Document MJJwkZ74Eo8oDmpyRJLJMgbV

mm~ DEPARTMENT 1 OF HEALTH 0 E HCCE LL EE N AA NN B frW L AaANTiEs&R E LMEEGNOANECNYT BBaacckkggrroouunndd DDooccuummeenntt 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 (DH). Useofor reference to this model without proper attribution to MDH s prohibited, MDH s not responsiblefor changes ormisuseof the model byothers. Exhi-bit 3750 33775500..00000011 STATE 07437954 STATE 07437954 Table of Contents ]able of Contents REL OLTBS mmm ----------l List of Tables: .............................................................................................................................................................. 3 istOf Fgures:...cce - - ne end List of Figures: ............................................................................................................................................................. 3 A RE---- List of Equations; ........................................................................................................................................................ 4 Acronyms. - 5 Acronyms .................................................................................................................................................................... 5 Executive Summary. 5 Executive Summary .................................................................................................................................................... 6 1.0 General Approach and Challenges forEstimatingWater Guidance Values. 8 1,0 General Approach and Challenges for Estimating Water Guidance Values ......................................................... 8 2.0Simple One-Compartment TK Model 10 2,0 Simple One-Compartment TK Model ................................................................................................................ 10 2.1 Model Inputs. 2 2.1 Model Inputs ................................................................................................................................................. 12 2.11 Elimination (HalfIfe). 2,1.1 Elimination (Half-lifel .............................................................................................................................. 12 2.12.OVFODIIHUIDMUOEN 1. 14 2,1,2 Volume of Distribution ........................................................................................................................... 14 2.1.3 Placental Transfer. I . - 15 2,1,3 Placental Transfer ................................................................................................................................... 15 2.1.8 BEAST INL2KE A BOY WEB ccc 16 2,1,4 Breastmilk Intake and Body Weight ....................................................................................................... 16 2.15 BOANIK FON c.crssssssmsmssssssmsssmsssssssssmsssns 16 2,1,5 Breastmilk partitioning ........................................................................................................................... 16 22 Preliminary EvaluaoftMioodenl ............ so---- ein 19 2.2 Preliminary Evaluation of Model ................................................................................................................... 19 22.1 Comparisonwith empirical data fromFromme andcolleagues (201). enn 19 2,2.1 Comparison with empirical data from Fromme and colleagues/20101 ................................................. 19 222 Comparison with empirical data from Mogensen and colleagues (2015)... 21 2.2.2 Comparison with empirical data from Mogensen and colleagues (2015) ............................................. 21 2.23 COMPAIiSON With MOGrESUEItfNrOMNVEgNT... enn 23 2.2.3 Comparison with modeling results from Verner .................................................................................... 23 2.3 Expansion Of Mo10 dSLeae dy:Sl tate DUIAHION vv enn 25 2.3 Expansion of Model to Steady-State Duration .............................................................................................. 25 23.1AQGONaI MOE ITPULS sss 38 2.3.1 Additional Model Inputs ......................................................................................................................... 28 23.1.1 DurofaBretastifeedoingn.......... si-- enn 28 2.3.1.1 Duration of Breastfeeding ............................................................................................................... 28 23.1.2 Water Intake Rate... -- enn 28 2.3.1.2 Water Intake Rate ............................................................................................................................ 28 2.8 SUOfM MOH MOGel PATaMeRers......uvsssssssssss 28 2,4 Summary of MDH Model Parameters ........................................................................................................... 28 3.0 Derivationof HealthBased Water GUIGANGE ValUCS ....vvonnvsnme 33 3.0 Derivation of Health-Based Water Guidance Values ........................................................................................ 33 3.1 Reference Doses andCorrespondingSerum Concentrations. , 5 3,1 Reference Doses and Corresponding Serum Concentrations ....................................................................... 33 3.2 Relative SOUICE COMEBUFIACOKONF rrr 3.2 Relative Source Contribution Factor ............................................................................................................. 34 32.1SelecotfRiSCoonr PFS... i. - _-- 3 3.2.1 Selection of RSC for PFOS ....................................................................................................................... 35 3.2.2 Selection of RSC for PFOA. 3 3.2.2 Selection of RSC for PFOA ....................................................................................................................... 36 3.3 Reasonable Maximum Exposure Scenarios 7 3,3 Reasonable Maximum Exposure Scenarios ................................................................................................... 37 33.1Scenario #1 - Exclusively formulai-nffaendt . . 38 3.3,1 Scenario #1 - Exclusively formula-fed infant ......................................................................................... 38 33.1.1 p05. 8 3.3,1,1 PFOS ................................................................................................................................................. 38 33.1.2 PFOA. - en ne en -- 3: 3.3.1.2 PFOA ................................................................................................................................................ 38 3.3.2 Scenar#i2o- Exclusively breastfed infant ES 3.3.2 Scenario #2 - Exclusively breastfed infant ............................................................................................. 39 332.0 PROS. enn 39 3.3.2.1 PFOS ................................................................................................................................................. 39 Useofo reference tothis modelwithoutproperattributiontoMOH isprohibited. 33775500..00000022 2 SSTTAATTEE 0077443377995555 3.8 CONCNSIONS/SUTINY cnn 41 3.3.2.2 PFOA ................................................................................................................................................ 40 3.4 Conclusions/Summary ................................................................................................................................... 41 4.0 References ......................................................................................................................................................... 42 APP-SEummNaryDofplIacenXtal andbreatrsanstfermStiudylk da... 45 APPENDIX I -Summary of placental and breastmilk transfer study data ............................................................ 45 ADDN REAEIENCES:.rrns 47 Appendix I References: ........................................................................................................................................ 47 APAPPEPNENDDIIXXIIII =-PPeeeerrRReveiveiewwererBiBoioggrarapphhicicaall IInnffoorrmmaattiioonn. ...............................................e.r.s..e.s..e.s..e.n..i.n..............S.E....-- ................... 4488 List of Tables: List of Tables: Table 1. Age-speciic volof durumte (Ve) dst factors is Table i. Age-specific volume of distribution (Vd) adjustment factors....................................................................................... 15 Tabl2e. Human milk intake for exclusively breasted infants and colclted <oresponing body weighs (3). 10 Table 2. Human milk intake for exclusively breastfed infants and calculated corresponding body weights (BW)................... 16 Tse3.Results of comparing MO.madeld POS fant serum concentrationts Fromme ta (2010)dat, 1 Table 3. Results of comparing MDH-modeled PFOS infant serum concentrations to Fromme et al. (2010) data .................... 19 Tle. Reosf coumpalrintgMsOHradcled PROA fant scrum concentrations o Fromect. (20101 4ta. 20 Table 4. Results of comparing MDH-modeled PFOA infant serum concentrations to Fromme et al. (2010) data .................... 20 Tables. Comparisonof MOH PROS ode results for exclusively breasted infant (using upper percent intake rtesv)s. Table 5. Comparison of MDH PFOS model results for exclusively breastfed infant (using upper percentile intake rates) vs. Vernet model es...... td Verner model results................................................................................................................................................... 23 Table6. Comparisonof MOH PFOA model reat fo excluiely resstiad infant using upper percentile ntke ate) vs. Table 6. Comparison of IVIDH PFOA model results for exclusively breastfed infant (using upper percentile intake rates) vs. Vernermodel resus. 2 Verner model results................................................................................................................................................... 24 Tali7, Drinkingwatrngesio ats forconsumers-ony and<alclaed responding Sod welghts OW)... 28 Table 7. Drinking water ingestion rates for consumers-only and calculated corresponding body weights (BW)..................... 28 Tas8 SummoafMrOyHmode inputparameters . To Table 8. Summary of MDH model input parameters ................................................................................................................. 30 List of Figures: List of Figure 1. Waterma vane to fetugnfnt . Figure 1. Maternal transfer to fetus/infant ................................................................................................................................. 8 Figure 2 Relativeconcentration comparisons of PFOS in bres, Thomsen, 2010 3nd MOH Tk model results... 18 Figure 2. Relative concentration comparisons of PFOS in breastmilk*, Thomsen, 2010 and MDH TK model results............... 18 Figure 3. Relativeconcentration comparison of PROA i reas, Thorsen, 2010 3d MOH TK del rss... 18 Figure 3. Relative concentration comparison of PFOA in breastmilk*, Thomsen, 2010 and MDH TK model results................ 18 Figar4e. Infant PF0S sarum concentrations precictedfo exclusively breastfed fans by MOK modelvs, estimated Figure 4. Infant PFOS serum concentrations predicted for exclusively breastfed infants by MDH's model vs. estimated ina ta pS 0 F105, FIOM CAL. 2010). 2) individual data points from Figure $5, Fromme et al. (2010) ...................................................................................... 20 Figure. Infant PFOR serum concentrations fo xcusely breastfed fants rectedby MOV' model vs. estimated Figure 5. Infant PFOA serum concentrations for exclusively breastfed infants predicted by MDH's model vs. estimated individu! datapont from gure $6, Fromme et a. (2010, 2 individual data points from Figure $6, Fromme et al. (2010) ...................................................................................... 21 Fig.uRerlatee Increase In infantPFS ru conceniaron at 11 month of age normal vo conceniradon at ih Figure 6. Relative increase in infant PFOS serum concentration at 11 months of age normalized to concentration at birth - MOH mde results foexclusively breastfed fanvs, estimated indica ata pont fom Figure 1, Mogenseent MDH model results for exclusively breastfed infant vs. estimated individual data points from Figure 1, Mogensen et EY al. (2015) ...................................................................................................................................................................... 22 Figur7e. Relative increase fant PFOA sir concentration a 11 anh of ag no0crone cn 5 Beth Figure 7. Relative increase in infant PFOA serum concentration at 11 months of age normalized to concentration at birth MOM de elfoexcusivoly resid fant vs, estimated ndidual ta pont om Figure 1, Moganseent MDH model results for exclusively breastfed infant vs. estimated individual data points from Figure 1, Mogensen et a (015. 2 al. (2015) ...................................................................................................................................................................... 22 Fi8g.Coumparriseon of MOH PROS model ressfo 31 excuse orasted infant (sig upper percent fake ats) Figure 8. Comparison of MDH PFOS model results for 1-yr exclusively breastfed infant (using upper percentile intake rates) Verner model esl. 2 vs. Verner model results .............................................................................................................................................. 24 igure. Comparison of MOH PFOA model elor s1-y xcusivly breastfed fant using per percent take rates) Figure 9. Comparison of MDH PFOA model results for 1-yr exclusively breastfed infant (using upper percentile intake rates) A vs. Verner model results .............................................................................................................................................. 25 Figure 10. Scenario #1schematic xcusely Formula Fed nant % Figure 10. Scenario #1 schematic - Exclusively Formula-Fed Infant.......................................................................................... 26 Figure 11. Sconaro #2schematic Excusively Breasfed nan: nw Figure 12. ExposureDecisionTree. 35 Figure 11. Scenario #2 schematic - Exclusively Breastfed Infant............................................................................................... 27 Figure 12. Exposure Decision Tree ............................................................................................................................................. 35 Figure 13. Excusivey forma fed nant PFOS serum concentrovaertaHieoin,s Sas an 95h percentile water take Figure 13. Exclusively formula-fed infant PFOS serum concentrations over a lifetime, based on 95th percentile water intake ate, 0RSCof 7%,202 WoLEr CORCENUON 1 L080 EAL rrr 38 rates, an RSC of 50%, and a water concentration of 0.060 t~giL................................................................................. 38 Useof or referencetothis modelwithoutproperattributionto MOH sprohibited. 33775500..00000033 3 STATEo7as79s6 STATE 07437956 Figure 14. Exclusively formala ed infant PFOA serum concentrations over fetime, based an 95th percentile water intake. Figure 14. Exclusively formula-fed infant PFOA serum concentrations over a lifetime, based on 95th percentile water intake ates, an RSC of 50%, anda water concentration of0.15 ug/L. 3 rates, an RSC of 50%, and a water concentration of 0.15 pg,/L................................................................................... 39 Figure 15. Exclusively breasted infantPEOSserumconcentrations ov3 eetmre, ased on Upper/95th percent Figure 15. Exclusively breastfed infant PFOS serum concentrations over a lifetime, based on Upper!95th percentile brcastmilk/wianttaeker rates, an RoSf50C%, and awater concentorfa0.t027iuog/nL. " breastmilk/water intake rates, an RSC of 50%, and a water concentration of 0.027 lag/L......................................... 40 Figure 16. Exclusively breastfed infant PFOAserum concentorvearatifeotinmse, based on Upper/S5th percentile Figure 16. Exclusively breastfed infant PFOA serum concentrations over a lifetime, based on Upper/95th percentile breastmilk/waterintake rates and an RSC of S0%, anaWatder CONCETTaton Of 0038HEL vv 41 breastmilk/water intake rates and an RSC of 50%, and a water concentration of 0.035 pg/L................................... 41 List of Equations: List of Equitations: Equation L Standardequation for calculating nonheacl baasendwatcer geuidarnce (aHEG). 3 Ec uation 1~ Standard equation for calculating noncancer health-based water guidance (nHBG) .............................................. 8 Equatio2n. Calculoaftimoon cquivalent dosecorTespONGIN. 0. SECC STU COMGENIZON. vv Ec uation 2. Calculation of human equivalent dose corresponding to a specific serum concentration ...................................... 9 Equation 3. Calculoaftsierounm CoNCenta10tmi4o05n and IGMANCE AE... 10 Ec uation 3. Calculation of serum concentration from dose and clearance rate ....................................................................... 10 Equation. Calculation of infant serum concentration a bith 2 Ec uation 4. Calculation of infant serum concentration at birth ................................................................................................ 12 Equations. Calcuoflianfatnti'sdoainly serum concentration, 2 Ec uation 5. Calculation of infant's daily serum concentration .................................................................................................. 12 Equation. Calculation of breastmilk concentration. 2 Ec uation 6. Calculation of breastmilk concentration ................................................................................................................ 12 Equation 7. Calculation of maternal daily serum concentration Ec uation 7. Calculation of maternal daily serum concentration ............................................................................................... 17 Use oof referetontchies model without proper attribtuotMiOoHn is prohibited. 33775500..00000044 4 STATE 07437957 STATE 07437957 AAccrroonnyymmss aaBcIcRii----baarsseccaiisttetedmdiiilnnk intake rate BBIWR -- body weight breastmilk intake rate CDCBW CDC -- - Centers for body weight Centers for DDiisseeaassee CCoonnttrrooll CCi-I -cocnofnifiddeennccee iinntteerrvvaall CCHaRRs--~ccllheeeaaarrlaatnnhccaeedvrraiastteoeries RHA=s intake rate - health advisories k=rate constant IR- intake rate k - rate constant ((LLnn 22//hhaallf--iliffee)) Lk LOOAAEE~LLg li-ltoelorwsweepsestrt ookbbislseoergrvrvaaabmbllbeeoaadddyvvewererssieegheetffffeecctt lleevveell UMLL//kDkklgg~H:--dd-l~-iMteilliirtntsenerrepsssepporeetkrrailkokDili~leloropgagarmraramtbmmoebbdnooytddwyyoefwwielH~eiehigagtlhhttthppeerr ddaayy. mg/L- MDH - ml~/L - mg/kg-d milligrams Minnesota millil~rams per iter Department per liter - milligram per kilogr of Health ambodyweight per d ay mg -millgram mg/kg-d - milligram per kilogram body weight per day MmIgR--mimlleigarnamintake rate UmmMlILkR//dde-aa:yvm--e-mamimnliililtnliltitetaeerkrresssrppapeetererrddkaaiyylogram body weight per day ng/mL- mL/kl~-d nl~/mL- nanogram per milliter - milliliters per kilol~ram nanol~ram per milliliter body weight per day NNHHANAES~-NNNataEitioonSnaall HHeeaalltthh aanndd NNuutrtriittiioonn EExxaammininaattiioonn SSuurrvveeyy NHnHOBBAGGE---L-nnnooonnccoaabnnscceeerrrvahhbeelaaellttahhd--bvbaearssseeeddewwfafatetceetrrlggeuuvieidldaannccee vvaalluuee OAT- organic anion transporter NOAEL - no observable adverse effect OAT - organic anion transporter level PFPPBBCPPKpKe---rppfhhlyuyssoiirooollocoghgicecamalilllcyya--blbasass(eeaddlopphhraaerrfmmearacrocekodiktnioneeattsiiccperfluoroalkyl substancoers PFAS) PRCAS -- perfiuorocarboxyletes PFC - perfluorochemicals (also PFCAs - perfluorocarboxyletes referred to as perfluoroalkyI substances or PFAS) PPFFOOAA-- ppeerrfflluuoorrooooccttaannooiicc aacciidd PPPRFFOOsSSh--s-peppreerfrffllluuuooorrrooooosucclttfaaonnneeatsseuusl.lffoonnaattee PPKFSpAhsa-rpmearcfolukoirnoestuilfconates PPPPKOWOD-SD--phpppaouoribimnlntitacoocwfofakddteienepperaartistrctyuursrete:em RRPRIWMfDDES--r--reeprffeueeabrrseleiocnnnccwaeebalddteeoorssmeesayxsitemmum exposure: RRSMCE---rreelaatsiovne asboluercmeacxoimnturmibuetxiponosfuarcetor 4RSC -harletllaftieve source contribution factor TK~ toxicokinetic t - half-life TK - toxicokinetic 1tg~/gL!L--mmicicrrooggrraamm ppeerr ilitteerr ((aallssoo kknnoowwnn aass ppaarrttss ppeerr bbiillllioionn)) 1UI~PggI--Rmm-iiccurrpoopggerrraampmercentile intake rate URAT -urate UPIR - upper URAT - urate anion transporter percentile intake rate anion transporter U VUiS-ES vPoA~l-uUE UmnientitoeeP fddSdiStsatAtatrteiesbsutEEinnovnviirroonnmmeennttaall PPrrootteeccttiioonn AAggeennccyy VaVd V~ AF - volume - volume of AF - volume of distribution distribution of distribution aaddjjuussttmmeenntt ffaaccttoorr W WIIRR-- wwaatteerr iinnttaakkee rraattee: Use oof reference to this model without proper attribution to MOH is prohibited. 33775500..00000055 5 SSTTAATTEE 0077443377995588. EExxeeccuuttiivvee SSuummmmaarryy TdTrhhieenkMMiininngnnweeasstoeotrt.aa DDIneepMpaarrtotmamfee2nn0tyt1oo6ff,HHteehaaellttUhhS((MEVnDDvHHi)r)oeenvvmaaellnuutaaattleePssrhohtuuemmcatainnonhheeAaaglletthhncrriyisskks(sUffSrroEomPmA)eexxippsosousseuudrreelittfooetccioomnentthaaemmailinntaahnnttss iinn advisories (HAS)of 0.07 g/L for perfluorooctanoic acd (PFOA) and perfluorooctane sulfonate (PFOS). Asa drinking water. In May of 2016, the US Environmental Protection Agency (USEPA) issued lifetime health advisories (HAs) of 0.07 tag/L for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). As a result, MOH initiated review of the basi of the USEPA HAs and a reassessment of MD's ownhealthbased guidance values for these two result, MDH initiated a review guidance values for these two chemicals, which were derived in 2007. of the basis of the USEPA HAs and a reassessment chemicals, which were derived in 2007. of MDH's own health-based TTmrgraa/dkdietiti-ioodnn)aballlylyy,,arnneoolnnacctaainvnceceesrrouhhreeacaleltthcho--bnbtaarssieebddutwwiaoatnteefrracggtuouriid(daRannSccCee),((nndHHiBvBiGGd))edaabrreye ddaeewrraiivvteeeddrbbiyyntmmaukluetrltiaipptllyeyiin(n1gg/kaag-rrdee)ffe.erreHenonccweeevddeoorss,ee P((RFROIfDSD.,, amngd/kPgF-dO)Abhyavaereulnaitiqvueescohuarrcaectceroinsttriibcsuttihoant faarcetonrot(RaSdCe)q,udaitveidleydadbdyraeswsaetderwhinetanukseirnagteth(iLs/ktgr-add)i.tiHonoawl eavpeprr,oaPcFhO.S and PFOA have unique characteristics that are not adequately addressed when using this traditional approach. PPFFOOAA aanndd PPFFOOSS bbiiooaaccccuummuullaattee iinnsseerruumm,,ccrroossss tthhee ppllaacceennttaa,, aanndd aarree eexxccrreetteedd iinnttoo bbrreeaassttmmiliklk.. RReesseeaarrcchh hhaass sshihhgoohwwennr ttthhhaaatnt bbmarreteaeasrstnmatlimlkciocclnaacknnenbbteeraaatimmoanajsjoo.rrAsslootuuhrroccueegoohffeeexxxpppooosssuuurrreees,,redresuursliutnlitginngignifinnaniicnnyffaaannrttessseehrorurumtm-tcceoornnmc,ceentnthitrrsaatptiiaorontnisscutthlhaaartt afareree-stage isof particular concern because (1) PFOS and PFOA are developmental toxicants; (2) infants consume a higher than maternal concentrations. Although exposures during infancy are short-term, this particular is of particular concern because (1) PFOS and PFOA are developmental toxicants; (2) infants consume a much life-stage much ggharrleefaa-tlteeirvrevvsooollfuumPmFeeOoSoffallniiqdquuiiPddFpOpeAer,r uutnnhieittsbbhoooddryyt-wwteeeiriggmhhettxttphhoaasnnurooelldsdeetrrhaccthhiialldcdcrreuenrn daaunnrddinaagddiuunlflttas;n; caaynncdda((n33)) rddeusuelutttooitnethhbeeodlloyonnbggueerlldiimemniinsnaattthiioaontn 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 IsInnceddneearrriiivvoiinndggehhpeeiaaclltttahhs--brbaeaassleeidsdtiggcuubiiuddatannmccaee,,xiMMmDDuHHmuuessxeepssoaasurrreeeaasssooinntauaabbtllieeomnma(ax.x2i.imm9uu5mmeexpxpeporoscsueunrrteele((RRwMMaEEt)e) raappippnrtrooaakaecchhr.a.tAAen)n tRRoMMeEEnsure. that even the most heavily scenario depicts a realistic that even the most heavily exposed individuals within the population will be protected. but maximum exposure situation (e.g., 95th percentile water exposed individuals within the population will be protected. MDH used this intake rate) to MDH used this RME ensure RME aapppprrooaacchh iinn tthhee ccoonntteexxttooff aa nnoovveell kkiinneettiicc mmooddeell ttoo ddeevveelloopp uuppddaatteedd wwaatteerr gguuiiddaannccee vvaalluueess ffoorr PPFFOOSS aanndd PPFFOOAA.. In order to ensure that MDH's revised health-based water guidance values were adequately protective of infants, a one-compartment toxicokinetic (TK) model was developetod predict serum concentrations of PFOS In order to ensure that MDH's revised health-based water guidance values were adequately protective of infants, a one-compartment toxicokinetic ITK) model was developed to predict serum concentrations of PFOS aiannnfddanPPtFFeOOxcAAluffrsroiomvmelbbyiirrfttehhd ttwhhirrtoohuugfghohraamtutttlaaaiinrnmemceeonnnttstooifftssuttteeeaadddwyyi-tsshttaactteeoncctooannmddiiitntiiaootnnessd.. TTwawwtooerRRMMstEEarsstccienegnnaaartriioobssitwwhe,errfeeoleelvvoaawlleuudaattbeeddya:: 11)) aann lifetime of drinking contaminated water; and 2) abreastfed infant exclusively breastfed for 12 months, followed infant exclusively fed with formula reconstituted with contaminated water starting at birth, followed by a lifetime of drinking contaminated water; and 21 a breastfed infant exclusively breastfed for 12 months, followed bbyya alilfiefteitmimee ooff ddrriinnkkiinngg ccoonnttaammiinnaatteedd wwaateter.r. IInn bbootthh sscceennaarriiooss,, tthhee ssiimmuullaatteeddininddiivviidduuaallssbbeeggaann felife wwiitthh aapprree-eexxiissttiinngg bbooddyy bbuurrddeenn tthhrroouugghh ppllaacceennttaall ttrraannssffeerr ffrormoama mmootthheerr aatt sstteeaaddyy--ssttaattee ccoonnddiittiioonnss.. MMDDHH ccoonndduucctteedd aann eexxppeeddiitteedd aanndd ffooccuusseedd rree--eevvaalluuaattiioonn ooff tthhee aavvaaiillaabbllee ttooxxiiccoollooggiiccaall iinnffoorrmmaattiioonn,, rreellyyiinngg iinn 0ppa0arr0tt0oo0nn0U5US1SEEaPPnAAd''ss0.220000110660hh1ee8aalmlttghh/kaaass-ssedesswssemmreeennttdeddrooiccvuuemmdeefnontrtssPF(((O(UUSSSEaEPPnAdA,, P22F00O11A66,3a))re((sUUpSSeEcEtPPiAAv,e, l22y00.116T6chc)e)))..coRRreerffeeesrrpeeonnnccdeeiddnoogssseeessr((uRRmffDDss))ooff concentrations 0.0000051 and concentrations are 0.063 0.000018 are 0.063 and 0.13 mg/L mg/kg-d were and 0.13 mg/L for PFOS and PFOA, respectively. derived for PFOS and PFOA, respectively. for PFOS and PFOA, respectively. The corresponding serum StSoeebrrueumtmhcceoonnmccoeesnntttrraaapttpiiorononpssraairraeetetthhbeeasbbiesessfttormmedeaearssiuuvrireengooaffniinnRtteIeDrrnntaahlladtdooissseeprffoootrrePcPtFFiOOvSSe aaofnnddpoPPtFeFnOOtRAi,,alaannhddeaaalrrteeh tethfhfeeerrceetsffo.orreIet ccisooninsmsipiddoeerrrteaedndt ttohabtetothtael mexopsotsaupreprforpormiatael bsaosuirscefos,r dinecrlivuidnigngapnotRefDntithalatiisnpgroteecostfivtderiionfokpionngtewnatitaelrhceoanltthaienfifengctPsF. OItSoisrimPpFoOrAt,ant tdhoaetstonotatlreexsuplotsiunresefrroumm calol nsocuerncetsr,aitncitlouhdnaitsngexpcoeteednttiahleisnegreustmiocnonocfednrtirnaktinigonwaastseorcicaotnetdaiwniitnhgtPhFeORSFoDrfPoFarOA, toxicologicaly relevant periodoftime. The exposure does not result in serum concentrations that exceed toxicologically relevant period of time. The exposure contributed from non-waer sources was the serum concentration associated with contributed from non-water sources was addressed the RfD for addressed a ttthhhirrsooucuaggshhet,thhteeheaapspepprllicuiamctaicotoninocofnefnaatrRRaetelilaaottniivvaeesSSsoooucuirraccteeeCdCoowninttrtrhiibbtuuhtteiiooRnnD(()RRSStCCo))wffaaatccettoorrr,e,xwwphohisiccuhhreaasl.lloMclaDtoeHscuasafferrdtaacctetthiioesonnUooSffEttPhhAeeERRxffpDDos((ouorrr eiinn Decision Tree this case, the Decision Tree process (USEPA 2000) along with recent serum concentration associated with the process (USEPA 2000) along with recent national RfD) to national (2013-2014 NHANES, CDC 2017) water exposures. M DH used the (2013-2014 NHANES, CDC 2017) and local (new. USEPA Exposure and local (new EEaasstt MMeettrroo rreessiiddeennttss,, NNeellssoonn 22001156)) bbiioommoonnititoorriinngg rreessuullttss ttoo iiddeennttiiffyy aann RRSSCC aappppoorrttiioonnmmeenntt ooff 5500%% foorr PPFFOOSSaanndd PPFFOOAA.. Use oof reference to this model without proper attribution to MOH is prohibited. 