~rom Mogensen et al, 2015 a~ 21 months, relative to concentraJon at birth Useoforreferetnotcheis modelwithout proper attrtoiMbOHustproihiboitend. 33774499..00002222 222 SSTTAATTEE 0077443366226677 2'9 22 33 CCoommppaarriissoonn wwiitthh m mooddeelliinngg ~re:.s~uJlltt.s, ff:rroomm VVeerrnneerr cDDro.rn.McMaenartrcrcVaVetrieonrnneserr,f,ooorffnttuhhreesiUUnngniivivenerfrsasinitttyys ooufpf MMtooon3ntrtyreeaaalrl,,s ddoefevvaeeglleooppaeenddd aagdedrnreaartfotuEEsxxlccyeelpl--rbboaavssieedddedmmoaoddreeallftttooceeosspttyiimmoaafttteehissseemrruoummdelo icMMtoDeDnrHHac.te.inTTonthhrseea,tVVi2oe)enrcrsnnoeefmorrprmmonououddnresedlilnsiignenlccinellucfuadtdineeostsns MM(uoPponFnOttotSee,3CCPyaaFerrOlaloAor,sssiooimmrfuuaPllgaaFettSiioao)nnn,sdsaaagnnnedddnre3rere)oqqmuuuaisitrrlyeeesrspnrooaonnlvlldyiydoettshhderreea(eegdii/rnnakppfguut:ttcssdo:a:yp1))y.) number of of this model number of to MOH conducted an amaitdoedddrdieaitlttiii.ooonnnaasll, evaluation, which compared the results 2) compound selection (PFOS, PFOA, or evaluation, which compared the results from the MDH PFHxS), and 3) from the MDH model with results produced by the Verner maternal dose (l~g/kg-day). MDH conducted model with results produced by the Verner an model. IItt sshhoouulHlddabblee vnnooettesedd utthsheaatdt ttwhhieethVVieenrrtnnheeerrVmmeorodndeeelrl uumssoeedddelddiiafffreferreetnhntet iisnnappmuutet vvaaasllutueheses fMfooDrr HsseevmveeorrdaaelllppaafrorraammPeFetOteeSrrssb::ut differ for PFOA (m(HVVoaeedlrfre-nnllieevrertosuussMueeDsddeHd33'..sw88 isyyteheelaianerrcsstthwewedhheVehrareleerfaan-ssiefrMMemDDofoHHd2e.uu3lsseeayeddrea2r2t.s.h33,etyyehesaeaarmsrMs).e)D. aHRRsaattmthhhoeeedrreMltthDhwaaHannsmaatmtottoededm emilpfpftiotieinrndggPtFttoOooiSccnhhcboaaurnntpggdoeerifattfhetheerefaVVhoeaerrlrPnfneFlerOirfAe mforodPeFlOtAo oMfD3.H8'syesaerlescfteordchoamlpf-alirfeisoofn2p.3urypeoasress, the MDH model was modified to incorporate a half-life Thfoer PbFrOeaAstomfi3l.k8 iynetaarksefroartcesomuspeadrisboynVeprunreprosaensd. colleagues (Verner, 2016) or the first 12 months were . Tccbarahleleccauusblltraamettieaeldsdktm((iIInninlttktaaakkikneeetar((akg3te//eks4grag-fdt-oe)rds=)=eux--cs00le.u.d3s31i1bv22yelxVxyeaabrggrneeeea((rsdtaadfnyedsda)c=i+oyn1lf1l5ea5s7an7.tg.)7s7u))eprsaaenn(sddVeenaarrtrneeeedssri,iimmn2ii0Tllaaa1rbr6l)iinenfomm2raaatgbhgnoenviiettf.uiurdsdMeteO1tto2Hotmthhsoeeelnemmtcheetsaeadwnn ere upper percentie intakes to repraeresaseonnabtle maximum exposure scenario. breastmilk intake rates for exclusively breastfed infants presented in Table 2 above. upper percentile intakes to represent a reasonable maximum exposure scenario. MDH selected = VMMeDrDHnHe''sr mmmooodddeeelll udussoeeesssaannnota.aggeMe-D-sspHpe'ecsicfimfiioccdaaeddljjuuwssattmsmeernnutnt ffwaaiccttthoorraffnoodrrvwvoioltluuhommueet ootfhfdeidsiVstdrtriiAbbFuuttfiiooornnc((oVVmddpaAArFFi))swwohnheeprrueeraapssostthehese. (see Section 2.12 for more information regarding the basis of the Va AF). Verner model does not. MDH's model was run with and without the Vd AF (See Section 2.1.2 for more information regarding the basis of the Vd AF). for comparison purposes. MOH conducted separate model uns for POS and PFOA using the draft Verner model with 1,000 erations and 2aM0mmD1aH6atteUecrroSnnnEaadlPluAddcooHtessedeealoostfefhp00A.a.d00rv0a0i3t3se00o88rmyipovggda/e/lkklugger--u)ddnaaasyyn..fdoTTrahheeP9F5mmO"aSatpteeaerrnrncndeaanlPltFdidOlooessAeewuawwstaiaenssrg bbithaantessaeekddderaoornfnattaaVe ewwoarfant0teee.rrr0m4cc4ooonnd/ceckeelngnwttrdir.taahtTtiiho1oen,n0s0ooe0ffs0iat.e00m.r70ea7 tupiioggn/np/LLust((satthnhede forwaterconcentration and 2016 USEPA Health Advisory for water concentration and adult water intake rates were used in model uns based on the MDH value) and a 95~h percentile water intake rate of 0.044 L/kg-d. These adult water intake rates were used in model runs based on the MDH model, same inputs model. TTEhhxeepoMMsuODrHHe FmmaocodtdeoerllswwHaaassnrrduubnnooffookrr paarnnoviininffdaaennsttbeerxxeccallsuutssmiiivvleelklyyibbnrtreeaakasesttrffeaetddesffooarnoodnnbeeoyydeeyaarwr,,ettihhgeehtddsuurfraoarttiioeoxnnclffuoosrriwvwehhliiyccbhhrttehhaeestUUfeSSdEEPPinAAfants. TTmEhohxeneptorrhsee,ussurue6llttsmsFaooocfnftottthrhhsee,3Hmmomaodondnedetlblhorr,ouuknnassnpdraaonn1vdd2idaamesoccnoobmmtrphepaaartsriiitmssmeooi-nnlkpoooiifnfntrrtaeesksseuaulrlrtteaiintnpeggrseiinsnaffenaandnntttebdssoeedbrryueumlwmoewccigooinhnnctcTseeanfbntoltrrreaaett5xiioco/nlnusssFiaavtiteb8blgyiir(tbtuhPhr,Fe,rOa11Sesmm)tfoeoandnnttdhihn,T,faa33bnltes:. 6m/ofingthur,e69m(oPnFOthA,).9 month, and 12 month time-points are presented below in Table 5/Figure 8 (PFOS) and Table 6/Figure 9 (PFOA). TTraaatbbelJsee) 55v.~s.CCVooemmrpnpeaarrrmisioosdnoeonlff MMreDsDuHHltsPP.FFOOSS mmooddeell rreessuullttss fofor eexxcclluussiivveelIvy bbrreeaassttffeedd iinnffaanntt {uussiinngguuppppeerr ppeerrcceenntitillee iinnttaakkee rates) vs, Verner model results ee [5[ws[om [REa] I -- Serum ConcentC rationT (4/1)-- [mith [iMon |3Mon | Mon | 9Mon |12Mon| Model Birth Predicted Serum Concentration (~g/L) 1 Mort 3 Mort 6 Mort 9 Mort 12 Mon Verner 50 885% 200 56 21 Verner 50th & 95th 11.0 14.8 20.0 25.6 29.1 30.5 percentile MDHmodel 160 256 355 505 65 76 M DH model (roto vs. emer ss| (063) 063) (064) 089) ) ) (ratio vs. Verner 95th sMiOteH)modelwith Vd| 16.0 302 530 771 EX Ts MDH model with Vd 24.5 16.0 (0. 65) 16.0 35.9 22.6 (0.63) 30.2 55.8 35.5 (0.64) 53.0 78.3 50.5 (0.64) 77.1 89.3 62.5 (0.70) 95.5 95.1 73.6 (0. 77) 111.9 A((srrFieodetro)oemvv.so. vVVeeerdrnneerr 55 95~h (0.65) (0.84) (0.95) (0.98) (1.1) (1.2) Useofor reference to this model without proper attribution toMOH isprohibited. 33774499..00002233 23 23 STSTAATTEE 0077443366226688 IFFingrutreeer88a.teCCsoo)mmpvpsa.orirVisseoornnneoorf)m~ oMMdODeKHl PPeRFsOOtS.~smm.ooddeell ess or results.fo~ yr2..yr exclusively exctus~'vety breasted breos~]~,d infnt #~f~nt (singupper (using u;~per percent int~ke ro~,.~) vs, V~rner model 53 ooo ii .S~ ....... = _ = .......................................... ....................................... ier ese prmremereer ~......... ................................ .................................................................................................. .................................................. snot Theserum concentrations stated by the MDH model a the ary tm:pols were between the 50% and 95 The serum concentrations estimated by the MDH model at the early time-points were between the 50th and 95:h percent alu generatedb th Verner mocel oth models se sla hl ie alues for PROS. However, percentile values generated by the Verner model. Both models used similar half-life values for PFOS. However, thre were diferences in several other parameters used within each model. Fo example, MOH sed higher there were differences in several other parameters used within each model. For example, MDH used higher breastmtiolkk ates and ale ge peciic Va AF, whereas the Veer model used reat take rates breastmilk intake rates and applied age-specific Vd AFs, whereas the Verner model used breastmilk intake rates that were simitolmeaarn intake rates and id not appalVyA AF. that were similar to mean intake rates and did not apply a Vd AF. MOH perfoarsmierd comparison to the Verner model for PFOA, shown below in Table and Figure, MDH performed a similar comparison to the Verner model for PFOA, shown below in Table 6 and Figure 9. Tabl6e. Comparison of MOH PFOA model ess for exclusively breastfed infnt (sing sperpercentile ake Table 6. Comparison of MDH PFOA model results for exclusively breastfed infant (using upper percentile intake ratesv)i. Vernermodel results. rates} vs. Verner model results. Wider Bith |iMon|r3Ma oSenri|d CoGncMrtae atinon| elM) on |i2Mon| Model Birth 1 Mon Predicted Serum Concentration (i~/L) 3 Mort 6 Mort 9 Mort 12 Mon VVeerrnneerr 50" 50th && 2211.44 5500.66 8877..11 111221.1 111199.77 11177..66 9955"thppeercrceentnitillee. WOH model G3yrtal | 194 | 387 71s Ta | oi MDH model [2.3yrt~/2] i os vemer 5ste oi | 02 030 039 7) (vs. Verner 95th %tile) WOH modelwith Bs | ee | ms | wma | awa | am2 M DH model with sayin 3.8 yr tt/2 (ovenerosisi rs | wen | ps0 | ese | wey | om (vs, Verner 95t~ %tile) WOH mowditheValAF| 19.1 Tor | teks | sz | 19a MDH model with Vd AF removed removed os vem95 escre 0s | 030 os oss) oe (vs, Verner 95t~ %tile) WOHmodelwth38y is | 1018 | 2010 | zea | 309 | sas MDH model with 3.8 yr hat+VdeAF half-life + Vd AF removed os | om | es | ew | an | wm removed fo ver5nie (vs, Verner 95th %tile) 4422.00 19.1 (0.45) 31.5 (0.75) 19.1 (0.45) 31.5 (0. 75) 113355.66 38.7 (0.29) 64.4 (0.47) 61.3 (0.45) 101.8 (0. 75) 223399.99 71.9 (0.30) 120.9 (0.50) 119.7 (0.50) 201.0 (0.84) 228888..00 100.3 (0.35) 171.1 (0.59) 164.9 (0.57) 281.4 (0.98) 229900,66 114.1 (0.39) 197.4 (0,68) 185.2 (0,54) 320.9 (1.1) 228899.66 121.1 (0.42) 212.2 (0,73) 194.4 (0,57) 341.5 (1.18) Useofor reference to this modelwithoutproper attribution to MiO sprobiH bited. 33774499..00002244 224 STATE o7e36260 STATE 07436269 iFFnigtruakreee8r9.esCCtooommsp.paorirVisseoornnneoor)f~ rMMoODdeKHl PPeFFsOOtAAs.mrnooddee~l~ results r~,su/ts for.for 1si ..yr exclusively exciusiw~/y breastfed fon using upper percent int~'~ke ro~e.~) vs, V~rner modd pe a i:iH . L ~. oTemem a erm i [oT ---- o fpr == snr 0 Age months) MOH nd Verner models used diferent aie values for POA (MDH used 2.3 years whereas Verner used 38 MDH and Verner models used different half-life values for PFOA (MDH used 2.3 years whereas Verner used 3.8 Vers) When he MOH made was run usin a hlof 3.8 yeas th precicied serum concentratiofnesl years). When the MDH model was run using a half-life of 3.8 years, the predicted serum concentrations fell bbeettwweeeenn VVeerrnneerr''ss 5500t"" aanndd 9955tTMh ppeerrcceennttiillee eessttiimmaatteess.. WWhheenn tthhee VVdd AAFF ppaarraammeetteerr wwaass rreemmoovveedd ffrroomm tthhee MMODHH. model, the predicted PFOA sri concentrations fo ter me pits ceeded the 95 percent als model, the predicted PFOA serum concentrations for later time points exceeded the 95th percentile values predicted by the Verner model. predicted by the Verner model. Comparisons between empirical data as well as modeling result from Verner and MDH mode resus were Comparisons between empirical data as well as modeling results from Verner and MDH model results were Within factorof 3 forall me points when comparable Rt fe aes were ized. within a factor of 2 for all time points when comparable half-life values were utilized. 2.3 Expansion of Model to Steady-State Duration 2.3 Expan.qor~ of Model to Steady-State Du~-aqon Due tothe long hlf ves of PFOS and PFOA, ary fe exposures wil tke many years be lined rom the Due to the long half-lives of PFOS and PFOA, early life exposures will take many years to be eliminated from the body. Aer encouraging stsware obtained fom infil estinogf the del the modeling ration was body. After encouraging results were obtained from initial testing of the model, the modeling duration was evtended olong term exposure. MDH sought Input rom se aera experts regarding the asequacy (ot extended to long-term exposure. MDH sought input from six external experts regarding the adequacy (e.g., fit for purpose) of the model and how to enhance accuracy of seu predictions. Ech reviewer submitted for purpose) of the model and how to enhance accuracy of serum predictions. Each reviewer submitted prlminary comment regarding he draft mode nd paripated in 3webased meting discussion, MOH preliminary comments regarding the draft model and participated in a web-based meeting discussion. MDH Tesponded to comments and made improvements the model baonsreeviedws nau. Reviewers were not responded to comments and made improvements to the model based on reviewer input. Reviewers were not explicitly asked o endorse or approve ofthe final made. See Append fo biographical informationom exch of explicitly asked to endorse or approve of the final model. See Appendix II for biographical information on each of th reviewers the reviewers. The expanded model was desighedto predict serum concentration profes or two exposure scenarios: )n The expanded model was designed to predict serum concentration profiles for two exposure scenarios: 1) an infant fed excusivly ith formal reconstituted with contaminated water starattibinrcgh. allowed by a infant fed exclusively with formula reconstituted with contaminated water starting at birth, followed by a Teoftdkieng contaminated wate (Fre 10 an 2) a nant ocusely beastie for 12 months, lifetime of drinking contaminated water (Figure :10); and 2) an infant exclusively breastfed for :12 months, ffoolllolwoweedd bbyy aa lliifefetitmimee ooff ddrriinnkkiinngg ccoonnttaammiinnaatteedd wwaatteerr ((FFiigguurree 111:1)).. IInn bbootthh sscceennaarriiooss,, tthhee ssiimmuullaatteedd iinnddiivviidduuaallss began fe with apr existing body burden through lacentl transit. Upper percentile make rtes were used began life with a pre-existing body burden through placental transfer. Upper percentile intake rates were used forthbreastfed fant scenario and 35 percent take fotes were used for tet intake 0 sma an AVE for the breastfed infant scenario and 95th percentile intake rates were used for water intake to simulate an RM E india individual. Use ofr reference to this model without proper tribution to MiOprohiH bited. Use of? or re[erence to this model without proper ottribudon to MDH is prohib#ed, 33774499..00002255 25 STATE orsse2r0 STATE 07436270 Figure 10. Scenario #1 schem-Eaxcltusiivecly FormalasFed Infant. Eeor] Maternal Serum Concentration steady sate) Placental| Transfer Placental Transfer Neonatal Serum Concentration bith) Formula FFeedd Offspring Serum Concentration bith osteacy-ste) CClleeaarraannccee Use oof reference to this model without proper attribution to MsD prohibH ited. 33774499..00002266 226% STATE 07436271 STATE 07436271 aL Maternal Serum CClleeaarraannccee | Placental Transfer `Concentration (birth) BBrreeaassttffeeeeddiinngg. LC Concentration CClleeaarraannccee (birth to 1 yr) ee Offspring Serum (>1yrtosteady-state) CClleeaarraannccee As noted above, infants born to exposed mothers will be born with an existing body burden resulting from maternal exposures only. Placental transfer factors of 0.42 and 0.87 were used for PFOS and PFOA, respectively, to calculate the initial infant serum concentration from the maternal serum concentration (see Section 2.1.3.) TThhee mmaatteerrnnaall sseerruumm ccoonncceennttrraattiioonnss wweerree aassssuummeedd ttoo bbee aatt sstteeaaddyy--ssttaattee aanndd EEqquuaattiioonn 33 ((rreeppeeaatteedd bbeellooww,, sseeee Section 2.0 for additional information) was used to calculate the steady-state serum concentration. mma (gag) x Water concentrarion (48) x hme mfl Water Intake Rate Clarence Rote 1) Serum Concentration (~-) = k~Tf~ x Water Concentration L Clearance Rate(k~Ud~) x 1000/2~7 I Clearance rates of 0.000081 and 0.00014 L/kg-d for PFOS and PFOA, respectively (see Section 2.0), were applied to the equation above. A time-weighted average (95th percentile) water intake rate of 0.047 L/kg-d, calculated from birth to 30-35 years of age, was used as the water intake rate. An iterative approach was engaged to identify the water concentration that would result in maternal and offspring serum concentrations that would never exceed a level of concern identified by MDH. See Section 3 below for results. metas tdeenen The input values for breastmilk partitioning, breastmilk intake rate, body weight, elimination (half-life), and vvoolluummee ooff ddiissttrriibbuuttiioonn ((VVdd)) wweerree tthhee ssaammee aass tthhoossee pprreesseenntteedd aabboovvee iinn SSeeccttiioonn 22..22.. AA ccoommpplleettee ssuummmmaarryy ooff model parameters is provided below in Table 8. staf hse het rer tn OH " Use of or refere~ce to this model without proper attribution to MDH is prohibited. 