Document pmGxNKEzvvnVm2QvKgMB3japX

Lhe AR 226 _ 1105 3M Lifetime Drinking Water Health Advisory for Perfluorooctanesulfonate Revision Date: April 19, 2002 Supercedes: July 7, 1998 `This document establishesa Lifetime Drinking Water Health Advisory (DWHA)of 4 pg/L (ppb) for perfluorooctanesulfonate (PFOS). The valueof 4 pg/L is a guideline and is `based on assumptions regarding consumptionofwater containing PFOS. The value may be adjustedif actual information exists which would make it appropriate to adjust the `source contribution factor. Authors 2 =" = %7 23 w Z=>= XR Fotn. 2.Clty v/03lez John L. Butenhoff, Ph.D., CIH, DABT Ru 8 19-2002 Robert Roy, Ph.D., DABT Authorization: Los 8Rffol bn 44113/0 Larry R. Jofinson, D.V.M., Ph.D., DABT Director, Corporate Toxicology z LarryR Zobel, M.D., MPH Staff VP. and Medical Director CONTAIN NO CBI 200191 Lifetime Drinking Water Health Advisory (DWHA) for PFOS Background" `The DWHA for PFOS was calculated using standard EPA methodology. Briefly, the following three equations were used: Rp = WOAED)orLOAEL) _ ike och weight --day (UF) we== (B/D) (10 kg)= = msLmg/oL r gLug/ Lifetime DWHA = DWEL xRSC = mg/L or ug/L Where: RID = Chronic Reference Dose [the estimate (with uncertainty spanning an oserndseirtiovfemsaugbngirtouudpes))ofthaatdaisillyikeexlypotosubreewtiotthhoeuthaupmparencipaobpluelartiisokn(oifncluding deleterious effects during a lifetime] NOAEL = No Observed Adverse Effect Level [the exposure level at which there are no statistically or biologically significant increases in the frequency or severity of adverse effects between the exposed population and the anoptprcoopnrsiiadteerceodnttroolb;esaodmveeresfef,ecntosrmtaoybebea pprroedcuurcseodrattotshpiescliefvieclabduvtertshee.y are effects] wLhOiAcEhLth=erLeoawreeststaOtbissteircavlelydoArdbvieorlosgeicEaflfleyctsiLgenviefilca[nttheiencxrpeoassuerse ilnevtehle at frequency or severity of adverse effects between the exposed population and the appropriate control] UF = Total Uncertainty Factor (chosen using EPA guidance). The total UF is creogmaprodsteo:d o1f) fiinvteesruhbu-mfaanctvoarrsiatbhialittya;tt2e)mepxtttroapaoclcaotiuonnt offorreusnucletrstfairnotmy with 1 000192 eexxppoesruimreen;t4a)l eaxntirmaaploltaotihounmfarno;m3L)OeAxtErLaptoolaNtOiAonELfr;omansdub5c)hrionnciocmptloetcehronic database to complete database. A modifying uncertainty factor (MF) may also be applied to account not accounted for in the five sub-UFs. for areas of scientific The standard EPA default factor for each of the five sub-UF's = 10; that for etlhiemMinFat=e t1.heSnuebe-dUFtosa<c1c0oumnatyfoarlasopabretiucsueladrwahreean oefxiusntcienrgtadianttya.reTdhuece or choiceofappropriate sub-UFs and the MF is accomplishoend a case- absys-ecsassoerbsa.sis using professionaljudgment by experienced risk DWEL = Drinking Water Equivalent Level [the concentration of a substance in drinking water that is not expected to cause any non-carcinogenic health effects in humans over a lifetime of exposure] cRhSmCei=caRlelfartoimvedrSionkuirncgewCaotnetrrirbeultatiiovne [tios tohteheprrospoourrtcieosn sofucehxpaossfuoroedtao nad air](in the absence of any other data the EPA default value = 20% is used) Lifetime Drinking Water Health Advisory (DWHA) = The concentration of a cnhoenmciacracliniongderniinckienfgfewcattseorvethraat ilsifneottimeexopfeecxtpeodstuorec,auwsitehaanymaardgvienrsoef safety. "References E Ciemanec, J.L et emerging issues. al. In: (1996). Noncancer risk Fan, AM. and Chang, assessment: present and L.W. (editors) Toxicology and RiNsekw AYsorske,sspmpe.n2t3:3-3P1r0in.ci(pcleosp,yoMfepthaopdesr,aatntdacAhpepdl)ications. Marcel Dekker, Dourson, M.L. et al. (1996). noncancer risk assessment. Evolution of Regulatory science-based Toxicology and uncertainty factors Pharmacolo2g4y: in 108-120. (copyofpaper attached) Environmental Protection Agency (1999). Integrated Risk Information System (IRIS). WWWaddress: http://www. epa gov/ncealiris.htm REengvuilraotnimoennstaalndProHteeaclttihonAdAvigseonriceys.