United States Office of Water EPA 822-R-16-003 Environmental Protection Mail Code 4304T May 2016 Agency Health Effects Support Document for Perfluorooctanoic Acid (PFOA) Perfluorooctanoic Acid – May 2016 i Health Effects Support Document for Perfluorooctanoic Acid (PFOA) U.S. Environmental Protection Agency Office of Water (4304T) Health and Ecological Criteria Division Washington, DC 20460 EPA Document Number: 822-R-16-003 May 2016 Perfluorooctanoic Acid – May 2016 ii BACKGROUND The Safe Drinking Water Act (SDWA), as amended in 1996, requires the Administrator of the U.S. Environmental Protection Agency (EPA) to periodically publish a list of unregulated chemical contaminants known or anticipated to occur in public water systems and that may require regulation under SDWA. The SDWA also requires the Agency to make regulatory determinations on at least five contaminants on the Contaminant Candidate List (CCL) every 5 years. For each contaminant on the CCL, before EPA makes a regulatory determination, the Agency needs to obtain sufficient data to conduct analyses on the extent to which the contaminant occurs and the risk it poses to populations via drinking water. Ultimately, this information will assist the Agency in determining the most appropriate course of action in relation to the contaminant (e.g., developing a regulation to control it in drinking water, developing guidance, or deciding not to regulate it). The PFOA health assessment was initiated by the Office of Water, Office of Science and Technology in 2009. The draft Health Effects Support Document for Perfluoroctanoic Acid (PFOA) was completed in 2013 and released for public comment in February 2014. An external peer-review panel meeting was held on August 21 and 22, 2014. The final document reflects input from the panel as well as public comments received on the draft document. Both the peer- reviewed draft and this document include only the sections of a health effects support document (HESD) that cover the toxicokinetics and health effects of PFOA. If a decision is made to regulate the contaminant, this document will be expanded. One of the challenges inherent in conducting this assessment was the wealth of experimental data published before and during its development. This section provides a synopsis of the approach used in identifying and selecting the publications reflected in the final assessment. Data were identified through the following: • Monthly/bimonthly literature searches conducted by EPA library staff (2009–2015) and New Jersey Department of Environmental Protection library staff (2012–2015). • Papers identified by EPA internal and external peer reviewers. • Papers identified through public comments on the draft assessments. • Papers submitted to EPA by the public. In mid-2013, the EPA library searches were expanded to cover all members of the perfluoroalkane carboxylate family (C4 through C12). Appendix A describes the literature search strategy used by the libraries. Through the literature search, documents were identified for retrieval, review, and inclusion in the HESD using the following criteria: • The study examines a toxicity endpoint or population not examined by studies already included in the draft document. • Aspects of the study design such as the size of the population exposed or quantification approach make it superior to key studies already included in the draft document. • The data contribute substantially to the weight of evidence for any of the toxicity endpoints covered by the draft document. • Elements of the study design merit its inclusion in the draft document based on its contribution to the mode of action (MoA) or the quantification approach. Perfluorooctanoic Acid – May 2016 iii • The study elucidates the MoA for any toxicity endpoint or toxicokinetic property associated with PFOA exposure. • The effects observed differ from those in other studies with comparable protocols. In addition to each publication being evaluated against the criteria above, the relevance of the study to drinking water exposures and to the U.S. population also were considered. The studies included in the final draft were determined to provide the most current and comprehensive description of the toxicological properties of PFOA and the risk it poses to humans exposed to it in their drinking water. Appendix B summarizes the studies evaluated for inclusion in the HESD following the August 2014 peer review and identifies those selected for inclusion in the final assessment. Appendix B includes epidemiology data that provide a high- level summary of the outcomes across the studies evaluated. Development of the hazard identification and dose-response assessment for PFOA has followed the general guidelines for risk assessment