27 33774499..00002277 SSTTAATTEE_0077443366227722 22.,33.,11 AAddddititiioonnaall MMooddse!l IInnppuuttss 23.1.1 Duratiofn Breastfeeding 2B~r3e~a'1s.t:ifDeeudraitnJgorh~aosfmBarneyasctfleeeardlinyi~established health benefit for infants, children, and mothers andisa key. stratotimeprgovye publi health. The American Academy of Pediatrics (AAP) recommends thatinfantsbe Breastfeeding has many clearly established health benefits for infants, children, and mothers and is a key strategy to improve public health. The American Academy of Pediatrics (AAP) recommends that infants be eexxcclluussiivveellyy bbrreeaassttffeedd ffoorr aabboouutt tthhee ffiirsrtst66 mmoonntthhss wwiitthh ccoonnttiinnuueedd bbrreeaassttffeeeeddiinngg aalloonnggssiiddee iinnttrroodduuccttiioonn ooff 6ccoo6mmppeplrleecmemneetnntotafarrmyyotffohoooeddrsssfoionrrMaaittnllneeeaassstot ti1ayyereaearpr.o.rAAtcccbcororerdadsiintnglgctteooditthnhgeea22t00s11i66x mBBorrneeatashststff,eeeewddiitinnhgg31RR.4eepppoeorrrttcCCeanarrtdd e((CxCcDOlCCu,s, i22v00e11l6y6)),, nneeaarlryly. b6r6eapsetrfceeednitnogf, mTohtehepresrcinenMt ibnrneeassotftaeerdeipnogrdt rborpepaesdtfeteod4in1g5aatt stixwemlvoentmhosn,twhsit.h M31D.4H pseelrceectnetdeaxncluesxcivleulsyive breastfeeding duration of one year for the RME scenario. Upper percentile breastmilk intake rates from Table: breastfeeding. The percent breastfeeding dropped to 41% at twelve months. MDH selected an exclusive breastfeeding duration of one year for the RME scenario. Upper percentile breastmilk intake rates from Table 1155--11 ooff tthhee UUSSEEPPAA 22001111 EExxppoossuurree FFaaccttoorrss HHaannddbbooookk ((sseeee TTaabbllee 22iinn SSeeccttiioonn 22..114.4abaobvovee)) wweerree uusseedd ffrroomm bbiirrtthh Usupppecttioofi11c22wmmaotoennrtthhissnotoafkfaeaggeae.t.tAAhtte 119225mmpooenrtcnhesnottofiflhaeagg(eses,,eefflluTuiaiddbliinentta7akkbeeelwwoaawss)sswwwaiisttcchuheseedddffrtrohomrmoubbgrrehateshtaemrsilktettooomfwswialitatfleet.erkr,, aanndd aann aaggee-- specific water intake at the 95th percentile (see Table 7 below) was used through the rest of life. 23.12 2.3.1/).. W Vaatteerr lIrnllt:aakkee RRaattee rNNaeepwiwdbbloyorrwnnissthddeearrgiievv,eeaaanlll,d, oobrrynnaeegaaerrllsyyeaavllell,noofafrttehheneieirranrunltuyrtirttihtiieoonnsarfmrooemmaslliiqtquhuoiiddssse..oLLfiiqqauudiuidldtsiin.nttaMakkDeeHrraamtteeessthppoeerdruounlniotigtbyboo(ddMyyinwwneeeisiggohhtttaffaallll Department rapidly with Department of Health (MDH), 2008) for deriving health-based water guidance uses age specific 95 percentile age, and by age seven are nearly the same as those of adults. MDH methodology (Minnesota of Health (MDH), 2008) for deriving health-based water guidance uses age specific 95th percentile wwaraaetteerrerpiilnnittcaaakkteeedrraaittneeTss,a, bwwlhheiicc7hhbeaalrroeewff.oouTunhndedsiienn wTTaaabtbleleer33i--n11taookffeUUrSSaEtEPePsAA'w'sser22e0011u11seEEdxxpp1o)ossfuuorrreeiFFnafaaccntttoosrrssexHHcalaunnsddibbvoeolooykkf((oEErPPmAuAl22a00-11f1e1)d) aaannnddd 2) forare for breastfed infants following oneyearof exclusive breastfeeding. The information in EPA's Table 3-1 also replicated in Table 7 below. These water intake rates were used 1) for infants exclusively formula-fed and breastfed infants following one year of exclusive breastfeeding. The information in EPA's Table 3-1 also 2) pprroovviiddeess ddaattaa tthhaatt aalllloowwss ffoorr ccaallccuullaattiioonn ooff ccoorrrreessppoonnddiinngg bbooddyy wweeiigghhttss ffoorrtthhee ccoorrrreessppoonnddiinngg aaggee ggrroouupp.. TTaabbllee 77.. DDrriinnkkiinngg wwaatteerr iinnggeesstt:iioonn rraa~t:eess f[oorr ccoonnssuummeerrss--oonnllyy aanndd ccaallccuullaatteedd ccoorrrreessppoonnddiinngg bbooddyy wweeiigghhttss (BW) | rem om TR [Wen Mean [osperc95et" nPertceintiele | Age Group mL/day day. mL/kgday BW kg)" Calculated BW mL/day day mL/kgday | swe) Calculated BW (~) [c<T1mmoonntthh Tao 470 | 113377 | 36 | e8s58s | a23w8 | 336.6 | [Tt1too<<33mmoonntthn [ss55a2 |m1919 | 446.6 | 1005533 | a2s85s | 337.7 | [Bt3 otoc<o6momnotnthhss s5s56 | a800 | s7o.0 | i11m71i |1173 | 66s.8 | [bt6Twotoo<<<t21oy2emamoronsntthhss | 446677 | 525373 | 81184 | w18a1034r7 |171s029 | 81819.95 | 21tto0<<32yeyeaarrss 308 227 1113.74 o81923 675 1141..97 23tto0<<63yeyeaarrss 8356 226 1138.77 599192 6522 1145.27 6to<1lyers 3 to < 6 years 6 to < 11 years si 17 301 1404 a7 299 382 21 511 17 18.2 30.1 999 52 1404 47 19.2 29.9 1111ttoo<< 1166 yyeeaarrss 663377 112 5533.11 19197766 335 5566.55 1166tto0 << 1188 yyeeaarrss 70022 1100 7700.22 18183833 3300 6622.88 [B1o8 <toa<i21yyeeaarss [818616 | 11 | a2 74.2 |o2s81s8 |336 | 7788.33 | leo>an2v1ayndeeaSr5ss1 percenat|kse awts12t r27 e |rom Tn o1e166 31, |USEPA 27011766.77 | 2 3092 | a42 | 7s 73.6 | ntlao) Mean and *(mL/day) + (m/v 8) 95th percentile + {mL/kg-day) intake rates taken from Table 3-1, USEPA 2011 22..44 Summary Sur]~lr~]al oOff: MMODHH MMooddeell PPaarraammeetteerrss bSSaeesrriuusmomfcctoohnnecceRIneDt.rnatAtinornaRsIatDarireieotanthhnseebebsetesistmtmametteeortfriiccaffodorariddleettoeerrarmlmidinnoiisnneggtiinonttteehrrennaahlluddmooassneessfpfoooprrulPPaFFtOOiAAonaa(nniddncPPlFFuOOdiSSngaannsddensssieetrrivvveeedd aasththee. subgroups) basis of the subgroups) thats likely RfD. An RfD that is likely tois to be without an estimate be without anof an appreciable risk a daily oral dose appreciable risk ofto of deleterious the human deleterious effects. It is important tha total population (including sensitive effects. It is important that total Use oof reference to this model without proper attribution to MsD prohibH ited. 33774499..00002288 228% STSTAATTEE 0077443366227733 eexxppoossuurree ffrroomm aallll ssoouurrcceess,, iinncclluuddiinngg ppootteennttiiaall iinnggeessttiioonnooffddrriinnkkiinnggwwaatteerr ccoonnttaaiinniinngg PPFFOOSS oorr PPFFOOAA,, ddooeess nnoott drreeessvuuelllttoiinpnessdeerrbuuymmMccDooHnnccpeernnetdtrriaactttiisoonnssserhhuiigmghhceeorrnttchheaannntrttahhteeiossneesrruaumtmvccaoornincoceuensntdtrreaavtteiioolnnopaamssessnootcciaiaalttesedtdawwgieitsthhottvhheeer RaRIfpDDe..TrTshhoeen'TTsKKfmmeotodidemelel rdeesvueltloipngedfrboymMacDoHnsptraendticPtsFsOeAruomr PcFoOnSceconntrcaetniotnrastaiot nvainriodurisnkdienvgewloatpemr,enitnacllusdtaignegsthoevesrearupmercsoonnc'esnltifreattimioen an individual is born with 3s a result of maternal exposure. resulting from a constant PFOA or PFOS concentration in individual is born with as a result of maternal exposure. drinking water, including the serum concentration an In order to ensure that health-based water guidance values for PFOS and PFOA are adequately protective for all IelIinxifeceolssrudttsaaieggvreeestlso,y, iwiennincctsllhuuudrdfeiionnrtgghmamumltooarhreeereahhclitoihggn-hhsbltlyayisteeeuxxtdppeoowdssaweeitddetrhiinngcffauaoninndtttassa,,nmcttiwewnoovaatRRleuMMdeEsEwassfotcceerenrnPaaFsrrtOiiaooSrsstaiwwnnegedrraeePtFeebOvivraAatllhauu,araeftteeoadldd:l:eo11wq))eudaaabnnteyiilnnyaffalapinnrftotetffteeeicddmtieveoffor all drinking contaminated water; and 2) an infantexclusively exclusively with formula reconstituted with contaminated drinking contaminated water; and 2) an infant exclusively breastfed for 12 months, followedby water starting at birth, followed by a breastfed for 12 months, followed by alifetime of lifetime of a lifetime of ddrriinnkkiinngg ccoonnttaammiinnaatteedd wwaateter.r. BBootthh sscceennaarriiooss bbeeggaann fliiffee wwiitthh aapprere--eexxiissttiinngg bbooddyy bbuurrddeenn tthhrroouugghh ppllaacceennttaall ttrraannssffeerr.. IInn parameters oordrer ttdooaacechhiieervvee aann RRMMEE are used, as described in ssTcceenanaarrib8ioob,,elaalommewi.ixxttuurree ooff ecennttrraal aanndd uuppppeerr ppeerrcceenntitillee vvaalluueess ffoorr tthhee vvaarriioouuss parameters are used, as described in Table 8 below. aMMnDDdHHdeccpaararereftfuumllellyyntssaeellleepccottleeidcdym.moAoddefelolrppmaaarlraaimmne-etdteeerrpsst,,hbbsaaenssseeiddtioovnintytthhaeenabbleeyssstitsaavovafaiitllahabbellemeossdcceiielen,nccweeh,,ieecxxhtteewrronnuaalll dppeepeerrorvrrieedvveiieeawwddcciootimmomnmeaneltnsts,, iannfdordmeaptairotnmreengtaarldpinoglicmyo.dAelforpmerafloirnm-adnecpet,h hsaesnnsoittivibtyeeannacloysnidsuocftethdeatmtohdiselt,iwmeh.icBhasweoduoldn ptrhoevpideerfaodrdmitaioncnealof tinhfeormmodaetlio,nMrDegHarndoitnegsmthoadtewl apteerrfocromnacenncter,athiaosnn,odturbaeteinoncoonfdburceatesdtfaeetdtihnisg,timaned. bBraesaesdtmoinlkthientpaekerforarmteasnacree othfe most sensitive parameters. the model, MDH notes that most sensitive parameters. water concentration, duration of breastfeeding, and breastmilk intake rates are the VVeerrnneerr aanndd ccoolllleeaagguueess ((22001166))ccoonndudcteudacagtglloeobbadall sseennsistitiivviittyy aannaallyyssiiss ooff tthhee VVeerrnneerr mmooddeell aanndd ffoouunndd tthhaatt mdduoursraatttiisooennnsooiftfibbvrreeeapasastrtfafeemeeeddtieinnrggs,., bbrreeaassttmmiillkk iinnttaakkee rraatteess,, aanndd mmaatteerrnnaall sseerruummy//bbrreeaassttmmiillkk ppaarrttiittioionniinngg wweerree aammoonngg tthhee most sensitive parameters. Use oof reference to this model without proper attribution to MDHs prohibited. 33774499..00002299 229 STATE 07436274 STATE 07436274 Tal8e Suramaorf MOH mac out pater Table 8, Summary of MDH model input parameters aie ConnearteConsan Model Parameter FOS Sve9n7 | Gen2erbad Description Some aes do EPR Half-life (t) Vaai|oaFFvOOOvAeTr (L#0 oo[ncBpg aunpcdhpeusriitrn2de0r0emd reCCsoomwevassel||SSSVeicaoaerevmhomyrbeeeeananVngdpbneb.sngydlcdcodesaowbomicyfsofn2Lpeos3srsoi1eu1td5cr0so3siaSrne.cosrgposPe.cOetLMRoe,c3fskwoooVifghrsevrcieaTrs.rhgaiMenheegh.t Volume of Distribution wa Hono ine mesma) |201 30d US20E16.Conwitahcnrti (Vd) aresramen |0Ta-2 Fon 961 Eoid eeavsoarfedantwinosno.o hr Br Vd Al~e Adjustment Facartiass, Pont 21 |constmniseret Content er wip honads.Thesora Factor (Vd AF) Coram) |jSCiPSstoi01iiavmmro1a0emenns0-r1i110r5 [CWuoeons ve Se | meCCsoomnnka) C|SFoCnScroreteutaaoredninmsonHaemsatkvkrsaprdeoetceatttr0hdoefrcrurolomtsocetonif,tsatnorffomeohuarnn4esrhch9.scsak6oTbnfhnSocohswpennvseatidnr7rsfs0ir5weonfh3nee0snd Clearance Rate (CR) Moers |CHrFrroroaotseAohea0mcseaotosdehoUdsRe)sEdSte|||wCeecdiobkyotiUSoCeecPedRIaDnIdE ||me(asUpehpdeaarkn)||sRSnagmrenssp1aeW ctbfrome a4Tthoannrtdmhe yeastaemeh. ailrens waas Ased Maternal Serum Cancun Semel Gaf) | Gaon) don propre wae dr vl Her Concentration Gad OR cle ae | Tero |maprt sdbndndlr"tchrngerteowlheru na0n<a tc Newborn Serum CFoFHmioeerrmnaiatstaeni(rnUs5eoxfo|||r mofanernawtenrnetoa1rrom0fbi1lwgeiipimoreoetodednde|||witmhCoGoumtUuepdpreeaoreanpdra||AHauponpodeudnpnpdrearnfcolehioMnmcOgrNpttrsdplratootitonsviedro.onawliahe.3e3otnri.Sno0 Concentration Value(s) Used PFOS 5.4 years (1,971 days) PFOA 2.3 Years (840 days) PFOS 0.23 L/k8 PFOA 0.17 L/k8 0-1 day - 2.4 1 - 30 days - 2.1 1 - 3 mons - 1.7 3-6 mons - 1.6 6-12 mons- 1.5 1 - 3 yrs - 1.4 3-5 yrs - 1.1 5-10 yrs - 1.2 >10 yrs - 1.0 Calculated CR = Vd (L/kg) x (Ln2/half-ti[e, days) PFOS 0.00008 L/kl~-d PFOA 0.00014 L/ks-d Calculated steady-state serum level (I~8/L) Calculated Maternal serum concentration (f~g/L) x Placental Transfer Factor Source Olsen et al. 2007 based on occupational workers Bartell et al. 2010 based on population exposed via drinkin8 water USEPA 2016, Hans et al. 2012 Friis-Hansen 1961 (also consistent with Felter et al. 2015) Calculated value. Same value calculated and used by USEPA 2016 Calculated (see Equation 3) MDH calculated value. Transfer Factor based on averas;e of reported mean maternal serum Value Type/ Description Central (mean valuet Central (mean value) Central (mean value) Central (based on mean half-life) Upper Elements of Central and Upper (based on mean transfer Confidence/Uncertainty Comment Same half-life values used by USEPA in their evaluations. Very limited data for PFOS. Several publications resardin8 PFOA, with averase halflife ransin8 from 2.3 to 3.8 years. Lack of accountin8 for backsround exposures can over estimate half-life. In the absence of life-stase specific information, the same half-life was used across all life stases. This remains an area of uncertainty. Same Vd used by Loccisano et al. 2013, Verner et al. 2016, and USEPA 2016. Consistent with extracellular fluid as volume of distribution. Early life stal~es are known to have higher body water content per unit weisht than adults. The adjustment factor is desisned to account for this known difference between infants and adults, in the context of PFOS and PFOA kinetic determinations for Vd. This is an area of uncertainty since the precise nature of the Vd is not known. However, removal of the Vd AF appears to result in overestimation of serum concentrations when compared to empirical data. Based on half-life information. In the absence of lifestase specific information the same half-life was used across all life stages. This remains an area of uncertainty. Assumes mother is at steady-state at time of delivery based on proposed water 8uidance level. Maternal exposure based on 95th percentile water ingestion rate. Limited individual matchin~ maternal serum to cord blood matchin8 pair data are available. Mean, median and upper percentile ratios are within a factor of 2. See Appendix I for more information. Use of or reference to th~s mode4 w]thout proper #~tHbudon to MDH is proh]bi~edo 3O 33774499..00003300 STATEgrazers STATE 07436275 Mode parameter | Valse ned source Va Toes Contrary Comment Model Parameter Value(s) Used Source stor ros OR [coos |Derscpnton (0.46 for PFOS and 0.87 orion, ecrepensu) -- for PFOA) to cord blood ratios (see Appendix I) wei es WO oe | Gamerosf | Ged ode ent r Breastmilk Coenen |remteran |TaterFcrowed | Cm | ntl ahmca opporparmts Concentration fUCeDSopaopecolnretpmnrrerrnaoonnseorwan||||| ooTmoennvemeAeeeHmnrpmerEornloieAattesesd||||moniewUwpetpmsserorene|| eE mowrmonairof 2n SxAbr or re Breastmilk Intake Rate nehfor wey | 