33775500..00000068 6 SSTTAATTEE 0077443377995599 The TK model developed by MDH predicts daily serum concentrations over a lifetime of exposure to a constant PFOA or PFOS The TK model PFOA or PFOS concentration n drinking water. ince the excretion via developed by MDH predicts daily serum concentrations concentration in drinking water. Since the excretion via breastmilk was significant, the calculation over a lifetime of exposure to a constant breastmilk was significant, the calculation ooff ddaaiillyy mmaatteerrnnaall sseerruumm ccoonncceennttrraattiioonnss iinnccoorrppoorraatteedd llossoooffcchsheermiscicaall vviiaa ttrraannssffeerr ttoo tthhee iinnffaanntt aass wweellll aass feexrxccorrmeetttiihooennbrrreeeappsrrteemsiseleknntteienddtbbayyketthhreeatccelleeaaanrrdaanntccheee rrbaartteee.a.sTTthhmeieliiknncffaoannnctt'essntddraaalitlyyioiinnn.ttaakkee ((aanndd tthhuuss tthhee mmooththeerr''ss lloossss)) wwaass ccaallccuullaatteedd from the breastmilk intake rate and the breastmilk concentration. AdAasstppaaafrrtrt ooomff ttphhueeblmmiosodhdeeedll sddteeuvdveieellsoo,ppmmaseenwntet,l,lpparreeddpiuiccbttleeiddshsseeedrruutmomxicccooonnkccienenentttriracattmiiooodnnesslsffr.roomImn ttahhdedeimmtiooodnde,ellMwwDeeHrreesocclooimmcipptaeardreeiddnpttuoot eefmmrpoipmririiscciaaxll externalpeerreviewers for advice on how to 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..o00n0d00i00n00g551t1oaatnnhdde 00R..i00D00s00(00011.8806mm3gga//nkkdgg-0:d.1ffo3orrmPPgFF/OOLSSfoaarnnddPFPPOFFSOOAaA,n, drreePssFppeOecAct,tiivvreeellsyyp..ecBBtaaissveeelddy'oo)nnattnhhdee assneeRrruSummCof 5pc5r0o0o%%nt,c,eectthnthietervaeMMtifDoDonrHHstTThcKKeoermxmrcoeoldsdupeseolilnvrrdeeelissnuyugfllttostsromiinnuthddleiiacc-aaRfttfeeeDdstthhi(aan0tft.a0wwn6ata3ttseeacrnrendccaoor0nni.co1ce.3ennHtmtorrgawate/tLiivooefnnorssr,ooPdfFfuO0e.S00.t60ao60n0tdaahnnePddFbOi00o.A.1a1,c55rcelgu~sm/gpuL/eLl,c,attrriveieessvplepyee1cnct)aittaivvuneerldleyy,a,onfaarrRPeeSFCOSof apnrodtePcFtOivAe, fcohrrothneiceexxcpluossiuvreelytfoormmotuhlae-rfsedanindfasnubt ssecqeuneanrito.trHaonswfeervetrh,rdouueghtobrtheeasbtmioialkccruemsuulltaetdivien nhiagtuherer of PFOS 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 eccxoocnnlccueesnintvtreralatytiiobonrnessaoosftff00e..d0022i7n7faaannntdds00ce..0n0a33r55iopg.g//TLLoffoeonrrsPPuFFrOOeSSparanondtdecPPtFFiOOoAnA,,ofrreeasslplpeesccettigivvmeeellnyy,t, saarroeef nnteehceceepssosspaaurrlyyatttooiobbnee, ptprhrooettfeeiccnttaiilvveheeffaoolrrthtth-hee based values for PFOS and PFOA were se at0.027 and 0.035 g/L, respectively. exclusively breastfed infant scenario. To ensure protection of all segments of the based values for PFOS and PFOA were set at 0.027 and 0.035 lag/L, respectively. population, the final health- BMBrreEeaasssttcffeeeneeaddriininogg wiissasiimmuppsoorertdtaainnnttgffeoonrrertthaheteissnhhgootrrthteaannheddallltoohnn:ggbttaeseremmd hhveaelaaulelttshh. ooBffybbdooettshiahganm m,oaotnthheRerMr Eaannsddceiinnnffaaarnnit.ot. dAAesspisscttatastteeaddraaeabblooivsvteeicaabnnut mRaMxEismcuemnaerxiopowsausreusseidtuiantigoennteoraetninsgurtehethhateaelvthe-nbatsheedmovasltuehse.avBiylydeesxipgons,eadniRndMiEvidsucaelnsawriiothdienptichtes paopreualalitsitiocnbut wmialxlibmeupmroteexcpteods.urTehseitmuaajtoiornittyoofentshuerepotphualtateivoennwtohuelmd oesxtpehreiaevnilcyeelxopwoesreedxpinodsiuvried.uaMlsDwHithrienctohmemepnodpsulathtiaotn women currently will be protected. women currently breastfeeding, and pregnant women who plan to The majority of the population would experience breastfeeding, and pregnant women who plan to breastfeed, continue to do so. Exclusive lower exposure. MDH recommends that breastfeed, continue to do so. Exclusive bbrreeaassttffeeeeddiinngg iiss rreeccoommmmeennddeeddbbyyddooccttoorrss aanndd ootthheerr hheeaalltthh pprrooffeessssiioonnaallss. tIst uisnulnilkikeellyy tthhaat ppootteennttiiaall hheeaalltthh rcceoosnnuccleetrrinnnssleeoxxwcceeereebddottdhhyeebkkunnroodwwennnsbbaeennnedefifbittrsseaoosfftbbmrireelaaksstctfofeeneecdedininntggr.a.tAAipponppslilcoaiftciPoFanOotSofifatothnhnede PffiinFnaaOllAhhseeoaaltltthhha--tbbaiasnsefeaddntvvsaalcluuaeenssrwweicillelliuuvllettiim thmeaa.tteellyy optimal result in optimal benefits from breastfeeding. lower body burdens and breastmilk benefits from breastfeeding. concentrations of PFOS and PFOA so that infants can receive the S1 Seerruumm ccoonncceenntrtraattiioonn ccoorrrreessppoonnddiinngg ttootthhee RRIfDD fiss uusseeffuull ffoorr iinnffoorrmmiinngg ppuubbilicc hheeaalltthh ppoolliiccyy aanndd iinntteerrpprreettiinngg ppooppuulalattiioonn.- bIbnaatsseeerddpreeexxtppionosgsuursreeesrs.u. mTThhliiessvevvlaaslluiueneiissndbbiaavissdeeuddaloosnn. population-basedparameters population-based parameters and and should should notbe not be used used for for clinical clinical assessmoefnotr assessment or for interpreting serum levels in individuals. Use oof reference to this model without proper attribution to MOH is prohibited. 7 33775500..00000077 SSTTAATTEE 0077443377996600 11.. 00 GGeenneerraall AApppprrooaacchh aanndd CChhaalllleennggeess ffoorr EEssttiimmaattiinngg W Waatteerr GGuuiiddaannccee VVaalluueess PPeerrfflluuoorrooooccttaannooiicc aacciidd ((PPFFOOAA)) aanndd ppeerrfflluuoorrooooccttaannee ssuullffoonnaattee ((PPFFOOSS)) aarree bbiiocaaccccuummuulalattiivvee cchheemmiiccaallss tthhaatt hhaavvee tthhee ppootteennttiiaall ttoo aaccccuummuullaattee wwiitthhiinn tthheebbooddyy oovveerr tthhee yyeeaarrss pprriioorr ttoo pprreeggnnaannccyy,, ccrroossss tthhee ppllaacceennttaa,, aanndd ppaarrttiittiioonn in rast hraor, sum snd resi concentrations wi be higher han the concentrations into breastmilk. Therefore, serum and breastmilk concentrations will be higher than the concentrations in Cntonmental og, contorted wie] 0 wha worn xpos in addon Beng bor with 3 environmental media {e.g., contaminated water) to which a woman is exposed. In addition to being born with an ising boy burden To cera rnsfer based on moernl scclton, ans my a xperence existing body burden from placental transfer based on maternal accumulation, infants may also experience ssuubbsseeqquueenntt hhiigghheerr eexxppoossuurreess,, eessppeecciaiallllyy ffrroomm bbrreeaassttffeeeeddiinngg ((SSeeee FFiigguurree 11 bbeellooww)). Figure 1. Maternal tronsfer to fetusinfant. [py [AFEi E acetate Placental Transfer [I Breastfeeding Rai nsn a Lit] T`Thhee MMDDHH ssttaannddaarrdd wwaatteerr gguuiiddaannccee mmeetthhooddoollooggyy,, bbaasseedd oonn lliifefe-s-stataggee ssppeeccififiicc ddrriinnkkiinngg wwaatteerr iinnttaakkee rraatteess,, ddooeess. tincorprat ody Burden bn nor te concerraon of enfonmental Cameo n rik. Ti not incorporate body-burden at birth nor the concentration of environmental chemicals in breastmilk. This ocumen, threo, describes amework developed bY WD Ihr mcrporte chica speci properties document, therefore, describes a framework developed by MDH that incorporates chemical-specific properties 503 and POR der ent protec wher Badin aos of PFOS and PFOA to derive sufficiently protective water guidance values. Atypical noncancer eatbased water kane aus (HBG) is luted combing a sfrence dose A typical noncancer health-based water guidance value (nHBG) is calculated by combining a reference dose ((RRFIDD)) wwiitthh aa wwaatteerr iinnttaakkee rraattee ((IIRR)) aanndd rreellaattiivvee ssoouurrccee ccoonnttrriibbuuttiioonn ffaaccttoorr ((RRSSCC)),, ssuummmmaarriizzeeddbbyytthhee ffoolllloowwiinngg. Canon MDH, 3000 equation {MDH, 2008): Eqsoron 1.Standard uation for let once hes based water gianc (HOG) qu~tion ~o Standard equation for calculating no~Kancer health-based water guidance (nHBG). enN)Lpars eg (J) xRSC x1000 LE 1000 a -- MDH HBGs represent a concentration of an environmental chemical in drinking water that is associated with ele han hh 1. standard Us Enronmentlotacion Agen (USA) ad MOH acco negligible human health risk. It is standard US Environmental Protection Agency (USEPA) and MDH practice to Inororate upper ni xpos ul nord 0 Grr. an adequate mar of sfetyfo mst posed incorporate upper-end exposure levels in order to ensure an adequate margin of safety for most of the exposed `ppooppuullaattiioonn ((((UUSSEEPPAA,, 22000044)),, ((MMDDHH,, 2200008)8)).). MMDDHH''ss mmeetthhooddoollooggyy ffoorr ddeerriivviinngg hheeaalltthh--bbaasseeddwwataeterrgguiudidaannccee uusseess iinnttaakkee rraatteess tthhaatt aapppprrooxxiimmaattee tthhee 9955tl"~ ppeerrcceenntitillee ((MMDDHH,, 22000088)) ttoo eennssuurree iinncclluussiioonn ooff mmoosstt ooff tthhee ppooppuullaattiioonn aanndd otc nd who ons Ir erento the wie om angle orc, uh pros protection of individuals who consume a large percentage of their water from a single source, such as a private ello ommnity wate spp MON ol, bse on dota sail ere ter gidance a 5 well or community water supply. MDH's goal, based on data availability, is to derive water guidance that is roti of ore 5 wel 3rc raion. Consatent wih ng tsupparted gharan. expose protective of short-term as well as chronic durations. Consistent with using data-supported higher-end exposure Toe, RE cemario av ba determin nd usd n MO TK odin, levels, RME scenarios have been determined and used in MDH's TK modeling. eter for boat contaminants re fen based ongerm exposes and yal conde the Criteria for bioaccumulative contaminants are often based on long-term exposures and typically consider the Tein eso tt um eu ht a an ten balance between dot nk an hn, In resulting steady-state serum levels that arise from the net balance between daily intake and elimination. In 501, USE dred ios of 00003 md or Fan PFOA Irn hi en Ader (1A) of 2016, USEPA derived RiDs of 0.00002 mg/kg-d for PFOS and PFOA. In deriving their Health Advisories (HAs) of 00..0077 pI~gg//LL,, UUSSEEPPAA cchhoossee ttoo uussee tthhee 9900t"h ppeerrcceenntitillee wwaatteerr iinnttaakkee rraattee ffoorr llaaccttaattiinngg wwoommeenn ((00..005544 LL//kkgg--dd)).. UUssiinngg. ke 5 lag ih FSC of 0.210 Eun sls 1 USEPA Met sth aon 1007 wet this intake rate along with an RSC of 0.2 in Equation 1 results in USEPA's lifetime health advisory of 0.07 lagiL. Us ofr erence to thi model without rape atlution to MOH rites. 33775500..00000088 s sareorien STATE 07437961 FFoorr ccoommppaaririssoonn,, iiff MMDDHH''ss ttyyppiiccaall cchhrroonniicc iinnttaakkee rraattee ((9355~:"~ ppeerrcceennttiillee lliifefetitmimee iinnttaakkee,, 00..004444 LL//kkgg--dd)) iiss uusseedd ttoo ccaallccuullaattee aawwaatteerr vvaalluuee bbaasseedd oonn UUSSEEPPAA''ss RRffDD aanndd RRSSCC,, tthhee rreessuullttiinngg wwaatteerr ccoonncceennttrraattiioonn wwoouulldd bbee 00..0099 ulagg/L/L.. bMMlODoaHHccddueemttueelrramtmiiinvneedenttahthauart etthhoefttPrraaOddSiittiioaonnndaallPaaFppOppArr,ooaaplccahhcefoonrtraddleetrrrivaiinnnsggfewwr,aatbteerrregguauiisddatalnn.kcceeanwwsaaissenrn,ootaaandddeeqiquguahatteeert0oyaadfddderreensstsssttkhheee trbraahiotteeeasRsc.cTTuhhmDfeeouccloaobnStnistvsieihddeenrFraaaOttutiiSoroennaonooffdfPaePFaFrOrOySlAy.-aflinfTeedheeePxxFtppOomoAsse,uurprfeeloacaraeennanddctakkhilinnstetertaetiianccdsssyf-eissrt,ffuaubtrrrtetehhcaeeosrrntdr-rmeeiitininilkffooontrrrscacesenddstfybbepyri,cttahhalneldyddeheeqivvgueeihllvoeaoplapmermnlyeet-nnl0ittfaesl bass of intake basis of taSahippgeppnrirRofofixxDciiasmmnaftaotltyreelhblyyiogffthihvueeerPFhhiOaantSllfa-vkalieevnsedr.sa.PteFHHsOoowcAwea. evrTveyhereir,,tnittmhfhii,ess to reach steady-state conditions is typically equivalent to generkallprtinhcaitplleon: btaesremdaotn cfoenssttaenatdeyxsptoasturee.vGeisvean three general principle is based on constant exposure. Given the ache d significantly higher intake rates early in life, it is likely that long-term late life steady-state levels are reached \ransfrred from mother o offspring. seofan infant intake rat (0.385 kg) and an RSC of 0.2 since ffaasstteerr,, aanndd eexxcceeeeddaanncceess ((ppeeaakk lleevveellss)) ooff sstteeaaddyy--ssttaattee lleevveellss mmaayy ooccccuurr,, eessppeecciaiallllyy ccoonnssiiddeerriinngg tthhee bbooddyy bbuurrddeenn transferred from mother to offspring. Use of an infant intake rate (0.285 L/kg-d) and an RSC of 0.2 (since ttrraannssppllaacceennttaall aanndd llaaccttaattiioonnaall eexxppoossuurree ooccccuurr)) wwoouulldd rreessuulltt iinn aa ccaallccuullaatteedd wwaatteerr ccoonncceennttrraattiioonn ooff 00..001144 pI~gg//LL.. However, this short erm infant intake rias baesed on an exposure duration of nly two months, does at take However, this short-term infant intake rate is based on an exposure duration of only two months, does not take into account te ferences between PFOS and PFOA toxicokinetic (TK) nr the body burdenat birth, and could into account the differences between PFOS and PFOA toxicokinetics (TK) nor the body burden at birth, and could be inconsistent with the dose metric used to derive the RID. 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,, 2012). Given th long hls of FOS and PFOA these igh short term exposures can result in prolonged 2011). Given the long half-lives of PFOS and PFOA, these high, short-term exposures can result in prolonged elevations of intemal body burdes over several ears, cluding critica mesofdevelopment, Fal ed and elevations of internal body burden over several years, including critical times of development. Formula-fed and nursing infants consaguremateer volume of qui on aper boc weigh basis than oder hidren and adult, nursing infants consume a greater volume of liquid on a per body weight basis than older children and adults. The availabe erature e5., (Frome, 2010), (Haus, 2011, (ondal, 2014), (Mogensen, 2015) reports higher The available literature (e.g., (Fromme, 2010), (Haug, 2011), (Mondal, 2014), (Mogensen, 2015)) reports higher PFS and PFOA serum levelns breastfed nants than inmaternal serum, providing direc evidence of higher PFOS and PFOA serum levels in breastfed infants than in maternal serum, providing direct evidence of higher exposures in breasted infants compared to mothers. Aphysiogicaly-based pharmacokinetic (PBPK) moe exposures in breastfed infants compared to mothers. A physiologically-based pharmacokinetic (PBPK) model Confirmed the importanocfe breastmilk 5 an important exposure pathway for PFOS and PFOA n infants confirmed the importance of breastmilk as an important exposure pathway for PFOS and PFOA in infants (Loccasana, 2013). Tis model also showed hat faitno accofourbnotth route ofexposure {reastil) and (Loccasano, 2013). This model also showed that failing to account for both route of exposure (breastmilk) and increase flu intake rates would result in a underestimation of serum concentrations thoughout much of increased fluid intake rates would result in an underestimation of serum concentrations throughout much of cary fe. A simple pharmacokinetic (PK model was developeby Verner and colleagues (Verner, 2016), which early life. A simpler pharmacokinetic (PK) model was developed by Verner and colleagues (Verner, 2016), which agindocumented breastmilk as a sinifican exposure pathway.Goth models ae coded using acs, a modeling again documented breastmilk as a significant exposure pathway. Both models are coded using acslX, a modeling program whic no longer avaable or supported (ito /acshcom/). I ortodadererss concerns regarding program which is no longer available or supported (http://acslx.com/). In order to address concerns regarding Higher, carly fe exposures, MOH created a spl one-compartment toxicokinetic 1K) model in Microsoft Excel higher, early life exposures, MDH created a simple one-compartment toxicokinetic (TK) model in Microsoft Excel 2015 to evaluate the importance of high erly fe exposures in formula.fed and breastfed infant. 2013 to evaluate the importance of high early life exposures in formula-fed and breastfed infants. f uP2nF5cO0t5Si oaannnoddfPPFFhOOoAAw aamreuecwwheelglloaaebbsssnootrrbobeetddhe nintotoodttshhe(dbbaoosddeyy) aaannndddaahroewnnoqotutimmckeeltytaatbbohollizciezhdee. TTmhhieercreefarfoolerree,l,mtthiheenaaatmmeooduuncntlteiiannrttehhdee) bbfoorddoyymiiss a a ftrthuheenespcbbotoionodsdnyey.,.oeMMf xhDDpoHoHwsuaamrggerrue,eceehassngwwdoiiertthsihsiUUncSSthoEEaPPrthaAAcetaaebnnrddoidzooyattthh(ideeorornsssoettf)hhaPatEtnOdssSeehrrauounmwmd quickly the chemicals are cPoFnOcAe.ntration i he bet concentration is the best dose metic or dose- eliminated (cleared) from dose metric for dose- response, exposure, and risk characterization of PFOS and PFOA. IInn ddeerriivviinngg tthhee RRffDDss ffoorr PPFFOOSS aanndd PPFFOOAA,, tthhee UUSSEEPPAA (((UUSSEEPPAA,, 220011663a)),, ((UUSSEEPPAA,, 22001166dd)))) uusseedd tthhee ffoolllolowwiinngg relationshtiopcalulate the human equivalent does that would correspond to the serum concentrations fom relationship to calculate the human equivalent doses that would correspond to the serum concentrations from animal studies. animal studies. Equation 2. Calculation of human equivalent dose corresponding to speci serum concentration Equation 2. Calculation of human equivaler~t: dose correspondir~g to a specific serum concentratior~o Dose (5my ) = serum concentration (mg x2clear)ance ve (5L ) aWWiciththhedcco.onnttSiitnneuuaooduuyss-seetxxapptoeosscuuorrneeditttooiobbniisoo,aacsccucuummmiuunllgaattivievCccohhneetmmaniitccaalles,x, pssoeesrruuumrme ccrooanntc,ceenantrtreraaattciiohoninessviienndccrrweehaaesseen uutnhnttiillassttteeesaaddoyfy-sastbtasttoeeripisstion reached. 5ready-state conditions, assuming a constant exposure rate, are achieved when the rates of absorption Use oofr reference to ths model without proper atibuton to MOH is proibited. 33775500..00000099 5 STATE O74a7o62 STATE 07437962 alma he by are acl Howes, costa eprsre ate does ot reflect ea ug xy and elimination from the body are equal. However, a constant exposure rate does not reflect reality during early Tio where ake ces Body wath, vem ofatin, i arpa mas (Hn wart din life, where intake rates, body weight, volume of distribution, and exposure matrix (drinking water used in formal brian ne all contr x. Th ado fal vo et ok ants or der formula or breastfeeding) are all in constant flux. The adoption of adult chronic steady-state kinetics for deriving arr nce AFo Cthy en At ems 70 OY xed OA ar 0 EY VOU. water guidance is difficult to justify when the most sensitive and highly exposed individuals are the very young. Treo, Mot deveonelCoompparser mode merporatns ta mot ral scence nd onepes Therefore, MDH developed a one-compartment TK model incorporating the most reliable science and concepts 1010125 ra ot te dance ht EE fo Segment othe eral population. to aid in the derivation of water guidance that is protective of all segments of the general population. 2.0 SSiimmppllee OOnnee-,-C-Coomrpnapratrtmmeenntt TTKK MMooddeell Serum canenrations eh bs mesa af xposre and bass or an AD, Trrtrs, a te unc lus Serum concentrations are the best measure of exposure and basis for an RfD. Therefore, a water guidance value hat sus a seruh concenation ah of Blo te srs Concent ceted with th WY, even when that results in a serum concentration at or below the serum concentration associated with the RfD, even when couringlor th comiosionafnawates gems wi ett ree cto, Ennton shove, Sm accounting for the contribution of non-water exposures, would be health protective. Equation 2, above, can be Tesatna goleeaae sr Concannon bse an st and eran rearranged to calculate serum concentration based on dose and clearance. Satin, Cidatonsh era conan om dose nd desrance te. Eql2atk)r~ 3o Calculatio~ of serum concerlbal:ior~ from dose arid deara~ce rate. soumcomcenvaion(28) (i850) Clarance hte;5) m~ mg Dose(~) Serum Concentration (T) = clearance Ra~e (~) wesWhere: P-- for woter ingestion - osen)yter te rteL)y water concentration (n78o) Dose ~ = Water Intake Rate ~ x Water Concentration T tres: for breastmilk - ose (240) = presse tae ec.) ese concerto (o2t) and lerance Rat (g.L) = vo xck Clearance Ra.~e \k~ dayJ = V~ x k tom vate of pn sn (5,) he Vd=VolumeofDistrib~tion(~) l,(2) k= hhaallff =-liliffee ((dd)) The om of dsbe utin (V4), 033 100.17 i or FOS 3nd PEON respecte, has bien charactaizbeyd The volume of distribution (Vd), 0.23 and 0.17 L/kg for PFOS and PFOA, respectively, has been characterized by eval es(40a Seton t 5.5. (e JPA 0160) ond econ 2.63 (USE 20160). combing several researchers (see Section 2.5.3 in (USEPA, 2016c) and Section 2.6.3 in (USEPA, 2016a)). By combining tthheessee VVidd eessttiimmaatteess wwiitthh tthhee hhaalflf--lliiffee ooff PPFFOOSS ((55..44 yyeeaarrss)) aanndd PPFFOOAA ((22..33 yyeeaarrss)),, UUSSEEPPAA ((UUSS EEPPAA 22001166aa,, c)) Cates he allowing csrance es, calculated the following clearance rates: pros: ozabx 05= oman by PFOS: 9 sarx36s 5 9d L 0.23~aa x 0.693 L d = O.O00081kg.d 9 5.4yr x 365-yr oor frre oth model ith prope tutMOiH roitnes Use of or reference to this model without proper attribution to MDH is prohibited, 33775500..00001100 010 sareorien STATE 07437963 pron 01i0 a7reo2eams0 ooo0L PFOA: L 0.693 L 0.17~--~ x 2.3 yr x d 365-- = O'O0014k9 d yr When alfetime mean water intake ate of 0.016 kgd (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 are 198:1 and 14:1 fo PROS and PFOA. respectively: mmgg//LL ((aarrbbiittrraarriillyy sseett ffoorr ccoommppaarriissoonn ppuurrppoosseess)),, tthhee rreessuullttiinngg sstteeaaddyy--ssttaattee sseerruumm ttoo wwaatteerr ccoonncceennttrraattiioonn rraattiiooss. are 198:1 and 114:1 for PFOS and PFOA, respectively: pros: PFOS: 198 198 mg T serum (Serum concertratono ) = 0e016s(zL)g)yx1m1BL(WateerrCConocenntrraatinon)) Concentration) = 000000 (gs) ron: 114 2Smgerum Concentration) =200.0001166 1((~ ggrL)y)X )yxx1m1 fB~ Ee((Wacareterr CCooovnnceceemnncatrraiaitnioon)n)) PFOA: 114 T (Serum Concentration) = 0000145L 7) ISInntccerraeedaayss-isinntggatttehheseellirffeutmtiimmoeewwwaaatteteerrciinonnttacakekenetrrraaattteeiottonottrhhaeteio9955otf"h 5pp4ee3:rrcceenatnnildte3rra1att4ee1oofffo00r.0F04O44SLk/n4kggd-ddP((FUUOSSAEE,PPArAe,,sp22e00c11t11i)v)errleeyss,uuldlttusseninoaathe sintecardeays-setdadteisyereuxmpotsourweaatenrdcaobnscoernbterdatdioonse:ratio of 543:1 and 314:1 for PFOS and PFOA, respectively, due to the increased daily exposure and absorbed dose: 000000 (5i ) #05: 543 m.72g Serum Concentration) =20000.4044(4LL(rg~))y)x m11 -8~(W(aatteeerrrCCCooonnncceeennnttrrraaattiiioronn))) PFOS: 543 ~ (Serum. Concentration) = L v ooo (7) ro: 218 2 ern concern 24 00.004444T((~ rL) g))yx Hmi1-B~efL-(aWr taeterrCCCooonrnccecennnttrrraasttiiioonnn))) m9 PFOA: 314 ~ (Serum Concentration) = 7-L42) Very limited empirical daa 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 calculated average PFOA concentration i finished iter in th 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 alo evaluated. Emmett's evaluation included oly those residents who reported from private well owners were also evaluated. Emmett's evaluation included only those residents who reported that their sole source of residential 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 occupation! exposure. The median serum concentration o average drinking 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 u1~g8//LL sseerruumm ttoo 33..5555 Jia/L wate, or 105, with an nterauarti ange between 62 an 162. For individual who used private wel a5 pg/L water, or 105, with an interquartile range between 62 and 162. For individuals who used a private well as tthheeiirr oonnllyy ssoouurrccee ooff rreessiiddeennttiiaall ddrriinnkkiinngg wwaatteerr,, rraattiiooss vvaarriieedd ffrroomm 114422 ttoo 885555 ((NN==66)).. TIInnheoorrMddeeDrrHttoomoaassdsseeelssscatthlhceeuliimatpmesacpatdoaoaffilcceyaarstrllyeyrfluifeme eceoxxnppcooessnuutrrreeasst,,iMMonODiHHn ccarrneeiaantfetadentdaabssoiinrnggnlleweicctoohmmpapnaarirtttmmaeelnntst,,eEErxuxccmeelPl-bFbaaOssSeeoddrTTPKKFmmOoAoddeell. TiccomohnpencacecMentnDttorHrfaatamtiinooonnidnebbflaaascsnteaeddlecxuooclnnlauttetshisheveamlmdyooatcthiolhyenerssr''eussrmussimeenrrgucumbomnrccceooeannncsctetrenamnttiirtorfalanottkriiionoonnnaaanettyidndeeeafarlli,nvvtervrybey.or.rsTnTuhhweesimtmhofoodadrenmelulilnww.itasifaselduussieenrfdusatmntootePeeexxFxacOalmSmuidsoniinreveePlttFyhhOeeA cccimooonnnpsssauuucmmmtpioitnnfiggaonccnooinonnftftaaacnmmotininnetaaxatcmteeliuddnsaiwwvtaeaetltdyeerwcraofftonoerrsru.oomnnDeeinayygeleabarirr.ne.taAAaskfttteem,erielthklhisifmsoirffniarostsntiteoyyneey,aearaar,,nr,dbbvoosettehrhsrussusccmeeanncaoafronriircoomessnutaalrassas-uftueimmdoeeniddnwfeaarnlietfeeecttaximmlccleeuuslaivteeldyover a sciomnusluamtipotniopneroifocdoonfta2m0,i0n0a0teddayws.ater. Daily intake, elimination, and serum concentration were calculated over a simulation period of 20,000 days. Useof or reference to this model without proper tribution to MsO prohibH ited. Use ojz or reference to this model without proper attribution to MOH is prohibited. 