forth by the National Research Council (1983) and EPA’s Framework for Human Health Risk Assessment to Inform Decision Making (USEPA 2014a). Other EPA guidelines used in the development of this assessment include the following: • Guidelines for the Health Risk Assessment of Chemical Mixtures (USEPA 1986a) • Guidelines for Mutagenicity Risk Assessment (USEPA 1986b) • Recommendations for and Documentation of Biological Values for Use in Risk Assessment (USEPA 1988) • Guidelines for Developmental Toxicity Risk Assessment (USEPA 1991) • Interim Policy for Particle Size and Limit Concentration Issues in Inhalation Toxicity Studies (USEPA 1994a) • Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry (USEPA 1994b) • Use of the Benchmark Dose Approach in Health Risk Assessment (USEPA, 1995) • Guidelines for Reproductive Toxicity Risk Assessment (USEPA 1996) • Guidelines for Neurotoxicity Risk Assessment (USEPA 1998) • Science Policy Council Handbook: Peer Review (2nd edition) (USEPA 2000a) • Supplemental Guidance for Conducting Health Risk Assessment of Chemical Mixtures (USEPA 2000b) • A Review of the Reference Dose and Reference Concentration Processes (USEPA 2002a) • Guidelines for Carcinogen Risk Assessment (USEPA 2005a) • Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens (USEPA 2005b) • Science Policy Council Handbook: Peer Review (3rd edition) (USEPA 2006a) • A Framework for Assessing Health Risks of Environmental Exposures to Children (USEPA 2006b) • Exposure Factors Handbook (USEPA 2011) • Benchmark Dose Technical Guidance Document (USEPA 2012) • Child-Specific Exposure Scenarios Examples (USEPA 2014b) Perfluorooctanoic Acid – May 2016 iv AUTHORS Joyce Morrissey Donohue, Ph.D. (Chemical Manager) Office of Water U.S. Environmental Protection Agency, Washington, DC Tina Moore Duke, M.S. (previously with Office of Water, U.S. Environmental Protection Agency) John Wambaugh, Ph.D. Office of Research and Development U.S. Environmental Protection Agency, Research Triangle Park, NC The following contractors supported the development of this document: Jennifer Rayner, Ph.D., D.A.B.T. Environmental Sciences Division Oak Ridge National Laboratory, Oak Ridge, TN Carol S. Wood, Ph.D., D.A.B.T. Environmental Sciences Division Oak Ridge National Laboratory, Oak Ridge, TN This document was prepared under the U.S. EPA Contract No. DW-8992342701, Work Assignment No. 2011-001 with Oak Ridge National Laboratory. The Lead U.S. EPA Scientist is Joyce Morrissey Donohue, Ph.D., Health and Ecological Criteria Division, Office of Science and Technology, Office of Water. The Oak Ridge National Laboratory is managed and operated by UT-Battelle, LLC., for the U.S. Department of Energy under Contract No. DE-AC05-00OR22725. Contributors and Reviewers Internal Contributors and Reviewers Office of Water, U.S. Environmental Protection Agency Elizabeth Doyle, Ph.D. (retired) Edward Hackett Office of Research and Development, U.S. Environmental Protection Agency Glinda Cooper, Ph.D. Barbara Glenn, Ph.D. Erin Hines, Ph.D. Christopher Lau, Ph.D. Matthew Lorber, Ph.D. Jaqueline Moya Linda Phillips, Ph.D. Paul White, Ph.D. Michael Wright, Sc.D. Perfluorooctanoic Acid – May 2016 v Office of Chemical Safety and Pollution Prevention, U.S. Environmental Protection Agency E. Laurence Libelo Andrea Pfehales-Hutchens, Ph.D. Tracy Williamson David Lai, Ph.D. (retired) Jennifer Seed, Ph.D. (retired) Office of Childrens Health Protection, U.S. Environmental Protection Agency Gregory Miller Office of Land and Emergency Management, U.S. Environmental Protection Agency External Reviewers James Bruckner, Ph.D. Department of Pharmacology and Toxicology University of Georgia, Athens, GA Deborah Cory-Slechta, Ph.D. Department of Environmental Medicine University of Rochester Medical Center, Rochester, NY Jamie DeWitt, Ph.D. Pharmacology and Toxicology East Carolina University, Greenville, NC Jeffrey Fisher, Ph.D. Biochemical Toxicology, NCTR U.S. Food & Drug Administration, Jefferson, AK William Hayton, Ph.D. College of Pharmacy (Emeritus) The Ohio State University, Columbus, OH Matthew Longnecker, M.D., Sc.D. Biomarker-based Epidemiology Group National Institute of Environmental Health Sciences, Research Triangle Park, NC Angela Slitt, Ph.D. Biomedical and Pharmaceutical Sciences University of Rhode Island, Kingston, RI Perfluorooctanoic Acid – May 2016 vi CONTENTS BACKGROUND ........................................................................................................................... iii ABBREVIATIONS AND ACRONYMS .................................................................................... xiv EXECUTIVE SUMMARY .......................................................................................................ES-1