010 wor (BIR) Calculated Maternal serum concentration (l~g/L) x Breastmilk Transfer Factor (0.013 for Pros and 0.052 for PFOA) Upper percentile values for exclusively breastfed infants (mL/kg-d) MDH calculated value. Transfer Factor based on average of reported mean maternal serum to breastmilk concentration ratios (see Appendix I) Table 15-I (USEPA 201i) Value Type/ Description factor x maternal serum) Elements of Central and Upper (based on mean transfer factor x maternal serum) Upper Confidence/Uncertainty Comment Limited individual serum to breastmilk data are available. Mean, median and upper percentile ratios are within a factor of 2. See Appendix I for more information. Use of upper percentile intakes is MDH policy. Birth to <2 mort-220 1 to < 3 mort- 190 iyecwoof nkaw [rSeHrAcwoTnibe| Upper | E mbes gcd coemeoe GeaeTcRdsnege Breastfeeding Duration 3 to< 6 mort- 150 6to< 12 mort- 130 I year of exclusive breastfeeding Terps [ onemimespoT nte aHenedheeoedmvrnognstmtottprhetseoaepprercempe1ohto,cserkperecenteCiond a Water Intake Rate pCSoemhiueemeesvrienoms= J emssewionfagcmnaheayreimoewn0 eeedo3w47emssAw.et (WIR) Age-specific 95th percentile values consumers only (mL/kg-d] Birth to <1 mon - 238 Selected by MDH to represent reasonable maximum exposure scenario. Table 3-i (USEPA 2011) Upper Upper CDC 2016 Minnesota specific data: 53.9 and 31.4% of mothers reported exclusively breastfeeding at three and six months. The percent reporting breastfeeding at twelve months dropped to 41%, the percent exclusively breastfeeding at this time point was not reported. Age-specific intakes used in model. For calculation of maternal serum concentration at time of delivery a time-weighted average water intake rate was calculated from birth to 30-35 years of age, resulting in a water intake rate of 47 mL/kg-d. 1 to < 3 mon- 285 3 to < 6 mon- 173 Soin13 6to< 12 mort- 129 Socom i to < 2yr- 75 Seahe 2 to < 3 yr-62 3 to < 6yrs-52 fei 6to< 11yrs-47 11 to < se 16yrs-35 freee thsmodel hutpape aun to MON sprob ic a 31 33774499..00003311 sare onaezrs STATE 07436276 E r| r B fier mer -- in Model Parameter Value{s) Used 16 to < 18 yrs-30 18 to < 21yrs- 36 Source Value Type/ Description Confidence/Uncertainty Comment _>21 yrs - 42 Body Weight Age specific values Table 3-1 for water Consistent calculated from intake ingestion exposure and with Central volume (mL/day) and Table 15-1 for (Mean) values intake rate (mL/kg-d). breastmilk ingestion exposure EsoonR 3749.0032 a32 STATE 07436277 3.0 DDeerriivvaattiioonn ooff HHeeaalltthh--BBaasseedd W Waatteerr GGuuiiddaannccee VVaalluueess Three components are used in th derivation of heal based water guidance values: 1) ameasure of tricity, Three components are used in the derivation of health-based water guidance values: 1) a measure of toxicity, ((RRIfDD));; 22)) rreellaattiivvee ssoouurrccee ccoonnttrriibbuuttiioonn ttoo aappppoorrttiioonn aa ffrraaccttiioonn ooff tthhee RRIfDD ttoo wwaatteerr iinnggeessttiioonn;; aanndd 33)) aa mmeeaassuurree ooff exposure, the water/breastrilk intake rte. Selctionof th RD and RC ae briefly described th folowing exposure, the water/breastmilk intake rate. Selection of the RfD and RSC are briefly described in the following Section. Water and breastmilk intake rates ar described in Sections 23.1.2 and 2.14, respectively. section. Water and breastmilk intake rates are described in Sections 2.3.1.2 and 2.1.4, respectively. 33o.:1L RReeffeerreennccee DDoosseess aanndd CCoorrrreessppoonnddiinn[~g SSeerruumm CCoonncceentnrtraattiioonnss MOH conducted an expeadniftoceusded re-evaluation ofthe avaliable toiclogcl information, eying n MDH conducted an expedited and focused re-evaluation of the available toxicological information, relyin~ in port on USEPA' 2016 health assessment docurents (USEPA, 20163) (USEPA, 20160). Several ey stds (e3. part on USEPA's 2016 health assessment documents ((USEPA, 2016a) (USEPA, 2016c)). Several key studies (e.g., Candidates or forming the basis of an RIO) were identified for PFOS and PFOA. candidates for forming the basis of an RfD) were identified for PFOS and PFOA. FFoorr PPFFOOSS,, tthhee sseennssiittiivvee hheeaalltthh eennddppooiinnttss iinncclluuddeedd ddeevveellooppmmeenntt,, lliivveerr cchhaannggeess,, ddeeccrreeaasseess iinn tthhyyrrooiidd hhoorrmmoonnee serum ovals, and immune suppression. Whi these effects were obseinrdivfferendt studies they were serum levels, and immune suppression. While these effects were observed in different studies they were observed at similar serum concentration evA tewogesnerat.ion reproductive study was selected s the study observed at similar serum concentration levels. A two generation reproductive study was selected as the study upon which to base the inal RID. This he same critica sty use by USEPAa the aso tshelr AD. The na upon which to base the final RfD. This is the same critical study used by USEPA as the basis of their RfD. The no abservable adverse fect evel (NOAEL) average serum concentration fom ths study was 626 mg/L. The observable adverse effect level (NOAEL) average serum concentration from this study was 6.26 mg/L. The human equalent dos correspondintog tiserum concentration cabn clea using Equatio2n human equivalent dose corresponding to this serum concentration can be calculated using Equation 2: Dose (2495)) = Serum coCnocnecnetnrattriaotnion ((7222))xx ctClearanceRaRtate((1--my) day) _=- 626 (28)00o0.0oo0o8o1 (1L ) = 000051 (2m2g ) Uncertainty factors of3 for potential interspecies diferences i toicodynamics, 10 for ntraspees variability Uncertainty factors of 3 for potential interspecies differences in toxicodynamics, 10 for intraspecies variability within the human population, and 3 for database deficiencies regarding Immunotoxicty were selected. Te within the human population, and 3 for database deficiencies regarding immunotoxicity were selected. The Value ofthe ndidualuncetinty actors are ulti, resulting in total uncertainty adjustment of 100. (For value of the individual uncertainty factors are multiplied, resulting in a total uncertainty adjustment of :~00. [For more information on how total uncertainty calciated se page 3 of (MOH, 2008). Application ofa otal more information on how total uncertainty is calculated see page 3 of (MDH, 2008). Application of a total uncertainty adjstment of 00 results nan RDof00000051 mk. (0.00053/100) The serum concentration uncertainty adjustment of 100 results in an RfD of 0.0000051 mg/kg-d (0.00051/100). The serum concentration corespondtoitnhgis RD i 0.063 mg/L. n addion to developmental effects dentiiedin the two generation corresponding to this RfD is 0.063 mg/L. In addition to developmental effects identified in the two generation ssttuuddyy,, iimmmmuunnee,, lliivveerr,, aanndd tthhyyrrooiidd ssyysstteemmss aarree aallssoo iiddeennttiiffiieedd aass aaddddititiivviittyy hheeaalltthh eennddppoionintsts.. For PFOA, th sensitive healthendpoints included development, er changes, immune suppression, and Kidney For PFOA, the sensitive health endpoints included development, liver changes, immune suppression, and kidney fects. These effects were observed in diferent tues, however, hey were observed at smilr serum effects. These effects were observed in different studies, however, they were observed at similar serum concentration vel. Adevelopmental stu was selected 3 the study upon which to ase the fra RID. This is concentration levels. A developmental study was selected as the study upon which to base the final RfD. This is th same citcl studyuse by USEPA as the basis of their ID Th lowest doe eel tested in this sty the same critical study used by USEPA as the basis of their RfD. The lowest dose level tested in this study resulted in helt effects; thereforea, NOAEL was not availble. The averag seu concentration at the lowest resulted in health effects; therefore, a NOAEL was not available. The average serum concentration at the lowest ose tested, 38 mal. ws denied 5 th LOREL The human equivalent dose corresponding o this serum dose tested, 38 mg/L, was identified as the LOAEL. The human equivalent dose corresponding to this serum concentration can be calculated using Equation 2 concentration can be calculated using Equation 2: Dose 19) (~ rng ) _ = Serum Serum i Concentration (22) Concen~ration (-m-~g-) x x Clearance C,earance ARate Rate (1--2=--) (~ L .) =_- 3822)c0o0.0o0onoa (gLh) Useof orreference to this model without proper attrtioMbDHuistproihiboitend. 3333 33774499..00003333 STATE 07436278 STATE 07436278 == 0o.0o0o3 (( 2) UUnncceertrtaaiinnttyy ffaaccttoorrss ooff 33 ffoorr ppootteennttiiaall iinntteerrssppeecciieess ddiifffefererenncceess iinn ttooxxiiccooddyynnaammiiccss,, 1100 ffoorr iinnttrraassppeecciieess vvaarriiaabbililiittyy within the human populati3ofno,r se of 3 LOREL ather than a NOAEL, and 3for database deficiencies within the human population, 3 for use of a LOAEL rather than a NOAEL, and 3 for database deficiencies regarding the ck of a acceptable wo generation study wre selected. Thevalouf ehe individual uncertainty regarding the lack of an acceptable two generation study were selected. The value of the individual uncertainty factors are multiple, esting na total uncertainty adjustment of 300. Application of a otal uncertainty factors are multiplied, resulting in a total uncertainty adjustment of 300. Application of a total uncertainty adjustment of 300 results nan RID f 0.000018 hg (0.0053/200). Th serum concentration corresponding adjustment of 300 results in an RfD of 0.000018 mg/kg-d (0.0053/300). The serum concentration corresponding ttoo tthhiiss RRFfDD iiss 00..1133 mmgg/L/L.. IInn aaddddiittiioonn ttoo ddeevveellooppmmeennttaall eeffffeeccttss iiddeennttiiffiieedd iinn tthhee ddeevveellooppmmeennttaall ssttuuddyy,, iimmmmuunnee,, ver, and kidney syste are ho entific 35 adtty health endints. liver, and kidney systems are also identified as additivity health endpoints. 3.2 Relative Source Contribution Factor 3,2 Relative Source Contributio~ Factor When MOH develops guidance values fora chemical, it considers the contribution of non ater exposures on When MDH develops guidance values for a chemical, it considers the contribution of non-water exposures to an individuals total exposure. The TK mel, a orginally conceived, predicts serum FOS orFOR concentrations individual's total exposure. The TK model, as originally conceived, predicts serum PFOS or PFOA concentrations rising directly and indie (e.5 breast) rom wter intake nly. However, exposures may aloocur from arising directly and indirectly (e.g. breastmilk) from water intake only. However, exposures may also occur from other sources. These other exposures re taken nt account by MOH through a Relative Source Contribution other sources. These other exposures are taken into account by M DH through a Relative Source Contribution ((RRSSCC)) ffaaccttoorr,, wwhhiicchh aallllooccaatteess aa ffrraaccttiioonn ooff tthhee RRfDD ttoo wwaatteerr eexxppoossuurreess aanndd tthhee rreemmaaiinniinngg ppoorrttiioonn ttoo ootthheerr Sources. In the case of FOS and PFOA, the RSC concept needed tobe pplied in framework rcogniing the sources. In the case of PFOS and PFOA, the RSC concept needed to be applied in a framework recognizing the long elimination haltives of POS 3nd PFOA, such tha person's serum concentration at any Gen ag is not long elimination half-lives of PFOS and PFOA, such that a person's serum concentration at any given age is not the rest of oy isher crn or recent exposures within the uration of concer, but ao fom ior her the result of only his or her current or recent exposures within the duration of concern, but also from his or her `eexxppoossuurreess ((oorr mmaatteerrnnaall eexxppoossuurreess)} ffrroomm yyeeaarrss ppaasstt.. NNoonn--wwaatteerr eexxppoossuurree ttoo PPFFOOSS hhaass bbeeeenn eexxaammiinneedd bbyy EEggeegghhyy aanndd LLoorrbbeerr ((EEggeegghhyy PPPP aanndd MM LLoorrbbeerr,, 22001112)}.. TThheessee researchers usd3 two-pronged approach: 1) exposure medi concentration data from mull sources and 2 researchers used a two-pronged approach: 1) exposure media concentration data from multiple sources and 2) based on serum concentrations reported i the 2003.04 NHANES Study. Forth rst approach Egeghy and based on serum concentrations reported in the 2003-04 NHANES Study. For the first approach, Egeghy and Lorber selected exposure mea concentration dat rom multiple sources inthe erature to estimated dll Lorber selected exposure media concentration data from multiple sources in the literature to estimated daily median and 95th prcentie exposure intakes for young children and aculs rom dust dit, water, and ai. median and 95th percentile exposure intakes for young children and adults from dust, diet, water, and air. Because of the sparsenes of media.spec ats, th authors characterized the esting intake estimataess Because of the sparseness of media-specific data, the authors characterized the resulting intake estimates as abject to considerable uncertainty. This uncertainty ws rater for the sper percentile states thnfo the subject to considerable uncertainty. This uncertainty was greater for the upper percentile estimates than for the median values. Due to th high uncertainty i the intake estimates and us of NHANES serum data thts ovra median values. Due to the high uncertainty in the intake estimates and use of NHANES serum data that is over a decade old, specially 35 th serum concentrations have ben decsessing ave me, MOH did not use th results decade old, especially as the serum concentrations have been decreasing over time, MDH did not use the results `ooff EEggeegghhyy aanndd LLoorrbbeerr ((22001111)) qquuaanntitittaattiivveellyy ffoorr RRSSCC aappppoorrttiioonnmmeentn.t. IInnsstteeaadd,, MMODHH uusseedd tthhee rreecceenntt NNHHAANNEESS bbiioommoonnititoorriinngg ddaattaa ((2200:1133--22001144)) aanndd EEaasstt M Meettrroo nneeww rreessiiddeenntt bbiioommoonnititoorriinngg ddaattaa ((2200:1144)),, ttoo eessttiimmaattee uuppppeerr--eenndd nonwate exposures for OS and PRO (ilar to option 2 n Egeghy nd Lober, 2011, which more non-water exposures for PFOS and PFOA (similar to option 2 in Egeghy and Lorber, 2011, which is more reflectiveof curent exposures. reflective of current exposures. MOH utizes the USEPA ExposureDecision Tee process (USEPA, 2000) o identify and selec the mast M DH utilizes the USEPA Exposure Decision Tree process (USEPA, 2000) to identify and select the most approprinte ASC. Th Decion Tree presents see of decion points at which th quality and quantity of appropriate RSC. The Decision Tree presents a series of decision points at which the quality and quantity of vale exposure data sre exalted ndatwhich the deriation of th RSC imately tered owsrd one of available exposure data are evaluated and at which the derivation of the RSC is ultimately steered toward one of Several conclusions ndcating an appropriate RSC. I ther chemical assests, MDH often lied upon the several conclusions indicating an appropriate RSC. In other chemical assessments, MDH often relied upon the percentage method, which is mended 10 eflect relative portions ofother {norwater ingestion) routes of percentage method, which is intended to reflect relative portions of other (non-water ingestion) routes of exposure and the elhoo for changing eves within those multe sources (MOH, 2008). The relevant exposure and the likelihood for changing levels within those multiple sources (MDH, 2008}. The relevant portions of the Exposure Decision Tee ar presented below. portions of the Exposure Decision Tree are presented below. Useofor reference to this model without proper attribution to MDH isprohibited. 