33775500..00001111 n STATE 07437964 STATE 07437964 30yeaofrges) 35" percentile water intake ate (0.044 kg.) and the allowing chemical pecic parameters: MMaatteerrnnaall sseerruumm ccoonncceennttrraattiioonn aatt ddeelliivveerryy wwaass ccaallccuullaatteedd uussiinngg EEqquuaattiioonn 33 aabboovvee,, aa ttiimmee--wweeiigghhtteedd ((ffrroomm bbiirrtthh ttoo 30 years of age) 95th percentile water intake rate (0.044 L/kg-d), and the following chemical specific parameters: + Holle POS 1.971 days and PFOA 840 days, Half-life: PFOS 1,971 days and PFOA 840 days, + VVoolluummee ooff DDiissttrriibbuuttiioonn (Ve): (Vd): PPFFOOSS 00..2233 LL//kkgg aanndd PPFFOOAA 00..1177 LL//kkgg,, aanndd ClCealeraarannccee RRaattee ((CCRR):): PPFFOOSS 00..000000008811 LL//kkgg--dd aanndd PPFFOOAA 00..0000001144 LL//kkgg--dd.. TTrahhneegiiennrff:aanntt'ss serum serum concentrationa concentration at birth birth was was calculated calculated based based on on maternal maternal serum serum concentrations concentrations and and placental placental transfer: Equatio4n. Calculation of nfan serum concentration at birt. Equation 4 Calculation of infant serum concentration at birth. Serum Cone. (9m)ay =_ Maternat serum conc. (m"g) x placental transfer factor For al subsequent day, the daly post-eimintion serum concentration ws cleat 5: For all subsequent days, the daily post-elimination serum concentration was calculated as: Equations. Caeuaton of infant's day serum concentration Equation 5. Calculation of infant's daily serum conc:entradono Serum Cone. (52) = |prev dey Serum cone. (32) +--SIEYNGH)_{, -y Serum Conc. (---) = Prey. day Serum Va 35) x Body Weight (ko) Today's Intake(rod) L ' V~ (~-~) x Bad), Weight (kg) Xe-k Duetothe magnitoufdthe 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 transfered othe infant 35 wel excretion representedby 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. Calculation of breastmilk concentration. Equation 6. Calculation of breastmilk concentration. Breasomitk cone. (m3)y= Maternal serum conc. (m5g2) x breasumitk transferfactor The various model input parametearnsdthe values used are describedinSection 2.1 below: The various model input parameters and the values used are described in Section 2.1 below. 2.1 Model Inputs 22..11..11 EElliimmiinn~attioior~n ((HHaalfit-il.liiffee)) Centers for Disease Control (CDC) 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 US population (COC 2017) I is important to consider tested, indicating widespread exposure in the U.S. population (CDC, 2017). It is important to consider background exposures because chemical nlf vs can be overestimated if background exposures are not taken background exposures because chemical half-lives can be overestimated if background exposures are not taken int accoun (Bartel 2012). Accurately accountifnogr onging background exposuisrvers dificult and most into account (Bartell, 2012). Accurately accounting for ongoing background exposures is very difficult and most Studies estimating halle have not taken i into account, esuling in potential overestimation studies estimating half-life have not taken it into account, resulting in potential overestimations. (USEPA, 20160). The arithmetic nd geometric meanhalf ves of PFOS in humans have been estimatedto be5.4 EEmmpipririiccaall ddaattaa rreeggaarrddiinngg tthhee hhaalflf--lliiffee ooff PPFFOOSS iiss lliimmiitteedd ttoo ooccccuuppaatitioonnaallllyy eexxppoosseedd wwoorrkkeerrss ((sseeee SSeeccttiioonn 22..55..22 ooff (USEPA, 2016c). The arithmetic and geometric mean half-lives of PFOS in humans have been estimated to be 5.4 Use oofr reference to this model without proper attribution to MiO sprohiH bited. 33775500..00001122 12 STATE 07437985, STATE 07437965 yyoeceacarursspa((t99i55o%n%accloownnoffiirddkeeennrccsee(Oiinnlttseeerrnvv,aal2l0((0CC7I)1).)3.T93h.-9i6-s6..9p9oyypeeuaalrrasst))iaaonnnddc44o..88nyyseeiaarrsssotf((92e9565d%%iCCn1Id4i4.v.0i0-d-5u5.a.88lysey(ae2ra4sr)sm,)a,lrreee,sspp2eecfcteitmivvaeellleyy,), bbwaiatssheeddaoomnnean age of 61 years at the occupational workers age of 61 years at the time of (Olsen, time of initial blood collection. Halt life information across 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 pspaearvrtetiriccauulllaarrersiinenaffaranncthtsse,,rsiissinnnootdteaavvveaaliliolaapbbilnlee.g. TTTKhheemohhdaaellf-lsliffe(Lvvoacaclluiueseaoonfof,55.2.4401yy1ee)aa,rrss(Vwweaarsnseruu,ssee2dd01bb6yy).UUSSEEPPAA ((UUSSEEPPAA,, 22001166c)) aanndd bbyy several researchers in developing TK models (Loccisano, 2011), (Verner, 2016)). The decline of PFOS in infants was indirectly evaluated using newborn blood spots collected by New York State. (splethoff, The decline (Spliethoff, 2008). Blood spot of PFOS in infants 2008). Blood spot cards from 11 was indirectly cards from 11 diferent dates were selected from an evaluated using newborn blood spots different dates were selected from an archive spanning collected by New archive spanning 1997 York 1997 to.State to 2a2t00o00t77.a.lTTowwfoo2,hh6uu4nn0ddrnreeeddwabanondrdfnfooirnrtftyayntiisnn.ddiiAvvciiddcuuoaarlldiiinnnffgaatnnott btbhlloeoooaddutsshppooorttsss,wwteehrereetseseemlpleeoccrttaeeldd tfforoerrneedaasccohhboosfef rtthvheeed11w11eddraaetteecsso,,nrrseeippsrtreeenssteennwttiiintnhgg a ahatloftiafleooff24,6.440yenaerwsbfoorrnPFinOfSa.nTtsh.isAvcaclouredinisgrteoastohneabaluythcolross,etthoettheemapdourlatlhtarlefn-Idfse oebssteimrvaetde dweerrievecdofnrsoismtent with a occupational exposure half-life of 4.4 years for occupational exposure studies. Due to the PFOS. This value is studies. Due to the limitations reasonably limitations of this blood close to the of this blood spot adult spot analysis, half-life analysis, MDHused the adult half life estimate derived from MDH used the adult half-life eessttiimmaatteess ffoorr tthhee TTKK mmooddeell tthhrroouugghhoouutt aallll felife ssttaaggeess.. UcUonnnppcuuebnbltliirssahhteeiddonddsaatotaaveffrrrootmmimttehheeweEEraaessttcoMMneestitrrsootebbnitioowm miootnhnitietoolririimnniggnasstttiuuoddnyyf,,acctooesnnoddfuucc6tt.ee3dydebbayyrMMsDDbHaH,s,enndoototeenddgttehhoaamttetddreeiccrcreemaaessiainnngg ssseeerrruuummm concentration and 7.2 years baonsindeividdual 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 (DH, 2015).This of 6.3 years based on geometric mean serum ((Nelson, 2016) and (MDH, 2015)). This pPpoRopOpuSullaaitntiitoohnneccgooennnsseiirssatteleddpooopffu11l44a99tiiionnnddiwivveiidrduueaalilssde((n66t77ifmmiaealdele,i,n 88t22heffepemumbaallliees))haaenndddliaatemmraeetauarnne.aaggBeeacoofkfg55r33ouyyeenaadrrsse..xpNNooosuddraaettasa ofonrnohhmaaltltfh-IeliffeEeaosoftf MPeFOtrSoinstthuedygweenreernalopttoapukleantioinntowearecidceonntiuftiehndestine thcaelcpuluabtliisonhse.d literature. Background exposures from the East Metro study were not taken into account in these calculations. TTorhheevrireea acaroreentssaeemvvieernraaaltl eppduubbdlrliiiccnaakttiiionongnsswaeetvveaarl.luuaaTtthiinenggfhhoalalllffo--wliiiffenegoohff PPaFFOOfAA iiennshthiuummmaataennsppwooeppruuellaasttiuioomnnmssareeixxzppeoodsseebddyeeEiittPhhAeerranoocdcccuaurppeaatitioonnaallllyy opprrreevssiaeenncttoee3.nd8dtyabbemeeallionrowaswte({((dUUmSSedEEdrPiPniAAka,,inn22g003.151w,66ra0aa)t)en:)gr:.e The following half-life estimates 15 - 8.1) -based on decreasing were summarized by EPA and are serum concentrations in twenty-six retired 33.M8 2:33M yweoarrkser(ms e(dBuiarrnis3e.5t, yweoarrkse-rsba(sBeudrroisneat asalre.al.rni22ge00es000o01,f,.5s22e-00r009u22.m1aa)ccci-iobn((aUcUseSSenEEtdPPrAAao,,tni22do00ne11s6c62rafe))ra.)o.sming20s0earudmul concentrations ts taken over ti in me twenty-six retired after treatment of 2ditr.rn3ienkaykiteinnmaggersnwwt-aastbtyeaessrrteeiidmnn,oW WneteshasettstVVeiirirmireggesiinneoiixaafpsaaoennsrddeudmLLbiitecttlfoeeonrHHceoeoccankkntiridnnaggta,i,oftOOnesHHr ff((riBoBlatmarrartttee2ilo0llnl0,eetatpadaubllu.llti22sc001t1va00e)kr).e.snuCCsooovbvvaoaertriritaatltitemeedssewiinaantcfcetluelrdru,edtgrdeeenatthdhtem eerwew,anaattgteeeor,rf 3.3tccrooeynnaesstam uumrmepspnttti(ioogsnenyosoomtefefmtlloro,cciatachllemooerrtaimhhnoo,emmreeeaxggnprgroooeswwe1ndn.vvb0eeeggf1eoetrtaea4bbla-l.eenssbd,7,aasaae)fnntdeddroeefnxxilpptrdooaissftuuiforreneere,ttnopocuetthsbheleiicnppvpuueblblrasliiscucmswwaabactotoeetntrrlceessdnuutppwrppalaltyytieaaort,nt swwgoefornrrkkdo,.emr,aage, 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 drinkingwater concentrations drinking water supply from a supply ((eBBsrrteeiddmeeaetetetsaabl.l.as22e001d100o)).n. EqEuxxeppsootssiuuorrneenawwiaarsseseessattniimdmaaittneetdedrrfvriooemwms.ddrrTiihnnekkiintnoggtwawlaatpteoeprrumm loanotiintoitonorreiivnnagglurreaestsueuldlttss(2aa,nn0dd08iinnsttuaabkkjeeects from the exposed area and 73 from areference area) included children, as well as adults. estimates based on questionnaires and interviews. The total population evaluated (2,008 the exposed area and 73 from a reference area) included children, as well as adults. subjects from 2.52f.o-5r3m-.e03r.y0Leuyabereacsrks,a(WavVvee,rraarggeeesi22d.e.99n))tsffoo[rrnffoootrremmieenrtriaLLilittttllleeevHHeoloccikkniinnLggubrreeecsskiiddreeennsttissdeaannntdds 55w.9.e9r-~e11l00o..w33eyryeetaahrrsasn((aLavivetereargaHegoce8k.58i.5)n) gffoorr residents] based on adecline in serumlevelsin former Lubeck, WV, residents [note initial levels residents] - based on a decline in serum levels in individuals who changed in Lubeck residents were individuals who changed residential lower than residential location (Seals Little Hocking location (Seals eett aatllh..e22a001s11s1)u.)m. pTTthhieeonaauutththhaootrressxipiddoeesnnuttriiffeiieewddattshhrureneeiefppooortmteenwnttiiiaall tliimmahiwittaaaitttieionornnssdioosftftrthihcetei,irraaannndaalalyypssoiitss:e:nttthhieealccrrbooissasss--ssieencctttriiooodnnuaalcledddeessbiyig.gnn,, 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 TTcohhleeleddceetccerrdeeiaanssiiNnneggwsseeYrrouurmkm Scctooanntcceeen(nstptrrlaaitteiitoohnnosfsf,ooff20PP0FF8O)O.AA Twwheeerreeteaamllspoooreeavvlaalltuuraaettneeddds iionnbisinneffraavnnettssd bwbaaessreeeddcooonnnsnniseetwwebnbotorrwnnitbbhllooaoohddaslspFpoIotftsse of 41 years. collected 4.1 years. This value i reasonably close in New York State (Spliethoff, This value is reasonably close (withian factor of 2) 2008). The temporal (within a factor of 2) to the trends to the adult half.Ife estimates of 2.3 to observed were consistent with a adult half-life estimates of 2.3 to 3.8 years. half-life of 3.8 years. DDuuee ttoo tthhee lliimmiittaattioionnss ooff tthhiiss bblloooodd ssppoott aannaallyyssiiss,, MMDDHH uusseedd tthhee aadduulltt hhaaflf-lliiffee eessttiimmaattee ooff 22..33 yyeeaarrss ffoorr tthhee TTKK mmooddeell tthhrroouugghhoouutt aalll felife ssttaaggeess.. Use oof reference to this model without proper attribution toMOH isprohibited. 33775500..00001133 113 SSTTAATTEE 0077443377996666 cRRoeensssuuillsttssteffnrrotomwmittthhheePEFEaaOssAtt MeMleeitmtrrioonabbtiiiooommnoronanittietoosrroiinfngg3.ss2ttuyudedayysrsshhoboawwseeeddd ttohhnaatgt eddoeemccerrteeraaissciinnmggessaeenrruusmmerccuoonmnccceeonnntctrreaantttiioronanstsiooovvneesrrattniimdmee3.ww4eerree years based on consistent with years based on individual resuits PFOA elimination individual results (Nelson, rates of (Nelson, 2016 and 3.2 years 2016 and (MDH, 2015). Background exposures were not taken into based on geometric mean serum concentrations and 3.4 (MDH, 2015}). Background exposures were not taken into aaccccoouunntt iinn tthheessee ccaallccuullaattiioonnss.. TTrohhueeteeelsliimomfiinneaaltitimioionnnathhiaaollnff-.liivvTeehsseoouffnPPdFeFrOOlSSyiaannngddmPPeFFcOOhAAanvviaarsryymggarrpeepaatetlalyyrsaammtooonninggvoddliiffvffeeergrelennotmtessrppueelcciaieerssf..iRtRreeanntaailol neexwxcicrtreehttiiaoocnntiiivssoeonrneeenoaoflftthhee tubular secretion and routes of elimination. tubular secretion and reabsorption (Han, 2012). Biliary excretion also occurs butdoesnotseem tobe The underlying mechanism appears to involve glomerular filtration with active reabsorption (Han, 2012). Biliary excretion also occurs but does not seem to be a major renal a major ffaaccttoorr ccoonnttrriibbuuttiinngg ttoo ssppeecciieess ddiiffffeerreenncceess.. SSeerruumm aallbbuummiinn hhaass bbeeeenn iiddeennttiiffiieedd aass tthhee pprriimmaarryy bbiinnddiinngg pprrootteeiinn iinn tithhmeepopprlltaaassnmmtaa.r.oSSlpepeeiccnidieeissffaaepprppeenetaairratttoionhhgaarvveeenassliimmeililliaamrribnbiainntddiioinnnggaaamffoffiinnnigittieivesasraainnodud;s; ttmhhaeemrrmeefafoolrriee,a, niitt sddpooeeecssiennso.ottLsesveeeeelmms ottfoo applllabayyumaainnn and totalproteinsare important role in total proteins are approximately70percent lower differentiating renal elimination approximately 70 percent lower in young infants than in adults (Sethi, 2016), among various mammalian species. Levels of in young infants than in adults (Sethi, 20:16), however, the albumin and however, the ppootteennttiiaall iimmppaacctt ooffththiissddififffeerreennccee oonn eelliimmiinnaattiioonn iiss uunnkknnoowwnn aatt tthhiiss ttiimmee.. HsHpuuemmcaiaennssssaatpuppdpieeeaadrrttthooushhaafvvaeer (tthHhaeens,sllo2o0ww1ee2s)s.tt PPTFFoOOdSSataaenn,ddrPPenFFaOOlAAorrregenananalilceelaliinmmiiionnnaatttiirooannnsrrpaaottreetaearnndd(OlloAoTnn)ggeepssrttothhaealilfnf-sllivihveaessveaabmmeooennnggsttthuhedeied both indirectly and directly for their species studied thus far (Han, 20:12). both indirectly and directly for their potential To date, potential interactions with perfluorinated chericals. Perfluorocarboxylates renal organic anion transporter (OAT) proteins have been studied interactions with perfluorinated chemicals. Perfluorocarboxylates r((PePFnFaCClAAsus))pthhaaakvveeetbbreeaeensnnpossrtuttedriesu,dtOtdooATaaig1grreaeeanatddteeOrrAeeTxx3tteernnettsitthdheaannipneptrehfrelfluuboaorsrooolssauutlleffrooannlaamtteeessmbP(PFrFSaSAnAse)s)..ofAAmmthooennpggrotthxheiemccaoolnntffuiirbrmumleeaddr PPceFFlCClAAs and treheniarl PuFpCtaAkuepttraaknespwoorutledrsf,aOciAliTtZataenPdFCOAATr3enarelstiduebuilnarthseecrbeatsioolna.teIrnalcomntermasbtr,adnueeotfothteheiprroexxipmreaslstiuobnuliantrhceellasp,iacanld tmheemirbrPFaCnAe uopfttahkeepwrooxuildmaflactiulibtualtaerPcFelClAs,rOeAnTa3l ,tuabnudlaUrRsAeTc1rewtioounl. dInbceotnhtreatsrta,ndsupoerttoerthseiinrveoxlpveredsisnioPnFCinAthreenaalpical tubular reabsorption (Han, membrane of the proximal tubular reabsorption (Han, 2012). t appears thata tubular cells, OAT4, and 20121. It appears that a key reason for URAT1 would key reason for the long PFCA plasma haf-ife in humans isthe be the transporters involved in PFCA renal the long PFCA plasma half-life in humans is the hhiigghh ppeerrcceennttaaggee ooff rreennaall ttuubbuullaarr rreeaabbssoorrppttiioonn ((>>9999%%).). EExxccrreettiioonn ooff PPFFOOSS aanndd PPFFOOAA aallssoo ooccccuurrss tthhrroouugghh bbiilliaarryy eexxccrreettiioonn.. RReennaall cclleeaarraannccee ooff PPFFOOAA hhaass bbeeeenn eessttiimmaatteedd tttoootbableecrrlooeuuggahhrllayyn99ic00neppmeearrclceeennattnoodff ftthehemeattlooettaaJllaccpllaeenaaerrasanenccmeeaicinnamqmauaellsee.rraaTtthss,e, wwshihgeenrrieefaiacssaniittceiissoeefsstttihimemaabttieleiddarttyoopbbaeetohonwnlalyyy44c00opmpeperarccreeenndtt otofof tthhee renal total renal elimination clearance in elimination in humans is not male and female in humans is not clear and Japanese clear and cobeusignlificdant. Increased macaques. The significance of could be significant. Increased fecal elimination of the biliary pathway fecal elimination of PFOS and compared PFOS and PPtoFFOOAA iinnaadduulltt hhuummaannsswwaass ddeemmoonnstsrtraatteedd aafftteerr aaddmmininisisttrraattiioonn ooffaa bbiillee aacciidd sseeqquueesstteerriinngg aaggeenntt ((GGeennusis,, 22001133).). TrTehhneealsseeprrruoumcmeshhasalelffs--lliaivlveoensse.eessWttihimimaalteteelddimttoiot--deddaattieenslliiikgkehetllysy hrreeappvrreeessbeeennettnbbgooattihhneeednnttreeerrgooahhreedpipanatgtiisccpaeancniddersrdeeinnfaafllepprrreoonccceeessssseeisns,,elrraiamtthihneearrtitthohnaa.nn mechanisms, an renal processes mechanisms, an understanding of potentia lfe:stage differences in humans continues to be alone. While limited insights have been gained regarding species differences understanding of potential life-stage differences in humans continues to be anin an area of elimination area of ccoonnssiiddeerraabbllee uunncceretrataininttyy.. IInn tthhee aabbsseennccee ooff lliffee--ssttaaggee ssppeeccififiicc en renal aanndd bbiilliiaarryy eexxccrreettiioonn iinnffoorrmmaattiioonn,, aannddtthhee vllaaacclkkueoosff ahhciigrghohsqqsuaualalililttyyfeessstttiaimgmeaastt.eess ooff PPFFOOAA aanndd PPFFOOSS hhaallff--lliviveess ffoorr iinnffaannttss,, tthhee MMODHH mmooddeell uusseess tthhee ssaammee hhaallff-fliiffee values across all life-stages. AAvahhlaualeflf-lulitiffieelivvzaaedlluubeeyooVfef55r..4n4eryyeeaaanrrdss ((c11o,.l99l77e11agdduaaeyysss)()VffeoorrrnPePrRF,OOS2S0ww1a6a)ss assneeldleeccbttyeeddEPbbAyyiMnMtDDhHHeiffooarrsuussseeesisinnmoeounurtrsmmooddee.l. TThhiiss iiss tthhee ssaammee value utilized by Verner and colleagues (Verner, 2016) and by EPA in their assessments. AAhhaallff-lliffee vvaalluuee ooff 22..33 yyeeaarrss ((884400 ddaayyss)) ffoorr PPFFOOAA wwaass sseelleecctteedd bbyy MMDDHHffoorr uussee iinnoouurr mmooddeell.. TThhiiss iis tthhee ssaammee. vvvaaallluuueee uouttf3iil.iiz8zeeddyebbaryys.EEPPAA iinn tthheeiirr aasssseessssmmeennttss.. VVeerrnneerr aanndd ccoolllleeaagguueess ((VVeerrnneerr,, 22001166)} uuttiillizizeedd tthhee hhiigghheerr hhaallff--liiffee value of 3.8 years. 2.1.2 VolofDuistrmibuteion T2h.:e1,2voVluomleumofe doifstDriisbturtibiounti(oVnd, /kg body weight) for PFOS and PFOA is believed to 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 lPPoFFnOOgAA:twweerermreeex00p..22o33suaarnnedda00n..d1177arLLe//kkmgg,o, srretessapppeepcclttiiivcveaelblyyle((UtUoSSEEoPPlAdA,e,r22c00h11i66lcd))reaannndadn((dUUSSadEEuPPlAAt,,s 220I0d11e66naat)i)..caTTlhhoeersseesiVVmdidlavvraallvuuaeelssueaasrreeweuursseeeddutffioolrrized 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 toMOH isprohibited. 1 33775500..00001144 STSTAATTEE 0077443377996677 ocboyylVVleeearrgnnueeerrs aa(nnLddo cccoooslllaleneadagg,uu2ees0s 1((VV3eer(rnn0e.er3r,3, 22a00n1166d0)).1((070.22f33oraaFnndOdS0.10a17n7 dffooFrr PPOFOROSSraaennspddecPPtFFiOOvAeA,lyrreessppeeccttiivveellyy) and and Loccisano Loccisano and and colleagues (Loccisano, 2013) (0.22 and 0.17 for PFOS and PFOA, respectively). MOH agrees with the Valuesof 0.23 3nd 0.17 i for PFS and PFOA, respectively for der chien and MDH agrees with the Vd values of 0.23 and 0.17 L/kg for PFOS and PFOA, respectively, for older children and Sus fats, however, have igher water content an shuld, hereto, hav a higher Vd based an adults. Infants, however, have higher water content and should, therefore, have a higher Vd based on tracelulr vom potentl The vale of exracellr ida. percent of body weght roughly plateaus extracellular volume potential. The volume of extracellular fluid as a percent of body weight roughly plateaus ound year of age (FisHansen, 1561) The MOH model nces an carfye stage Vi dimen cer around 3 years of age (Friis-Hansen, 1961). The MDH model includes an early-life stage Vd adjustment factor bbaasseedd oonn iinnffoorrmmaattiioonn ffrroomm TTaabbllee |I ooff FFrriiisi-sH-Haannsseenn ((11996611)) rreeggaarrddiinngg tthhee eexxttrraacceelllluullaarr wwaatteerr aass aa ppeerrcceennttaaggee ooff bod weight (BH). Age specific Vd aciusimen factors wer caluated by MOH and ae resented n he tale body weight (BW). Age-specific Vd adjustment factors were calculated by MDH and are presented in the table veiw: below: TTaabbllee 11.. AAgt~ee-s--psepceicfiificc vvoolluummee ooff ddiissttrriibbuuttiioonn ((VVe~)) aaddjjuussttmmeenntt ffaaccttoorrss.. [3 EacaiulrWater | ColVeAdeusitmenteFaidorTM A~e Cid rars h-- 0-1 day 130d 557 1-30 days 13months 22 1-3 months > months Eo 3-6 months 12 months 270 6-12 months Tver 6 1-2 years dyes 267 2-3 years Extracellular Water as % of BW* 44.5 39.7 32.2 30.1 27.4 25.6 26.7 Calculated Vd Adjustment Factor** 44.5/18.7 = 2.4 39.7/18.7 =2..1 32.2/18.7 = 1.7 30.1/18.7 = 1.6 27.4/18.7 = 1.5 25.6/18.7 = 1.4 26.7/18.7 = 1.4 3-5 years Stoves 20 5-10 years 10.5 years 07 10-15 years a Tl Fo GT *from Table I of Friis-Hansen, :1961. 21.4 22.0 18.7 2onsr-1z 21.4/18.7 =1.1 22.0/18.7 = 1.2 i8.7/i8.7 = 1 ** calculated by MDH Caracllar water content tha adults (eter, 201). To vad abrupt changes within the model, the miolnt T`Thhee 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)) aloe. The Gay Vd AF beeen ane midpnt and th next were calculated oy nea interpolation. verl use value. The daily Vd AF between one midpoint and the next were calculated by linear interpolation. Overall, use the Vi AF Improve model ess ncompa1riesmoian dat se ection 2 nd Tabi 3 nd 4). of the Vd AF improved model results in comparison to empirical data (see section 2.2 and Tables 3 and 4). 2:13 Placental Transfer 2.1.3 Placental Transfe~ Several sudies measured maternal and cord serum eves of POS an PFOA near the tiof dmeleery (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 permitting am estimation of placenta raster and ical ody burden the newborn nant. sAeppendie or permitting an estimation of placental transfer and initial body burden in the newborn infant. See Appendix I for Tore informaton. more information. The reprted mean aio of cor to maternal concentrations anged fom 0.31 (Fromme, 2010) 00.60 The reported mean ratios of cord to maternal concentrations ranged from 0.31 (Fromme, 2010) to 0.60 reported mean atios rom thse tucies were 0.42. 0.87 for POS and POA (espectely. Tres alswere ((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 mmoodedle.l. TThhee ppllaacceennttaall ttrraannssffeerr vvaalluueess uusseedd bbyy LLoocccciissaannoo aanndd ccoolllleeaagguueess ((LLooccccaassiinnoo,, 22001122)) nierner and colleagues (Verner, 016) were 0.4 and 0.65 respectively, o POS nd 0.45 an 0.75, and Verner and colleagues (Verner, 2016) were 0.46 and 0.45, respectively, for PFOS and 0.46 and 0.78, respecte fo PFOA respectively, for PFOA. Use ofr reference tothis mode without proper atribution to MiOproibHite. 