EPA-823-P-18-001 Public Comment Draft Human Health Toxicity Values for Hexafluoropropylene Oxide (HFPO) Dimer Acid and Its Ammonium Salt (CASRN 13252-13-6 and CASRN 62037-80-3) Also Known as “GenX Chemicals” 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 DRAFT FOR PUBLIC COMMENT – DO NOT CITE OR QUOTE NOVEMBER 2018 Human Health Toxicity Values for Hexafluoropropylene Oxide (HFPO) Dimer Acid and Its Ammonium Salt (CASRN 13252-13-6 and CASRN 62037- 80-3) Also Known as “GenX Chemicals” Prepared by: U.S. Environmental Protection Agency Office of Water (4304T) Health and Ecological Criteria Division Washington, DC 20460 EPA Document Number: 823-P-18-001 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 DRAFT FOR PUBLIC COMMENT – DO NOT CITE OR QUOTE NOVEMBER 2018 Disclaimer This document is a public comment draft for review purposes only.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 DRAFT FOR PUBLIC COMMENT – DO NOT CITE OR QUOTE NOVEMBER 2018 Acknowledgments This document was prepared by the Health and Ecological Criteria Division, Office of Science and Technology, Office of Water (OW) of the U.S. Environmental Protection Agency (EPA). OW leads for the assessment include Brittany Jacobs, PhD; Greg Miller, MS; and Jamie Strong, PhD. OW scientists who provided valuable contributions to the development of this assessment include Joyce Donohue, PhD and Barbara Soares, PhD. The Agency gratefully acknowledges the valuable contributions of EPA scientists from the Office of Pollution Prevention and Toxics, including Catherine Aubee; Amy Babcock, MPH, DABT, MRSB; Amy Benson, MS, DABT; Tracy Behrsing, PhD; Chris Brinkerhoff, PhD; Tala Henry, PhD; and Laurence Libelo, PhD. This document was provided for review by staff in the following EPA Program Offices and Regions: • Office of Water • Office of Chemical Safety and Pollution Prevention, Office of Pesticide Programs • Office of Chemical Safety and Pollution Prevention, Office of Pollution Prevention and Toxics • Office of Chemical Safety and Pollution Prevention, Office of Science Coordination and Policy • Office of Land and Emergency Management • Office of Air and Radiation, Office of Transportation and Air Quality • Office of Air and Radiation, Office of Air Quality Planning and Standards • Office of Policy • Office of Children’s Health Protection • Office of Research and Development • Regions 1–10 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 Introduction and Background ........................................................................................... 1 1.1 History of Assessment of GenX Chemicals ..................................................................... 1 1.2 Uses of GenX Chemicals under TSCA ............................................................................ 2 1.3 Occurrence ....................................................................................................................... 3 1.4 Other Assessments of GenX Chemicals........................................................................... 4 1.4.1 North Carolina Assessment....................................................................................... 4 1.4.2 Report by the National Institute for Public Health and the Environment ................. 4 2.0 Nature of the Stressor ........................................................................................................ 5 2.1 Chemical/Physical Properties ........................................................................................... 5 2.2 Environmental Fate .......................................................................................................... 8 2.2.1 Water ......................................................................................................................... 8 2.2.2 Air ............................................................................................................................. 8 2.2.3 Sediments and Soils .................................................................................................. 9 2.2.4 Biodegradation .......................................................................................................... 9 2.2.5 Incineration ............................................................................................................... 9 2.2.6 Bioaccumulation ....................................................................................................... 9 2.3 Toxicokinetics ................................................................................................................ 10 2.3.1 Absorption............................................................................................................... 10 2.3.2 Distribution ............................................................................................................. 12 2.3.3 Distribution during Gestation and Lactation........................................................... 13 2.3.4 Metabolism ............................................................................................................. 14 2.3.5 Excretion ................................................................................................................. 14 2.3.6 Pharmacokinetic Clearance and Half-life Data ....................................................... 15 3.0 Problem Formulation ....................................................................................................... 20 3.1 Conceptual Model .......................................................................................................... 20 3.2 Overall Scientific Objectives ......................................................................................... 22 3.3 Methods .......................................................................................................................... 23 3.3.1 Literature Search Strategy and Results ................................................................... 23 3.3.2 Study Screening Process and Study Evaluation...................................................... 24 3.3.3 Approach for Derivation of Reference Values ....................................................... 25 3.3.4 Measures of Effect .................................................................................................. 26 4.0 Study Summaries .............................................................................................................. 27 4.1 Acute Toxicity Studies ................................................................................................... 27 4.2 Short-Term Toxicity Studies .......................................................................................... 29 4.3 Subchronic Toxicity Studies .......................................................................................... 32 4.4 Chronic Toxicity and Carcinogenicity Studies .............................................................. 34 4.5 Reproductive and Developmental Toxicity Studies ....................................................... 37 4.6 Other Studies .................................................................................................................. 40 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 4.6.1 Immunotoxicity Studies .......................................................................................... 40 4.6.2 Mechanistic Studies ................................................................................................ 40 4.6.3 Genotoxicity Studies ............................................................................................... 41 4.7 Mode of Action .............................................................................................................. 42 5.0 Summary of Hazard ......................................................................................................... 43 5.1 Hepatic ........................................................................................................................... 43 5.2 Hematological ................................................................................................................ 44 5.3 Renal............................................................................................................................... 45 5.4 Developmental/Reproductive ......................................................................................... 46 5.5 Immune System .............................................................................................................. 46 5.6 Cancer............................................................................................................................