Drinking Water Health Advisory for …

1 Drinking Water Health Advisory for Perfluorooctane Sulfonate (PFOS) united states environmental protection agency Office of Water Mail Code 4304T EPA 822-R-16-004 May 2016 Drinking Water Health Advisory for Perfluorooctane Sulfonate (PFOS) May 2016 1 Drinking Water Health Advisory for Perfluorooctane Sulfonate (PFOS) Prepared by: environmental protection agency Office of Water (4304T) Health and Ecological Criteria Division Washington, DC 20460 EPA Document Number: 822-R-16-004 May 2016 Drinking Water Health Advisory for Perfluorooctane Sulfonate (PFOS) May 2016 2 ACKNOWLEDGMENTS This document was prepared by the Health and Ecological Criteria Division, Office of Science and Technology, Office of Water of the environmental protection agency (EPA).

2 The agency gratefully acknowledges the valuable contributions of EPA scientists Barbara Glenn, ; Erin Hines, ; Michael Wright, ; John Wambaugh, ; Thomas Speth, ; and Daniel Hautman. This Health Advisory was provided for review by and comments were received from staff in the following EPA program Offices: Office of Chemical Safety and Pollution Prevention Office of Children s Health protection Office of General Counsel Office of Land and Emergency Management Office of Policy Office of Research and Development Office of Water Drinking Water Health Advisory for Perfluorooctane Sulfonate (PFOS) May 2016 3 CONTENTS ACKNOWLEDGMENTS .. 3 ABBREVIATIONS AND ACRONYMS .. 7 EXECUTIVE SUMMARY .. 10 1 INTRODUCTION AND BACKGROUND.

3 12 Safe Drinking Water Act .. 12 Current Advisories and Guidelines .. 14 Uses of PFOS .. 15 2 NATURE OF THE STRESSOR .. 16 Physical and Chemical Properties .. 16 Occurrence and Sources of Exposure .. 17 Surface Water and Groundwater .. 17 Drinking Water .. 18 Food .. 19 Ambient Air .. 22 Indoor Dust .. 22 23 Biosolids .. 23 Consumer Products .. 24 environmental Fate .. 25 25 25 Bioaccumulation .. 25 Toxicokinetics .. 26 Human Biomonitoring Data .. 27 3 PROBLEM FORMULATION .. 28 Conceptual Model .. 28 Conceptual Model Diagram for Exposure via Finished Drinking Water .. 28 Factors Considered in the Conceptual Model for PFOS .. 30 Analysis Plan .. 32 Health Advisory Guidelines.

4 32 Establishing the Data Set .. 32 Approach for HA Calculation .. 33 Measures of Effect .. 34 Relative Source Contribution .. 35 Drinking Water Health Advisory for Perfluorooctane Sulfonate (PFOS) May 2016 4 4 EFFECTS ASSESSMENT .. 36 Noncancer Health Effects .. 36 Animal Toxicology .. 36 Human Epidemiology Studies .. 37 Noncancer Mode of Action (MOA) .. 41 Cancer .. 42 Animal Cancer Bioassays .. 42 Human Epidemiology Studies .. 42 Cancer Mode of Action .. 43 Weight of Evidence Classification .. 43 5 DOSE-RESPONSE ASSESSMENT .. 43 Uncertainty Factors .. 46 RfD Determination .. 47 6 Health Advisory VALUES .. 48 Relative Source Contribution .. 48 Lifetime Health Advisory .

5 49 7 CANCER RISK .. 51 8 EFFECTS CHARACTERIZATION .. 51 Uncertainty and Variability .. 51 Use of Epidemiology Data .. 52 Consideration of Immunotoxicity .. 53 Alternative Exposure Scenarios .. 55 Relative Source Contribution Considerations .. 55 Sensitive Populations: Gender Differences .. 57 Sensitive Populations: Developmental Effects .. 57 9 ANALYTICAL METHODS .. 57 10 TREATMENT TECHNOLOGIES .. 58 11 REFERENCES .. 62 Drinking Water Health Advisory for Perfluorooctane Sulfonate (PFOS) May 2016 5 TABLES Table 1-1. State Guideline Values for PFOS ..14 Table 1-2. International Guideline Values for PFOS ..14 Table 2-1. Chemical and Physical Properties of PFOS ..17 Table 5-1. Human Equivalent Doses Derived from the Modeled Animal Average Serum Values.