33775500..00001155 is 15 stare onaTses STATE 07437968 22I.,1n1.t4.a,4k.eBBrrraeeteaasssttfmomriilekkxcIInlnuttasaikkveeela~ynnbddreBBaosotddfyyedWWeineifigagnhhttst, and data used to calculate corresponding body weights for the fist yearof fe, were obtained Intake rates for exclusively year of life, were obtained rom Table 15-1 of USEPA breastfed infants, and data from Table 15-1 of USEPA's 2011 used 2011 Exposure FactorsHandbook (EPA 2011). to calculate corresponding body weights Exposure Factors Handbook (EPA 2011), for the first TTaabbllee 22., HHuummaann mmiillkk iinnttaakkee ffoorr eexcdluussiivveellyy bbrreeaassttfeedd iinnffaanntt:ss aanndd ccaallccuullaatteedd ccoorrrreessppoondnidnigr~g bbooddyy wweeiigghhtl:ss ((BBWW).), GrAgogeuep | ML/day | mikgMMdeeaaanny| Group mL/da mL/kg-da m<<ao~nth 551100 115500 o<3 | 60 month i to < 3 690 140 CCwoaillclgual)atte"edd | 33.a4 4.9 Upper Percentile** mi/day| mi/kgday| CWalicuklaat)ed rnL/da rnL/kg-da Calculated 9050 22200 a4.33 52 980 190 5.2 month 3w<6 | 70 70 1000 Z2 3 to < 6 770 110 7.0 1000 150 6.7 months | months <1 | 620 7s 100 77 6 to < 12 620 83 7.5 1000 130 7.7 months months anand apes pee SK te hen ro TOUR 51 GPATORT Mean and upper percentile intake rates taken from Table 15-1, USEPA 2011 nla) nig *(mL/day) + (mL/kg-day) "Upper prc pried5 ma pus 2 andar devon. **Upper percentile is reported as mean plus 2 standard deviations. CCoonnssiisstteenntt wwiitthh guidance (MDH D2M0H0D8'H),s'stchcuuerrrrueepnnpttemmrepetethhrocoeddnootliloolggeyyinootffauuksseiinrnaggtaaesnn aRRnMMdEEcsoscrcerenenasarpiriooonfdfooirndgderebirovivdiinynggwperpiorgtohettecstcitwivveeerheheeasaelllttehhc-tbbeaadsseefoddr use givinnautltihdhuaeeesnTTciKKentmm(eMoondDddeeeHldl..2tUU0op0pap8ppe)ep,rrrthoppexeerircucmeeapntnpteietillretephbbeerrr9ee5caaessntttmmpilielilrkkiniictnanttkaeaekkebenraryrtateaatstediedsainrrneedegppcrrtoeewrssreoeennsstttpaaaonnccddooaimmrnpdgipdlibleaaovttidiioaoyntnwioooefnfmisgmethaeotssatsuwhureereermeddesoaoerrnleeevscsatttleiimudme.aaftoteerdduse v(asleureas ,in2te0n1)d.ed to approximate the 95th percentile by adding two standard deviations to the mean value (USEPA, 2011). W Wailitlthhyiinbnottdhhyeewmmeoiodgdehelt,l,sttbhheeetm mwieiddeppnooioinnntteninmittdimipoeeinffotoraeenaadcchhthaaeggneeeggxrtroowuuepprwweaacssalssceeuttleqaqtueuadallbttyoolttihhneeearmmeienaatnnerpbbooolddatyyiowwnee.iiggThhhtitsvvaaallpuupeer..oTTahhceeh davaoiliydsboadbyruwpteigbhotdsybweetiwgehetnchoannegemsidapnodinkteeapnsd tthheeonveerxatlwl ebroedcyawlceuilgahtetdtibmyelisneeraiersinclteorspeotloattihoendi. sTchrisetaeppvraolaucehs in attshihveneogiUdUlesSStEEaoPPnbAArbuiEEprxtxtphpbsooossaduturyr3eewFFteaao7icgc4tthoo1trrsscwhHeHaaeannkngdsdebbsooofoaokgn.ked.stTTkahheteeeipobbsnootiddhnyyetwwhoeeevieiyggrehhaattlral atb2t0obb0di5iyrt,thhwuewswiiaagnsshgtssdeteaitmttaaaettf33s.r38e.o3krmi8egstk,hgce,lottNhshaeeettimmooeentahaanneCbbediniirsrtttchehrrewwtfeeeoirigvgahHhtleutaeffloostrrhin staintgilteitocsn (bDirotnhashaute,3720to10)4.1 wBoedeyksweolfgghetsstaintiotnhein[3thseagyeeagrro2u0p05w,eurseinCgaldcautlaatfreodbmytehxeteNnadtiionngatl hCeesnlteoprefodrlHneeaflrthom Stothlhtedaeeticcrseetanincgttseeerr(gDrooooffunttphah.ehetuWtwewa,oto2ep0rpr1reie0vnv)it.iooaBkuuoessdrggyarrtwooeuuesppiwgsseh((rt1se111iintn0ott<he<e1r1p66loalaasannttddaegd11e66ingattrooosiu<<mp22i11lw))aeruurnnetmtiailclnaiinttlcrerueerlaa.acctehhededdtbythheeex88te00nkkdgginvvgaalltuuheee for 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 S(S2k.ee1iv1vme.e.,rSraa2lBl0r1sse1ttu)uad,dsiite(emHssailmmukege,apasa2sur0utr1irt3eeio)ddr,~mmLiar~autgte,err2nna0al1l 1ss)eerruFumrmoaamnnmddebb,rree2aa0s1st0tmm)i,illakknccdoonn(cKceaenrntrtrmraaattniio,onn2ss0oo0ff7PP)FFOtOhSSeraaennbddyPPpFFeOOrAAmi((t((CuCanargriiooauun,, e22s00t11i55m)),a,te of mp(pKaearimrattini,ttio2iro0nant1iini1nog}gs, ffo(rHfrooambmurgemma,asa2ttt0emer1irn1lnak)a,llt(oLsseiemurra,uut2mem0r1iinn1nattol)o, sbb(eFrreerroauasmmsttmmmcioelinl,kkc2eaa0nnn1tdd0ra)pp,trriaeeonidndcictrt(iaiKoonanngreroomfffarbbnorr,eemaa20ss0.tt00mm71i)ill)Kkk,atccrhoorennmcrceeaenbntn,yrtrap2at0eiti0oro7mnn)ssi.t0.tiTnThhg0.eea0rrn1ee8eppo(soLrtrivttme,edadte of 2m0e1a1n) fraortioPsFOoSf barnedasftrmomilk0t.o02m6aKtiemrn,al20s1e1ru)mt0c0o.n1c0e9n(tLrua,tio2n01ra1n)gfeorfrPoFmOA0..0T1he(Kaavrermraagne,s2o0f0t7h)etore0p.o0r1t8ed(Lmiue,an tf2raah0tte1iio1omss)efffaroronrommPvaFttlOhhueSeesssaeenassdcttruuforddosiisemesss0wwu.e0eer2rsee6 00(s.K.0e0im11e33,A2aap0nnp1dd1e00}n..0t0do55220| .fof1oo0rrr9mPPo(FFLrOOiueSS, aia2nnn0fdd1o1rPPmFF}aOOftoAiA,ro,nPrr)eFesstOpopAeecc.catTtilihvcveeuelllayay.tv.eeMMrPaDDFgHHOesSssoeaelnlfeedtcchttPeeeFddrOettAhpheoebrraateevvadeesrrtmaamggeieelaknooff tccuhoosenencdcmeenbentyatrrnLaaottvciioacolniunssseasffnrrooaocmamrnocdcsoosrcrrsoreeltuslsdpepiaooegnnsudde(iissnne(ggeLommAcapcatipetesrearnnnnadoal,ilxss2Iee0fr1rou3urm)mmacconoordnenccVeiennnftoterrraamttaiiaronotnnidosscnnoni)nltloooeeuuarcrgammruloceodusedlale(.tlVe.eTTrPnhhFeeeOrS,bbrr2aee0naa1dss6tt)PmmiFwilOlekkArtterrbaar0nne.ssa0ffse1ert2rmv2vaiallaklnuudeess 0.014, respectively, for PFOS and 0.038 and 0.058, respectively, used by Loccisano and colleagues (Loccisano, 2013) and Verner 0.014, respectively, for PFOS and 0.038 and 0.058, respectively, fo PFOA and colleagues for PFOA. (Verner, 2016) were 0.0122 and se of or reference to this model without proper attribution to MiO prohibH ited. 33775500..00001166 1s 16 STATE_07437960 STATE 07437969 TTprhhoeepmmoasateteedrrnwnaaalltsseeerrguuumimdccaoonncnceceevnnatltrruaaetutiisooinnngaatt Eddeqeluliiavvteeirroyynww3aas(sscceaaellcScueucllatatiteoednd aa2.s0)aa, ssDtteueaaeddyty--ssttthaaetteemccaoognnnccieetnuntdtrreaattoiiofonnexbbcaarsseeetiddooonnnvittahhee tbpbrhrreoeeapaisosnttsfmmeainldiltkk,w,2stathtwheeerlcclgaal3ulcc5iduuolalaanntgtciiooeoinnnvoogafflumddeaaatiuiellysyrinnmmagalatEteeeqrxrnunpaaaoltlsioussnreeerr3uvumi(mseccdeoornniScnceekecninttniotrgrnaawtta2iioto.0nen)ssr. Diainnnuccdeoorretpopxooctrrrhaeaettteiemdodnallogrossnessitpuoofdfreccehhoesefmeemixbcnicayctrltevaevhtiiiladoenttcrravlainenaassrffeearnrctteoo te:the infant as well as ongoing maternal exposure via drinking water and excretion represented by the clearance rate: Equation 7. Calculation of maternal daly serum concentration Equal:k:~n 7o Calculation of maternal daily serum concentration. Serum Cone. (22) = [prs daySerum cone, (72) 1 To40YE(nt5a)kelmBgo)dLywoesisghtotIrngf)ant (ng) mPParrteeeggrnnnaaannlccyyseaarnnuddmllaacccottnaacttieioonnntraaarreetissoiigngnnaiiffniicdcabannrtetammsatatmteeirrlnnkaalcl oeenllciimemniitnnraaatttiioioonnnsrr.oouuAttececssoffroodrrinPPgFFOOtSSo aaLnnoddcePPsFFaOOnAAo tathnhadttgcgrorelealatelatlgyyuieimsm,ppaamcacttternal sSPmeeFarrOutuSemmranccnaoodl nnscPceeFernOuntAmtr,raatcrtiieoosonnpncessectaanitttvrttaehhlteeiyo,eentnnshddaanoondfdfuabrasriseinxxgammsaotomrnnltiltykhh cpllaoraccenttgcaanettiainoontnnrcpayepti(reoLirniooosc.ddiAsaaacrencedoa,ardpp2pipn0r1rgoo3x)xti.oimmaTLatohteceelclyyeisma11pni44oraaiacnnanddld44dc00aotppllaeeerarrccgeeeupnnoetrtst,looemwwdeaeirtnrefrfonorral PFOS and PFOA, respectively, than during early pregnancy (Loccisano, 2013). The empirical data reported in sreavterearl pluobssliocfatPiOonAs afsroomdmaotecrnaulamsdeeercurmneavsteresuins mPaRtOSe,rnal serum concentrations, in genera 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. Maternal serum PFOS concentrations decreasedby about ine percent afer six months of breastfeeding relative Maternal serum PFOS concentrations decreased by about nine percent after six months of breastfeeding relative ttoo ccoonncceennttrraattiioonnss aatt ddeelliivveerryy ((mmeeaann dduurriinngg pprreeggnnaannccyy aanndd aatt ddeelliivveerryy 33..55 ulagg//LL aanndd 33..22 utagg//LL aatt ssiixx mmoonntthhss)) (Fromme, 2010), For PFOA, maternal serum concentrations decreased by 115 percent at delivery (mean during (Fromme, 2010). For PFOA, maternal serum concentrations decreased by 11.5 percent at delivery (mean during concentration decreased byabout 38 percent rom pregnancy throughsi months of lactation. pprreeggnnaannccyy 22..66 upgg//LL aanndd aatt ddeelliivveerryy 22..33 upgg//LL)) aanndd ddeeccrreeaasseedd aann aaddddiittiioonnaall 2266 ppeerrcceenntt aafftteerr ssiixx mmoonntthhss ooff bbrreeaassttffeeeeddiinngg ((mmeeaann aatt ddeelliivveerryy 22..33 gpg//LL aanndd 11..77 ulagg/iLL aatt ssiixx mmoontnhths)s.). OOvveerarallll,, tthhee ttoottaall mmaatteerrnnaall PPFFOOAA sseerruumm concentrations decreased by about 38 percent from pregnancy through six months of lactation. Decreases in maternal FOS and PFOA serum concentrations have also been rerted by others. Mondl and Decreases in maternal PFOS and PFOA serum concentrations have also been reported by others. Mondal and ccoolllleeaagguueess ((MMoonnddaall,, 22001144)) rreeppoorrtteedd aann aavveerraaggee ooff tthhrreeee ppeerrcceenntt ppeerr mmoonntthh ooff bbrreeaassttffeeeeddiinngg,, wwhhiicchh wwoouulldd rreessuulltt in an 18 and 36 percent decrease over sx and twelve months, respectively. When upper percent nant in an 18 and 36 percent decrease over six and twelve months, respectively. When upper percentile infant breastmilk intake raes seeTable2) were incorporated nto the MDH model, maternal PFOS serum breastmilk intake rates (see Table 2) were incorporated into the MDH model, maternal PFOS serum concentration decreasedby 12 percent after sx moonfbretasthfeedsing and 24 percent after one year of concentration decreased by 12 percent after six months of breastfeeding and 24 percent after one year of breastfeeding. Adjustment of the modtoeusle mean infant breastmilk intake rates (see Table 2) rested in breastfeeding. Adjustment of the model to use mean infant breastmilk intake rates (see Table 2) resulted in smaller decreases in maternal PFOS serum concentration (9 and 17 percent after six and twelve months, smaller decreases in maternal PFOS serum concentration (9 and 17 percent after six and twelve months, respectively). respectively). Incorporation of upper pInrcoodrupcoerdataio8n opfeurpcepnetr percentile infant breastmilk dpeecrrceeansteileininmfaatnetrbnraelassetmruilmk intake ates see Table cinotnackeentrraatetsio(nseaefTerabsliex 22m))oninnttthhhseeoMMfODbHHremmaoosddteeflleffeoordr iPP3nFFOgOdAA 73 pp(psereoerredcceeuTnanctbetldddeeeacc2)rr4,ee8asamsspaeeelralaceffetrtenrdrtedoocennrceeeraeyyseaeaesarse.r.iiWnW nhthmeeeanrntenttrhahneelalmmPasoFeddOreueAlml swweacarossunaamcdecjdnuotsnrjtcaeetdiunotttnoroscaatcoftionteonsnresiidswdideexerrrmemmoeoenbaatshnnesrinnovffefoadnbntr(te4bba0rrseeatafanessdettmmd6ii1nillkkgpenianrtntcaadekknaeet7rra3aafttteeessr (see Table 2), smaller decreases in maternal PFOA serum concentration were observed (40 and 61 percent after ssiixx aanndd ttwweellvvee mmoonntthhss,, rreessppeectcitviveelyly)).. Thomsen and colleagues specifically studied the impact of reasteding on PFOS and PFOA breastmilk Thomsen and colleagues specifically studied the impact of breastfeeding on PFOS and PFOA breastmilk concentrations inten Norwegian mothers (Thomsen, 2010}, Breastrik samples were collected monthly from concentrations in ten Norwegian mothers (Thomsen, 2010). Breastmilk samples were collected monthly from about two weeks p to twelve months after birth. Depuration rates of PFOS and PFOA were estimated to be 3.8 about two weeks up to twelve months after birth. Deputation rates of PFOS and PFOA were estimated to be 3.8 and 7.8 percent pr month of breastfeeding. MDH used WebPlotDigitzer (WebPlotDigtizer, 2017) to and 7.8 percent per month of breastfeeding. MDH used WebPIotDigitizer (WebPIotDigitizer, 2017) to a`apppprrooxxiimmaattee tthhee ddaattaa iinn FFiigguurree 22 ffrroomm tthhee ppaappeerr bbyy TThhoommsseonn aanndd ccoolllleeaagguueess ((TThhoommsseonn eett aall..,, 22001100)).. WebPlotDigtizer is web-based tool used to extract data from pots, imaes, and maps. The approximated data WebPIotDigitizer is a web-based tool used to extract data from plots, images, and maps. The approximated data Useof or reference to this model without proper tribution to MsO prohibH ited. 33775500..00001177 17 STATEorazroro STATE 07437970 wwaass tthheenn ccoommppaarreedd ttootthhee ddeeppuurraattiioonn rraatteess pprreeddiicctteedd bbyy tthhee MMDDHH mmooddeell ((sseeee FFiigguurreess 22 aanndd 33 bbeellooww)).. TThhee MMODHH mmooddeell pprreeddiiccttioinosn cclloosseellyy rreesseemmbblleedd tthhee eemmpipririiccaall ddaattaa.. FFiigguurr~e* 22.. RRe.leal~tdivvee ccoonnccze,nnrtmattiioonn ccoommppaorriissoonnssoqffPPFFOO~Sf iinn bbrrae~aossttmmiillkk~,, TThhoommssezn'n,, 22001100 aanndd MMODHH TK model results 0: --_-- 4 Ew LI 2 ---- ------ TMMhODoHHmsMMeoonddeeetllal(U.pep2ae0n1r0Siaesrkest 1) ............................................................................................................................................................................... Thomsen et al, 2010....................................................................... o 50 w 1% 0 x 0 x0 "0 ormtaesto cocentotionirt mp oar *normalized to concentration in Jirst sample Days FFiigguurree &3. RReelfaotti;vvee ccoonncceennrtraotti/oonn ccoommppaarriissoonnooff PPFFOOAA iinn bbrreeoazs~ttmmiilfkk*,, 7Thhoommss~e*nn,, 22001100 oanndd MMDDHH TTKX mmooddeel/result. 0 gw 8 Iw x To 50 ) 150 0 SO: i O0 :i 90: ormto cocentotonift ample *normalized to concentration in ~irst sample -- Thomsen etal. 2010 --MMOOHHMMoodreell ((UtpepaemralreestSricka1)t 1) 0 I) w x0 w 2@.} 2 50 3-00 ~,.~0 4@% oDnayss Useofor reference to this modelwithoutproper attribution to MOHis prohibited. 33775500..00001188 18 18 STATE 07437971 STATE 07437971 OH used avaiable empirical dota, as well a ess, rom ahr models of POS and ROA (Fromme, 2010), 22..22 PPrreelliimmiinnaarryy EEvvaalluuaattiioonn ooff MMooddeell MDH used available empirical data, as well as results, from other models of PFOS and PFOA ((Fromme, 2010), ((MMooggeennsseenn,, 22001155)))) dduurriinngg cchhrroonniicc aanndd eeaarrllyy lliiffee eexxppoossuurree ccoonnddiittiioonnss ttoo aasscceerrttaaiinn wwhheetthheerr tthhee ssiimmppllee,, oonnee-- compartment NOH model produces aprapriae rest. Ft each model comparison, the mother's serum compartment MDH model produces appropriate results. For each model comparison, the mother's serum Concenration at delvery was 35m 1 be asteadyState and her ongoing exponre (estimated from he concentration at delivery was assumed to be at steady-state and her ongoing exposure (estimated from the ublshed materml Seu concentration) duing th otation period wos included the MDHmodel MOM ls published maternal serum concentration) during the lactation period was included in the MDH model. MDI-I also ade special requests for dataim some cass, but not all daa wer avaible or use, including nvidia made special requests for data in some cases, but not all data were available for use, including individual maternal pared dt. maternal:child paired data. 22.,22.,11 CCoomrpnaprairissoonn wwiitt[h] eemmpipririiccaall ddaattaa ffrroomm FFrroommrmnee aanndd ccoolllleeaa[guueess (2010) Fromme and colleagues investigated maternal and fant ody burdens of PROS and PFOA during the i months Fromme and colleagues investigated maternal and infant body burdens of PFOS and PFOA during the six months following Birth. There were S0patcgants, the jority of which exclusively breasted thei fants (37 fants following birth. There were 50 participants, the majority of which exclusively breastfed their infants (37 infants were xchsivly brea&sprtediomeindan,t breasted, arial breasted, and 1 fan received were exclusively breastfed, 6 predominantly breastfed, 6 partially breastfed, and 1 infant received no reas] Blood concentrations were collected fom 38.47 thers durin pregnancy, at dey, and at sx breastmilk). Blood concentrations were collected from 38 -47 mothers during pregnancy, at delivery, and at six mmoonntthhss ppoosst-t-ddeelilivveerryy.. MMeeddiiaann aanndd 9955LTMh ppeerrcceenntitillee bbrreeaassttmmiillkk ccoonncceennttrraattiioonnss wweerree rreeppoorrtteedd ffoorr 4444 mmootthheerrss.. Te MOH model was evaluated by inserting he eano 95 percentile maternal serum concentratiaont The MDH model was evaluated by inserting the mean or 95th percentile maternal serum concentration at evry and allowing the moe 0 predict the infant seu concentratiotn deve nd ot & months. The MOH delivery and allowing the model to predict the infant serum concentration at delivery and at 6 months. The MDH model Incorporated ether th ma or the upper percent reas intake aes nd contsponding body model incorporated either the mean or the upper percentile breastmilk intake rates and corresponding body wweeiigghhttss ffoorr eexxcclluussiivveellyy bbrreeaassttffeedd iinnffaannttss ((TTaabbllee 22)).. ood concentrations wre reported fo3r fetal cord samp4l0 ienfsant, a ix months after birth, and 24 Blood concentrations were reported for 33 fetal cord samples, 40 infants at six months after birth, and 24 infants at 19 montns aftr ih The mean and 95% percentile maternal an fant blood <oncentratons at six infants at 19 months after birth. The mean and 95th percentile maternal and infant blood concentrations at six months of age reportebyd Frommeand colleagues (Fromme, 2010) and those predicted oy the MOH model ae months of age reported by Fromme and colleagues (Fromme, 2010) and those predicted by the MDH model are `ssuummmmaarriizzeedd bbeellooww ffoorr PPFFOOSS ((TTaabbllee 33,, FFiigguurree 44)).. Table 3. Results of comparing MOH modeled PEOS infant serum conceirationsfoFrommae a. (2010) dat. Table 3o Results of comparing MDH.-modeled PFOS infant serum concentrations to Ftomme et al, (2010} data. Conceniraton | Frommeea2010| MONT ode" Concentration Vater serom Maternal - serum J ssn At birth Mean ost percent| 011410 alicenust 95th Percentile Fromme et al. 2.010 MDH TK Model* 3.s .all 6.1 ,g/L (set to meosured velue) | atiRatio ooff ode Model ttoo Messed Measured AAtt 66mmoonntthhss MMeeaann| 3.2 ug/l. 22.99 p.gg//L*a 00.9911a 9955t"h PPeerrcceenntitillee| 6.3ug/l. 9 4.9g.g/"Lb 00..7788b" resi Breastmilk AAtt 66mmoonntthhss MMeeddiiaann| 00..0044 p.gg//LL ((mmeeddiiaann)) | 00..003388 p.gg//LL#a" 00.9955 55% pecan | 008ug freee asa 95th Percentile 0.08 .g/L 0.064 .g/L#b 0.80 To an Infant - serum Reb wean | 13 Lars 13 At birth Mean ost percemie| 22181. seran 1 95th Percentile i.i .g/L 2.2 ,g/L 1.47 .g/L# 2.56 pg/L# 1.34 1.2 Mmontts wean | 33s UTIuOaNGAE Wosuast vaAF|| WLhuo vase wihToouwvia At 6 months Mean 55% percent| 32 lL Tou ust fos vg 95th Percentile 3.3 pg/L 8.1 .g/L With Vd AF 3.7 .giL~ 7.9 pg/Lb Without Vd AF 5.45 p.giL" 11.3 IJ.g/Lb With Vd AF 1.12a 0.98b Without Vd AF 1.65" 1.4b oo terra scum Infant:Maternal serum ao months invasion viae Ratio @6 months ean| 103 i i Mean 1.03 With Vd AF 1.3a Without Vd AF 1.9a 05" parce| 129 To 5 95th Percentile 1.29 1.6b 2.3b Til tometer eave srarl eBi a Boga aewa STE *MDH model included meternal loss via breastmilk as well as ongoing exposure during lactodon. Ongoing exposure was estimoted by st ed eocet nter me see back cdculodng a dose based on moternol serum concentration ot time o/delivery. Use ofr reference tothis mode without proper atribution to MiOproibHite. P 19 33775500..00001199 stare onarerz STATE 07437972 Sctcocrteton ndesemcretion cst ming temart sna cern eras #Breastmilk concentration and infant serum concentration calculated by multiplying the maternal serum concentration by the breastmilk engeotepnvonttfor epe trans,ferfactor and placental transfer,factor, respectively. temea et ns te le To aModel utilized mean breastmilk intake rate,for infant (see Table 2). outed at ee os eter re To2e bModel utilized upper percentile breastmilk intake rate for infant (see Table 2). 70S concentrations were abiined for 14 individual infant rom cord lod and at ag mane (Fromme et PFOS concentrations were obtained for 14 individual infants from cord blood and at age 6 months (Fromme et aal.l. 22001100,, FFiigguurree $$55)).. SSttuuddyy ddaattaa ccoolllleecctteedd aatt 1199 mmoonntthhss aafftteerr bbiirrtthh wwaass nnoott uusseedd bbeeccaauussee bbrreeaassttffeeeeddiinn8g hhaadd Ceased and ongoing exposures were uncertain. MDH usedWeSPIODigitzer crate an approsmatio of the ceased and ongoing exposures were uncertain. MDH used WebPIotDigitizer to create an approximation of the at presented n Figure 5 and compared the approximateresultstothe MOHmodel base on per data presented in Figure $5 and compared the approximated results to the MDH model based on upper ernie makeras (UPI) and mean east ak ate (MIR), and with and wiinout th merporation percentile intake rates (UPIR) and mean breastmilk intake rates (MIR), and with and without the incorporation CFV AF Results ar presented in Figure . of a Vd AF. Results are presented in Figure 4. CSimated ndiidual dato points om Figure 55, Fromme eta. (2010) FFiib.gluurer4e4.. tInnJfbanntt PPFFOOS5 sseerruumm ccoonncceennttrraattioinozn~s p prerdiceteddf.foiorrecexcxlctufusiesvivedldyy breastfed infants by MOH's model vs. esUma~~d individual d~t~ poMts jr'om Figure $5, Fr'omm~. ~t geu 2giEe. --pr i. _-= - mT] wana eZ F mwano s juin mmm JE : 5 8) eo -- : Age yes) Age (yrs) Unt prcee rote es ole 3, ith and i crn 045 ~ UPIR - upperpercentile breastmilk intake rates (see Table 2), with end without incorporating a VdAF. ne eat ko ob 3 i ton estin03g5 ~ MIR - mean breastmilk intake rates (see Table 2), with and without incorporating a Vd AF. Cte ar tr eo tSrn 13 30a1d 8 Data points are individual serum measurements estimated,from Fromme et al, 20~0 at birth and 5 months. MOH so evaluated is odel outputs fo PFOAbycomparing her 0 cata resented in Fromme, 201, sod MDH also evaluated its model outputs for PFOA by comparing them to data presented in Fromme, 20:[0. Blood ConcentraotfiPoOnRs ware reportedfo 3 feta od sample, 40 fants at i months after bh 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 after bith. Th mean nd 95 percent maternal and fant blood concentrations a sx infants at 19 months after birth. The mean and 95th percentile maternal and infant blood concentrations at six months of age reportebydFrommeand colleagues (Fromme, 3010), and those predicied by th MDH model, months of age reported by Fromme and colleagues (Fromme, 20:[0), and those predicted by the MDH model, re summarized blow fof PFOA Tale 4, Fire 5 are summarized below for PFOA (Table 4, Figure 5). Tabl3e. Results of comparingMOHmodeled PFOA infant serum concentatons o Fromme tal (2010) da lable 4. Results of compaHn8 MDH-modeled PFOA infant serum concentrations to Fromme et al, (2010) data. CCoonncceenntrtraattiioonn |FFrroormnrmneeeettalal,.22001100 |MD MDHH TKMMoodT deell* K| Tem Maternal - J 2310 At birth Mean 2.3 p.g/L 9955~"h PPeerrcceenntitillee| 55..22 ppLgg/!LL 2.3 p.g/L 5S.22ulezg/itL J -- (set to measured value) Aomontts Mean | 174k ans At 6 months Mean 5 perce| 39 p/. friend 95th Percentile i.i ~tg/L~ 1.9 ~tg/Lb ssc 6 monte Breastmilk @6 months Aomonths Mean | afoydecsin |0057 si At 6 months Mean NA (only detected in 0.057 p.g/L~ omen 2% of samples) 05 percent | 02541. oops 95th Percentile 0.25 I.tg/L 0.10 p.g/Vb RRaattiioo ooff MModoelttoodMMeeeaassuulrreedd asst0.65 ~ Gis0.49b 6 montis @6 months o: x0.40b seofor referetontchies model without proper attrtioMbOHuistproihiboitend. 0 20 33775500..00002200 sare onarers STATE 07437973 `CCoonncceennttrraattiioonn | FFrroommmmee eettaall.. 22001100|MDHTMDKH TMK Mooddel*el"| RRaattiioo ooff MModoelttodoMMeeaeassuurlreedd a Infant - Ronn wn [1700 200m! 2 At birth Mean 1.7 pg/L 9955t"h PPeerrcceenntitillee| 33..77 upgg//lL atmos wean |80pett TWoIvAeE WrihaeVIA||W0R5A%VIAE WithTooutVAT At 6 months Mean 8.0 pg/L 9955t"h PPeerrcceenntitillee| 119.95.5pgpg//LL 2.0 p.giL# 44..55 uptgghiL"# With Vd AF 7.9 pg/La 2211..22 pIa.gg/Lb Without Vd AF 12.7 pg/La 3B3.a1 pgg/gLb 1.2 11.22 With Vd AF 0.99a [11.11b Without Vd AF 1.6~ 11.77?b an atmarolm Infant:Maternal serum Fat 8% months wnvar Wine vaar Ratio @6 months With Vd AF Without Vd AF eon [47 7 fs Mean 4.7 7.2~ 11.5~ 052 perce | 50 fie) va 95th Percentile 5.0 11.2b 17.4b NH el ie lal 1 5B ot 70 5 Btn Eo KE DT *MDH model included maternal loss via breastmilk as well as ongoing exposure during lactation (using back calculated dose based on or amamearnmot on Fah maternal serum concentration at time oj: delivery). eat netomatoettn cle yg he el umcrtby heh ~Breastmilk concentration and infant serum concentration calculated by multiplying the maternal serum concentration by the breastmilk enero tts oa eh transferfactor and placental transferfactor, respectively. aoeno eo poe Toe 2 aModel utilized mean breastmilk intake rate for infant (see Table 2). em eager it mre ho oe bModel utilized upper percentile intake rate for infant (see Table 2). PFOA concentrations were btind fom the cord blo of 4 india infant a bith and from blood PFOA concentrations were obtained from the cord blood of :14 individual infants at birth and from blood ample at ag6 months (Frameet 3 3010, Fre 6). MON used Web zt to crete an samples at age 6 months (Fromme et al. 2010, Figure $6). MDH used WebPIotDigitizer to create an Sopronmatonaf th dota and compar the Sppronmated su the MOH model ess based on per approximation of the data and compared the approximated results to the MDH model results based on upper ppeerrcceenntitillee bbrreeaassttmmililkk iinnttaakkee rraatteess wwiitthh ((ssoolliidd lliinnee)) aanndd wwiitthhoouutt ((ddootttteedd lliinnee)) iinncclluussiioonn ooff tthhee VVdd AAFF.. Figur5e font PFOAserum concentrations fr exclusively rested non predictedby MOH model, Figure 5./n~fbnt PFOA serum concentretions f~r exc/usive,y brees~fed infen% predicted by MDH's model tmaed nahidoat dots pos rom Figwe 56. Fromme t a. 2010 es~irnot~,d individual d~ points.~}om Yiqure 56, Fromme ~ Olo (2010)~ I= Fo J 2fEi a. _--- 3 nUPrIeRawwo/VvvdAeFn.n: _- E n. l_=.z-- ---------- ee i 3. = o o o or os: os AAggee ((yyrrss)) UP por een resi te tes ae. nd wiht cin OVOA * UPIR - upperpercentile breastmilk intake rates (see Table 2), with and without incorporating a VdAF. S ev aoe ae atnotessskeon eSawbo eoorp 73 or 848 PS ** MIR - mean breastmilk intake rates (see Table 2), with and without incorporating a Vd AF. Data points are individual serum measurements estimated~rom Fromme et al, 2010 at birth and 6 months. 22..22..22 CCoommppaaririssoonn wwiitthh eemmpipririiccaall dda~ttaa ffrroomm MMoog~e:ennsseenn aanndd cco:olllleeea~guueess ((22001155)) timaormteaesurded sera concentrations of FOS and PFOA were axamind in Faroese ith cohort at Estimated or measured serum concentrations of PFOS and PFOA were examined in a Faroese birth cohort at Geary and atages 1,1, nd 60marthto detertmheipncet of brasioing (Mogensen, 2015. The delivery and at ages :11, :18, and 60 months to determine the impact of breastfeeding (Mosensen, 20:15). The thors simared sei concentrations th fom maternal er coneenetons ung Facts of 0.73 and authors estimated serum concentrations at birth from maternal serum concentrations using factors of 0.72 and 058 1or POS and OR respect, bascatoi between Cord and marl pregnancy serum 0.34 for PFOS and PFOA, respectively, based on ratios between cord and maternal presnancy serum Concenrations previously mate oro sa conor. Crewer reasted excuse or amedion concentrations previously estimated for the same cohort. Children were breastfed exclusively for a median uationaf 4 moh, lowebdy part resstieeding with Supplementarybaby100d ora median of duration of 4.5 months, followed by partial breastfeeding with supplementary baby food for a median of 4 Useofr referetontchies modelwithoutproper attrtioMbOuistpriioedn. n 21 33775500..00002211 sraTeordsrans STATE 07437974 ons MDH usd WesPotigier stmt sexu concentrations or OS nd POA ith an t 11 months. MDH used WebPIotDigitizer to estimate serum concentrations for PFOS and PFOA at birth and at :1:1 mans of a5 ro tector rested Fars of agen t 115, The relate magi range months of age from trajectories presented in Figure 1 of Mogensen et al. 2015. The relative magnitude change in erm concentrations tom Bh 1 monotf ghe for he cleven hide who wre at as prisly in serum concentrations from birth to 11 months of age for the eleven children who were at least partially `bbrreeaassttffeedd wwaass ccoommppaarreedd ttoo tthhee mmaaggnniittuuddee iinn rreellaattiivvee cchhaannggee pprredeicdteidcbbytytethhdee MMDDHH mmooddeell ((eexxcclluussiivvee bbrreeaasstt fecdng Toe comparisons for EOS and PFOAar resented Slow in Fe6sand 7, respect. feeding). The comparisons for PFOS and PFOA are presented below in Figures 6 and 7, respectively. oMrfoiegtehnsMlaOettHilvmeo(d1ee0l1e5e.saldffornclPAuGSseurmecamdaatfvoatton es1immteendtnoafoielratsrsitsofocmonFceen1t Mogensen et el, (2015), gj2 mp- e--T -- hA n wmwearsa fw mT RwNOAT I B twn = . AAggee ((ddaayyss)) UP. pe pnt reine oe, ithrdit cpio 45 ~ UPIR upperpercentile breastmilk intake rotes (see Table 2), with and without incorporating a Vd AF. antmeter ot mbmepSgOA ~ MIR - mean breostmilk intake rates (see Table 2), with and without incorporating a Vd AF. Sonia it ones po oon eo 51 5 li TR Data poinZs are individual serum rneasurernen[s estimated,from Mogensen et al, 20~ aZ :Z~ months, reladve to concentration at birth ure 7. Alt sus in fat PFOA serum concentrationat1 months of agenormeled to concentration Yi.qur~ 7o Reletive ~,ncrease in hTfmnt PFOA serum concentration at ~1 months o] ego norm~fized to concentration ct areh: MOH mod seo for lusty rasled fot vo estates nail dota pots fom Fre 1 birth .- MDH model re.suf~:s ~or exdusively brea.s~f~d in~an~ vs. e.sdma~~td Mdiv/du~! d~ta po/nLs ~r'om F~gure .