Document LKrvgGv56Ko6geqyQx92Dk2y3

Internal Correspondenecee ------------ To: Dr. John Butenhoff, Manager Corporate Toxicology From: Dr. Robert Roy Corporate Toxicology Subject: Draft Drinking Water Health Advisory (DWHA) - PFOS Date: July 7, 1999 John -- TPFhOeSa.ttaTchheeddrdaoftcuDmWeHntApirsebsaenstesdtohne aderreivfaetrieonnceofdaosderaf(tRflDi)fewtihmiecDh WwaHsAdfeorrived using a conservative, composite uncertaintyfactor (UF). Avery based similar process of on available data) RID has development been used by (e.g. EPA selection of appropriate UFs for Arochlor 1016; this is also included for your reference (Appendix). Ifyou have questions or would like to discuss, please let me know. Rob 0C362 DRAFT - Lifetime Drinking Water Health Advisory (DWHA) for PFOS Background' The DWHA for PFOS was calculated using the following three equations were used: standard EPA methodology. Briefly, pw QOAOL)Dor COMED boy va-dgy wer = BD2V0 TdaKy D ot or git Lifetime DWH. = DWEL x RSC = mg/L or ug/L Where: RID = Chronic Reference Dose [the estimate (with uncertainty spanning an order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be without appreciable risk of deleterious effects during alifetime] NOAEL = No Observed Adverse Effect Level [the exposure level at which there are no statistically or biologically oarppsreovperriiattyeofcoandtrvoelr;sseoemffeecetfsfebcetstwmeaeyn significant increases in thefrequency bteheperxopdousceedd patoptuhlisatlieovnelabnudt tthheey are not considered effects] to be adverse, nor to be a precursor to specific adverse tLhOerAeEaLre=sLtaotwiestsitcalOlbysoerrbvieodloAgidcvaellrysesigEnfiffeicctanLtevienlcr[etahseeesxipnotshuerefrleeqveulenactywhoirch severity of adverse effects between the exposed population and the appropriate control] UF = Total composed Uncertainty Factor (chosen using of five sub-factors that attempt to EPA guidance). The total UF account for uncertainty with is regard to: 1) interhuman variability; 2) extrapolation of results from 1 003G63 DRAFT -- eexxppeorsiumreen;t4a)l eaxntirmaaploltaotihounmfarno;m 3L)OeAxtErLaptoolaNtOioAnELfr;omansdub5c)hrionnciocmptloectheronic 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 the MF = 1. Sub-UFs <10 factor for may also each of the five sub-UFs = 10; that be used when existing data reduce for or eolfiampinpartoeprtiheatneeseudbt-oUaFcscoaunndt ftohreaMpFaritsicauclacroamrpelaiosfhuendceorntaainctya.seT-hbye-cchaosiece basis using professionaljudgment by experienced risk assessors. DWEL = Drinking Water drinking water that is nof Equivalent Level [the concentration oaf substance expected to cause any non-carcinogenic health in effects in humans over a lifetime of exposure] cRhSmCei=caRleflartoimvedrSionkuirncgewCaotnetrrirbeultatiiovne[tios tohteheprrospoourrtcieosn sofucehxpaossfuoroedtoanad airl(in the absenceof any other data the EPA default value = 20% is used) Lifetime chemical Drinking Water in drinking water Health that is Advisory (DWHA) = The concentration not expected to cause any adverse ofa noncarcinogenic effects over a lifetime of exposure, with a margin of safety. "References, Cemiecrmgainnegc,isJ.sL ueest. alI.n: (1F9a9n5.).AMN.onacnandcCehrarnigs,k aLs.sWe.ss(medeintto:rs)prTeosxeinctolaongdy and Risk Assessment: Principles, Methods, and Applications. New York, pp. 293-310. (copy ofpaper attached) Marcel Dekker, Dourson, M.L. et al. (1995). noncancer risk assessment. Evolution of science-based uncertainty factors in Regulatory Toxicology and Pharmacology 24: 108-120. (copyofpaper attached) Environmental System (IRIS). Protection Agency (1999). Integrated Risk Information WWWaddress: htip://www.epa.govincealiris.htm REengvuilraotnimoennstaalndPrHoetaelcttihonAdvAigseorniceys.