(19W99)W. WOfafdidcreesosf:Water. Drinking Water http://www.epa.gov/OST/Tools/dwstds0. html 000193 2 IL Lifetime Drinking Water Health Advisory (DWHA) for PFOS Step 1. RfD Calculation Rp = WOAED)orLOAEL) _ FR) 1 boty weig-dhaty `NTOheAENOLA=E0L.1f5rommgt/hkegs-idxa-ymo[nNtOh AmEoLnkferoymsstiuxd-ymwonatsh cmhoonskeenyovorearl tchaepsBuMlDeLsotufdoy.r hraetpsatboeccealluuslearthaedmeonnokmeayofst8udpypNmO(AdiEeLtarryepcroensceennttrsaatiloonw)efrorexmpaolseuarendlefveelmailnea species with greater similarity to humans.] UF =300 [total UF = 300 (10x3x10x1x1). [also refer to Appendix]: Individual sub-UFs were as follows Interhuman (person-to-person variability) = 10 [standard EPA default] Extrapolation from experimental animal-to-human (interspecies ~~ variability) = 3 [used non-human primate] Extrapolation to chronic exposure (chronicity) = 10 [based on exposure duration longer than subchronic but significantly less than chronic (6 months in a non-human primate); PFOS also appears to accumulate in the body on repeated exposure due to poor elimination] LOAEL to NOAEL = 1 [standard default - NOAEL used] Incomplete database = 1 [significant data accumulated on chemical, including results of cancer bioasssay and extensive human epidemiological data] Modifying Factor = 1 [rman data available; significant data accumulated on chemical; sensitive endpoint established in studies; uncertainties accounted for in other sub-factors] 200194 3 Therefore: R= L 0. IkgE= D 0005 mgkg day = 0.5 1gd) Note: The precision associated with the RD is usually one significant figure, therefore, RfD should be rounded to = 0.5 pg/kg-day In. Lifetime Drinking Water Health Advisory (DWHA) for PFOS Step 2. DWEL Calculation ower BDD2V)L/(Dd0aOykkg)) _ mg/L0p or pgiL DWEL=05sgli2gLdiada) Oke) _,, wll nm. Lifetime Drinking Water Health Advisory (DWHA) for PFOS Step 3. Lifetime DWHA Calculation Lifetime DWHA= DWEL xRSC = mg/L or pg/L [Lifetime DWHA= (17.5 ig 11)(02)=3.5 4|gL (ppb) This is rounded to 4 g/L (ppb) . 000195 APPENDIX . Precedent exists (see Arochlor example, below) for a reduction in sub-UF (ie. versus using standard defaults = 10 for each sub-UF) when the experimental data warrant. Based on the significant amount of available toxicological data for tPoFbOeSth(ein"ctlouxdiicn"gmdeattabaoflriotem)sittuidsiveesroynreoltehvearntFCtosuisnewhbiocthh pPrFofOeSssiisohnaylportihskesized aavsasielsabslmeendattaa.nd toxicological judgment to "adjust" the sub-UFs based on `The EPA-derived uncertainty factor RuIsDedfobryAEroPcAhlwoars1011006;isan7xM1F0o1fmg/wkags-daalys.o The total used. Reductions ianndsupbr-oUfeFsssi(ofnraolmjauddegfmaeunltt v(asilmuielaorft1o0t)hweecraesmeafdoreRbIaDsdeedriovnattihoen afvoariPlFaOblSe).data "The following is excerpted from the IRIS file for Arochior 1016: Arochlor 1016: UNCERTAINTY AND MODIFYING FACTORS (ORAL RID) UF A 3-old actor s applied to account for sensitive individuals, The resus of these studies, a well as data for human exposure to PCBS, indicate that infants exposed transplacentally represent asensiive subpopulation. A factor of3i applied for extrapolation from rhesus monkeys to human. A full 10-fold factor or interspecies extrapolation is nt considered necessary because of similarities in toxic responses and metabolism of PCBS between monkeys and humans and the general physiologic simiary between these species. In addon, the rhesus monkey data are predictive of other changes noted in human studies sich as chloracne, hepatic changes, and effects on reproductive funciion. A factor of 3 is applied because of imitations in the data base. Despite the extensive amount of animal laboratory data and human epidemiologic information regarding PCBs, the issue of male reproductive effects is not directly addressed and two-generation reproductive studies are not available. As the study duration was considered as somewhat greater than subchronic, but ess than chronic, a partial factor of3 is used to account for extrapolation from a subchronic exposure to a chronic RID. MF None 000196 5