33774499..00003344 3344 SSTTAATTEE_0077443366227799 gure 1. pore Decision Tee Figure i2. Exposure Decision Tree. (Aco SEP 00 ok ers crsons USE 2000dc, ny rn es re secsfor (Adaptedfrom USEPA 2000 - box numbers correspond to USEPA 2000 document, only relevant boxes are selectedJ~or rset eon presentation below) 7 12. [[ iIddeennttiitfyy ppoopuplautiolna(st)ooiffcocoonnncc(eersrnn orcas 22. [ iIddeennttiitfyy rreelleevvaanntt eexxppoossuurree sources/pathways apnesrdnis nigra or 3: A[arvee aaddeeqquuaattee ddaattaa aavvaaiillaabbllee ttoo ddeessccriribbee. central tendencies & high-ends for relevant exposure sources/pathways? TwNo o[ere siti aotspictrrsc Are there sufficient data, physical/chemical roar, emt property, fate & transport, &/or Teatro generalized information available to Caracas ths Hethoasof xr a characterize the likelihood of exposure to | on8A,/r yYoes mngetsat tneest AArree tthheerree ssiiggnniiffiiccaanntt kknnoowwnn oorr ppootteennttiiaall uses/sources other than the source of vr concern? Yes rd Is there some information available to make a characterization of expoosssure? opr ih cig for) 1133.. aAppppoorrttiioonn tthhee RRfDD iinncclluuddiinn8g8800%%. cceeiillininsgi2/020%% fflloooorr uussiinn8g ppeerrcceennttaaggee approach (with ceiling & floor). vo sc Fem orionmarts !~ .~.~;[ Perform apportionment as ero ox 1 ce sone), ........................................ ~, described in Box 13 (see above), `wwiitthh aa5500%%cceeiilinlgi/2n0g%/f2flloo0oo%rr.. T`Thhee 8800 ppeerrcceenntt cceeiilliinngg wwiitthhiinn tthheeDeDceicsisiioonnTTrreeee iiss ttoo eennssuurree tthhaatt tthhee hheeaalltthh--bbaasseedd ggooaall wwililll bbee llooww eennoouugghh ttoo roids adequate roraction of ndhiduals has 0a xp0ur du 03mof te xEOsTe sors, Mer provide adequate protection for individuals whose total exposure is, due to any of the exposure sources, higher hance natedbyte vale at (U5 EPA 2000) Tis so creases he margin of sft 0 scour than currently indicated by the available data (US EPA 2000). This also increases the margin of safety to account for posal kw se of E508 Sc Eu oncertatons ar he bet ear of PROS 40 PFOA for possible unknown sources of exposure. Since serum concentrations are the best measure of PFOS and PFOA posure thse value an be used maofcthe ID in th Deion Trea proces exposure, these values can be used in place of the RfD in the Decision Tree process. 3.1 Selection of RC for PROS 3.2.3 Se]ectior~ of RSC for PFOS High quality ton! ad Minnsot- sec data scutes are avai which stabs han err High quality national and Minnesota-specific data sources are available which establish human serum concentratofioFCnSs actos many mdi, aug dita for fants and ung children a ot valle, concentrations of PFOS across many individuals, although data for infants and young children are not available. Goin thong hl of POS, he monitoring resus och ast Melo (new eigen) and NHANES Given the long half-life of PFOS, these biomonitoring results from the East Metro (new residents) and NHANES an be compared 1 he serum conentation of 0063 g/L catesponding he PEOS AD to provide sight can be compared to the serum concentration of 0.063 mg/L corresponding to the PFOS RfD to provide insight in th magne of nanwatar expoRrS, (ese ne tht th serum concniation efor forming into the magnitude of non-water exposures. [Please note that this serum concentration is useful.for informing Publ heh policy and terortng poutbased exposures. Ts vl sedon opin sed pubfic health policy and interpreting population-based exposures. This value is based on population-based `ppaarraammeetteerrss aanndd sshhoouulldd nnoott bbeeuusseeddf.oforr cclfiinniiccaall aasssessesmsesnmtooerrfn~ootrr iinntteerrpprreettiinngg sseerruumm lleevveellss iinn iinnddiivviidduuaalsls..] (CC2DD0CC13((C-C2DD0CC1,,422)00b11i77o))mhhoaanssitbboeereeinnngmmreeeasasusulurtrsiinnwggerePP:FFOOgSSeoiinnmetththereissceemrrueummaonoff0t.thh0ee04gg9ee9nneemrrgaal/lLppoaopnpudulla9at5tiio"onnpessriincneccneeti11l99e99909... 0TT1hh8ee5mmmogos/sLtt.rreeIccteiensnt.t (2013-2014) biomonitoring results were: geometric mean 0.00499 mg/L and 95th percentile 0.0185 mg/L. It is Useoforreference to this model without proper attribution to MDH isprohibited. 3355 33774499..00003355 SSTTAATTEE_0077443366228800 tiimompp4o-orfrottlaadnntdtrttooopnnsooittneecetthh2aa0tt0tt3hh-ee01ggee(nnteehreraalslpeporopuupmluallaettviieoolnns (u(NsNHeHdAANNiEnESES)g)essgeehrruyumamnlldeevvLeeollsrsbhheaarvv2ee01bb1ee)ee.nnTddheeeccrr2ee0aa1ss3ii-nn1gg4oodvvaeetrrattipimrmeoe,v,iwwdieitththhaae33 mtoos4t-forledcednrtopdastiancreeg2a0r0d3in-0g4`b(tahcekgsreoruunmd'lesveerlsumusleedvelinsiEntghegehyUaSngdenLeorrablerpo2p0u1la1t).ioTnhse. 2013-14 data provide the most recent data regarding 'background' serum levels in the US general populations. wMMeDDrHeH'scEEaaosstt MnMeetnttrroooaePPEFcCCocnbbtiioatommmiooennniatittdooerrdiinnpggubpplrrioocjjeewccatttsesarammspuplpleepddlyaa(ssNuuebblssseoetnt,oof2f0pp1e6e)oo.ppllTeervleivaiitnnmggeiinnnttththoeerEEeaamsstot vMMeeettrroo rreeggiioonn wwhhoo perfluorochemicals were connected to perfluorochemicals (PFCs) was added to the public water system a contaminated public water supply (Nelson, (PFCs) was added to the public water system (PWS) 2016). (PWS) and volunteer participants Treatment to remove and volunteer participants hhaadd PPFFOOSS. bbElalosootoddMelletevvreeollrssemmseieadasesnuutrrseedd(aNat=t1tt5hh6rr)eeeewettirimemeealppsoooiinnsttassm::p22l00e00d88,,in220201011004,,.aaTnnhdde22s00e114i4.n.diAAvssidppuaalrast ooifrftdththneeotllaahsstat vbbeiioohmmisootnonirtiitocorarliinneggxpeefofffsoourrtrt,,ennteeoww tEhaestcMonettaromirneastideednwtast(eNr=,s15o6t)hweierseearlsuom ssaammpplleeds cinan20b1e4c. oTnhseisdeerineddivrideuaplsrdeidsneotnohftaMvaeinthniisetsovortiecaalnoenx-pwoastuerer to exposures (geometric mean the contaminated water, so exposures (geometric mean 0.0072 mg/L and 95th percentile 0.021 their serum samples can be considered 0.0072 mg/L and 95th percentile 0.021 mg/L). These levels are sightly higher than representative of Minnesota non-water mg/L). These levels are slightly higher than etthhxeepoNNsHHeAAdNNtEEoSSco22n00t11a33m--i11n44avvtaaellduueewssatbbeurut.t aarree nnoottiicceeaabbllyy lloowweerr tthhaann tthhee EEaasstt MMeettrroo ppooppuullaattiioonn tthhaatt wweerree hhiissttoorriiccaallllyy exposed to contaminated water. iDDnaayttaaouoonnngPPcRFhOOilSSdrsseeenrruu(mSmlcehlevevceetllessri,inn 2ii0nn1ffa2a)nn,ttss(aaWrruee,nn2oo0t1t 5aa)vv,aaiaillaanbbdllee(;;Hahhrooewwse,evv2ee0rr1,,7t)th.heerrTeeheaasrreee pppuuubbbllliiicccaaatttiiiooonnnsss rirenedggiaacrraddtiiennggthassteerrtuhumem lleevveellss geometric means in young children geometric means and 95 percentile values in young ((Schecter, 2012), (Wu, 2015), and and 95th percentile values in young children are similar to adultlevels. Therefore, available (Harris, 2017)). These publications indicate that the children are similar to adult levels. Therefore, available ddaattaa ssuuppppoorrttss tthhee uussee ooff uuppppeerr--eenndd ppeerrcceenntitillee vvaalluueess ffrroomm NNHHAANNEESS aanndd tthhee EEaasstt MMeettrroo nneeww rreessiiddeenntt aass ccoonnsseerrvvaattiivvee rreepprreesseennttaattiioonnss ooff '`bbaacckkggrroouunndd!' nnoonn--wwataeterriinnggeessttiioonn rroouutteess ooff eexxppoossuurree.. TT8oo0%aass(ispsisettriiDnneiicddieesnnitotiinffyyTiinrnegge,aannUSaapEppPprAroop2pr0ri0iaa0tt)eeaRRnSSdCCs((aauppppoborrtttiioonrnammcaeoennnstctettrootvawwteaaitvtdeeerr ii(nn9gg5eesstptiieoornnc))enffotoirrlPPe)FFOOsSSerMMuDDmHHvattloouooekkfttrhhoeemccteehiilleiinngg ooff r8e0c%en(tpebrioDmeocniistioonriTnrgeed,atUaSrEoPmA 2t0h0e0E)aasntdMseutbrtorancetewdraesciodnenstesrv(awthiviech(9w5athspselirgchetnlytilhei)gsheerrutmhavnatluhee 2fr0o1m3-t2h0e14 NHANES 95 percentile value) as follows: recent biomonitoring data from the East Metro NHANES 95th percentile value) as follows: new residents (which was slightly higher than the 2013-2014 + 80% Celling =80%of the serum concentration associated with the RID = 0.053 mg/L x 0.8 = 0.0504 mg/L Sub80t%raCcteiiliongn o=f8t0h%e osef rthuem sleevruelmascsoonccieatnetdrawtiiotnh ansosno-cwiaatteedr wexitphostuhreesR,fDas=re0f.l0e6c3temd gb!yLtxhe0.985=0p.e0r5c0e4ntmilge/L value based Subtraction value based on the new East Metro residents (0.021 mg/L) from the of the serum level associated with non-water exposures, on the new East Metro residents (0.021 mg/L), from the 80% celing = 0.0504 mg/L 0.021 as reflected by the 95th percentile 80% ceiling = 00504 mg/L- 0.021 mmgg//LL == 00..00229944 mmgg/L/L.. TThhiiss vvaalluuee ooff 00..00229044 mL mg/L rreepprreesseennttss tthhee rreessiidduuaall oorr mmaaxxiimmuumm sseerruumm lleevveell tthhaatt ccaann bcbeeellaianppgp.poorrttiioonneedd ttoo eexxppoossuurree vviiaa wwaatteerr iinnggeessttiioonn,, wwhhiillee ssttiillll kkeeeeppiinngg tthhee ttoottaall sseerruumm lleevveell bbelolw tthohee88w00%% + Tcheielinrgesidual or maximum serum level that can be apportioned to exposure via ingestionof water (0.0294 mg/t) is approximately 50% of the The residual or maximum serum level that (0.0294 mg/L) is approximately 50% of the serum can be serum concentratiaon the RID apportioned to exposure concentration at the RfD (0.063 m/l). via ingestion (0.063 mg/L). of water wBBaaatsseeerdd ioonnngettshhtiiissonii.nnffooIrtrmmsahatotiiuoolnnd aabnneddnttohhteeedUUSStEEhPPaAAtDDheeeccriiesssiiuoolnntsTTrroefeeeth((iees..gga,.n, abblooyxxss886Cd):),o, MMnoDDtHHsusspeeplleoecrcttteerddaiaasnningRRtSShCCeooffa55p0p0%o%rtffooirronPPmFFeOOnSSt of wwaatteerr iinnggeessttiioonn.soItusrhceosultdob8e0npoertecedntt.hat the results of this analysis do not support raising the apportionment of water ingestion sources to 80 percent. 3.2.2 Selection of RSC for PFOA 3Hi,2g,h2quSaeliletcytbioinomoonfiRtSoCrifnogrdPaFtaOAar alsoavailable for PFOAand a similar approach to apportionment of the RSC as described High quality as described for PFOS wasalsoundertaken for PFOA. biomonitoring data are also available for for PFOS was also undertaken for PFOA. Biomonitoring results from the PFOA and a similar approach to Biomonitoring results from the East Metro (new residents) apportionment of the RSC East Metro (new residents) `aanndd NNHHAANNEESS wweerree uusseedd iinn ccoommppaarriissoonn ttoo tthhee sseerruumm ccoonncceennttrraattiioonn ccoorrrreessppoonnddiinngg ttoo tthhee PPFFOOAA RRIfDD ooff 00..1133 mmgg//LL uttoo ppsrroofvveioiddeeifniinnfssouiirggmhhilttnnignttpooubttlhhieechmmeaaaglgntnihittupuoddleeicooyffonnnoodnn-i-wwnataettreeprrreeetxxippnogosspuuorrpeeussl..a[[tPPilloeenaa-ssbeeannsooetdteeexttphhoaasttuthrhieisss.sseeTrrhuuimmvccaoolnunceceeinsntbrtaraastteiiodonnosins population-based porameters and should not beusedfor use[ulfor informing public health policy and interpreting population-based parameters and should not be used for clinical assessment or for interpreting serum ievels population-based exposures. This value is based on clinical assessment or J:or interpreting serum levels iinn induviduols.] individuals.] Useofo reference to this model without proper attribution toMOH sprohibited. 33774499..00003366 636 STATE 07436281 STATE 07436281 CC(2DD0CC13((C-C2DD0CC1,,422)00b11i77o))mhohaanssitbboeereeinnngmmreeeasasusulurtrsiinnwggerePP:FFOOgAAeoiinmettthhreeissceemrrueumamnoof0f .tth0he0e1gg9ee4nnemergraa/llLppaoopnpudull9aat5titioohnnpsseiirnnccceeent11i99l9e999.0..TT0hh0ee55mm7oomssgtt/rrLeeccIeetnntst important to (2013-2014) important to note that the biomonitoring note that the general results general population (NHANES) serum levels have been were: geometric mean 0.00194 mg/L and 95th population (NHANES) serum levels have been decreasing percentile decreasing over time, witha 0.00557 mg/L. It over time, with a 2is 2 ttoo33--ffoolldd ddrroopp ssiinnccee 22000033--0044 ((tthhee sseerruumm lleevveellss uusseedd iinn EEggeegghhyy aanndd LLoorrbbeerr 22001111).). TThhee 22001133--1144 ddaattaa pprroovviiddee tthhee mmoosstt rreecceenntt (N=156) wer ddaattaa rreeggaarrddiinngg e also sampled b'baacckkggrroouunndd"' sseerruumm lleevveellss iinn for PFOA in 2014: geometric tthhee mea UUSS ggeenneerraall n 0.0018 m ppooppuulalattiioonnss.. g/L and 95th NNpeeerwwceEEnatasistlteM M0ee.t0trr0oo5 rrmeegss/iidLdeennttss These levels aresimilar but (N=156) were also sampled These levels are similar but slightly lower than the NHANES 2013-14 values. for PFOA in 2014: geometric mean 0.0018 mg/L slightly lower than the NHANES 2013-14 values. and 95th percentile 0.005 mg/L. DDaattaa oonn PPFFOOAA sseerruumm lleevveellss iinn iinnffaannttss aarree nnoott aavvaaiillaabbllee;; hhoowweevveerr,, tthheerree aarree ppuubblliiccaattiioonnssrreeggaarrddiinnggsseerruumm lleevveellss iinn mYyeooauunnnggs ccahhniidllddr9re5entnh(((SpScechrhceeecntcteteirrl,,e 22v0011a22)),,li((WnWuyuu,oe, u22ns001g155)c),h,iaalnndddre((nHHaaarrrreriisssi,,mi22l00a1r177t))o.). TThheessee ppuubblliiccaattiioonnss iinnddiiccaattee tthhaatt tthhee ggeeoommetertriicc adult levels, Therefore, avilable data support the use of upper-end percentile values from NHANES and the East Metro new means and 95th percentile values in young children are similar to adult levels. the use of upper-end percentile values from NHANES and the East Metro new resident as Therefore, resident as conservative available data conservative support rreepprreesseennttaattiioonnss ooff b'baacckkggrroouunndd'' nnoonn-wwaatteerr iinnggeessttiioonn rroouutteess ooff eexxppoossuurree.. T8Too0%aass(ispsisettriiDnneiicddieesnnitotiinffyyTiinrnegge,aannUSaapEppPprAroop2pr0ri0iaa0tt)eeaRRnSSdCCs((aauppppoborrtttiioonrnammcaeoennnstctettrootvawwteaaitvtdeeerr ii(nn9gg5eesstptiieoornnc))enffotoirrlPPe)FFOOsAAe,r, uMMmDDvHHalttuooeookfkrttohhmee tccheeeliliinngg ooff recent biomonitoring data rom 2013-2014 NHANES (which was slightly higher than the new East 80% (per Decision Tree, USEPA 2000) and subtracted a conservative (95th percentile) serum value recent biomonitoring data from 2013-2014 NHANES (which was slightly higher than the new East Metro from the Metro rreessiiddeennttss 9595th ppeerrcceenntitillee vvaalluuee)) aass