EPA-823-R-18-307 Public Comment Draft Human Health Toxicity Values for Perfluorobutane Sulfonic Acid (CASRN 375-73-5) and Related Compound Potassium Perfluorobutane Sulfonate (CASRN 29420-49-3) This document is a Public Comment draft. It has not been formally released by the U.S. Environmental Protection Agency and should not at this stage be construed to represent Agency policy. This information is distributed solely for the purpose of public review. This document is a draft for review purposes only and does not constitute Agency policy. DRAFT FOR PUBLIC COMMENT – DO NOT CITE OR QUOTE NOVEMBER 2018 Human Health Toxicity Values for Perfluorobutane Sulfonic Acid (CASRN 375-73-5) and Related Compound Potassium Perfluorobutane Sulfonate (CASRN 29420 49 3) Prepared by: U.S. Environmental Protection Agency Office of Research and Development (8101R) National Center for Environmental Assessment Washington, DC 20460 EPA Document Number: 823-R-18-307 NOVEMBER 2018 This document is a draft for review purposes only and does not constitute Agency policy. DRAFT FOR PUBLIC COMMENT – DO NOT CITE OR QUOTE NOVEMBER 2018 Disclaimer This document is a public comment draft for review purposes only. This information is distributed solely for the purpose of public comment. It has not been formally disseminated by EPA. It does not represent and should not be construed to represent any Agency determination or policy. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. i This document is a draft for review purposes only and does not constitute Agency policy. DRAFT FOR PUBLIC COMMENT – DO NOT CITE OR QUOTE NOVEMBER 2018 Authors, Contributors, and Reviewers CHEMICAL MANAGERS Jason C. Lambert, PhD, DABT Elizabeth Oesterling Owens, PhD CONTRIBUTORS Michelle Angrish, PhD Xabier Arzuaga, PhD Johanna Congleton, PhD Ingrid Druwe, PhD J. Allen Davis, MS Kelly Garcia, BS Carolyn Gigot, BA Andrew Greenhalgh, BS Belinda Hawkins, PhD, DABT Ryan Jones, MSLS Andrew Kraft, PhD April Luke, PhD Elizabeth Radke, PhD Michele Taylor, PhD Samuel Thacker, BA Andre Weaver, PhD Amina Wilkins, MPH Michael Wright, ScD DRAFT DOCUMENT PREPARED BY U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment (NCEA) EXECUTIVE DIRECTION Tina Bahadori, ScD NCEA Center Director Mary Ross, PhD NCEA Deputy Center Director Samantha Jones, PhD NCEA Associate Director Emma Lavoie, PhD NCEA Assistant Center Director for Scientific Support PRIMARY INTERNAL REVIEWERS David Bussard, PhD Kris Thayer, PhD Questions regarding the contents of this document may be directed to the National Center for Environmental Assessment in the U.S. Environmental Protection Agency’s Office of Research and Development. ii This document is a draft for review purposes only and does not constitute Agency policy. DRAFT FOR PUBLIC COMMENT – DO NOT CITE OR QUOTE NOVEMBER 2018 Contents 1.0 Background .......................................................................................................................... 1 1.1 Physical and Chemical Properties .................................................................................... 1 1.2 Occurrence ....................................................................................................................... 2 1.3 Toxicokinetics .................................................................................................................. 3 1.3.1 Overview ................................................................................................................. 3 1.3.2 Absorption............................................................................................................... 5 1.3.3 Distribution ............................................................................................................. 5 1.3.4 Metabolism ............................................................................................................. 6 1.3.5 Elimination .............................................................................................................. 6 1.3.6 Summary ................................................................................................................. 8 2.0 Problem Formulation .......................................................................................................... 9 2.1 Conceptual Model ............................................................................................................ 9 2.2 Objective ........................................................................................................................ 11 2.3 Methods.......................................................................................................................... 11 2.3.1 Literature Search ................................................................................................... 11 2.3.2 Screening Process ................................................................................................. 11 2.3.3 Study Evaluation ................................................................................................... 12 2.3.4 Data Extraction ..................................................................................................... 14 2.3.5 Evidence Synthesis ............................................................................................... 15 2.3.6 Evidence Integration and Hazard Characterization .............................................. 15 2.3.7 Derivation of Values ............................................................................................. 17 3.0 Overview of Evidence Identification for Synthesis and Dose-Response Analysis........ 20 3.1 Literature Search and Screening Results ....................................................................... 20 3.2 Study Evaluation Results ............................................................................................... 22 4.0 Evidence Synthesis: Overview of Included Studies ........................................................ 25 4.1 Thyroid Effects .............................................................................................................. 25 4.1.1 Human Studies ...................................................................................................... 25 4.1.2 Animal Studies ...................................................................................................... 25 4.2 Reproductive Effects ...................................................................................................... 26 4.2.1 Human Studies ...................................................................................................... 26 4.2.2 Animal Studies ...................................................................................................... 27 4.3 Offspring Growth and Early Development .................................................................... 30 4.3.1 Human Studies ...................................................................................................... 30 4.3.2 Animal Studies ...................................................................................................... 30 4.4 Renal Effects .................................................................................................................. 31 4.4.1 Human Studies ...................................................................................................... 31 4.4.2 Animal Studies ...................................................................................................... 31 4.5 Hepatic Effects ............................................................................................................... 33 iii This document is a draft for review purposes only and does not constitute Agency policy. DRAFT FOR PUBLIC COMMENT – DO NOT CITE OR QUOTE NOVEMBER 2018 4.5.1 Human Studies ...................................................................................................... 33 4.5.2 Animal Studies ...................................................................................................... 33 4.6 Lipids and Lipoproteins ................................................................................................. 34 4.6.1 Human Studies ...................................................................................................... 34 4.6.2 Animal Studies ...................................................................................................... 34 4.7 Other Effects .................................................................................................................. 35 4.7.1 Human Studies ...................................................................................................... 35 4.7.2 Animal Studies ...................................................................................................... 35 4.8 Other Data ...................................................................................................................... 35 4.8.1 Tests Evaluating Genotoxicity and Mutagenicity ................................................. 38 5.0 Evidence Integration and Hazard Characterization ...................................................... 39 5.1 Thyroid Effects .............................................................................................................. 42 5.2 Developmental Effects ................................................................................................... 42 5.3 Reproductive Effects