~, Mogensen et al. (2015). f$2 2HgB owEoww 2 22 =prE mTE Rm ae e oy) m Em E raT:.Tr _TET Age (days) Uprising oS ~ UPIR - upperpercentile breastmilk intake rates (see Table 2), with and without incorporating a VdAF. sak motbo eeb wn ponep SOA ~ MIR - mean breastmil~ intake rates (see Table 2), with and without incorporating a Vd Coettn ese eSportsev cron Data points are individual serum measurements estimated/rom Mogensen et al, 2015 at 11 months, relative to concentration Ww mu--rmwe--rvea--nr--n ot birth Useofor referetnotciesmodelwithout proper attrtobMOuH triieodn. 33775500..00002222 22 sateonsarers STATE 07437975 22..22.,33 CCoommppaarriissoor~n wwii!t:hh m mooddeelliinngg rreessuullttss ffrroomm VVeerrnneerr cDDror.n. cMMeanartrcrcaVVteierornnneserr,f,ooor fnttuhhreesiUUnngniivivenerfrsasinitttyys ooufpf MMtooonnt3rtyrOeaaalrl,,s ddoefevvaeeglleaoppaeenddd aageddnrreaafrftotuEEsxxlccyeelpl--rbboaavssieedddedmmoaodddeerlal ftttooceeosspttyiimmoaafttteehissseemrruoumdmel to MDH. The Verner model includes Monte Carlo simulations concentrations for nursing infants up to 3 years of age and MDH. The Verner model includes Monte Carlo simulations and requires only thre inputs: 1) generously provided a draft copy and requires only three inputs: 1) number of of this model number of to iitteerraattiioonnss,, 22)) ccoommppoouunndd sseelleeccttiioonn ((PPFFOOSS,, PPFFOOAA,, oorr PPFFHHSxS),), aanndd 33)) mmaatteerrnnaall ddoossee ((l~gg//kkggd-daayy)).. MMODHH ccoonndduucctteedd aann amadoddddieittliio.onnaall eevvaalluuaattiioonn,, wwhhiicchh ccoommppaarreedd tthhee rreessuullttss ffrroomm tthhee MMDDHH mmooddeell wwiitthh rreessuullttss pprroodduucceedd bbyy tthhee VVeerrnneerr model. IItt sshhoouulldd bbee nnootteedd tthhaatt tthhee VVeerrnneerr mmooddeelluusseedd ddiifffeerreenntt iinnppuutt vvaalluueess ffoorr sseevveerraall ppaarraammeteetersrs:: Ha(HlVaeflrf-lnliievvreessusuuessdeedd3.ww8iyittehhaiinrnstthhweeheVVreeerranneserrMmmDooHddeeullseaadrree2.3tthhyeeeassraasm)m.ee aaRssattthhheeerMMtDDhaHHnmmaotodtdeeemllpfftooirrngPPFFtOOocSShbbauunttgddeiifftfeehrer ffVooerrrPPnFFeOrOAA model to MDH (Verner used 3.8 model to MDH's selected half-Ife of 2.3 years, years whereas MDH used 2.3 selected half-life of 2.3 years, the MOH model was modified to incorporate years). Rather than attempting to change the the MDH model was modified to incorporate a half-life Verner a half-life ffoorr PPFFOOAA ooff 33..88 yyeeaarrss ffoorr ccoommppaarriissoonn ppuurrppoosseess.. ThThee bbrreeaassttmmiillkk iinnttaakkee rraatteess uusseedd bbyy VVeerrnneerr aanndd ccoolllleeaagguueess ((VVeerrnneerr,, 22001166)) ffoorr tthhee ffiirrsstt 1122 mmoonntthhss wweerree. ccbaralelccauuslltaamttieelddk ((iIInnntttaaakkkeee r((aggt//ekskgg-fd-o)rd=)-e-x~-c00l.u.3s31i1v22elxxyaabggreeea((sddtaafyeysd)s+)i+nf11a55n77t..s77))praaennsddenaatrreeedssiiimmniTillaaabrrliienn m2maaagbgnonivitteuu.ddMeeDttooHtthsheeelemmceetaeadnn upper percentile breastmilk intake upper percentile intakes to rates for intakes to represent exclusively represent a reasonable maximum exposure scenario. breastfed infants presented in Table 2 above. a reasonable maximum exposure scenario. MDH selected VMeMrDDnHH'e'ssr mmmooodddeeelll udussoeeesssaannnot.aaggMeeD-ssHpp'eecscifimfiioccdaaeddljjuuwssattmsmeernnutnt ffwaaiccttthoorraffnoodrrvwvoiotlluhuommueet ootfhfdeidsiVstdrtriiAbbFuuttfiiooornnc((oVVmddpaAArFFi))swwohnheeprrueeraapssosttehhsee. (see Section 2.1.2 for more information regarding the basi of the Vd 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. MMDDHH ccoonndduucctteedd sseeppaarraattee mmooddeell rruunnss ffoorr PPFFOOSS aanndd PPFFOOAA uussiinngg tthhee ddrraafftt VVeerrnneerr mmooddeell wwiitthh :11,,000000 iitteerraattiioonnss aanndd a2m0am1t6aetreUnrSnaEalPl AddooHsesaeelootfhf 00..0000330088 t/,tgk/gk-gd-daayy.. TThhee mmaatteerrnnaall ddoossee wwaass Advisory value) and a 95 percentile water bbaasseeddoonnawa awtaeterr ccoonncecnetrnattiornaootff0i0.o.00n77 intake rate of 0.044 L/kg-d. These same ulagg//LL t(thhee inputs for water concentration and 2016 USEPA Health Advisory for water concentration and adult water intake rates were used in model runs based on the MDH value) and a 95Lh 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. TTExhhpeeoMMsuDDrHHeFammcootddoeerllswwHaaassnrdruubnnooffookrr paarnnoviininffdaaennsttbeerxxeccallsuutssmiiivvleelklyyibbnrtreeaakasesttrffeaetddesffooarrnoodnnebeoyydeeyaarwr,,ettihhgeehtddsuurfraoarttiieooxnnclffuoosrrivwwehhliyiccbhhrttehhaeestUUfSeSdEEPPinAAfants. TEhxeporseusureltsFaocftotrhse Hmoadnedlborouknspraonviddaescobmrpeaarsitsmoinlkoifntraekseulrtaitnegsinafnadntbsoedryuwmecigonhctsenftorraetxicolnussaiveblyitbhr,ea1smtfoednth,3infants. month, 6 month,9 month, and 12 The results of the model runs and month, 6 month, 9 month, and 12 month time-points are presented below in Table 5/Figure 8 (PFOS)andTable: a comparison of resulting infant serum concentrations at birth, 1 month, 3 month time-points are presented below in Table 5/Figure 8 (PFOS) and Table 66//FFiigguurree 99 ((PPFFOOA)A.). TFTaaatbeblsel)e55v.s..CCVooemmrpnpeaarrrismioosndoeonflf MMreODsuHHltsPPFFOOSS mmooddeell rreessuullttss ffoorr eexxcclluussiivveellyy bbrreeaassttffeedd iinnffaanntt ((uussiinngg uuppppeerr ppeerrcceentnitlilee iinnttaakkee rates} vs. Verner model results IN Model Predicted Serum Concentration (I~/L) Verner50 & 85% | iB1ni1rt0hh [am1o1M8onn |"33M2M0oo0rnt [ 66M2M5oo5nn 9M92oM9o1nn | 11223M0Mo5onrt | percentile Vetoer 50t" percentile & 95th us11.0 24.5 359:[4.8 35.9 sss20.0 55.8 78325.6 78.3 89329.1 89.3 95.130.5 95.1 {MMrODaHHtivmmoio.odVdeeelmler 95 | 1(160660.50) (220266.36) (30355545.5) 0s5060.s05 76622).55 777337.66) se) (ratio vs. Verner 95t~ (0.65) (0.63) (0.64) (0.64) (0.70) (0.77) MOH %tile)modelwith Vd | 16.0 307 50 771 5 Tis AMFDrHemmoovdeedl with Vd A(rFotroemvsovVeerdner 95 (065) :16.0 (0.65) (084)30.2 (0.84) (055) 53.0 (0.95) (058) 77.:1 (0.98) I]95.5 (1.1) 2) :1:1:1.9 (1.2) (srtaetio) vs. Verner 95~' %tile) Use oof reference to this model without proper attribution toMOH isprohibited. 33775500..00002233 223 SSTTAATTEE 0077443377997766. IFnitgaukree r5.atCeos)mpvsa.riVseronneorfmMoDdHePreFsOuSltmsodelresults for 1-yrexclusively breastfedinfant using upper percentile iie = foo oe i I ed rr TThhee sseerruumm percentile vccaoolnnucecesenntgrteranatetiirooanntssedeessbttyiimmtaahtteeeVddebbrynyettrhheemoMMdeODlHH. mmootoddheellmoaadtt etthlhese eeuaasrrelldyy tstiimimveea--pproohiiannlttfss. iwwfeerrveealbbueeettswwfeeoeernnPOtthhSee.550H0tohwaaennvdder99,55th ttbphrheeeerarrceseetnwwmtieeillrerkeeviddanilitufffaefekesreergenrneacctneeeesssraiianntnessddeevavbepeyrpralatlihl eeoodttVhhaeeegerrr-nppsepaarerrcmaaimmfoeidetceteeVlr.rdssBAuuoFsstshee,ddmwwwhoieidttrheheilisnnasueesaatecchdheh smVmioemodredinlalee.rrl. hmoFaoorldfr-eeelilxfxeaaummvspaepllduleee,b,srMMefoaODsrHHtPmFuiuOlsskeeSdd.inHhhtiioaggkwhheeeervrraetre, s tbhraetawstemrielksiinmtialkaer troatmeesaanndinatpapkelierdataegsea-nsdpedciidficoVtdaApFpsl,ywhVedreAaFs. the Verner model used breastmilk intake rates that were similar to mean intake rates and did not apply a Vd AF. DH perforsmimeiladr comparison tothe Verner model for PFOA, showin below in Table6 and Figure3. MDH performed a similar comparison to the Verner model for PFOA, shown below in Table 6 and Figure 9. Table6. Comparison of MOHPFOA Troatbele) 6ve, .(3Voemrnpearrismoondeolf MreDsuHltsP.FOA rates) vs, Vetoer mode[ results, Model VernerS07 E Birth Verner 50t~' & 95" percentie 95th percentile MDH model (23 yr tal | 19.1 MDH model [2.3 yr t~/~] (os vemer 95" sie) | (035) (vs. Verner 95~h %tile) MDH model with 3s MDH model with 38yrti 3.8 yr t~/2 ts vemessetie) | 079 (vs. Verner 93t~ %tile) MDH modelwith VG AF| 18.1 MDH model with Vd AF removed removed to ve9m5estre) | 1045) (vs. Verner 95t~ %tile) MDH model with38yr | 315 MDH model with 3.8 yr hal fe + Vd AF half-life + Vd AF removed wr removed (v5. Ver95n etire) (vs. Verner 95th %tile) Birth 2!.4 42.0 19.1 (0.45) 31.5 (0. 75) 19.1 (0.45) 31.5 (0. 75) model model | | | || | resus results iMon 1 Mon 50.6 135.6 38738.7 (029) (0.29) ia64.4 0a (0.47) 1361_.3 1((0o0.t41s58)) 101.8 7s (0. 75) for exclusively breasted infant usingupper for exclusively brea~tf=d infa~-~t (using upper Predicted erom Concentration (1g/) Predicted Serum Concentration | 3Mon | 6Mon | SMon 3 Mort 6 Mort 1 Ti97 87.1. 1.12.1. 2399 2505 239.9 288.0 719 1003 141 71.9 100.3 030) 035) 039) (0.30) (0.35) 1209 ma 197.4 120.9 171.1 9 Mort 11_9.7 290.6 114.1 (0.39) 197.4 (0350) 059) tos) (O.SO) 10.7 1649 185.2 1_1_9.7 (0.39) 164.9 (0.58) 1_85.2 030) 0s) 084) (0.50) 2010 2814 3209 201.0 (0.57) 281.4 (0.64) 320.9 (089) 1098) an (0.84) (0.98) (1.1) percentile intake. percentile intake | i2Mon 12 Mon 1176 1_1_7.6 296 289.6 1211 121.1 032) (0.42) m2 212.2 073) (0.73) 504 1_94.4 057) (0.57) sas 341.5 1s) (1. I8) Useof or reference to this modelwithoutproper attribution to MOH isprohibited. 33775500..00002244 224 STATE 07437977 STATE 07437977 Figure 9. Comparison of MDH PFOA model results for 1-yr exclusively breastfed infant (using upper percentile 3 7 gw te i Te ite ---- evi MMDDHH aanndd VVeerrnneerr mmooddeellss uusseedd ddiiffffeerreenntt hhaalflf--lliiffee vvaalluueess ffoorr PPFFOOAA ((MMDDHH uusseedd 22..33 yyeeaarrss wwhheerreeaass VVeerrnneerr uusseedd 33..88 years). When the MDH model was run usin8 a half-life of 3.8 years, the predicted serum concentrations fell bbeettwweeeenn VVeerrnneerr''ss 5500thaanndd 9955t"h ppeerrcceenntitillee eessttiimmaatteess.. WWhheenn tthhee VVdd AAFF ppaarraammeetteerr wwaass rreemmoovveedd ffrroomm tthhee MMODHH. mmooddeell,, tthhee pprreeddiicctteedd PPFFOOAA sseerruumm ccoonncceenntrtraattiioonnss ffoorr llaatteerr ttiimmee ppooiinnttss eexxcceeeeddeedd tthhee 9955"t~peprecrecnetnitillee vvaalluueess. re predicted by the Verner model. corp rT TTA Comparisons between empirical data as well as modelin8 results from Verner and MDH model results were within a factor of 2 for all time points when comparable half-life values were utilized. 2.3 Exp~nsion of Model to Steady-St.~te DL~ration os Due to the IonB half-lives of PFOS and PFOA, early life exposures will take many years to be eliminated from the body. After encourasin~ results were obtained from initial testin8 of the model, the modelin8 duration was extended to Ions-term exposure. MDH sousht input from six external experts resardin8 the adequacy (e.8., fit ms mre r sammt ie ffoorr ppuurrppoossee)) ooff tthhee mmooddeell aanndd hhooww ttoo eennhhaannccee aaccccuurraaccyy ooff sseerruumm pprreeddiiccttiioonnss.. EEaacchh rreevviieewweerr ssuubbmmitittteedd preliminary comments resardin8 the draft model and participated in a web-based meetin discussion. MDH responded to comments and made improvements to the model based on reviewer input. Reviewers were not explicitly asked to endorse or approve of the final model. See Appendix II for biosraphical information on each of the reviewers. i AAA A 1 The expanded model was designed to predict serum concentration profiles for two exposure scenarios: :~) an infant fed exclusively with formula reconstituted with contaminated water startin8 at birth, followed by a lifetime of drinkin8 contaminated water (Fisure 10); and 2) an infant exclusively breastfed for 12 months, followed by a lifetime of drinking: contaminated water (Fi~:ure :~2). In both scenarios, the simulated individuals ne besan life with a pre-existin8 body burden throush placental transfer. Upper percentile intake rates were used ffoorr tthhee bbrreeaassttffeedd iinnffaanntt sscceennaarriioo aanndd 99_5~TMth ppeerrcceenntitillee iinnttaakkee rraatteess wweerree uusseedd ffoorr wwaatteerr iinnttaakkee ttoo ssiimmuullaattee aann RRMMEE individual. sre ------------ 33775500..00002255 .25 -- STATE 07437978 Figure 10. Scenario #1 schem-Eaxcltusiivecly Formula Fed Infant. Figure .[0, Scenario #2 s(:hemod(: - Exclusively pri ] Maternal Serum Concentration steady --stte) Placental| Transfer Placental Transfer Neonatal Serum Concentration bith) Formula Fed Offspring Serum Concentration {birthtosteacy-ste) CClleeaarraannccee Use oof reference to this model without proper attribution toMOH isprohibited. 33775500..00002266 2% 26 SSTTAATTEE 0077443377997799 Figure 11. Scenario #2 schematic- Exclusively Breastfed Infant. Maternal Serum | Placental Transfer IoRnA (birth) Ie CClleeaarraannccee peste Breastfeeding Clearance mn Offspring Serum (>1yrtosteady-state) Clearance 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, ttoo ccaallccuullaattee tthhee iinniittiiaall iinnffaanntt sseerruumm ccoonncceennttrraattiioonn ffrroomm tthhee mmaatteerrnnaall sseerruumm ccoonncceenntrtraattiioonn ((sseeee SSeeccttiioonn 22..11..33..)) The maternal serum concentrations were assumed to be at steady-state and Equation 3 (repeated below, see Section 2.0 for additional information) was used to calculate the steady-state serum concentration. omnes (18) 7 et) er Gmrreon CF) 1588 mg Water Intake Rate earenceRee (5) Serum Concentradon (~) = ~ x ~a~er Concentration ~Clearance Rate (k~7~) x ~000 #g CClleeaarraannccee rraatteess ooff 00..000000008811 aanndd 00..0000001144 LL//kkgg--dd ffoorr PPFFOOSS aanndd PPFFOOAA,, rreessppeeccttiivveellyy ((sseeee SSeeccttiioonn 22..00)),, wweerree aapppplliieedd 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. The input values for breastmilk partitionins, 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. eforetohsmsteetonto Mo sp 33775500..00002277 .27 I STATE 07437980 223,.31,1AdAddidtiitko;nnaall MMooddeell IInnppuuttss 2r2.e33a.,s11tS:icDDeu~draritanitgoionhnaoosffm[Bakeenaaysstctflfeeeeaerdliiyqngegstablished heath benefit or infant, children, and mothers and fa key sseBxttrrcrealaatutessegitgfvyyeeelttodyoinibimgmrpephraraoossvvteeemdpapufnubybrlliicacclbehhoaeeuaraltlytlthteh.hs.etTTafhhbieelirsAAhsm6meedmerorihinccetaaahnnlsthAAwccibaateddhneeecmmfoiytynstooifffonPrPueeeidnddifaaibatnrtrrteiiscac,sssct((fhAAeiAledPPdr)ie) nnrrge,ecoacolnoomdmnmgmmseeionndtdhedsesirnttshthraaaotntdduiinncifftsaainanottnksseobbyfee 6eccoox6cmmplpueplsrleeicvmmeeenleytnntbotafarrermyyaostfftohofeooedddrsssfoffioornrraMaabittonleuneateasstshtoteti1afyyireresaeartp.ro6.rAAmtcccobcornoretrhdadissintnwgfgeittteohodittchnhogeena2t2tin00s11ui66ex dmBBorrbneerataeshsatstsff,etefeeweddieitidnnhiggn3gRR1eae4plpooponrertgtrscCCideaanerdtdine((CxtCrcDDolCCud,s,ui22cv00tei1l1o6y6n)),,onnfeeaarrllyy b6bbrr6reeeaapassestttrfffceeeeeeedndditiinnongggf..mdTTuohhrteeahteppireeosrnrccinoeefnnMtot inbbnerrneeeyaasessotatftieafeeoredreiinptnhgogerddtRrrboMorppeEppaeesscddtefenttaeoordi44ion11.g%5Uaaaptttpstteiwxwreempllvevoerenctmmehnosotn,intwlhthesits,bh.reMM3a1DDs.t4HHmipssleeeklrleceicecntttneeatddkeeaaxancnltueeexsxscicvllfeuurlssyoiivvmeeTable 2ub15-p5r1e-t1aos0otf1ffe2ttehhmdeeoinnUUgtSShEEdsPPuAAroaf22tia00og11en.11oEAEfxtxopp1noo2essuumyrroeeeanrFtFahfaocsctortooftrrhsseaHHeRaa,MnndfEdlbbusoiocdooekiknnat(ssareeikoeee. TTwUaaapbbslpleeesrw22iptiinencrhSSceeeedcnctttfiiiolroenonmb22r..be14ra.e4asatbsamtbomiolivkvleeikn)ttwwaoekewreraeetraeuurtsse,eesddafnrffordromoammnTbbaaiibgrtlteehh specific water intake a th up to 12 months of age. At specific water intake at the 857 percentile (see Table 7 below) was used through the esto Ife. 12 months of age, fluid intake was switched from breastmilk to water, percentile (see Table 7 below) was used through the rest of life. and an age- 95th 22N5..1e3.2wSWb.,o2arWntsaedtererriiInvntetaaakkele lRoRar.attneeeal lof thei nutrition from quid. quid intake ratesper unitboyweight al oDrNapeepipwdiadlbrlyyotrmwwneisintthhtdeaaorggfieveH,e,eaaaannlllddt, hobbr(yyMnaaDeggHaee)r,lssyee2avv0leel0,nn8o)aafrrftehorneniederaeanrrlruyitnrtthihgtehioenssaaalfmrmoeembaaaslisqttheuhoodidssswee. oaoLffirqaauddgiuduulltitisn.d.taaMMnkcODeeHHruasmmteeessetathphgoeoedrsdopoulelnoociiggt fyybio((cMdM3yii5nnwnneeepsisgeoohtrttaacfaelnl t wwaDraaeettpeerarerrptiilmnnittceaaaknkteteedorrafaittnHeeTsse,,aawwlbthhehii(cc7MhhbDeaaHlrroee)w,ff.o2ou0Tu0nhn8ded)siifennowTTraaadbtbelelreeriv33iin--n11gtaoohkffeeUUarlSSathEeE-PsbPAawA'sseer22de0011wu11saeEtEedxxrpp1ogosusfuiudorraeeniFFncafeaaccntuttoossrressesxHHacalgaunensddisbbvpoeoeloocykkiffic((oEEr9PPm5AuAthl22a0p0-1ef11er1)cd)eaaannnntdiddle2) aforer brreepalisctaiteeddiinnfaTnatbslefo7llboewilonwg .oTnheeyse weoafteearxcinlutarskiveerabeteasstwieeerediungs.edT1h)efoirnfinoframnattsioenxcinluEsPivAe'lsy Tobe 3-Lalso formula-fed and 2) provides data for breastfed provides data that allows for calculation infants following one year that allows for calculation ofof of corresponding body weights exclusive breastfeeding. The corresponding body weights forthe corresponding age information in EPA's Table for the corresponding age group. 3-1 also group. Table Table 77. Drinking Drinking water water ingestion ingest:ion rraatteess f~oorr ccoonnssuummeerrss--oonnlyy anand ccaallccuullaatteedd ccoorrrreessppoonnddiir@ ng bbooddyy wweeiigghhttss (BW) TT heeow Men ssbeenie Age Group mL/day Mean rnL/kg- Ca/cu/ated mL/day 95th Percentile mL/kg- Calculated mn doy | Bwika)* aay | SBwirkg) <<1 1momnontthh 311ttto00.<<<633mmmoononnttthhhs 610.<12months 3 to < 6 months 6 to < 12 months 1Lttoo<<22yeyeaarrss 22 ttoo<< 33yyeeaarrss 33 ttoo<<66yeyeaarrss 66 to0<111yyeeaarsrs 1i1ttoo <<1166yyeeaarrss a47r0o s5s5a2 555566. 64677 303088 335s6 3382 E51N1 6637 day ay 137 | us 119 80 53 | 2627 26 | |a21 T | 1217 12 | 34 [ess BW (kg)* 3.4 858 | a3day 238 | e4s.6 | a1o0s53s| a2s85s | 7.0 1171 173 8.8 1147 129 11,4 us13.7 as2 18.2 en893 912 |e 7652 | o9m99 [se52 | sai 30.1 53.1 | were 1404 1976 | 3s47 35 | BW (k~/)~ 363.6 373.7 626.B 8s8.9 12911.9 gar 14.7 a9219.2 EX)29.9 ses56.5 T6t0<18years 702 10 702 1883 23 16 to < 18 years 702 10 70.2 1883 30 62.8 18t0<21 years sie fi 742 2818 73 18 to < 21 years 816 11 74,2 2818 36 78.3 > 21ers 27 | 6 767 5092 76 > 21 years 1227 16 76. 7 3092 42 73.6 ea ans 95h cei te es ake om Tai 31, USE 011 Mean and 95th percentile intake rates taken from Table 3-1, USEPA 2011 miJan) + megoo) *(mL/day) + (mL/kg-day) 2.4 Summary of MOH Model Parameters bSS2ae,es4rriuusSmmoufccmtoohnnmecceaeRnIrntDytr.raaotAttii:nooMnnRssDDaaHrriesMtathnhoeedeebsbmetesistmtIa:mmateeretartorimiccfaefootdrearirddlseyettoeerrarmlmidinnoiisnneggitinnottteehrrennaahlluddmooassneepssoffpoourrlPaPtFFiOOoAAn aanniddncPPlFuFdQOiSSngaannsdednsssieetrrivvveeedd as as the the sbuabsgisrooufpths)e tRhfaDt. iAsnkeRflD tisoabneewsittimhoautte aonf aapdparielycioarballediosskeotfo dtehleetheurmioauns epfofepcutsla. tionis(iinmcplourdtinangtsheantsittivoetal subgroups) that is likely to be without an appreciable risk of deleterious effects. It is important that total Useof or reference to this model without proper attribution to MsO prohibH ited. 33775500..00002288 228 STATEo7asrost STATE 07437981 reeexxsppuoolstsuuirnreesfferrrooummm aaclllol nsscooeuunrrtccreeasst,,iiionnnccslluuhddiiignnhggerppootttheeannnttiitaahlleiinsnggeeerssuttmiiooncnooonfcf eddnrrtiinrnkakiitnniggownwaatasetserorccicoaontntetadaiinwniiintnghg PtPhFFeOOSSRDoo.rr TPPhFFeOOAAT,,Kddmoooeedssennloott developed by MOH predicts serum concentrations a various developmental stages overa person' lifetime result in serum concentrations higher than the serum concentration associated with the RfD. The TK model developed by MDH predicts serum concentrations at various developmental stages over a person's lifetime rirenedssiuuvllittidinungaglffrirosombmoraanccoowninststhtaa2nn5tt PPrFFeOOsAuAlotorrofPPFFmOOatSSeccroonnnaclceenenxtptrroaasttuiioroenn.iinn ddrriinnkkiinngg wwaatteerr,, iinncclluuddiinngg tthhee sseerruumm ccoonncceennttrraattiioonn aann individual is born with as a result of maternal exposure. IInn oorrddeerr ttoo eennssuurree tthhaatt hheeaalltthh--bbaasseedd wwaatteerr gguuiiddaannccee vvaalluueess ffoorr PPFFOOSS aanndd PPFFOOAA aarree aaddeeqquuaatteellyy pprrootteeccttiivvee ffoorraallll Ielixifecelssuttsaaiggveeesls,y, iwinnicctllhuuddfiionnrggmummlooarreerehhcioiggnhhslltyyiteeuxxtppeoodssweeiddthiinncffaaonnntttss,a,mttiwwnooatRReMMdEEwasstcceeenrnsaatrraiiorotssiwwnegearreet eebvivraatllhuu,aaftteeodld:l:o11w))edaabnnyiinnaffalainnftteffteeiddme of 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 wwaatteerr.. BBootthh sscceennaarriiooss bbeeggaann lliiffee wwiitthh aapprere--eexxiissttiinngg bbooddyy bbuurrddeenn tthhrroouugghh ppllaacceennttaall ttprraaarnnassfmfeeertr..eIrInnsooarrrddeeerurstteood,aaccahhsiiedevevesecaarnnibRRedMMEEinssTcceenanaarrib8ioob,,elaalommewi.ixxttuurree ooff cceennttrraall aanndd uuppppeerr ppeerrcceenntitillee vvaalluueess ffoorrtthhee vvaarriioouuss parameters are used, as described in Table 8 below. MaMnDDdHHdeccapararereftfuumlllelyyntssaeellleepccottleeidcdy.mmoAoddefelolrppmaaarlraaimmnee-tdteeerrpsst,,hbbsaaenssseeiddtioovnintytthhaeenabbleeyssstitsaaovvfaaiitlaahbbellemeossdcceiielen,nccweeh,,ieecxxhtteewrronnuaalll dppeepeerrorvrrieedvveiieeawwddcciootimmomnmeaneltnsts,, information regarding model performance, and departmental policy. A formal in-depth information regarding model performance, has not been conducted at ths time. Based on sensitivity analysis of the model, which would has not been conducted at this time. Based on the performanocfe provide additional the performance of tthhee mmooddeel,l, MMDDHH nnootteess tthhaatt wwaatteerr ccoonncceenntrtraattiioonn,, dduurraattiioonn ooff bbrreeaassttffeeeeddiinngg,, aanndd bbrreeaassttmmiillkk iinnttaakkee rraatteess aarree tthhee mmoosstt sseennssiittiivvee ppaarraammeteetersrs.. VVeerrnneerr aanndd ccoolllleeaagguueess ((22001166)) ccoondnucdteudacagtgllooebbadall sseennsistitiivviittyy aannalayslisyoosfftithhsee VVeerrnneerr mmooddeell aanndd ffoouunndd tthhaatt dmduoursraatttiisooennnsooiftfibbvrreeeapasastrtffaeemeeeddtieinnrggs,., bbrreeaassttmmiillkk iinnttaakkee rraatteess,, aanndd mmaatteerrnnaall sseerruumm//bbrreeaassttmmililkk ppaarrttiittioionniinngg wweerree aammoonngg tthhee most sensitive parameters. Use oof reference to this model without proper attribution toMOH isprohibited. 33775500..00002299 229 STSTAATTEE 0077443377998822 Table 8, Summary of MDH model input parameters arModel Parameter Half-life (t) Valuels) Used FOSS [Ohne od PFOS 5.4 years (1,971 - cant days) oeR r b0 [saocheet 00mm PFOA 2.3 Years (840 - mponn ercpoes days) Source Olsen et al. 2007 based on occupational workers Bartell et al. 2010 based on population exposed via drinking water oS Volume of Distribution Foi (Vd) PFOS 0.23 L/kg PFOA 0.17 L/kg Var [OTT Vd Age Adjustment Taman | Tiaas Factor (Vd AF) |fSGpCaSSiSirnitolmmomaroaeomwovfoomsrieeni-tsse1arso6on) Clearance Rate (CR) 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) (Ln2/hatJ~-Iife, days) | A a USEPA 2016, Hans et al. [me2012 Fr TT Friis-Hansen 1961 (also |ereheres consistent with Felter et |Som al. 2015) Cg Calculated value. Same oer value calculated and [vanons used by USEPA 2016 Va Ter Cam Value Type/ Sesion Description oSirem ed OR Central Veimed soci. (mean value) SISio a nmeeeoVikoane acsnetyesg n omw aaarerAteoeyroenoerenra cosoFvhnOeRo cos rgoitVn thocneerntogeheeei. Central S00, ed APA ot.Comet th ops (mean value) Con|rrreytsvsaemtrepsotedtowrssoaernooannaonAbo NesoSan hiones Central (mwa| avs tt 1d wt ne tr 08 08 (mean value) Frerc mEiOpv noaHnenear ce spahrarrtot a rooicdnadssafa meoTt asVoRrTsEo heppne Eornen soahnen Central nesc former oe a ol wo 1d (based on fir mean half-life) Confidence/Uncertainty Comment Same half-life values used by USEPA in their evaluations. Very limited data for PFOS. Several publications regarding PFOA, with average halflife ranging from 2.3 to 3.8 years. Lack of accounting for background exposures can over estimate half-life. In the absence of life-stage specific information, the same half-life was used across all life stages. 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 stages are known to have higher body water content per unit weight than adults. The adjustment factor is designed 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 lifestage specific information the same half-life was used across all life stages. This remains an area of Maternal Serum Concentration Newborn Serum Concentration PFOS 0.00008 L/kg-d fostered PFOA 0.00014 L/kg-d Coca neyos Calculated steady-state onmiesat) serum level (pg/L) Ged Calculated eatin Materna! serum meron Al concentration (t~g/L) x earn Placental Transfer Calculated (see Equation 3) MDH calculated value. Transfer Factor based on average of reported mean maternal serum uncertainty. Tor a hy Hoy Upper Cipte ionp mwaactheie ntese e oe oacr Elements of Hoc rnc arft able ew, en Central and oepetotr heaa Upper eit tama (based on Assumes mother is at steady-state at time of delivery based on proposed water guidance level. Maternal exposure based on 95th percentile water ingestion rate. Limited individual matching maternal serum to cord blood matching pair data are available. Mean, median and upper percentile ratios are within a factor of 2. See Appendix I for more information. [Te --------------r) EB) Factor mean transfer 30 33775500.00003300 stare rane STATE_07437983 Model Parameter Breastmilk Concentration Breastmilk Intake Rate (BIR) Vals ved Soiree VanTyp Value(s) Used Source (045105705087|tocodbioogrotin |oetsaoiprion (0.46 for PFOS and 0.87 eric) ee pont) we for PFOA) to cord blood ratios (see Appendix I) Geded VO Cte Calculated Nimrarirm | ant at ted Maternal serum comenain gx |an veorfegoneed concentration (pg/L) x eas str |mean mers erm Breastmilk Transj:er ocr Towers Factor 00or505300d | camerotnis (0.013 for PFOS and 062lepine ppenin) 0.052 for PFOA) Teperpric |Tob 1 T(E Upper percentile vfr orcnsa | 200 values for exclusively MDH calculated value. Transfer Factor based on average of reported mean maternal serum to breastmilk concentration ratios (see Appendix I) Table 15-1 (USEPA 2011) Value Type/ Description factor x maternal serum) Elements of Central and Upper (based on mean transfer factor x maternal serum) Upper nied breastfed (m L/kg-d) infants ContesUnearinyComment Confidence/Uncertainty Comment Cr aT i Be Limited individual serum to breastmilk data are ialMs,mean sn perpercentie available. Mean, median and upper percentile ratios wincirsofS Appenede. are within a factor of 2. See Appendix I for more oman, information. of Use of pp pec upper percentile es intakes NHB is MDH policy. Birth to <1 mon-220 1to < 3 mort- 190 essenOusion | bysicoefoesnxws e Breastfeeding Duration 3 to< 6 mort- 150 6to< 12 mon- 130 i year of exclusive breastfeeding Water Intake Rate (W~R) Reespecieos Age-specific 95th pevarevsies percentile values Corer ony consumers only pave (m L/kg-d) Bintoctmon Birth to <1 mon-238 1to < 3 mon- 285 Sta<men- 17 3 to < 6 mort- 173 6to< 12 mort- 129 Tocne 7 :~ to < 2yr - 75 |SERIBNYTS Selected by MDH to repre evansle represent reasonable monncrpoure maximum exposure en. scenario. |TS TUSEA ROT] Table 3-1 (USEPA 2011) mOtChTs poees xlscrhst$e39s3 sSatiLrgeoeF Upper Upper |FogJ osS erviwiucstisncpemgacencotct gcotonhmtn ottTefremhtosr epawpoteremmddnoSa0onsht4o r peo1tls5pro2,a.wcr3ho4ie07mntp5t A gcerevceneeea. sptosraxtniedstn-gSt 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 4:[%, 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. soils 2 to < 3 yr- 62 3 to < 6 yrs-52 6 to < 11yrs-47 11 to < 16 yrs-35 seo a free10 hismodelwitoutproperatu toMOHspros. 