6 45 Table 5-2. Candidate RfDs Derived from HEDs from the Pharmacokinetic Model Average Serum Values ..47 FIGURES Figure 2-1. Chemical Structure of PFOS Anion ..16 Figure 3-1. Conceptual Model for PFOS in Finished Drinking Water ..29 Drinking Water Health Advisory for Perfluorooctane Sulfonate (PFOS) May 2016 6 ABBREVIATIONS AND ACRONYMS alpha AFFF aqueous film forming foams ALT alanine transaminase ASBT apical sodium dependent bile acid transporter AUC area under the curve beta BAF bioaccumulation factor BCF bioconcentration factor BMF biomagnification factor BUN blood urea nitrogen bw body weight C Celsius CASRN Chemical Abstracts Service Registry Number CCL Contaminant Candidate List CDC Centers for Disease Control and Prevention CDR chemical data reporting CI confidence interval CL cl earance CWA Clean Water Act dL deciliter DL detection limit DNT developmental neurotoxicity DWEL Drinking Water equivalent level DWI Drinking Water intake ECF electro-chemical fluorination EPA

7 environmental protection agency EWG environmental Working Group FDA Food and Drug Administration FR fecundability ratios g gram GAC granular activated carbon GJIC gap junctional intercellular communication HA Health Advisory HDL high density lipoprotein HED human equivalent dose HESD Health Effects Support Document Hg mercury IRIS Integrated Risk Information System kg kilogram km kilometer Koc organic carbon- Water partitioning coefficient Kow octanol- Water partition coefficient KO knockout L liter LC/MS/MS liquid chromatography/tandem mass spectrometry Drinking Water Health Advisory for Perfluorooctane Sulfonate (PFOS) May 2016 7 LDL low density lipoprotein LOAEL lowest observed adverse effect level LOD limit of detection LOQ limit of quantitation g microgram m2 square meter m3 cubic meter mg milligram mi mile mL milliliter mm millimeter MOA mode of action mol mole MRL minimum reporting level ng nanogram NHANES National Health and Nutrition Examination Survey NOAEL no observed adverse effect level NTCP sodium taurocholate cotransporting polypeptide OR odds ratio OST organic solute transporter PAC powdered activated carbon PBDE polybrominated diphenyl ether PFAS perfluoroalkyl substance PFBS perfluorobutane sulfonate PFCs perfluorinated compounds PFDA perfluorododecanoic acid PFHpA perfluoroheptanoic acid PFHsA

8 Perfluorohexanoic acid PFHxS perfluorohexane sulfonic acid PFOA perfluorooctanoic acid PFOS perfluorooctane sulfonate PFOSA perfluorosulfonamide PFPeA perfluoropentanoic acid pg picogram PK pharmacokinetic PND postnatal day POD point of departure POE point of entry POSF perfluorooctanesulfonyl fluoride POU point of use PPAR peroxisome proliferator activated receptor alpha ppb parts per billion ppm parts per million PTFE polytetrafluoroethylene PWS public Water systems REACH Registration, Evaluation, Authorization and Restriction of Chemicals Drinking Water Health Advisory for Perfluorooctane Sulfonate (PFOS) May 2016 8 RfD reference dose RSC relative source contribution SDVB polystyrenedivinylbenzene SDWA Safe Drinking Water Act SGA small for gestational age SPE solid phase extraction T3 triiodothyronine T4 thyroxine t1/2 chemical half-life TMF trophic magnification factor TNSSS Total National Sewage Sludge Survey TPO thyroid peroxidase TSCA Toxic Substances Control Act TSH thyroid-stimulating hormone TTR transthyretin UCMR 3 third Unregulated Contaminant Monitoring Rule UF uncertainty factor UFA interspecies uncertainty factor UFD database deficiency uncertainty factor UFH intraspecies uncertainty factor UFL LOAEL uncertainty factor UFS subchronic uncertainty factor USGS Geological Survey UV

9 Ultraviolet Vd volume of distribution VLDL very low density lipoprotein Drinking Water Health Advisory for Perfluorooctane Sulfonate (PFOS) May 2016 9 EXECUTIVE SUMMARY Perfluorooctane sulfonate (PFOS) is a synthetic, fully fluorinated organic acid; it is used in a variety of consumer products and is generated as a degradation product of other perfluorinated compounds. Because of strong carbon-fluorine bonds, PFOS is stable to metabolic and environmental degradation. PFOS is one of a large group of perfluoroalkyl substances (PFASs) that are used to make products more resistant to stains, grease, and Water . These compounds have been widely found in consumer and industrial products, as well as in food items.

10 In 2002 the only major manufacturer voluntarily agreed to phase out production of PFOS. Exposure to PFOS in the united states remains possible due to its legacy uses, existing and legacy uses on imported goods, degradation of precursors, and extremely high persistence in the environment and the human body. PFOS was detected in blood serum in up to 99% of the general population between 1999 and 2012; however, the levels of PFOS in blood have been decreasing since companies began to phase out production. Water resources contaminated by PFOS have been associated with releases from manufacturing sites, industrial sites, fire/crash training areas, and industrial or municipal waste sites where products are disposed of or applied.