(19W99).WOfafdidcreesosf:Water. Drinking Water http://www epa.govIOST/Tools/dwstds0.html 2 003564 DRAFT -- I Lifetime Drinking Water Health Advisory (DWHA) for PFOS Step 1. RfD Calculation Rp COAL) or LOUD) ys ay (UF) NOAEL = 0.15 mglkg-day [NOAEL from 6-month monkey oral capsule study] UF = 900 (rounded up = 1000) [total UF = 900 (10x3x10x1x3). UFs were as follows [also refer to Appendix]: Individual sub- 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 - NOAELused] Incomplete database = 3 [significant data accumulated on chemical; results of the 2-year bioassay are still pending] Modifying Factor = 1 [human data available; significant data accumulated on chemical; sensitive endpoint established in studies; uncertainties accounted for in other sub-factors] 3 C00355 DRAFT -- Therefore: RD =Mimi 2 0.00015 mg/kg day = (0.2 pg/kg -day) tNhoetree:forTeh,eRpIrDecsihsoiuolndabsesorcoiautneddedwittoh =th0.e2 RfugDliksg-usduaaylly one significant figure, n Lifetime Drinking Water Health Advisory (DWHA) for PFOS Step 2. DWEL Calcula'ion or RD) (0 ke) DIWEL = =2 = Lda200 = gffl]. , or ug/. IL DWEL= rule27 Ada)y (OKD) 7 ory . mn. Lifetime Drinking Water Health Advisory (DWHA) for PFOS Step 3. Lifetime DWHA Calculation Lifetime DWHA = DWEL x RSC = mg/L or ug/L Lifetime DWHA = (7 1027102) =10 ig L (ppb) 4 00356 DRAFT -- APPENDIX Precedent exists (see Arochior example, below) for a reduction in sub-UFs (i.e. versus using standard defaults = 10 for each sub-UF) when the experimental data warrant. Based on the significant amount of available toxicological data for PFOS (including data from s`udies on other FCs in which PFOS ishypothesized to be the "toxic" metabolite) it is very relevant to use both professional risk assessment and toxicologicz! judgment to "adjust" the sub-UFs based on available data. The EPA-derived RfD for Arochlor 1016 is 7x 10% mg/kg-day. The total uncertainty factor used by EIA was 100; an MF of 1 was also used. Reductions in sub-UFs (from a default veiue of 10) were made based on the available data and professional judgment (similtaor the case for RfD derivation for PFOS). The following is excerpted from the IRIS file for Arochlor 1016: Arochlor 1016: UNCERTAINTY AND MODIFYING FACTORS (ORAL RD) UF -- Afi factor is ape 0 accountfor sense indiduals, The fest of hese studies, wel as data for human exposure o PCBS, indicate nat nfants exposed transplacental represenat sensitve subpopulation. A factor of3 is appfor extrapolation rom thesus monkeys fo human. A ul 101k foto fo trspecies extrapolation isnot considered necessary becauseof smiaiies nx: responses and metabolismof PCBs batween monkeys and humans an the general physcogi smiarty between these species. Inaddiion, the sus monkey data ae predictiveof other changes noted inhuman sues such as chioracn, hepatic changes, andefectson feproductive function. A fctor of 3 i applied because of imitations inthe data base. Despite the etensiv amount of animal laboratory data and human epidemiologic information regarding PCS, he issueof male reproductive ffct is not rectly addressed and wo-generation reproductive suds are not avaiable. As the sud; duration was considered as somewhat greater than subchronic, but es than chronic, aparal facotfo3irs ustoaeccodunt for extrapolation fom a shchronic exposure 0a chronic RID. ME- None 5 00357