ffoolllolowwss:: + 50% 80% Celling Ceiling = = 80%of 80% of the the serum serum concentration concentration associated associated with with tthhee RRffDD = = 00..113300 mmgg//LL x 00..88 == 00..110044 mmgg//LL + SvSauulbbutterraabccattsiioeonnd oo0ff tth2he0e1ss3ee-rr2uu0mm14lleeNvveHellAaaNssEssSooccdiiaaattteeadd(ww0i.itt0hh05nn5oo7nn-m-gww/aaLtt)ee,rrfeerxxoppmootsshuurerees8s,,0%aasscrreeeffllleleccitt=eneddgbb0yy.10tt4hhmeeg99/55Lth~pp0ee.rrc0ce0en8nt5iti7llee mg/L= 0.0984 mL. This value of 0.0984 value based on 2013-2014 NHANES data mg/L = 0.0984 mg/L. This value of 0.0984 mL represents the (0.00557 mg/L), from mg/L represents the residual the 80% residual or maximum serum level that can ceiling = 0.104 mg/L- 0.00557 or maximum serum level that can bbee aappppoorrttiioonneedd ttoo eexxppoossuurree vviiaa wwaatteerr iinnggeessttiioonn,, wwhhiillee ssttiillll kkeeeeppiinngg tthhee ttoottaall sseerruumm lleevveell bbeellooww tthhee 8800%% cceeliilinngg.. ThThee rreessiidduuaall oorr mmaaxxiimmuumm sseerruumm lleevveell tthhaatt (0.0984 mg/t) is approximately 75% of the ccaann ser bbee um caaopppnpocorerttniiotonrneaeddtittaoooneexxtpphoeossRuuIrrDee (vv0iia.a1ii3nnmgggee/ssLttii)oo.nn ooff wwaatteerr (0.0984 mg/L) is approximately 75% of the serum concentration at the RfD (0.13 mgiL). TrThehigissarccdaaillnccguullbaaattiicooknngrssuuogguggneedsstetssxpaaonnsuRRrSSeCC ioonfftgghrreeeaapttoeeprruttlhahatanino55no00%f%cbbouunttcleleerssnss tt(hheaa.nn 8i8n00f%%a.n.tHsH)oowawenevdveetrrh,,eggpiivrveoencnettshhseeolluiimtmliiitteneedddiiinnnffotorhrmemaaUttSiioEonnPA Decision Tree (e.g. box 5C), MDH regarding background exposure in Decision Tree (e.g., box 8C), MDH selected an RSC the population selected an RSC ofof of 50% for concern 50% for PFOA water ingestion. (i.e., infants) and the process PFOA water ingestion. outlined in the USEPA 33..33 RReea~s;~onsoab~l~eabMleaMxaiximmuumm EExxppoossuurree SScceern~a::r~iriooss AAss mmeennttiioonneedd aabboovvee,, ttwwoo eexxppoossuurree sscceennaarriiooss wweerree eexxaamminineedd:: 11)) aann iinnffaanntt eexxcclluussiivveellyy ffeedd ffoorrmmuullaa rreeccoonnssttiittuutteedd wawniitthihncfcaoonnntttaeaxmmcilinnuaasitteveeddlywwabartteeearrsststftaaerrdttiinfnoggr aa1tt2bbmiiorrttnhhtahasnn,dd fccoononttiinlnuuiilnbnggyodiinrnwgigeeneskstitiindoognn coofofncctooannmttiaanmmaiitnneaadtteewddatwweaartteetrhrrtthohurrogouhuggfhhe.lliiffeBeo;; taahnnddof22)) tahneisnefasncet neaxrciloussiavreelypbrreesaesnttfeedd gforrap1h2imcaolniltnhysF,ifgoulrloeswe10d abnydd1ri1n,krinesgpeccotnivtaelmy,inianteSdecwtiaotner2.t3hrough life. Both of these scenarios are presented graphically in Figures 10 and 11, respectively, in Section 2.3. AAnnititeerraattiivvee pprroocceessss wwaass uusseedd ttoo iiddeennttiiffyy tthhee wwaatteerr ccoonncceennttrraattiioonn tthhaatt rreessuulltteedd iinn mmaaiintnaitniangiaansseierrnuugmm caconondncceeenxntptroraastutiirooennpaaatrt aoomrrebbteeellorowwin55p00u%t%s((uRRsSSeCC)d) ooafrfetthhpeerossveeirrduuemmd ccaoobnnoccveeenntitrnraaTttaiiobolnneaa8ss.ssoocciiaatteedd wwiitthh tthhee RRIfDD.. TThhee cchheemmicicaall-ssppeecicfifiicc and exposure parameter inputs used are provided above in Table 8. Useofo reference to this model without proper attribution toMOH sprohibited. 33774499..00003377 3377 STSTAATTEE 0077443366228822 3.3.1 Scenario #1 Excusvely formalaed infan: Scenario #:t.- Exclusively formula.-fed inf:ant 3311008 :. ~,'~,1. i PFO5 Thewater concentration tht maintained PEOS serum concentration at or below an RoSfS0C5 0.063 x The water concentration that maintained a PFOS serum concentration at or below an RSC of 50% (i.e., 0.063 x 00..55==00..00331155 mmgg//LL)) tthhrroouugghhoouutt lliiffee wwaass 00..006600 upgg/iLL.. Fwiagutreer1i3n.tokEexcoutsiev,eloynfRoSrCmofuSe05d6faanntda PwAaGtSersecornucmenctornacteinotnraotifon0s.0v60eurg/aL. etme, based on 5th percentile fom / fl sen) iBSneecccraaeuuassseee ooifnfttthhheee wlloaonntggerhhaaclolffn--lcIifefene,trtthaheteiPFoFnOO(SS0.ss0ee6rr1uumumgcc/ooLnncrceeanntstrraatttiihooennpccruuerdrvievcteisedvvaePrrRyyOffSllaasteaarnnuddmeecvvoennnceaansstmmraaaltllil oiinnnccarrbeeommveeenntttaahlel50 pinecrrceeanstetihnrtehsehowldatfeo r nearly years. concentration (0.061 pg/L) raised the predicted PFOS serum concentration above the 50 percent threshold for nearly 9 years. 331.2000 3~3.k.2 PFOA The water concentration that maintained PFOR serum concentration for exclusively formula-fed infants at or The water concentration that maintained a PFOA serum concentration for exclusively formula-fed infants at or beloawn RSCof50% 60x 0..5- 01.085 m3 g/L) throughout Hewa0.15 sgf below an RSC of 50% (i.e., 0.13 x 0.5 = 0.065 mid/L) throughout life was 0.15 t~g/L. Useof orreference tothismodel without proper attribution to MDHisprohibited. 33774499..00003388 3388 SSTTAATTEE_0077443366228833 Fwiagtuerre n14t.okeExclruastiev,elyanfoArSmCuolfa-5f0e%d,ianfnondtawPaFtOeArsceornucmercotnrcaetnotnraotfi0o.n1s5okvear. etme, based on 95th percentile w~er intcke r~es, on R.5C ~'~f ,50%, ~nd ~ w~er ~:o~,~:er,~tr~~',,Jon of 0,.t.5 ~,~g,il., el som ON Jom ~~ fo 5 S-- set) ScSeoerrnuucmmecncootnnrcceaentntitrraoatntiioo0n.n0.1ss6 uwwgee/rrLeerassiesenesdnittivsheeittsooetccrhhuiaamnnvcgsoeeenssceiinnntwwraaattteeirronccooannbcceoenvtnertratathtieioo5nn0ssp,.eAArnnceiinnnctcrreteahasrseeesiihnnatlthdheefwowraatmteearrre than one year.concentration year. to 0.16 t~/L raised the serum concentration above the 50 percent threshold for more than one 3.3.2 Scenario #2 ~ Exclusively breastfed infant "~ ~ -' Scenario #2 ..... Exclusively breastfed infant 332.2008 AaA3rss3e2ss.tet~axa.cttPeleFuddsOiiinvnSeSSleyeccfttoiioronmnu33l..a33-..f11e..11d,,2aswwianatfateenrtrsc.coonHcnoecnwetenrvtaertarit,oiontnhioosffw00a..t00e66r001cg~o8/n/cLLeniisstrpparrtooitteeocncttbiivaveesetthdhrrooonuuggfhhooroumuuttlflaif-eeffeofodriiinnnfddainivvtiisdduiusaalnlssotwwhhoo bssauiurfeofffaiiecccxicieceunlnmuttusllylyivappetrlriyoovttfeeeoccrmtmtaiivtvueeelraffn-oofarerldiinenaffxasapnnoittnsssfuwawrnhehtosow.aiaHrtrheeowseeuexxcbvclesluuress,iaitvvheeeinlslyytwbbtrarreeateaanssrstftceffeoreddnicnffeobnrretarayarsyetteimaoairnlrkwwb.hahsAeeetnndacwcoooannntssfeioiddrremercruiinonl~agn-ttfhcehedeeccninhhrtfraoornnnotiaisccfti0si.n0oo6tn0 fJbI~oiLorLa.m,cocpprurreemeddtuiihcclaattenteidvdoePPnmFRyOOaeSStaessrreenarranuulmdmexellpexevovceeselluessrdeffootwrrheeeitxhx5ccl0sluu%ussbiiRvvsSeeelClqyyutbbehrrrneeetaastsshrtatoffleneddsdfoeiinrnrffainannentatbssrerleexyaxcsc1ete9meedydiltekath.hreAesstsenaerrwouurammdteerccrtooconnoccnmeecanneittnnrarttrataaiiottnniioaoPnantFtoOtthfShe0es.0eRR6rIfD0uDm for more than one year and exceed the 50% RSC threshold for nearly :19 years. In order to maintain PFOS serum cboenlceonwterraetdio1n0s0.a0t2o7r pbge/lL.ow the 50% RSC serum concentration. 0.0315 m1) the water concentration had to concentrations at or below the 50% RSC serum concentration (i.e., 0.0315 mid/L) the water concentration had to be lowered to 0.027 lal~/L. Useofor referencetothis modelwithoutproperattributionto MOH isprohibited. 33774499..00003399 3 STATE o7asezss STATE 07436284 Figure 15. Exclusivelybreastfed infont PFOS serum concentrations overa fetime,basedon Upper/95th ppeer.rcceenntidllee bbrree~,a~smtifmk/iwlok~/erwniantttooekkere rrea~tee,s,s,, oonn RRSSCC oofj: 5500!%%, onndd oawwaote~rv ccoonncceennttrroattiioor~n oof0f0.,002277 ka. pfo a fo Suet EEvevnaaessmmanallll iinnccrreemmeennttaall iinnccrreeaassee iinn tthhee wwaatteerr ccoonncceenntrtraattiioonn i, 0.028 (i.e., 0.028 ui~gg//LL)) rraaiisseedd tthhee sseerruumm ccoonncceennttrraattiioonn aabboovvee 5500%% RRSSCC tthhrreesshhoolldd ffoorr mmoorree tthhaann tthhrreeee mmoonntthhss dduurriinngg eeaarrllyy fe.life. TThheerreeffoorree,, tthhee hheeaalltthh--bbaasseedd wwaatteerr ggofuuiitddhaaenn5cc0ee%fftoohrrrPPeFFsOOhSSolwwdaastshssaeetttcaaottul00d..00o22c77cuularg~/a/LLsattoorebbseeulpptrrooottfeecectxtiipvvoeesooufrf eddeeovvveelelooarppmmseuenbntctahalrloccnooinncccpeeerrrnnissoadaonnfdd tttoiomppe.rreevveenntt eexxcceeeeddaannccee of the 50% threshold that could occur as a result of exposure over a subchronic period of time. 33227508 AAarssesstetaxactteleuddsiiinnvSeSleyeccfttoiiornmoun3l.a33-..f3:L.e12d.,2aa,as wwianaftateenrtrsc.coonHncocewenentvrteraartt,iiootnnhioosff0w0.a.t1$e55rgl~c/go/nLLceiissntpprrroaottteeicoctntiivbveeastthehdrrooouungghhfooourutmtulilifaee-fofoerrd iiinnnddfiiavvniidtdsuuaaisllssnowwthhoo. sufficiently protective for infantswhoare exclusively breastfedforayear are exclusively formula-fed as infants. However, this water concentration sufficiently protective for infants who are exclusively breastfed for a year whenconsidering the based on formula-fed when considering the chronic infants is chronic not bbiiooaaccccuummuulalattiivvee mmaatteerrnnaall eexxppoossuurree wwiitthh ssuubbsseeqquueenntt ttrraannssffeerr iinn bbrreeaasstmtmiliklk.. AAtt aa wwaatteerr ccoonncceennttrraattiioonnooff00.1.155. Wft~oa8r//mLL,o, rpprreeeddtiihccattenedd4PPyFFeaOOrAAsssaeenrrduumemxclleeevveeedllsstffhooerr5eex0xcc%lluuRssSiivvCeeltlyyhrbberrseehaaosslttdffeefddoriinnmffoaarnntetssteexxcchee9eeyddaeatthhrnees.sseerruumm ccoonncceenntrtraattiioonn aatt tthhee RRffDD for more than 4 years and exceed the 50% RSC threshold for more than 9 years. In order to maintain PFOA serum concentrations ator below the 50% RSC serum concentration (.c., 0.065. mg/L), the In order to mg/L), the water concentration had to be lowered to 0.035 ug/L maintain PFOA serum concentrations at or below the water concentration had to be lowered to 0.035 lag/L. 50% RSC serum concentration (i.e., 0.065 Useoforeference to this model without proper attribution toMOH sprohibited. 33774499..00004400 a4O0 STSTAATTEE0707443366228855 Fre 16. Exclusively breasted font PFOA serum concentrations avr a fete, baseand Upoer/Sth percentile breastmilk/waterintake rates and an RoS f 5C 0%, and o water concentration of 0.035 ug/L. 3 Lal/ I | \L ser vem small incremental incase nthe water concentration (0036 ug) asd the serum concentration above Even a small incremental increase in the water concentration (0.036 t-tg/L) raised the serum concentration above the S0pacent threshoflodr approximately one month durin cay We. Therefore he heathbased water the 50 percent threshold for approximately one month during early life. Therefore, the health-based water dancefor PFOA was st a 0.03 UL10 be protofedecvetlopimevnteal concerns. guidance for PFOA was set at 0.035 iagiL to be protective of developmental concerns. 2.4 Conclusions/surmary 3.4 Conciusions/Su m m~.tl"y Duetothe bicaccumulative atuofrPOeS and POR, chronic exposure to mothrs and th subsequent transfer Due to the bioaccumulative nature of PFOS and PFOA, chronic exposure to mothers and the subsequent transfer Tolnfans through beasticeing reed th highest exposures and lowest acceptable water concentrations to infants through breastfeeding resulted in the highest exposures and lowest acceptable water concentrations der he scant valinoey MOH. To ensure proectonaf segment ofthe popuaton, the nl MOH under the scenarios evaluated by MDH. To ensure protection of all segments of the population, the final MDH helt based value for PROS and PFOAwere st ot 0.027 and 003 Rl respectucly. health-based values for PFOS and PFOA were set at 0.027 and 0.035 pg/L, respectively. Sreasieaings important or he shot and long es halt ofbotha mother and fa. MOH used an AVE Breastfeeding is important for the short and long term health of both a mother and infant. MDH used an RME Scenario to generate th heh based voloes fo POS and PFOA. An AME scenario depictas relic bt scenario to generate the health-based values for PFOS and PFOA. An RME scenario depicts a realistic but ram exposure atin 0 re hat even the aot hel posed ids with the population maximum exposure situation to ensure that even the most heavily exposed individuals within the population lle protected. Tnemarty of he population experience ower exposes thn the AME MDH ecormends will be protected. The majority of the population experience lower exposures than the RM E. M D H recommends hat women cently breasteeding, and pregnant women who lan 0brcasteet conteto Gos. Excaie that women currently breastfeeding, and pregnant women who plan to breastfeed, continue to do so. Exclusive breasteeding recommendedby decors and othr heath professionals. 1s unliely ht potential health breastfeeding is recommended by doctors and other health professionals. It is unlikely that potential health concerns exceed th known benefits of brestfcding. Appiaton of th ral neath based vues will utimotely concerns exceed the known benefits of breastfeeding. Application of the final health-based values will ultimately eit n ower boc burdens and breastmilk concentions of FOR and PFOR that fats co rece the result in lower body burdens and breastmilk concentrations of PFOS and PFOA so that infants can receive the cptmal benef rom breastfeeding. optimal benefits from breastfeeding. Useofor reference to this model without proper attribution to MDH isprohibited. 33774499..00004411 a41 STATE. orssezse STATE 07436286 4.0 References BBaarrtteelll,S,Se..x((p22o00s11u22r)e.).s,BBiiaaanssdiinnpohhtaaellnff-tlififaeeleesssottliiummtiaaottneesss. uuJssoiiunnrggnallologgofccooEnnxcpceoensntutrrraaettiiSoocnnierrnecegergaenrssdeiosEnnisvinniirtothohneenmppernetrsaelneEcpeoisodfefbembaiacocnklkogggrcryoo.uuenn2d2d, 2e9x9p.o3s0u3r.es, and potential solutions. Journal o,f Exposure Science and Environmental Epidemielogy., 22, CCaarriioouu,,BRR2.9,BL9Be-3VVBi0eezy3eycr..ra.anndd,(,2AA0Y1Y5a)am.maPadrdafal,,uAoArBoBeaerlrrkreeyblbii,a, cDDidZZa(alPlkkFooA,,ASS) DDlueuvrreaalnnsdda,,nCCd PPporololflloiolnneoos,, iPPn MMbaraerraccshhtaanmniddl,k,,J1--mCCatLLeeerbblnlaaannlcc,a, n1J-d?PcAAhnnottriigdgnnaacc,, sBeLreumBizofecF.r. e(n2c0h15w)o. mPeernfluaonrdotahlkei1rnaecwidbo(rPnFsA.A) Elenvveilrsoannmdenptrontfielersnaitniobnroela,st4m,il7k1,.8m1.aternal and chord CCDDCC.. ((2200sh1~ei66)tr)u.p.CmsCe:ne/otn/fetueFrwrrsnsefsnfooccrdhrcDDwigisosoeemvaafessbeenreCCasonotndnitetrtroeholdel iaairnnngndd/epPPwdrrtbee/vov2eren0nnt1stiGi.oobEnnr..nevaBBsirrrteoefaansesmtetf[deeeineentddgIiirnnnetggeproRRnreeatppctoioaorrrnttdaCCloo,ardr8d.d4.., Retrieved 7~-8~. Retrieved ffrroomm CCoDCC.. ((2200Eh1~n7t7t)vp).i.sCrC:eo/n/enwtnmewteernwrstsf.ac[olodrrcCh.DD~eiimossieveca/aabsslreese.CaCosoUntnptfetrdreooaldlt~aaennndgddT/apPPbrdrleefev/vs2e,e0nnJt&tiai6oonbnnura(e(rCCayODsC2C)tf0.)e.1e7FFd,oouiunVrrgotthrhleNuNpamotaerittiOoconnaneara.dll.RRpRedeeptfpo.rorirtetvooennd HHfuruommmaann EExxppoossuurree ttoo. hEintvpisr:o/nJmuwewnntsacldCchgeomvijceaxlsp.oUsuprdearteepdorTta/bilnedse, xJahntumalry 20~7, Volume One. Retrieved from Donahue, 5, KP Kleinman, MW Gillman, Oken. (2010). Trends https://www.cdc.6ov/exposurereport/index.html. Donahue, S., KP Kleinman, MW Gillman, E Oken. (2050). Trends iinn BBiirrtthh W Weeiigghhtt aanndd GGeessttaattiioonnaall LLeennggtthh AAmmoonngg S3Si6inn4g.glldeeottioo:nn1TT0ee.rrm1m09BBi7irr/tthAhs0sGiinn.0tthbhe0e1UU3nneii3tte1edd81SScttabattaeefss,S, 1$999900--22000055.. OObbsstetettrriiccss aanndd GGyynneeccoollooggyy,, 211255((22 ((pptt.. 1$))),, 335577-- EEggeegghhyy PP and M 364. doi: PP and M Lorber. (2011). An assessment of $O.