31 33775500.00003311 statearesrons STATE_07437984 Model Parameter Vals ved Value(s) Used Totocib3y0 16 to < 18 yrs - 30 Source VanTyp Value Type/ oesaipion Description Tad WOW Body Weight (BW) 18 to < 21yrs- 36 >_21 yrs - 42 [Ag spoon Tae foray | Conder Age specific values Croem dake |ngetan pers nd| wi Gerd calculated from intake uncnlaond | 15 tor es nes volume (mL/day) and sk at(hg. | rss esi intake rate (mL/kg-d). Table 3-1 for water ingestion exposure and Table 15-1 for breastmilk ingestion Consistent with Central (Mean) values exposure ContesUnearinyComment Confidence/Uncertainty Comment seo a fren 10 hismodewitoutproperatu toMOHspros. 33775500.00003322 32 satearesross STATE_07437985 33.,00 DDeerriivvaattiioonn ooff HHeeaalltthh--BBaasseedd WWaatteerr GGuuiiddaannccee VVaalluueess Three components ae used in the deraton of healt based wate guidance values: 1) measur of toxic, Three components are used in the derivation of health-based water guidance values: 1) a measure of toxicity, ection Water and breastmilk nake rates ae escribed in Sections 2.3.1.2 nd 2.14 respectively. ((RRIfDD));; 22)) rreellaattiivvee ssoouurrccee ccoonnttrriibbuuttiioonn ttoo aappppoorrttiioonn aa ffrraaccttiioonn ooff tthhee RRffDD ttoo wwaatteerr iinnggeessttiioonn;; aanndd 33)) aa mmeeaassuurree ooff e`exxppoossuurree,, tthhee wwaatteerr//bbrreeaassttmmiillkk iinnttaakkee rraattee.. SSeelleeccttiioonnooftf thhee RRffDD aanndd RRSSCC aarree bbrriieeffllyy ddeessccrriibbeedd iinn tthhee ffoolllolowwiinngg section. Water and breastmilk intake rates are described in Sections 2.3.1.2 and 2.1.4, respectively. 33.,11 RReeffeerreennccee DDoosseess aanndd CCoorrrreessppoorn~ddiinng SSeerruumm CCoonncceenntlr:na~ttiioonnss MOH conducted an expedited and focused re-evaluation of th avaiable toxicological formation, eying in MDH conducted an expedited and focused re-evaluation of the available toxicological information, relying in paran USEPAs 201 health assessmant documents (USEPA, 20163) (USEPA, 20160). Several ey ste (5. part on USEPA's 2016 health assessment documents ((USEPA, 2016a) (USEPA, 2016c)). Several key studies (e.g., Conidae for forming the bas of an ID) were ented for FOS an POA, 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 levels, and immune suppression. Whi thes effects were Gbserved afferent tiheeywsere serum levels, and immune suppression. While these effects were observed in different studies they were observed at Smilr serum concenteation levels. A two generation reproductivestudy was selected as th study observed at similar serum concentration levels. A two generation reproductive study was selected as the study Upon which to base th inal RD. Tis he same critica sty usedbyUSEPA as the bass of her AD. The no upon which to base the final RfD. This is the same critical study used by USEPA as the basis of their RfD. The no observable avers fect vel (NOAE] average sur concentration fom this ty ws 6.26 mg. The observable adverse effect level (NOAEL) average serum concentration from this study was 6.26 mg/L. The Puan equnalent dos corresponding hs serum concentration canbe calcted vig Equation human equivalent dose corresponding to this serum concentration can be calculated using Equation 2: Dose((g1e9s)) _= Serum coCnocnecnetnrattriaotnion ((722))xx ciClearancRe aRtate (aLy) ~ 626 (22) 0000081 (1) = 000051 (22) Uncertainty factorsof 3forpotential interspecies diferences in toxkodynamics, 10forintaspecies variability Uncertainty factors of 3 for potential interspecies differences in toxicodynamics, 10 for intraspecies variability within the humanpopulation, and 3 or database deficiencies regarding immunctoxihy were selected. The within the human population, and 3 for database deficiencies regarding immunotoxicity were selected. The ale ofthe ndhidusl uncertainty actors ar multiple, esling in atotal uncertainty adjustment of 100. (or value of the individual uncertainty factors are multiplied, resulting in a total uncertainty adjustment of 100. [For mor information on how otal uncertainty scalase pe 3of (MDH 200). Applicaoftairoanl more information on how total uncertainty is calculated see page 3 of (MDH, 2008). Application of a total uunncceerrttaaiinnttyy aaddjjuussttmmeenntt ooff 110000 rreessuullttss iinn aann RRIfDD ooff 00..00000000005511 mmgg//kkgg--dd ((00..0000005511//110000)).. TThhee sseerruumm ccoonncceennttrraattiioonn ortesponting otis Dis 0.063 mg/L. nacition to developmental effects dnt fied in thewo generation corresponding to this RfD is 0.063 mg/L. In addition to developmental effects identified in the two generation Stuy ne ver, and tyr syst are sls denied 35 addty health endpoints. study, immune, liver, and thyroid systems are also identified as additivity health endpoints. or PFOR, the sensitive health endpoints included development er changes, immune suppression, and Kidney For PFOA, the sensitive health endpoints included development, liver changes, immune suppression, and kidney ffct. Theseeffectswere observed in dferent sues, however, they were abseted at sir serum effects. These effects were observed in different studies, however, they were observed at similar serum ccoonncceennttrraattiioonn lleevveellss.. AA ddeevveellooppmmeennttaall ssttuuddyy wwaass sseelleecctteedd aass tthhee ssttuuddyy uuppoonn wwhhiicchh ttoo bbaassee tthhee ffiinnaall RRIfDD.. TThhiiss iiss th ame crcl studyuid by USEPA 3 the bass of thir ID The lowest dos evel tested in this uy the same critical study used by USEPA as the basis of their RfD. The lowest dose level tested in this study rested in health effects therefore, NOAEL ws not avaiable. Th average serum concenteation at the lowest resulted in health effects; therefore, a NOAEL was not available. The average serum concentration at the lowest ose este, 38 mg, was dent s the LOAEL The human equivalent ose oresponding ths serum dose tested, 38 mg/L, was identified as the LOAEL. The human equivalent dose corresponding to this serum Concentration canbe caluated using Equation concentration can be calculated using Equation 2: bose (220g ) == eran concentrationration72(2)) x carance terLL ) --= 30(22) ronoons (iL ) Use ofor reference to this model without proper atibution to MOH isprbibited. = 33 33775500..00003333 stare oraarses STATE 07437986 = 00053 (22) wUUinntccheierntrtataihinnettyyhuffaamccattonorrpssopoouffl33aftfooirornpp,oott3eenfntotiriaalul siinnttoeerrfassppeLecOciiAeeEssLddriifaffetehrreeernnctceehssaiiannn ttoNoxOiiccAooEddLyynnaaanmmdiic3cssf,,or1100dfafotoarbinantstrreaasdspepfeeicicieeiessnvcvaiarerisiaabbililiittyy wfrreaeicgtghtaaoirrnrdisitnnhaggreetthhhmueumllltaaaiccnpkiopoifodfa,panunrleaaasctcuicolcetenipp,nttg3aabbifnloleeratttuwowsteooaloggfeeunanneceLrerOraattAtaiiEioonLnntryssatttuauhdddejyyruwwtshetearmrneeenassteeoNllefeOccAt3teEe0dd0L..., TTaAhpnhpedelvvi3acalfalouutreeiodoonafftoatthbheeatsfoiinetndaddlivieidfudiuncuaciaeellnrctuuainneiccsneetryrttaaiinnttyy faaaddcjjttuuhosisrsttsmmRaeerDnnetitsmoo0ffu.l331ti003p00limerrged/esL,su.rtletsIssnuninaltaiannngdRRinIfdDDatoootoifdft0ea.vlt00e.u00l0n0io00cp01e1m8ro8etamnmietnng/at/yhlkggae--dfddfjue((cs00tt..ms000de055en33tn//to33fi00)03i.0)d.0TTi. nhhAteephpsseeleidcrrueaumvtmieolccnooopnonmcfceeaennntttotrartaalattliisotoununndcccyeo,orrritrraemeismnspuptyoonnnedd,iinngg Ttovetrh,isaRnfDKiisdn0e.1y3ymstge/Lm.saInraedlditsionidteontdifeiveedloapsmadednittiavlietyffehceatsltihdeenntdipfioeidntins.the developmental study, immune, liver, and kidney systems are also identified as additivity health endpoints. 3.2 Relative Source Contribution Factor iWW 3n,hd2heievnRnideMMulaaODltHH'ivteddoeetSvavleeolleuooxrpppcssoesgguuC uriiedod.aannnTtcchreieebvvuTaaXtlliuoumeenossdfefFoolrar,acaatsocchhroeermmgiciicanalal,,liittcccooonnncsesiiiddveeerrdss, ttphh ercceooncnttrriisbbeuurttuiiomonnoPoFffOnnSooonrn-wwPaFatOteeArr ceeoxxnppcooessnuutrrreeassti(tooonaasnn oaainrtridihssieivinrnigdgsuoddauiirrrl'eceseccsttto.llyytaTaalhnneeddsxpeiinnododsitiurrheereeccrt.tlleTyyxh(peee.o.gTsg.Ku. rbbmerrseoeadaasesetltm,itailkaskk))oeffnrrirognomintmaowwlalayactctceeoorruniincnntettbaiavkykeeedM,oonOnpylrHy.e.dtHHihcoortwswoeusevgevehrerura,m, ReeexxPlppFaooOtssiSuvueroreerSssoPummFraOacyAyeacaClolossnnootocroceiccnbucturrutaritoffiornoonmsm Rso(RoSthSuCrCe)c)reffssaa.occuttIoorncrrte,, hswwe.hhTciihacceshhseeaaollflolootPchcaFaettOereSsseaxaapnffdorasrPucFartieOocsRn,toaotfriehf totthhaneRkSeRRCnIfDDcitnotnotoocwewaapacttctenoerueneeextdxppeboodyssuMturoreDebssHeaaathpnnprddolttuihhgeedhrrnaeeammRfaaeriilnanaiimtninveggewppSoooorrrtuktiirocornenecCt0ooognoonittthzrhiieebnrrugtitohne tlslohoonenuggrrceeelelsiim.msiIinnonuaafthtotliienoolntncyahhhsiaaesllfo-olvfirvePehFsseOrooSffcauPPnrFFrdOOeSSnPtFaaOonnrAdd,rPPethFFcOeeOAnAtR,,SessCxuupcccohohsnttuchrehaeptsataawnippeteeehrrdissenoodnnt'h'tsseodssubeererrauutammippocclnooiennodccfeeincnntortanracaftertiairoonmnn,aeabwtuotaarnnlkyysrggeiicvfvoeeognnnmaaizghgiensgiossrtnhnhoeoettr ethxeporseusruelst o(foronmlaytehrisnaolr hexeprocsuurrreesn)t rom years past. or recent exposures within the duration of concern, but also from his or her exposures (or maternal exposures) from years past. NrNeoosnnewa-wractaheteerrrseeuxxsppeoodssuuarreewottosopPPrFFoOOnSSghheaadssabbpeepeeronnaecehxx:aamm1i)inneeexddpobbsyyuEErggeeemsghehydyiaaannddcoLLnoocrerbbneetrrra((tEEiggoeengghhdyyaaPPPPfaarnnoddm MMmiulLLtooirrpbbleeerr,,so22u00r11c11e).s. aTThnhedess2ee) bLrbeoaasrssebeeaeddrrcooshnneelrsseseecrrtuueusmdemdeccxoaopnntocwcseeounnt-rptrerraaomttneiioodgnniessadrrcaeeopppnopocrrreottneaetddcrhaiin:tni1ttoh)hneeedx22ap00to00as33uf--rr00eo44mmNHmeHAudAlNiatNEiEpcSSloenSScsttueoududnyryt.rc.aeFFtosiooirnntthtdhehaetffaieirssfrrttaoaam tppupprmrreoouaatlctcoihhp,e,lesEEtsggioeemuggarhhtcyyeedsaanndaaddnildy 2) BmmLeeoecdrdbaiieuaarsnnesaaeonnlfeddctt99he5e5dttshhepxapppreeorsrcescenuenerntesitsillmeeoefeemdxxeippadooicssouaurnrseecpeeiincnnitttarfaakiktceeiossdnafftoodarr,ayyttaoohuufennroaggmuccthhhmiolidrusreleticnnphlaeaarnnasddcotuaaedrdrcuuielzltstessdinffrtrothohmemerddliuetuessstrt,a,itdduniireeetit,,nttwwoaaakeetrset,eri,mtaaiannmteddadtaaeiidrrs..aailsy smsBuueebbdcjjiaeeuaccstntet0vooalfccutooehnsne.ssiDisddpueearerraasbbtelolneetehuusensncceoheriftgrmathaieniuntdnytciy.ae.-rsTTtphhaieiisscnituufyinnccicedneratrtttaaahi,inntithtnyyetwwaakaaeusstehggsorrtreeisaamtatceethrreasffrooaarrcntttedhhreeuizsuueeppdpoptefehrrNeHppreAeerNscruEelSntcintsielgeerieenusstamttikimdemaaatettaeesssttimtthhhataatnenissffoooavrrsettrhhaee oldmfeeeccEdaagiddaeeenghoovyllad,la,uneeedsss.ppLeeDoccruabiealelltrlyyo(aat2ssh0e1tth1hh)eeigqsshueearrunuutnmimcteacctrootinanvcicenelentyynttfrironaartttiihRooSennCssinahhtpaaapkvvoeeertebbiseotnenimnmeaddnteetecc.srreeaIaannsssdiitnneuggasdeoo,vvoeMefrrONttHiHimmAueeN,s,EeMMSdODtshHHeruddrimidedcdennnaootttaNuutssHheeAaNttthEhieSes.oerevsseuurlltass bnobiofioonEmmwgooaengntihtietyoorrraiiennnxdggpodLdsaoautrtrabaees((r22f(002o11r0331P--122F)00O11qS44u)a)anaandnntiddtPaFEEtiOavasAsettly(MMseifeomtitrrrlooaRrSnnCteeawwopprrpeeiossoriintddioeeinnntmtnbbeEiinoogtmme.ogoInhnniystittoaeornariiddnn,ggLModdbDaaetHtrao,u((2s22e0001d11414t),h),,wethoireceecshsettniiimstmamaNttoHeerAeuuNppEppSeerr--eenndd rneofnle-cwtaivteerofexcpuorrseunretsexfoporsPuFreOsS. and PFOA (similar to option 2 in Egeghy and Lorber, 2011, which is more reflective of current exposures. aDMpDpHrHopuwrtiiilaiztezesRttShCh.ee TUUhSSeEEPPDAAecEEixsxpipooosnsuuTrrreeeDeDecepricesissiieoonnntsTTrareeseerppirreoocceeossfssd((eUUcSSisEEiPPoAAn,, p22o00i00n00t)s) tatoot wiiddieecnnthtiiffytyhaaennqdduaeslleieltecycttantthhdeeqmmuoaosnstttity of asaavevpavapieirlrlaoaabblpllreceiaoeentexxcpplRouoSsssCiuuo.rrneTeshddieaanttdDaaiecaacarritseeiioneegnvvaaaTnllruueaaaepttepeprddroeaapsrnneiddnattaastet awwRhshCie.iccrihheIstthhooeeftddhdeeeercriciivsvhiaaoettmniioionpcnaooolinffatttsshhseeaetsRRswSSmhCCeinciitshsuu,tllhttieMimmDqaatuHteeallolyyiftytssettaeneneerdrreeelqddiuettdaoonuwwtpaiatoryrdndootof hnneee of of pespeexervprcecoeersannulttracaegogaenencmmdlueestttihhoheonodsld,i,iknwewdhlhiiichiccaohhotidinissgfoiinarnnttceehananpdndpegedridontopgoriearreveteffellelRecScwtCirr.teehIllnaiatntoiivtvteheheopprsooercrthtmiieouolmnntssiiocpoaflfletaosshtohseueerrsrcs(e(mnnsoeo(nnmMt-wswDa,HatM,eteDr2riH0ni0ng8oge)fest.esttinTioohnrne))lrirereoodluuettuveepassnotoonffthe peoxrptoisounrseoafntdhethEexpliokseulirheooDdecfiosriocnhaTnrgeinagrelepverelssewnittheidn btehlooswe. multiple sources (MDH, 2008). The relevant portions of the Exposure Decision Tree are presented below. Useofor reference to this model without proper attribution to MOH isprohibited. Use oj~ er re[erence te this model without preper ottribuden to MDH is prohibited, 33775500.00003344 EY 34 STATEo7asrost STATE 07437987 Figure 12. Expoure Decision Tree. Figiur~~ t2. Exposme Decision Tr~o (Adaptedfrm USEPA 200 ox amber corso0 USEPA 2000 document, an ees boxes are selectoedr (AdaptedJ~rom USEPA 2000 - box numbers correspond to USEPA 2000 document, only relevant boxes are selectedJ~or resentotan beow) presentation below) 1. [ iIddeennttiiffyy ppooppuullaattioino(ns()osof)f ccoonncceerrnn sucess: 22. IIddeennttiiffyy rreelleevvaanntt eexxppoossuurree sources/pathways 2 -- readitdaabole tuodstc. | Are adequate data available to describe convaltendences ghendslor | central tendencies & high-ends for prrelevant exposure sources/pathways? LeNo o [He trereats,sfyisccailnl Are there sufficient data, physical/chemical reper, te. anpon, or property, fate & transport, &/or Senralied formation siblteo generalized information available to Craracteize th habhondfexpose 0 characterize the likelihood of exposure to eYess rethre saint kaw or patntl Are there significant known or potential 6. | mesfthcrthransch sereesof uses/sources other than the source of concen? concern? LeYes Bhthor esomrii tuntmpiivie 8A"/~ is there some information available to make a chrscteriatioonf pour make a characterization of exposure? 1133:. aAppppoorrttiioonn tthhee RRIfDD iinncclluuddiinngg 8800%% Cuneo oor wing percenags ceiling/20% floor using percentage Spr(ithclloog) approach (with ceiling & floor). 8 tom siemens Yes 8C, I Perform apportionment as SdRescribed on 13 se sow) described in Box 13 (see above), with a 50% ceiling!20% floor. TpTrhhoeev8i80d0eppeaerdrceceqenuntatctceeeiiplinrnoggtwewictitthhiioinnn ftthohreeiDDnedecicivisisidioounanlTTsrrweeheoiisssettootoeetnnaslsuuerreexptthohasttutthrheeehhdeeaualltththo-babaanssyeeoddfsgtoohaeal ewwixillpllobbseeuroloewwsoeeunnrooceuusgg,hhhttioogher ttfphohraroannvpiodccseuusrirarebedlnneettlqulyyunaikintnendoidpcwarinotetcsedoacbubtyrtiyoctenethhsdfeoofraavveinaxadpilaioavsbbiudleerueadd.laastStaawhe((UoUSsSseEEetPProAAutam22l00c0e0o0x0]np.c).oeTsTnhuthirrisseatlaiisls,osondsuiinenaccrtrreoeeataashsneeeyssbottehhsfeetthmmmeeaaarergsxgipuinnorseooufforfsesaPsfaFeoOtuySrftctoeaossnea,cdcchtcPoigouOhunyeAntrt feoxrpopsousrseib,lethuensknvoawlunessocuarcebse used in pace of the Din the Decision Tree of exposure. Since serum concentrations are pthreocbese.st measure of PFOS and PFOA exposure, these values can be used in place of the RfD in the Decision Tree process. 3.2.1 Selection of RSC or PFOS 3.2.:1 Select:ior~ of RSC for PFOS igh ality national and Minnesotaspecific datasources re avaliable which establish human serum High quality national and Minnesota-specific data sources are available which establish human serum concentrations of FOS across many individuals, although data for infants and young chien rentavaible. concentrations of PFOS across many individuals, although data for infants and young children are not available. Given the long half of FOS, hes bormonitring results fom the Eas Metro (new residents) and NHANES Given the long half-life of PFOS, these biomonitoring results from the East Metro (new residents) and NHANES cam be compared he serum concentration of 0.063 mJ cortesponding othe PFOS RD to provid might can be compared to the serum concentration of 0.063 mg/L corresponding to the PFOS RfD to provide insight into the magnitude ofnon-wate exposures, [eae ne that tis serum concentration uiefufor informing into the magnitude of non-water exposures. [Please note that this serum concentration is use.futj~or in.forming public health poi and interpreting populationbosed exposures This value is baseodn population-based pubfic health policy and interpreting population-bused exposures. This votue is based on population-based rameters and shoukd no be usedfor clical assessmenfot nteroretin serum evel in ndviduots parameters and should not be used,for cfinicul assessment or~or interpreting serum levels in individuals.] 2013-2014] biomonitoring result wre: geometric mean 0.00498 mg/L and S5percent 00155 mg/L Its CCDDCC ((CCDDCC,, 22001177)) hhaass bbeeeenn mmeeaassuurriinngg PPFFOOSS iinn tthhee sseerruumm ooff tthhee ggeenneerraall ppooppuullaattiioonn ssiinnccee 11999999.. TThhee mmoosstt rreecceenntt (2013-2014) biomonitoring results were: geometric mean 0.00499 mg/L and 95~h percentile 0.0185 mg/L. It is Use ofrreferetnotcheismodel withou proper tribtoMuOHtipiroobens. 3s 35 33775500..00003355 STATEorasnose STATE 07437988 0iimm4ppo-orortltaadnntdtrttooopnnsooittneecetthh2aa0tt0tt3hh-ee04ggee(nnteehreraalsl epproouppmuulllaaettviieoolnns (u(NsNHeHdAANNiEnESES)g)essgeehrruyumamnlldeevvLeeollsrsbhheaarvv2ee0b1b1ee)ee.nnTddheeeccrr2ee0aa1ss3ii-nn1gg4oodvvaeetrrattipimrmoee,v,iwwdieitthhthaae33 most recent data regarding `background' serum levels to 4-fold drop since 2003-04 (the serum levels used in most recent data regarding 'background' serum levels in the US general populations. Egeghy and Lorber 2011). The in the US general populations. 2013-14 data provide the MDH's East Metro PFC biomonitoring project sampled asubset ofpeopleliving inthe East Metro region who were connected to a contaminated public water supply (Nelson, 2016). Treatment to MDH's East Metro PFC biomonitoring project sampled a subset of people living in the were connected to a contaminated public water supply (Nelson, 2016). Treatment to remove East Metro remove region who pbpelerorffolluduolorerovoceclhhseemmmeiicacasalulssr(e(PPdFFaCCtssh)) rwwaeasse aatddiddmeeeddpottoionttthshe:e ppuubblliicc wwaatteerr ssyysstteemm ((PPWWSS)) aanndd vvoolluunntteeeerr 2008, 2010, and 2014. As part of the last ppaarrttiicciippaannttsshhaadd PPFFOOSS biomonitoring effort, new East Metroresidents (N=156) were also sampled in 2014. These individuals did not have historical exposure to. blood levels measured at three time points: 2008, 2010, and 2014. As part of the last biomonitoring effort, new East Metro residents (N=156) were also sampled in 2014. These individuals did not have historical exposure to etthhxeepoccsoounnrtteaasmm(iignneaaottmeeeddtrwwiaactteemrre,,assnoo tt0hh.ee0ir0r7ss2eemrrugum/mLssaaanmmdppll9ee5sstcchaapnnerbbceeencctooinnlsseiid0d.ee0rre2ed1d mrrgee/ppLrr)ee.sseeTnnhtteaasttieivveleeoovefflMMsiainnrnneeesssioogthtaatlnnyoohnni--gwwhaeatrteetrrhan the NHANES 2013-14 exposures (geometric the NHANES 2013-14 values mean values but are 0.0072 but are noticeably lower than the East mg/L and 95th percentile 0.021 noticeably lower than the East Metro mg/L). Metro population that were historically These levels are slightly higher than population that were historically eexxppoosseedd ttoo ccoonnttaammiinnaatteedd wwaateter.r. iDDnaayttaaouoonnngPPcFFhOOilSSdrsseeenrruu(mSmclhleeevcvetleesrli,insn2ii0nn1ffa2a)nn,ttss(aWauree, nn2oo0t1t 5aa)vv,aaiaillaanbbdllee(;;Hahhrooewwse,evv2ee0rr1,,7)tth.heerrTeeheaasrreee pppuuubbbllliiicccaaatttiiiooonnnsss rirenedggiaacrraddtiinentgghatsseetrrhuuemm lleevveellss dgginaeetoyoamomeustenurtpgripicccohrmmtiledesaartennhnsse a(au(nnSddcoh99sfe55cuthtpeepppre,eerr2rcc-0eee1nnt2nit)dil,leep(Wevvraauclle,uunee2tss0i1liine5n )yvy,aooaluununndeggs(ccHfhhraiiorlldrmdirsreN,ennH20Aaa1rrNee7E)ssS)i.immaTinihlladaerrstetthooepaauEddbauusllitclttaMllteeeivovteenlrlssso..innTTdehheiwecrraeretfeefosoritrehed,ea, ntaatvtvahaaiseillaabbllee conservative representations of `background! non-water ingestion rooufetxpoesurse. data supports the use of upper-end percentile values from NHANES and the East Metro conservative representations of 'background' non-water ingestion routes of exposure. new resident as TToo aassssiisstt iinn iiddeennttiiffyyiinngg aann aapppprroopprriiaattee RRSSCC ((aappppoorrttiioonnmmeenntt ttoo wwaatteerr iinnggeessttiioonn)) ffoorr PPFFOOSS MMODHH ttooookk tthhee cceeliliinngg ooff r88e00c%%en((tppeebrrioDDmeeoccniiisstiiooonnriTTnrrgeeeed,,atUUaSSfEErPPoAAm 22t00h00e00)E) aaasnntddMsseutburtorabncettewdrraaecsaocinodscneensrtetvsrav(etawithivdvieech((9w955athsppseelrircgcehentntliytillheei))gshseeerrruutmmhavvnaatlluhueee ff2rr0oo1mm3-tt2hh0ee14 NHANES 95 percentile value)a follows: recent biomonitoring data from the East Metro NHANES 95Lt~ percentile value) as follows: new residents (which was slightly higher than the 2013-2014 + 8800%% CCeeiilliinngg == 8800%% ooff tthhee sseerruumm ccoonncceennttrraattiioonn aassssoocciiaatteedd wwiitthh tthhee ARIfDD == 00..006633 mmgg//LL xx 00..88 == 00..00550044 mmgg//LL = SSuubbttrraaccttiioonn ooff tthhee sseerruumm lleevveell aassssoocciiaatteedd wwiitthh nnoonn--wwaatteerr eexxppoossuurreess,, aass rreefflleecctteedd bbyy tthhee 9595th ppeerrcceennttiillee vvmaagll/uueLe=bbaa0ss.ee0dd29oo4nnmttghh/eeL.nneeTwhwisEEavasastlt uM Meeetotfrroo0.rr0ee2ss9iid4deemnngttss/L((00r..0e02p2r11emmseggn//tLLs)),tffhrreoomrmesttihhdeeua88l00o%%r cmceeaiilxliininggm=u= m00..s00e55r00u44mmmlggev//LelL-t00h.a.0t022c11an be apportioned to exposure via mg/L = 0.0294 mg/L. This value be apportioned to exposure via water ingestion, while still of 0.0294 mg/L represents water ingestion, while still keeping the the residual keeping the total serum level below the 0% or maximum serum level that can total serum level below the 80% cceelillinngg.. ThThee rreessiidduuaall oorr mmaaxxiimmuumr sseerruumm lleevveell tthhaatt ccaann bbee aappppoorrttiioonneedd ttoo eexxppoossuurree vviia iinnggeessttiioonn ooffwwaatteerr ((00..00229948 mragg//tL)) iiss aapppprrooxxiimmaatteellyy 5500%% ooff tthhee sseerruumm ccoonncceennttrraatiotniaoatnt tthhee RRIfDD ((00..006633 mmgg/iLL)).. wBBaaatsseeedrd ioonnngettshhtissioiinnn.ffooIrtrmmsahatotiiuoolnnd aabnneddnttohhteeedUUSSthEEaPPtAAtDDheeeccriiesssiiuoolnntsTTrroeefeeth((iee.sg.g.a,.n,abblooysxxiSs8CCd)),o, MMnoDDtHHsusspeeplleoecrcttteerddaiaasnninRRgSStCChoeoffa55p0p0%o%rtffooirronPPFmFOeOSnS.t of wwaatteerr iinnggeessttiioonn.soItusrhceosultdo b8e0npoertecedntt.hat the results of this analysis do not support raising the apportionment of water ingestion sources to 80 percent. 33..22.,22 SSeelleeccttiioonn ooff RRSSCC ffoo~r PPFFOOAA HHiigghh qquuaalilittyy bbiioom moonnititoorriinngg ddaattaa aarree aallssooavaavialilaabbllee ffoorr PPFFOOA aannddaa ssiimmiillaarr aapppprrooaacchh ttoo aappppoorrttiioonnmmeenntt ooff tthhee RRSSCC `aaassndddeeNssHccrAriiNbbeEeddSffwooerrrPPeFFOuOsSSewwdaaissn caalolssmoopuaunrndideserorttnaaktkoeennthffeoorrsePPFrFOuOAmA..cBoBiniocoemmnootnrinatittooirroiinnnggcorreresrsueulslttpssoffnrrdooimmngtththeoe tEEhaaessttPMMFeOetAtrroRoI((Dnneoefww0rr.ee1ss3iiddmeegnn/ttssL]) to provide insight nto the and NHANES were used in to provide insight into the magnitude of non-water exposures. [Please note that this comparison to the serum concentration corresponding to magnitude of non-water exposures. [Please note that this serum concentration the PFOA RfD of 0.13 serum concentration smg/L is uusseeffuullffoorr iinnffoorrmmiinngg ppuubblliicchheeaalltthh ppoolliiccyy aanndd iinntteerrpprreettiinngg population-based parametersand should not beusedfo cppiooippnuuclolaalttaiiosonsn-e-bsbaosssmeeeddnetexoxpproosfsuourrreeissn..teTTrhhpirisevtviaanlluguees eiissrbbuaamssleeeddveoolnns in pinodpiuidlautoilosn.-]based parameters and should not be used for cfinicol assessment or for interpreting serum levels in individuals.] Use oof reference to this model without proper attribution to MOHisprohibited. 33775500..00003366 3366 SSTTAATTEE 0077443377998899 (CC2DD0CC13((C-C2DD0CC1,,422)00b11i77o))mhhoaanssitbboeereeinnngmmreeeasasusulurtrsiinnwggerPPeFF:OOgAAeoiinnmetththreeissceemrrueumamnoof0f .tth0he0e1gg9ee4nnemergraa/llLppaoopnpudull9aat5titioohnnpsseiirnnccceeent11i99l99e99,0..TT0hh0ee55mm7oomssgtt/Lrre.eccteeinnstt important to (2013-2014) important to note that the biomonitoring note that the general results general population (NHANES) serum levels have been decreasing were: geometric mean 0.00194 mg/L and 95th percentile population (NHANES) serum levels have been decreasing over time, with 0.00557 mg/L over time, with aIt a 2is 2 tto033--foolldd ddrroopp ssiinnccee 22000033--0044 ((tthhee sseerruumm lleevveellss uusseedd iinn EEggeegghhyy aanndd LLoorrbbeerr 22001111).). TThhee 22001133--1144 ddaattaa pprroovviiddee tthhee mmoosstt rreecceenntt ddaattaa rreeggaarrddiinngg (N=156) were also sampled b'baacckkggrroouunndd"' sseerruumm lleveevlsieinntlthhsee UUSS ggeenneerraall ppooppuulalattiioonnss.. for PFOA in 2014: geometric mean 0.0018 mg/L and 95th NNpeeerwwceEEnatasistlteMM0ee.t0trr0oo5 rrmeegss/iidLde.ennttss T(Nh=es1e56l)evwelesrearaelsso siammbpliuetdlsfiogarhtPrlFyOlAoiwne2r0t1h4a:ngtehoemNeHtAricNEmSe2a0n103.