$097/AOG.ObO~3e3585cbd5f5 Lorber. (20&~). An assessment of tthhee eexxppoossuurree ooff AAmemriceanstrtoopiperefrcfliuuooarroooonccttaasnnee ssuullffoonnaattee:: A A EnccvooimmrppoaanrrmiisesoonnntaoolffEeepssittdiimemmaaitteoedldoiignnytta.akk2ee1w,wii1tt5hh0-vv1aa6llu8u.eess iinnffeerrrreedd ffrroomm NNHHAANNEESS ddaattaa.. JJoouurrnnaalloof[EExxppoossuurree SScciieennccee aanndd Emmett, ., FS Shor, Environmental Emmett, E., FS Sharer, H Zhang, D FreemanC, Desai, Epidemiology., 2~, $50-$68. H Zhang, D Freeman, C Desai, LLMM SShhaaww.,. ((22000066).). CCoommmmunuintityy EExxppoossuurree ttoo PPeerrfflluuoorrooccttaannooaatete:: RReellaattiioonnsshhiippss BBeettwweeeenn SSeerruumm CCoonncceentnrtraattiioonnss aanndd EExxppoossuurree SSoouurrcceess.. JJoouurrnnaall oof[ Fei, C., JKOOccMcccuulpapauatgithioolnniaanll,aaRnnEddETEnvnaivrrirooonnJmmnOelenesnteta,nal.l MM(e2ed0di07cic)ii.nneePe((JrOOflEEuMMor,)i, n44a88t,,e77d55C99h--e77r77n0i0.c.als and Fetal Growth: AStudy within the Fei, C., JKDaMnicsLhauNgathilionn,alREBiTratrhoCnoeh,orJ tO.lsEennv.i(r2o0n0m7e)n.tPaelrHfleuaolrtinhaPteerdspCechteimveics,als11a5n(d11)F,eta16l 7G7r-o1w68t2h.: A Study within the FFealltteerr,, 5. GP Daston, SYEuling, AH Piersma,MS Tassinari. (2015). Assessment of health risks resulting Danish National Birth Cohort. Environmental Health Perspectives, 2~5(~$), &677-$682. S., GP Daston, SY Euling, AH Piersma, MS Tassinari. (20~5). Assessment of health risks resulting ffrroomm eeaarrllyy-iliffee eexxppoossuurreess:: AArree ccuurrrreenntt cchheemmiiccaall ttooxxiicciittyy tteessttiinnggpprorottooccoollss aanndd rriisskk aasssseessssmmeenntt mmeetthhooddss Frit Hanaasddeeneq,quuBaa.tt(ee1??95CC1r)ri.itticcBaaolldRRyeevWviiaeetwwessriinCn oTTmooxpxiaiccrootlloomggeyyn,,t44s55(i(3n3))C,,hi22l15d99r-e-22n4:444.C.hanges During Growth and Related Changes in Body Friis-Hansen, BCo. m(p~o9s6i5t)i.oBn.odPyedWiaattreircsC,o2m8(p2a),rtm16e9-n1ts51i.n Children: Changes During Growth and Related Changes in Fromme,BoH.d,yCCMoomspcoh,sitMionM.orPoevdiitaztr,ic|sA,l2b8a-(2A)l,ej~a6n9d-r~e8,5.S Boehmer, M Kiranoglu, Faber, | Hannibal, O Genzel- FrommeB, oHr.o,vCicMzeonsyc,h,BKMolMetozrkoov,itzW,VIoAlklbela.-A(le20ja10n)d.rer,eS-BaonedhmPoesrt,naMtaKlirEaxnpoogsluur,eF tFoaPbeerrf, lIuHorainnnaitbeadl,C0omGpeonuzneld-s Genus, (5(BP,PoFFrLCCoC)suv).ri.ctzEEiensnvn,viyiDrr,ooBBnnimmKrekoehnlonetlttazaz.lkl oSS(,c2ci0iWee1nn3cc)Vee.ol&G&kaesTTlt.eerc(co2hhin0nno5tole0loos)g.tgyiyPn,,rao44l-44E,a,ln77id15m2i2Pn33a-o-t77si1t~on22na99to.a.fl Exposure to Perfiuorinated Perfluorinated Compounds Compounds Using Genuis, Cholestyramine and Chlorella pyrenoidosa. ISN Toxicology, Article ID 657845. S., L Curtis, D Birkholz. (2053). Gastrointestinal Elimination of Perfluorinated Compounds Cholestyramine and Chloretla pyrenoidosa. 15RN Toxicology, Article ID 657849. Using HHaann,, XX..,,DDLL NNaabbb, bMMH,H RRuusssselelll,, GGLL KKeennnneeddyy,, RRWW RRiicckkaarrdd.. ((22001522).). RReennaall EElliimmiinnaattiioonn ooff PPeerrfflluuoororcoacarbrobxoyllaatteess Harts, M.((,PPSFFCCLAAs)sR.)i.fCCahshe-emSmihicimacaalnlR,ReAesseMeaarCrcaclhhafiinant,TTooXnxiYicceoo,llooAggyMy..,,M22o55r,,a,3355T--F4466W..ebster, E Oken, SK Sagiv. (2017). Predictors of Per- Harris, Ma.n,dSLPaRlyiffalsu-oSrhoiamlkaynl, SAuMbsCtaanlacfeat(, PXFAYSe), APlMasMmaorCao,nTcFenWtreabtsitoenrs, EinO6k-e1n0, YSeKaSraOglivd. A(2m0e~ri7)c.aPnrCehdiilcdtroerns. of Per- Environmental Science & Technology, and Polyfluoroalkyl Substance (PFAS) Environmental Science & Technology, Advance Access: DOI: 10.1021/acs.est.6605811 Plasma Concentrations in 6-$0 Year Old American Advance Access: DOh ~O.2022/acs.est.Sb0582~ ChiMren. HHaauugg,, L., SS HHuubbeerr,,GG BBeecchheerr,, CCTThhoommsseonn,,. ((22001515).). CChhaararactceterriissaattiioonn ooff hhuummaann eexxppoossuurree ppaatthhwwaayyss ttoo pIpneetrrefflrlunuoaortriiinonanatate,edd3cc7,oomm6p8p7oo-uu6nn9dd3ss -- CCoommppaarriinngg eexxppoossuurree eessttiimmaatteess wwiitthh bbiioommaarrkkeerrss ooff eexxppoossuurree.. EEnnvviirroonnmmeenntt Karman, A. | Ericson, International, Karrman, A., I Ericson, 8 an Bavel, 37, 687-693. B van Bavel, PPOO DDaarrnneerruudd,, MM AAuunnee,, AA GGllyynnnn,, SS gnel, Lignell, GG LLiinnddssttrroomm.. ((22000077).). EExxppoossuurree ooff PTPerererfnfldiuu,oor1rii9nn9aa6tt-ee2dd00CC4hh,eemimincicSaawllessdttehhnrr.oouuEggnhhviLLraaoccnttamatetiinootnna::LlLeHeveveaelllssthoofPfeMMrasatpteccchhteeiddvesHH,uu1mm1aa5n,n 2MM2ii6lll-<k2a3a0nn.dd SSeerruumm aanndd aa TTeemmppoorraall Kim, 5... KT Lee, CS Kang, Trend, $996-2004, Kim, S.-K., KT Lee, CS Kang, L Tao,K Kannan, KR Kim, CK Kim, in Sweden. Environmental Health LTao, K Kannan, KR Kim, CK Kim, J Lee, PS PaYrWkYo,o, JY Ha, Perspectives, ~5, 226-230. JS Lee, PS Park, YW Yoo, JY Ha, YYSS SShhiinn,, JJHH LLeeee.. (i(22m0p01l~1i)c).a.tDDiioissntstrriifbbouruttipioronennooaftfappleerarffniluduooprrooosccthhneeamtmaiilccaaellxsspobbseeuttrwweese.eennEssneavrriaaroaannnmddenmmitilalkklPfrrooolmlmuttithohene,ss1aa5mm9e,e 1mm6o9ot-thh1e7e4rr.ss aanndd LLuiu,, JJ,., J Ui, Y Liu, HM implications Li, Y Liu, HM Chan, Y Zhao, 2 Cai, Y Wu. for prenatal and postnatal Chan, Y Zhao, Z Cai, Y Wu. (2011). Comparison on gestation and lactation exposure exposures. Environmental Poflution, ~59, ~69-~74. (20~). Comparison on gestation and lactation exposure ooff ppeerrffiluuoorriinnaatteedd ccoommppoouunnddss ffoorr nneewwbboornrnss.. EEnnvviirroonnmmeenntt IInntteerrnnaattiioonnaall,, 3377,, 1~220066--1~221~22.. Useofo reference to this model without proper attribution toMOH sprohibited. a42 33774499..00004422 STSTAATTEE0707443366228877 LLoocccicsainsoofa,APAn,F.o,OJJ,LAL CCaanamdmpbPpeFbleOllSl JJirrn,, tMMhEEeAmAnondndeekrrseseyenna,,nHdHJJhCCullmeewawenelllluIsIlIi.I.n(g(22a0011P11)B.)P. KEEvvmaoaldluueaalt.tiioonRneaagnnulddapptorreredydiTciotcixotinicooooflnfogppyhhaaarrnmmdaaccookiknineettiiccss Pharmacology, 59, 157-175. of PFOA and PFOS in the monkey Pharmacology, 59, 157-175. and human using a PBPK model. Regulatory Toxicology and LLooccccisiasnaon,AoA,., MMPP LLoonngsnneecckkeerr,, JILL CCaammppbbelelll Jrr,, MMEE AAnnddeerrsseenn,, HHFF CClleewweellll lIlI.I. ((22001133).). DDeevveellooppmmeennttooff PPBBPPKK MMooddeellss Enffovorir rPPoFFnOOmAAeananntddaPlPFHFOeOSaSlftfoho,rrPHaHruutmmaAan.n PP76rr,eesg2nn5-aa5nn7cc.yy aanndd LLaaccttaattiioonn LLiifef SSttaag~eess.. JJoouurrnanlaoofl[ TTooxxiiccoollooggyy aanndd MMODHH. ((22Eo000f0n8P8v)r.)ir.oopMMnoiminsnneenednestsRaooultltHaaeseDDaeReleptphlaaa,rtrPtitmmnageretntnAtot.o,Hofe7fHa6Hel,aet2lha5tlRt-hh5i..s7k.SStLtaiamtteietmmsoeenfntGtorofoj'uNNneedeewddataaennrdd.RReeRaaestsoroninaeabvbleledennfeerssossm((5S0ONNAARR)) iinn tthhee MMoatttteerr ohiftPor:o/p/uossreudc RheualelsthRsetlaattei,ngmnt.ousH/edailvths/RehisykiLskim/ritusloesf/Guraotuenr/dhwraitseorn.arR0e8trpidefv.ed from MM ODHH.. (2015). Minnesota DepartmentofHealth. Environmental Health &Biomonitoring http://www.health.state.mn.us/divs/eh/risk/rules/water/hrlsonarO8.pdf. (2015). Minnesota Department of Health. Environmental Health & Biomonitoring AAddvviissoorryy PPaanneell JJuunnee 99,, 22001155 MMeeeettiinngg BBaacckkggrroouunnddMMataetreirioasls.. RReettrriieevveedd ffrroomm hitp://usshealth state, mn. divs ped]tracking/panel/2015unematerials. pd. Midasch, O.,H Drexler, N Hart, MW Beckmann, J Angerer, 2007). Transplacental exposure http://www.health.state.mn.us/divs/hpcd/trackin~/panel/2015Junematerials.pdfi Midasch, O., H Drexler, N Hart, MW Beckmann, J An~erer,. (2007). Transplacental exposure ooff nneeoonnaatteess ttoo appenerdrfflElunuovoriroroooocnctmtaeannnetessauullffHooennaaaltttehe,aa8nn0dd, pp6ee4r3rff-llu6u4oo8rro.oooccttaannooaattee::aa ppiilloott ssttuuddyy.. IInntteerrnnaattiioonnaall AArrcchhiivveessooffOOccccuuppataitioonnaall Minnesota Department of Health (DH). (2008). and Environmenta! Health, 80, 643-648. Minnesota Department of Health (MDH). (2008). SSttaatteemmeenntt ooff NNeeeedd aanndd RReeaassoonnaabblleenneessss ((SSOONNAAR)R,), JJuullyy 1111,, h22i00tp00:8/8..fSSuunuppppoorhrtetaddlootcchusutmmaeetnnet,t rreellaattiinn~gmntt.oousHH/edeaialvlstt/hhehRR)iiissskkk/LLriimumliiettsss/ffwoaotrreGGr/rrhooiuusonnnddawrwa0a8tteeprdrfRRuulleess.. RReeltriieevveedd ffrroomm Mogensehnt,tpU:/P/wGwrwan.hdejae!athn,.sFtaNteie.mlsnen.,usP/dWievisn/ee,h/risBkud/rtuz!-eJso/rwgaentesrejnh,rls(o2n01a5r)O. 8B.rpedafstfeeding as an Exposure Pathway for Perfluorinated Alkylates. Environmental Scienc&e Technology, 49, 10466-10473. Mo~ensen, U., P Grandjean, F Nielsen, P Weihe, E Budtz-Jorsensen,. (2015). Breastfeedin~ as an Exposure Pathway for Perfluorinated Alkylates. Environrnentat Science & Technology, 49, 10466-10473. MMoonnddaal,l,BDDr,.e,aRRstHHfeeerrenndaainnnddgAee:zz PW Woeteleldndtooinna,l, BBExGGcrAAerrtmmisostntrrooRnongug,t, eLLjjfGGoiribbMssoootnnh,,eMMrJJs LaLoonppdeezIzmE-Epslspipicinnaotosisaoan,,sHHfMMoI SIShnhifinan,n,tTTEFxFlpeleotctschuherre,er.,t.o((.22001144)). PBerrefalsutofreoeadlikny~l:AAcidPs.oteEnntviailroEnxmcernettiaolnHReaolutteh fPoerrsMpeoctthieverss,a1n2d2(I2m)p,li1c8a7t-io16n2s.for Infant Exposure to Monroy, R. K Morrison, K TeAtokins,on, C Kubwabo, BStewart, WG Foster,. (2008). Perfluoroalkyl Acids. Environmental Health Perspectives, 122(2), 187-192. Monroy, R., K Morrison, K Tea, S Atkinson, C Kubwabo, B Stewart, WG Foster,. (2008). SSeerruumm lleevveellss ooff pRpeeersrfefllauuroocrrhoo,aal1lkk0yy8ll,cc5oo6mm-6pp2oo.uunnddss iinn hhuummaann mmaatteerrnnaall aanndd uummbibliliiccaall ccoorrdd bblloooodd ssaammplpeless.. EEnnvviirroonnmmeennttaall Nelson, Nelson, RJJb..ae((ss22ee00d1a16r6o)c.)hn., J[[1PuP0een8rres,soo35,nn6aa2-l6l02CC1.o5ommMmemuenutiincnicagatAtiiogonennrrdeea~gaaarrndddiinnM8gatMMeDDriHHalMMsNNor((EEtaahssett AMMdevetitrrsooo))ryPPFFPCCanbbeiiloommooontnihtietoorEriinnnv~girpporrnoomjjeeecncttt addlaattaa Health Tracking and Blomonitoring Program. based on June 9, 20:~5 Meeting A~enda and Materials Health Trackin~ and Biomonitorin~ Program. for the Advisory Panel to the Environmental Olsen, G.,hhittItpMp:!:!B/wufrwurwss,w.hhDeeJaalE!tthhhrs.eststamatateen..,mmJFnnWr..uosuh/dsli/viscd/hhip,vcdsA/t/MrahScoekaicnca~dt:/,JptJaLrnBeault/c2e2kn00h1i1o55fnJfuug,nnLe/emRpamtZaaeontbreeierlai,all!s/s(.~20pp0ddf7]f)].. Halt of Serum Olsen, GE.,liJmMinBatuirroinso, fDJPeErhfrleusomroaonc,tJaWnesFurlofeohnlaicthe,,APMerfSleuaocraoth, eJxLaBneusteulnfhoonfaf,teL,RaZnodbePle,.rf(2lu0o0r7o).ocHtaanlfo-laifteeoifnSReetruimred SchectFeFElArlluuim,oorrinNooaccMhthiaeoelmnmiikieoc-afaBlalPsPPesr,rrofolAduduoMucrctotCiioaooclnntaafW Wnao,eorsrKkkkueelrKfraosst.n.oaE,EtnenJv,AviiPrrCooenonrmmflieuenoantrtoacaTlhliLeHHxGeneaeaaonlnltetth,hs,uPPLeleSfrorssnHppaeyectectn,tiiavvaeennTssd,R,, P11H11ea55rr,,frlu11i2o2s9r9,o88-oM-11ca33tl0a0l5n5,,o.aL tBeitinnbRauertinr.ed (2012). Schecter, A., N (2012). Polyfluoroalkyl Malik-Bass, AM Polyfluoroalkyl Compounds in Texas Children from Birth through 12 Years of Age. Calafat, K Kato, JA Colacino, TL Gent, LS Hynan, TR Harris, S Malla, Compounds in Texas Children from Birth throush :~2 Years of A~e. Environmental L Birnbaum. Environmental Sethi, P.,HHCeeaAalWltthhhiptPeeer,rssppBeecSctCitivvueemssm,,i~n122g00s,,,559R90N0--55H99i44n..es,S Muralidhars, JV Bruckner,. (2015). Ontoogfpelansmya proteins, Sethi, albumin and binding of diazepam, cyclosporine, and P., CA White, BS Cummings, RN Hines, S Muralidhara, albumin and binding of diazepam, cyclosporine, and deltamethrin. Pediotric Research, JV Bruckner,. (2016). Onto~eny of deltamethrin. Pediatric Research, 79(3), 409-415. plasma proteins, 79(3), 409-415. SSpplilieetthhoolPfff,r, oHHg..r,,aLLmTTaaBool,,oSoSdMMSSSphohatavsveefrro,,rKKEMMxpAAollsdduooruuess,A, sKKsAAesPPsaamssessn,,tKK: KKDaaenncnnlaainnn,i,nGGgAALeEEvaeadldoson,no.f,. P((e22r00f008l8)u.)o.rUUinssaeetooefdf NCNeoewmwbpbooorurnnndSSsccrrieeneenNnieinnwg~.. York State Infants. Environmental Scienc&e Technology, 42114), Program Blood Spots for Exposure Assessment: Declininl~ Levels York State Infants. Environmental Science & Technology, 42(14), 5361-5367. of Perfluorinated 5361-5367. Compounds in New TThhoommsseenPn,e,rCf.,Cu, oLLSSriHHnaaauutgge,,dHHCoSSmttipiggouuummn,,dMMs,FFPrrooolsshhyaaburugog,m, iSSnLLaBBtoeordraadDdwiweplehllel,,nGyGl BBEccthhheeerrr,s,., ((a22n001d100)P.)o.lCCyhchahalnnoggreeissnaiintneCCdooBnniccpehenentnrtyraalttsiiooinnnss ooff NPoerrwfiuegoiriannatBerdeaCsot-mMpilokunddursi, nPgoTlwybelrovme iMnoantetdhsDoipfhLeancytaltEiotnh.ersE,nvainrdoPnmoelyncthalloSricniaetnecde &BipTheecnhnyolsloingy, 44, 9N5o5r0w-e9g5i5a6n. Breast-M ilk durin8 Twelve Months of Lactation. Environmental Science & Technology, 44, USEPA. USEPA. ((922500500000)-.)9. 5UU5S56E.EnvnivriroonnmmeennttaallPPrrootteeccttiioonn AAggeennccyy ((EEPPAA).). OOffffiiccee ooff WWotaeter.r. M Meethtodholoogdyf~ooorrlDDeoreirgivviinyngg AAmmbbiieenntt W Waatteerr QQuuaalifittyy CCrriitteerriai ~foorr tthhee PPrrootteeccttiioonnoofJ~HHuummoann HHeealatlthh.. EEPPAA--5B2222--8B--0O00--0O0044.. OOccttoobbeerr 22000000.. RReettrriieevveedd fromhttps://nepis.epa,gov/Exe/ZyPDF.c5i/20003D2R PDF?Dockey=20003D28. PDF. UUSSEEPPAA.. ((22000044)).. OOffffiicceeooffSScciieennccee AAddvviissoorr.. SSttaaffffPPaappeerr:: RRiisskk AAsssseessssmmeenntt PPrriinncciipolleess oanndd PPrraaccttiicceess.. Useofo reference to this model without proper attribution toMOH sprohibited. a433 33774499..00004433 STSTAATTEE0707443366228888 USEPA. (2011). USEnvironmental protection Age-Nnaticonyal Centerfor Environmental Assessment. Exposure USEPA. (2011). US Environmental Protection Agency - National Centerfor Environmental Assessment. Exposure Factors Handbook. 2011 Edition. Retrieved from Factors Handbook. 2011 Edition. Retrieved from tts:/clpub epa.ov/nceais/recordislay lm?eid=236252, https:!/cfpub.epa.gov/ncea/riskirecordisplay.cfm?deid=236252. USEPA. (20165). US Environmental Protection Ageney- Office of Water Health Effects Support Document for USEPA. (2016a). US Environmental Protection Agency - Office of Water. Health Effects Support Document for Perfluorooetanoic Acid (PFOR). Retrieved from hts pa.fov/sites/production/fes/2016 Perfluorooctanoic Acid (PFOA). Retrieved from .h..~t-t.~p..~.s-~/./.~.w-...w...~.w.....~.e..p..-a.~:g~-.v../.~s..i.t.~.e..~s../.p..~r...~..-d..~u....c..t-i~.~..~.n.j..f..!~Le..~s../~~ 05/documents/ofoa hesd finatolin.pdf 05/documents/pfoa hesd final-plain.pall UUSSEEPPAA.. ((22001166cc)).. UUSS EEnnvviirroonnmmeennttaall PPrrootteeccttiioonn AAggeennccyy -- OOffffiiccee ooff WWaateterr.. HHeeaalltthh EEffffeeccttss SSuuppppoorrtt DDooccuummeenntt ffoorr Perfluorooctane Sulfonate (PROS). etieved rom htps://u cpa gov stes/production/f2e01s6/. Perfluorooctane Sulfonate (PFOS). Retrieved from htts:[/www.ea~gov/s!tes/roduction/files/201605/documents/hesd pfsfinal-pain pdf 05/documents/hesd pros final-plain.pdf UUSSEEPPAA.. ((220011664d).). UUSS EEnnvviirroonnmmeennttaall PPrrootteeccttiioonn AAggeennccyy -- OOffffiiccee ooff WWataeter.r.DDririnnkkiinngg WWaatteerr HHeeaalltthh AAddvviissoorryy ffoorr Perflucrooctane Sulfonate (PROS). Retrieved fromhttps: agov/sitesproduction/f20e1s6:/ Perfluorooctane Sulfonate (PFOS). Retrieved from https://www.epa~gov!s!tes/roduction/fi/es/201605/documents/plos health advisory fina-plain pdf 05/documents/pros health advisory final-plain.pall Verner, M.A. Neuets, ET Jensen, Fromme, wVolkel, UC Nygaard, BGranum, MP Longnecker,. (2016). A Verner, M.-A., F Ngueta, ET Jensen, J Fromme, W Volkel, UC Nygaard, B Granum, MP Longnecker,. (2016). A SSiimmppllee PPhhaarrmmacaockoiknineettiicc MMooddeell ooff PPrreennaattaall aanndd PPoossttnnaattaall EExxppoossuurree ttoo PPeerrfflluuoorrooaallkkyyll SSuubbssttaanncceess ((PPFFAASSs)s.). Environmental cence & Technology, 50, 78.985 Environmental Science & Technology, 50, 978-986. WebPlotDigitizr. (2017). Version 3.11 Released (an 17, 2017). Retrieved from WebPIotDigitizer. (2017). Version 3.11 Released (Jan 17, 2017). Retrieved from tp: farinfooWebaPlottDigitiser/ http:/!arohatgi.info/WebPIotDigitizer/ Wu, X. DH Bennett, AM Calfa, K Kato, M Stryner,E Andersen, RE Moran,0 TancrediNS Tule, I Hertz- Wu, X., DH Bennett, AM Calafat, K Kato, M Stryner, E Andersen, RE Moran, DJ Tancredi, NS Tulve, I Hertz- Picotto, (2015). Serum concentrations of perfluorinated compounds (PFC) amon selected Picciotto,. (2015). Serum concentrations of perfluorinated compounds (PFC) among selected populations of children and adults in Calfornia, Environmental Research, 135, 264-273. populations of children and adults in California. Environmental Research, 135, 264-273. Useofor reference to this model without proper attribution to MDH isprohibited. 33774499..00004444 4444 SSTTAATTEE_0077443366228899 APPEENNDDIIX |I --- Summmmaarry ooff pl~acern~ttal~ arnidbbre~aesatsmtmili[kttrraar~nssffi~e:~rr ssttuuddyy ddaotta&. plcentl Tanster Placental Trans[er Several studies measured maternal and cord serumlevels of POS an PFOA ear the time of delvry thereby Several studies measured maternal and cord serum levels of PFOS and PFOA near the time of delivery, thereby Permifpnlacemgtal aarsems anad kasl bodiyburndennathiPwoonnant permitting an estimation of placental transfer and initial body burden in the newborn infant. 2705 Maternal Serum andCordBlood Concentration summary ) PFOS Maternal Serum and Cord Blood Concentration Summary SudDescipion | PrOSNtamalSetum | p08Cardlood |#R0SCordbiod a Study Description PFOS Maternal Serum PFOS Cord Blood Concetestion 5/1) |_ concentration 1g) ateratlio Concentration (laglL) Concentration (pg/L) PFOS Cord Blood to Maternal Ratio Mean Median 95th or Mean Median 95th Or Mean Median 95th or Fssookanpesal ax Tittlemier et al. 2004 - 36.9 Max 16.7 Max 0.45 Max pooled samples Boer 3007 iT 5 Fei et al. 2007- maternal 29.9 11 0.37 Emesr samples taken in second trimester [Miascherarzoor [tai| | [7a|| fos | Midasch et al. 2007 12.1 7.2 0.60* [Monroyeval2008 161[6st| [739 eos | [oss om | Monroy et aL 2008 (Fommeetai2010 [35[32 [61[31 10 [27 [onlos [0% Fromme et ol. 2010 [veioLzot --|sas4[2908[13388|1st6 14m [eer [053 [oso [050 Liu et al. 2011 [metoizori [ss| [sa l20 [36 [osx | fos Kim et al. 2011 (corauerai0i5 [367 [3065 [285 [326 5iis [aos[0% 03% [oss Cariou et al. 2015 16.19 14.54 7.19 6.08 0.44 0.42 3.5 3.2 6.1 i.i 1.0 2.2 0.31 0.31 0.36 3.184 2.922 13.188 1.686 1.470 6.674 0.53 0.50 0.50 5.6 9.4 2.0 3.6 0.36 0.38 3.67 3.065 24.5 1.28 1.115 8.04 0.35 0.36 0.33 "nim |031 031 [033 **Minimum 0.31 "Mami 080 030 | 031 **Maximum 0.50 see [03 0d 09 **Average 0.40 "Geometreiacn [042 1039 | 039 **Geometric Mean 0.39 indi marco os ts ange om 0410030 *Individual maternal:cord blood ratios ranged from 0.41 to 0.80 eatenTim 3 pated ame) 0dFo 31 (ae sem eased second imei, il vrses **Excluding Tittlemier et al. {pooled samples) and Fei et al. {maternal serum measured in second trimester). In all other studies rt me ko wi week she de. maternal samples were taken at or within first week after delivery. FO Watermat Serum and Cod Blood Concentration Summary Study Description Terie etal 3001p eConcnanteatfeyn) ||e e_Conncaneatie n (1) in s r[eaevnena[r2 Tittlemier et al. 2004 -pooled [i oer [32 [[ | J[] =] samples Fi2007tpaoren | 45 5 Fei et al. 2007- maternal Samen omovsin samples taken in second meter trimester [Miascherora00r [as| | [sar|__| tae| | Midasch et el. 2007 [orroyval2005 [20[181 | [asa [iss| [os [ow | Monroy et al. 2008 (Fommeerai2010 [23 [15 [52 [17 1s [37 onJom [on Fromme et aL 2010 [dveioLzott [16%[161[585 [15 sas [asm[on [oss [ii Liu et al. 201I [metoizoti [16| [32 [ii [a7Joes | [om Kim et ~1. 2011 (Cormwerar2055 [122[10% [731 losisom_|706 [ors [om [oss Cariou et al. 2015 PFOA Maternal Serum Concentration (pg!L) Mean Median 95th or Max 2.2 4.5 2.75 2.24 2.3 1.655 1.6 1.22 1.81 1.9 1.264 1.045 5.2 5.879 3.2 7.31 il tel ord od as ang om 09210155 wream""envrteaiiMieeamnn| 01[0082888057 [0[0080878834 ||| [o010817m003 * individual maternal:cord blood ratios ranged from 0.92 to 1.95 PFOA Cord Blood Concentration (pg/L) Mean Median 95th or Max 3.4 3.7 3.41 1.94 1.7 1.5 1.1 0.919 1.58 1.4 3.7 1.115 6.442 2.7 0.860 7.06 **Minimum **Maximum **Average **Geometric Mean PFOA Cord Blood to Maternal Ratio Mean Median 95th or Max 1.55 0.82 1.24" 0.87 0.74 0.91 0.69 0.75 0.87 0.74 0.88 0.82 0.74 0.88 0.83 0.83 0.71 1.1 0.84 0.97 UUsseeo#f foorrrreeffeerreenncceettootthhiissmmooddelelwwiitthhoauuttpprrooppeerraattttrriibbuuttiioonnttoo MMDDHHiisspprroohhiibbiieteedd.. a4s5 33774499..00004455 SSTTAATTEE_0077443366229900 Cut Talemer 1 (pled sams) and FL. (ae sem esr second ines. arses **Excluding Tittlemier et al. (pooled samples) and Fei et al. (maternal serum measured in second trimester). In all other studies arnt eps wes ke oo i et week she den. maternal samples were taken at or within first week after delivery. The reported mean atofcoord to maternal concentrations anged fom 0.31 (Fromme, 2010) 100.60 The reported mean ratios of cord to maternal concentrations ranged from 0.31 (Fromme, 2010) to 0.60 eported mean aio from thes. tudes were 0.42 nd 0.87 for OS an POA respectcly. These average ((MMiiddaasscchh,, 22000077)) ffoorr PPFFOOSS aanndd ffrroomm 00..6699 ((KKiimm,, 22001111)) ttoo 11..2244 ((MMiiddaasscchh,, 22000077)) ffoorr PPFFOOAA.. TThhee aavveerraaggee ooff tthhee reported mean ratios from these studies were 0.42 and 0.87 for PFOS and PFOA, respectively. These average vvaalluueess wweerree uusseedd bbyy MMDDHH iinn eevvaalluuaattiinngg tthhee ssiimmppllee TTKK mmooddeell.. restr Tronter Breastmilk Trans/er Several studies measured maternal serum concentarnadbtrieaosnts, thereby permiin a estimate of Several studies measured maternal serum concentrations and breastmilk, thereby permitting an estimate of ertitoning fom maternal serum nt reas and prediction of breastmilk concentrations. partitioning from maternal serum into breastmilk and prediction of breastmilk concentrations. 20S Maternal Serum and Brest Concentration Summary PFOS Maternal Serum and Breastmilk Concentration Summary SudsDespion ros Maalsoum| FRGBassi | Pros sammie Study Description PFOS Maternal Serum CCoonncceenntrtraattiioonn ((pugg//LL)) PFOS Breastmilk CCoonncceentnrtraattiioonn ((pugg//LL)) ror Mean Median 95th or Mean Median 95~h oeMax or PFOS Breastmilk to MMaatteerrnnaall RRaattiioo Mean Median 95[h or Farmanetal 2007 Karrman et al. 2007 [Fommeetai 3010 Lu etal. 2011 Fromme et al. 20!0 Liu et al. 2011 meta 2011 Kim et al. 2011 Garou etl 2075 Cariou et al. 2015 [207 |187 |#80 [0201[odes [047 [oto[oms [ool| 20.7 [32 [20 [63 | Joos [00s|_loow[oon | 3.2 [331.18844 [56 | Toa Joost| fons Joou| [oom] 5.6 [567 [50s [245 [oot[<Gieoomae[tVWreii0nocriho%iimueemn[||||o00000o00011101n"832||||| 0000000001113422 |||f|o0a00o000ti111ss53| 3.67 18.7 2.9 [229.92222 3.065 Max 48.0 0201 0.166 0.47 0.010 6.3 0.04 0.08 [11331.18888 [000.05566 [000.04422 | 00.115988 [000.01188 9.4 0.061 0.13 0.011 24.5 0.04 <LOQ 0.376 0.011 Minimum Maximum Average Geometric Mean 0.009 0.014 [000.01144 0.009 0.014 0.012 0.012 Max 0.01 0.013 000.01155 | 0.014 0.015 PFOA Maternal Serur and PFOA Maternal Serum and Suis Descpton Study Description Fromme val 2010 Fromme et al. 2010 Gauciol 2071 Liu et 01. 2011 im eta 2015 Kim et al. 2011 Corio 2085 C~riou et ~21. 2015 east concentration Summa Breastmilk Concentration Summary | PROAMoeralSerum| FROR res PFOA Maternal Serum CCoonncceentnrtraattiioonn ((pgg//LL)) PFOA Breastmilk CCoonncceentnrtraattiioonn ((pugg//LL)) eon eon | Midian Mean Median 95th Mean Median 95th FRORes ns PFOA Breastmilk to MMaatteerrnnaall RRaattiioo Ea Mean Median 95th i on avoaer 1.7 [Tess[Tass [sem [socedcstonoiaatne [11 [ois oom [0b| 1.655 [ie | [52 Joon| [oor foo | foo] 1.6 [12 [56% [751 [oot[tGoeaoVi[mvnoieiersoamgsnne|[|| o00000010o82053692||00008986 |lo000a20o0o42nse34| 1.22 1.5 1.264 1.045 or Max 3.9 5.879 3.2 7.31 or Max Only 2% 0.25 detection rate 0.181 0.121 1.44 0.041 0.077 0.041 <LOQ 0.308 Minimum Maximum Average Geometric Mean 0.109 0.026 0.034 0.096 0.096 0.096 or Max 0.064 0.245 0.024 0.042 The reported mean atoof breastmilk to maternal serum concentration ange fom 0.01 (Karman, 2007)to The reported mean ratios of breastmilk to maternal serum concentration range from 0.01 (Karrman, 2007) to Teported mean tio fom thes tudes were 6.013 and 0.052 for 105and POA respectively. These average 00..001188 ((LLiiuu,, 22001111)) ffoorr PPFFOOSS aanndd ffrroomm 00..002266 ((KKiimm,, 22001111)) ttoo 00..110099 ((LLiiuu,, 22001111)) ffoorr PPFFOOAA.. TThhee aavveerraaggee ooff tthhee reported mean ratios from these studies were 0.013 and 0.052 for PFOS and PFOA, respectively. These average vvaalluueess wweerree uusseedd bbyy MMDDHH iinn eevvaalluuaattiinngg tthhee ssiimmppllee TTKK mmooddeell.. Useof orreference to this model without proper attribution to MDHisprohibited. 33774499..00004466 4466 STATE orssezst STATE 07436291 AAppppeennddibx~ |I RReeffeerreencnec~e.s~: FEFeneivi,,iCCr..oeenttmelan.l.t((a22l0000H7e7)a)..ltPPheerPrfefllruusooprreiincntaaittveeedds,CCh1he1em5mi(ci1ca1al)lss:1aa6nn7dd7-FF1eet6taa8ll2GGrroowwthth:: AASSttuuddyy wwiitthhiinn tthhee DDaanniisshh NNaattiioonnaall BBiirrtthh CCoohhoortrt.. Environmental Health Perspectives, 115(11):1677-1682. FFrroommmmee,, HH..,eettaall. 2(200101)0.). PPrree-- aanndd PPoossttnnaattaall EExxppoossuurree ttoo PPeerrfflluuoorriinnaatteeddCCoommppoouunnddss ((PPFFCCs)s.). EEnnvviirroonnmmeennttaall SScciieencnec&&e TTeecchhnnoollooggyy,, 4444:: 77112233--77112299.. MKKiaalrrkrrmmaaannnd,,SAAe,.,rueettmaalal..n(d(2200a00T77e)).m. pEEoxxrppaoolssuuTrrreeenoodff,PP1ee9rrf9fl6luu-oo2rr0iin0n4aa,tteeiddn CCShwheeemdmiecicnaa.llssEntthvhrirorouougnghmheLLnatacactltaatHtiieooannl::tLhLeePvveeerllssspooefcftMMiavatetscc,hhee1dd15HH:uu22mm6aa-nn230 Milk and Serum and a Temporal Trend, 1996-2004, in Sweden. Environmental Health Perspectives, 115:226-230. iKKmiipmml,,i5cSa..-t.Ki..o,neesttfaao.lr. (p(22r00e1n11a1)t).a.lDDiaissnttdrriibpbuoutstiitoonnnatooafflppeeexrprffollusuuoorrreooscc.hheeEmmnivicciaarllossnmbbeeenttwtwaeeleennPolssleeurrtaaioaannn,dd1mm5i9il-lkk16ffr9ro-om1m74tt.hhee ssaammee mmootthheerrss aanndd implications for prenatal and postnatal exposures. Environmental Pollution, 159:169-174. LinLueiu,w,b1Jo,.,renteastl.a.l.E((n22v00i12r12o))n..mCCeoonmmtppaInartrieissroonnantiooonnnagglee,sst3taa7t:tii1oo2nn06aa-nn1dd21lla2a.ccttaattiioonn eexxppoossuurree ooff ppeerrfflluuoorriinnaatteedd ccoommppoouunnddss ffoorr newborns. Environment International, 37:2206-:1212. MMiiddaasschc,h0O,.. eettala.l. ((22000077).). TTrarnspalancenstalpeexxlppoosasuurrceeooeff nnneeootnnaatateesstltoo ppeerrfflulourooroocotacnteasnuelsfounlaftoenaaantnded ppeerrfflluuoororooocctatnaonoaatet:ea:a ppiilloott ssttuuddyy.. IInntteerrnnaattiioonnaall AArrcchhiivveess ooff OOccccuuppaatitioonnaall aanndd EEnnvviirroonnmmeennttaall HHeealatlthh,, 8800::664433--664458.. sMMaoomnpnrlrooeysy,., RRE,n.,veeittraoalln..m((e22n00t00a88)l)..RSSeseeerruaurmmchll,eevve1el0sl8so:o5f6f-pp6ee2r.rfflluuoorrooaallkkyyll ccoommppoouunnddss iinn hhuummaann mmaatteerrnnaall aanndd uummbibliliiccaall ccoorrdd bblloooodd samples. Environmental Research, 108:56-62. TTNioittrtllteehmmeirieenrr,,Ca.Sn. aoetdtiaaal..n2(2P0o00p04u4)l)a..tiPPorrneesss.eennOccreegaoofnf oAAhnniaioolnonigiccenPPeeCrrfofllmuupooorruiinnnaadttsee,dd 6OO6rr:gg3aa9nn5ii9cc-CC39oo6mm4p.poouunnddss iinn SSeerruumm CCoolllleecctteedd ffrroomm Northern Canadian Populations. Organohalogen Compounds, 66:3959-3964. Useofo reference to this model without proper attribution toMOH sprohibited. 