-01041v8almuegs/.L and 95th percentile 0.005 mg/L. These levels are similar but slightly lower than the NHANES 2013-14 values. DDaattaa oonn PPFFOOAA sseerruumm lleevveellss iinn iinnffaannttss aarree nnoott aavvaaililaabbllee;; hhoowweevvere,r, tthheerree aarree ppuubblliiccaattiioonnssrereggaarrddiinnggsseerruumm lleevveellss iinn myyooeuuannnggsccahhniidllddr9re5entnh(((SpScechrhceeecnctteteirrl,,e22v00a11l22u)e),,s((iWWnyuu,o, u22n001g155)c),h,iaalnndddre((nHHaaarrrreriisss,,i22m00i11l77a)t)o.r). TaTdhhueelssteelppeuvuebbllslii.ccaTathtiieoornnessfoiirnnedd,iiccaaavttaeeiltthahbaalttetthdhaeetaggeesooummpepteortrriitcc theuseofupper-end percentile values from NHANESandthe 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 'bbaacckkggrroouunndd'' nnoonn--wwaatteerr iinnggeessttiioonn rroouutteess ooff eexxppoossuurree.. T8Too0%aass(ssipisestrt iiDnneiicddieesnnitotiinffyyTiinrnegge,aannUSaapEppPprAroop2pr0ri0iaa0tt)eeaRRnSSdCCs((aauppppoborrtttiioonrnammcaeoennntsctettrootvwwaeataittvdeeerr ii(nn9gg5eesstptiieoornnc))enffotoirrlPPe]FFOOsAAe,r, uMMmDDvHHalttuooeoofkkrtothhmee tccheeieilliinngg ooff recent biomonitoring data from 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 residents 95 ppeerrcceenntitillee vvaalluuee)} aass ffoolllolowwss:: residents 95Lh = 50% 80% Ceiling Ceiling = = 80%of 80% of the the serum serum concentration concentration aassssoocciiaatteedd wwiitthh tthhee RRfiDD = = 00..113300 mmgg//LL xx 00..88 = = 00..110044 mmgg//LL SvSauulbbulterraabccattsiioeonnd oooffntth2he0e1ss3ee-rr2uu0mm14lleeNvveHellAaaNssEssSooccdiiaaattteeadd(ww0i.itt0hh05nn5oo7nn-m-wwga/atLtee,rrfeerxxoppmoosstuuhrreees8s,,0a%sscrreeelfflllieenccgtte=edd0.bb1yy0t4thhemeg99/55Lthp~epr0ec.rec0ne0t5ni5til7lee mg/L= 0.0984 mg/L. This value of 0.0984 value based on 2013-2014 NHANES data mg/L = 0.0984 mg/L. This value of 0.0984 mg/L 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 bbceeelaaplpp.poorrttiioonneedd ttoo eexxppoossuurree vviiaa wwaatteerr iinnggeessttiioonn,, wwhhiillee ssttiillll kkeeeeppiinngg tthhee ttoottaall sseerruumm lleevveell bbeellooww tthhee 8800%% Thceeilinrge.sidual or maximum serum level that can be apportioned to exposure via ingestionofwater (0.0984 mg/t) is approximately 75% of the The residual or maximum serum level that (0.0984 rag/L) is approximately 75% of the serum can be serum concentratiaon the RD (0.13 mg/L). apportioned to exposure via ingestion concentration at the RiD (0.13 mg!L). of water TrThehigissarccdaaillnccguullbaaattiicooknngrssuouguggngedesstetssxpaaonnsuRRrSSeCC ioonfftgghrreeeaapttoeeprruttlhhaatanino55no00%f%cbbouunttcleleerssnss tt(eh.haiannnf88a00n%%.t.sHH)oowawenevdveertrh,,eggpiivrveoencnettshhseeoulltiimlmiiitnteeeddd iiinnnffotorhrmemaaUttSiioEonnPA Decision Tree (e.g, box 8C), MDH selected an RSC regarding background exposure in the population Decision Tree (e.g., box 8C), MDH 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 3.3F~ :>- RReeaassoo~n-a..abbllee Maximum Maxils .~I~T~ EExxpopsourse~ Scenarios ~-e qc-~ ..... ' ~ `. As m. en. tio. ned. ab. ove. , t. wo. exp. osu. re. sce. nar. ios~,:w.~ e~8rte10e.~xamined: 1) an infant exclusively fed formula reconstituted waAwinsitthmihnecfcaononntntitotaeanxmmecidlinnuaasaittbeveoeddvleyww,abattrwteeearorsstsetftxaaeprrdottiinsfnouggrreaa1tt2sbbcmieiorrnttnhhatrhaaiosnns,ddwfccooeolnrnltetioinenwuuexiidannmbggyiniindnegrgdiee:nsskt1tiii)onoangnncooifofnnccftaooannnmtttiaaenmmxaictinnlueaasdttieveweddaltywweafarettdeetrhrforttohrhmurroguohuulaggfhher.elliicffBeoeo;;ntaashnntiddtouf22te)) d these scenarios are presented an infant exclusively breastfed these scenarios are presented graphicalilny Figures 10 and 11, respectively, in Section 2.3 for 12 months, followed by drinking contaminated water through graphically in Figures 10 and 11, respectively, in Section 2.3. life. Both of AAnn iitteerraattiivvee pprroocceessss wwaass uusseedd ttooiiddeenntitiffyy tthhee wwaatteerr ccoonncceennttrraattiioonn tthhaatt rreessuulltteedd iinn mmaaiintnaitniangiaanssieernruugmm caconondncceeenxntptroraastutiirooennpaaattrooarrmebbteeellorowwin55p00u%%ts((uRRsSSeCC)d) ooafrfetthhpeerossveeirrduuemmd ccaoobnnoccveeenntitrnraaTttaiiboolnne aa8ssssoocciiaatteedd wwiitthh tthhee RRIiDD.. TThhee cchheemmicicala-Pssppeecicfifiicc and exposure parameter inputs used are provided above in Table 8. UUssee oof ol~ or rreeffeerreennctee tt~o t~hhiiss mmooddeell wwiitthhoouutt pprrooppeerr oattttrriibbuuttiioonn t~oo MMODHH iiss pprroohhiibbiitteedd.. 33775500..00003377 3377 SSTTAATTEE 0077443377995900 33.,33.1,:1S.cSecnearrtiaor:~#o #:11-.- EExxcclluussiivveellyy ffoorrnmtuullaa.--tf:eedd Jinnff:aanntt T3h3e.w1a1tePPrFFO0c5Soncentration that maintainead PFOS serum concentration ator belowan RSC of 50% Le, 0.083 0.5 =00315 mg/L) throughout fe was 0.060 g/L. The water concentration that maintained a PFOS serum 0.5 = 0.0315 mg/L) throughout life was 0.060 pg/L. concentration at or below an RSC of 50% (i.e., 0.063 x lFw=iaiggtuuerrreei1.tn53.t,aEkExecklrduautsseiisvv,eellayynffooRrrSmmCuuolI~fa7-0-ff%eedd,innaffoannndtat PPwRraOOtSSersseecrorunumcmencctoornnaccteeinrott,nrrafatdioo0nn.ss06oo0vveuergr/aaL.ffifeecdimmee,, bboasseedd oonn 9955tthh ppeerrcceenntitillee water intake rates, an RSC qf 50~, ~rtd a water concer~tmtion qf 0.060 . oT ~~ i ston) BiBneecccraaeuuassseeeooifnfttthhheee wlloaonntggerhhaaclolfn-flcifeeen,,tttrhhaeetiPPoFFnOO(SS0.ss0ee6rr1uumgm/ccLoo)nnrccaeeinsntetrrdaatttiihooennpccruerudviecritissevvdveePrerFyyOffSllaastteaarnnuddmeecvvoeennncaeasnmstamrlaatllil oiinnnccarrbeeommveeenntttaahlle 50 percent threshold for nearly years. increase in the water concentration (0.061 percent threshold for nearly 9 years. lag/L} raised the predicted PFOS serum concentration above the 50 3312008 T3h,3e,1w.a2tPeFrOcAoncentration that maintaineda PFOA serum concentration for exclusively formula-fed infants at or below anRSCof 50% 2.x005=.0.0165mg3/L) throughout fe was The water concentration that maintained a PFOA serum concentration below an RSC of 50% (i.e., 0.13 x 0.5 = 0.065 mg/L) throughout life was 0.15 pg/L. for exclusively 0.15 lade formula-fed infants at or Useofor referencetothis modelwithoutproperattribution to MOH isprohibited. 33775500..00003388 338 STATE 07437991 STATE 07437991 Fwiagtuerer1i4.ntEoxkeclruastiesv,eloynfoArmuoSlfa-0fCe%d,nafonndta PwFaOtAersceornucmenctornacteinotnroaftion0.s15auvegr. ifetime, basedon 95h percentie ww NC foo ol ~~ --J SE i Het) SSceeorrnuucmmecncootnnrcceaentnttitrroaoattniioo0nn.1ss6 gwwe/erLreerassiesenesdnittivsheetitsooectcrhhuiaamnnvgcgeoeenssceiinnntwwraaattteeirronccooannbcceoenvtnerttrahatetiioo5nn0ss..pAAernnceiinnncctrreteahasrseeesiihnnottlhhdeeowwraatmteoerrr e than one yearconcentration year. to 0.16 ~g/L raised the serum concentration above the 50 percent threshold for more than one 3.3.2 .~.:.~,..~. SScr.eenna,r:~ior Io #2 ~ #,........ EEx,,c,.lluus.~ilv,,eellyy bbrieeaassttffeedd iinnffaanntt 33210605 AAs3sr~sse3s.t2eta.ax:tLctelePuddsriioinnvseSSleyeccfttoiioronmnu33l..a33-..f11e.1.d,1a,aswwiantafeaterntrsc.coonHncoecwneetnvrteraartt,iiootnnhosoffw00a..t00e66r00cgIo~/ngc/LLeniisstrpparrtooitteeocncttbiivaveesetthdhrrooonuuggfhhooroumuuttlIlaiff-eefeffodorriiinnnfddainivvtiisdduiusoanllssowtwhhoo sbuaifureoiffacieccixceiecunnlmtutulslylyivapeptrlriyoovttfeeeoccrmtmtaiivtvueeelraffn-oofarerldiinenaffxasapnnoittnsssfuwawrnhehtosow.iaatHrrheoewseeuexxbcvcsleluuerss,qiiutvvheeeilnslyytwbbtrarreeateaanssrstftceffeoreddnifcnfboeornreataarsyaytetemiaoiarnlrkwwb.hahseAeetnndacwcoooannntssfeioiddrremercruiinonlagng-cttfheheedenctcinhhrrfraaoonntntioiisccfoisnn0o.0t60 gfbi~o/igorL/aLm.,cocpprurreeemddtuiihcclaattenteidvdaenPPemFFyOOaeSStaessrreenarraunulmdmexellpexevovceeselluessrdeffootwrrheeietxhx5ccl0sluu%ussbiiRvvsSeeelClqyyutbbehrrrneeetaastshsratotfleneddsdffeiionnrrffaiaannnrttbsslreyeeaxxsc1cte9emeeyddilektat.hhrAeestssIaenerwrouuramdmteeccrrooctnnooccenmencanteitrnnraatttratiaiiootnninoPnaaFtoOttfhShe0es.0eRR6rIfD0Dum for more than one year and exceed the 50% RSC threshold for nearly 19 years. In order to maintain PFOS serum cbeonlocweenrtedra10ti0a.ot0n2ors7 bpge/lL.ow the 50% RSC serum concentration (.., 0.0315 mg/L) thewaterconcentration hadto concentrations at or below the 50% RSC serum concentration (i.e., 0.0315 mg/L) the water concentration had to be lowered to 0.027 lag/L. Useoforreferetnotchiesmodel without proper attribtuotMOiHoins prohibited. 33775500..00003399 339 STATE 07437982 STATE 07437992 Figure 15. Exclusivelybreastfed infont PROS serum concentrations over fetime, based on Upper/sth percentilebreastmilk/iwaterintake rates, anRSCof 50%, and a water concentration o0f.027 ug/L. oo fon || Suet EEvevnaaessmmanlalll iinnccrreemmeennttaall iinnccrreeaassee iinn tthhee wwaatteerr ccoonncceenntrtraattiioonn i. 0.028 (i.e., 0.028 gp/gL/L)) rraaiisseedd tthhee sseerruummcocnocnecnetnrtarattiioonn aabboovvee 5500%% RRSSCC tthhrreesshhoolldd ffoorr mmroree tthhaann tthhrreeee mmoonntthhss dduurriinngg eeaarrllyy lliiffee.. TThheerreeffoorree,, tthhee hheeaalltthh--bbaasseedd wwaatteerr ggofuuiitddhaaenn5cc0ee%ffootrrhPPreFFsOOhSSolwwdaastshssaeetttcaaottul00d..00o22c77cuuprgg//aLLsattoorebbseeulpptrrooottfeecectxtiipvvoeesooufrf eddeeovvveelelooarppmmseuenbntctahalrloccnooinncccpeeerrrnnissoadaonnfdd tttoiompperr.eevveenntt eexxcceeeeddaannccee of the 50% threshold that could occur as a result of exposure over a subchronic period of time. 33220608 AAarssessettaxactteleuddsiiinnveSSleyeccfttoiorinmoun3l.a33-..f13.e.21d.,2aaa,s wwianaftateenrtrsc.coonHncocewenentvrteraartt,iiootnnhioosff0w0.a.t1:1e55rcg#og/n/cLLeniisstrpparrototiteeocncttiibvvaeesttehhdrrooouungghhfooourutmtulIliffaee-fffoeord iiinnnddfiiavvniidtdsuuaiasllssnowwthhoo sufficiently protective for infantswhoare exclusively breastfed foayerar are exclusively formula-fed as infants. However, this water concentration sufficiently protective for infants who are exclusively breastfed for a year when considering the based on formula-fed when considering the chronic infants chronic is not bbiiooaaccccuummuulalattiivvee mmaatteerrnnaall eexxppoossuurree wwiitthh ssuubbsseeqquueenntt ttrraannssffeerr iinn bbrreeaasstmtmiliklk.. AAtt aa wwaatteerr ccoonncceennttrraattiioonn ooff 00..:1155 WfI~oagr//LLm,,opprrreeeddtiicctthee4ddayPPeFFaOnOrAAsssaeenrrduumemxlcleeevveeedllsstffhooerr5eex0xcc%lluuRssSiivvCeeltlyyhrbberrseehaaosslttdffeefddoriinnmffoaarnntetssteexxccheeeeayddetathnrhese.sseerruumm ccoonncceenntrtraattiioonn aatt tthhee RRIfDD for more than 4 years and exceed the 50% RSC threshold for more than 9 years. In order to maintain PFOA serum concentrations at or below the 50% RSC serum concentration (., 0.065 mg/L) the water concentration had to be lowered to 0.035 g/L In order to maintain PFOA serum concentrations at or below the mg/L), the water concentration had to be lowered to 0.035 pg/L. 50% RSC serum concentration (i.e., 0.065 Use oof reference to this model without proper attribution to MOH isprohibited. 33775500..00004400 4WOo SSTTAATTEE 0077443377998933 pFeirgcuerneti16l.ebErxecalusstimviellkyb/rweaatsetrifnetdaiknefornattePsFaOnAdsaenruRmSCcoofnce0n%t,ratainodnsawoavetrear fcoencten,trbaatsieodn oonfU0p.0p35erug//3L5.th percentile bre~s~milk/wo~er lnt~k~ ro~e,~ ond ~n R.SC o~ 50%, ~nd ~~ wo~:e.r concen~ution o~ 0,035 ~g/f.., 3foo 3I fo vr Tee eee pr tEEhveevn5a0aespsmemanrlacllelniitnncctrrheermmeesenhntotalaldl oiinnrccrraeepaapssreeoixinnimtthaheteewwlayattoeenrreccomononccneetnnhtrtrdaauttriioionnng((e00a..0r0l33y66Ipgfeg/./LLT))heararieisfseoedrett,hheethsseeerhrueumamltcchoo-nnbccaeesnentdtrraawttaiiotoennraabboovvee guidance for PFOA was set at 0.035 g/Lto the 50 percent threshold for approximately guidance for PFOA was set at 0.035 pg/L to be protofedecvetloipmevnteal concerns. one month during early life. Therefore, the be protective of developmental concerns. health-based water 3:.~4. ,,Cq-oCno~c~lcul ussiiooin"~ssi/'SSuuI"mrlmmaar/"y't' Duetothe bioaccumulative natoufPrFOeS and PFOA, chronic exposure to mothers and the subsequent transfer ttuDo0nuideinnefftraaonnttththsseettshhbcrreiooonuauagcrghichoubsbmrreeeuvaalaassltttiuflveaeeeteeddndiianntbgguyrrreMeesOsouHufl.ltPteeFdTdOoSiinenatnthnhsdeeurPhheiFiggpOhhrAeeos,sttect cheetrxxoipponoonisscouuferrexeaplssloaassnneuddgremlloeotwonwteemsssttootfaahctcechcreeespptpataoanbpbdulleletahwwteaiatostneeu,rbr stccheooeqnncufceieennnantlttrrtMaartatDiinooHsnnfsser health-based values under the scenarios health-based values for PFOS and evaluated by for PFOS and PFOA were set at 0.027 and 0.035 gL, respectively. MDH. To ensure protection of all segments of the population, PFOA were set at 0.027 and 0.035 pg/L, respectively. the final MDH Breastfeeding is important forthe short and long term healthofboth a mother and infant, MDH used an RME ssmBcareecxnaiasemrtfiuoentemtodoageingxegrpenoneisseiruriamartoetpeesottirhhtteaueanthhtieeofaaonllrttthhto-h-beebanassssehuedrodervvtataahllunauetdesseloffvonoergrnPPtteFFhrOOemSSmaahannesddtaltPPhhFeFOaOoAvAfi.l.byAAoentnhxRRpaoMMmsEeodssticchneeednniraavrariinidoodudadilneesfppwaiiicnctttst.hasiManDrreetHaahllieiusstsptiieoccdpbbuauluntattRioMnE wwtmihilaallltxbbiwmeeouppmmrroeottneeexcccpttueoerdsdr.u.ernTTethhlseeyitmbmuraaaejtaojioosrtirnifttyeytoeoodfeif nntthgsh,eueraeppnootdphpuauplrltaaetetgiivonoenannneettxhxwppeeoermrmiieoeennsncct eehwehlloaoowvwieeplyrlraeeenxxxptppoooosssbeuurrdereeaisssntdttfhhievaaeindnd,uttahchleoesnRwRtMiMiEnthE.ui.enMMttoDhDedHHoprresoeocp.couoEmlaxmcmtmiloeeunnsniddvsse ctbbhroraeenaatcseswtrtfofneemseededeiixnnncggceueiisdrrrreteenhccetoloymkmnbmmoreeewannnsddteebfeeddneebbdfyyiintddgsoo,cocatftnoobdrrrssepaaarsenntgddfneooeattdnhhiteenwgrr.ohhmeeAaapelpltntlhhiwcpparhrtoooiffoeepnsslsasoinifoonnttaohalelssb..irenItaasiissuthfnueelneaildlikk,teehcllbyoytanthshtaienatdut evppoaottloteuenedntsotiiaawsilloll.hheeuEalaxltlcttihlhmuastiveely rocreeposstnuuiclmlettariilnnnsblleoeonwxwecefeeriretbbsdooftddhryyeombbkuunbrrroddeweeannnssstbfaaeennendddeifnbbigtrrs.eeaaossfttbmmireillkakscctoofenneccedeninntgtrra.attAiioponnpsslicooafftiPPoFFnOOSoSfaatnnhdde PFOA so tha infants can final health-based values PFOA so that infants can receive the. will ultimately receive the optimal benefits from breastfeeding. Useofor reference to this model without proper attribution to MOH isprohibited. 33775500..00004411 a41 STATE 07437984 STATE 07437994 4.0 References BBaarrtetlle,5lSe..x((p22o00s11u22r)e.).s,BBiiaaanssdiinnpohhatalelfnfl-tliiiffaeeleesssotltiiumtmiaaottneesss. uuJssoiiunnrggnalIolo8gofccooEnnxcpceoensntutrrraaettiiSoocnnierrneecggerreeassnssdiiEoonnnvniinrttohhneemeppnrreetssaeelnnEccpeeioodfefmbbiaaocclkkogggrryoo.uunn2d2d, Cariou, Re220x9B9p9.o-33Vs00eu3y3r.er. sa,nda,nAd potential solutions. Journal of Yamada,A Berrebi, D Zalko, $ Exposure Science and Environmental Epidemiology., 22, Durand, C Pollono, P Marchand, -C Leblanc, 1 Antignac, Cariou, B LeR., B B Le ize. . (2015). Perfluoroalkyl oid (PFAA) Veyrand, A Yamada, A Berrebi, D Zalko, S Bizec.. (2015}. Perfluoroalkyl acid (PFAA} levels and Durand, C levels and profiles Pollono, profiles inP in breast milk, maternal and chord Marchand, J-C Leblanc, J-P Antignac, breast milk, maternal and chord COC. (201ss6ee)rr.uummCeoonftfeFFrrrseefnnoccrhhDiwwsooemmaesenen CaaonnnddttrthoheleiairrnnndeePwwrbbeovorernnnsts.i.oEEn.nnvvBiirrreooannsmmtefenentetdIIinnnttgeerrRnneaapttoiioornntaalCla,,r3d84.4,, 7R71e1-t-8r81i1.e.ved from CDC. COC. ((220h01h1t7t6t)tp.)p.ssCC:///eevwnonwtwetwrwess.fcfrcoodsdrce.DD~giioosseuvea/a/bsbsreereeCCaaososntnttfetrlroeeoldel diaaninn~ndd/gpPP/drprfeed/v2viee0/nn12tt6i0ioob1nn6r.eb(aBrCDserCets)fase.stetiFdfeeoineuelrdd~tiinrhneggpNraRoetreiptpcooaonrrarttdlcC.ppRadaerdrfpddf..o.rtReontrieHvuemdafnroEmxposure to CDC. (20E1n7v)i. rCoennmteenrtsafol rChDeimsiecaasles.CoUnptdroaltaenddTaPbrleevs,enotinouna(rCyD2C0).17F,ouVrothluNmaetiOonnea.l RReetproiretvoend Hfruomman Exposure to DonahueEhh,tnt5,pvisri:oK/P/nwmKwtlewenit.naccpmdldaCcen.h,l~gesMoomvviW/c/eea:xlxGsppi.oloUs/msupaurdnree,asvrteeEepdpOookrTeertatnf/b.iinlendw(sd2e,e0xJx1.a0hhw)nt.tummaTllr.rye2n0d1s7i,n Volume One. Birth Weight Retrieved from and Gestational Length Among DonahueS,inSg.,leKtPonKlTeeinrmmaBni,rtMhsWinGtihllemUanni,tEedOSkteant.es(,2011909)0.-T20re05n.dsOibnstBeitrtrhicWs oenigdhGt yannedcoGleogsyta,ti1o1n5a1l2Le(pnt.gt1h)A, m35o7n-g Egeghy PS33P66in44a.g.nldeddotooiMi::n1lLTO0oe.r.1rbm10er90.7B9/i72Art0/Oh1As1G0)i.nG.O.tbAh0Oneb10aU31sens33iet1es38ds11mSc8ebt1nadtctSebo5sfaf5, t1h9e90e-x2p0o0s5u.reObofstAetrimcs aendtrGoypineercfcoilougoayr,oon1c1t5as(n2e(psut.lf1o)n),at3e5:7A- Egeghy PccEPonovmmaipnpradaornriMimsseooLnnntoaroobflfeeeErs.pstit(iid2mem0maa1itt1eoe)ldd.oAgiinynnt,taaaksk2ees1ew,wsiis1ttm5hh0e-vvn1aa6tllu8uo,eefssthiinenffeeerrxrrpeeoddsffurrroeommofNNAHHmAANNeEEricSSaddnaasttaato.. JouorfExnpoasulre Science perfluorooctane sulfonate: Journal oJ:Exposure Science Aaanndd. EEmmmmeett,t,EPeE.nr.v,fiFlFroSSuonSSrmhohocaeftrneeartnra,,olHaHZEthpeZ:ihadaeRnnemg,li,aotDD!ioFogFnryrsee.h,eei2mmp1asa,nnB,1,e5tCC0w-DD1eee6ess8naai.i,S, eLLrMMumSShhCaoanwwc.,.en2(2t0r00a60t)6.i).onCCsoomammnmdunuEinxtiptyyosEEuxxrpepSooosusurruceetrtseoo. Journal of Fei, C., IOOPK eMccrcefuLlupacoaurgtouiohcnitpaann,laaoanRanEdtdteET:EnainvRriveooirlrnaooetnnni,ommneOasenlhsntleiatpnals.l MMB(e2eed0tdiw0ic7cei)ien.nneePeS((JrIeOfOrlEuEuMmMo)r),i,Cn44oa88nt,,ec7d7e55nC99th-r-ea77mt77iio00c.n.aslsanadndExFeptoasluGreroSwotuh:rceAs.SJtouudrynwailtohfin the Fei, C., Felt, 5J,KDDaGaMnnPicissDLhhaasuNNtgaaothtniliio,onnn,SaaRYllEBEBuiTilrraitthrnhog,CCnoeoAh,hoHrJotOrP.ti.lseEEernsnnvm.viai(rr,2oo0nMn0mmS7ee)nT.ntaPtsaasellirHHnfleauearoal.rltti(hnh2a0PPt1eee5r)drss.ppCeAechscteitsimvveeesiscss,a,mls11e11na55tn((d1o11f1F))h,e,eta11a6ll67t7G7h7r--or11iw6s68kt8s2h2,:r.eAsuSittuidngy within from the Felter, Sc., aGPrlDfayesteoxnp,osSuYreEsu:linAgr,eAcHurPrieenrstmcahe, mMiScaTlatsosxiincairtiy. t(2es0t1i5n)g. pArsosteoscsomlseannt dofihkeaalsthsersisskmsernetsumletitnhgofdrosm ris Haneaasddaeenerlq,qyuu-Bla.aiftet(ee1??e9x6CC1pr)ori.itstiiuccBraaoelldsRRy:eeAvWviriaeeetwwcessuririnCrneoTTnmootpxxicaicchrooetllmomoggeicyyn,a,tl44st55o(i(x3n3)i)cC,,hiti22yl11dt99re-e-s2n2t:4i4n44gC. hparnogtoecsoDlsurainndg risk assessment methods Growth and Related Changes in FFrrioism-Hmaen,BBsooeH,ddnCyy, BCC.oMomo(m1ps9opcs6hoi1,st)i.itMiooBnnoM..doPyPreoeW dvdiaiiaatztrte,riircc|ssCA,,lo22bm88a(r(p22Aa))l,r,etmj11a66en99dn--rt11se88,11in.. Children: Changes During Boehmer, M Kiranogl, Growth Faber, | and Related Hannibal, O Changes Genzel- in Fromme(BB,PooHFrCr.oos,v)vC.iiccMzzEeenonvnsyiyc,r,ho,8BnKMmKoeloMnelettotazzrlkkoSoovc,,iitWzW eV,noclIVeAkoell&bklae.T-l.eAc((leh220n0ja1o10nl0)od.)gr.eyPP,,rreSo4--4B,aaonn7edd1h2mPP3o-oes7srt,1tnn2aMa5tta.aKll irEEaxxnppooogssluuur,reeF ttFooaPPbeeerrrf,fllIuuHoorraiinnnnaaittbeeaddl,CC0oommGpeponouzunenldd- ss Genus, (5,PFLCCs)u.rEtinsviroBinrmkheonltza.l S(2c0ie13n)c.e &GasTtercohinntoelostgiyn,a4l4E,l7i1mi2n3a-t7i1o2n9o.f Perfluorinated Compounds Using Genuis, Han, X. SCCDh.L,hooLlNleaCesbsutbtryyt,irrsaMa,mmHDiinnBReeiursaakshnneoddllz,CC.hGhi(Lt2oo0rrKe1eetl3nlal)n.ppeGycyrlraee,snntorRoioiWddinootsRseaias.c.tkianIIrSaSdR.lANNE2lTT0imo1ox2xiin)icc,aootlliooRoggenyny,ao, lfAAPErrtleicicrmlefeilunIoIaDD6tr5iin6o75an87teo84fd499P.C.eorfmlpuooruoncdasr Using boxyla te s HHaarnri,sX,.,M((.DPP,LFFCSCNALAsaR)sib.f)b.a,sCChMhSeeHhmmiimRcicauaansll,sRReeAlels,sMeeGaaLrCroccKlhheainifnnnt,eTTdooXyxx,iYicceRoo,WlloAoggMRyy.i,,cMk22a55r,,do.33T55(-2-Fr4406W61.e.2ab)s. tR,eern,al E Elimination of Perfluorocarboxylates Oken, SK Sagv. (2017). Predictors of Per- Harris, MaEa.nnn,vddSiLPrPooRolnlyiymffafellsunu-tooSrarhooliamaSllckakyinyle,lnSSAcuuMebb&ssCttaaTanenlacccfheeant((o,PPlXFoFAgAYySSe,)),AAPPdlMlvaasasmMnmacaoerCCaoA,oncTnccFceeesnWstn:rteraabDttOsiioItoe:nnrss,10Eiin.nO1660k--2e113n00/,oYYSceKesaaSrerasOOtglilv6dd.6AA(0m2m5e08re11ir7i1cc).aanPnCrhCeidhliidcldrtoreernsn..of Per- HHaauugg,, LL.,EpSeSnrvHHfiulrubuobeonerrmri,,neGGanttBeBaedelcccShhoceeirmer,p,ncoCCeuTTn&hhdooTsmmes-sceCohnonn,mo,.plo(a(g22r0y0i1,13n1A)g.)d.evCCxahphnaoacrsearaucArtceectercerieisssstasait:tmiiDoaonOntehoosfflOwhhi.uut1mmh0a2abnn1i/oaeemcxxasppr.ookessesuurtr.rsSeeobppf0aa5ettx8hhp1wwo1aasyuyrssett.ooEnvironment pInetreflrunoartiinoantae,d3c7,om68p7o-u69n3d.s - Comparing exposure estimates with biomarkers of exposure. Environment KKaarrrrmmaann,IP,neAAtre,.f,rln|IuaorEtririioiccnsnsaooatnnle,,,d98BC7hvv,eaa6mnn8i7cBB-aaa6vlv9esel3l,t,. hPPrOOouDDgaahrrnnLeaercrtuuaddt,i,oMMn: AALuuennveee,l, sAAoGGfllMyyannntn,c, hS5eiLdgignHneuellm,l,aGGnLLMiininddkssttarrnoodmmS..e((r22u000m077).)a.ndEExxappooTsseuumrrpeeooorffal "PTerernfldu,o1ri9n9a6t-e2d00C4h,eimnicSawlesdtehnr.ouEgnhviLraocntmaetinotna:lLHeevaellsthoPf eMrsaptcehcteidveH,u1m1a5,n 2M26il-k2a3n0d. Serum and a Temporal Kim, 5K, KT Lee, C5 Kang,LTao, K Kannan, KR Kim, CK Kim, Trend, 1996-2004, in Sweden. Environmental Health Kim, S.-K., KT Lee, CS Kang, LTao, K Kannan, KR Kim, CK Kim, J Lee, PS PaYrWkYo,o, Y Ha, Perspectives, 115, 226-230. JS Lee, PS Park, YW Yoo, JY Ha, YYS SShhiinn,, JJH LLeeee.. ((i22m00p1l11i1)c.)a.tDDiioisnststrriifbbouurttipioronennooaftfappleerarflnluudooprrooosccthhneeammtiaiclcaaellxsspbboseeuttwrweeesee.nnEssneevrriaaraaannnmddenmmtiiallkklPfforrololmmtittohhnee,ss5aa9mm,ee 1mm6oo9t-thh1e7e4rr.ss aanndd LLiiu,,J.,1,J1iLp1mi,e,rpYLflliiLcuiau,ot,rioiHHnnMVastefCCodhhracanpon,r,mepYnoZZauthhanaaldooas,n,2ZfdoCCrapaioni,,seYYtwnW bWaoutu.ra.nl s((e2.2x00pE11on11)sv.)ui.rreCCosono.mmmEpepannartviriirIssonoontnnemroonennanttggiaeeolsnsPtataao,ttllii3uoo7tnn,ioaa1nn2n,0dd165l-laa91cc2,tt1a1a2t6t.iio9o-nn17ee4xx.ppoossuurree ooff perfluorinated compounds for newborns. Environment International, 37, 1206-1212. 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TThhoommsseenPn,er,Cf.l,C, uLLoSSrHiHnaaauutgge,,dHCoSSmttipiggouuummn,,dMMs,FFPrrooolsshhyaaburugog,m, iSSnLLaBBtoeordraadDdwiweplehllel,,nGyG! BBEecthhheerrrs,,., ((a22n00d1100P))o..lCCyhchahalnnoggreeissnaiintneCCdooBnniccpehenentnrtyraalttsiiooinnnss ooff NorwegianBreast Milk during Twelve MonofLtacthatison. Environmental Science Perfluorinated Compounds, Polybrominated Diphenyl Ethers, and Polychlorinated Norwegian Breast-Milk during Twelve Months of Lactation. Environmental Science & Technology, Biphenyls in & Technology, 4444,, 9550-95556. USEPA. USEPA. ((922500500000)-.)9. 5UU5,SS6.EEnnvviirroonnmmeennttaallPProrotteeccttiioonnAAggeennccyy ((EEPPAA).). OOffffiiccee ooff WWataeter.r. MMeetthhooddoollooggyyffoorDr eDreirviviinngg AAmmbbiieenntt fWWraaotmteerhriQQtuupasal:ifi/ttyy/CnCreiprtiiteesrr.iiaeafpfoaor.rg0tthhvee/EPPxrreoo/tt2eeyccPttDiioFonn.coo5ffiHH/2uu0mm0a0a3nn02HHeRealaPtlDthhF..2EDEPoPAcA-k-88e22y22=--8B2-0-O00000--3O0D00244.8. OOPOccFt.toobbeerr 22000000.. RReettrriieevveedd UUSSEEPPAA.. (2004). OfficeofScience Advisor. StaffPaper: Rsk Assessment Principles ondPractices. from https://nepis.epa,gov!Exe!ZyPDF,cgi!2OOO3D2R.PDF?Dockey=2OOO3DJR.PDF. (2004). O]~j~ice of,Science Advisor. ,stall:Paper: Risk Assessment Principles and Practices. UUssee oof altar rree~ffeerreennccee t~o t~hhiiss mmooddeell wwii~thhoouutt pprrooppeerr aattttrriibbuuttiioonn t~oo MMODHHisispprorohhiibbiiteeedd.. a43 33775500..00004433 SSTTAATTEE 0077443377998966 UUSSEEPPAA.. ((F22o00c11t1o1)r)..s UUHsSanEEdnnbvvoioirrkoo.nnmm2ee0nn1t1taallEdPPirrtooittoeencc.ttiioRoenntAAriggeeevnnecdcy-yf-rNNoamattiioonnaallCCeentneterrf.foorrEEnvnivriroonnmmeentnatallAAsssseessssmmenetn.t. EExxppoossuurree Fhiatcotso:rs/JHctapnudbb.oepoak.g2ov0/1n1ceEad/irtiiosnk./rReceotrrideivsepdlafyrocmfm?deid=236252. USEPA. USEPA. ((hP22et00trp11f6s6l2au:)/o.)/.rcoUUfopSScutEEban.nnevvoipiirracoo.ngnAmcmoievedn/nnt(tacPaleFlOaPPA/r)rro.oisttkeec/cRrtteeiitocornonireAAdvgigseeedpnnlacfcyryy.o-c-mfOOmfhffif?iitcdcpeeesi:doof/=f/W W2ua3nta6uetw2er.5.re.2p.HHaeeagaloltthhv/EEfsfffeeicctttsseSSsuu/pppppororrott dDDuiooecccsuutmm2ie0eon1nnt6t /ff:oorr 0P/edrfolucourmoeoncttsa/npoficoaA_chides(PdFOfAin).al-Rpleatirine.voedd from https://www.epa.gov/sites/production/fi!es/2016- USEPA. USEPA. (2016c). US Environmental 05/documents/pfoa hesd (2016c). US Environmental Protection Age-nOfcfiyce final-plain.pdf Protection Agency - Office ooff WWataeter.r. HHeeaalltthh EEffffeeccttss SSuuppppoorrtt DDooccuummeenntt ffoorr Perfluorooctane Sulfonate (PFOS). Retrieved from https://www.epa.gov/sites/production/files/2016: 0P5e/rdfloucouromoecnttasn/eheSsudlfopnoatse (fPinFaOl Sp)l.aiRn.eotdrfieved from https://www.epa~gov/s!tes/production/files/2016- USEPA. (0250/1d6o0c).umUSenEtnsv/hierosndmepnftoasl fPinroatl-epcltaiionn.pAdfge-nOfcficye of Water. Drinking Water Health Advisory for USEPA. (P2e0r1f6ludo).roUoSctEannveirSounlmfoennattael (PPFroOSte).ctioRnetArgieenvceyd f- rOofmfichetiopfsW:/a/tuewrw.wD.eripnak.ignogv/Wsiatteesr/HpreoadltuhctAidovn/isfoireys/fo20r16: 05/documents/pfos health advisoryfinal. painpdf Perfluorooctane Sulfonate (PFOS). Retrieved from https://www.epa~gov/s!tes/production/files/2016- Verner, Verner, M.-A. F Ngueta,ET Jensen, 05/documents/pros health M.-A., F Ngueta, ET Jensen, J | Fromme, advisory Fromme, W Volkel, UC Nygaard, final-plain.pdf W Volkel, UC Nygaard, BB GGrarnuma, MMPnPLLounognngemncekce,kre,r.,. ((22001166).). AA EnSSviiimmrpploleenmPPehhnaartrmomalacSocckoiikeninnecetetiicc&MMToeodcdehelnlooolfofgPPyrr,eenn5a0at,taa9ll7aa8nndd98PP6o.ossttnnaattaall EExxppoossuurree ttoo PPeerrfflluuoorrooaallkkyyll SSuubbssttaanncceess ((PPFFAASSS)s.). WebPlotDigitizr. (2017). Version 3.11 Released (lan 17, 2017). Environmental Science & Technology, 50, 978-986. WebPIotDigitizer. (2017). Version 3.11 Released (Jan 17, 2017). RReettrriieevveedd ffrroomm itp: farohiatgiinfo/WebplotDigitzer/ WWuu,,X.,X, DH Bennett, AM Calafat, K Kato, M Stryner, http://arohatgMnfo/WebPIotDigitizer/ DH Bennett, AM Calafat, K Kato, M Stryner, E E AAnnddeerrsseenn,, RREE MMoorraann,, DDJJ TTaannccreredid,i, NNSS TTuullvvee,, |I HHeerrttzz.- PPiiccccoitottoto,.,. ((22001155).). SSeerruumm ccoonncceennttrraattiioonnss ooff ppeerrfflluuoorriinnaatteedd ccoommppoouunnddss ((PPFFCC)) aammoonngg sseelleecctteedd ppoopuplautiolnasootffcichhioillddnrreesnn aanndd aadduulltss iinn CCaallfifoorrnniiaa.. EEnnvviirornomnmeenntatl RReesseeaarrcchh,, 113366,, 226644--227733,. Use oof reference to this model without proper attribution to MOHisprohibited. 