33774499..00004477 a47 STSTAATTEE 0077443366226922 AAPPPPEENNDDIIXX IIII--- PPeeeerr RReevviieewwee~r" BBiioogg~raapphhiicca;~ll II~n--f~oforrmmaattioi~o-n~ ODrr.. JJeefj~frreeyy FFiisshheerr -~ TODorrx..ieJcfeoilfforrgeeiyycaFFliissRhheeesrreaiisrcaahr.reessHeeeaarrwccahhsttoofxxoiirccmoaellroolggyisstat wPwriiotthfhettshhseeorUU.i.SnS..tFhFeooooDddepaaannrddtDDmreruunggt AAodfdmmiEnniinvsiistrrtoraanttmiieoonnnt,,aNNlaatHtieiooannlatalhl CCSecenintetneecrref,fooCrrollege TofoxPiucbolliocgiHceaalltRhesaetatrhceh.UHnievwerassiftoromf GeerloyrgaiPar(oUfGeAs)s.orHine tjhoeinDedepthaertmUneivnetrosiftEynovfirGoenomrgeinatailn 2000 and served as Health Science, College Department Head of Public Health at Department Head of the Department of Environmental Health Sciences from 2000 to 2006 and the University of Georgia (UGA). He joined the University of Georgia in 2000 of the Department of Environmental Health Sciences from 2000 to 2006 and Directorof and served Director of theas the WIInnrttieegrrhddtiissPccaiipptlltiinenraasrryoynTTAooxFxii,ccoowlloohggeyyrePPrrhooeggrrwaaamms aaPtrtiUUncGGiAApafflrroIomnmve22s00t0i06g6a--t22o00r110a0.n.dHHSeeesnsippoeernntSt c22e55ynyeteaiarsrssinaattt httheheeToTTxooixxciisccooHllaoozggayyrdLLsaabbDoiorvraiatstoiororyny,, W anrdigThetchPnaitctaelrsAodnviAsFoBr, fworhethree OhpeewraatsioPnrainlcTipoaslicInolvoegsytigBaratonrcahnd Senior Scientist in the Toxics Hazards Division and Technical Advisor for the Operational Toxicology Branch. Dr. Fisher's research interests ae in the development and application of pharmacokinetic and biologically based `emDxmrapa. ottFhshiueesrmmheaesatr.i'tsiccRaraeellcsmemenoaotdrldceyehl,lssiwnttitootehraaessFsccDteseAr,rtataarhieienn inhhheaetashalelbtthhedceiriossvmkkesseloffiprronmovmmoelneevtnneavdviniirrdnoonntamhmpeepenlunticsataaeltl,i,oofffnooPoooBddfP--pKbbhoomarronrndmeeealaacsnnoddfkoioornccercctuuuicppgaaastntiiadoonnnbdaailolplcecodhhgieeaimctmiraiiclcclayasl.lbaOrs.ed eFixsphoesr'usrecsh.emRieccaelnttlyo,cwolitohgFyDmAo,dheelihnags ebxepceormieencinevionlvceluddeins twhoerkuisnegoiftPhBPcKhlmoroidnealtsefdoarnddrungosn-acnhdlopreidnaiatteridcs. Dr. stsFiooissllkvvheeeannsrt'stssse,,cshsffuumeeeemllnssti,,c,appeleestsstottixiiccimiciddaoeetlssoi,,nggpypeelmrarcccohhtldlaooertrlaiaintotgeen,,erPPxFpFaOeOArAi,en, naaocnnsefddsifobbnlicisvlespuephdnteehrssne,onwluooAAnl.rd.keHHirneesgthhawaanssiddthdienevcgveheillonlooruppinteeaeddrteoPPdBBaPPnaKdKndmmneonoododneneal-tlcssahlfflooodrrroiuunsssiaeemteeiidtnnrccyaa,nncceerr piqqrtiusuuakainnttaaitsifrfsyyyeiisntnshggmyrmmeoeneitttd,aabebaoxsoiltlsiiimssimnamtrioonoffgdsseolonaltlcvvsteeananttnitodmmnihaixxulttmuturarraneenssss.aafennDrddr.oddfFeesivvoseehllvelooerppnhiitnasnsg,gu3bbni0ioodylleooegragsirictcsaaoalnlflldyyienmmxgopoteitnirivviuaaetttneeecrddoe mmianonopdddheeynlssseiooffolnroargtttiahhcleaeldhhomyysoppidmooettelhhtiaarnyllag,ammaiinccd- mhphoaaitdssueitlttrarsaa.riiynn-eHetdhedsywsereaovvesiderraaalVlxiiggssriraitaniddnurugoaadSttceeeinessntttstuuidasdtenendnatttshstuaahmnneddaCnhppseoo.smsDtitddcr.oaoclFctitosIorhnraedalurlshffteaerllslyol3oIwnw0ssstyoioetnnautrttsehheeooffcceToooxnnxpccieeecrppoiteltssnogcaayennddiinnaa1ppp9phpl9yli6iscciaaoattlnoiiodognniactooafltf hpmpehhoyNydsIseiOoililSnocHggliTccoaaaangflldt mLaobdoeralst.orHye iwna1s99a9.VisDiutirnigngStchieisnttisimtea,thtehealCshoesmeircvaeldInasduAsdtjruynIcntstPitruotfeesosfoTroixnictoheloDgeypianr1t9m9e6ntaonfdPahtatrhmeacNoIOlSoHgyTaft aaLPnnaBddbPoKTTroomaxxotioidccreooyllloiiongngygy:~aa9itn9t 9W Wl.arbrDiioggurhhratitntogSSrtttyaahttaieesniUUtinmmniavilevese,rsrahisnetitydy.a.lhsDDuormr..saenFFirsisvs.heheedHrraehhsaahAssadsppjuusubebnlrlciisvtshehPdeerddoonfooevvsseeesrvorer11ri66an00ltnhppaeaatppiDeeorrnessaplooanpnrtamppnhehealanrsrtmmaoanacfdocPkoahikdanivnreimetstiaoiccrcssyolaabonnogddayrds ffOPoorBrgrPattKnhhieezmaDDotoidooDDen,l,.inAAgTDTrSS.inDDRFRlia,,sUbhUSoeSrrEaEPstPeoAArrayvanenadddnoimnnnooantnl-sh-pepraorInofndiftitethorgounamragntaaiinonznsiaza.tlaHitLioeoinnhessa.S.scHHiseeeenrwwvceaeadsssaIaonnsUUts.siS.et.uvddteeeerlalSeeltggenaaeatrtteeiionffngooarrClotthphmeaemniNNetolosrertteahh,ndAAwttalhlaadinncvttihisiccoerTTvyrareelbaauotatayytredds cOhrlgoarnoifzoartimona.nDdrd. iFcihslhoerraasceervtiecdcoindthuseinIngterPnAa-tpiornoapol sLeifde CSacriecnicneosgeInnsRtiitsukteGuiSdteeleirniensg. CHoemims Pitateste,Pwrehsiicdhenetvaoflutahteed cBiholloorgoifcoarlmMoadnedlidnicghSlopreocaiaclettyicSeacctidiounosifngthEePSAo-cpireotpyoosfedToCxiacrcolinooggye,nrReiskvGiufidoeeliwsneevese.rraHletisoxPicaosltoPgyrejsoidurennatlso,f tahned wwBMaoaiosdsleoCClgoioi-cn-PaPgrlairiMnnccoitippdhaaeellliUnIInnngivvveeSessptrteisiggciaaitattolootryrf ooGSnneeocaartigoNNianaattioinoofnnttaahhlleeIInSnfassolttlciititoueuftttye2ess0o0foo3fT.fHoHexHaeieclaotlwtlhhoags((yNNa,IImHrHe)e)v--msiseubuwppepperoorrorfttofeerdtdhswweeovoNrerakrktassilhhotonooappxlicooAonncloaMMgadaytethjmhoeeyuommrafntaSaitclicscia,aelalnncdes sMuobdceolminmgitatteteheonUAncivuetresiEtyxpoofsGureeorGguiaidienlithnee fLaelvleolsf 2(0A0E3G.LsH)efwroams 2a0m04e-m2b0e10r oafntdheScNieanticoenAadl vAicsaodryemBoyaorfdSfcoirentchees AsUUucSSbaEEcdPPoeAAmm((ym220o0itf00te77T-e-o22x0o0i1nc10o0Al))o.c.guiHHtceaeelEiisSsxcaapinnoesnaaucddreeshhoGoaccnudimmdeaeenlmimnabebsesLerooecorvfifealtttshheee(AeSSdEiAAGtBBoLSsrs)fffooforrrroddTmioiooxxx2iici0nno0laa4onn-g2idd0capp1lee0rSrcacchhinledloonrcrSaaetcsteie.e..nHcOHree.eiAFisdsivsahisfefoeerlrllyhlooawBwsooo.affr.dtt.hhfeeor the AddUeneciggavrrdeeereeesmiiitynny,obbifiaooTnlloodogxgaiyycPoffrhlroo.oDm gm.icitatnhhl eeZSocUUoinlenionivgvceyeer/rsssTiaiottnyxyidoocffaonlNNoeeagbbsyrrsaaofsscrkkioaaamteaaMtteiKKdaeeimtaaoirrrnnUefenoyyi.r,vTaearoMMsx.ti.cSSy.o.. loddgeeiggcrraeeleeSiicnniebbniicooelloso.ggyyDffrr.rooFmmishWWerrriigghhahtst State a B.S. State University, and a Ph.D. in Zoology!Toxicology from Miami University. Dr. Gory Ginsberg -- Dr. Gary Ginsberg - tDDror..xGGaiarcryyoGGliionnossgbbiseeirsrtggethhiaasss b baesesnaeeaststomoxexeinicctoosllofonoggiissrtteaamttettdhhieealCCoponrnnonegcertcaitmiccsuuttanDDdeepepavarartltmumaeetnnitotnooffofPPucuboblnliitccaHHmeieanalatltnhh,t,swwhihneecrroeenhhseeumsisettrhhee lleeaadd tppporurxoobidldcuiuocsclthotsesg,d,isttehthxeoetnebbnususiiilitlevtteeerlinnysvkvoiinrarosocnsnhmemiselesdnnrmtet,,en'nffostosoohdfdeoaprplrtrrooheddmruuececltdtassit,a,elaadpnnirddsosuagaervsva.aamrriDiseert.tayynGodoifnfesoovbttaehhlreeugrraitmmsioeeandddijioaaufnaaccnnotddnftaeeacxxmuppliotonyssauuanrrtteestshsinoeouurcYrcaocelnesess..SucmHHheeeoorhhlaassof pPuubblliischHeedaletxhteannsdivieslayssoinstcahnitldprenr'sohefaoltfehcrsoemlamstuendoiitsrysuemse.dDicr.inGeinastbtehrge UisniavdejrusnicttyfoafcCuoltnyneacttthiceuYtaHleeaSltchhoCoelnotfer cAcPaacummabpdlpuiceussm.H.yHeoHaefelhthShacaasisnedssneecirrsevvaeepsaddnseooislnnsta.aantnDnrpu.urmmoGbfbieenesrsrosbooefrfrUgoUsf.rS.ce.coEEemninvvmvieirudroonhnniitmmsyeePnmnhtetaDadllifcPPrirnorooemtteeaUcctCtttiioohonnennAAUiggnneei1vnn9ecc8ryy6s,iaatyddvvoiisfsooCrroyynccnooemmcmtmiictiutttteeHeesseaaaltnnhddCNNeaatntitioeonnraall Academy of Science panels. Dr. Ginsberg received his PhD from UConn in 1986. seofor reference to this model without proper attribution to MsO prohibH ited. 33774499..00004488 348 STSTAATTEE 0077443366228933 Or. JudyLakin - Dr. Judy LaKind - JJEuupddiyydeLLmaaiKKoiilnndod,g,yPPhah.n.DDd.. PiisusbPPlrireecssiHiddeeaelnnttthoo,ffULLnaaikKviinneddrsAAissostsofyocciMiaaattreeyss,l, aLLnLCdC,,SaacnnhddooAAlddojjfuunnMcectdtiAAcssissnooec.ciiaaSttheeePPrirosofafeeshssesoaorl,rt, hDDaeenppdaarrettnmmveeinrntotnoomffental stsEcecpicieeihdnnnteitimicssattilowwlaionittgahhylyeeasxxnippsdeerfPrtotiruissbreeleicgiinunHleeaexxtappolotrohsys,uusrUrueepnpissvocceriietresn,nicctaeye,n,odaafssMssteaastsresy-emloafenstndhstoeSof-mcfshhcheuoiuoemmnlnacaotnenf Mrhheeeevaidaleilttcwhhsin.rreiis.sDkkrSss.,h, ebbLiaiiosokmmiaononhdinehtiataoolsrtrhiisnnapggn,o,dkssececniineenavntnitiridoffiinccpmuaabennlddnitsahled teieemxxcptthleeinnncsiscaiitavvieel ollaynynsooaonnlyfseeuixxsnppcfoooessrruurrtreeeag.-iunaalintnanddytortrryiihssekks-urrripeeslplkaaoattersetd,sdeasissnsssduumeeesssnt,a,ttiiennp-ccrolloufuc-ddethiisnensgg,-scwcchehiieiillgnddhcrreieennn'rg'ses vpeeoixextpwpeonostss.iuuarrDleerss.riLttsooaksKeeainnnnvdvdiirhrobaoensnnmmesefpeinonttkstaraelelnlccaahhtneeedmmditpiccuoaabllsl,i,shtthheeed cimhepmliiccaatliounsse,ofenuvnicreorntameinnttyailn cthheemiricsaklassisnehssummeannt mpirlokc,esasn,dwteiimgeh-indgeppeontdeenntciael arinskdsdaisntdribbeutnieofniatsl raenalaltyesdistoof eceMxhxapperoomyssluiucararene.ld.iunsDDerr.r,.iesLLknaaavkKsiiirnnsoddensmhhsaamessenttntaaatuulaggchnhhtdteggmarrqiaacuddaautulsaiacttineechhlleeeumvvmieesllatcncrooymu.urrisslkSee,hsseasaanettdrTTvthheimees eoJJo-ondhhenntpssheHeHnooedpdpekiknitionncrsseiaUUalnnnibdivoveaderrirsssditistrtyiyboafaunnttiddohenttJhahoeleuarUUnnnnaiaivllvyeoesrifrsssiiottyyf ooff TToMfooaxxEirixyccplooaollnosodgugyryienaannSricddsikeEEnnancvsveisirreaoosnnnsdmmmeEeennnntvttaaialrlnoHHdneemaaaelqlnttuhthaaaatlinncEddcphiEEdennemvvmiiiirrsootolnrnoymmg.yee.SnnthteDIIrn.nstteeeLrrrvannekaasittniioodoninnaathllPearaennesdddidiiitsesonprptiaaa-ssEltltbeAAocsstassrooodccsriiaaottthfeeethEEIdednititJteooorrrunrffanootarirtolthnhoaeefl JJSooouucrirnneaatlyl oooEfnff vEEEixxxrpppoooonsssmuuuerrrneeetaSSSlccciiieeHennenacccleeetaaahnnnadddnhdhEaanPssvrsisoretoernvcemetideoornonntnaAnldvnvuEuimpmseeioderreroyodmuuCisosouloaandgddvyvli.ilssooDrrryy. committees including the Maryland's Children's LaKind is President-Elect for the International Society committees including the Maryland's Children's Environmental Health and Protection Advisory Council. M Mr~. MMiikkee PPoouuls~eenn-- Wike Poulsen haadegsree in chemistry from Stanford Universityand amaster' degree in technology and policy ffMPrrroiokommegrttPhahomeeuoMlMsfaeastnsshsaehacaOchsrhuaeusgsedetoettngtssrDeIIeennpssaitntirittutcuhmtteeeenmootffisTTotefercycEhhfnnrnvoooilmlorogogySny.mt.aennMMftioiakkrleed QhhUuaaanssliivbbteyee.reesnniPtyraaiaottornotxdxoiicacojomolloioanggisiisnttegt rfoD'osErrQdss.eeegvvhreeeennewtteaienesennteayynceeheaannrrosvslioiirnngoyttnhhmaeeennCCdtllaepelaoannlicuuypp consultant for fifteen years and ascientific research analyst or two Program of the Oregon Department of Environmental Quality. Prior consultant for fifteen years and a scientific research analyst for two years. to joining years. DEQ, he was an environmental aMMrsr.s.ePPsoosumulelssneetnnfpporrrootvvhiidedeesdditerriissskkhoaasswsseeedsssstmhmaeetnntet xssuupppoppsoorurttrtffeooorPtthCheeBPPionorrfttillasahnndrdesHHualartrbsbioonrr ffteehddeeergraralelaSStueupspteerprffouutnnedndtpiparrolojjceeacctnt,.ceTTrhhreeisrrkiistskko haahnususdmmeaatsnhnssesm..OeTTrnooet gfffouuolrlnllyytpheeuevbvlaasililtcuuehaaetstaeehlonntwoohnent-d-occsaatirhcrccaoiiltnnoeooggxgiespetnonisitccuoreeedffeffteevoccettlPsso,C,pBMMsaiinkkineeafpwwispoohrrrokkraeeecsddhulfftfosoorrrinffeiivvtvehaeleyyueegaaatrrerissnagwwteiPisttChthBpEEoiPPstAeAknsRRtetieagogliiioocnnanfna11nc00tesrttoofrxxirsiiockcmootlloooggiissttss barnedastthfeeeOdirengg,onThpeubtliecahmemaoltdhiftoixedicoeqlougaitsitotnosfdoerveasloipngalneacpopmrpoaarcthmfeonrte,vfailrusat-tionrgdePrCkBinreitsikcsmtoodienlfanustsedfrobmy EPA. TTcbhhoreeemapttseaetarfaemtmemdettihnhneegtnn. PTwwBhoPoerKrkkteeemaodddmewwliimstth.hoAAdPTiTCfSiSBeDD-d1RR5ess3qccuimieeainntltitkoiissncttsossnfaaconenrnddatoorstatihhnteeigrorlenrrsecesosaeem naadprrccdahhoreetsmrresssettntooot,ccifoonirmmfsaptpn-ataorsrreedweetthrhreeekimmncaoeoldtdciecuelllmawwtoieidttdhehbl 33yu--staaehnndeddbt88hy--rEeePA. models using data from Inuit women compartment PBPK models. PCB-153 models using data from Inuit women and their infants. milk concentrations and their infants. and doses to infants were calculated by the three GaGisivvseeennssttmhheeenctcllogosuseiednnaeensscsse.ooffDtthEheQrrseeissmuuplllttissf,,ittehhdeetsshiiemmeppvllaeelrruaEEtPPiAAonmmooodfdetelhlewwbarasesassseetllfeeeccettededidnffgoorrpaiinntcchlluwusasiiyoonniniinrniOOskrreeagsgsooennsDDsmEEeQQntirisssbkky using ttiahhsseeskeEEtsoPPsAAminemmfnaoontddtgeseullbidttaooasneddcdeeevov.eneDlolEtpohQepaascttiaamalbbcpllueleilfiaooeftifdenidnfthfraaiensnktettvrroiaissltkkuhaaaetddimojjuounststothmmfeerethnsnettfffbraaroccemttaooesrrsxtsfpe((oIeIRsdRAuAinrFFsges))tpttohahaatPhttCwBccaSaaynnanibbndeeroiuustsskheeeaddrsttsoboeisccosaaamllcccceuuunllmaatsutteelbappytooiuttnesenginntgtiiaall cbcrihhiseektmmpito:cica/lia/nslusf.a.vnu((tAsAdppebppaaeesnsendtddiaxiotxnDe.tDinhioner.cuaslc/ullaatfepdurbissk/tdootchse/mcuo/thHeurmsafnroHm ealetxphoRsiusrkeAtsosPeCsBssmeanndt other Guidance.pdf) bioaccumulating http://www~deq.state.~r~us/~q/[~ubs/d~cs/cu/HumanHealthRiskAssessmentGuidance.~df) DDrr.. MMaarrcc--AAnnddrr~e VVeertnoeerr-MMHeaaarlrcct-h-AA,nnSddcrrh~ooVVleerornfneePrrubwwloiorcrkkHsseaaalsstaha,nn UAAnssissviiessrttsaainntttPPdrreooffMeeossnssotorrraaattltthh(eeCaDDnaeedppaa)ar.rttmmHeeennstt ooaff OOclacccumupespamattibioooennraalolfaatnnhddeEEnUnvnviiirrvoeonrnsmmietennttdaaell bHMMaoeosnanetlttdrhre,paahSllacrPPhumoubaoblclliioccokfiHHnPeeeauatlblittlhichc RR(HePeesBseaPeaKlat)rhrcc,mhhUodInInneivsslettiiritstnuiutgtetee~an((dIdIReRSqSMuPPaUoUnMnMt)it.)rt.eaMaMtail avr(recCc'as'sstnrrareeudscsaete)au.arrrHecce-hhppirrspoorajpoleesjecrottcsytasrmfefoloecacmutuissboenmmsrohosoistfptlsltyyh(eooQnnSUPppnRhhi)yvysetsiroiosolieltoov~gagildiccueaaaltllleyy: dbeavseedlopphmaenrmtaalcoekinxeticp(tPoBoPeKsn) vmiuroodnermleinngetaalndchqemuiacnatlitsatiinvethsetrwuocmtubrea-pnrdoppoesrttnyarteallaltyiotnhsrhoiupgsh(QbrSePaRst) fteoedeivnagl.uaHtee. `ddeeeaeavrvrneenelelododhppihmeisdsePPnPhBth.a.PDDlK..eimxinnpoodBBeisiooulllrsoeoggotyyfoffpreerornomsmviisrttohtheneenmtUUenoninrivgvteaaerlnrssicicihtt~epomddluuilcuaQQtlasuunetinbsbettehcoec~3rweMMfooionmnntebtrerbxaaapnllods((CupCaroanensaatdandasa)as.t)ae. sllDDysuumrtrehiinnrnotgguihhgniieshspiPPbhdh.rDee..Dma,.is,otMfMleaoaergrdcicicnsgt.udHiees. odfevbereloapstedcaPnBcPeKr amnodddelesvoeflpoeprmsiesntetntneourrgoatonxicicpitoyl.lutAafnttesr tcoomrepflineteinegxphoissuPrhe.0a.s,sheesscmonetnitninueedpwideomriolkoogniicPnsBtPugdKies of breast cancer and developmental neurotoxicity. After completing his Ph.D., he continued working on PBPK Useofo reference to this model without proper attribution toMOH sprohibited. a49s 33774499..00004499 SSTTAATTEE 0077443366229044 tmmooodddeoelaliinnsggecdduournriidnnggpohhsiitssdppoocoststotddroaoclctttoorrraaaillnittrnragaiiinnniinengngvaaittrttohhneemeKKnaatrraoollliinnesspkkiaadeIInmnsistotiilttuouttgeeyttiainnt tSShwweeedHdeaenrn.v.aHrHdee MtthehedeinncmmaloovvSeecdhdottoool/BBBoorssittgoohnnam((UUaSSnAAd)) `Women's Hospital. His background in both toxicology and environmental epidemiology led hi to pioneer the to do a second postdoctoral training in environmental epidemiolog at the Harvard Medical School/Brigham and Women's Hospital. His background in both toxicology and environmental epidemiology led him to pioneer the uussee ooff PPBPPKK mmooddeelliinngg iinn eeppiiddeemmioiollooggiicc ssttuuddiieess,, aann aapppprrooaacchh tthhaatt aalllloowweeddrerecocnosntsrtuructcitinngg ccoommpplleettee eexxppoossuurree pMprraoorfficilleehssasaannaddutiinhnvoveersesttdiiggaaanttdiinngcgott-hhaeeuteefhfffoeerccettdss aoofpfpccrhhoeexmmiimiccaaatllesslddyuu2rr5iinngpgeddeiirff-ffererereevnnitet wwweiidnnddpoaowpwessrsooffavvnuudllnnreeercraaebibilvilteitydy..nuOOvmveeerrrotthuhese yyaeewaaarrrss,d, s for his innovative work in environmental health. Marc has authored and co-authored approximately his innovative work in environmental health. 25 peer-reviewed papers and received numerous awards for Dr. Rachel Worley - Dr. Rachel Wodey- RRaacchheell RRooggeerrss WWoorrlleeyy iiss aann EEnnvviirroonnmmeennttaall HHeeaalltthh SScciieennttiisstt aatt AATTSSDDRR iinn tthhee DDiivviissiioonn ooff CCoommmmunuintityy HHeeaalltthh IMInnAvveesistntiigEganatvtiiioornnossn,,mSSeccniiteeannlcceeS SSuuppppoorrtt tudies/R BBrraanncchh.. RRaacchheell hhaass hheerr eproductive Toxicology BBSS fr iinn om CChheemmiissttryy ffrroomm tthhee UUnniivveerrssiittyy ooff GGeeoorrggiiaa ((22000066)),, Brown University (2008), and a PhD in Toxicology aann from the University of Georgia (2016). Her formal training is MA in Environmental Studies/Reproductive Toxicology from from the University of Georgia (20:~6). Her formal training is in computational Brown University in computational toxicology and she (2008), and a PhD toxicology and she actsas a PFAS. in Toxicology acts as a PFAS ssuubbjjeecctt m maatttteerr eexxppeerrtt aatt AATTSSDDRR. Useofo reference to this model without proper attribution toMOH sprohibited. 33774499..00005500 55O0 STSTAATTEE0704743366220955