33775500..00004444 a44 STSTAATTEE 0077443377996977 APPENDIX | ~ Summary of placental and breastmilk transfer study data. Placental Transfer Several studies measured maternal and cord serum levels of PFOS and PFOA near the time of delivery, thereby permittin~ an estimation of placental transfer and initial body burden in the newborn infant. PFOS Maternal Serum and Cord Blood Concentration Summary Study Description Tittlemier et el. 2004 - mEmnme pooled samples Fei et al. 2007- maternal samples taken in second m=" Midaschetal trimester Midasch et al. 22000077. Monroy eal 2006 Livetal. 2011 FMroonmromyeeett aolf. 22000180 Fromme et a!. 2010 Liu et al. 2011 Kim et al. 2011 ER Curiou et aL 2015 PFOS Maternal Serum CCoonncceennttrraattioinon(lag/L(ug)/L) PFOS Cord Blood CCoonncceennttrraattioinon(pg/L(g/)L) PFOS Cord Blood to MMaatteerrnnaall RRaattiioo Mean 36.9 Median 95th or Max Mean 16.7 Median 95th or Max Mean 0.45 Median 95th or Max lel [erer 29.9 11 0.37 [PT[["]|] [[1a 11626..11195[T 1144.55i4 | [7771..2199T [e6.o08sT |e [eo0ea.6s0r*[|aaT|T| [33.s5 "332.2 "Te6.r1 Ti1.r1 Ti1.o0 722.22 Jos0.44 0.31 Jos0.42 0.31 To0s.36 | [331.18844 [229.92222 [131.3.118868[116.68865[114.74700 [666.76744 [005.533 [o0s.50o [005.500 | 5.6 9.4 2.0 3.6 0.36 0.38 FELEE 3.67 3.065 24.5 1.28 1.115 8.04 0.35 0.36 0.33 **Minimum 0.31 **Maximum 0.50 **Average 0.40 *Individual maternahcord blood ratios ranged from 0.4~ to 0.80 **Geometric Mean 0.39 **Excluding Tittlemier et al. (pooled samples) and Fei et al. (maternal serum measured in second trimester). In all other studies maternal samples were taken at or within first week after delivery. PFOA Maternal Serum and Cord Blood Concentration Summary Study Description W Ersm Tittlemier et al. 2004 - pooled samples PFOA Maternal Serum Concentration (pg/L) Mean Median 95t~' or TR Ryee a Max [T - T 2.2 PFOA Cord Blood Concentration (pg/L) Mean 3.4 Median 95th or Max PFOA Cord Blood to Maternal Ratio Mean Median 95th or Max 1.55 Fei et al. 2007- maternal 4.5 3.7 0.82 samples taken in second trimester Midosch etl 007 Midasch et al. 2007 Monroy etal 208 FMFrrooonmmrmmoeyeeeetttaaafl.l.. 22200001~800 Gietal 2011 KLKiiiummeeettt~a1la..l.222000111111 CCaurriioouu eettaalL. 22001155 am| | sa | naw | | 2.75 3.41 1.24" [22a [imi | iss [iss Tow [om |__| 2.24 1.81 1.94 1.58 0.87 0.87 [22.33 Ti1.s9 --1s5.22 111.77 Ti1.a4 133.77 To0.n74 Jo0s.7a4 [1655 [1.068 [587 [15 [1415 easz 091 [oss [11 | [111..66655TT1.264"T553..22879Ta11r..51 T--1.115 T2627..7442To00e..96s19 |0.88 [112.222 101.a04s5 [77.3311Tos0.i91s9 Jo0s.8e600 [770.066 007.755 [008.822 Ear **Minimum 0.74 k **Maximum 0.88 Jo0.7m1 | 1.1 lo0.8s4 | [009.977 | **Average 0.83 **Geometric Mean 0.83 * individual maternal:cord blood ratios ranged from 0.92 to 1.95 Use o~" or re~ference to this model without proper attribution to MDH is prohibited, 45 33775500..00004455 STATE 07437998 Cute Teweerr.kpoldwisales) awnedtFsLhe.d(eaee semmessed insecond mest. nlatersues **Excluding Tittlemier et al. (pooled samples) and Fei et al. (maternal serum measured in second trimester). In all other studies maternal samples were taken at or within first week after delivery, The reported mean aio of cord to maternal concentrations anged om 0.31 (Fromme, 2010) 100.60 The reported mean ratios of cord to maternal concentrations ranged from 0.31 (Fromme, 2010) to 0.60 (Midaich, 2007) for PROS and fom 069 im,201) t 1.24 (Vidach, 200) for POTheRaver.age ofthe (Midasch, 2007) for PFOS and from 0.69 (Kim, 2011) to 1.24 (Midasch, 2007) for PFOA. The average of the Teported mean fais fom these tucies were 42nd 0.87 for OS and PFOA respectively. These average reported mean ratios from these studies were 0.42 and 0.87 for PFOS and PFOA, respectively. These average alueswere used by MOH in evaluating thesmple T model values were used by MDH in evaluating the simple TK model. BBrereasatsmtmitiklkTTrraannssf/eerr Several sues measure maternal serum concentanrdbarteiasotn, thereby permiting a estimate of Several studies measured maternal serum concentrations and breastmilk, thereby permitting an estimate of partvionng rom matena serum nto beast and prediction of east concentrations. partitioning from maternal serum into breastmilk and prediction of breastmilk concentrations. EOSMaternal Serum and Brest Concentration Summary PFOS Maternal Serum and Breastmilk Concentration Summary SusDescription Pros arena Serum | 08 area | POS reac Study Description PFOS Maternal Serum PFOS Breastmilk Concemteaion 43/0) | Concentration) | Maternal ati Concentration (pg/L) Concentration (pg!L) 5 Mean Median 95th or Mean Median 95th PFOS Breastmilk to Maternal Ratio Mean Median 95t" Rarmanetal 2007 Karrman et al, 2007 Fromme tol 2010 Fromme et a!. 2010 Guoetal 2011 Liu et al. 2011 im etal 2011 Kim et al. 2011 Caro tl 2075 Cariou et uL 2015 [[[s3223a0.022.77s |[[221215.869s.777 [sSoe |T3068 3.184 5.6 2.922 3.065 Max or voor x |[l#1e468.305s.05|[[00020.200%11oooo00iw..i1064sz6 J[|o0000o14..M409s7a785x|[[6o00o.011ms0[o[aoo00..o00us0194 [[[00oM.oooo00uuar11ssx3 [oaas JoTooswt 13.188 9.4 0.056 0.061 0.042 wea foTomse0,198 0.13 Jo[ooonu| 0.018 0.011 0.014 G[00..oa00m11se54 MMMiianniimumuunmm|| 00001180|| 000.000100489 || 0.015 000011s 0.01 GeometrMieAacxvnriemiriauagmene|| 00001132 || 0000.,000011112224 || 0000..000011113335 Geometric Mean 0.012 0.013 PFOA Matera Serum and Beasmitk concentration Summa PFOA Maternal Serum and Breastmilk Concentration Summary Sy ecimion | PROA Matemal Seu | FORBers | FORBrea Study Description PFOA Maternal Serum CCoonncceentnrtraattiioonn ((pugg/!LL)) PFOA Breastmilk CCoonncceentnrtraattiioonn ((luagg//LL)) ean | Medan | 95% | Nica | Medan| 93% | ean | Meco| 55 Mean Median 95th Mean Median 95th PFOA Breastmilk to MMaatteerrnnaall RRaattiioo Mean Median 95th Frame al 2070 Fromme et af. 2010 Geil 2011 Liu et al. 2011 im tl 2011 Kim et al. 2011 Carol 2035 Cariou et a!. 2015 7 vax oy vin Gvooexs 1.7 Toss [126 [se [odiesect[onoiaatne [1 [ois[aos [oaks 1.655 ie [132 Joon| loom loos| foo 1,6 12 [166 751 oot [dGeoomaetrVV[iAciaoveniisraaasngyne|o|| 0000o010020856532||| a0003%6 ||lo00aco02ooe24se65: 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 0.024 0.245 0.094 0.063 The reported mean aio of breastmilk to maternal serum concentration angefrm 0.1 (Karman, 2007) 0 The reported mean ratios of breastmilk to maternal serum concentration range from 0.01 (Karrman, 2007) to 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 tics fom thes tucks were 6.013 and 0.052 for OS and PFOA respect. These average reported mean ratios from these studies were 0.013 and 0.052 for PFOS and PFOA, respectively. These average Values were used y MDH in evaluating he simpleTK model. values were used by MDH in evaluating the simple TK model. Use ofr referenceto tis modelwithout properatrioution to MOH i protes. i Use oj~or reference W this model without proper ottribution to MDH is prohibited. 46 33775500..00004466 stare onaaTess STATE 07437999 Appendix | References FFEeneiiv,,iCCr..oeenttmlea.nl.t((a22l000H07e7)a.).ltPPheerPrffellruusooprreiincntaaittveeedds,CCh1he1em5mi(c1ic1aa)ll.ss1aa6n7n7dd-1FFe6et8taa2ll.GGrroowwthth:: AA SSttuuddyy wwiitthhiinn tthhee DDaanniisshh NNaattiioonnaall BBiirrtthh CCoohhoortrt.. Environmental Health Perspectives, 115(11):1677-1682. FFrroommmmee,, HH..,eett aa.l. 2(200101)0.). PPrree-- aanndd PPoossttnnaattaall EExxppoossuurreettoo PPeerrfflluuoorriinnaatteedd CCoommppoouunnddss ((PPFFCCss)).. EEnnvviirroonnmmeennttaall SScciieennccee && TTeecchhnnoololgoyg,4y44,4:: 77112233--77112299.. KKaarrrmrmaann, A,A.., eettala.l. 2(200007)7.). EExxppoossuurree ooff PPeerrlfluuoorriinnaatteedd CChheemmicicaallss tthhrroouugghh LLaaccttaattiioonn:: LLeevveellss ooff MMaattcchheedd HHuummaann MWiillkk aanndd SSeerruumm aanndd aa TTeemmppoorraall TTrreenndd,, 11999966--22000044,, nin SSwweeddeenn.. EEnnvviirroonnmmeennttaall HHeeaalltthh PPeerrssppeeccttiivveess,, 111155::222266--223300.. iKKmiimpml,,iScSaK.-t.Ki.o,neesttafalol.r. (2p2r00e1n11a1)t).a.lDDiaissnttdrriibpbouusttitioonnnatooafflppeeexrprffollusuuoorrreooscc.hheeEmmnivicciaarllossnmbbeeenttwtwaeeleennPolssleeurrtaaioaannn,dd1mm5i9ill-kk16ffr9ro-om1m74tth.hee ssaammee mmootthheerrss aanndd implications for prenatal and postnatal exposures. Environmental Pollution, 159:169-174. LnLieiuuw,,bJo.,J,reenttsa.all..E((n22v00i11r11o))n..mCCeoonmmtppaIarntireissroonnnatiooonnnagglee,sst3taa7tt:iio1o2nn0aa6nn-dd12ll1aa2ccttaattiioonn eexxppoossuurree ooff ppeerrffliuuoorriinnaatteedd ccoommppoouunnddss ffoorr newborns. Environment International, 37:1206-1212. MMiiddaasscchh,, 0O.. eettaa.l. 2(200070)7.). TTrraannssppllaacceennttaall eexxppoossuurree ooff nneeoonnaatteess ttoo ppeerrfflluuoorrooooccttaanneessuullffoonnaattee aanndd ppeerrfflluuoorrooooccttaannooaattee:: aa ppliloott ssttuuddyy.. IInntteerrnnaattiioonnaall AArrcchhiivveess ooff OOccccuuppaatitioonnaall aanndd EEnnvviirroonnmmeennttaall HHeeaaltlthh,, 8800::664433--664488.. MsMaoomnpnrloreoysy,., RRE.n.,,veeittraoa.nl.m((e22n00t00a88l))..RSSeeseerruaurmmchlle,evv1ee0lls8s:oo5f6f-pp6ee2r.rfflluuoorrooaallkkyyll ccoommppoouunnddss iinn hhuummaann mmaatteerrnnaall aanndd uummbibliliiccaall ccoorrdd bblloooodd samples. Environmental Research, 108:56-62. TNTioittrtllteehmmeirieenrr,,CaS..naoetdtiaaall..n((2P2o00p00u44l))a..tiPPorrneesss.eennOccreegooafnf oAAhnniaioolnonigiccenPPeeCrrfofllmuupooorruiinnnaadttsee,dd 6OO6rr:gg3aa9nn5ii9cc-CC39oo6mm4p.poouunnddss iinn SSeerruumm CCoolllleecctteedd ffrroomm Northern Canadian Populations. Organohalogen Compounds, 66:3959-3964. Use oof reference to this model without proper attribution to MOH isprohibited. 33775500..00004477 a47 SSTTAATTEE 0077443388000000 AAPPPPEENNDDIIXX II1l --,--,-- PPeeeerr RReevviieewweerr" BBiioog]rraapphhiicc;all IInnffoorrmmaattiioonn or. Jeffrey Fishe-r Dr. Je~rey Fisher- TDDorrx.iJJceeoflffforrgeeiyycFaFilisshRheeesrreaiisrcaahr.reessHeeeaarrwccahhsttoofxxoiirccomoleloorgglisasytt wwPirittohhfttehhseesUUoi.n.r5S..tFhFeooooDddepaaannrddtDDmreruunggt AAodfdmmiEnniinvsiistrrtoraantmtiieoonnnt,,aNNlaatHtieiooannlatalhl CCSeceninettneecrre,ffooCrrollege TooDfofexpPPiuacubrobltllioimccgeiHHnceteaaallHltRtehheasaadtetaottrfhhceehth.UUeHnniDeivveweeprarasssriittfytomoreofmnf tGGeereoolfyorrgEaginiPaavir((orUUfoGeGnAsmA)s.e)o.nrtHHianeeltjjohHoieeinaneDledtdehptthShaeceritmUUennneicivnevesterorsfsifrittoEyymnoov2ffir0GGo0ene0omortrgeoginiaa2t0aiin0ln6H22ae00na00ld00thaaDiSnnrddceiecsstneeocrrrveve,eoddfCtoaahlssleege WDIInrnettieepgrrahddtriitssmPccaiiepptnlltiitnenraHasrreyoyanTTdAoooxFxiBficc,thoowlelohoggeDyyreePPprrahooregtgmrrwaaeammnstaaPtort fiUUnEcGGinAApvaifflrroroInomnmmvee22sn00t0it0a6g6la--t22Ho00re11a0a0.lnt.hdHHSSeeceisnseippnoeecrnnetsStc22fir55eoynymteeiasar2trs0si0ana0ttthtttoheheeT2oT0Tx0ooix6xciiscacooHnlladoozggDayyrirdLLesaacbbDtooiorvrraiaotstofiorotrhyny,e, W anrdigThetchPnaitctaelrsAodnviAsFoBr, fworhethree OhpeewraatsioPnrainlcTipoarlicInolvoegsytigBraatnocrha.nd Senior Scientist in the Toxics Hazards Division and Technical Advisor for the Operational Toxicolosy Branch. DmDra.r.thFFeiissmhhaeetrri''sscarrleessmeeoaarrdccehhliinntttoeerraeessscttessrtaaarrieeniinhnettahhleethddeeivsvekeslloofpprmmoemennettnaavinnrddonaamppeppnllticiaaclta,iotfniooooofndf-ppbhhoaarrrnmmeaacaconkodiknionecetctiuiccpaaatnniddonbbaiiloolcloohgseiimcciaalclllayylbbaasseedd eFemixxsapphotoehssreu'umrsreecassht..iecmRRaeilecccemaenlotnldttlyoey,x,lsiwwcitoiottlhhoagsFFycDDeAmA,ro,tdahheienelihhhnaaegssaelbbtxheepcceroiorsmimkeseenfciirnoenvvmioonllvcevelneuddvdieiirnonsnttwhmhoeerekuunisstneaegol,ofwffioPPtoBBhdPPc-KKbhlommorornodiedenealaltssnedffdoooarrcnddcdrruuunpggoassnt-iaaocnnnhddalolppreceidhdnieaaiamtttreriicidccassl.. DDrr.. sstFiooissllkvvheeaensnrt'stssse,,cshffsuuemeeemllnssi,t,c,appeleestssotttixiiccimiciddaoeetlssoi,,nggyppeelmrarcccohthldalotoerirloaiannttgaeel,,erPPxFpFaOQeArAi,en, naaocnnsefddsifobbnliicsvlsepuephdnhteersesn,onwlouAoAnl.rd.keHHirneesgthhawaanssidthddineecgvvheeillolnoorupipnteeaeddrteoPPdBBaPPnaKdKndnmmeonoododneneal-tlcssahlfflooodrrroiunusssiaeemteeiitdnnrccyaa,nncceerr piqqrtiusuuakainnttaaitsifrfsyyyeiitsnnhsggmyrmmeoeneitttda,abebaoxsolitlsiiimssimnamtrioonoffgdsseolonlatlvcvseteananttnitmodminxhaixtultumutrraraenenssss.aafennDrddr.oddfFeesivvsoeehllvelooreppnhiitnasnsg,gu3bbni0ioodylleoeogragsirictcsaoaalnlflldyyienmmxgopoteitinrivviuaaetttneeecrddoe mmianonopdddheeynlssseiooffonloorargtttiahhcleaedlhhomyysoppimdooettelhhtaiarylnla,agmmaiinccd- hpaitsuirtaairyn-ethdysreoviedraalxigsrianduroadteensttsuadenndthsuamndanpso.sDtdr.ocFtiosrhaelr hfaelsl3ow0syoenartshoefceoxnpceerpitesncaendinappphlyisciaotloiognicoafl mphoysdieollinog8icaanld mLhmoaaodbsdeotlerrsaals.ti.noeHrHdyee wiwsneaa1vss9e9ara9a.VVli~issDiriuattiridnniuggnagSStcetcihieeisnstnttutiiidssmtetenaa,ttthsttehaheneadlCCshphoeoemssmietdcircavoalecldtIIonanrsddauulAssdftetjrrluylyonIIwcnntsssttPioitrtnuouttfteeehseoosffocTTrooonixxnciiectcphooetllsoDogegayypnadiinnrat11p99mp99el66inctaaatnnoioddfnPaathtoattfhrhpmeehayNcNsoIIOilOooSSlogHHgy.iTTcaaaflftt aaPLnnBaddPbKoTTroomaxxotioidccreooyllloiiongngyyg19aait9nt9WW l.raibDriogsurhhratitntSogStrttayahttaieesniUUtinmmniavilevese,rsrahisnetitydy.a.lhsDDuormr..saenFFirsisvs.heheedHrrhaehasahsAspadsupjbusulebnirlcissvthhePdeerddoonfooevvsseeesrvorer11ri66an0l0tnhppaaeatppiDeeorrnessaplooapnnrtamppnhehealanrsrtmmaoanacfdocPkoahikdanivnreimetstiaoiccrcssyolaabonnosddayrds ffOPoroBrgrPattKnhhieemzaDDotodaiDDeo,nl,i.nAAgTTDrSS.inDDRFRlia,,sbhUUoeSSrraEEstPPeoAArryvaaennadddnoimnnnooantnl-sh-pepraorInofndiftitethroounrmraggtaaainnoninsizza.alatHtiLieooinnhessa.S.scHHiseeeenrwwvceaeadsssaIaonnsUU.t.sSiS.et.uvddteeeerSlalteelesgneaaarttiteeinoffgnooarrClotthphmeaemniNNetolosrertteahh,ndAAwttlahlaadinncvttihisiccoeTrTvyrareelbaauotatayytredds OccBihhrollglooaorrgnooiifcfzoaoarlrtmimoMnoaad.nneDddlridd. iniFccgihhslSlhooperreroociaasaceclerettvtyieiccdSaeaocccnitidditohuunsesoiinfnIntggtheEEerPPnSAAoa-c-tppiiorrenootpapyoolossLfeeifTddeoCCxSiacacrireoccnliinconoegogsyg,eeInnnrseRRtviiitissukketweGGeuruSiidtdfeeoelerliirnsnineeegvsse..CraHHoleemtiimsosxPPiitatcaesostelt o,PPgwryrehjseiocidushrenineatdvolasofe,lfutnatahhntteeedd wwMBoaaiodssleoCClsoiio-cn-PaPgrliraiMnntccoitippdhaaeellliUnIInnngivvveeSessrptsteiiiggctaaiyattolootyrrf ooSGnneeaocartigoNNianaattioiioofnnnttahalhleeIISnnfassolttlciititoueuftttye2ess0o0foo3fTfH.oHexHaeieclaotlwtlhhaoss((yNNa,IImHrHee))v--msisebuuwppepeproorrrofttofeertddhswweeovoNrerakrktassilhhotnoooappxlicooAonncloaMMgadaytethjmhoeeyummraontfaaitSlicscca,ailelanncdes sMuobdceolminm8itatteteheonUAncivuetresiEtyxpoofsGureeorGguiaidienlithnee fLaelvleolsf 2(0A0E3G.LSH)efwraosm a20m0e4-m2b0e1r0oafntdheScNieanticoenAadl vAicsaodryemBoyaorfdSfcoirentchees sUAUuSSbEEccPPoAAma((m22o00iftd00tTe77o-e-x22ei0o0c1n1o0l0mA)o).c.giuycHHteaeelEiissSxcaapinnoesnaaucddreeshhGooaccnudimmdeeaemnlminbaebesesrLroecooviffealtttshheee(AeSSdEiAAGtBBoLssrs)fffooforrrroddTmioiooxxx2iici0nno0laa4onn-g2idd0capp1lee0rrScacchnhiledloonrcrSaaetcsteie.e..ncDHHre.eeAFsidsiavsafhiseefoerlrlllyhooawwBosoaoaffr8d.tt5hh.feeor the AddUneeciggavrrdeeereeesmiiitynny,obbifaiooTnllodoosxgayiycPoffrhlroo.o0m gm.ictatihnhl eZeSocUUoinelninoivvcgeeeryrss/siTiatotynyxdioocffaonlNNoeeagbbsyrrsaaofsscrkkioaaamteaaMtteiKKdaeeimtaaoirrrnUnfenoeyiry,ve,aTarosMMxi.ti.cSSy.o.. loddgeegiscrraeeleeSiicnniebbniicooelloso.ggyyDffrr.rooFmmishWWerririgshhahtst State a B.S. State University, and a Ph.D. in Zoolo~y/Toxicolosy from Miami University. Dorr.. GGaarryy GGiinnssbbeerrgg --- OtDro.rx. iGGcaoarlryyogGGsitinnossbbneesrrtggehhraaissskbbaeeseesnnesaasttmooesxncictoolsloofggoirisstrteaamttettdhhieealCCoponrnnonegcertcaitimccsuuttanDDdeepepavarartltmumaeetnnitotnooffofPPucuboblnliitccaHHmeieanalatlthnh,t, swwhihneecrreoenhhseeumissetthrhee lleeaadd tppporurxoobidldcuiuocsclthotsesg,d,isttehthxeoetnebbnsuusiiittlevteeerlninysvkvoiirnraooscnsnhmemiselesdnnrmtet,,en'nffostosoohdfdeoaprplrtrrooheddmruuececltdtassit,a,elaadpnnirddsoasvguaersvaa.amrDriser.taiynGodoifenfoesottvbthaeheylreurgraitmmsioeeandddijioaaufnaaccnnotddnftaeeacxxmuppliootnsysauuanrrtteestshsioneouurcYrcaocelnesess..uScmHHheeeorohhlaassof PpuubblliischHeedaletxhtaennsdivieslayssoinstcahnitldprreonf'seshseoralothf creolmamteudniistsyuemse.dDicr.inGeinasbtehr8e UisniavdejrusnicttyfoafcCuoltnyneacttthiceutYaHleeaSlcthhoCoelnotfer cc`PaaummAbplpiuccuss.Ha.eoHHadfeelthShhecaaaissmnedssnyeecirrsevvaeepsddasnooiesnnsta.aanntDnrupu.mrmoGbfbieenesrsrsboooefrfrgUoU.f.SrS.ce.coEEemninvvmvieirudroonhnniitmmsyeePnmnhtDetaafdllricPPoirnrmooetteeaUcctCtttiioohonnennAAUigsnneei1vnn9ecc8ryy5s.iaatyddvvoiissf ooCrroyynccnooemmcmtmiictiutttteeHeesseaaalnnthddCNNeaatntiitooennraall Academy of Science panels. Dr. Ginsberg received his PhD from UConn in 1986. Useofor reference to this model without proper attribution to MOHisprohibited. 33775500..00004488 848 STATE 07438001 STATE 07438001 ODrr.. JJuuddyy LLaaKKiinndd -- JEJuupddiyydeLLmaaikKoiilnndod,g, yPPhah.n.DDd.. PiissubrPleirescisHiddeeaenlnttthoo,ffULLnaaikvKieinrnsddiAAtsysssooofcciMiaaattreesys,l, aLLnLLCdC,,SaacnnhddooAAlddojjfuunnMcectdtiAAcssissnooec.ciiaaStteheePPrirsoofafeehssessaoolrr,t,hDDaeenppdaarerttnmmveeinrntotnoomffental scientist with expertise in exposure scence, asseosfhsummanehenaltth risks, biomonitoring, scientific and Epidemiology and Public Health, University of Maryland School of Medicine. She is a health and environmental scientist with expertise in exposure science, assessment of human health risks, biomonitoring, scientific and teteexccthhennnisicciavalellaaynnaoalnlyysseiixsspffooosrrurrreeegg-uuallanatdtoorrryyisssku-urppepploaorttret,,d aaisnnsddusestst,aaittneec--loouff-dttihhneeg--csshcciiileednnrcecnee'srreevveiixeepwwsos.s.urDDerr.s. LLtaoaKKeiinnnvddihhraaossnmsseppnootkkaeelnncaahnnemddicppauulbbsll,iisshthheeedd implications of extensively on implications of uncertainty inthe risk assessment process,weighing potential risks and benefits elated to exposure- and risk-related issues, including children's exposures to environmental chemicals, uncertainty in the risk assessment process, weighing potential risks and benefits related to the cchheemmiiccaall uussee,, eennvviirroonnmmeennttaall cchheemmiiccaallss iinn hhuummaann mmililkk,, aanndd ttimimee--ddeeppeennddeennccee aanndd ddiissttrriibbuuttiioonnaall aannaallyyssiiss ooff eMexaxpproyoslsuuarnree.d. inDDrr.i.sLLkaaakKsiinnsddeshhsaamssetntaatuuaggnhhtdt ggarrqaauddautuiaactteechlleeemvveielsl tccrooyuu.rrssSeehsseaatst TTehheerJoJvoonhhtennhssseHHooepdpkikitionnrssiaUUlrnibivoveaerrrssdiisttyyofaanntddhetthJheoeuUUrnnniaivlveeorrsfsiittyy ooff Toxicology and Environmental Health and Environment International and is past Associate Editor fo the Maryland in risk assessment and aquatic chemistry. She serves on the editorial boards of the Journal of Toxicology and Environmental Health and Environment International and is past Associate Editor for the JJoouurrnnaall ooff EExxppoossuurree SScciieennccee aanndd EEnnvviirroonnmmeennttaall EEppiiddeemmioiollooggyy.. DDr.r. LLaakKiinndd iiss PPrreessiiddeenntt--EElleecctt ffoorrtthhee IInntteerrnnaattiioonnaall SSoocciieettyy ooEfnfvEEixxrppooonssmuuerrneetaSSlcciiHeeennaccleetaahnnaddnhdhaaPssrssoeetrervvceteiddooonnnAdnnvuuimmseoerrryoouuCssouaanddvcvi.issoorryy ccoommmmitittteeeess iinncclluuddiinngg tthheeMMarayrlylaanndd''ss CChhiillddrreenn''ss Environmental Health and Protection Advisory Council. M Wr.~MMiikkeePPoouul~seenn-- Mike Poulsen has a degree in chemistry from Stanford University aanmastd er's degree in technology and policy from Mike from the Massachusetts Institute of Technology. Mike Poulsen has a degree in chemistry from Stanford the Massachusetts Institute of Technology. M ike has been a University has been a toxicologit or seventeen years inthe Cleanup. and a master's degree in technology and policy toxicologist for seventeen years in the Cleanup PPrrooggrraammooff tthhee OOrreeggoonn DDeeppaarrttmmeenntt ooffEnEvnivriroonnmmeentnatall QQuuaaltliyty.. rPirioorr ttoo jjooiinniinngg DDEEQQ,, hhee wwaass aann eennvviirroonnmmeennttaall ccoonnssuullttaanntt ffoorr ffiiffteteeenn yyeeaarrss aanndd aa sscciieenntitiffiicc rreesseeaarrcchh aannaallyyssttffoorr ttwwooyeyeaarrss.. MaMrs.rs.ePPsoosumulelssneetnnfpporrrootvvhiidedeesdditerriissskkhoaaswssseeedsssstmhmaeetnntet xssuupppoppsoorurttrtffeooorrPtthCheeBPPionorrfttillasahnndrdesHHualartrbsbioonrr ffteehddeeergraralelaSStueupspteerrpffouutnneddntppirarolojjceeacctnt..ceTTrhheerirsriiksskkto humans. To assessment humans. To fully evaluate non- carcinogenic effets, Mike for the site showed that exposure to PCBs in fully evaluate non-carcinogenic effects, Mike worked for five years with fish results in the greatest worked for five years with EPA Region 10 toxicologists potential cancer risk to EPA Region 10 toxicologists aanndd tthhee OOrreeggoonn ppuubblliicc hheeaalltthh ttooxsiiccoolloogiisstt ttoo ddeevveelloopp aann aapppprrooaacchh ffoorreevavlauluaattiinngg PPCCBB iriskssttooikinnffaasnnttss ffrroomm bTbrhreeeaaststetffaeeemedditinnhgeg,n. TTwhhoeerktteeeadammwimmtohodAdifTifiiSeeDddReesqqcuuiaeatnttiioiosnntsssfofaornrdaasoistinhngeglrleercceoosemmaprpacarhrtetmmresentntot,,cffoiirmrspstt-ao-rorreddeetrrhekkiimnnoeetdtiiecclmmowoiddteehll3-uussaeendddbb&yy EEPPAA.. TchoempteaarmtmethnetnPwBPoKrkemoddewlisth. APTCSBD-1R5s3cmieinltkisctosnacnendtorathteiornrsesaenadrcdhoesressttoocionmfapntasrewethree mcoadlecl wuiltbhay3tt-ehaedndt8h-ree models using data rom 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 GGaisivvseeennssttmhheeencctllogosuseiednnaeensscsse.ooffDtthEheeQrrseeissmuuplllttissf,,ittehhdeetsshieimmeppvllaeelrruEaEtPPiAAonmmooofddetelhlewwbaarsseassseetllefeccetteeedddinffgoorrpaiinntcchlluwusasiiyoonniniinrniOOskrreeaggsoonnsDDeEEsQQsirsimsbkkyeunsitnsg the EPA model to devealtaoblpe of infant risk adjustment assessment guidance. DEQ simplified the evaluation of the the EPA model to develop a table of infant risk adjustment factors (IRAFs) breastfeeding factors (IRAFs) that can pathway that can be usedtocalculate potential in risk assessments by using be used to calculate potential tcriihssekkmittocoaliinnsff.aann(ttAsspbpbaeanssededidxoonDnittnhhee ccaallccuullaatteedd rriisskk ttootthhee mmootthheerrss ffrroomm eexxppoossuurree ttoo PPCCBBSs aannddootthheerrbbiiooaaccccuummulualattiinngg cihtepm:/ic/aulws.ww(AdpepaenstdaixtDe.ionr.us/la/pubs/docs/cufHumanHealthiskAssessmentGuidapdnfc)e http ://www.d eq. state.o r. u s/I q/p u bsid ocs/c u/H u m a n H ea It h Ri s kAssess m e ntG u ida nce. pdf) DDrr.. MMaarrcc--AAnnddrrPe VVeerrnneerr--- HMMeaaarlrcct-h-AA,nnSddcrrh~ooVVleerornfneePrrubwwloiorcrkkHsseaaalssthaa,nn UAAnssissviiessrttsaainntttPPdrreooffMeeossnssotorrraaatltthh(eeCaDDneaepdpaaar.rttmmHeeennitts ooaff OOclacccumupsepamatitbioooennraalloaafnntddheEEnUnvnviiivrroeornnsmmietenntdtaaell MbHMoaeonsantelrttdhre,paahSllacrPPhmuouabobcillioccokfiHHnePeeaualtbltitlhhicc RR(HePeesBseaPeaKlat)rhrcc,mhhUodIInnneissvltetiiitrtnusugitttee~an((dIdIReRSqSMuPPaUUonMntM)it.)rt.eaMaMtail avr(ercCc'as'sstnrarrueedcssatee)u.aarrrHecc-ehhpirpsporrapoolejsjereotccyttassrmeffoloecacmutuissboenmmsrohosoistfptlsltyyh(eooQnnSUPppnRhhi)yvysetsirooisoleiltoov~gagildicuceaaaltllelyy: dbeavseedlopphmaenrmtaalcoekxipnoestuicre(PtBoPeKn)vmiroodnemleinngtaalncdhqemuiacnatlitsatiinvethsetrwuoctmubrea-pnrdoppoesrttnyatreallaltyiotnhsrhoiupgsh(QbrSePaRst) fteoedeivnagl.uaHtee. earned his Ph.D. in Biology from the Universit du Qubec Montreal (Canada). During his developmental exposure to environmental chemicals in the womb and postnatally through earned his Ph.D. in Biology from the Universit~ du Quebec ~ Montreal (Canada). During his Ph.D., Marc breastfeeding. Ph.D., Marc He ddeevveellooppeedd PPBBPPKKmmododeellssooff ppeerrssiisstteenntt oorrggaanniicc ppoolllluuttaannttss ttoo rreeffiinnee eexxppoossuurree aasssseessssmmeenntt iinn eeppiiddeemmiioollooggiicc ssttuuddiieess. ooff bbrreeaasstt ccaanncceerr aanndd ddeevveellooppmmeennttaall nneeuurorototoxixciciittyy.. AAfftteerr ccoommpplelettiinngg ihiss PPhh..DD..,, hhee ccoonnttiinnuueedd wwoorkringkooninPPnBBPPgKK Use oof reference to this model without proper attribution to MOHisprohibited. a49 33775500..00004499 SSTTAATTEE 0077443388000022 `tmmooodddeoleialinngsgeddcuournriidnnggpohhsiitssdppoocoststotdrdoaoclctttoorrraaaillnittrnragaiininniinenggnvaaittrttohhneemeKKnaatrraoollliinnesspkkiaadeIInmnsistotiilttuouttgeeytr aiintn tSShwweeedHdeaenrn.v.aHHrede MtthehedeinncmamloovvSeecdhdottoool/BBrooissgtthooannrn((UUaSSnAAd)) `Women's Hospital. His background in both toxicology and environmental epidemiology led him to pioneer the to do a second postdoctoral training in environmental epidemiology 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 PPBBPPKK mmooddeelliinngg iinn eeppiiddeemmioiollooggiicc ssttuuddiieess,, aannaapppprrooaacchh tthhaatt aalllloowweedd rreeccoonnssttrruuccttiinngg ccoommpplleettee eexxppoossuurree. ppMrraoorfficilleehssasaannaddutiinhnvoveersesttdiiggaaanttdiinngcgott-hhaeeuteefhfffoeerccettsds aoofpfcpchrheoexmmiimcicaaatllesslddyuu2rr5iinngpgeddeiriffffereerreveinntetwwweiidnnddpoaowpwessrsoofvfauvnludnlenrreeacbraielbiivilteitydy..nOuOvmveeerrr otthuheesyyaeewaaarrsrs,d, s for bMisaricnnhoavsataiuvtehowroerdk ainn dencvoi-raountmheonrteadlahpepalrtohx,imately 25 peer-reviewed papers and received numerous awards for his innovative work in environmental health. Or. Rachel Worley - Dr. R~hel Worley- RRaacchheell RRooggeerrss W Woorrlleeyy iiss aann EEnnvviirroonnmmeennttaall HHeeaalltthh SScciieennttiisstt aatt AATTSSDDRR iinn tthhee DDiivviissiioonn ooff CCoommmmunuintityy HHeeaalltthh MIInnviveesnsttiigEgaantvtiiioornnossn,,mSSeccniiteeannlcceeStSSuuudpippeposo;rrRtteBBprrraaondncuchch.t.iRRvaeacchhTeeollxihhcaaosslhhoegeryr BBSSiinn from CChheemmisisttrryy ffrroomm tthhee UUrniivveerrssiittyy ooff GGeeoorrggiiaa ((22000066)),, Brown University (2008), andaPhD in Toxicology aann fMrAominthEenUvirnonimvenetoarlfSGsetuiodrtigeiysa/R(e20p1r6o)d.ucHteivrefToromxaiclotlorgayinfrionmg sBinrcoowmnpuUtantivieornsaitlyt(o2x0i0c8o)l,oagyndanadPshhDe inacTtsoaxsicoaloPFgAyS. subject matter expert at ATSDR from the University of Georgia (2016). subject matter expert at ATSDR. Her formal training is in computational toxicology and she acts as a PFAS Use oof reference to this model without proper attribution to MOH isprohibited. 33775500..00005500 5500 SSTTAATTEE 0077443388000033